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3,600 |
Breath-synchronized electrical stimulation of the expiratory muscles in mechanically ventilated patients: a randomized controlled feasibility study and pooled analysis
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BACKGROUND: Expiratory muscle weakness leads to difficult ventilator weaning. Maintaining their activity with functional electrical stimulation (FES) may improve outcome. We studied feasibility of breath-synchronized expiratory population muscle FES in a mixed ICU population (“Holland study”) and pooled data with our previous work (“Australian study”) to estimate potential clinical effects in a larger group. METHODS: Holland: Patients with a contractile response to FES received active or sham expiratory muscle FES (30 min, twice daily, 5 days/week until weaned). Main endpoints were feasibility (e.g., patient recruitment, treatment compliance, stimulation intensity) and safety. Pooled: Data on respiratory muscle thickness and ventilation duration from the Holland and Australian studies were combined (N = 40) in order to estimate potential effect size. Plasma cytokines (day 0, 3) were analyzed to study the effects of FES on systemic inflammation. RESULTS: Holland: A total of 272 sessions were performed (active/sham: 169/103) in 20 patients (N = active/sham: 10/10) with a total treatment compliance rate of 91.1%. No FES-related serious adverse events were reported. Pooled: On day 3, there was a between-group difference (N = active/sham: 7/12) in total abdominal expiratory muscle thickness favoring the active group [treatment difference (95% confidence interval); 2.25 (0.34, 4.16) mm, P = 0.02] but not on day 5. Plasma cytokine levels indicated that early FES did not induce systemic inflammation. Using a survival analysis approach for the total study population, median ventilation duration and ICU length of stay were 10 versus 52 (P = 0.07), and 12 versus 54 (P = 0.03) days for the active versus sham group. Median ventilation duration of patients that were successfully extubated was 8.5 [5.6–12.2] versus 10.5 [5.3–25.6] days (P = 0.60) for the active (N = 16) versus sham (N = 10) group, and median ICU length of stay was 10.5 [8.0–14.5] versus 14.0 [9.0–19.5] days (P = 0.36) for those active (N = 16) versus sham (N = 8) patients that were extubated and discharged alive from the ICU. During ICU stay, 3/20 patients died in the active group versus 8/20 in the sham group (P = 0.16). CONCLUSION: Expiratory muscle FES is feasible in selected ICU patients and might be a promising technique within a respiratory muscle-protective ventilation strategy. The next step is to study the effects on weaning and ventilator liberation outcome. Trial registration: ClinicalTrials.gov, ID NCT03453944. Registered 05 March 2018—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03453944.
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3,601 |
“En la Lucha”: Strategies to Improve HIV Care for Puerto Ricans with Opioids Use Disorders
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BACKGROUND: Clínica Bienestar is a comprehensive HIV primary care clinic for Spanish-speaking Latinx with opioids use disorders (OUD). This article describes the barriers and trajectories to HIV viral suppression for Puerto Ricans with a transnational profile and dual diagnoses (HIV and OUD), and the strategies applied to increase retention in care. METHODS: Case study methodology was used to select two patient life histories that illustrate the most common pathways to success in reducing HIV viral load to undetectable and achieving OUD long-term recovery. RESULTS AND DISCUSSION: Patients’ major challenges included: (1) Persistent migrating while seeking substance use treatment services with limited or no support from their sending and hosting communities; (2) Intersectional stigmas; (3) Untreated trauma; (4) Language and cultural barriers. Clínica Bienestar’s service model included ten strategies to retain patients in care (e.g., Case management to identify cases with high social isolation), six emerged as central to addressing transnational challenges.
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3,602 |
Pediatric Resident Engagement With an Online Critical Care Curriculum During the Intensive Care Rotation*
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Residents are often assigned online learning materials as part of blended learning models, superimposed on other patient care and learning demands. Data that describe the time patterns of when residents interact with online learning materials during the ICU rotation are lacking. We describe resident engagement with assigned online curricula related to time of day and ICU clinical schedules, using website activity data. DESIGN: Prospective cohort study examining curriculum completion data and cross-referencing timestamps for pre- and posttest attempts with resident schedules to determine the hours that they accessed the curriculum and whether or not they were scheduled for clinical duty. Residents at each site were cohorted based on two differing clinical schedules—extended duration (>24 hr) versus shorter (maximum 16 hr) shifts. SETTING: Two large academic children’s hospitals. SUBJECTS: Pediatric residents rotating in the PICU from July 2013 to June 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-hundred and fifty-seven pediatric residents participated in the study. The majority of residents (106/157; 68%) completed the curriculum, with no statistically significant association between overall curriculum completion and schedule cohort at either site. Residents made more test attempts at nighttime between 6 pm and 6 am (1,824/2,828; 64%) regardless of whether they were scheduled for clinical duty. Approximately two thirds of test attempts (1,785/2,828; 63%) occurred when residents were not scheduled to work, regardless of time of day. Forty-two percent of all test attempts (1,199/2,828) occurred between 6 pm and 6 am while off-duty, with 12% (342/2,828) occurring between midnight and 6 am. CONCLUSIONS: Residents rotating in the ICU completed online learning materials mainly during nighttime and off-duty hours, including usage between midnight and 6 am while off-duty. Increasing nighttime and off-duty workload may have implications for educational design and trainee wellness, particularly during busy, acute clinical rotations, and warrants further examination.
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3,603 |
The Influence of Essential Oils on Gut Microbial Profiles in Pigs
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SIMPLE SUMMARY: In recent years, the intake of ultra-processed foods has increased dramatically worldwide. Missing natural foods in the diet raise the need of biologically active food components that could compensate for this deficiency and help maintain proper immune status. In this study, the microbial changes in pigs as experimental animals were assessed as influenced by consumption of oregano extract combination with peppermint and thyme essential oils. The results demonstrated that the combination of plant extracts had a positive effect on the gastrointestinal tract of animals by increasing the number of probiotic bacteria. Based on the results obtained it may be outlined that the combination of oregano extract and peppermint and thyme essential oils can be promising ingredient as a functional component for the development of the new nutraceutical preparation. ABSTRACT: In recent years, the intake of ultra-processed foods has increased dramatically worldwide. Missing natural foods in the diet raise the need of biologically active food components that could compensate for this deficiency and help maintain proper immune status. This study used pigs as an animal model for the assessment of the impact of consumption of Origanum vulgare plant extract combined with Mentha piperita and Thymus vulgaris essential oils on microbial profile in intestines. A single group of weaned pigs received basal diet, while the other group basal diet supplemented with plant extract and two essential oils in the form of bilayer tablets prepared using “liquid/solid” phase technology. Metagenomic sequencing was performed with the aim to investigate changes of microbial communities in ileum, caecum, and colon. The results demonstrated that the combination of essential oils was non cytotoxic, and had a positive effect on the microbial composition in the large intestine of pigs due to significant increase in the number of probiotic bacteria. The amount of Lactobacillus was 2.5 times and Bifidobacterium 1.9 times higher in the animal group fed with supplement. The combination, however, had some negative impact on the variety of minor species in the distal part of the ileum. Additional studies need to be performed to obtain knowledge on how combinations of essential oils can change bacterial variety in the proximal part of the gastrointestinal tract.
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3,604 |
Identification of Modulators of HIV-1 Proviral Transcription from a Library of FDA-Approved Pharmaceuticals
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Human immunodeficiency virus 1 (HIV-1) is the most prevalent human retrovirus. Recent data show that 34 million people are living with HIV-1 worldwide. HIV-1 infections can lead to AIDS which still causes nearly 20,000 deaths annually in the USA alone. As this retrovirus leads to high morbidity and mortality conditions, more effective therapeutic regimens must be developed to treat these viral infections. A key target for intervention for which there are no current FDA-approved modulators is at the point of proviral transcription. One successful method for identifying novel therapeutics for treating infectious diseases is the repurposing of pharmaceuticals that are approved by the FDA for alternate indications. Major benefits of using FDA-approved drugs include the fact that the compounds have well established toxicity profiles, approved manufacturing processes, and immediate commercial availability to the patients. Here, we demonstrate that pharmaceuticals previously approved for other indications can be utilized to either activate or inhibit HIV-1 proviral transcription. Specifically, we found febuxostat, eltrombopag, and resveratrol to be activators of HIV-1 transcription, while mycophenolate was our lead inhibitor of HIV-1 transcription. Additionally, we observed that the infected cells of lymphoid and myeloid lineage responded differently to our lead transcriptional modulators. Finally, we demonstrated that the use of a multi-dose regimen allowed for enhanced activation with our transcriptional activators.
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3,605 |
Phenolome of Asian Agrimony Tea (Agrimonia asiatica Juz., Rosaceae): LC-MS Profile, α-Glucosidase Inhibitory Potential and Stability
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Functional beverages constitute the rapidly increasing part of the functional food section and represent an area with a wide range of products including herbal-based beverages. We carried out screening investigations of the extracts of 85 Rosaceous tea plants. Among the extracts analyzed Agrimonia asiatica herb extract demonstrated the highest inhibitory activity against the enzyme α-glucosidase (20.29 µg/mL). As a result of chromato-mass-spectrometric profiling of A. asiatica herb with high-performance liquid chromatography with photodiode array and electrospray triple quadrupole mass-spectrometric detection (HPLC-PDA-ESI-tQ-MS) 60 compounds were identified, including catechins, ellagitannins, flavones, flavonols, gallotannins, hydroxycinnamates, procyanidins, most for the very first time. The analysis of the seasonal variation of metabolites in A. asiatica herb demonstrated that the phenolic content was highest in summer samples and lower in spring and autumn. HPLC activity-based profiling was utilized to identify compounds of A. asiatica herb with the maximal α-glucosidase inhibitory activity. The most pronounced inhibition of α-glucosidase was observed for agrimoniin, while less significant results of inhibition were revealed for ellagic acid and isoquercitrin. The evaluation of phenolic content in A. asiatica herbal teas with the subsequent determination of α-glucosidase inhibiting potential was discovered. Maximum inhibition of α-glucosidase was observed for hot infusion (75.33 µg/mL) and the minimum for 30 min decoction (159.14 µg/mL). Our study demonstrated that A. asiatica herbal tea is a prospective functional beverage in which dietary intake may help to reduce blood glucose.
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3,606 |
Grape (Vitis vinifera L.) Seed Oil: A Functional Food from the Winemaking Industry
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Wine production is an ancient human activity that generates several by-products, which include some constituents known for their potential in health care and for their role in the food or cosmetic industries. Any variety of grape (Vitis vinifera L.) contains nutrients and bioactive compounds available from their juice or solid parts. Grape seed extract has demonstrated many activities in disease prevention, such as antioxidant effects, which make it a potential source of nutraceuticals. Grape seed is a remarkable winery industry by-product due to the bioactivity of its constituents. Methods for recovery of oil from grape seeds have evolved to improve both the quantity and quality of the yield. Both the lipophilic and hydrophilic chemicals present in the oil of V. vinifera L. make this wine by-product a source of natural nutraceuticals. Food and non-food industries are becoming novel targets of oil obtained from grape seeds given its various properties. This review focuses on the advantages of grape seed oil intake in our diet regarding its chemical composition in industries not related to wine production and the economic and environmental impact of oil production.
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3,607 |
Current Societal Views about Sustainable Wildlife Management and Conservation: A Survey of College Students in China
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SIMPLE SUMMARY: Wildlife conservation and management has become a very complex public policy issue in China as concerns about animal welfare and empathy for animals have emerged, especially in the younger generation. Science-based conservation policy and strategy that focus on sustainable management are perceived as less irrelevant today and can often be in conflict with emerging attitudes and values. Sustainable wildlife management adheres to the conservation concept of effective combination of species conservation and sustainable utilization, with an aim to establish a long-acting species conservation model that promotes all-round development of ecology, society, and economy, and has traditionally formed the basis of conservation management. This study designed a semi-structured questionnaire, which aimed to assess attitudes of Chinese college students towards sustainable wildlife management and wildlife conservation, and investigate the role of demographic and other characteristics on attitude. From October 2018 to April 2019, nine universities (including “Double First-Class” universities, first-tier universities, second-tier universities), and four three-year colleges in China were selected as survey sites, where face-to-face interviews were conducted among students. The results show that students broadly support the sustainable wildlife management but not in issues relating to “Animal Welfare and Rights” and “Trophy Hunting”. Students with lowest support for the theory and practice of sustainable wildlife management are vegetarians, freshmen, and those who have taken environmental protection electives in their educational program. ABSTRACT: Wildlife conservation and management has become a very complex public policy issue in China as concerns over on animal welfare and empathy for animals have grown. Science-based conservation strategies that are oriented toward sustainable wildlife management (SWM) are under threat as these new attitudes and values emerge and take hold. This study accesses the attitudes of college students towards SWM and wildlife conservation, and investigates demographic characteristics influencing their attitudes in China, a country that is traditionally associated with consumptive use of wildlife and SWM, but where new ideas about wildlife conservation are emerging. From October 2018 to April 2019, nine universities (including “Double First-Class” universities, first-tier universities, second-tier universities), and four three-year colleges in China were selected as survey locations, and face-to-face interviews were conducted with 1991 students. A total of 1977 questionnaires were recovered, of which 1739 were valid, with a completion rate of 88%. A Likert seven-point scale method was used to score students’ attitudes, and a classification and regression tree (CART) was used to analyze whether their attitudes were affected by their demographic characteristics. The results show that although students are broadly supportive of the theory of SWM, some are deeply antagonistic about on SWM on issues that arouse strong emotions such as “Animal Welfare and Rights” and “Trophy Hunting”. Demographic characteristics of students affect their degree of support for the SWM with support for SWM lower among vegetarians, freshmen, and students who have taken environmental protection electives. This research suggests that the theory of SWM requires to be refreshed and adapted to appeal to the younger generation of Chinese students, with SWM principles integrated into the environmental education programs of universities and three-year colleges. More attention should also be attached to media publicity by the government about wildlife conservation so as to enhance awareness of the need for SWM.
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3,608 |
Approaching Gravity as a Continuum Using the Rat Partial Weight-Bearing Model
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For decades, scientists have relied on animals to understand the risks and consequences of space travel. Animals remain key to study the physiological alterations during spaceflight and provide crucial information about microgravity-induced changes. While spaceflights may appear common, they remain costly and, coupled with limited cargo areas, do not allow for large sample sizes onboard. In 1979, a model of hindlimb unloading (HU) was successfully created to mimic microgravity and has been used extensively since its creation. Four decades later, the first model of mouse partial weight-bearing (PWB) was developed, aiming at mimicking partial gravity environments. Return to the Lunar surface for astronauts is now imminent and prompted the need for an animal model closer to human physiology; hence in 2018, our laboratory created a new model of PWB for adult rats. In this review, we will focus on the rat model of PWB, from its conception to the current state of knowledge. Additionally, we will address how this new model, used in conjunction with HU, will help implement new paradigms allowing scientists to anticipate the physiological alterations and needs of astronauts. Finally, we will discuss the outstanding questions and future perspectives in space research and propose potential solutions using the rat PWB model.
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3,609 |
Plant Disease Classification: A Comparative Evaluation of Convolutional Neural Networks and Deep Learning Optimizers
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Recently, plant disease classification has been done by various state-of-the-art deep learning (DL) architectures on the publicly available/author generated datasets. This research proposed the deep learning-based comparative evaluation for the classification of plant disease in two steps. Firstly, the best convolutional neural network (CNN) was obtained by conducting a comparative analysis among well-known CNN architectures along with modified and cascaded/hybrid versions of some of the DL models proposed in the recent researches. Secondly, the performance of the best-obtained model was attempted to improve by training through various deep learning optimizers. The comparison between various CNNs was based on performance metrics such as validation accuracy/loss, F1-score, and the required number of epochs. All the selected DL architectures were trained in the PlantVillage dataset which contains 26 different diseases belonging to 14 respective plant species. Keras with TensorFlow backend was used to train deep learning architectures. It is concluded that the Xception architecture trained with the Adam optimizer attained the highest validation accuracy and F1-score of 99.81% and 0.9978 respectively which is comparatively better than the previous approaches and it proves the novelty of the work. Therefore, the method proposed in this research can be applied to other agricultural applications for transparent detection and classification purposes.
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3,610 |
Chicken Astrovirus (CAstV) Molecular Studies Reveal Evidence of Multiple Past Recombination Events in Sequences Originated from Clinical Samples of White Chick Syndrome (WCS) in Western Canada
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In this study, we aimed to molecularly characterize 14 whole genome sequences of chicken astrovirus (CAstV) isolated from samples obtained from white chick syndrome (WCS) outbreaks in Western Canada during the period of 2014–2019. Genome sequence comparisons showed all these sequences correspond to the novel Biv group from which no confirmed representatives were published in GenBank. Molecular recombination analyses using recombination detection software (i.e., RDP5 and SimPlot) and phylogenetic analyses suggest multiple past recombination events in open reading frame (ORF)1a, ORF1b, and ORF2. Our findings suggest that recombination events and the accumulation of point mutations may have contributed to the substantial genetic variation observed in CAstV and evidenced by the current seven antigenic sub-clusters hitherto described. This is the first paper that describes recombination events in CAstV following analysis of complete CAstV sequences originated in Canada.
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3,611 |
Searching for New Directions for Energy Policy: Testing Three Causal Models of Risk Perception, Attitude, and Behavior in Nuclear Energy Context
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Although many risk studies investigate perceptions, attitudes, and behaviors, the causal relationships among them have not yet been verified. Thus, further investigations of these relationships are necessary. This study analyzes three causal models consisting of three components: perceptions (i.e., perceived risk in this study), attitudes (i.e., satisfaction), and behavior (i.e., support for policy). This study checks these relationships in the context of nuclear energy policy. Using a hierarchical regression model, this study tests three different models between the three components: (1) Model 1 (a high-involvement model), (2) Model 2 (a low-involvement model), and (3) Model 3 (a hedonic model). First, in the high-involvement model, behavior is affected by perceptions and attitudes. In particular, attitudes mediate the relationship between risk perceptions and satisfaction. Second, in the low-involvement model, attitudes indirectly affect perceptions through behaviors. Third, in the hedonic model, behaviors affect attitudes, and risk perceptions do not mediate that relationship. This causal model does not depend on perceptions of the benefits and drawbacks of nuclear power. Our analysis shows that Model 1 is fully significant, and Model 2 and 3 are only partially significant.
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3,612 |
Sustainable Production of Hydrogen by Steam Reforming of Ethanol Using Cobalt Supported on Nanoporous Zeolitic Material
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Cobalt catalysts supported on Y zeolite and mesoporized Y zeolite (Y-mod) have been studied in steam reforming of ethanol (SRE). Specifically, the effect of the mesoporosity and the acidity of the y zeolite as a support has been explored. Mesoporous were generated on Y zeolite by treatment with NH4F and the acidity was neutralized by Na incorporation. Four cobalt catalysts supported on Y zeolite have been prepared, two using Y zeolite without mesoporous (Co/Y, Co/Y-Na), and two using Y zeolite with mesoporous (Co/Y-mod and Co/Y-mod-Na). All catalysts showed a high activity, with ethanol conversion values close to 100%. The main differences were found in the distribution of the reaction products. Co/Y and Co/Y-mod catalysts showed high selectivity to ethylene and low hydrogen production, which was explained by their high acidity. On the contrary, neutralization of the acid sites could explain the higher hydrogen selectivity and the lower ethylene yields exhibited by the Co/Y-Na and Co/Y-mod-Na. In addition, the physicochemical characterization of these catalysts by XRD, BET surface area, temperature-programmed reduction (TPR), and TEM allowed to connect the presence of mesoporous with the formation of metallic cobalt particles with small size, high dispersion, and with high interaction with the zeolitic support, explaining the high reforming activity exhibited by the co/y-mod-Na sample as well as its higher hydrogen selectivity. It has been also observed that the formation of coke is affected by the presence of mesoporous and acidity. Both properties seem to have an opposite effect on the reforming catalyst, decreasing and increasing the coke deposition, respectively.
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3,613 |
Blockage of Store-Operated Ca(2+) Influx by Synta66 is Mediated by Direct Inhibition of the Ca(2+) Selective Orai1 Pore
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SIMPLE SUMMARY: Store-operated calcium channels constituted from the proteins Orai and STIM are important targets for development of new drugs, especially for the treatment of auto-immune diseases. Also, interference with channel function is linked to reduced cancer cell progression, making these channels potential targets for anti-cancer drug development. Therefore, inhibitors need to be evaluated for both their binding selectivity and their potential to interfere with cancer progression. Here, we investigated the inhibitor Synta66 and determined its site of binding via both patch clamp recordings and computational approaches and evaluated its potency as anti-cancer agent in glioblastoma multiforme cells. Our findings show that Synta66 is a highly selective ligand to the Orai1 pore and efficiently blocks store operated calcium entry in glioblastoma cells. Still, in the tested cell lines, Synta66 did not reduce cell viability. We therefore suggest Synta66 as a precise tool to observe interference of store-operated Orai1 channel function in vitro and of resulting downstream effects. ABSTRACT: The Ca(2+) sensor STIM1 and the Ca(2+) channel Orai1 that form the store-operated Ca(2+) (SOC) channel complex are key targets for drug development. Selective SOC inhibitors are currently undergoing clinical evaluation for the treatment of auto-immune and inflammatory responses and are also deemed promising anti-neoplastic agents since SOC channels are linked with enhanced cancer cell progression. Here, we describe an investigation of the site of binding of the selective inhibitor Synta66 to the SOC channel Orai1 using docking and molecular dynamics simulations, and live cell recordings. Synta66 binding was localized to the extracellular site close to the transmembrane (TM)1 and TM3 helices and the extracellular loop segments, which, importantly, are adjacent to the Orai1-selectivity filter. Synta66-sensitivity of the Orai1 pore was, in fact, diminished by both Orai1 mutations affecting Ca(2+) selectivity and permeation of Na(+) in the absence of Ca(2+). Synta66 also efficiently blocked SOC in three glioblastoma cell lines but failed to interfere with cell viability, division and migration. These experiments provide new structural and functional insights into selective drug inhibition of the Orai1 Ca(2+) channel by a high-affinity pore blocker.
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3,614 |
Healthcare Professional in the Loop (HPIL): Classification of Standard and Oral Cancer-Causing Anomalous Regions of Oral Cavity Using Textural Analysis Technique in Autofluorescence Imaging
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Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche–Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia.
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3,615 |
Quantification of the Ability of Natural Products to Prevent Herpes Virus Infection
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Background: Herpes simplex virus (HSV) is usually dormant and becomes apparent when body conditions decline. We investigated the anti-HSV activity of various natural and synthetic compounds for future clinical application. Methods: Mock- and HSV-infected Vero cells were treated for three days with various concentrations of samples. For short exposure, 100-fold concentrated virus were preincubated for 3 min with samples, diluted to normal multiplicity of infection (MOI), before the addition to the cells. Anti-HSV activity was evaluated by the chemotherapy index. Results: Alkaline extracts of the leaves of Sasa sp. (SE) and pine cone (PCE) showed higher anti-HSV activity than 20 Japanese traditional herb medicines (Kampo formulas), four popular polyphenols, and 119 chromone-related compounds. Exposure of HSV to SE or PCE for 3 min almost completely eliminated the infectivity of HSV, whereas much longer exposure time was required for Kakkonto, the most active Kampo formulae. Anti-HSV activity of PCE and Kakkonto could be detected only when they were dissolved by alkaline solution (pH 8.0), but not by neutral buffer (pH 7.4). Anti-HSV activity of SE and povidone iodine was stable if they were diluted with neutral buffer. Conclusions: The present study suggests the applicability of SE and PCE for treatment of oral HSV and possibly other viruses.
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3,616 |
Short-Term Exercise Progression of Cardiovascular Patients throughout Cardiac Rehabilitation: An Observational Study
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Cardiac rehabilitation (CR) is a highly recommended secondary prevention measure for patients with diagnosed cardiovascular disease. Unfortunately, participation rates are low due to enrollment and adherence issues. As such, new CR delivery strategies are of interest, as to improve overall CR delivery. The goal of the study was to obtain a better understanding of the short-term progression of functional capacity throughout multidisciplinary CR, measured as the change in walking distance between baseline six-minute walking test (6MWT) and four consecutive follow-up tests. One-hundred-and-twenty-nine patients diagnosed with cardiovascular disease participated in the study, of which 89 patients who completed the whole study protocol were included in the statistical analysis. A one-way repeated measures ANOVA was conducted to determine whether there was a significant change in mean 6MWT distance (6MWD) throughout CR. A three-way-mixed ANOVA was performed to determine the influence of categorical variables on the progression in 6MWD between groups. Significant differences in mean 6MWD between consecutive measurements were observed. Two subgroups were identified based on the change in distance between baseline and end-of-study. Patients who increased most showed a linear progression. In the other group progression leveled off halfway through rehabilitation. Moreover, the improvement during the initial phase of CR seemed to be indicative for overall progression. The current study adds to the understanding of the short-term progression in exercise capacity of patients diagnosed with cardiovascular disease throughout a CR program. The results are not only of interest for CR in general, but could be particularly relevant in the setting of home-based CR.
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3,617 |
Use of Hyaluronic Acid (HA) in Chronic Airway Diseases
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Hyaluronic acid (HA) is a key component of the extracellular matrix of the lungs. A unique attribute of HA is its water-retaining properties, so HA has a major role in the regulation of fluid balance in the lung interstitium. Hyaluronic acid has been widely used in the treatment of eyes, ears, joints and skin disorders, but in the last years, it has been also proposed in the treatment of certain lung diseases, including airway diseases, due to its anti-inflammatory and water-binding capacities. Hyaluronic acid aerosol decreases the severity of elastase-induced emphysema in murine models, prevents bronchoconstriction in asthmatics and improves some functional parameters in chronic obstructive pulmonary disease (COPD) patients. Due to the protection of HA against bronchoconstriction and its hydration properties, inhaled HA would increase the volume of airway surface liquid, resulting in mucus hydration, increased mucous transport and less mucous plugging of the airways. In addition, it has been seen in human studies that the treatment with nebulised HA improves the tolerability of nebulised hypertonic saline (even at 6% or 7% of concentration), which has been demonstrated to be an effective treatment in bronchial secretion management in patients with cystic fibrosis and bronchiectasis. Our objective is to review the role of HA treatment in the management of chronic airway diseases.
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3,618 |
Effects of the Human Gut Microbiota on Cognitive Performance, Brain Structure and Function: A Narrative Review
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Enhancing or preserving cognitive performance of personnel working in stressful, demanding and/or high tempo environments is vital for optimal performance. Emerging research suggests that the human gut microbiota may provide a potential avenue to enhance cognition. This review examines the relationship between the human gut microbiota, including modulators of the microbiota on cognition and/or brain function. For this narrative review, a total of n = 17 relevant human research items of a possible 1765 published between January 2010 and November 2018 were identified. Two overarching design methods for synthesis were observed: correlational or pre/post intervention. Limited correlational design studies linking microbiota to cognitive/brain structure endpoints existed (n = 5); however, correlations between microbiota diversity and enhanced cognitive flexibility and executive function were observed. Gut microbiota intervention studies to improve cognition or brain function (n = 12) generally resulted in improved cognition (11/12), in which improvements were observed in visuospatial memory, verbal learning and memory, and aspects of attentional vigilance. Limited studies were available to draw a detailed conclusion; however, available evidence suggests that gut microbiota is linked to cognitive performance and that manipulation of gut microbiota could be a promising avenue for enhancing cognition which warrants further research.
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3,619 |
Analyzing Malaria Disease Using Effective Deep Learning Approach
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Medical tools used to bolster decision-making by medical specialists who offer malaria treatment include image processing equipment and a computer-aided diagnostic system. Malaria images can be employed to identify and detect malaria using these methods, in order to monitor the symptoms of malaria patients, although there may be atypical cases that need more time for an assessment. This research used 7000 images of Xception, Inception-V3, ResNet-50, NasNetMobile, VGG-16 and AlexNet models for verification and analysis. These are prevalent models that classify the image precision and use a rotational method to improve the performance of validation and the training dataset with convolutional neural network models. Xception, using the state of the art activation function (Mish) and optimizer (Nadam), improved the effectiveness, as found by the outcomes of the convolutional neural model evaluation of these models for classifying the malaria disease from thin blood smear images. In terms of the performance, recall, accuracy, precision, and F1 measure, a combined score of 99.28% was achieved. Consequently, 10% of all non-dataset training and testing images were evaluated utilizing this pattern. Notable aspects for the improvement of a computer-aided diagnostic to produce an optimum malaria detection approach have been found, supported by a 98.86% accuracy level.
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3,620 |
Optimization of Point-Shear Wave Elastography by Skin-to-Liver Distance to Assess Liver Fibrosis in Patients Undergoing Bariatric Surgery
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Background: Obesity is a primary limiting factor in liver stiffness measurement (LSM). The impact of obesity has always been evaluated in terms of body mass index (BMI), without studying the effects of skin-to-liver distance (SLD) on LSM. We studied the impact of SLD on LSM in a cohort of obese patients undergoing bariatric surgery and intra-operatory liver biopsy. Materials and Methods: 299 patients underwent LSM by point-shear wave elastography (ElastPQ protocol), with two different ultrasound machines. SLD was measured as the distance between the skin and the liver capsule, perpendicular to where the region of interest (ROI) was positioned. We used the following arbitrary cut-offs: <5.7 kPa, F0–1; 5.7–7.99 kPa, F2; ≥8 kPa, F3–4. Results: We developed two logistic regression models using elastography–histology agreement (EHA) as the dependent variable and SLD as the independent variable. The model based on the second machine showed strongly more performant discriminative and calibration metrics (AIC 38.5, BIC 44.2, Nagelkerke Pseudo-R2 0.894, AUROC 0.90). The SLD cut-off value of 34.5 mm allowed a correct EHA with a sensitivity of 100%, a specificity of 93%, negative predictive value of 100%, positive predictive value of 87%, an accuracy of 96%, and positive likelihood ratio of 3.56. Conclusion: The impact of SLD is machine-dependent and should be taken into consideration when interpreting LSM. We believe that our findings may serve as a reference point for appropriate fibrosis stratification by liver elastography in obese patients.
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3,621 |
Born to Eat Wild: An Integrated Conservation Approach to Secure Wild Food Plants for Food Security and Nutrition
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Overlooked in national reports and in conservation programs, wild food plants (WFPs) have been a vital component of food and nutrition security for centuries. Recently, several countries have reported on the widespread and regular consumption of WFPs, particularly by rural and indigenous communities but also in urban contexts. They are reported as critical for livelihood resilience and for providing essential micronutrients to people enduring food shortages or other emergency situations. However, threats derived from changes in land use and climate, overexploitation and urbanization are reducing the availability of these biological resources in the wild and contributing to the loss of traditional knowledge associated with their use. Meanwhile, few policy measures are in place explicitly targeting their conservation and sustainable use. This can be partially attributed to a lack of scientific evidence and awareness among policymakers and relevant stakeholders of the untapped potential of WFPs, accompanied by market and non-market barriers limiting their use. This paper reviews recent efforts being undertaken in several countries to build evidence of the importance of WFPs, while providing examples of cross-sectoral cooperation and multi-stakeholder approaches that are contributing to advance their conservation and sustainable use. An integrated conservation approach is proposed contributing to secure their availability for future generations.
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The Effects of Frequency and Duration of Handling on the Development of Feline Upper Respiratory Infections in a Shelter Setting
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SIMPLE SUMMARY: Stress in cats residing in a shelter environment is a significant contributor to the development of upper respiratory disease (URD). Previous studies have shown that positive interactions can reduce stress and enhance the immune system. However, little is known on how the frequency and duration of daily handling affects a cat’s likelihood of developing URD. The goal of this study was to record the daily frequency and duration of handling of clinically healthy cats that were relinquished at a closed admission shelter and determine if these parameters were associated with a statistically significant increased risk of developing URD. While no parameters were statistically significantly associated with an increased hazard of developing URD, we found that cats that did not develop URD were handled more frequently than cats that did develop URD. Our results suggest that increased frequency and duration of handling does not appear to increase the risk of URD signs and may reduce the incidence of URD development. These results are important for the shelter community in developing handling and hygiene protocols for shelter cats. ABSTRACT: Reducing stress is important to maintaining the health of shelter cats and decreasing the risk of upper respiratory disease (URD). The aim of this study was to determine if the frequency and/or duration of daily routine handling of shelter cats affects the likelihood of URD development. At a closed admission shelter, each cat free of URD on intake was given a cage card for recording handling data. These data included: date and times when the cat was handled, duration of handling, if and when the cat developed signs of URD, and the handler identity. Cox regression was used to determine the relationship between these factors and URD development. We found cats that did not develop URD were handled significantly more than cats that did (1.1 times per day vs. 0.7 times per day, p < 0.001). Increased frequency of handling had a borderline significant effect on the hazard of developing URD (HR 0.37; CI: 0.13–1.1; p = 0.066). No other parameters were significantly associated with the development of URD; however, small sample size may be responsible for this finding. A larger study is needed to elucidate the relationship between handling and URD development.
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Retrospective Case-Control Study of 2017 G2P[4] Rotavirus Epidemic in Rural and Remote Australia
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Background: A widespread G2P[4] rotavirus epidemic in rural and remote Australia provided an opportunity to evaluate the performance of Rotarix and RotaTeq rotavirus vaccines, ten years after their incorporation into Australia’s National Immunisation Program. Methods: We conducted a retrospective case-control analysis. Vaccine-eligible children with laboratory-confirmed rotavirus infection were identified from jurisdictional notifiable infectious disease databases and individually matched to controls from the national immunisation register, based on date of birth, Aboriginal status and location of residence. Results: 171 cases met the inclusion criteria; most were Aboriginal and/or Torres Strait Islander (80%) and the median age was 19 months. Of these cases, 65% and 25% were fully or partially vaccinated, compared to 71% and 21% of controls. Evidence that cases were less likely than controls to have received a rotavirus vaccine dose was weak, OR 0.79 (95% CI, 0.46–1.34). On pre-specified subgroup analysis, there was some evidence of protection among children <12 months (OR 0.48 [95% CI, 0.22–1.02]), and among fully vs. partially vaccinated children (OR 0.65 [95% CI, 0.42–1.01]). Conclusion: Despite the known effectiveness of rotavirus vaccination, a protective effect of either rotavirus vaccine during a G2P[4] outbreak in these settings among predominantly Aboriginal children was weak, highlighting the ongoing need for a more effective rotavirus vaccine and public health strategies to better protect Aboriginal children.
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Screening of Fish Cell Lines for Piscine Orthoreovirus-1 (PRV-1) Amplification: Identification of the Non-Supportive PRV-1 Invitrome
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Piscine reovirus (PRV) is the causative agent of heart and skeletal muscle inflammation (HSMI), which is detrimental to Atlantic Salmon (AS) aquaculture, but so far has not been cultivatable, which impedes studying the disease and developing a vaccine. Homogenates of head kidney and red blood cells (RBC) from AS in which PRV-1 had been detected were applied to fish cell lines. The cell lines were from embryos, and from brain, blood, fin, gill, gonads, gut, heart, kidney, liver, skin, and spleen, and had the shapes of endothelial, epithelial, fibroblast, and macrophage cells. Most cell lines were derived from the Neopterygii subclass of fish, but one was from subclass Chondrostei. Cultures were examined by phase contrast microscopy for appearance, and by quantitative polymerase chain reaction (qPCR) for PRV-1 RNA amplification and for the capacity to transfer any changes to new cultures. No changes in appearance and Ct values were observed consistently or transferable to new cultures. Therefore, 31 cell lines examined were unable to support PRV-1 amplification and are described as belonging to the non-supportive PRV-1 invitrome. However, these investigations and cell lines can contribute to understanding PRV-1 cellular and host tropism, and the interactions between virus-infected and bystander cells.
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Quantification of Receptor Occupancy by Ligand—An Understudied Class of Potential Biomarkers
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SIMPLE SUMMARY: Molecular complexes, such as those comprised of ligands such as hormones binding to their target receptors, are key determinants of health and disease. While research has focused on measuring receptors or ligands independently as biomarkers, very little attention has been given to measuring ligand-receptor complexes, in part, due to the limited availability of suitable technologies to do such measurements. This has led to underappreciation of ligand-receptor complexes as biomarkers in disease, including in cancer. In this commentary, the potential role of ligand-receptor complexes and their importance as biomarkers in cancer is discussed. We also describe a novel RNA aptamer-based technology, designated as ligand-receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the ligand occupancy of receptors and has potential use as a biomarker discovery platform. ABSTRACT: Molecular complexes, such as ligand–receptor complexes, are vital for both health and disease and can be shed into the circulation in soluble form. Relatively little is known about the biology of soluble ligand–receptor complexes. The functional importance of such complexes and their potential use as clinical biomarkers in diagnosis and therapy remains underappreciated. Most traditional technologies used to study ligand–receptor complexes measure the individual levels of soluble ligands or receptors rather than the complexes themselves. The fraction of receptors occupied by ligand, and the potential clinical relevance of such information, has been largely overlooked. Here, we review the biological significance of soluble ligand–receptor complexes with a specific focus on their potential as biomarkers of cancer and other inflammatory diseases. In addition, we discuss a novel RNA aptamer-based technology, designated ligand–receptor complex-binding aptamers (LIRECAP), that can provide precise measurement of the fraction of a soluble receptor occupied by its ligand. The potential applicability of the LIRECAP technology as a biomarker discovery platform is also described.
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Induction of Chicken Host Defense Peptides within Disease-Resistant and -Susceptible Lines
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Host defense peptides (HDPs) are multifunctional immune molecules that respond to bacterial and viral pathogens. In the present study, bone marrow-derived cells (BMCs) and chicken embryonic fibroblasts (CEFs) were cultured from a Leghorn line (Ghs6) and Fayoumi line (M15.2), which are inbred chicken lines relatively susceptible and resistant to various diseases, respectively. The cells were treated by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly(I:C)) and, subsequently, mRNA expression of 20 chicken HDPs was analyzed before and after the stimulation. At homeostasis, many genes differed between the chicken lines, with the Fayoumi line having significantly higher expression (p < 0.05) than the Leghorn line: AvBD1, 2, 3, 4, 6, and 7 in BMCs; CATH1, CATH3, and GNLY in CEFs; and AvDB5, 8, 9, 10, 11, 12, 13 in both BMCs and CEFs. After LPS treatment, the expression of AvBD1, 2, 3, 4, 5, 9, 12, CATH1, and CATHB1 was significantly upregulated in BMCs, but no genes changed expression in CEFs. After poly(I:C) treatment, AvBD2, 11, 12, 13, CATHB1 and LEAP2 increased in both cell types; CATH2 only increased in BMCs; and AvBD3, 6, 9, 14, CATH1, CATH3, and GNLY only increased in CEFs. In addition, AvBD7, AvBD14, CATH1, CATH2, GNLY, and LEAP2 showed line-specific expression dependent upon cell type (BMC and CEF) and stimulant (LPS and poly(I:C)). The characterization of mRNA expression patterns of chicken HDPs in the present study suggests that their functions may be associated with multiple types of disease resistance in chickens.
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Well-Being at Work after Return to Work (RTW): A Systematic Review
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Background: Employees’ well-being at work after the return to work (RTW) is considered a key aspect of rehabilitation and maintenance of workability. This systematic review aimed at identifying the common psychosocial factors that predict the subjective and psychological well-being in RTW processes after having a long-standing health problem or disability. Objective: To evaluate the subjective and psychological well-being at work of employees with chronic or long-standing health problems or those returning to work after any cause of disability. Data source: Systematic review of articles published in English or Spanish using PsycINFO, PsycARTICLES, MEDLINE, Psychology, and Behavioral Sciences Collection, and Pubpsych. An additional study was identified by contacting expert academics in the field. The search equations used included terms such as Return to Work, Long-Standing Health Problems or Disability, Work Health Balance, and job satisfaction or subjective well-being. Eligibility criteria for the studies: Studies that included a measure of employees’ well-being at work following return to work were selected for the review. Evaluation of the studies and synthesis methods: The studies were selected using predefined fields which included quality criteria. Results: Of the 264 articles returned by the initial search, a total of 20 were finally selected. Results were organized around the three different theoretical approaches for understanding RTW and its antecedents and consequences: (a) RTW and autonomy at work have a positive effect on psychological well-being; (b) job demand is linked to less job satisfaction, whereas a higher level on the work–health balance is associated with job satisfaction and work engagement; (c) internal and external support is linked to job satisfaction in the case of a disease. Limitations: The evidence provided by the results is restricted by the limited availability of studies focusing on well-being at work following return to work. Moreover, the studies identified are of different kinds, thereby preventing comparisons. Conclusions and implications of the main findings: Employees’ subjective well-being after return to work has received very little attention to date. Given its importance in the current configuration of the labor market, it should be the object of more research.
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Trust, Connection and Equity: Can Understanding Context Help to Establish Successful Campus Community Gardens?
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Campus community gardens (CCGs) can potentially improve student health and wellbeing, mitigate social and ecological problems, and nurture university-community relationships. However, CCGs are located in complex socio-political and ecological settings and many community gardens struggle or fail. However, few studies have assessed the socio-political/ecological context of a garden setting prior to its development to understand the potential barriers and enablers of success. Our study assessed the socio-spatial context of a proposed CCG at a student university accommodation site. We engaged diverse university and community stakeholders through interviews, focus groups and a survey to explore their perceptions of the space generally and the proposed garden specifically. Visual observations and public life surveying were used to determine patterns of behavior. Results confirmed known problems associated with an underutilized site that provides little opportunity for lingering or contact with nature; and unknown barriers, including socially disconnected stakeholders and community distrust of the university. The research also uncovered positive enablers, such as stakeholder appreciation of the social, wellbeing and ecological benefits that a CCG could deliver. Our findings suggest that an in-depth exploration of a proposed garden context can be an important enabler of its success.
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Plasmonic Sensors for Monitoring Biological and Chemical Threat Agents
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Sensors are excellent options owing to their ability to figure out a large number of problems and challenges in several areas, including homeland security, defense, medicine, pharmacology, industry, environment, agriculture, food safety, and so on. Plasmonic sensors are used as detection devices that have important properties, such as rapid recognition, real-time analysis, no need labels, sensitive and selective sensing, portability, and, more importantly, simplicity in identifying target analytes. This review summarizes the state-of-art molecular recognition of biological and chemical threat agents. For this purpose, the principle of the plasmonic sensor is briefly explained and then the use of plasmonic sensors in the monitoring of a broad range of biological and chemical threat agents is extensively discussed with different types of threats according to the latest literature. A conclusion and future perspectives are added at the end of the review.
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Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins
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Decoration proteins are viral accessory gene products that adorn the surfaces of some phages and viral capsids, particularly tailed dsDNA phages. These proteins often play a “cementing” role, reinforcing capsids against accumulating internal pressure due to genome packaging, or environmental insults such as extremes of temperature or pH. Many decoration proteins serve alternative functions, including target cell recognition, participation in viral assembly, capsid size determination, or modulation of host gene expression. Examples that currently have structures characterized to high-resolution fall into five main folding motifs: β-tulip, β-tadpole, OB-fold, Ig-like, and a rare knotted α-helical fold. Most of these folding motifs have structure homologs in virus and target cell proteins, suggesting horizontal gene transfer was important in their evolution. Oligomerization states of decoration proteins range from monomers to trimers, with the latter most typical. Decoration proteins bind to a variety of loci on capsids that include icosahedral 2-, 3-, and 5-fold symmetry axes, as well as pseudo-symmetry sites. These binding sites often correspond to “weak points” on the capsid lattice. Because of their unique abilities to bind virus surfaces noncovalently, decoration proteins are increasingly exploited for technology, with uses including phage display, viral functionalization, vaccination, and improved nanoparticle design for imaging and drug delivery. These applications will undoubtedly benefit from further advances in our understanding of these versatile augmenters of viral functions.
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Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection
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SIMPLE SUMMARY: In our systematic review and meta-analysis of eight observational studies including a total of 1016 patients, we demonstrated excellent pooled inter-observer agreement among Genito-Urinary radiologists when adopting the novel Vesical Imaging-Reporting and Data System (VI-RADS) criteria in the pre-trans-urethral resection of bladder tumor (TURBT) assessment for non-muscle (NMIBC) vs. muscle-invasive bladder cancer (MIBC) detection. ABSTRACT: The Vesical Imaging-Reporting and Data System (VI-RADS) has been introduced to provide preoperative bladder cancer staging and has proved to be reliable in assessing the presence of muscle invasion in the pre-TURBT (trans-urethral resection of bladder tumor). We aimed to assess through a systematic review and meta-analysis the inter-reader variability of VI-RADS criteria for discriminating non-muscle vs. muscle invasive bladder cancer (NMIBC, MIBC). PubMed, Web of Science, Cochrane, and Embase were searched up until 30 July 2020. The Quality Appraisal of Diagnostic Reliability (QAREL) checklist was utilized to assess the quality of included studies and a pooled measure of inter-rater reliability (Cohen’s Kappa [κ] and/or Intraclass correlation coefficients (ICCs)) was calculated. Further sensitivity analysis, subgroup analysis, and meta-regression were conducted to investigate the contribution of moderators to heterogeneity. In total, eight studies between 2018 and 2020, which evaluated a total of 1016 patients via 21 interpreting genitourinary (GU) radiologists, met inclusion criteria and were critically examined. No study was considered to be significantly flawed with publication bias. The pooled weighted mean κ estimate was 0.83 (95%CI: 0.78–0.88). Heterogeneity was present among the studies (Q = 185.92, d.f. = 7, p < 0.001; I2 = 92.7%). Meta-regression analyses showed that the relative % of MIBC diagnosis and cumulative reader’s experience to influence the estimated outcome (Coeff: 0.019, SE: 0.007; p= 0.003 and 0.036, SE: 0.009; p = 0.001). In the present study, we confirm excellent pooled inter-reader agreement of VI-RADS to discriminate NMIBC from MIBC underlying the importance that standardization and reproducibility of VI-RADS may confer to multiparametric magnetic resonance (mpMRI) for preoperative BCa staging.
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Longitudinal Predictors of Self-Regulation at School Entry: Findings from the All Our Families Cohort
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Self-regulation is the ability to manage emotions, modulate behaviors, and focus attention. This critical skill begins to develop in infancy, improves substantially in early childhood and continues through adolescence, and has been linked to long-term health and well-being. The objectives of this study were to determine risk factors and moderators associated with the three elements of self-regulation (i.e., inattention, emotional control, or behavioral control) as well as overall self-regulation, among children at age 5. Participants were mother–child dyads from the All Our Families study (n = 1644). Self-regulation was assessed at age 5. Risk factors included income, maternal mental health, child sex, and screen time, and potential moderation by parenting and childcare. Adjusted odds ratios of children being at risk for poor self were estimated using multivariable logistic regression. Twenty-one percent of children had poor self-regulation skills. Risk factors for poor self-regulation included lower income, maternal mental health difficulties, and male sex. Childcare and poor parenting did not moderate these associations and hostile and ineffective parenting was independently associated with poor self-regulation. Excess screen time (>1 h per day) was associated with poor self-regulation. Self-regulation involves a complex and overlapping set of skills and risk factors that operate differently on different elements. Parenting and participation in childcare do not appear to moderate the associations between lower income, maternal mental health, male sex, and screen time with child self-regulation.
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Quercitrin Ameliorates Hyperlipidemia and Hepatic Steatosis in Ovariectomized Mice
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Nonalcoholic fatty liver disease (NAFLD) is associated with progressive metabolic diseases. Estrogen deficiency increases the NAFLD risk among postmenopausal women. Thus, effective agents to prevent and treat NAFLD in postmenopausal women are required. Quercitrin (Quer) is a natural glycosylated flavonoid with antimicrobial, anti-inflammatory, and hypolipidemic effects. This study investigated whether Quer improves dysregulated lipid metabolism and suppresses hepatic steatosis in ovariectomized (OVX) mice as an experimental model mimicking postmenopausal women. Mice were assigned to the following four groups: SHAM, OVX, OVX + β-estradiol (0.4 mg/kg diet), and OVX + Quer (500 mg/kg diet). Mice were administered a diet with or without Quer for three months. OVX mice displayed significantly higher body mass, epidermal fat, and liver weights than those of SHAM mice. However, these levels were reduced in Quer-treated mice. Quer treatment reduced the levels of serum lipid metabolites, including triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Furthermore, Quer reduced liver lipid steatosis and inhibited the expression of proinflammatory cytokines, such as tumor necrosis factor-α, IL-6, and IL-1β. The results of the present study indicate that Quer improves dysregulated lipid metabolism and reduces hepatic steatosis and inflammation by compensating for estrogen deficiency, suggesting that Quer may potentially exert protective effects during hepatic steatosis in postmenopausal women.
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The Impact of Experience, Length of Service, and Workplace Preparedness in Physicians’ Readiness in the Response to Disasters
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With an increasing number of natural and man-made disasters, the need for preparedness in all levels of management is obvious. Among healthcare professionals responding to these emergencies, physicians are of particular importance due to their significant roles as leaders and frontline workers in minimizing morbidity and mortality of the affected population. This study analyses the preparedness of 549 physicians from all medical centers in Lublin, Poland to formulate their observations, suggestions, and recommendations concerning the improvement of the chain of response in disaster management. The results of this study show that the perceived preparedness of physicians for disaster management and response is not as high as it should be, and the majority of the respondents perceived their disaster preparedness insufficient. Training of physicians in disaster management and principles of disaster medicine is needed, by focusing on the specificity of rescue response to emergencies following disasters, and medical and non-medical aspects of the response with particular emphasis on a management approach covering all hazards.
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Curcumin: Could This Compound Be Useful in Pregnancy and Pregnancy-Related Complications?
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Curcumin, the main polyphenol contained in turmeric root (Curcuma longa), has played a significant role in medicine for centuries. The growing interest in plant-derived substances has led to increased consumption of them also in pregnancy. The pleiotropic and multi-targeting actions of curcumin have made it very attractive as a health-promoting compound. In spite of the beneficial effects observed in various chronic diseases in humans, limited and fragmentary information is currently available about curcumin’s effects on pregnancy and pregnancy-related complications. It is known that immune-metabolic alterations occurring during pregnancy have consequences on both maternal and fetal tissues, leading to short- and long-term complications. The reported anti-inflammatory, antioxidant, antitoxicant, neuroprotective, immunomodulatory, antiapoptotic, antiangiogenic, anti-hypertensive, and antidiabetic properties of curcumin appear to be encouraging, not only for the management of pregnancy-related disorders, including gestational diabetes mellitus (GDM), preeclampsia (PE), depression, preterm birth, and fetal growth disorders but also to contrast damage induced by natural and chemical toxic agents. The current review summarizes the latest data, mostly obtained from animal models and in vitro studies, on the impact of curcumin on the molecular mechanisms involved in pregnancy pathophysiology, with the aim to shed light on the possible beneficial and/or adverse effects of curcumin on pregnancy outcomes.
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Clinical Impact of Small Bowel Capsule Endoscopy in Obscure Gastrointestinal Bleeding
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Background and objectives: The most frequent indications for small bowel capsule endoscopy (SBCE) are obscure gastrointestinal bleeding (OGIB) and iron deficiency anemia (IDA). The aim of this study was to evaluate the diagnostic yield (DY) of SBCE in overt and occult OGIB, as well as its impact on the clinical outcome. Materials and Methods: This study retrospectively included all cases of OGIB investigated by SBCE in a tertiary care referral center, between 1st January 2016 and 31st December 2018. OGIB was defined by overt or occult gastrointestinal bleeding, with negative upper and lower endoscopy. Occult gastrointestinal bleeding was either proved by a fecal test or presumptively incriminated as a cause for IDA. DY was defined as the detection rate for what were thought to be clinically significant findings. DYs for overt and occult bleeding were assessed and compared. Gender, age, hemoglobin levels, NSAID consumption and the use of anticoagulants were recorded. Following SBCE results, individual therapeutic decisions were made, and follow-up data were recorded. Results: 224 SBCE examinations were performed for OGIB, of which 148 were for overt OGIB, and 76 for unexplained IDA. Positive findings were found in 139 patients, resulting in an overall DY for OGIB of 62%, higher in overt OGIB (75%) compared to IDA (37%). The most frequent findings were small bowel angioectasias (62.2% in overt OGIB and 78.5% in IDA). On multivariate logistic regression analysis, only hemoglobin level <10 g/dL and anticoagulants were the variables independently associated with positive findings. All patients received medical, endoscopic or surgical treatment and had good clinical outcome during follow-up. Conclusion: SBCE has a high diagnostic yield and a positive impact on management of patients with OGIB.
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Immunological Perspective for Ebola Virus Infection and Various Treatment Measures Taken to Fight the Disease
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Ebolaviruses, discovered in 1976, belongs to the Filoviridae family, which also includes Marburg and Lloviu viruses. They are negative-stranded RNA viruses with six known species identified to date. Ebola virus (EBOV) is a member of Zaire ebolavirus species and can cause the Ebola virus disease (EVD), an emerging zoonotic disease that results in homeostatic imbalance and multi-organ failure. There are three EBOV outbreaks documented in the last six years resulting in significant morbidity (>32,000 cases) and mortality (>13,500 deaths). The potential factors contributing to the high infectivity of this virus include multiple entry mechanisms, susceptibility of the host cells, employment of multiple immune evasion mechanisms and rapid person-to-person transmission. EBOV infection leads to cytokine storm, disseminated intravascular coagulation, host T cell apoptosis as well as cell mediated and humoral immune response. In this review, a concise recap of cell types targeted by EBOV and EVD symptoms followed by detailed run-through of host innate and adaptive immune responses, virus-driven regulation and their combined effects contributing to the disease pathogenesis has been presented. At last, the vaccine and drug development initiatives as well as challenges related to the management of infection have been discussed.
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Evaluating the Efficacy of a Mobile App (Drinks:Ration) and Personalized Text and Push Messaging to Reduce Alcohol Consumption in a Veteran Population: Protocol for a Randomized Controlled Trial
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BACKGROUND: Alcohol misuse is higher in the UK Armed Forces than in the general population. Previous research has shown that interventions delivered via smartphones are efficacious in promoting self-monitoring of alcohol use, have utility in reducing alcohol consumption, and have a broad reach. OBJECTIVE: This single-blinded randomized controlled trial (RCT) aims to assess the efficacy of a 28-day brief alcohol intervention delivered via a smartphone app (Drinks:Ration) in reducing weekly self-reported alcohol consumption between baseline and 3-month follow-up among veterans who drink at a hazardous or harmful level and receive or have received support for mental health symptoms in a clinical setting. METHODS: In this two-arm, single-blinded RCT, a smartphone app that includes interactive features designed to enhance participants’ motivation and personalized messaging is compared with a smartphone app that provides only government guidance on alcohol consumption. The trial will be conducted in a veteran population that has sought help through Combat Stress, a UK veteran’s mental health charity. Recruitment, consent, and data collection will be carried out automatically through the Drinks:Ration platform. The primary outcome is the change in self-reported weekly alcohol consumption between baseline (day 0) and 3-month follow-up (day 84) as measured using the Time-Line Follow back for Alcohol Consumption. Secondary outcome measures include (1) change in the baseline to 3-month follow-up (day 84) Alcohol Use Disorder Identification Test score and (2) change in the baseline to 3-month follow-up (day 84) World Health Organization Quality of Life-BREF score to assess the quality of adjusted life years. Process evaluation measures include (1) app use and (2) usability ratings as measured by the mHealth App Usability Questionnaire. The primary and secondary outcomes will also be reassessed at the 6-month follow-up (day 168) to assess the longer-term benefits of the intervention, which will be reported as a secondary outcome. RESULTS: The study will begin recruitment in October 2020 and is expected to require 12 months to complete. The study results will be published in 2022. CONCLUSIONS: This study assesses whether a smartphone app is efficacious in reducing self-reported alcohol consumption in a veteran population that has sought help through Combat Stress using personalized messaging and interactive features. This innovative approach, if successful, may provide a means to deliver a low-cost health promotion program that has the potential to reach large groups, in particular those who are geographically dispersed, such as military personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT04494594; https://clinicaltrials.gov/ct2/show/NCT04494594 INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/19720
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Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis
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The Type I Interferons (IFN-Is) are innate antiviral cytokines that include 12 different IFNα subtypes and IFNβ that signal through the IFN-I receptor (IFNAR), inducing hundreds of IFN-stimulated genes (ISGs) that comprise the ‘interferome’. Quantitative differences in IFNAR binding correlate with antiviral activity, but whether IFN-Is exhibit qualitative differences remains controversial. Moreover, the IFN-I response is protective during acute HIV-1 infection, but likely pathogenic during the chronic stages. To gain a deeper understanding of the IFN-I response, we compared the interferomes of IFNα subtypes dominantly-expressed in HIV-1-exposed plasmacytoid dendritic cells (1, 2, 5, 8 and 14) and IFNβ in the earliest cellular targets of HIV-1 infection. Primary gut CD4 T cells from 3 donors were treated for 18 hours ex vivo with individual IFN-Is normalized for IFNAR signaling strength. Of 1,969 IFN-regulated genes, 246 ‘core ISGs’ were induced by all IFN-Is tested. However, many IFN-regulated genes were not shared between the IFNα subtypes despite similar induction of canonical antiviral ISGs such as ISG15, RSAD2 and MX1, formally demonstrating qualitative differences between the IFNα subtypes. Notably, IFNβ induced a broader interferome than the individual IFNα subtypes. Since IFNβ, and not IFNα, is upregulated during chronic HIV-1 infection in the gut, we compared core ISGs and IFNβ-specific ISGs from colon pinch biopsies of HIV-1-uninfected (n = 13) versus age- and gender-matched, antiretroviral-therapy naïve persons with HIV-1 (PWH; n = 19). Core ISGs linked to inflammation, T cell activation and immune exhaustion were elevated in PWH, positively correlated with plasma lipopolysaccharide (LPS) levels and gut IFNβ levels, and negatively correlated with gut CD4 T cell frequencies. In sharp contrast, IFNβ-specific ISGs linked to protein translation and anti-inflammatory responses were significantly downregulated in PWH, negatively correlated with gut IFNβ and LPS, and positively correlated with plasma IL6 and gut CD4 T cell frequencies. Our findings reveal qualitative differences in interferome induction by diverse IFN-Is and suggest potential mechanisms for how IFNβ may drive HIV-1 pathogenesis in the gut.
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Krankenhausmedizinische Interventionen in der neurologischen Anschlussrehabilitation
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Treatment in hospitals differs from treatment in rehabilitation centers from a legal perspective because German law mandates that in hospitals physicians and other qualified personnel must be on duty at all times. This is not required for inpatient rehabilitation centers. Since this Act was passed more than 30 years ago, more acute medical interventions are now carried out and the number of older people in the population has increased. As a result patients are nowadays older, more multimorbid and therefore have a greater risk for medical complications. This is especially true for postacute neurological care. For this reason, the original legal framework for neurological rehabilitation treatment has become questionable. Therefore, we prospectively tested how often patients in inpatient neurorehabilitation suffer from complications that require immediate attention by qualified personnel. In 759 patients observed over a period of 6 months we found 602 complications requiring immediate interventions by physicians (e.g. falls, urinary tract infections, other forms of fever, diarrhea associated with Clostridium difficile, pneumonia, respiratory insufficiency, sepsis, epileptic seizures and arrhythmia). On average at least three acute care interventions occurred per day at the facility examined. We conclude that neurological inpatient rehabilitation has outgrown its legal foundations and now incorporates hospital care.
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In This Issue: December 2020
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No evidence for sylvatic cycles of chikungunya, dengue and Zika viruses in African green monkeys (Chlorocebus aethiops sabaeus) on St. Kitts, West Indies
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BACKGROUND: Dengue, chikungunya and Zika viruses (DENV, CHIKV and ZIKV) are transmitted in sylvatic transmission cycles between non-human primates and forest (sylvan) mosquitoes in Africa and Asia. It remains unclear if sylvatic cycles exist or could establish themselves elsewhere and contribute to the epidemiology of these diseases. The Caribbean island of St. Kitts has a large African green monkey (AGM) (Chlorocebus aethiops sabaeus) population and is therefore ideally suited to investigate sylvatic cycles. METHODS: We tested 858 AGM sera by ELISA and PRNT for virus-specific antibodies and collected and identified 9704 potential arbovirus vector mosquitoes. Mosquitoes were homogenized in 513 pools for testing by viral isolation in cell culture and by multiplex RT-qPCR after RNA extraction to detect the presence of DENV, CHIKV and ZIKVs. DNA was extracted from 122 visibly blood-fed individual mosquitoes and a polymorphic region of the hydroxymethylbilane synthase gene (HMBS) was amplified by PCR to determine if mosquitoes had fed on AGMs or humans. RESULTS: All of the AGMs were negative for DENV, CHIKV or ZIKV antibodies. However, one AGM did have evidence of an undifferentiated Flavivirus infection. Similarly, DENV, CHIKV and ZIKV were not detected in any of the mosquito pools by PCR or culture. AGMs were not the source of any of the mosquito blood meals. CONCLUSION: Sylvatic cycles involving AGMs and DENV, CHIKV and ZIKV do not currently exist on St. Kitts. [Image: see text]
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Electroencephalographic features in patients undergoing extracorporeal membrane oxygenation
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BACKGROUND: Neurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome. METHODS: Retrospective analysis of all patients undergoing venous–venous (V–V) or venous–arterial (V–A) ECMO with a concomitant EEG recording (April 2009–December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge. RESULTS: A total of 139 patients (54 [41–62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno–arterial (V–A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25–16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24–82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories. CONCLUSIONS: In adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.
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Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We?
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Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00940-4) contains supplementary material, which is available to authorized users.
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Comparison of oral versus intravenous tranexamic acid in total knee and hip arthroplasty: A GRADE analysis and meta-analysis
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BACKGROUND: The efficacy and safety of oral tranexamic acid (TXA) remain controversial because of the small number of clinical studies. The aim of the present study was to compare the efficacy and safety of oral TXA with intravenous TXA in patients undergoing total hip arthroplasty and total knee arthroplasty in a systematic review and meta-analysis. METHODS: We conducted a meta-analysis to identify randomized controlled trials (RCTs) involving oral and intravenous TXA in total hip arthroplasty and total knee arthroplasty up to December 2019 by searching databases including PubMed, Web of Science, Embase, the Cochrane Controlled Trials Register, the Cochrane Library China Biology Medicine, China National Knowledge Infrastructure, China Science and Technology Journal Database and Wanfang. The mean difference or standard mean difference was used to assess continuous outcomes such as hemoglobin (Hb) drop, total blood loss, drain blood loss, and length of hospital stay, with a 95% confidence interval. Relative risks with a 95% confidence interval were used to assess dichotomous outcomes such as transfusion rate and the incidence of deep venous thrombosis and calf muscular vein thrombosis. Review Manager was used for the meta-analysis. RESULTS: Ten RCTs containing 1080 participants met the inclusion criteria. We found no significant differences in terms of the average Hb drop (P = .60), total blood loss (P = .60), transfusion rate (P = .99), drain blood loss (P = .91), length of hospital stay (P = .95), and the incidence of deep venous thrombosis (P = .55) and calf muscular vein thrombosis (P = .19) between oral and IV TXA. CONCLUSIONS: Compared with the IV TXA, oral TXA has similar effects on reducing the Hb drop, total blood loss, transfusion rate, drain blood loss, and length of hospital stay without increasing the risk of calf muscular vein thrombosis and deep venous thrombosis. Furthermore, oral TXA is easy to access and administer, which decreases the workload of nurses and even delivers cost-saving benefits to the health care system. We thus conclude that oral TXA may be an optimal approach in total joint arthroplasty. However, more high-quality and multicenter RCTs are still needed to confirm our conclusions. REGISTRATION: The current meta-analysis was registered on PROSPERO (International Prospective Register of Systematic Reviews), and the registration number was CRD42018111291.
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Structural equation modeling test of the pre-intentional phase of the health action process approach (HAPA) model on condom use intention among senior high school students in Tianjin, China
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Based on the Theory of Health Action Process Approach (HAPA) Model, this study aimed to investigate factors associated with condom use intention in Chinese adolescents. In 2017, we conducted a cross-sectional study using stratified cluster, convenience sampling method to assess condom use intention among senior high school students in Tianjin, China. One thousand eighty two senior high school students were anonymously surveyed through self-administered questionnaires. Structural equation modelling was used to assess the pre-intentional phase of HAPA model. Among the participants, 41.5% (449/1082) were male, 54.1% (585/1082) were female, 4.4% (48/1082) were gender-deficient. The average age was 16.7 years. The final pre-intentional phase of HAPA model was acceptable (CFI = 0.95; GFI = 0.94; RMSEA = 0.06). Action self-efficacy (r = 0.60) had a strong direct effect on condom use intention. The pre-intentional phase of HAPA model is valid to assess condom use intention among Chinese senior high school students. The pre-intention phase of the HAPA model could be applied to guide AIDS health educations of students, and further research is needed to evaluate the effect.
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Integrated TCGA and GEO analysis showed that SMAD7 is an independent prognostic factor for lung adenocarcinoma
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The lack of effective markers leads to missed optimal treatment times, resulting in poorer prognosis in most cancers. Drosophila mothers against decapentaplegic protein (SMAD) family members are important cytokines in the transforming growth factor-beta family. They jointly regulate the processes of cell growth, differentiation, and apoptosis. However, the expression of SMAD family genes in pan-cancers and their impact on prognosis have not been elucidated. Perl software and R software were used to perform expression analysis and survival curve analysis on the data collected by TCGA, GTEx, and GEO, and the potential regulatory pathways were determined through gene ontology enrichment and kyoto encyclopedia of genes and genomes enrichment analysis. It was found that SMAD7 and SMAD9 expression decreased in lung adenocarcinoma (LUAD), and their expression was positively correlated with survival time. Additionally, SMAD7 could be used as an independent prognostic factor for LUAD. In general, SMAD7 and SMAD9 can be used as prognostic markers of LUAD. Further, SMAD7 is expected to become a therapeutic target for LUAD.
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3,648 |
Clinical implications and nomogram prediction of long noncoding RNA FRGCA as diagnostic and prognostic indicators in colon adenocarcinoma
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Colorectal cancer, especially colon adenocarcinoma (COAD), is associated with significant morbidity and mortality worldwide. Long noncoding RNA (lncRNA) has been implicated in tumorigenesis. The aim of the present study was to elucidate the potential diagnostic and prognostic values of lncRNA FRGCA in COAD. The data of 438 COAD patients were retrieved for analysis. Diagnostic significance was evaluated using tumor and nontumor tissues. Prognostic significance was evaluated using a Cox proportional regression model. Stratified analysis was performed to identify associations between clinical factors and lncRNA FRGCA expression. A nomogram was constructed using the clinical factors and lncRNA FRGCA for survival prediction. Enrichment analysis identified gene ontologies and metabolic pathways of mRNAs with high Pearson correlation coefficients with lncRNA FRGCA. lncRNA FRGCA was highly expressed in tumor tissues of COAD and demonstrated diagnostic value (area under curve = 0.763, P < .0001). Prognostic significance analysis indicated that lncRNA FRGCA had prognostic value in COAD [adjusted P < .001, hazard ratio (HR) = 0.444, 95% confidence interval (95% CI) = 0.288–0.685] and high expression of lncRNA FRGCA indicated better survival in COAD. A nomogram was evaluated for prediction of survival at 1, 3, and 5 years. Enrichment analysis revealed many mRNAs involved in the structural constituents of the mitochondrial inner membrane and translational termination, protein binding, translation, ribosome, oxidative phosphorylation, and metabolic pathways, especially the nucleoplasm. Differentially expressed in tumor vs nontumor tissues, lncRNA FRGCA had both diagnostic and prognostic implications in COAD, which may be associated with ribosome metabolism, oxidative phosphorylation, and nucleoplasm-related metabolic pathways.
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Full-endoscopic decompression for thoracic ossification of ligamentum flavum: surgical techniques and clinical outcomes: A retrospective clinical study
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BACKGROUND: Many complications are associated with thoracic open decompression surgery, such as dural tears and neurological deficits. The clinical outcomes are also not satisfactory. Full-endoscopic decompression of the lumbar spinal canal has achieved satisfactory results for the treatment of lumbar spinal stenosis. This surgery may be used for the treatment of thoracic ossification of the ligamentum flavum (OLF) under local anesthesia. The aim of our study is to introduce the surgical techniques used for full-endoscopic decompression for thoracic OLF and to evaluate its safety and efficacy. METHODS: Fourteen patients with thoracic OLF (4 combined with dural ossification) underwent full-endoscopic decompression surgery. An interlaminar approach was performed. The anchoring method was used to establish the working passage. Spinal cord exposure began at a space between the ossification and the spinal cord, and dorsal and contralateral decompression were performed with the “Over the Top” technique. The modified Japanese Orthopedic Association score (11 points) was used to evaluate the efficacy during follow-up. At the same time, the visual analogue scale score for assessing back pain before and after the operation was evaluated. RESULTS: The average operation time was 159.73 ± 62.09 minutes, and the hospitalization time was 7.43 ± 1.79 days. The follow-up period ranged from 8 to 22 months. Neurological function was improved. There were no serious complications. Dural tears occurred in 5 patients, intraoperative neurological deterioration occurred in 1 patient, and intraoperative headache and neck pain occurred in 1 patient. CONCLUSION: Full-endoscopic decompression is an effective, safe surgical technique for thoracic OLF even the cases combined with dural ossification.
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Placebo use and outcome quality: A protocol for systematic review and meta-analysis
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BACKGROUND: The Pharmaceutical industry sponsorship, research outcome and quality has been already evaluated for clinical trials in order to analyze if this kind of sponsorship affects the results of clinical trials. In this sense, this study has the aim to investigate whether placebo use allows positive outcomes regarding efficacy and safety compared to synthetic medicines. METHODS: We designed and registered a study protocol for a systematic review for methodology data. We will only randomized clinical trials that use placebo as comparator. The main outcome will be the evaluation of placebo use regarding the tendency for positive results (efficacy and security) when comparing to synthetic medicines. PubMed, Cochrane, LILACS (BVS), Web of Science, Scopus, and Excerpta Medica dataBASE (EMBASE) databases will be searched. Gray literature will be identified through the databases Proquest (Dissertation and Theses), OpenGrey and Google Scholar. Two review authors will independently assess trial quality and will extract data in accordance with standard Cochrane methodology. If necessary, we will also contact authors for additional information. The Cochrane Collaboration's risk of bias tool will be used. If feasible, it means homogenous data, we will conduct random effects meta-analysis. Subgroup analyses will be conducted for different justifications for placebo use and for studies sponsored/not sponsored by the pharmaceutical industry. RESULTS: Our present findings will indicate the effects of placebo use as comparator regarding efficacy and safety of the oral synthetic medicines. DISCUSSION: This systematic review will identify, summarize, and analyze if there is a trend for positive efficacy and safety results for synthetic medicines in clinical trials when compared with placebo and if the justification for placebo use is considered ethically acceptable. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018110829
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A delayed diagnosis of late-onset pulmonary hemorrhage in a toddler with Henoch-Schönlein purpura after regression of skin rash: A case report and literature review
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RATIONALE: Pulmonary hemorrhage is a rare but fatal complication of Henoch-Schönlein purpura (HSP), and more easily ignored in children than in adults due to the absence of clinically evident hemoptysis. Moreover, despite being sporadically reported, given that pulmonary hemorrhage may develop after regression and even disappearance of skin rash, the asynchronous progression of skin and lung lesions poses escalating challenges in the timely diagnosis. We herein presented a delayed diagnosis of late-onset pulmonary hemorrhage in a child with HSP after regression of purpuric rash. PATIENT CONCERNS: A 6-year and 3-month child with a history of self-resolved purpuric rash three weeks ago, presented acutely with cough and dyspnea but without fever. DIAGNOSES: The decreased hemoglobin and diffuse ground-glass opacities of both lungs on CT scan weren’t comprehensively evaluated. The child was initially misdiagnosed as pneumonia. INTERVENTIONS: Antibiotic treatment was initiated. However, no improvement of respiratory status was found following aggressive combination therapy. Bronchoscopy was subsequently performed. OUTCOMES: An diffuse alveolar hemorrhage with low inflammatory profile was noted after a bronchoscopy. Considering the history of HSP, the diagnosis of HSP-associated pulmonary hemorrhage was ultimately confirmed and the patient received corticosteroids with satisfactory results. LESSONS: Pulmonary hemorrhage could occur in children with HSP at late onset of disease after regression of skin rash. New-onset respiratory symptoms in patients with a history of HSP should heighten suspicion for pulmonary hemorrhage, particularly if presenting with lack of fever, sudden drop of hemoglobin, new pulmonary infiltrates and unresponsiveness to antibiotics therapy. Bronchoscopy should be performed early to confirm the diagnosis, specifically for children.
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Predicting article citations using data of 100 top-cited publications in the journal Medicine since 2011: A bibliometric analysis
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BACKGROUND: Publications regarding the 100 top-cited articles in a given discipline are common, but studies reporting the association between article topics and their citations are lacking. Whether or not reviews and original articles have a higher impact factor than case reports is a point for verification in this study. In addition, article topics that can be used for predicting citations have not been analyzed. Thus, this study aims to: (1).. provide a visualization dashboard for the 100 top-cited articles related to article types and (2).. inspect major medical subject headings (i.e., MeSH terms in PubMed) to help predict citations. METHODS: We searched PubMed Central and downloaded 100 top-cited abstracts in the journal Medicine (Baltimore) since 2011. Four article types and 7 topic categories (denoted by MeSH terms) were extracted from abstracts. Contributors to these 100 top-cited articles were analyzed. Social network analysis and Sankey diagram analysis were performed to identify influential article types and topic categories. MeSH terms were applied to predict the number of article citations. We then examined the prediction power with the correlation coefficients between MeSH weights and article citations. RESULTS: The citation counts for the 100 articles ranged from 24 to 127, with an average of 39.1 citations. The most frequent article types were journal articles (82%) and comparative studies (10%), and the most frequent topics were epidemiology (48%) and blood and immunology (36%). The most productive countries were the United States (24%) and China (23%). The most cited article (PDID = 27258521) with a count of 135 was written by Dr Shang from Shandong Provincial Hospital Affiliated to Shandong University (China) in 2016. MeSH terms were evident in the prediction power of the number of article citations (correlation coefficients = 0.49, t = 5.62). CONCLUSION: The breakthrough was made by developing dashboards showing the overall concept of the 100 top-cited articles using the Sankey diagram. MeSH terms can be used for predicting article citations. Analyzing the 100 top-cited articles could help future academic pursuits and applications in other academic disciplines.
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Impact of neurological diseases on family planning: A single-center experience
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This cross-sectional study aimed to assess the impact of epilepsy, myasthenia gravis (MG), and multiple sclerosis (MS) on pregnancy and family planning decision-making in a cohort of Saudi women. Women with epilepsy, MG, and MS were recruited consecutively at the time of their follow-up visits at a neurology clinic. Data were collected using 3 standardized questionnaires, and presented using descriptive statistics. A logistic regression was performed to determine variables associated with decisions regarding abstaining from pregnancy and encouraging other women to conceive. A total of 272 (83 epilepsy, 69 MG, and 120 MS) women with a mean age of 29.9 ± 8.0 years participated. The proportion of women who abstained from or postponed pregnancy was 41.2% and 31.4%, respectively. The concerns mentioned most often were disease worsening during pregnancy, peripartum and postpartum, side effects of medications on the unborn child, and inability to care for the child. Older age was independently associated with the decision to abstain from pregnancy (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.04 - 1.25). Higher knowledge levels were independently associated with encouraging other women to have children (OR 1.3, 95% CI 1.11–1.53). Over 50% of women reported that they were not counseled on issues related to pregnancy and childbirth. In conclusion, we identified a major influence of epilepsy, MG, and MS on pregnancy and family planning. Comprehensive counseling programs are needed to help women with these neurological diseases make informed family-planning decisions.
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3,654 |
Erythropoietin combined with traditional Chinese medicine for chemotherapy-induced anemias: A protocol of systematic review and meta-analysis
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BACKGROUND: As far as we know, several systematic review and meta-analysis have assessed the safety and efficacy of erythropoiesis-stimulating agents (ESAs) in the patients with chemotherapy-induced anemia (CIA). But no study assesses the safety and efficacy of ESAs combined with traditional Chinese medicine (TCM). The aim of our study is to assess the efficacy and safety of ESAs combination with TCM for patients with CIA and will provide a higher level of evidence for clinical applications. METHODS: This protocol adheres to the preferred reporting items for systematic reviews and meta-analysis protocol statement. The source of literature will be a structured search of the following 7 electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, and Wanfang Database. Records will be independently evaluated by 2 reviewers. Disagreements will be resolved through consensus or third-party adjudication. Review Manager 5.3 software (Cochrane Collaboration, Copenhagen Denmark) will be used to perform meta-analysis. For dichotomous variables, odds ratio with 95% confidence intervals will be obtained by the Mantel–Haenszel method. For continuous data, mean difference with 95% confidence intervals will be used. P < 0.05 will be considered to be statistically significant. RESULTS: This study will be performed to test the efficacy and safety of ESAs combined with TCM for CIA in patients with cancer. CONCLUSIONS: The result of this study will be promoted mainly in 2 ways: publish in peer-reviewed journals in the fastest way; and promotion in domestic and foreign conferences. INPLASY REGISTRATION NUMBER: INPLASY202080041.
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3,655 |
Small but protective social capital against suicide ideation in poor communities: A community-based cross-sectional study
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Coupled with the lowest level of social connectedness, South Korea has the highest suicide rate among the Organization for Economic Co-operation and Development countries. A possible link between community and suicide is social capital imprinted in social connectedness. This study explores whether social capital is protective against suicide ideation in relation to the poverty level of communities, and whether the associations are specific to certain elements of social capital. A total of 908 participants were included to assess cross-sectional association of social capital at individual level with suicide ideation by comparing between poor (government-leased apartments) and non-poor communities (nongovernment-leased apartments). Logistic regression analyses were performed to examine various social capital dimensions in relation to suicide ideation. Suicide ideation was far higher among those living in the poor communities (poor communities 12%; non poor communities 6.3%) and the level of social capital was lower in the poor communities. Nevertheless, the protective effect of social capital, in particular, the cognitive dimension against suicide ideation was demonstrated only in the poor communities (eg, odds ratio = 0.27, 95% confidence interval: 0.12–0.58 for trust in the poor communities). Low income was significantly associated with suicide ideation only in the poor communities, but depression and resilience were associated with suicide ideation both in the poor and non-poor communities. To increase the reliability of the results, established measures based on relevant literature were utilized, but measures on bridging social capital and social network might have relatively low reliability. As to protection against suicide ideation, the extent of reliance on social capital was higher in poor communities than in non-poor communities, in particular, the cognitive dimension was likely to activate in this regard.
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Emerging Pandemic Diseases: How We Got to COVID-19
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3,657 |
Chemogenetic Inhibition of Infralimbic Prefrontal Cortex GABAergic Parvalbumin Interneurons Attenuates the Impact of Chronic Stress in Male Mice
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Hypofunction of the prefrontal cortex (PFC) contributes to stress-related neuropsychiatric illnesses. Mechanisms leading to prefrontal hypoactivity remain to be determined. Prior evidence suggests that chronic stress leads to an increase in activity of parvalbumin (PV) expressing GABAergic interneurons (INs) in the PFC. The purpose of the study was to determine whether reducing PV IN activity in the Infralimbic (IL) PFC would prevent stress-related phenotypes. We used a chemogenetic approach to inhibit IL PFC PV INs during stress. Mice were first tested in the tail suspension test (TST) to determine the impact of PV IN inhibition on behavioral responses to acute stress. The long-term impact of PV IN inhibition during a modified chronic variable stress (CVS) was tested in the forced swim test (FST). Acute PV IN inhibition reduced active (struggling) and increased passive coping behaviors (immobility) in the TST. In contrast, inhibition of PV INs during CVS increased active and reduced passive coping behaviors in the FST. Moreover, chronic inhibition of PV INs attenuated CVS-induced changes in Fos expression in the prelimbic cortex (PrL), basolateral amygdala (BLA), and ventrolateral periaqueductal gray (vlPAG) and also attenuated adrenal hypertrophy and body weight loss associated with chronic stress. Our results suggest differential roles of PV INs in acute versus chronic stress, indicative of distinct biological mechanisms underlying acute versus chronic stress responses. Our results also indicate a role for PV INs in driving chronic stress adaptation and support literature evidence suggesting cortical GABAergic INs as a therapeutic target in stress-related illnesses.
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3,658 |
Respiratory, growth, and survival outcomes of infants with tracheostomy and ventilator dependence
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BACKGROUND: Outcome of infants with tracheostomy have not been well described in the literature. Our objective was to describe the respiratory, growth, and survival outcomes of infants with tracheostomy. METHODS: A retrospective study was conducted on 204 infants born between 2005 and 2015 with tracheostomy at <1 year of age and follow-up in the Infant Tracheostomy and Home Ventilator Clinic up to 4 years of age. RESULTS: The mean age at tracheostomy was 4.5 months with median age of 3 months. Median age of decannulation was 32 months. The time from tracheostomy placement to complete discontinuation of mechanical ventilation was 15.4 months and from tracheostomy to decannulation was 33.8 months. Mortality rate was 21% and median age of death was 18 months. Preterm infants with acquired airway and lung disease (BPD) and born at <28 weeks’ gestation had a significantly higher survival rate compared to term infants. The z-scores for weight and weight for length improved from the time of discharge (mean chronological age 6.5 months) to first year and remained consistent through 3 years. CONCLUSIONS: Premature infants had a higher rate of discontinuation of mechanical ventilation and decannulation compared to term infants. These infants showed consistent growth and comparable survival rate. IMPACT: Infants with tracheostomy and ventilator dependence followed in a multidisciplinary clinic model may have improved survival, growth, and earlier time to decannulation. Preterm infants with acquired airway and lung disease (BPD) with tracheostomy had a higher survival rate compared to term infants with various tracheostomy indications. The age at tracheostomy in infants was 4.5 months and of decannulation was 37 months. Time from tracheostomy to complete discontinuation of mechanical ventilation was 15.4 months. Addition of this data to the sparse literature will be crucial in counseling the families and education of medical staff.
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3,659 |
Systemic IL-6 and Severe Asthma
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3,660 |
Interleukin-1β induces human cementoblasts to support osteoclastogenesis
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Injury of the periodontium followed by inflammatory response often leads to root resorption. Resorption is accomplished by osteoclasts and their generation may depend on an interaction with the cells in direct contact with the root, the cementoblasts. Our study aimed to investigate the role of human cementoblasts in the formation of osteoclasts and the effect of interleukin (IL)-1β hereupon. Extracted teeth from healthy volunteers were subjected to sequential digestion by type I collagenase and trypsin. The effect of enzymatic digestion on the presence of cells on the root surface was analyzed by histology. Gene expression of primary human cementoblasts (pHCB) was compared with a human cementoblast cell line (HCEM). The pHCBs were analyzed for their expression of IL-1 receptors as well as of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). In a co-culture system consisting of osteoclast precursors (blood monocytes) and pHCBs, the formation of osteoclasts and their resorptive activity was assessed by osteo-assay and ivory slices. The cells obtained after a 120 min enzyme digestion expressed the highest level of bone sialoprotein, similar to that of HCEM. This fraction of isolated cells also shared a similar expression pattern of IL-1 receptors (IL1-R1 and IL1-R2). Treatment with IL-1β potently upregulated RANKL expression but not of OPG. pHCBs were shown to induce the formation of functional osteoclasts. This capacity was significantly stimulated by pretreating the pHCBs with IL-1β prior to their co-culture with human blood monocytes. Our study demonstrated that cementoblasts have the capacity to induce osteoclastogenesis, a capacity strongly promoted by IL-1β. These results may explain why osteoclasts can be formed next to the root of teeth.
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Flux sampling is a powerful tool to study metabolism under changing environmental conditions
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The development of high-throughput ‘omic techniques has sparked a rising interest in genome-scale metabolic models, with applications ranging from disease diagnostics to crop adaptation. Efficient and accurate methods are required to analyze large metabolic networks. Flux sampling can be used to explore the feasible flux solutions in metabolic networks by generating probability distributions of steady-state reaction fluxes. Unlike other methods, flux sampling can be used without assuming a particular cellular objective. We have undertaken a rigorous comparison of several sampling algorithms and concluded that the coordinate hit-and-run with rounding (CHRR) algorithm is the most efficient based on both run-time and multiple convergence diagnostics. We demonstrate the power of CHRR by using it to study the metabolic changes that underlie photosynthetic acclimation to cold of Arabidopsis thaliana plant leaves. In combination with experimental measurements, we show how the regulated interplay between diurnal starch and organic acid accumulation defines the plant acclimation process. We confirm fumarate accumulation as a requirement for cold acclimation and further predict γ–aminobutyric acid to have a key role in metabolic signaling under cold conditions. These results demonstrate how flux sampling can be used to analyze the feasible flux solutions across changing environmental conditions, whereas eliminating the need to make assumptions which introduce observer bias.
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3,662 |
Logical design of oral glucose ingestion pattern minimizing blood glucose in humans
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Excessive increase in blood glucose level after eating increases the risk of macroangiopathy, and a method for not increasing the postprandial blood glucose level is desired. However, a logical design method of the dietary ingestion pattern controlling the postprandial blood glucose level has not yet been established. We constructed a mathematical model of blood glucose control by oral glucose ingestion in three healthy human subjects, and predicted that intermittent ingestion 30 min apart was the optimal glucose ingestion patterns that minimized the peak value of blood glucose level. We confirmed with subjects that this intermittent pattern consistently decreased the peak value of blood glucose level. We also predicted insulin minimization pattern, and found that the intermittent ingestion 30 min apart was optimal, which is similar to that of glucose minimization pattern. Taken together, these results suggest that the glucose minimization is achieved by suppressing the peak value of insulin concentration, rather than by enhancing insulin concentration. This approach could be applied to design optimal dietary ingestion patterns.
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Author Correction: Human motor cortex relies on sparse and action-specific activation during laughing, smiling and speech production
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3,664 |
Utilizing genome-scale models to optimize nutrient supply for sustained algal growth and lipid productivity
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Nutrient availability is critical for growth of algae and other microbes used for generating valuable biochemical products. Determining the optimal levels of nutrient supplies to cultures can eliminate feeding of excess nutrients, lowering production costs and reducing nutrient pollution into the environment. With the advent of omics and bioinformatics methods, it is now possible to construct genome-scale models that accurately describe the metabolism of microorganisms. In this study, a genome-scale model of the green alga Chlorella vulgaris (iCZ946) was applied to predict feeding of multiple nutrients, including nitrate and glucose, under both autotrophic and heterotrophic conditions. The objective function was changed from optimizing growth to instead minimizing nitrate and glucose uptake rates, enabling predictions of feed rates for these nutrients. The metabolic model control (MMC) algorithm was validated for autotrophic growth, saving 18% nitrate while sustaining algal growth. Additionally, we obtained similar growth profiles by simultaneously controlling glucose and nitrate supplies under heterotrophic conditions for both high and low levels of glucose and nitrate. Finally, the nitrate supply was controlled in order to retain protein and chlorophyll synthesis, albeit at a lower rate, under nitrogen-limiting conditions. This model-driven cultivation strategy doubled the total volumetric yield of biomass, increased fatty acid methyl ester (FAME) yield by 61%, and enhanced lutein yield nearly 3 fold compared to nitrogen starvation. This study introduces a control methodology that integrates omics data and genome-scale models in order to optimize nutrient supplies based on the metabolic state of algal cells in different nutrient environments. This approach could transform bioprocessing control into a systems biology-based paradigm suitable for a wide range of species in order to limit nutrient inputs, reduce processing costs, and optimize biomanufacturing for the next generation of desirable biotechnology products.
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3,665 |
Osmolyte homeostasis controls single-cell growth rate and maximum cell size of Saccharomyces cerevisiae
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Cell growth is well described at the population level, but precisely how nutrient and water uptake and cell wall expansion drive the growth of single cells is poorly understood. Supported by measurements of single-cell growth trajectories and cell wall elasticity, we present a single-cell growth model for yeast. The model links the thermodynamic quantities, such as turgor pressure, osmolarity, cell wall elasto-plasticity, and cell size, applying concepts from rheology and thin shell theory. It reproduces cell size dynamics during single-cell growth, budding, and hyper-osmotic or hypo-osmotic stress. We find that single-cell growth rate and final size are primarily governed by osmolyte uptake and consumption, while bud expansion requires additionally different cell wall extensibilities between mother and bud. Based on first principles the model provides a more accurate description of size dynamics than previous attempts and its analytical simplification allows for easy combination with models for other cell processes.
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3,666 |
Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment
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Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Surgery combined with chemotherapy has been recommended as a curative regimen for HCC. Nevertheless, the anticancer mechanisms of chemicals in hepatocellular carcinoma remain unclear. Pyroptosis is a type of programmed necrosis, and its mechanism in hepatocellular carcinoma is poorly understood. The efficacy and mechanism of arsenic trioxide nanoparticles in the treatment of HCC were explored in this research. Arsenic trioxide alone and arsenic trioxide nanoparticles were conveniently administered to mice intratumorally using a needle. Compared with As(2)O(3), As(2)O(3) nanoparticles (As(2)O(3)-NPs) showed better inhibition, promoted greater LDH release, and induced cell morphology indicative of pyroptosis in vitro. Compared with the free drug, As(2)O(3)-NPs increased GSDME-N expression and decreased Dnmt3a, Dnmt3b, and Dnmt1 expression in Huh7 cells. In vivo, As(2)O(3)-NPs induced a significant decrease in the expression of Dnmt3a, Dnmt3b and Dnmt1, but significantly upregulated the expression of GSDME-N (gasdermin E (GSDME) was originally found to be related to deafness; recently, it has been defined as a gasdermin family member associated with pyroptosis). As(2)O(3)-NPs inhibited tumor growth more strongly than As(2)O(3) or control, a finding likely attributed to the downregulation of PCNA and DNMT-related proteins and the upregulation of GSDME-N.
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BE-PIGS: a base-editing tool with deaminases inlaid into Cas9 PI domain significantly expanded the editing scope
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3,668 |
Genetically engineered T cells for cancer immunotherapy
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T cells in the immune system protect the human body from infection by pathogens and clear mutant cells through specific recognition by T cell receptors (TCRs). Cancer immunotherapy, by relying on this basic recognition method, boosts the antitumor efficacy of T cells by unleashing the inhibition of immune checkpoints and expands adaptive immunity by facilitating the adoptive transfer of genetically engineered T cells. T cells genetically equipped with chimeric antigen receptors (CARs) or TCRs have shown remarkable effectiveness in treating some hematological malignancies, although the efficacy of engineered T cells in treating solid tumors is far from satisfactory. In this review, we summarize the development of genetically engineered T cells, outline the most recent studies investigating genetically engineered T cells for cancer immunotherapy, and discuss strategies for improving the performance of these T cells in fighting cancers.
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3,669 |
E6-induced selective translation of WNT4 and JIP2 promotes the progression of cervical cancer via a noncanonical WNT signaling pathway
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mRNA translation reprogramming occurs frequently in many pathologies, including cancer and viral infection. It remains largely unknown whether viral-induced alterations in mRNA translation contribute to carcinogenesis. Most cervical cancer is caused by high-risk human papillomavirus infection, resulting in the malignant transformation of normal epithelial cells mainly via viral E6 and E7 oncoproteins. Here, we utilized polysome profiling and deep RNA sequencing to systematically evaluate E6-regulated mRNA translation in HPV18-infected cervical cancer cells. We found that silencing E6 can cause over a two-fold change in the translation efficiency of ~653 mRNAs, most likely in an eIF4E- and eIF2α-independent manner. In addition, we identified that E6 can selectively upregulate the translation of WNT4, JIP1, and JIP2, resulting in the activation of the noncanonical WNT/PCP/JNK pathway to promote cell proliferation in vitro and tumor growth in vivo. Ectopic expression of WNT4/JIP2 can effectively rescue the decreased cell proliferation caused by E6 silencing, strongly suggesting that the WNT4/JIP2 pathway mediates the role of E6 in promoting cell proliferation. Thus, our results revealed a novel oncogenic mechanism of E6 via regulating the translation of mRNAs.
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3,670 |
dIAP: Knowledge Sharing Amidst the Pandemic
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3,671 |
Multisystem Inflammatory Syndrome in Children (MIS-C) — Recent Updates
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3,672 |
Diverse Pathophysiology of Sudden Unexpected Death in Epilepsy in Children
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3,673 |
Therapeutic Clowning in Pediatric Practice: A Novel Concept to Think About in India
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3,674 |
Role of Flexible Bronchoscopy in Ventilator-Dependent Neonates
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OBJECTIVE: To assess the usefulness and safety of flexible bronchoscopy in ventilated neonates with extubation failure. METHOD: This was a prospective observational study. Flexible bronchoscopy was done in eligible patients with failure of extubation form invasive ventilation. The main outcome measure was to find the presence of any anatomic or dynamic abnormalities of the airways of these patients and the organism profile of bronchoalveolar lavage (BAL) fluid. RESULTS: Forty-eight babies (68.8% preterm) were enrolled in the study. The most common finding on bronchoscopy was airway edema seen in 13 (27%) patients. BAL culture was positive in 29 (74%) patients. Overall treatment was modified in 35 (73%) patients based on bronchoscopy findings/BAL culture. Majority of infants (83.3%) tolerated the procedure very well. CONCLUSION: Flexible bronchoscopy provides useful information in the management of newborn babies with extubation failure.
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3,675 |
Effect of Robot-Assisted Gait Training on Selective Voluntary Motor Control in Ambulatory Children with Cerebral Palsy
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This pilot study investigated the efficacy of a four week robot-assisted gait training in twelve children with spastic diparesis. Short-term results and a 3-month follow-up showed statistically significantly increased selective motor control, walking farther distances, gross motor score, and decreased joint contractures.
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3,676 |
Author Correction: Activation of SIRT6 by DNA hypomethylating agents and clinical consequences on combination therapy in leukemia
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3,677 |
Is puberty a risk factor for back pain in the young? a systematic critical literature review
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BACKGROUND: Back pain is a common condition that starts early in life and seems to increase markedly during puberty. A systematic review was performed in order to investigate the link between puberty and back pain, using some Bradford Hill criteria for causality. OBJECTIVES: We sought to obtain answers to the following questions: 1) Is there an association between puberty and back pain? If so, how strong is this association? And do the results remain unchanged also when controlling for age and sex? 2) Are the results of the studies consistent? 3) Is there a dose–response, showing a link between the increasing stages of puberty and the subsequent prevalence of back pain? 4) Is there a temporal link between puberty and back pain? DESIGN: A systematic critical literature review. METHODS: Systematic searches were made in March 2014 in PubMed, Embase, CINAHL and PsycINFO including longitudinal or cross-sectional studies on back pain for subjects <19 years, written in French or English. The review process followed the AMSTAR recommendations. Interpretation was made using some of the Bradford-Hill criteria for causality. RESULTS: Four articles reporting five studies were included, two of which were longitudinal. 1) Some studies show a weak and others a strong positive association between puberty and back pain, which remains after controlling for age and sex; 2) Results were consistent across the studies; 3) There was a linear increase of back pain according to the stage of puberty 4) Temporality has not been sufficiently studied. CONCLUSION: All our criteria for causality were fulfilled or somewhat fulfilled indicating the possibility of a causal link between puberty and back pain. Future research should focus on specific hypotheses, for example investigating if there could be a hormonal or a biomechanical aspect to the development of back pain at this time of life. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12998-014-0027-6) contains supplementary material, which is available to authorized users.
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3,678 |
Immunization Coverage in Migrant School Children Along the Thailand-Myanmar Border
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The objective of this project was to document and increase vaccine coverage in migrant school children on the Thailand-Myanmar border. Migrant school children (n = 12,277) were enrolled in a school-based immunization program in four Thai border districts. The children were evaluated for vaccination completion and timing, for six different vaccines: Bacille Calmette-Guerin (BCG); Oral Polio vaccine (OPV); Hepatitis B vaccine (HepB); Diphtheria, Pertussis and Tetanus vaccine (DTP); Measles Containing Vaccine or Measles, Mumps and Rubella vaccine (MMR); Tetanus and Diphtheria containing vaccine (Td). Vaccine coverage proportions for BCG, OPV3, DTP3, HepB3 and measles containing vaccine were 92.3, 85.3, 63.8, 72.2, and 90.9 % respectively. Most children were able to receive vaccines in a time appropriate manner. School-based immunization programs offer a suitable vaccine delivery mechanism for hard-to-reach populations. However, these data suggest overall low vaccine coverage in migrant populations. Further efforts toward improving appropriate vaccine coverage and methods of retaining documentation of vaccination in mobile migrant populations are necessary for improved health.
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3,679 |
Treatment of at-level spinal cord injury pain with botulinum toxin A
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STUDY DESIGN: Randomized, double-blinded, placebo-controlled, cross-over study. OBJECTIVE: To explore whether botulinum toxin A (BoNTA) could be effective for treating at-level spinal cord injury (SCI) pain. SETTING: Outpatient SCI clinic, New York, USA. METHODS: Participants were randomized to receive subcutaneous injections of either placebo or BoNTA with follow-up (office visit, telephone, or e-mail) at 2, 4, 8, and 12 weeks to assess the magnitude of pain relief post injection. Crossover of participants was then performed. Those who received placebo received BoNTA, and vice versa, with follow-up at 2, 4, 8, and 12 weeks. RESULTS: Eight participants completed at least one of the two crossover study arms. Four completed both arms. The median age of the eight participants was 45 years (range 32–61 years) and 75% were male. All had traumatic, T1-L3 level, complete SCI. Although our data did not meet statistical significance, we noted a higher proportion of participants reporting a marked change in average pain intensity from baseline to 8 and 12 weeks post-BoNTA vs. post-placebo (33% vs. 0%). At 2 and 4 weeks post-BoNTA, almost all participants reported some degree of reduced pain, while the same was not seen post-placebo (83% vs. 0%). CONCLUSION: The subcutaneous injection of BoNTA may be a feasible approach for the control of at-level SCI pain and is worthy of further study. SPONSORSHIP: The onabotulinumtoxinA (BOTOX) used in this study was provided by Allergan (Irvine, CA).
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3,680 |
Restoration of hand function with long-term paired associative stimulation after chronic incomplete tetraplegia: a case study
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INTRODUCTION: This case study explores the gains in hand function in an individual with a chronic spinal cord injury (SCI). The intervention was long-term paired associative simulation (PAS). We aimed to provide PAS until full recovery of hand muscle strength occurred, or until improvements ceased. CASE PRESENTATION: A 46-year-old man with traumatic C7 AIS B tetraplegia was administered PAS three times per week. After 24 weeks, PAS was combined with concomitant motor training of the remaining weak hand muscles. Outcome measures included the manual muscle test (MMT), motor-evoked potentials (MEPs), F-responses, hand functional tests, and the spinal cord independence measure (SCIM). DISCUSSION: After 47 weeks of PAS the subject had improved self-care and indoor mobility and was able to perform complex motor tasks (SCIM score improved from 40 to 56). His left hand regained maximum MMT score (total 75; increase of score from baseline condition 19); the effect remained stable in the 32-week follow up. In the right-hand muscles, MMT scores of 4–5 were observed in follow up (total 71; increase from baseline 48). Improved values were also observed in other outcomes. This is the first demonstration of long-term PAS restoring muscle strength corresponding to MMT scores of 4–5 in an individual with chronic SCI. The effect persisted for several months, indicating that PAS induces stable plastic changes in the corticospinal pathway.
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3,681 |
Chronic prostatitis effectively managed by transurethral prostatectomy (TURP) in a spinal cord injury male
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INTRODUCTION: Spinal cord injury (SCI), specifically suprasacral SCI, results in high intravesical pressures, elevated post-void residual and urinary incontinence which are all risk factors for urinary tract infections (UTIs). The management of UTIs usually is conservative medical antibiotic treatment. However, recurrent UTIs in the SCI patient population warrant further investigation. The method of urinary drainage (intermittent or indwelling urinary catheters, urinary diversion) and untreated complications of NLUTD (vesicoureteral reflux, stone formation, chronic incomplete emptying of the bladder) are risk factors for recurrent UTIs (rUTIs). Removal of these UTI risk factors and improving urinary drainage are goals of urologic management; however, when conservative interventions do not succeed, surgery may be a viable solution in select cases of rUTIs. CASE PRESENTATION: We present a case of complicated persisting rUTIs and associated urethral discharge in a middle-aged SCI male who manages his bladder with intermittent catheterization (IC). We detail the evaluation and management approach that leads to an eventual transurethral prostatectomy (TURP) as a final solution for his rUTIs. Fortunately, the surgical intervention was successful, and the patient is free of UTIs after 4 years of follow-up. DISCUSSION: In SCI male patients with rUTIs and suspected chronic prostatitis, TURP may be a valuable treatment option once all predisposing factors have been remediated.
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3,682 |
Targeted therapeutic options and future perspectives for HER2-positive breast cancer
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Over the past 2 decades, there has been an extraordinary progress in the regimens developed for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Trastuzumab, pertuzumab, lapatinib, and ado-trastuzumab emtansine (T-DM1) are commonly recommended anti-HER2 target agents by the U.S. Food and Drug Administration. This review summarizes the most significant and updated research on clinical scenarios related to HER2-positive breast cancer management in order to revise the guidelines of everyday clinical practices. In this article, we present the data on anti-HER2 clinical research of neoadjuvant, adjuvant, and metastatic studies from the past 2 decades. We also highlight some of the promising strategies that should be critically considered. Lastly, this review lists some of the ongoing clinical trials, findings of which may soon be available.
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3,683 |
Artificial intelligence that determines the clinical significance of capsule endoscopy images can increase the efficiency of reading
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Artificial intelligence (AI), which has demonstrated outstanding achievements in image recognition, can be useful for the tedious capsule endoscopy (CE) reading. We aimed to develop a practical AI-based method that can identify various types of lesions and tried to evaluate the effectiveness of the method under clinical settings. A total of 203,244 CE images were collected from multiple centers selected considering the regional distribution. The AI based on the Inception-Resnet-V2 model was trained with images that were classified into two categories according to their clinical significance. The performance of AI was evaluated with a comparative test involving two groups of reviewers with different experiences. The AI summarized 67,008 (31.89%) images with a probability of more than 0.8 for containing lesions in 210,100 frames of 20 selected CE videos. Using the AI-assisted reading model, reviewers in both the groups exhibited increased lesion detection rates compared to those achieved using the conventional reading model (experts; 34.3%–73.0%; p = 0.029, trainees; 24.7%–53.1%; p = 0.029). The improved result for trainees was comparable to that for the experts (p = 0.057). Further, the AI-assisted reading model significantly shortened the reading time for trainees (1621.0–746.8 min; p = 0.029). Thus, we have developed an AI-assisted reading model that can detect various lesions and can successfully summarize CE images according to clinical significance. The assistance rendered by AI can increase the lesion detection rates of reviewers. Especially, trainees could improve their efficiency of reading as a result of reduced reading time using the AI-assisted model.
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3,684 |
A non-enveloped arbovirus released in lysosome-derived extracellular vesicles induces super-infection exclusion
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Recent developments on extracellular vesicles (EVs) containing multiple virus particles challenge the rigid definition of non-enveloped viruses. However, how non-enveloped viruses hijack cell machinery to promote non-lytic release in EVs, and their functional roles, remain to be clarified. Here we used Bluetongue virus (BTV) as a model of a non-enveloped arthropod-borne virus and discovered that the majority of viruses are released in EVs. Based on the cellular proteins detected in these EVs, and use of inhibitors targeting the cellular degradation process, we demonstrated that these extracellular vesicles are derived from secretory lysosomes, in which the acidic pH is neutralized upon the infection. Moreover, we report that secreted EVs are more efficient than free-viruses for initiating infections, but that they trigger super-infection exclusion that only free-viruses can overcome.
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3,685 |
Full-length cDNA sequence analysis of 85 avian leukosis virus subgroup J strains isolated from chickens in China during the years 1988–2018: coexistence of 2 extremely different clusters that are highly dependent upon either the host genetic background or the geographic location
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During the process of transmission and spread of avian leukosis virus subgroup J (ALV-J) in chickens worldwide, the viral genome is constantly changing. A comprehensive and systematic study of the evolutionary process of ALV-J in China is needed. In this study, we amplified the full-length viral cDNA sequences of 16 ALV-J isolates of Yellow-chicken origin and analyzed and compared these sequences with another 69 ALV-J strains isolated during the years 1988–2018. These isolates were then sorted into 2 clusters: cluster I included isolates that mainly originated from the layers and White-feather broilers from northern China; cluster II included isolates mainly from the Yellow-chicken, most of them being from southern China. According to the sequence homologies of the whole genome and gag, pol, gp85, and gp37 genes, the ALV-J strains are more likely to randomly change in different directions from the original strain HPRS-103 as time passes. The results of entropy analysis of the sequences of gag, pol, and env revealed that the env gene had the largest variation, and the gag gene nonconserved sites are mainly concentrated in p19, p10, and p12. In addition, 84.71% (72/85) of the isolates had the 205-nucleotide (nt) deletion in the 3′UTR region, and 30.59% (26/85) of the isolates had the 125-nt to 127-nt deletion in the E element. Our study provides evidence for the coexistence of 2 extremely different clusters of ALV-J prevailing in China and in some other countries during the period of 1988–2018 and implies that the clusters are highly dependent on the host genetic background and the geographic location.
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3,686 |
Sunflower seed oil containing ginseng stem–leaf saponins (E515-D) is a safe adjuvant for Newcastle disease vaccine
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Vaccination is an effective method to prevent Newcastle disease (ND) in chickens. Marcol 52 and #10 white oil are mineral-based adjuvants and can be found in commercial inactivated ND virus vaccines. The present study demonstrated that a vegetable origin oil E515-D had lower polycyclic aromatic hydrocarbons and higher flash point than the commercial products Marcol 52 and #10 white oil. E515-D could be mixed with an aqueous phase containing ND virus antigen to form a stable water-in-oil vaccine emulsion and exhibited more potent adjuvant effects on the immune response than Marcol 52 and #10 white oil. Moreover, the absorption of E515-D–adjuvanted vaccine was faster than absorption of Marcol 52- and #10 white oil-adjuvanted vaccines when ND virus vaccines were injected in broilers. Therefore, E515-D was safe and could be a suitable adjuvant used in vaccines for food animals. In addition，E515-D is not easy to be flammable during shipping and storage owing to its higher flash point.
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3,687 |
Finding and Closing the Gaps in the Tuberculosis Elimination Campaign
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3,688 |
Urtication (flogging with stinging nettles) and flagellation (beating with rods) in the treatment of paralysis
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Urtication and flagellation were used as a last resort in the treatment of paralysis when all other means were exhausted, and very few cases are reported in the literature. Two cases were identified and reviewed, one of urtication (flogging with nettles) and one of flagellation (beating with rods). In both cases the symptoms were alleviated, but there was insufficient detail to evaluate the therapeutic value of each treatment.
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3,689 |
Effect of overground locomotor training on ventilatory kinetics and rate of perceived exertion in persons with cervical motor-incomplete spinal cord injury
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STUDY DESIGN: Pre-post, pilot study. OBJECTIVES: To characterize ventilatory (V(E)) responses to exercise following warm-up walking in individuals with chronic incomplete spinal cord injury (iSCI) during constant work rate (CWR) exercise. Secondarily, to investigate V(E) and tidal volume (V(T)) variability, and ratings of perceived exertion (RPE) before and after overground locomotor training (OLT). SETTING: Research laboratory. METHODS: A 6-min CWR walking bout at preferred pace was used as a warm-up followed by 6 min of rest and a second 6-min CWR bout at above preferred walking pace. The second CWR bout was analyzed. Breath-by-breath ventilatory data were examined using a curvilinear least squares fitting procedure with a mono-exponential model. V(E) and V(T) variability was calculated as the difference between the observed and predicted values and RPE was taken every 2 min. RESULTS: Participants (n = 3, C4–C5) achieved a hyperpneic response to exercise in V(E) and V(T). OLT resulted in faster ventilatory kinetics and reductions of 24 and 29% for V(E) and V(T) variability, respectively. A 30% reduction in RPE was concurrent with the reductions in ventilatory variability. CONCLUSIONS: OLT may improve ventilatory control during CWR in patients with cervical motor-iSCI. These data suggest that in some participants with iSCI, ventilation may influence RPE during walking. Future research should investigate mechanisms of ventilatory variability and its implications in walking performance in patients with iSCI.
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3,690 |
Correction: Effect of behavioral change intervention around new-born care practices among most marginalized women in self-help groups in rural India: analyses of three cross-sectional surveys between 2013 and 2016
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3,691 |
Effect of surgical intraocular pressure lowering on retinal structures—nerve fibre layer, foveal avascular zone, peripapillary and macular vessel density: 1 year results
| null |
3,692 |
Correction to: Cancer immunotherapy with γδ T cells: many paths ahead of us
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3,693 |
Perinatal THC exposure via lactation induces lasting alterations to social behavior and prefrontal cortex function in rats at adulthood
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Cannabis is the world’s most widely abused illicit drug and consumption amongst women during and surrounding the period of pregnancy is increasing. Previously, we have shown that cannabinoid exposure via lactation during the early postnatal period disrupts early developmental trajectories of prefrontal cortex maturation and induces behavioral abnormalities during the first weeks of life in male and female rat progeny. Here, we investigated the lasting consequences of this postnatal cannabinoid exposure on synaptic and behavioral parameters in the adult offspring of ∆9-tetrahydrocannabinol (THC)-treated dams. At adulthood, these perinatally THC-exposed rats exhibits deficits in social discrimination accompanied by an overall augmentation of social exploratory behavior. These behavioral alterations were further correlated with multiple abnormalities in synaptic plasticity in the prefrontal cortex, including lost endocannabinoid-mediated long-term depression (LTD), lost long-term potentiation and augmented mGlu2/3-LTD. Finally, basic parameters of intrinsic excitability at prefrontal cortex pyramidal neurons were similarly altered by the perinatal THC exposure. Thus, perinatal THC exposure via lactation induces lasting deficits in behavior and synaptic function which persist into adulthood life in male and female progeny.
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3,694 |
Essential roles of S100A10 in Toll-like receptor signaling and immunity to infection
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Toll-like receptors (TLRs) are key pattern recognition receptors that mediate innate immune responses to infection. However, uncontrolled TLR activation can lead to severe inflammatory disorders such as septic shock. The molecular mechanisms through which TLR responses are regulated are not fully understood. Here, we demonstrate an essential function of S100A10 in TLR signaling. S100A10 was constitutively expressed in macrophages, but was significantly downregulated upon TLR activation. S100A10-deficient macrophages were hyperresponsive to TLR stimulation, and S100A10-deficient mice were more sensitive to endotoxin-induced lethal shock and Escherichia coli-induced abdominal sepsis. Mechanistically, S100A10 regulated macrophage inflammatory responses by interfering with the appropriate recruitment and activation of the receptor-proximal signaling components and eventually inhibited TLR-triggered downstream signaling. These findings expand our understanding of TLR signaling and establish S100A10 as an essential negative regulator of TLR function and a potential therapeutic target for treating inflammatory diseases.
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3,695 |
Correction to: Is psychosis a multisystem disorder? A meta-review of central nervous system, immune, cardiometabolic, and endocrine alterations in first-episode psychosis and perspective on potential models
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3,696 |
Correction to: Abstracts: 31st European Congress of Pathology
| null |
3,697 |
Erratum
| null |
3,698 |
Clinical and genetic characterization of nephropathy in patients with nail-patella syndrome
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Nail-patella syndrome (NPS) is a multi-system disorder characterized by hypoplastic nails, hypoplastic patella, skeletal deformities, and iliac horns, which is caused by heterozygous variants of LMX1B. Nephropathy ranging from mild urinary abnormality to end-stage renal disease occurs in some individuals with NPS. Because of the low prevalence of NPS and the lack of longitudinal studies of its kidney involvement, the clinical, pathological, and genetic features characterizing severe nephropathy remain unclear. We conducted a Japanese survey of NPS with nephropathy, and analyzed their clinical course, pathological features, and factors associated with severe renal phenotype. LMX1B gene analysis and luciferase reporter assay were also performed. Among 13 NPS nephropathy cases with genetic validation, 5 patients who had moderate-to-massive proteinuria progressed to advanced chronic kidney disease or end-stage renal disease. Pathological findings in the early phase did not necessarily correlate with renal prognosis. Variants associated with deteriorated renal function including a novel variants were confined to the N-terminal region of the LIM domain and a short sequence in the LMX1B homeodomain, which were distinct from reported variants found in isolated nephropathy without extrarenal manifestation (LMX1B-associated nephropathy). Luciferase reporter analysis demonstrated that variants in patients with severe renal phenotype caused haploinsufficiency, but no dominant-negative effects on promoter activation. A distinct proportion of NPS nephropathy patients progressed to end-stage renal disease in adolescence or young adulthood. Patients with moderate or severe proteinuria, especially those with variants in specific regions of LMX1B, should be monitored for potential deterioration of renal function.
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3,699 |
Efficacy and safety of subthreshold micropulse laser compared with threshold conventional laser in central serous chorioretinopathy
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PURPOSE: To compare the efficacy and safety of subthreshold micropulse laser (SML) with threshold conventional laser (TCL) in central serous chorioretinopathy (CSC). METHODS: Prospective, randomized, double-masked, non-inferiority, 12-week clinical trial. Patients were randomly assigned 1:1 to SML group or TCL group. Patients in the SML group were treated with 577 nm micropulse laser. The spot size was 160 µm, the duty cycle was 5% and exposure time was 0.2 s. The power was 50% threshold tested. Patients in the TCL group were treated with 577 nm continuous laser. The power was 100% threshold tested. The primary outcome was the mean change in best-corrected visual acuity (BCVA) at week 12, with a non-inferiority limit of five letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts. RESULTS: Eighty-eight patients were enroled. Seventy-seven patients were male. Forty-four patients were in SML group and 44 in TCL group. At week 12, SML was equivalent to TCL with a gain of 6.23 ± 8.59 and 6.61 ± 6.35 letters, respectively, (SML–TCL difference: −0.38 letters; 95% confidence interval (CI):−3.58–2.81; P(non-inferiority) = 0.0026). There was no statistically significant difference between the two groups (t = 0.240, P = 0.811). At week 12, the proportion of patients whose SRF had been totally absorbed was 63.63 and 81.82% respectively for SML and TCL groups. There was no statistically significant difference between the two groups (χ(2) = 3.67, P = 0.056). CONCLUSIONS: Both SML and TCL can improve visual acuity in CSC. SML was non-inferior to TCL in the improvement of BCVA.
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