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3,500 |
Arachidonic acid metabolism is elevated in Mycoplasma gallisepticum and Escherichia coli co-infection and induces LTC4 in serum as the biomarker for detecting poultry respiratory disease
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Outbreaks of multiple respiratory diseases with high morbidity and mortality have been frequently reported in poultry industry. Metabolic profiling has showed widespread usage in metabolic and infectious disease for identifying biomarkers and understanding of complex mechanisms. In this study, the non-targeted metabolomics were used on Mycoplasma gallisepticum (MG) and Escherichia coli (E.coli) co-infection model in serum, which showed that Leukotriene C4 (LTC4), Leukotriene D4 (LTD4), Chenodeoxycholate, Linoleate and numerous energy metabolites were varied significantly. KEGG enrichment analysis revealed that the metabolic pathways of linoleic acid, taurine and arachidonic acid (AA) were upregulated. To further characterize the consequences of co-infection, we performed an AA metabolic network pathway with metabolic products and enzyme genes. The results showed that the expression of LTC4 increased extremely significant and accompanied with different degree of infection. Meanwhile, the AA network performed the changes and differences of various metabolites in the pathway when multiple respiratory diseases occurred. Taken together, co-infection induces distinct alterations in the serum metabolome owing to the activation of AA metabolism. Furthermore, LTC4 in serum could be used as the biomarker for detecting poultry respiratory disease. ABBREVIATIONS: MG: Mycoplasma gallisepticum; E.coli: Escherichia coli; AA: Arachidonic acid; LTC4: Leukotriene C4; CRD: chronic respiratory diseases; KEGG: Kyoto Encyclopedia of Genes and Genomes; LTs: leukotrienes; PGs: prostaglandins; NO: nitric oxide; HIS: histamine; PCA: Principal Component Analysis; PLS-DA: Partial Least Squares Discriminant Analysis; CCU: color change unit; UPLC: ultra-performance liquid chromatography; MS: mass spectrometry; DEMs: differentially expressed metabolites; ELISA: enzyme-linked immunosorbent assay; SD: standard deviation; VIP: Variable importance in the projection
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3,501 |
Nuclear Receptors as Autophagy-Based Antimicrobial Therapeutics
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Autophagy is an intracellular process that targets intracellular pathogens for lysosomal degradation. Autophagy is tightly controlled at transcriptional and post-translational levels. Nuclear receptors (NRs) are a family of transcriptional factors that regulate the expression of gene sets involved in, for example, metabolic and immune homeostasis. Several NRs show promise as host-directed anti-infectives through the modulation of autophagy activities by their natural ligands or small molecules (agonists/antagonists). Here, we review the roles and mechanisms of NRs (vitamin D receptors, estrogen receptors, estrogen-related receptors, and peroxisome proliferator-activated receptors) in linking immunity and autophagy during infection. We also discuss the potential of emerging NRs (REV-ERBs, retinoic acid receptors, retinoic acid-related orphan receptors, liver X receptors, farnesoid X receptors, and thyroid hormone receptors) as candidate antimicrobials. The identification of novel roles and mechanisms for NRs will enable the development of autophagy-adjunctive therapeutics for emerging and re-emerging infectious diseases.
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3,502 |
Fibrotic Changes and Endothelial-to-Mesenchymal Transition Promoted by VEGFR2 Antagonism Alter the Therapeutic Effects of VEGFA Pathway Blockage in a Mouse Model of Choroidal Neovascularization
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Many patients with wet age-related macular degeneration do not respond well to anti- vascular endothelial growth factor A (VEGFA) therapy for choroidal neovascularization (CNV), and the efficacy of anti-VEGFA decreases over time. We investigated the hypothesis that fibrotic changes, in particular via endothelial-to-mesenchymal transition (EndoMT), play a role in CNV and alter the therapeutic effects of VEGFA pathway blockage. Induction of EndoMT of primary human retinal endothelial cells led to a significantly reduced response to VEGFA at the level of gene expression, cellular proliferation, migration, and tube formation. Suppression of EndoMT restored cell responsiveness to VEGFA. In a mouse model of spontaneous CNV, fibrotic changes and EndoMT persisted as the CNV lesions became more established over time. VEGFA receptor-2 (VEGFR2) antagonism further induced fibrosis and EndoMT in the CNV. The combination of VEGFR2 antagonism and fibrosis/EndoMT inhibition was more effective than either individual treatment in reducing CNV. Our data indicate that fibrosis and EndoMT are involved in the progression of CNV, are exacerbated by VEGFR2 inhibition, and could provide an explanation for the reduced efficacy of anti-VEGFA treatment over time.
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3,503 |
Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise
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SIMPLE SUMMARY: In recent years, immunotherapy has emerged as a pillar in the fight against cancer. However, the heterogeneity within the tumor microenvironment poses challenges to the efficacy of immunotherapy treatment strategies and may contribute to treatment resistance, progression and relapse. Hence, researchers have used transcriptional spatial profiling techniques to uncover the complex cancer immune profile while retaining critical spatial information of different cell types. This would help identify the source of tumor heterogeneity and uncover pathogenic mechanisms, potential drug targets and novel biomarkers. In this review, we discuss various approaches for transcriptional spatial profiling of cancer tissues such as in situ hybridization, digital spatial profiling and an emerging technology known as Visium Spatial Gene Expression Solution. We highlight the strengths and limitations of the different technologies and the potential and promise they hold in the advancement of cancer immunotherapy. ABSTRACT: Intratumoral heterogeneity poses a major challenge to making an accurate diagnosis and establishing personalized treatment strategies for cancer patients. Moreover, this heterogeneity might underlie treatment resistance, disease progression, and cancer relapse. For example, while immunotherapies can confer a high success rate, selective pressures coupled with dynamic evolution within a tumour can drive the emergence of drug-resistant clones that allow tumours to persist in certain patients. To improve immunotherapy efficacy, researchers have used transcriptional spatial profiling techniques to identify and subsequently block the source of tumour heterogeneity. In this review, we describe and assess the different technologies available for such profiling within a cancer tissue. We first outline two well-known approaches, in situ hybridization and digital spatial profiling. Then, we highlight the features of an emerging technology known as Visium Spatial Gene Expression Solution. Visium generates quantitative gene expression data and maps them to the tissue architecture. By retaining spatial information, we are well positioned to identify novel biomarkers and perform computational analyses that might inform on novel combinatorial immunotherapies.
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3,504 |
Non-Immersive Virtual Reality for Post-Stroke Upper Extremity Rehabilitation: A Small Cohort Randomized Trial
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Immersive and non-immersive virtual reality (NIVR) technology can supplement and improve standard physiotherapy and neurorehabilitation in post-stroke patients. We aimed to use MIRA software to investigate the efficiency of specific NIVR therapy as a standalone intervention, versus standardized physiotherapy for upper extremity rehabilitation in patients post-stroke. Fifty-five inpatients were randomized to control groups (applying standard physiotherapy and dexterity exercises) and experimental groups (applying NIVR and dexterity exercises). The two groups were subdivided into subacute (<six months post-stroke) and chronic (>six months to four years post-stroke survival patients). The following standardized tests were applied at baseline and after two weeks post-therapy: Fugl–Meyer Assessment for Upper Extremity (FMUE), the Modified Rankin Scale (MRS), Functional Independence Measure (FIM), Active Range of Motion (AROM), Manual Muscle Testing (MMT), Modified Ashworth Scale (MAS), and Functional Reach Test (FRT). The Kruskal–Wallis test was used to determine if there were significant differences between the groups, followed with pairwise comparisons. The Wilcoxon Signed-Rank test was used to determine the significance of pre to post-therapy changes. The Wilcoxon Signed-Rank test showed significant differences in all four groups regarding MMT, FMUE, and FIM assessments pre- and post-therapy, while for AROM, only experimental groups registered significant differences. Independent Kruskal–Wallis results showed that the subacute experimental group outcomes were statistically significant regarding the assessments, especially in comparison with the control groups. The results suggest that NIVR rehabilitation is efficient to be administered to post-stroke patients, and the study design can be used for a further trial, in the perspective that NIVR therapy can be more efficient than standard physiotherapy within the first six months post-stroke.
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3,505 |
Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning
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SIMPLE SUMMARY: Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. ABSTRACT: Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug–target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches.
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3,506 |
Neutralizing Antibodies Targeting the Conserved Stem Region of Influenza Hemagglutinin
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Influenza continues to be a public health threat despite the availability of annual vaccines. While vaccines are generally effective at inducing strain-specific immunity, they are sub-optimal or ineffective when drifted or novel pandemic strains arise due to sequence changes in the major surface glycoprotein hemagglutinin (HA). The discovery of a large number of antibodies targeting the highly conserved stem region of HAs that are capable of potently neutralizing a broad range of virus strains and subtypes suggests new ways to protect against influenza. The structural characterization of HA stem epitopes and broadly neutralizing antibody paratopes has enabled the design of novel proteins, mini-proteins, and peptides targeting the HA stem, thus providing a foundation for the design of new vaccines. In this narrative, we comprehensively review the current knowledge about stem-directed broadly neutralizing antibodies and the structural features contributing to virus neutralization.
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3,507 |
Development of Monoclonal Antibodies and Antigen-Capture ELISA for Human Parechovirus Type 3
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Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis, and sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising diagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a specific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3 infection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0. We used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate hybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive to the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping showed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized HPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the HPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably used for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other related viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future research and ensure HPeV3-specific diagnosis.
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3,508 |
Elucidating the Inhibitory Effect of Resveratrol and Its Structural Analogs on Selected Nucleotide-Related Enzymes
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Resveratrol, the most widely studied natural phytochemical, has been shown to interact with different target proteins. Previous studies show that resveratrol binds and inhibits DNA polymerases and some other enzymes; however, the binding and functioning mechanisms remain unknown. The elucidated knowledge of inhibitory mechanisms of resveratrol will assist us in new drug discovery. We utilized molecular docking and molecular dynamics (MD) simulation to reveal how resveratrol and structurally similar compounds bind to various nucleotide-dependent enzymes, specifically, DNA polymerases, HIV-1 reverse transcriptase, and ribonucleotide reductase. The results show that resveratrol and its analogs exert their inhibitory effects by competing with the substrate dNTPs in these enzymes and blocking elongation of chain polymerization. In addition, the results imply that resveratrol binds to a variety of other ATP-/NTP-binding proteins.
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3,509 |
Association of Infectious Disease Physician Approval of Peripherally Inserted Central Catheter With Appropriateness and Complications
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IMPORTANCE: Peripherally inserted central catheters (PICCs) are frequently used to deliver intravenous antimicrobial therapy. However, inappropriate PICC use may lead to patient harm. OBJECTIVE: To evaluate whether infectious disease physician approval prior to PICC placement for intravenous antimicrobials is associated with more appropriate device use and fewer complications. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of 21 653 PICCs placed for a primary indication of intravenous antimicrobial therapy between January 1, 2015, and July 26, 2019, was conducted in 42 hospitals participating in a quality collaborative across Michigan among hospitalized medical patients. MAIN OUTCOMES AND MEASURES: Appropriateness of PICCs was defined according to the Michigan Appropriateness Guide for Intravenous Catheters as a composite measure of (1) single-lumen catheter use, (2) avoiding use of PICCs for 5 days or less, and (3) avoiding use of PICCs for patients with chronic kidney disease (defined as an estimated glomerular filtration rate <45 mL/min/1.73 m(2)). Complications related to PICCs included catheter occlusion, deep vein thrombosis, and central line–associated bloodstream infection. The association between infectious disease physician approval, device appropriateness, and catheter complications was assessed using multivariable models, adjusted for patient comorbidities and hospital clustering. Results were expressed as odds ratios with 95% CIs. RESULTS: A total of 21 653 PICCs were placed for intravenous antimicrobials (11 960 PICCs were placed in men [55.2%]; median age, 64.5 years [interquartile range, 53.4-75.4 years]); 10 238 PICCs (47.3%) were approved by an infectious disease physician prior to placement. Compared with PICCs with no documented approval, PICCs with approval by an infectious disease physician were more likely to be appropriately used (72.7% [7446 of 10 238] appropriate with approval vs 45.4% [5180 of 11 415] appropriate without approval; odds ratio, 3.53; 95% CI, 3.29-3.79; P < .001). Furthermore, approval was associated with lower odds of a PICC-related complication (6.5% [665 of 10 238] with approval vs 11.3% [1292 of 11 415] without approval; odds ratio, 0.55; 95% CI, 0.50-0.61). CONCLUSIONS AND RELEVANCE: This cohort study suggests that, when PICCs were placed for intravenous antimicrobial therapy, infectious disease physician approval of PICC insertion was associated with more appropriate device use and fewer complications. Policies aimed at ensuring infectious disease physician approval prior to PICC placement for antimicrobials may improve patient safety.
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3,510 |
Integrating Genomics and Clinical Data for Statistical Analysis by Using GEnome MINIng (GEMINI) and Fast Healthcare Interoperability Resources (FHIR): System Design and Implementation
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BACKGROUND: The introduction of next-generation sequencing (NGS) into molecular cancer diagnostics has led to an increase in the data available for the identification and evaluation of driver mutations and for defining personalized cancer treatment regimens. The meaningful combination of omics data, ie, pathogenic gene variants and alterations with other patient data, to understand the full picture of malignancy has been challenging. OBJECTIVE: This study describes the implementation of a system capable of processing, analyzing, and subsequently combining NGS data with other clinical patient data for analysis within and across institutions. METHODS: On the basis of the already existing NGS analysis workflows for the identification of malignant gene variants at the Institute of Pathology of the University Hospital Erlangen, we defined basic requirements on an NGS processing and analysis pipeline and implemented a pipeline based on the GEMINI (GEnome MINIng) open source genetic variation database. For the purpose of validation, this pipeline was applied to data from the 1000 Genomes Project and subsequently to NGS data derived from 206 patients of a local hospital. We further integrated the pipeline into existing structures of data integration centers at the University Hospital Erlangen and combined NGS data with local nongenomic patient-derived data available in Fast Healthcare Interoperability Resources format. RESULTS: Using data from the 1000 Genomes Project and from the patient cohort as input, the implemented system produced the same results as already established methodologies. Further, it satisfied all our identified requirements and was successfully integrated into the existing infrastructure. Finally, we showed in an exemplary analysis how the data could be quickly loaded into and analyzed in KETOS, a web-based analysis platform for statistical analysis and clinical decision support. CONCLUSIONS: This study demonstrates that the GEMINI open source database can be augmented to create an NGS analysis pipeline. The pipeline generates high-quality results consistent with the already established workflows for gene variant annotation and pathological evaluation. We further demonstrate how NGS-derived genomic and other clinical data can be combined for further statistical analysis, thereby providing for data integration using standardized vocabularies and methods. Finally, we demonstrate the feasibility of the pipeline integration into hospital workflows by providing an exemplary integration into the data integration center infrastructure, which is currently being established across Germany.
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3,511 |
Patient-perceived treatment burden of tuberculosis treatment
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BACKGROUND: Treatment for tuberculosis lasts for a minimum of 6 months. The treatment burden experienced by patients in a low-incidence setting where directly observed therapy is the standard of care is not well-known. METHODS: Patients receiving tuberculosis treatment through the chest clinic at a tertiary hospital in Sydney, Australia, participated in a semi-structured interview. The interviews explored the treatment burden experienced by patients and possible solutions to ameliorate this burden. Interviews were conducted until data saturation was achieved. They were recorded, transcribed and analysed using NVivo 12 software. RESULTS: Twenty participants (80% male, mean age 40 years) with pulmonary (n = 13) and extra-pulmonary (n = 7) tuberculosis were interviewed. Participants experienced healthcare, financial, social and medication burdens along with lifestyle changes due to treatment. Medication intake was challenging due to the high number of pills, and 55% (n = 11) of patients experienced fatigue amongst other side effects. Patients found clinic-based directly observed therapy inconvenient, especially those working and/or studying. Suggestions to lessen treatment burden included reducing medication burden and better access to health services. CONCLUSION: Tuberculosis treatment is associated with substantial treatment burden for patients. Measures to reduce treatment burden including alternative treatment delivery methods which are more accommodating to patients than clinic-based directly observed therapy, such as video directly observed therapy or partially self -administered treatment, should be considered on a case-by-case basis.
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3,512 |
Novel PGK1 determines SKP2-dependent AR stability and reprograms granular cell glucose metabolism facilitating ovulation dysfunction
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BACKGROUND: Disordered folliculogenesis is a core characteristic of polycystic ovary syndrome (PCOS) and androgen receptors (ARs) are closely associated with hyperandrogenism and abnormalities in folliculogenesis in PCOS. However, whether the new AR binding partner phosphoglycerate kinase 1 (PGK1) in granulosa cells (GCs) plays a key role in the pathogenesis of PCOS remains unclear. METHODS: We identified the new AR binding partner PGK1 by co-IP (co-immunoprecipitation) in luteinized GCs, and reconfirmed by co-IP, co-localization and GST pull down assay, and checked PGK1 expression levels with qRT-PCR and western blotting. Pharmaceuticals rescue assays in mice, and metabolism assay, AR protein stability and RNA-seq of PGK1 targets in cells proved the function in PCOS. FINDINGS: PGK1 and AR are highly expressed in PCOS luteinized GCs and PCOS-like mouse ovarian tissues. PGK1 regulated glucose metabolism and deteriorated PCOS-like mouse metabolic disorder, and paclitaxel rescued the phenotype of PCOS-like mice and reduced ovarian PGK1 and AR protein levels. PGK1 inhibited AR ubiquitination levels and increased AR stability in an E3 ligase SKP2-dependent manner. Additionally, PGK1 promoted AR nuclear translocation, and RNA-seq data showed that critical ovulation-related genes were regulated by the PGK1-AR axis. INTERPRETATION: PGK1 regulated GCs metabolism and interacted with AR to regulate the expression of key ovulation genes, and also mediated cell proliferation and apoptosis, which resulted in the etiology of PCOS. This work highlights the pathogenic mechanism and represents a novel therapeutic target for PCOS. FUNDING: National Key Research and Development Program of China; National Natural Science Foundation of China grant.
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3,513 |
Doctor’s burnout and interventions
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3,514 |
Insights into the genetic diversity, recombination, and systemic infections with evidence of intracellular maturation of hepadnavirus in cats
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Hepatitis B virus (HBV) is a human pathogen of global concern, while a high diversity of viruses related to HBV have been discovered in other animals during the last decade. Recently, the novel mammalian hepadnavirus, tentatively named domestic cat hepadnavirus (DCH), was detected in an immunocompromised cat. Herein, a collection of 209 cat sera and 15 hepato-diseased cats were screened for DCH using PCR, resulting in 12.4% and 20% positivity in the tested sera and necropsied cats, respectively. Among the DCH-positive sera, a significantly high level of co-detection with retroviral infection was found, with the highest proportion being co-detection with feline immunodeficiency virus (FIV). Full-length genome characterization of DCH revealed the genetic diversity between the nine Thai DCH sequences obtained, and that they phylogenetically formed three distinct monophyletic clades. A putative DCH recombinant strain was found, suggesting a possible role of recombination in DCH evolution. Additionally, quantitative PCR was used to determine the viral copy number in various organs of the DCH-moribund cats, while the pathological findings were compared to the viral localization in hepatocytes, adjacent to areas of hepatic fibrosis, by immunohistochemical (IHC) and western blot analysis. In addition to the liver, positive-DCH immunoreactivity was found in various other organs, including kidneys, lung, heart, intestine, brain, and lymph nodes, providing evidence of systemic infection. Ultrastructure of infected cells revealed electron-dense particles in the nucleus and cytoplasm of hepatocytes, bronchial epithelial cells, and fibroblasts. We propose the intracellular development mechanism of this virus. Although the definitive roles of pathogenicity of DCH remains undetermined, a contributory role of the virus associated with systemic diseases is possible.
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3,515 |
Orchard layout and plant traits influence fruit yield more strongly than pollinator behaviour and density in a dioecious crop
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Mutualistic plant-pollinator interactions are critical for the functioning of both non-managed and agricultural systems. Mathematical models of plant-pollinator interactions can help understand key determinants in pollination success. However, most previous models have not addressed pollinator behavior and plant biology combined. Information generated from such a model can inform optimal design of crop orchards and effective utilization of managed pollinators like western honey bees (Apis mellifera), and help generate hypotheses about the effects of management practices and cultivar selection. We expect that the number of honey bees per flower and male to female flower ratio will influence fruit yield. To test the relative importance of these effects, both singly and simultaneously, we utilized a delay differential equation model combined with Latin hypercube sampling for sensitivity analysis. Empirical data obtained from historical records and collected in kiwifruit (Actinidia chinensis) orchards in New Zealand were used to parameterize the model. We found that, at realistic bee densities, the optimal orchard had 65-75% female flowers, and the most benefit was gained from the first 6-8 bees/1000 flowers, with diminishing returns thereafter. While bee density significantly impacted fruit production, plant-based parameters-flower density and male:female flower ratio-were the most influential. The predictive model provides strategies for improving crop management, such as choosing cultivars which have their peak bloom on the same day, increasing the number of flowers with approximately 70% female flowers in the orchard, and placing enough hives to maintain more than 6 bees per 1000 flowers to optimize yield.
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3,516 |
Mental Health of Medical Workers in COVID-19 Pandemic: Restrictions and Barriers
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3,517 |
Lingual Osseous Choristoma Causing Odynophagia in a Young Female
| null |
3,518 |
Discovery and Validation of Urinary Molecular Signature of Early Sepsis
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OBJECTIVES: Identify alterations in gene expression unique to systemic and kidney-specific pathophysiologic processes using whole-genome analyses of RNA isolated from the urinary cells of sepsis patients. DESIGN: Prospective cohort study. SETTING: Quaternary care academic hospital. PATIENTS: A total of 266 sepsis and 82 control patients enrolled between January 2015 and February 2018. INTERVENTIONS: Whole-genome transcriptomic analysis of messenger RNA isolated from the urinary cells of sepsis patients within 12 hours of sepsis onset and from control subjects. MEASUREMENTS AND MAIN RESULTS: The differentially expressed probes that map to known genes were subjected to feature selection using multiple machine learning techniques to find the best subset of probes that differentiates sepsis from control subjects. Using differential expression augmented with machine learning ensembles, we identified a set of 239 genes in urine, which show excellent effectiveness in classifying septic patients from those with chronic systemic disease in both internal and independent external validation cohorts. Functional analysis indexes disrupted biological pathways in early sepsis and reveal key molecular networks driving its pathogenesis. CONCLUSIONS: We identified unique urinary gene expression profile in early sepsis. Future studies need to confirm whether this approach can complement blood transcriptomic approaches for sepsis diagnosis and prognostication.
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3,519 |
Current Insight of Collagen Biomatrix for Gingival Recession: An Evidence-Based Systematic Review
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Collagen (Col) is a naturally available material and is widely used in the tissue engineering and medical field owing to its high biocompatibility and malleability. Promising results on the use of Col were observed in the periodontal application and many attempts have been carried out to inculcate Col for gingival recession (GR). Col is found to be an excellent provisional bioscaffold for the current treatment in GR. Therefore, the aim of this paper is to scrutinize an overview of the reported Col effect focusing on in vitro, in vivo, and clinical trials in GR application. A comprehensive literature search was performed using EBSCOhost, Science Direct, Springer Link, and Medline & Ovid databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) collagen OR scaffold OR hybrid scaffold OR biomaterial AND (2) gingiva recession OR tissue regeneration OR dental tissue OR healing mechanism OR gingiva. Only articles published from 2015 onwards were selected for further analysis. This review includes the physicochemical properties of Col scaffold and the outcome for GR. The comprehensive literature search retrieved a total of 3077 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 15 articles were chosen for further review. The results from these articles indicated that Col promoted gingival tissue regeneration for GR healing. Therefore, this systematic review recapitulated that Col enhances regeneration of gingival tissue either through a slow or rapid process with no sign of cytotoxicity or adverse effect.
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3,520 |
Insulator Based Dielectrophoresis: Micro, Nano, and Molecular Scale Biological Applications
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Insulator based dielectrophoresis (iDEP) is becoming increasingly important in emerging biomolecular applications, including particle purification, fractionation, and separation. Compared to conventional electrode-based dielectrophoresis (eDEP) techniques, iDEP has been demonstrated to have a higher degree of selectivity of biological samples while also being less biologically intrusive. Over the past two decades, substantial technological advances have been made, enabling iDEP to be applied from micro, to nano and molecular scales. Soft particles, including cell organelles, viruses, proteins, and nucleic acids, have been manipulated using iDEP, enabling the exploration of subnanometer biological interactions. Recent investigations using this technique have demonstrated a wide range of applications, including biomarker screening, protein folding analysis, and molecular sensing. Here, we review current state-of-art research on iDEP systems and highlight potential future work.
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3,521 |
Separation of Glycyrrhizic Acid and Its Derivants from Hydrolyzation in Subcritical Water by Macroporous Resin
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Glycyrrhizic acid (GL) and its derivants, glycyrrhetinic acid 3-O-mono-β-d-glucuronide (GAMG) and glycyrrhetinic acid (GA) hydrolyzed in subcritical water, are bioactive substances and edulcorators. In this work, a separation strategy for these three substances was established. The effects of adsorbent and eluent were investigated by static/dynamic adsorption and multi-stage desorption with the mechanism analysis. The adsorption of them onto EXA50 resin was well fitted by the pseudo second-order kinetic model. The optimal dynamic adsorption flow rate was 6 bed volume (BV)/h, and water of pH = 12 was used to elute GL at 4 BV/h, then n-buthanol was used subsequently to elute GA at 1 BV/h, and finally 90% ethanol was applied to elute GAMG at 2 BV/h. As a result, purities of these compounds increased, which demonstrated that this adsorption-desorption technology was simple and efficient, and indicated the potential for large-scale purification and preparation of GL and its derivants in the future.
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3,522 |
Radiomics for Gleason Score Detection through Deep Learning
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Prostate cancer is classified into different stages, each stage is related to a different Gleason score. The labeling of a diagnosed prostate cancer is a task usually performed by radiologists. In this paper we propose a deep architecture, based on several convolutional layers, aimed to automatically assign the Gleason score to Magnetic Resonance Imaging (MRI) under analysis. We exploit a set of 71 radiomic features belonging to five categories: First Order, Shape, Gray Level Co-occurrence Matrix, Gray Level Run Length Matrix and Gray Level Size Zone Matrix. The radiomic features are gathered directly from segmented MRIs using two free-available dataset for research purpose obtained from different institutions. The results, obtained in terms of accuracy, are promising: they are ranging between 0.96 and 0.98 for Gleason score prediction.
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3,523 |
Selective Targeting of αvβ5 Integrin in HepG2 Cell Line by RGDechi15D Peptide
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Recently, the research community has become increasingly concerned with the receptor αvβ5, a member of the well-known integrin family. Different ongoing studies have evidenced that αvβ5 integrin regulates not only physiological processes but also a wide array of pathological events, suggesting the receptor as a valuable biomarker to specifically target for therapeutic/diagnostic purposes. Remarkably, in some tumors the involvement of the receptor in cell proliferation, tumor dissemination and angiogenesis is well-documented. In this scenario, the availability of a selective αvβ5 antagonist without ‘off-target’ protein effects may improve survival rate in patients with highly aggressive tumors, such as hepatocellular carcinoma. We recently reported a cyclic peptide, RGDechi15D, obtained by structure-activity studies. To our knowledge it represents the first peptide-based molecule reported in the literature able to specifically bind αvβ5 integrin and not cross react with αvβ3. Here we demonstrated the ability of the peptide to diminish both adhesion and invasion of HepG2 cells, an in vitro model system for hepatocellular carcinoma, to reduce the cell proliferation through an apoptotic process, and to interfere with the PI3K pathway. The peptide, also decreases the formation of new vessels in endothelial cells. Taken together these results indicate that the peptide can be considered a promising molecule with properties suited to be assessed in the future for its validation as a selective therapeutic/diagnostic weapon in hepatocarcinoma.
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3,524 |
Cytotoxicity of Oleandrin Is Mediated by Calcium Influx and by Increased Manganese Uptake in Saccharomyces cerevisiae Cells
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Oleandrin, the main component of Nerium oleander L. extracts, is a cardiotoxic glycoside with multiple pharmacological implications, having potential anti-tumoral and antiviral characteristics. Although it is accepted that the main mechanism of oleandrin action is the inhibition of Na(+)/K(+)-ATPases and subsequent increase in cell calcium, many aspects which determine oleandrin cytotoxicity remain elusive. In this study, we used the model Saccharomyces cerevisiae to unravel new elements accounting for oleandrin toxicity. Using cells expressing the Ca(2+)-sensitive photoprotein aequorin, we found that oleandrin exposure resulted in Ca(2+) influx into the cytosol and that failing to pump Ca(2+) from the cytosol to the vacuole increased oleandrin toxicity. We also found that oleandrin exposure induced Mn(2+) accumulation by yeast cells via the plasma membrane Smf1 and that mutants with defects in Mn(2+) homeostasis are oleandrin-hypersensitive. Our data suggest that combining oleandrin with agents which alter Ca(2+) or Mn(2+) uptake may be a way of controlling oleandrin toxicity.
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3,525 |
Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor
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The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC.
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3,526 |
Pollution Weather Prediction System: Smart Outdoor Pollution Monitoring and Prediction for Healthy Breathing and Living
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Air pollution has been a looming issue of the 21st century that has also significantly impacted the surrounding environment and societal health. Recently, previous studies have conducted extensive research on air pollution and air quality monitoring. Despite this, the fields of air pollution and air quality monitoring remain plagued with unsolved problems. In this study, the Pollution Weather Prediction System (PWP) is proposed to perform air pollution prediction for outdoor sites for various pollution parameters. In the presented research work, we introduced a PWP system configured with pollution-sensing units, such as SDS021, MQ07-CO, NO2-B43F, and Aeroqual Ozone (O(3)). These sensing units were utilized to collect and measure various pollutant levels, such as PM2.5, PM10, CO, NO(2), and O(3), for 90 days at Symbiosis International University, Pune, Maharashtra, India. The data collection was carried out between the duration of December 2019 to February 2020 during the winter. The investigation results validate the success of the presented PWP system. In the conducted experiments, linear regression and artificial neural network (ANN)-based AQI (air quality index) predictions were performed. Furthermore, the presented study also found that the customized linear regression methodology outperformed other machine-learning methods, such as linear, ridge, Lasso, Bayes, Huber, Lars, Lasso-lars, stochastic gradient descent (SGD), and ElasticNet regression methodologies, and the customized ANN regression methodology used in the conducted experiments. The overall AQI values of the air pollutants were calculated based on the summation of the AQI values of all the presented air pollutants. In the end, the web and mobile interfaces were developed to display air pollution prediction values of a variety of air pollutants.
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3,527 |
Feasibility and Reliability of SmartWatch to Obtain 3-Lead Electrocardiogram Recordings
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Some of the recently released smartwatch products feature a single-lead electrocardiogram (ECG) recording capability. The reliability of obtaining 3-lead ECG with smartwatches is yet to be confirmed in a large study. This study aimed to assess the feasibility and reliability of smartwatch to obtain 3-lead ECG recordings, the classical Einthoven ECG leads I-III compared to standard ECG. To record lead I, the watch was worn on the left wrist and the right index finger was placed on the digital crown for 30 s. For lead II, the watch was placed on the lower abdomen and the right index finger was placed on the digital crown for 30 s. For lead III, the same process was repeated with the left index finger. Spearman correlation and Bland-Altman tests were used for data analysis. A total of 300 smartwatch ECG tracings were successfully obtained. ECG waves’ characteristics of all three leads obtained from the smartwatch had a similar duration, amplitude, and polarity compared to standard ECG. The results of this study suggested that the examined smartwatch (Apple Watch Series 4) could obtain 3-lead ECG tracings, including Einthoven leads I, II, and III by placing the smartwatch on the described positions.
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3,528 |
Dibromopinocembrin and Dibromopinostrobin Are Potential Anti-Dengue Leads with Mild Animal Toxicity
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Dengue infection is one of the most deleterious public health concerns for two-billion world population being at risk. Plasma leakage, hemorrhage, and shock in severe cases were caused by immunological derangement from secondary heterotypic infection. Flavanone, commonly found in medicinal plants, previously showed potential as anti-dengue inhibitors for its direct antiviral effects and suppressing the pro-inflammatory cytokine from dengue immunopathogenesis. Here, we chemically modified flavanones, pinocembrin and pinostrobin, by halogenation and characterized them as potential dengue 2 inhibitors and performed toxicity tests in human-derived cells and in vivo animal model. Dibromopinocembrin and dibromopinostrobin inhibited dengue serotype 2 at the EC(50)s of 2.0640 ± 0.7537 and 5.8567 ± 0.5074 µM with at the CC(50)s of 67.2082 ± 0.9731 and >100 µM, respectively. Both of the compounds also showed minimal toxicity against adult C57BL/6 mice assessed by ALT and Cr levels in day one, three, and eight post-intravenous administration. Computational studies suggested the potential target be likely the NS5 methyltransferase at SAM-binding pocket. Taken together, these two brominated flavanones are potential leads for further drug discovery investigation.
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3,529 |
Providing Guidance During a Global Viral Pandemic for the Care of Patients With Inflammatory Bowel Disease
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3,530 |
Flavonoid Profiles of Two New Approved Romanian Ocimum Hybrids
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Basil (Ocimum spp.) is a traditional herbal medicine abundant in antioxidants such as phenolic compounds. As part of a diet, this herb is proved to have some roles in decreasing the risk of cancer, and in the treatment of inflammation and neurodegenerative diseases. This study aims to explore the total phenolic and flavonoid content of two new basil hybrids growing in Romania, namely “Aromat de Buzau” (AB) and “Macedon” (MB). The antioxidant capacity of those two species was also analyzed by DPPH and cyclic voltammetry. Six different flavonoids, such as catechin (+), rutin, hyperoside, naringin, naringenin, and genistein, were separated, identified, and quantified by HPLC–DAD chromatography, for the first time, from romanian basil hybrids. The main flavonoid of the extracts was found to be naringin which is present in the highest amount (26.18 mg/kg) in “Aromat de Buzau” (O. basilicum) methanolic extract. These results suggest that dietary intake of these new hybrids can be a source of antioxidant compounds.
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3,531 |
Potential Treatment of Breast and Lung Cancer Using Dicoma anomala, an African Medicinal Plant
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Globally, cancer has been identified as one of the leading causes of death in public health. Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are known to be less toxic to the normal cells and are classified into acetylenic compounds, phenolics, terpenes, and phytosterols. Dicoma anomala is a perennial herb belonging to the family Asteraceae and is widely distributed in Sub-Saharan Africa and used in the treatment of cancer, malaria, fever, diabetes, ulcers, cold, and cough. This review aimed at highlighting the benefits of D. anomala in various therapeutic applications with special reference to the treatment of cancers and the mechanisms through which the plant-derived agents induce cell death.
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3,532 |
An Injectable Hyaluronan–Methylcellulose (HAMC) Hydrogel Combined with Wharton’s Jelly-Derived Mesenchymal Stromal Cells (WJ-MSCs) Promotes Degenerative Disc Repair
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Intervertebral disc (IVD) degeneration is one of the predominant causes of chronic low back pain (LBP), which is a leading cause of disability worldwide. Despite substantial progress in cell therapy for the treatment of IVD degeneration, significant challenges remain for clinical application. Here, we investigated the effectiveness of hyaluronan–methylcellulose (HAMC) hydrogels loaded with Wharton’s Jelly-derived mesenchymal stromal cell (WJ-MSCs) in vitro and in a rat coccygeal IVD degeneration model. Following induction of injury-induced IVD degeneration, female Sprague-Dawley rats were randomized into four groups to undergo a single intradiscal injection of the following: (1) phosphate buffered saline (PBS) vehicle, (2) HAMC, (3) WJ-MSCs (2 × 10(4) cells), and (4) WJ-MSCs-loaded HAMC (WJ-MSCs/HAMC) (n = 10/each group). Coccygeal discs were removed following sacrifice 6 weeks after implantation for radiologic and histologic analysis. We confirmed previous findings that encapsulation in HAMC increases the viability of WJ-MSCs for disc repair. The HAMC gel maintained significant cell viability in vitro. In addition, combined implantation of WJ-MSCs and HAMC significantly promoted degenerative disc repair compared to WJ-MSCs alone, presumably by improving nucleus pulposus cells viability and decreasing extracellular matrix degradation. Our results suggest that WJ-MSCs-loaded HAMC promotes IVD repair more effectively than cell injection alone and supports the potential clinical use of HAMC for cell delivery to arrest IVD degeneration or to promote IVD regeneration.
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3,533 |
Synthesis of “All-Cis” Trihydroxypiperidines from a Carbohydrate-Derived Ketone: Hints for the Design of New β-Gal and GCase Inhibitors
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Pharmacological chaperones (PCs) are small compounds able to rescue the activity of mutated lysosomal enzymes when used at subinhibitory concentrations. Nitrogen-containing glycomimetics such as aza- or iminosugars are known to behave as PCs for lysosomal storage disorders (LSDs). As part of our research into lysosomal sphingolipidoses inhibitors and looking in particular for new β-galactosidase inhibitors, we report the synthesis of a series of alkylated azasugars with a relative “all-cis” configuration at the hydroxy/amine-substituted stereocenters. The novel compounds were synthesized from a common carbohydrate-derived piperidinone intermediate 8, through reductive amination or alkylation of the derived alcohol. In addition, the reaction of ketone 8 with several lithium acetylides allowed the stereoselective synthesis of new azasugars alkylated at C-3. The activity of the new compounds towards lysosomal β-galactosidase was negligible, showing that the presence of an alkyl chain in this position is detrimental to inhibitory activity. Interestingly, 9, 10, and 12 behave as good inhibitors of lysosomal β-glucosidase (GCase) (IC(50) = 12, 6.4, and 60 µM, respectively). When tested on cell lines bearing the Gaucher mutation, they did not impart any enzyme rescue. However, altogether, the data included in this work give interesting hints for the design of novel inhibitors.
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Photodynamic Inactivation of Methicillin-Resistant Staphylococcus aureus by a Natural Food Colorant (E-141ii)
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This study evaluates the photosensitizing effectiveness of sodium copper chlorophyllin, a natural green colorant commonly used as a food additive (E-141ii), to inactivate methicillin-sensitive and methicillin-resistant Staphylococcus aureus under red-light illumination. Antimicrobial photodynamic inactivation (aPDI) was tested on a methicillin-sensitive reference strain (ATCC 25923) and a methicillin-resistant Staphylococcus aureus strain (GenBank accession number Mh087437) isolated from a clinical sample. The photoinactivation efficacy was investigated by exposing the bacterial strains to different E-141ii concentrations (0.0, 1.0, 2.5, 5.0, 10.0, and 20.0 µM) and to red light (625 nm) at 30 J cm(−2). The results showed that E-141ii itself did not prevent bacterial growth for all tested concentrations when cultures were placed in the dark. By contrast, E-141ii photoinactivated both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) under red-light illumination. However, different dose responses were observed for MSSA and MRSA. Whilst the MSSA growth was inhibited to the detection limit of the method with E-141ii at 2.5 µM, >10 µM concentrations were required to inhibit the growth of MRSA. The data also suggest that E-141ii can produce reactive oxygen species (ROS) via Type I reaction by electron transfer from its first excited singlet state to oxygen molecules. Our findings demonstrate that the tested food colorant has great potential to be used in aPDI of MRSA.
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3,535 |
‘Be on the TEAM’ Study (Teenagers Against Meningitis): protocol for a controlled clinical trial evaluating the impact of 4CMenB or MenB-fHbp vaccination on the pharyngeal carriage of meningococci in adolescents
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INTRODUCTION: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. METHODS AND ANALYSIS: The ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci; hyperinvasive meningococci; all meningococci; those meningococci expressing vaccine antigens and; other Neisseria spp. A sample size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. ETHICS AND DISSEMINATION: This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055); the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. TRIAL REGISTRATION NUMBERS: ISRCTN75858406; Pre-results, EudraCT 2017-004609-42.
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3,536 |
A Software Architecture for the Industrial Internet of Things—A Conceptual Model
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The Internet of Things (IoT) is an emerging concept that has revolutionized the use of new technologies in everyday life. The economic impact of IoT becoming very important, and it began to be used in the industrial environment under the name of the Industrial Internet of Things (IIoT) concept, which is a sub-domain of IoT. The IIoT changes the way industrial processes are controlled and monitored, increasing operating efficiency. This article proposes a software architecture for IIoT that has a low degree of abstraction compared to the reference architectures presented in the literature. The architecture is organized on four-layer and it integrates the latest concepts related to fog and edge computing. These concepts are activated through the use of fog/edge/gateway nodes, where the processing of data acquired from things is performed and it is the place where things interact with each other in the virtual environment. The main contributions of this paper are the proposal and description of a complete IIoT software architecture, the use of a unified address space, and the use of the computing platform based on SoC (System on Chip) with specialized co-processors in order to be able to execute in real-time certain time-critical operations specific to the industrial environment.
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3,537 |
Therapeutic Uses of Red Macroalgae
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Red Seaweed “Rhodophyta” are an important group of macroalgae that include approximately 7000 species. They are a rich source of structurally diverse bioactive constituents, including protein, sulfated polysaccharides, pigments, polyunsaturated fatty acids, vitamins, minerals, and phenolic compounds with nutritional, medical, and industrial importance. Polysaccharides are the main components in the cell wall of red algae and represent about 40–50% of the dry weight, which are extensively utilized in industry and pharmaceutical compounds, due to their thickening and gelling properties. The hydrocolloids galactans carrageenans and agars are the main red seaweed cell wall polysaccharides, which had broad-spectrum therapeutic characters. Generally, the chemical contents of seaweed are different according to the algal species, growth stage, environment, and external conditions, e.g., the temperature of the water, light intensity, nutrient concentrations in the ecosystem. Economically, they can be recommended as a substitute source for natural ingredients that contribute to a broad range of bioactivities like cancer therapy, anti-inflammatory agents, and acetylcholinesterase inhibitory. This review touches on the main points of the pharmaceutical applications of red seaweed, as well as the exploitation of their specific compounds and secondary metabolites with vital roles.
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3,538 |
Factors Associated With Influential Health-Promoting Messages on Social Media: Content Analysis of Sina Weibo
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BACKGROUND: Social media is a powerful tool for the dissemination of health messages. However, few studies have focused on the factors that improve the influence of health messages on social media. OBJECTIVE: To explore the influence of goal-framing effects, information organizing, and the use of pictures or videos in health-promoting messages, we conducted a case study of Sina Weibo, a popular social media platform in China. METHODS: Literature review and expert discussion were used to determine the health themes of childhood obesity, smoking, and cancer. Web crawler technology was employed to capture data on health-promoting messages. We used the number of retweets, comments, and likes to evaluate the influence of a message. Statistical analysis was then conducted after manual coding. Specifically, binary logistic regression was used for the data analyses. RESULTS: We crawled 20,799 Sina Weibo messages and selected 389 health-promoting messages for this study. Results indicated that the use of gain-framed messages could improve the influence of messages regarding childhood obesity (P<.001), smoking (P=.03), and cancer (P<.001). Statistical expressions could improve the influence of messages about childhood obesity (P=.02), smoking (P=.002), and cancer (P<.001). However, the use of videos significantly improved the influence of health-promoting messages only for the smoking-related messages (P=.009). CONCLUSIONS: The findings suggested that gain-framed messages and statistical expressions can be successful strategies to improve the influence of messages. Moreover, appropriate pictures and videos should be added as much as possible when generating health-promoting messages.
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3,539 |
A one-year time frame for voice prosthesis management. What should the physician expect? Is it an overrated job?
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Management of late complications represents the main reason for reluctance in using voice prosthesis rehabilitation. The aim of this paper is to report our experience by describing the one-year management of a large cohort of patients in order to clarify how demanding management is in terms of burden on clinicians. Between June 2017 and June 2018, each access made at the Otolaryngology Clinic of our Institute for issues related to prosthesis by 70 laryngectomised patients rehabilitated by voice prosthesis was registered in a specific database. A review of the data provided information on the incidence, management and outcomes of adverse events encountered during the selected time frame. In addition, a T test was used to evaluate the differences between irradiated and non-irradiated patients and between primary and secondary tracheo-oesophageal-puncture. Leakage through the prosthesis was the most common cause for access (51.86%). The median number of accesses per patient per year was 3.47. The speech therapist autonomously managed 18.1% of accesses. The median number of accesses per patient per year needing a physician was 2.84. The median lifetime of the prosthesis was 4.85 months. Radiotherapy or modality (primary or secondary) of the puncture did not influence the number of accesses per year or the prosthesis lifetime. This retrospective analysis of results highlighted the most frequent issues and the most effective measures to deal with them, which allowed us to define a systematic algorithm to standardise and ease long-term outpatient management.
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3,540 |
Artificial Intelligence and Health in Nepal
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The growth in information technology and computer capacity has opened up opportunities to deal with much and much larger data sets than even a decade ago. There has been a technological revolution of big data and Artificial Intelligence (AI). Perhaps many readers would immediately think about robotic surgery or self-driving cars, but there is much more to AI. This Short Communication starts with an overview of the key terms, including AI, machine learning, deep learning and Big Data. This Short Communication highlights so developments of AI in health that could benefit a low-income country like Nepal and stresses the need for Nepal’s health and education systems to track such developments and apply them locally. Moreover, Nepal needs to start growing its own AI expertise to help develop national or South Asian solutions. This would require investing in local resources such as access to computer power/capacity as well as training young Nepali to work in AI.
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3,541 |
Contemporary Patterns of Multiple Organ Dysfunction in Trauma: Erratum
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3,542 |
The Emerging Role of Community Pharmacists in Remote Patient Monitoring Services
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Remote physiologic monitoring (RPM) services involve the transmission of patient-collected physiologic data to the healthcare team. These data are then analyzed to determine what changes may be needed to enhance patient care. While pharmacists may not be recognized as billing providers through some payers, there are opportunities for pharmacist collaboration with providers to enhance patient access to RPM services. Community pharmacist services are traditionally tied to a product, but pharmacists are skilled in medication management, disease state evaluation, and patient counseling, which are skills that can contribute to an elevated RPM program.
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3,543 |
Is There a Role for Absorbable Metals in Surgery? A Systematic Review and Meta-Analysis of Mg/Mg Alloy Based Implants
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Magnesium (Mg) alloys have received attention in the literature as potential biomaterials for use as absorbable implants in oral and maxillofacial and orthopedic surgery applications. This study aimed to evaluate the available clinical studies related to patients who underwent bone fixation (patients), and received conventional fixation (intervention), in comparison to absorbable metals (comparison), in terms of follow-up and complications (outcomes). A systematic review and meta-analysis were performed in accordance with the PRISMA statement and PROSPERO (CRD42020188654), PICO question, ROBINS-I, and ROB scales. The relative risk (RR) of complications and failures were calculated considering a confidence interval (CI) of 95%. Eight studies (three randomized clinical trial (RCT), one retrospective studies, two case-control studies, and two prospective studies) involving 468 patients, including 230 Mg screws and 213 Titanium (Ti) screws, were analyzed. The meta-analysis did not show any significant differences when comparing the use of Mg and Ti screws for complications (p = 0.868). The estimated complication rate was 13.3% (95% CI: 8.3% to 20.6%) for the comparison group who received an absorbable Mg screw. The use of absorbable metals is feasible for clinical applications in bone surgery with equivalent outcomes to standard metal fixation devices.
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3,544 |
Heterogeneous Influences of Social Support on Physical and Mental Health: Evidence from China
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Employing a national representative survey (the China Labor-force Dynamics Survey 2016, CLDS2016) data (N = 14246), this paper examines the heterogeneous influences of social support on individual physical and mental health in China. Social support is characterized by four dimensions: emotional support, tangible or instrumental support, interaction or exchange support, and community support. Physical health is measured by self-rated health and body mass index (BMI), while mental health is measured by depression, hopelessness, failure, fear, loneliness, and meaninglessness. The results indicate that different dimensions of social support have heterogeneous effects on individual physical and mental health. Specifically, the correlation between emotional support and individual physical health is not significant, but emotional support is significantly related to some mental health variables. Tangible or instrumental support is significantly related to individual self-rated physical health but not to BMI or mental health. Interaction or exchange support is significantly correlated with individual self-rated health and some mental health variables. In general, there are significant correlations between community support, and individual physical and mental health. The results also suggest that the influences of social support on physical and mental health of individuals at different ages (<60 years and ≥60 years) are heterogeneous. The results of this study provide direction for the dimension selection of social support to promote individual health.
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3,545 |
Community Pharmacists’ Perceptions of Patient Care Services within an Enhanced Service Network
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Background: Pharmacists are positioned as an accessible source of patient care services (PCS). Despite the adversity community pharmacies continue to face, the expanding opportunity of offering PCS continues to be a pathway forward. Objective: To identify community pharmacists’ perceptions to deliver PCS within an enhanced service network. Methods: One-on-one semi-structured phone interviews were conducted as part of a mixed-methods approach. Interview transcripts were analyzed using a consensus codebook to draft thematic findings. Participants were recruited from an electronic survey targeting community pharmacists from the New York chapters of the Community Pharmacy Enhanced Services Network (CPESN). Results: Twelve pharmacists were interviewed with four main themes identified. The majority of study participants were pharmacy owners (92%) devoting an average of 15 h/week to PCS and 8 h/week addressing social barriers. The main themes identified include: (1) perceptions of pharmacy profession, (2) reimbursement models and sustainability of PCS, (3) provision of patient care services, and (4) how PCS address social determinants of health. Conclusions: Offering PCS opportunities for patients is a direction many community pharmacists have embraced and are working to succeed. Ongoing research is needed focusing on community pharmacists’ self-perceptions of the clinical impact and role they hold in an evolving healthcare system.
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3,546 |
Identification of New Rofecoxib-Based Cyclooxygenase-2 Inhibitors: A Bioinformatics Approach
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The cyclooxygenase-2 receptor is a therapeutic target for planning potential drugs with anti-inflammatory activity. The selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was selected as a pivot molecule to perform virtual ligand-based screening from six commercial databases. We performed the search for similarly shaped Rapid Overlay of Chemical Structures (ROCS) and electrostatic (EON) compounds. After, we used pharmacokinetic and toxicological parameters to determine the best potential compounds, obtained through the softwares QikProp and Derek, respectively. Then, the compounds proceeded to the molecular anchorage study, which showed promising results of binding affinity with the hCOX-2 receptor: LMQC72 (∆G = −11.0 kcal/mol), LMQC36 (∆G = −10.6 kcal/mol), and LMQC50 (∆G = −10.2 kcal/mol). LMQC72 and LMQC36 showed higher binding affinity compared to rofecoxib (∆G = −10.4 kcal/mol). Finally, molecular dynamics (MD) simulations were used to evaluate the interaction of the compounds with the target hCOX-2 during 150 ns. In all MD simulation trajectories, the ligands remained interacting with the protein until the end of the simulation. The compounds were also complexing with hCOX-2 favorably. The compounds obtained the following affinity energy values: rofecoxib: ΔGbind = −45.31 kcal/mol; LMQC72: ΔGbind = −38.58 kcal/mol; LMQC36: ΔGbind = −36.10 kcal/mol; and LMQC50: ΔGbind = −39.40 kcal/mol. The selected LMQC72, LMQC50, and LMQC36 structures showed satisfactory pharmacokinetic results related to absorption and distribution. The toxicological predictions of these compounds did not display alerts for possible toxic groups and lower risk of cardiotoxicity compared to rofecoxib. Therefore, future in vitro and in vivo studies are needed to confirm the anti-inflammatory potential of the compounds selected here with bioinformatics approaches based on rofecoxib ligand.
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3,547 |
Promoting Equity, Social Justice, and Saving Lives with Life Jacket and Clothing Policies
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Worldwide, diverse racial/ethnic groups have disproportionately higher drowning rates. Learning to swim and wearing life jackets decrease drowning risk. We evaluated aquatic facilities’ policies regarding use of life jackets, clothing, and diapers through a lens of social justice, equity, and inclusion to ensure they met the needs of the diverse high-risk groups they serve and changing aquatic activities and programs. Public recreational pools, beach and waterpark facilities in the US and international organizations were surveyed regarding their policies on life jacket use, clothing, and diapers between 2015 and 2016. A total of 562 facilities responded, mostly pools. Almost all facilities allowed wearing life jackets in the shallow end but less so in the deep end, and wearing of T-shirts, shorts, and clothes for modesty reasons. Policies varied most on wearing non-swim clothes. Almost universal requirement of diapers applied to infants only. Respondents’ reported themes included cost, access, safety, hygiene and equipment maintenance. Reviewed policies generally reflected facilities’ responsiveness to diverse populations’ specific needs. However, policy variations around wearing clothing and swim diapers could be costly, confusing, and impede participation in aquatic activities by vulnerable populations, specifically young children and racial and ethnic minorities. Standardization of these policies could assist aquatic facilities and their users. A best-practices-based policy is outlined.
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3,548 |
Associations of Socio-Demographic, Clinical and Biochemical Parameters with Healthcare Cost, Health- and Renal-Related Quality of Life in Hemodialysis Patients: A Clinical Observational Study
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We examined factors associated with healthcare cost, health-related quality of life (HRQOL), and kidney disease quality of life (KDQOL) in hemodialysis patients. We conducted a cross-sectional study on 160 patients from January to April 2019 at a hemodialysis center. Socio-demographic, clinical, and laboratory parameters and quality of life (QOL) (using KDQOL-SF-v1.3) were assessed. Monthly healthcare costs were extracted from the hospital information system. The means of healthcare cost, HRQOL, and KDQOL were VND 9.4 ± 1.6 million, VND 45.1 ± 21.9 and VND 51.3 ± 13.0, respectively. In the multivariate analysis, the healthcare cost was higher in patients with a longer hemodialysis vintage (regression coefficient (B): 0.74; 95% confidence interval (95% CI): 0.25; 1.23), comorbidity (B: 0.77; 95% CI: 0.24; 1.31); and lower in those with a higher hematocrit concentration (B: −0.07; 95% CI: −0.13; −0.01). Patients that lived in urban areas (B: 9.08; 95% CI: 2.30; 15.85) had a better HRQOL; those with a comorbidity (B: −14.20; 95% CI: −21.43; −6.97), and with hypoalbuminemia (B: −9.31; 95% CI: −16.58; −2.04) had a poorer HRQOL. Patients with a higher level of education (B: 5.38~6.29) had a better KDQOL; those with a comorbidity had a poorer KDQOL (B: −6.17; 95% CI: −10.49; −1.85). In conclusion, a longer hemodialysis vintage, a comorbidity and a lower hematocrit concentration were associated with higher healthcare costs. Patients who lived in urban areas had a better HRQOL and a higher level of education led to a better KDQOL. Patients with a comorbidity had a lower HRQOL and KDQOL. Malnourished patients had a lower HRQOL.
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3,549 |
Psychosocial Aspects of Female Breast Cancer in the Middle East and North Africa
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Breast cancer, the most common cancer among women in the Middle East and North Africa (MENA) region, is associated with social and psychological implications deriving from women’s socio-cultural contexts. Examining 74 articles published between 2007 and 2019, this literature/narrative review explores the psychosocial aspects of female breast cancer in the MENA region. It highlights socio-cultural barriers to seeking help and socio-political factors influencing women’s experience with the disease. In 17 of 22 Arab countries, common findings emerge which derive from shared cultural values. Findings indicate that women lack knowledge of breast cancer screening (BCS) and breast cancer self-examination (BSE) benefits/techniques due to a lack of physicians’ recommendations, fear, embarrassment, cultural beliefs, and a lack of formal and informal support systems. Women in rural areas or with low socioeconomic status further lack access to health services. Women with breast cancer, report low self-esteem due to gender dynamics and a tendency towards fatalism. Collaboration between mass media, health and education systems, and leading social-religious figures plays a major role in overcoming psychological and cultural barriers, including beliefs surrounding pain, fear, embarrassment, and modesty, particularly for women of lower socioeconomic status and women living in crises and conflict zones.
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3,550 |
Resting-State Isolated Effective Connectivity of the Cingulate Cortex as a Neurophysiological Biomarker in Patients with Severe Treatment-Resistant Schizophrenia
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Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t(45) = 7.659, p = 0.008) and theta (t(45) = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.
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3,551 |
Heterologous Combination of ChAdOx1 and MVA Vectors Expressing Protein NS1 as Vaccination Strategy to Induce Durable and Cross-Protective CD8+ T Cell Immunity to Bluetongue Virus
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The sequence of non-structural protein NS1 of bluetongue virus (BTV), which contains immunodominant CD8+ T cell epitopes, is highly conserved among BTV serotypes, and has therefore become a major tool in the development of a universal BTV vaccine. In this work, we have engineered multiserotype BTV vaccine candidates based on recombinant chimpanzee adenovirus (ChAdOx1) and modified vaccinia virus Ankara (MVA) vectors expressing the NS1 protein of BTV-4 or its truncated form NS1-Nt. A single dose of ChAdOx1-NS1 or ChAdOx1-NS1-Nt induced a moderate CD8+ T cell response and protected IFNAR(-/-) mice against a lethal dose of BTV-4/MOR09, a reassortant strain between BTV-1 and BTV-4, although the animals showed low viremia after infection. Furthermore, IFNAR(-/-) mice immunized with a single dose of ChAdOx1-NS1 were protected after challenge with a lethal dose of BTV-8 in absence of viremia nor clinical signs. Additionally, the heterologous prime-boost ChAdOx1/MVA expressing NS1 or NS1-Nt elicited a robust NS1 specific CD8+ T cell response and protected the animals against BTV-4/MOR09 even 16 weeks after immunization, with undetectable levels of viremia at any time after challenge. Subsequently, the best immunization strategy based on ChAdOx1/MVA-NS1 was assayed in sheep. Non-immunized animals presented fever and viremia levels up to 10(4) PFU/mL after infection. In contrast, although viremia was detected in immunized sheep, the level of virus in blood was 100 times lower than in non-immunized animals in absence of clinical signs.
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3,552 |
True Negatives: Disseminating Research on Null, Inconclusive, and Confirmatory Findings in Cardiovascular Science
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3,553 |
Correlation study between blood cytokines and lymphocytes in early postoperative critical patients with compromised immune function
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Major surgery due to traumatic injury can activate early systemic postoperative pro-inflammatory responses and postoperative immunosuppression. However, the interaction between them is complex and not entirely clear. This study was performed in postoperative patients admitted to the intensive care unit (ICU) to elucidate the correlation between the systemic cellular immunity function and circulating cytokines levels in the early postoperative period. Twenty-four cases of postoperative patients admitted to the ICU were enrolled in this study. Twelve hours after admission, blood routine examination and measurement of circulating cytokines (interleukin-2 [IL-2], IL-4, IL-6, IL-10, IL-17A, interferon-γ, tumor necrosis factor-alpha [TNF-α], TNF-β, granulocyte-colony stimulating factor [G-CSF], and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were performed. The correlation analysis between cytokines levels and absolute peripheral blood lymphocyte count or lymphocytes/neutrophils ratio was analyzed. The cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, G-CSF, and GM-CSF) levels were increased above the normal upper limit at 12 hours after surgery. The number of leukocytes and neutrophils were markedly increased. In contrast, the absolute count and relative ratio of lymphocytes decreased below the lower normal limit. Spearman correlation analysis showed a moderate negative correlation between absolute peripheral blood lymphocyte count and IL-2 or IL-4 level. A low-negative correlation between absolute peripheral blood lymphocyte count and GM-CSF levels was detected. We also found that lymphocytes/neutrophils ratio was also negatively correlated with plasma IL-2, IL-4, or GM-CSF level. In ICU patients with compromised immune function in the early postoperative period, the elevated levels of IL-2, IL-4, and GM-CSF may be the compensatory responses to systemic immunosuppression.
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3,554 |
Erratum
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3,555 |
A second C-reactive protein (CRP) test to detect inflammatory burst in patients with acute bacterial infections presenting with a first relatively low CRP
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A first C-reactive protein (CRP) test, as often performed by clinicians during the presentation of patients with an acute bacterial infection, might be misleading. The aim of our study was to explore the dynamic between a second CRP test taken within 12 hours from admission CRP test in a cohort of patients diagnosed with acute bacterial infection in comparison to CRP in a control group of apparently healthy individuals. This was a historical cohort study comprised of all patients admitted to the Sourasky Tel-Aviv Medical Center, Israel, between July 2007 and March 2016. The study cohort included adult patients who were diagnosed as having an infection, assumed to be of bacterial etiology (cellulitis and erysipelas, pneumonia, cholecystitis, pyelonephritis, or septicemia), who had a CRP test during the first 6 hours of hospital admission (baseline CRP), and a successive CRP test up to 12 hours from the first one (recurrent CRP). The control group was of healthy subjects who attended our medical center for a routine annual check-up. The study included 950 patients. Baseline CRP ranged from 0.04 to 454 mg/L. The median CRP velocity was 0.53 mg/L/h. Patients were grouped by baseline CRP into 4 groups (CRP < 10, 10–74.9, 75–199.9, ≥200). There was an increase in median CRP velocity between the first (0.48 mg/L/h) and the second (0.93 mg/L/h) groups, which then was decreased in the next 2 groups (0.46 and −2.58 mg/L/h, respectively). In 45 of 103 (44%) patients of the group of baseline CRP concentration less than 10 mg/dL with bacterial diagnosis, there was a complete overlap with CRP values of apparently healthy individuals during their routine annual checkup. A first single low CRP result cannot exclude the presence of a significant bacterial infection. Patients with acute bacterial infection might present with a relatively low CRP value that at times correspond to normal limit CRP concentrations. A second test, obtained within 12 hours of admission, might serve as an important tool to identify patient with an evolving inflammatory burst commonly seen during acute bacterial infection.
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3,556 |
Knowledge, Attitudes, and Intentions towards HIV Pre-Exposure Prophylaxis among Nursing Students in Spain
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Human immunodeficiency virus (HIV) infection is one of the main causes of morbidity and mortality worldwide. Among the preventive approaches proposed to control this disease is pre-exposure prophylaxis (PrEP), whose effectiveness depends on the medication adherence. The aim of the present study was to determine the knowledge and attitudes about PrEP among a sample of Spanish nursing students as well as their intentions of receiving it in case it was indicated. An observational cross-sectional descriptive study was carried out. A total of 570 nursing students from the University of Santiago de Compostela (Spain), ≥18 years old and of both sexes were invited to self-complete a questionnaire between February and March 2020. A total of 352 students decided to participate in the study. Participants had low knowledge [overall knowledge score 1(0–2)] and a neutral attitude towards PrEP. The intention of receiving PrEP improved significantly after the completion of the questionnaire and the administration of information about PrEP (p = 0.039; before: 23.58% and after: 93.77%). Nursing staff play an important role in the prevention of sexually transmitted diseases, so their training in preventive strategies, such as PrEP, could help to reduce the incidence of new cases of HIV infection.
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3,557 |
Towards Distributed Recycling with Additive Manufacturing of PET Flake Feedstocks
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This study explores the potential to reach a circular economy for post-consumer Recycled Polyethylene Terephthalate (rPET) packaging and bottles by using it as a Distributed Recycling for Additive Manufacturing (DRAM) feedstock. Specifically, for the first time, rPET water bottle flake is processed using only an open source toolchain with Fused Particle Fabrication (FPF) or Fused Granular Fabrication (FGF) processing rather than first converting it to filament. In this study, first the impact of granulation, sifting, and heating (and their sequential combination) is quantified on the shape and size distribution of the rPET flakes. Then 3D printing tests were performed on the rPET flake with two different feed systems: an external feeder and feed tube augmented with a motorized auger screw, and an extruder-mounted hopper that enables direct 3D printing. Two Gigabot X machines were used, each with the different feed systems, and one without and the latter with extended part cooling. 3D print settings were optimized based on thermal characterization, and both systems were shown to 3D print rPET directly from shredded water bottles. Mechanical testing showed the importance of isolating rPET from moisture and that geometry was important for uniform extrusion. The mechanical strength of 3D-printed parts with FPF and inconsistent flow is lower than optimized fused filament, but adequate for a wide range of applications. Future work is needed to improve consistency and enable water bottles to be used as a widespread DRAM feedstock.
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3,558 |
Upper and Lower Respiratory Signs and Symptoms in Workers Occupationally Exposed to Flour Dust
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A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms. Fifty five percent of the bakers were allergic, and 37.1% showed sensitization to occupational allergens. Abnormal spirometries were found in 15% of bakers, while fractional exhaled nitric oxide (FeNO) was above the normal reference in 24.5% of them. Moreover, 23.8% of bakers were found to be hyposmic. Population mean peak nasal inspiratory flow (PNIF) was in the normal range even if almost all the workers suffered from neutrophilic rhinitis at nasal cytology with the number of nasal neutrophils increasing with the increase of the duration of exposure to flour dust (p = 0.03). PNIF and FEV1 (forced expiratory volume in the 1st second) showed a positive correlation (p = 0.03; r = 0.19). The Tiffeneau index decreased with the increase of dust (p = 0.017). A similar result was obtained once we divided our population into smokers and non-smokers (p = 0.021). Long-term exposure to bakery dusts can lead to a status of minimal nasal inflammation and allergy.
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3,559 |
Do Protected Areas Matter? A Systematic Review of the Social and Ecological Impacts of the Establishment of Protected Areas
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There is growing interest in evaluating the effects of establishing protected areas (PAs). However, the mechanisms through which the establishment of PAs achieved significant positive effects remain unclear, and how different conservation mechanisms have achieved significant positive social and ecological benefits has also not been sufficiently studied. In this study, we systematically reviewed exemplary cases from Asia, Africa, and South America, using panel data to assess the conservation effectiveness of nature reserves and national parks. By surveying 629 literature samples reported in 31 studies, we found that the establishment of PAs has positive influences on poverty reduction, family incomes, household expenditure, employment, forest cover, biodiversity, carbon sequestration, and a reduction in forest fragmentation. Furthermore, we analyzed the specific aspects that influence the publication of a paper in a high-impact journal. We found that publication is more likely when the research uses panel data, matching methods of data analysis, large samples, and plots or PAs as research units and has significant evaluation results. Our results suggest that future studies should use panel data and matching method analysis to assess the impacts of PAs from multiple perspectives and focus on the effectiveness of specific conservation mechanisms in achieving positive effects.
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3,560 |
Improvement of Dietary Diversity and Attitude toward Recommended Feeding through Novel Community Based Nutritional Education Program in Coastal Kenya—An Intervention Study
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Community-based nutritional intervention to improve the practice of dietary diversity and child nutrition by community health workers (CHWs) involving Nyumba Kumi as small neighborhood units (SNUs) in communities has not yet been explored. This study was conducted in two villages in rural Kenya between 2018 and 2019. In total, 662 participants (control vs. intervention: n = 339 vs. n = 323) were recruited. The intervention group received education on maternal and child nutrition and follow-up consultations. The custom-tailored educational guidelines were made based on Infant and Young Child Feeding and the mother and child health booklet. The educational effects on household caregivers’ feeding practice attitude and child nutritional status were analyzed using multiple linear regression. After the intervention, a total of 368 household caregivers (187 vs. 181) and 180 children (113 vs. 67) were analyzed separately. Between the groups, no significant difference was found in their background characteristics. This study successfully improved the dietary diversity score (β = 0.54; p < 0.01) and attitude score (β = 0.29; p < 0.01). The results revealed that the interventions using CHWs and SNUs were useful to improve dietary diversity and caregivers’ attitudes toward recommended feeding. This research has the potential to be successfully applied in other regions where child undernutrition remains.
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3,561 |
The Thermal Conductivity of 3D Printed Plastic Insulation Materials—The Effect of Optimizing the Regular Structure of Closures
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In the interest of environmental protection, attention should be paid to improving energy efficiency, through the use of appropriate insulations. They can be used in the construction industry, for plastic window frames, and the thermal insulation of buildings. It is also possible to use these materials in the electronics industry, for hermetic casings of devices, in the aviation industry, as well as in the food industry, as collective packaging for frozen food. The technology of using additive 3D printing to create prototype insulating materials made of plastic is proposed in this article. Multi-layer materials, with quadrangle, hexagonal, and triangle closures were designed and printed. A mathematical model was developed, and then experimentally verified. Quadrangle and hexagonal structures were shown to be useful, and triangle structures to be of little use. The optimal size of closure was determined to be 10 mm, with no convection, and 6 mm, with possible convection. The lowest thermal conductivity of the insulation was 0.0591 W/(m·K) for 10 mm single-layer quadrangle and hexagonal closures with an insulation density of 180 kg/m(3).
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3,562 |
Downside: The Perpetrator of Violence in the Representations of Social and Health Professionals
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Gender-based violence is a widespread phenomenon and pandemic that affects women’s lives. Many interventions have been activated for perpetrators, but the dropout rate is still high. In order to draw up guidelines for responsibly and sustainably dealing with the phenomenon, this study is aimed at investigating the professionals’ perception of the perpetrator as a useful element in designing innovative intervention policies. Open interviews were carried out with welfare and health professionals and the Grounded Theory Methodology was used to analyze the collected data. These results detect attitudes of social health personnel and their feelings of impotence towards gender-based perpetrators because of the emergence of an inevitable repetitiveness of the violent behavior, as well as the “normality of violence” in a patriarchal culture and its “transversality”. This reflective knowledge allows for the opportunity to develop best transformative attitudes toward the phenomenon. According to the results, it is urgent to establish an active and convinced alliance with the healthy part of the man, through specific prevention paths, in order to activate an authentic motivation for change and its sustainability.
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3,563 |
Nursing Education in Catalonia: Novice Professionals’ Appraisal of Its Quality and Usefulness. Does Mobility Play a Role?
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The present study aimed to examine the relationship between the quality of undergraduate education perceived by novice nurses and their retrospective satisfaction with their education. It also studied the relationships between the perceived usefulness of their education for their current jobs and the quality of the jobs held by novice nursing professionals. The moderator role of mobility in this relationship was also analyzed, as it reflects a boundary condition in which additional preparation or job opportunities may occur. The study used data from the graduates’ survey carried out by the Agència per a la Qualitat del Sistema Universitari de Catalunya (AQU) in 2017. The analysis of data from 644 graduates of Catalan Universities in 2014 highlights different functions of two types of knowledge and skills; those directly related to science and the practice of nursing are stronger predictors of retrospective satisfaction with nursing education. In turn, the perception of the usefulness of horizontal skills, such as transversal and communication skills, plays a stronger role in predicting job quality. The results about the role of mobility were not conclusive, and more research is needed to clarify its influence on nursing education and subsequent professional practice.
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3,564 |
The Importance of Genuineness in Public Engagement—An Exploratory Study of Pediatric Communication on Social Media in China
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There is a growing need for the public to interact with pediatricians through social media in China, and genuineness is a crucial factor contributing to effective communication, but few studies have examined the relationship between genuineness and its effect on public engagement. This study developed a four-dimension framework including self-disclosure, genuine response, functional interactivity, and genuineness in Chinese culture to investigate the effect of genuineness in the communication of Chinese social media influencers in pediatrics on public engagement. Content analysis was employed to examine these dimensions and the related public engagement in 300 social media posts on the largest microblogging site in China. The findings indicate that genuine response was positively associated with the number of comments and positive comments, while negatively related to the number of shares. Functional interactivity made the site more appealing, resulting in likes and shares. Genuineness in Chinese culture was reflected in engagement through sharing posts by the public. This study is the first to develop an integrated framework to measure genuineness in online health communication and contributes to the understanding of the effect of genuineness on Chinese public engagement in social media.
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3,565 |
Tuberculosis and Other Airborne Microbes in Occupational Health and Safety
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Airborne pathogens and non-malignant infectious diseases such as tuberculosis are highly contagious and can have severe effects on healthcare workers. The symptoms of these diseases take time to manifest, which can prevent workers from noticing that they have been exposed until symptoms appear. The current paper sought to assess the occupational safety and preventative measures taken in laboratories in Spain, and to compare these measures with those reported by other studies worldwide. A cross-sectional study of workers (35–50 years old) was conducted using a web survey (N = 30), and a bibliometric analysis was carried out in the Scopus database (92 documents were selected). The occupational safety and health measures were inadequate, according to the opinions of the workers. The training (p < 0.01), the amount of work (p < 0.05), and how the workers followed their protocols (p < 0.001) were linked to incidents and exposure to airborne pathogens. The most significant previous publication was a report (848 citations) stating that the previous variables linked to exposure are vital for prevention. Most works focused on countries like the U.S.A. (p = 0.009) were reviews, with a limited number of studies focused on occupational safety.
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3,566 |
University Students’ Purchase Intention and Willingness to Pay for Carbon-Labeled Food Products: A Purchase Decision-Making Experiment
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Carbon labeling describes carbon dioxide emissions across food lifecycles, contributing to enhancing consumers’ low-carbon awareness and promoting low-carbon consumption behaviors. In a departure from the existing literature on carbon labeling that heavily relies on interviews or questionnaire surveys, this study forms a hybrid of an auction experiment and a consumption experiment to observe university students’ purchase intention and willingness to pay for a carbon-labeled food product. In this study, students from a university in a city (Chengdu) of China, the largest carbon emitter, are taken as the experimental group, and cow’s milk is selected as the experimental food product. The main findings of this study are summarized as follows: (1) the purchase of carbon-labeled milk products is primarily influenced by price; (2) the willingness to pay for carbon-labeled milk products primarily depends on the premium; and (3) the students are willing to accept a maximum price premium of 3.2%. This study further offers suggestions to promote the formation of China’s carbon product-labeling system and the marketization of carbon-labeled products and consequently facilitate low-carbon consumption in China.
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3,567 |
Modeling Product Manufacturing Reliability with Quality Variations Centered on the Multilayered Coupling Operational Characteristics of Intelligent Manufacturing Systems
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For intelligent manufacturing systems, there are many deviations in operational characteristics, and the coupling effect of harmful operational characteristics leads to the variations in quality of the work-in-process (WIP) and the degradation of the reliability of the finished product, which is reflected as a loss of product manufacturing reliability. However, few studies on the modeling of product manufacturing reliability and mechanism analysis consider the operating mechanism and the coupling of characteristics. Thus, a novel modeling approach based on quality variations centered on the coupling of operational characteristics is proposed to analyze the formation mechanism of product manufacturing reliability. First, the PQR chain containing the co-effects among the manufacturing system performance (P), the manufacturing process quality (Q), and the product manufacturing reliability (R) is elaborated. The connotation of product manufacturing reliability is defined, multilayered operational characteristics are determined, and operational data are collected by smart sensors. Second, on the basis of the coupling effect in the PQR chain, a multilayered product quality variation model is proposed by mining operational characteristic data obtained from sensors. Third, an integrated product manufacturing reliability model is presented on the basis of the variation propagation mechanism of the multilayered product quality variation model. Finally, a camshaft manufacturing reliability analysis is conducted to verify the validity of the proposed method. The method proposed in this paper proved to be effective for evaluating and predicting the product reliability in the smart manufacturing process.
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3,568 |
Spanish Costaleros’ Physical Activity and Their Quality of Life
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(1) Physical activity is one of the most influencing factors in people’ quality of life. Likewise, the costaleros of the Holy Week of Andalusia (Spain) carry out an important effort with high intensity during an extended time without any preparation. This study was the aim of knowing the intensity of the physical activity practiced by the costaleros in relation to their quality of life. (2) A transversal study was carried out with 1057 costaleros in Andalusia (Spain), where 930 were male and 127 female, between the ages of 18–61 years old (31.26 ± 7.60). For this purpose, descriptive, inferential, and correlative analyses were developed. Accelerometers (ActiGraph) were used during the procession to know the intensity of physical activity and the SF-36 test to know the self-perceived state of health and quality of life. (3) The intensity of physical activity practiced by costaleros is moderate, and it is related with their quality of life. In addition, positive associations are found between general health and physical activity. (4) Participants’ quality of life is associated with physical activity and freedom from injury. In addition, the measurement by accelerometry provides real data on the intensity of the effort made.
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3,569 |
Metabolomics in Sleep, Insomnia and Sleep Apnea
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Sleep-wake disorders are highly prevalent disorders, which can lead to negative effects on cognitive, emotional and interpersonal functioning, and can cause maladaptive metabolic changes. Recent studies support the notion that metabolic processes correlate with sleep. The study of metabolite biomarkers (metabolomics) in a large-scale manner offers unique opportunities to provide insights into the pathology of diseases by revealing alterations in metabolic pathways. This review aims to summarize the status of metabolomic analyses-based knowledge on sleep disorders and to present knowledge in understanding the metabolic role of sleep in psychiatric disorders. Overall, findings suggest that sleep-wake disorders lead to pronounced alterations in specific metabolic pathways, which might contribute to the association of sleep disorders with other psychiatric disorders and medical conditions. These alterations are mainly related to changes in the metabolism of branched-chain amino acids, as well as glucose and lipid metabolism. In insomnia, alterations in branched-chain amino acid and glucose metabolism were shown among studies. In obstructive sleep apnea, biomarkers related to lipid metabolism seem to be of special importance. Future studies are needed to examine severity, subtypes and treatment of sleep-wake disorders in the context of metabolite levels.
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3,570 |
Analysis of the Codon Usage Pattern of HA and NA Genes of H7N9 Influenza A Virus
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Novel H7N9 influenza virus transmitted from birds to human and, since March 2013, it has caused five epidemic waves in China. Although the evolution of H7N9 viruses has been investigated, the evolutionary changes associated with codon usage are still unclear. Herein, the codon usage pattern of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), was studied to understand the evolutionary changes in relation to host, epidemic wave, and pathogenicity. Both genes displayed a low codon usage bias, with HA higher than NA. The codon usage was driven by mutation pressure and natural selection, although the main contributing factor was natural selection. Additionally, the codon adaptation index (CAI) and deoptimization (RCDI) illustrated the strong adaptability of H7N9 to Gallus gallus. Similarity index (SiD) analysis showed that Homo sapiens posed a stronger selection pressure than Gallus gallus. Thus, we assume that this may be related to the gradual adaptability of the virus to human. In addition, the host strong selection pressure was validated based on CpG dinucleotide content. In conclusion, this study analyzed the usage of codons of two genes of H7N9 and expanded our understanding of H7N9 host specificity. This aids into the development of control measures against H7N9 influenza virus.
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3,571 |
The Application of Porphyrins and Their Analogues for Inactivation of Viruses
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The problem of treating viral infections is extremely relevant due to both the emergence of new viral diseases and to the low effectiveness of existing approaches to the treatment of known viral infections. This review focuses on the application of porphyrin, chlorin, and phthalocyanine series for combating viral infections by chemical and photochemical inactivation methods. The purpose of this review paper is to summarize the main approaches developed to date in the chemical and photodynamic inactivation of human and animal viruses using porphyrins and their analogues and to analyze and discuss the information on viral targets and antiviral activity of porphyrins, chlorins, of their conjugates with organic/inorganic compounds obtained in the last 10–15 years in order to identify the most promising areas.
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3,572 |
Adaptive Estimation for Epidemic Renewal and Phylogenetic Skyline Models
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Estimating temporal changes in a target population from phylogenetic or count data is an important problem in ecology and epidemiology. Reliable estimates can provide key insights into the climatic and biological drivers influencing the diversity or structure of that population and evidence hypotheses concerning its future growth or decline. In infectious disease applications, the individuals infected across an epidemic form the target population. The renewal model estimates the effective reproduction number, R, of the epidemic from counts of observed incident cases. The skyline model infers the effective population size, N, underlying a phylogeny of sequences sampled from that epidemic. Practically, R measures ongoing epidemic growth while N informs on historical caseload. While both models solve distinct problems, the reliability of their estimates depends on p-dimensional piecewise-constant functions. If p is misspecified, the model might underfit significant changes or overfit noise and promote a spurious understanding of the epidemic, which might misguide intervention policies or misinform forecasts. Surprisingly, no transparent yet principled approach for optimizing p exists. Usually, p is heuristically set, or obscurely controlled via complex algorithms. We present a computable and interpretable p-selection method based on the minimum description length (MDL) formalism of information theory. Unlike many standard model selection techniques, MDL accounts for the additional statistical complexity induced by how parameters interact. As a result, our method optimizes p so that R and N estimates properly and meaningfully adapt to available data. It also outperforms comparable Akaike and Bayesian information criteria on several classification problems, given minimal knowledge of the parameter space, and exposes statistical similarities among renewal, skyline, and other models in biology. Rigorous and interpretable model selection is necessary if trustworthy and justifiable conclusions are to be drawn from piecewise models. [Coalescent processes; epidemiology; information theory; model selection; phylodynamics; renewal models; skyline plots]
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3,573 |
Full-Spectrum Analysis of Bioactive Compounds in Rosemary (Rosmarinus officinalis L.) as Influenced by Different Extraction Methods
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Rosmarinus officinalis is a potent antioxidant herb rich in polyphenols. Ultra-high-performance liquid chromatography, coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS), enables an exhaustive, full-spectrum analysis of the molecular constituents of natural products. The study aimed to develop a rapid UHPLC method to contribute new insights into the phytochemical composition of rosemary and to assess the performance of nine different procedures for extraction. These include fresh tissue homogenization, fresh and dry leaf decoction, and their respective fermentation, Soxhlet extraction, and sonication using water and methanol. Different extraction methods were found to recover quite different groups of polyphenols within 11 min during 20 min of analysis. Soxhlet extraction, yielded very high concentrations of rosmarinic acid (33,491.33 ± 86.29 µg/g), luteolin-7-O-glucoside (209.95 ± 8.78 µg/g), carnosic acid (2915.40 ± 33.23 µg/g), carnosol (22,000.67 ± 77.39 µg/g), and ursolic acid (5144.27 ± 28.68 µg/g). UHPLC-ESI-QTOF-MS enabled the detection of more than 50 polyphenols, including phenolic acids, flavonoids, and terpenoids in the various extracts. Of these, sagerinic acid ([M − H](−) m/z 719.16), salvianolic acid A ([M − H](−) m/z 493.11) and B ([M − H](−) m/z 717.15), and a pentacyclic triterpenoid corosolic acid ([M − H](−) m/z 471.34) were detected for the first time in rosemary. Soxhlet extraction was found to be the most efficient method, followed by dry leaf decoction. The UHPLC-ESI-QTOF-MS methodology for the analysis proved to be very efficient in the identification and characterization of targeted and untargeted bioactive molecules in the rosemary.
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3,574 |
Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?
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The recent identification of senescent cells in periodontal tissues has the potential to provide new insights into the underlying mechanisms of periodontal disease etiology. DNA damage-driven senescence is perhaps one of the most underappreciated delayed consequences of persistent Gram-negative bacterial infection and inflammation. Although the host immune response rapidly protects against bacterial invasion, oxidative stress generated during inflammation can indirectly deteriorate periodontal tissues through the damage to vital cell macromolecules, including DNA. What happens to those healthy cells that reside in this harmful environment? Emerging evidence indicates that cells that survive irreparable genomic damage undergo cellular senescence, a crucial intermediate mechanism connecting DNA damage and the immune response. In this review, we hypothesize that sustained Gram-negative bacterial challenge, chronic inflammation itself, and the constant renewal of damaged tissues create a permissive environment for the abnormal accumulation of senescent cells. Based on emerging data we propose a model in which the dysfunctional presence of senescent cells may aggravate the initial immune reaction against pathogens. Further understanding of the role of senescent cells in periodontal disease pathogenesis may have clinical implications by providing more sophisticated therapeutic strategies to combat tissue destruction.
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3,575 |
Molecular Characterization and Developing a Point-of-Need Molecular Test for Diagnosis of Bovine Papillomavirus (BPV) Type 1 in Cattle from Egypt
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SIMPLE SUMMARY: Bovine papillomatosis is a disease caused by bovine papillomavirus (BPV), which is a diverse group of oncogenic viruses that challenge cattle industry, resulting in significant economic losses. The present study investigated the occurrence of bovine papillomatosis among cattle (n = 308) with cutaneous warts on the head and neck from New valley Province, Egypt through molecular detection of BPV-1, -2, -4, -5, and -10. The work also involved a phylogenetic analysis of the positive samples for detection of the genetic relatedness of the virus. Interestingly, BPV-1 DNA was detected in 84.6% of the collected samples. Furthermore, the study included the development of an isothermal nucleic acid amplification test, which is a field test combining molecular and lateral flow immunoassays for point-of-need testing appropriate for veterinary use in resource-limited settings. Collectively, our study provided interesting data related to the combined use of molecular and immunoassays methods in the detection of the virus besides better understanding the genetic relatedness of the circulating genotypes of BPV-1 in Egypt. Our study suggested further research to explore more about the other genotypes of BPV in the Egyptian environment that could be helpful for the implementation of control strategies for combating this disease. ABSTRACT: Bovine papillomatosis is a viral disease of cattle causing cutaneous warts. A diagnosis of this viral infection is very mandatory for combating the resulting economic losses. Given the limited data available about bovine papillomavirus (BPV) in Egypt, the present study involved the molecular diagnosis of bovine papillomavirus type-1 (BPV-1), -2, -4, -5, and -10 in cattle presenting cutaneous warts on the head and neck from New Valley Province, Egypt. The phylogenetic analysis of the detected types of BPV was also performed, followed by developing a point-of-need molecular assay for the rapid identification of identified BPV types. In this regard, a total of 308 cattle from private farms in Egypt were clinically examined, of which 13 animals presented cutaneous warts due to suspected BPV infection. The symptomatic animals were treated surgically, and biopsies from skin lesions were collected for BPV-1, -2, -4, -5, and -10 molecular identification using polymerase chain reaction (PCR). The presence of BPV-1 DNA was confirmed in 11 collected samples (84.6%), while BPV-2, -4, -5, and -10 were not detected. Sequencing of the PCR products suggested the Egyptian virus is closely related to BPV found in India. An isothermal nucleic acid amplification test (NAAT) with labeled primers specific for the BPV-1 L1 gene sequence, and based on recombinase polymerase amplification (RPA), in combination with a lateral flow strip assay for the detection of RPA products, was developed and tested. The point-of-need molecular assay demonstrated a diagnostic utility comparable to PCR-based testing. Taken together, the present study provides interesting molecular data related to the occurrence of BPV-1 in Egypt and reveals the genetic relatedness of the Egyptian BPV-1 with BPV-1 found in buffalo in India. In addition, a simple, low-cost combined test was also validated for diagnosis of the infection. The present study suggests the necessity of future investigations about the circulating strains of the virus among the cattle in Egypt to assess their genetic relatedness and better understand the epidemiological pattern of the disease.
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3,576 |
Rapid Expansion of Virus-Specific CD4(+) T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus
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The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4(+) T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4(+) T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4(+) T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4(+) T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3(+)CD4(+) T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3(+)CD4(+) T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4(+) T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease.
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3,577 |
High-Precision CO(2) Column Length Analysis on the Basis of a 1.57-μm Dual-Wavelength IPDA Lidar
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For high-precision measurements of the CO(2) column concentration in the atmosphere with airborne integrated path differential absorption (IPDA) Lidar, the exact distance of the Lidar beam to the scattering surface, that is, the length of the column, must be measured accurately. For the high-precision inversion of the column length, we propose a set of methods on the basis of the actual conditions, including autocorrelation detection, adaptive filtering, Gaussian decomposition, and optimized Levenberg–Marquardt fitting based on the generalized Gaussian distribution. Then, based on the information of a pair of laser pulses, we use the direct adjustment method of unequal precision to eliminate the error in the distance measurement. Further, the effect of atmospheric delay on distance measurements is considered, leading to further correction of the inversion results. At last, an airborne experiment was carried out in a sea area near Qinhuangdao, China on 14 March 2019. The results showed that the ranging accuracy can reach 0.9066 m, which achieved an excellent ranging accuracy on 1.57-μm IPDA Lidar and met the requirement for high-precision CO(2) column length inversion.
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3,578 |
Targeted Therapy of Hepatocellular Carcinoma Using Gemcitabine-Incorporated GPC3 Aptamer
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Hepatocellular carcinoma (HCC) is the most common malignancy of the liver, which can progress rapidly and has a poor prognosis. Glypican-3 (GPC3) has been proposed to be an important diagnostic biomarker and therapeutic target for HCC. Aptamers have emerged as promising drug delivery vehicles because of their high binding affinity for target molecules. Herein, we developed G12msi, a gemcitabine-incorporated DNA aptamer, targeting GPC3, and evaluated its binding specificity and anti-tumor efficacy in GPC3-overexpressing HCC cell lines and murine xenograft models. GPC3-targeted aptamers were selected by using the SELEX process and the chemotherapy drug gemcitabine was internally incorporated into the aptamer. To determine the binding affinity and internalization of the G12msi, flow cytometry and confocal microscopy were performed on GPC3-positive HepG2, Hep3B, and Huh7 cells, as well as a GPC3-negative A431 cell. The anti-tumor activities of G12msi were evaluated with in vitro and in vivo models. We found that G12msi binds to GPC3-overexpressing HCC tumor cells with high specificity and is effectively internalized. Moreover, G12msi treatment inhibited the cell proliferation of GPC3-positive HCC cell lines with minimal cytotoxicity in control A431 cells. In vivo systemic administration of G12msi significantly inhibited tumor growth of HCC HepG2 cells in xenograft models without causing toxicity. These results suggest that gemcitabine-incorporated GPC3 aptamer-based drug delivery may be a promising strategy for the treatment of HCC.
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3,579 |
Roma Health: An Overview of Communicable Diseases in Eastern and Central Europe
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The Roma are Europe’s largest minority. They are also one of its most disadvantaged, with low levels of education and health and high levels of poverty. Research on Roma health often reveals higher burdens of disease in the communities studied. This paper aims to review the literature on communicable diseases among Roma across Eastern and Central Europe. A PubMed search was carried out for communicable diseases among Roma in these parts of Europe, specifically in Romania, Bulgaria, Hungary, Serbia, Slovakia, the Czech Republic and North Macedonia. The papers were then screened for relevance and utility. Nineteen papers were selected for review; most of them from Slovakia. Roma continue to have a higher prevalence of communicable diseases and are at higher risk of infection than the majority populations of the countries they live in. Roma children in particular have a particularly high prevalence of parasitic disease. However, these differences in disease prevalence are not present across all diseases and all populations. For example, when Roma are compared to non-Roma living in close proximity to them, these differences are often no longer significant.
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3,580 |
Improving the Quality of Care in Care Homes Using the Quality Improvement Collaborative Approach: Lessons Learnt from Six Projects Conducted in the UK and The Netherlands
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The Breakthrough Series Quality Improvement Collaborative (QIC) initiative is a well-developed and widely used approach, but most of what we know about it has come from healthcare settings. In this article, those leading QICs to improve care in care homes provide detailed accounts of six QICs and share their learning of applying the QIC approach in the care home sector. Overall, five care home-specific lessons were learnt: (i) plan for the resources needed to support collaborative teams with collecting, processing, and interpreting data; (ii) create encouraging and safe working environments to help collaborative team members feel valued; (iii) recruit collaborative teams, QIC leads, and facilitators who have established relationships with care homes; (iv) regularly check project ideas are aligned with team members’ job roles, responsibilities, and priorities; and (v) work flexibly and accept that planned activities may need adapting as the project progresses. These insights are targeted at teams delivering QICs in care homes. These insights demonstrate the need to consider the care home context when applying improvement tools and techniques in this setting.
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3,581 |
Towards an Integral Therapeutic Protocol for Breast Cancer Based upon the New H(+)-Centered Anticancer Paradigm of the Late Post-Warburg Era
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A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H(+)) dynamics of cancer, allows for the understanding and integration of the many dualisms, confusions, and paradoxes of the disease. The new H(+)-related, wide-ranging model can embrace, from a unique perspective, the many aspects of the disease and, at the same time, therapeutically interfere with most, if not all, of the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC reviewed here may be beneficial for all types and stages of the disease. In this vein, we have attempted a megasynthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide-ranging approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of the pH-related drugs that are available nowadays for the treatment of breast cancer is advanced.
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3,582 |
Antibody Response to Canine Adenovirus-2 Virus Vaccination in Healthy Adult Dogs
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Background: Re-vaccination against canine adenovirus (CAV) is performed in ≤3-year-intervals but its necessity is unknown. The study determined anti-CAV antibodies within 28 days of re-vaccination and factors associated with the absence of antibodies and vaccination response. Methods: Ninety-seven healthy adult dogs (last vaccination ≥12 months) were re-vaccinated with a modified live CAV-2 vaccine. Anti-CAV antibodies were measured before vaccination (day 0), and after re-vaccination (day 7, 28) by virus neutralization. A ≥4-fold titer increase was defined as vaccination response. Fisher’s exact test and multivariate regression analysis were performed to determine factors associated with the absence of antibodies and vaccination response. Results: Totally, 87% of dogs (90/97; 95% CI: 85.61–96.70) had anti-CAV antibodies (≥10) before re-vaccination. Vaccination response was observed in 6% of dogs (6/97; 95% CI: 2.60–13.11). Time since last vaccination (>3–5 years, OR = 9.375, p = 0.020; >5 years, OR = 25.000, p = 0.006) was associated with a lack of antibodies. Dogs from urban areas were more likely to respond to vaccination (p = 0.037). Conclusion: Many dogs had anti-CAV pre-vaccination antibodies, even those with an incomplete vaccination series. Most dogs did not respond to re-vaccination. Based on this study, dogs should be re-vaccinated every 3 years or antibodies should be determined.
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3,583 |
Effect of Tourist Activities on Fecal and Salivary Glucocorticoids and Immunoglobulin A in Female Captive Asian Elephants in Thailand
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SIMPLE SUMMARY: How tourist camp activities affect individual elephant welfare is an important and highly debated topic. Saliva and fecal samples were collected monthly for 1 year from 44 female Asian elephants that participated in three programs (saddle-, bareback-, or no-riding), and analyzed for glucocorticoids (GC) and immunoglobulin A (IgA). The hypothesis was that better welfare would be associated with low GC and high IgA concentrations. Both biomarkers showed significant variation with respect to camp size, riding activities, tourist-to-elephant ratios and seasonality, but not always consistently between feces and saliva, and not always in the predicted direction. However, there was no clear indication that riding per se negatively affected these two biomarkers. The lack of consistent responses highlights the difficulty in interpreting physiological data in relation to management factors, and suggests more work is needed to differentiate between potential chronic (feces) and acute (saliva) responses. ABSTRACT: Asian elephants have been an important part of wildlife ecotourism in Thailand for over two decades. Elephants in tourist camps are exposed to a variety of management styles and daily activities that can potentially affect health and welfare. This study investigated relationships between a novel welfare biomarker, immunoglobulin A (IgA), and daily camp activities, and compared results to glucocorticoid (GC) measures. Often no-riding camps are portrayed as providing better welfare than camps that offer riding. Therefore, we predicted that elephants at no-riding camps would have lower GC and higher IgA concentrations, and a low GC/IgA ratio. Forty-four female elephants from six elephant camps were divided into three groups based on riding activities: saddle-riding, bareback-riding, and no-riding. Fecal and salivary samples were collected monthly for 1 year along with evaluations of body condition, foot health, and wounding. Camp environment and management varied among camps, although the major difference was in riding activities. Concentrations of GCs and IgA varied among the working groups, but not always consistently between sample matrices. Overall fecal glucocorticoid metabolite concentrations were lowest in the saddle-riding group. Only in one bareback-riding camp did the elephants exhibit a potentially positive welfare response with a low GC/IgA ratio over time. Other results varied between the two biomarkers, with considerable variability across camps, suggesting there is more to good welfare than whether elephants participate in riding or not. Several other human-induced stressors, like chaining, ankus use, and limited social opportunities are likely to be impacting well-being and should be considered to ensure management practices meet physical and psychological welfare needs.
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3,584 |
Extracellular Vesicle-Based Nucleic Acid Delivery: Current Advances and Future Perspectives in Cancer Therapeutic Strategies
|
Extracellular vesicles (EVs) are sophisticated and sensitive messengers released by cells to communicate with and influence distant and neighboring cells via selective transfer of bioactive content, including protein lipids and nucleic acids. EVs have therefore attracted broad interest as new and refined potential therapeutic systems in many diseases, including cancer, due to their low immunogenicity, non-toxicity, and elevated bioavailability. They might serve as safe and effective vehicles for the transport of therapeutic molecules to specific tissues and cells. In this review, we focus on EVs as a vehicle for gene therapy in cancer. We describe recent developments in EV engineering to achieve efficient intracellular delivery of cancer therapeutics and avoid off-target effects, to provide an overview of the potential applications of EV-mediated gene therapy and the most promising biomedical advances.
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3,585 |
Neuronal octopamine signaling regulates mating-induced germline stem cell increase in female Drosophila melanogaster
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Stem cells fuel the development and maintenance of tissues. Many studies have addressed how local signals from neighboring niche cells regulate stem cell identity and their proliferative potential. However, the regulation of stem cells by tissue-extrinsic signals in response to environmental cues remains poorly understood. Here we report that efferent octopaminergic neurons projecting to the ovary are essential for germline stem cell (GSC) increase in response to mating in female Drosophila. The neuronal activity of the octopaminergic neurons is required for mating-induced GSC increase as they relay the mating signal from sex peptide receptor-positive cholinergic neurons. Octopamine and its receptor Oamb are also required for mating-induced GSC increase via intracellular Ca(2+) signaling. Moreover, we identified Matrix metalloproteinase-2 as a downstream component of the octopamine-Ca(2+) signaling to induce GSC increase. Our study provides a mechanism describing how neuronal system couples stem cell behavior to environmental cues through stem cell niche signaling.
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3,586 |
Mortality prediction models, causal effects, and end-of-life decision making in the intensive care unit
| null |
3,587 |
Detection of West Nile virus in a common whitethroat (Curruca communis) and Culex mosquitoes in the Netherlands, 2020
|
On 22 August, a common whitethroat in the Netherlands tested positive for West Nile virus lineage 2. The same bird had tested negative in spring. Subsequent testing of Culex mosquitoes collected in August and early September in the same location generated two of 44 positive mosquito pools, providing first evidence for enzootic transmission in the Netherlands. Sequences generated from the positive mosquito pools clustered with sequences that originate from Germany, Austria and the Czech Republic.
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3,588 |
Molecular Characterization of Influenza C Viruses from Outbreaks in Hong Kong SAR, China
|
In 2014, the Centre for Health Protection in Hong Kong introduced screening for influenza C virus (ICV) as part of its routine surveillance for infectious agents in specimens collected from patients presenting with symptoms of respiratory viral infection, including influenza-like illness (ILI). A retrospective analysis of ICV detections up to week 26 of 2019 revealed persistent low-level circulation, with two outbreaks having occurred in the winters of 2015 to 2016 and 2017 to 2018. These outbreaks occurred at the same time as, and were dwarfed by, seasonal epidemics of influenza types A and B. Gene sequencing studies on stored ICV-positive clinical specimens from the two outbreaks have shown that the hemagglutinin-esterase (HE) genes of the viruses fall into two of the six recognized genetic lineages (represented by C/Kanagawa/1/76 and C/São Paulo/378/82), with there being significant genetic drift compared to earlier circulating viruses within both lineages. The location of a number of encoded amino acid substitutions in hemagglutinin-esterase fusion (HEF) glycoproteins suggests that antigenic drift may also have occurred. Observations of ICV outbreaks in other countries, with some of the infections being associated with severe disease, indicates that ICV infection has the potential to have significant clinical and health care impacts in humans. IMPORTANCE Influenza C virus infection of humans is common, and reinfection can occur throughout life. While symptoms are generally mild, severe disease cases have been reported, but knowledge of the virus is limited, as little systematic surveillance for influenza C virus is conducted and the virus cannot be studied by classical virologic methods because it cannot be readily isolated in laboratories. A combination of systematic surveillance in Hong Kong SAR, China, and new gene sequencing methods has been used in this study to assess influenza C virus evolution and provides evidence for a 2-year cycle of disease outbreaks. The results of studies like that reported here are key to developing an understanding of the impact of influenza C virus infection in humans and how virus evolution might be associated with epidemics.
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3,589 |
Pneumomediastino em um paciente com COVID-19
| null |
3,590 |
Forecasting influenza in Europe using a metapopulation model incorporating cross-border commuting and air travel
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Past work has shown that models incorporating human travel can improve the quality of influenza forecasts. Here, we develop and validate a metapopulation model of twelve European countries, in which international translocation of virus is driven by observed commuting and air travel flows, and use this model to generate influenza forecasts in conjunction with incidence data from the World Health Organization. We find that, although the metapopulation model fits the data well, it offers no improvement over isolated models in forecast quality. We discuss several potential reasons for these results. In particular, we note the need for data that are more comparable from country to country, and offer suggestions as to how surveillance systems might be improved to achieve this goal.
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3,591 |
Three-gene prognostic biomarkers for seminoma identified by weighted gene co-expression network analysis
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Testicular germ cell tumors (TGCTs) are common in young males, and seminoma accounts for a large proportion of TGCTs. However, there are limited records on the exploration of novel biomarkers for seminoma. Hence, we aimed to identify new biomarkers associated with overall survival in seminoma. mRNA-seq and clinical traits of TGCTs were downloaded from UCSC XENA and analyzed by weighted gene co-expression network analysis. After intersection with differentially expressed genes in GSE8607, common genes were subjected to protein-protein interaction (PPI) network construction and enrichment analyses. Then, the top 10 common genes were investigated by Kaplan–Meier (KM) survival analyses and univariate Cox regression analyses. Ultimately, TYROBP, CD68, and ITGAM were considered three prognostic biomarkers in seminoma. Based on correlation analysis between these genes and immune infiltrates, we suggest that the three biomarkers influence the survival of seminoma patients, possibly through regulating the infiltration of immune cells. In conclusion, our study demonstrated that TYROBP, CD68, and ITGAM could be regarded as prognostic biomarkers and therapeutic targets for seminoma patients.
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3,592 |
DDX56 Binds to Chikungunya Virus RNA To Control Infection
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DEAD box RNA helicases regulate diverse facets of RNA biology. Proteins of this family carry out essential cellular functions, and emerging literature is revealing additional roles in immune defense. Using RNA interference screening, we identified an evolutionarily conserved antiviral role for the helicase DDX56 against the alphavirus Sindbis virus (SINV), a mosquito-transmitted pathogen that infects humans. Depletion of DDX56 enhanced infection in Drosophila and human cells. Furthermore, we found that DDX56 also controls the emerging alphavirus chikungunya virus (CHIKV) through an interferon-independent mechanism. Using cross-linking immunoprecipitation (CLIP-Seq), we identified a predicted stem-loop on the viral genomic RNA bound by DDX56. Mechanistically, we found that DDX56 levels increase in the cytoplasm during CHIKV infection. In the cytoplasm, DDX56 impacts the earliest step in the viral replication cycle by binding and destabilizing the incoming viral genomic RNA, thereby attenuating infection. Thus, DDX56 is a conserved antiviral RNA binding protein that controls alphavirus infection.
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3,593 |
Global health education in medical schools (GHEMS): a national, collaborative study of medical curricula
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BACKGROUND: Global health is the study, research, and practice of medicine focused on improving health and achieving health equity for all persons worldwide. International and national bodies stipulate that global health be integrated into medical school curricula. However, there is a global paucity of data evaluating the state of global health teaching in medical schools. This study aimed to evaluate the extent of global health teaching activities at United Kingdom (UK) medical schools. METHODS: A national, cross-sectional study assessing all timetabled teachings sessions within UK medical courses for global health content during the academic year 2018/19. Global health content was evaluated against a comprehensive list of global health learning outcomes for medical students. RESULTS: Data from 39 medical courses representing 86% (30/36) of eligible medical schools was collected. Typically, medical courses reported timetabled teaching covering over three-quarters of all global health learning outcomes. However, a wide degree of variation existed among granular global health learning objectives covered within the different medical courses. On average, each learning outcome had a 79% [95% CI: 73, 83%] probability of being included in course curricula. There were a number of learning outcomes that had a lower probability, such as ‘access to surgeons with the necessary skills and equipment in different countries’ (36%) [95% CI: 21, 53%], ‘future impact of climate change on health and healthcare systems’ (67%) [95% CI: 50, 81%], and ‘role of the WHO’ (54%) [95% CI: 28, 60%]. CONCLUSIONS: This study served as the first national assessment of global health education and curricula within UK medical schools. Through a formalised assessment of teaching events produced by medical schools around the country, we were able to capture a national picture of global health education, including the strengths of global health prioritisation in the UK, as well as areas for improvement. Overall, it appears broad-level global health themes are widely discussed; however, the granularities of key, emerging areas of concern are omitted by curricula. In particular, gaps persist relating to international healthcare systems, multilateral global health agencies such as the WHO, global surgery, climate change and more.
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3,594 |
Diagnosing skull fracture in children with closed head injury using point-of-care ultrasound vs. computed tomography scan
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Diagnostic and therapeutic interventions in children for traumatic brain injury, which is known as the most important complication in trauma, require special attention. This study aimed to evaluate the accuracy of point-of-care ultrasound (POCUS) in diagnosing skull fracture in children with closed head injury in comparison with computed tomography (CT) scan. The current prospective cross-sectional study was conducted on children (0–14 years old), who were referred to the emergency department of a general teaching hospital in Shiraz, southern Iran (January–March 2018), with close head injury and were suspected of bone fracture. The participants were selected using a convenience sampling. The results of POCUS performed by emergency medicine (EM) residents were compared with the results of CT scan, which was reported by radiologists and considered a gold standard. Then, diagnostic tests were calculated. A total of 168 children were enrolled, with the mean ± standard deviation age of 6.21 ± 3.99. The most affected areas in the skull were the frontal (34.5%) and occipital areas (33.3%). POCUS had a sensitivity and specificity of 81.8% (95%CI, 48.2–97.7%) and 100% (95%CI, 97.7–100%), respectively. Positive and negative predictive values were 100% and 98.7%, with an accuracy of 98.8% in comparison with CT scan in the diagnosis of skull fracture. Conclusion: The results showed that POCUS with a portable ultrasonography machine, performed by the EM’s physicians, have high diagnostic precision and can be considered a tool in the management of patients with closed head injury.
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3,595 |
Evaluation of semi-quantitative compared to quantitative cultures of tracheal aspirates for the yield of culturable respiratory pathogens – a cross-sectional study
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BACKGROUND: Diagnosis of lower respiratory tract infections (LRTI) depends on the presence of clinical, radiological and microbiological findings. Endotracheal suction aspirate (ETSA) is the commonest respiratory sample sent for culture from intubated patients. Very few studies have compared quantitative and semi-quantitative processing of ETSA cultures for LRTI diagnosis. We determined the diagnostic accuracy of quantitative and semi-quantitative ETSA culture for LRTI diagnosis, agreement between the quantitative and semi quantitative culture techniques and the yield of respiratory pathogens with both methods. METHODS: This was a cross-sectional study conducted at the Aga Khan University clinical laboratory, Karachi, Pakistan. One hundred and seventy-eight ETSA samples sent for routine bacteriological cultures were processed quantitatively as part of regular specimen processing method and semi-quantitatively. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy was calculated for both methods using clinical diagnosis of pneumonia as reference standard. Agreement between the quantitative and semi quantitative methods was assessed via the kappa statistic test. Pathogen yield between the two methods was compared using Pearson’s chi-square test. RESULTS: The quantitative and semi-quantitative methods yielded pathogens in 81 (45.5%) and 85 (47.8%) cases respectively. There was complete concordance of both techniques in 155 (87.1%) ETSA samples. No growth was observed in 45 (25.3%) ETSA specimens with quantitative culture and 37 (20.8%) cases by semi-quantitative culture. The diagnostic accuracy of both techniques were comparable; 64.6% for quantitative and 64.0% for semi-quantitative culture. The kappa agreement was found to be 0.84 (95% CI, 0.77–0.91) representing almost perfect agreement between the two methods. Although semi-quantitative cultures yielded more pathogens (47.8%) as compared to quantitative ETSA cultures (45.5%), the difference was only 2.3%. However, this difference achieved statistical (chi-square p-value < 0.001) favoring semi-quantitative culture methods over quantitative culture techniques for processing ETSA. CONCLUSION: In conclusion, there is a strong agreement between the performances of both methods of processing ETSA cultures in terms of accuracy of LRTI diagnosis. Semi-quantitative cultures of ETSA yielded more pathogens as compared to quantitative cultures. Although both techniques were comparable, we recommend processing of ETSA using semi-quantitative technique due to its ease and reduced processing time.
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3,596 |
Chronic disorders of consciousness: a case report with longitudinal evaluation of disease progression using 7 T magnetic resonance imaging
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BACKGROUND: Outcome prediction for patients with disorders of consciousness (DOC) is essential yet challenging. Evidence showed that patients with DOC lasting 1 year or longer after a brain injury were less likely to recover. However, the reasons why outcomes of DOC patients differ greatly remain unclear. With a variety of analytical methods and through quantitative behavioral assessments, we aimed to track the progression of a patient with severe brain injury, in order to advance our understanding of the underlying mechanisms of DOC. CASE PRESENTATION: We performed a longitudinal study for a 52-year-old male DOC patient who has remained in the state for 1.5 years with comprehensive rehabilitative therapies. The patient underwent 3 times of assessments of Coma Recovery Scale-Revised (CRS-R) and ultra-high-field 7 T magnetic resonance imaging (MRI). Both topologic properties and brain microstructure were analyzed to track disease progression. We observed dynamic increases of fiber densities with measurements at three time points (t1:1.5 M, t2:7.5 M t3:17.5 M). Specifically, fiber densities of the superior longitudinal fasciculus and arcuate fasciculus nerve fiber bundles improved mostly in the visual, verbal, and auditory subscales, which was consistent with the CRS-R scores. Moreover, the graph-theory analyses demonstrated that network topologic properties showed an improvement although the disease duration exceeded 1 year. CONCLUSIONS: DOC patients with a course longer than 1 year remain possible to improve, and including evaluation methods such as WM connectome analysis and graph theory could be potentially valuable for a more precise assessment of patients with a longer course of DOC.
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3,597 |
Impact of systematic screening for AmpC-hyperproducing Enterobacterales intestinal carriage in intensive care unit patients
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BACKGROUND: Empirical antimicrobial therapy (EAT) is a challenge for community-acquired, hospital-acquired and ventilator-associated pneumonia, particularly in the context of the increasing occurrence of third-generation cephalosporin-resistant Enterobacterales (3GCR-E), including extended-spectrum beta-lactamase Enterobacterales (ESBL-E) and high-level expressed AmpC cephalosporinase-producing Enterobacterales (HLAC-E). To prevent the overuse of broad-spectrum antimicrobial therapies, such as carbapenems, we assessed the performance of screening for intestinal carriage of HLAC-E in addition to ESBL-E to predict 3GCR-E (ESBL-E and/or HLAC-E) presence or absence in respiratory samples in ICU, and to evaluate its potential impact on carbapenem prescription. MATERIALS AND METHODS: This monocentric retrospective observational study was performed in a surgical ICU during a 4-year period (January 2013–December 2016). Patients were included if they had a positive culture on a respiratory sample and a previous intestinal carriage screening performed by rectal swabbing within 21 days. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios were calculated for the screening for intestinal carriage of ESBL-E, HLAC-E and 3GCR-E (ESBL-E and/or HLAC-E) as predictor of their absence/presence in respiratory samples. Impact of HLAC-E and ESBL-E reporting on EAT was also studied. RESULTS: 765 respiratory samples, retrieved from 468 patients, were analyzed. ESBL-E prevalence was 23.8% in rectal swab and 4.4% in respiratory samples. HLAC-E prevalence was 9.0% in rectal swabs and 3.7% in respiratory samples. Overall, the 3GCR-E prevalence was 31.8% in rectal swabs and 7.7% in respiratory samples. NPVs were 98.8%, 98.0% and 96.6% for ESBL-E, HLAC-E and 3GCR-E, respectively. Over the study period, empirical antimicrobial therapy was initiated for 315 episodes of respiratory infections: 228/315 (72.4%) were associated with negative intestinal carriage screening for both HLAC-E and ESBL-E, of whom 28/228 (12.3%) were treated with carbapenems. Of 23/315 (7.3%) cases with screening for positive intestinal carriage with HLAC-E alone, 10/23 (43.5%) were treated with carbapenems. CONCLUSION: Systematic screening and reporting of HLAC-E in addition to ESBL-E in intestinal carriage screening could help to predict the absence of 3GCR-E in respiratory samples of severe surgical ICU patients. This could improve the appropriateness of EAT in ICU patients with HAP and may prevent the overuse of carbapenems.
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3,598 |
Correlation Between the Clinical Severity, Bacterial Load, and Inflammatory Reaction in Children with Mycoplasma Pneumoniae Pneumonia
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Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 10(5) (54 cases), ≥10(5) and <10(6) (71 cases), ≥10(6) and <10(7) (112 cases), ≥10(7) and ≤10(8) (114 cases), and >10(8) (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group.
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3,599 |
The qSOFA score combined with the initial red cell distribution width as a useful predictor of 30 day mortality among older adults with infection in an emergency department
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PURPOSE: This study aimed to investigate whether the qSOFA and initial red cell distribution width (RDW) in the emergency department (ED) are associated with mortality in older adults with infections who visited the ED. METHODS: This was a retrospective study conducted in 5 EDs between November 2016 and February 2017. We recorded age, sex, comorbidities, body temperature, clinical findings, and initial laboratory results, including the RDW. The initial RDW values and the qSOFA criteria were obtained at the time of the ED visit. The primary outcome was 30 day mortality. RESULTS: A total of 1,446 patients were finally included in this study, of which 134 (9.3%) died within 30 days and the median (IQR) age was 77 (72, 82) years. In the multivariable analysis, the RDW (14.0–15.4%) and highest RDW (> 15.4%) quartile were shown to be independent risk factors for 30 day mortality (OR 2.12; 95% CI 1.12–4.02; p = 0.021) (OR 3.35; 95% CI 1.83–6.13; p < 0.001). The patients with qSOFA 2 and 3 were shown to have the high odds ratios of 30-day mortality (OR 3.50; 95% CI 2.09–5.84; p < 0.001) (OR 11.30; 95% CI 5.06–25.23; p < 0.001). The qSOFA combined with the RDW quartile for the prediction of 30 day mortality showed an AUROC value of 0.710 (0.686–0.734). CONCLUSION: The qSOFA combined with the initial RDW value was associated with 30-day mortality among older adults with infections in the ED. The initial RDW may help emergency physicians predict mortality in older adults with infections visiting the ED.
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