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Performance of a capnodynamic method estimating cardiac output during respiratory failure - before and after lung recruitment
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Respiratory failure may cause hemodynamic instability with strain on the right ventricle. The capnodynamic method continuously calculates cardiac output (CO) based on effective pulmonary blood flow (CO(EPBF)) and could provide CO monitoring complementary to mechanical ventilation during surgery and intensive care. The aim of the current study was to evaluate the ability of a revised capnodynamic method, based on short expiratory holds (CO(EPBFexp)), to estimate CO during acute respiratory failure (LI) with high shunt fractions before and after compliance-based lung recruitment. Ten pigs were submitted to lung lavage and subsequent ventilator-induced lung injury. CO(EPBFexp), without any shunt correction, was compared to a reference method for CO, an ultrasonic flow probe placed around the pulmonary artery trunk (CO(TS)) at (1) baseline in healthy lungs with PEEP 5 cmH(2)O (HL(P5)), (2) LI with PEEP 5 cmH(2)O (LI(P5)) and (3) LI after lung recruitment and PEEP adjustment (LI(Padj)). CO changes were enforced during LI(P5) and LI(Padj) to estimate trending. LI resulted in changes in shunt fraction from 0.1 (0.03) to 0.36 (0.1) and restored to 0.09 (0.04) after recruitment manoeuvre. Bias (levels of agreement) and percentage error between CO(EPBFexp) and CO(TS) changed from 0.5 (− 0.5 to 1.5) L/min and 30% at HL(P5) to − 0.6 (− 2.3 to 1.1) L/min and 39% during LI(P5) and finally 1.1 (− 0.3 to 2.5) L/min and 38% at LI(Padj). Concordance during CO changes improved from 87 to 100% after lung recruitment and PEEP adjustment. CO(EPBFexp) could possibly be used for continuous CO monitoring and trending in hemodynamically unstable patients with increased shunt and after recruitment manoeuvre. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10877-019-00421-w) contains supplementary material, which is available to authorized users.
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3,301 |
Pulmonary function in extremely low birth weight infants with bronchopulmonary dysplasia before hospital discharge
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OBJECTIVE: To compare pulmonary function in extremely low birth weight (ELBW) infants with bronchopulmonary dysplasia (BPD) studied at 34–36 weeks postmenstrual age (PMA) with a reference group of “healthy” infants born at 34–36 weeks. We hypothesized that ELBW infants have decreased functional residual capacity (FRC) and respiratory compliance (Crs). STUDY DESIGN: Pulmonary function testing was performed at 34–36 weeks PMA in infants with BPD and within 96 h of age in infants delivered at 34–36 weeks. RESULTS: Twenty BPD patients and 20 healthy infants were studied. FRC (18.9 versus 26.2 mL/kg; adjusted 95% CI 5.0, 10.9; P < 0.001) and Crs (0.80 versus 1.29-mL/cm H(2)O/kg; 95% CI 0.31, 0.71; P < 0.001) were decreased in BPD patients. Respiratory resistance was increased in BPD patients. CONCLUSIONS: ELBW infants with BPD have decreased pulmonary function compared to healthy infants delivered at 34–36 weeks. This suggests that infants with BPD have smaller lung volumes.
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3,302 |
Pancytopenia during SARS-CoV-2 infection()
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3,303 |
One-year experience of hybrid closed-loop system in children and adolescents with type 1 diabetes previously treated with multiple daily injections: drivers to successful outcomes
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OBJECTIVE: To evaluate the effect of a 1-year hybrid closed-loop (HCL) system on glycemic control in children and adolescents with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI). METHODS: This was a 1-year observational study, as a continuation of the previous 3 months prospective study of pediatric patients with T1D conducted at Sidra Medicine in Qatar. The study enrolled individuals aged 7–18 years with T1D > 1 year, on MDI with self-monitoring of blood glucose or continuous glucose monitoring, with no prior pump experience, and with an HbA1c level < 12.5% (< 113 mmol/mol). After the first 3 months of HCL use, patients were followed at 6, 9 and 12 months, where HbA1c was obtained and pump data were collected. RESULTS: All 30 participants (age 10.24 ± 2.6 years) who initiated HCL completed 12 months of HCL system use in Auto Mode. The participants used the sensor 88.4 ± 6.5% of the time with Auto Mode usage 85.6 ± 7.4% during 12 months of HCL system use. HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline, to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at 3 months (p = 0.02) and remained stable to 7.1 ± 0.6 (54 ± 6.6 mmol/mol) at 12 months (p = 0.02). TIR (70–180 mg/dL) increased from 46.9% at baseline to 71.9% at 1 month and remained above 70% during the 12 months of HCL use. CONCLUSION: HCL system (MiniMed 670G) in children and adolescents previously treated with MDI significantly improves glycemic outcomes (HbA1c and Time in Ranges) immediately during the first month. This improved glycemic control was maintained over the 1 year following Auto Mode initiation.
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3,304 |
Mitteilungen der DGRh - Veranstaltungen der Rheumaakademie
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3,305 |
Outcomes and management approaches of resuscitative endovascular balloon occlusion of the aorta based on the income of countries
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BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries’ income based on the World Bank Country and Lending Groups. METHODS: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and (2) low-to-middle income countries (LMICs). Propensity score matching extracted 1:1 matched pairs of subjects who were from an LMIC or a HIC based on age, gender, the presence of pupillary response on admission, impeding hypotension (SBP ≤ 80), trauma mechanism, ISS, the necessity of CPR on arrival, the location of REBOA insertion (emergency room or operating room) and the amount of PRBCs transfused in the first 24 h. Logistic regression (LR) was used to examine the association of LMICs and mortality. RESULTS: A total of 817 trauma patients from 14 countries were included. Blind percutaneous approach and surgical cutdown were the preferred means of femoral cannulation in HICs and LIMCs, respectively. Patients from LMICs had a significantly higher occurrence of MODS and respiratory failure. LR showed no differences in mortality for LMICs when compared to HICs; neither in the non-matched cohort (OR = 0.63; 95% CI: 0.36‑1.09; p = 0.1) nor in the matched cohort (OR = 1.45; 95% CI: 0.63‑3,33; p = 0.3). CONCLUSION: There is considerable variation in the management practices of REBOA and the outcomes associated with this intervention between HICs and LMICs. Although we found significant differences in multiorgan and respiratory failure rates, there were no differences in the risk-adjusted odds of mortality between the groups analyzed. Trauma surgeons practicing REBOA around the world should joint efforts to standardize the practice of this endovascular technology worldwide.
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3,306 |
Hämatoonkologie und Intensivmedizin: Vom Tabu zur Conditio sine qua non
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Intensivists are confronted with a broad spectrum of specific clinical problems while caring for critically ill cancer patients. These include defining proper goals of intensive care treatment, managing acute respiratory failure with diverse differential considerations, treating immunologic side-effects of ever new and innovative cancer therapies, as well as numerous clinical scenarios which may exclusively arise in cancer patients. To help clinicians handle such challenges, the initiative Intensive Care in Hematologic and Oncologic Patients (iCHOP) has been dealing with these topics for several years. Supported by several Austrian and German medical societies of intensive care medicine, hematology and oncology, the first “Consensus statement for cancer patients requiring intensive care support” has only recently been released. Acute respiratory failure and its management continues to be a major focus in critically ill cancer patients due to its frequency and its prognostic impact. While noninvasive oxygenation strategies were considered the gold standard of therapy, more recent high-quality data do not show clinical benefits of such techniques including high flow nasal oxygen. On the contrary, several studies revealed an unidentified etiology of an acute respiratory failure as the only potentially modifiable risk factor for adverse outcome. Consequently, evidence-based and rigorously applied diagnostic algorithms are of utmost importance in these patients. Furthermore, intensivists are increasingly confronted with the rising incidence of various and new immunotherapy-associated toxicities and their management.
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3,307 |
Fluid management in ARDS: an evaluation of current practice and the association between early diuretic use and hospital mortality
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BACKGROUND: Acute respiratory distress syndrome (ARDS) and volume overload are associated with increased hospital mortality. Evidence supports conservative fluid management in ARDS, but whether current practice reflects the implementation of that evidence has not been described. This study reports the variability in contemporary fluid management for ICU patients with ARDS. We compared routine care to trial protocols and analyzed whether more conservative management with diuretic medications in contemporary, usual care is associated with outcomes. METHODS: We performed a retrospective cohort study in nine ICUs at two academic hospitals during 2016 and 2017. We included 234 adult patients with ARDS in an ICU at least 3 days after meeting moderate-severe ARDS criteria (PaO(2):FIO(2) ≤ 150). The primary exposure was any diuretic use in 48 to 72 h after meeting ARDS criteria. The primary outcome was hospital mortality. Unadjusted statistical analyses and multivariable logistic regression were used. RESULTS: In 48–72 h after meeting ARDS criteria, 116 patients (50%) received a diuretic. In-hospital mortality was lower in the group that received diuretics than in the group that did not (14% vs 25%; p = 0.025). At ARDS onset, both groups had similar Sequential Organ Failure Assessment scores and ICU fluid balances. During the first 48 h after ARDS, the diuretic group received less crystalloid fluid than the no diuretic group (median [inter-quartile range]: 1.2 L [0.2–2.8] vs 2.4 L [1.2-5.0]; p < 0.001), but both groups received more fluid from medications and nutrition than from crystalloid. At 48 h, the prevalence of volume overload (ICU fluid balance >10% of body weight) in each group was 16% and 25%(p = 0.09), respectively. During 48–72 h after ARDS, the overall prevalence of shock was 44% and similar across both groups. Central venous pressure was recorded in only 18% of patients. Adjusting for confounders, early diuretic use was independently associated with lower hospital mortality (AOR 0.46, 95%CI [0.22, 0.96]). CONCLUSIONS: In this sample of ARDS patients, volume overload was common, and early diuretic use was independently associated with lower hospital mortality. These findings support the importance of fluid management in ARDS and suggest opportunities for further study and implementation of conservative fluid strategies into usual care.
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3,308 |
Hostility, compassion and role reversal in West Virginia’s long opioid overdose emergency
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BACKGROUND: West Virginia is a largely rural state with strong ties of kinship, mutual systems of support and charitable giving. At the same time, wealth inequalities are extreme and the state’s drug overdose fatality rate stands above all others in the USA at 51.5/100,000 in 2018, largely opioid-related. In recent years, harm reduction services have been active in the state but in 2018 Charleston’s needle and syringe program was forced to close. This paper considers the risk environment in which the state’s drug-related loss of life, and those attempting to prevent it, exist. METHODS: This rapid ethnographic study involved semi-structured interviews (n = 21), observation and video recordings of injection sequences (n = 5), initially recruiting people who inject heroin/fentanyl (PWIH) at the Charleston needle and syringe program. Snowball sampling led the research team to surrounding towns in southern West Virginia. Telephone interviews (n = 2) with individuals involved in service provision were also carried out. RESULTS: PWIH in southern West Virginia described an often unsupportive, at times hostile risk environment that may increase the risk of overdose fatalities. Negative experiences, including from some emergency responders, and fears of punitive legal consequences from calling these services may deter PWIH from seeking essential help. Compassion fatigue and burnout may play a part in this, along with resentment regarding high demands placed by the overdose crisis on impoverished state resources. We also found low levels of knowledge about safe injection practices among PWIH. CONCLUSIONS: Hostility faced by PWIH may increase their risk of overdose fatalities, injection-related injury and the risk of HIV and hepatitis C transmission by deterring help-seeking and limiting the range of harm reduction services provided locally. Greater provision of overdose prevention education and naloxone for peer distribution could help PWIH to reverse overdoses while alleviating the burden on emergency services. Although essential for reducing mortality, measures that address drug use alone are not enough to safeguard longer-term public health. The new wave of psychostimulant-related deaths underline the urgency of addressing the deeper causes that feed high-risk patterns of drug use beyond drugs and drug use.
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3,309 |
DASFAA 20202 Special Issue Editorial
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3,310 |
Treatment of Giant Cell Arteritis and Takayasu Arteritis—Current and Future
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PURPOSE OF REVIEW: Guidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies. RECENT FINDINGS: While glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA. SUMMARY: Tocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking.
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3,311 |
Strategies for having a more effective and less toxic CAR T-cell therapy for acute lymphoblastic leukemia
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In the recent years, using genetically modified T cells has been known as a rapid developing therapeutic approach due to the heartwarming results of clinical trials with patients suffering from relapsed or refractory (R/R) hematologic malignancies such as R/R Acute Lymphoblastic Leukemia (R/R ALL). One of these renowned approaches is Chimeric antigen receptors (CARs). CARs are synthetic receptors with the ability to be expressed on the surface of T lymphocytes and are specifically designed to target a tumor-associated antigen (TAA) of interest. CAR-expressing T cells have the capability of proliferating and maintaining their immunological functionality in the recipient body but like any other therapeutic approach, the safety, effectiveness, and specificity enhancement of CAR T cells still lingers in the ambiguity arena. Genetic manipulation methods, expansion protocols, infusion dosage, and conditioning regimens are all among crucial factors which can affect the efficacy of CAR T cell-based cancer therapy. In this article, we discuss the studies that have focused on various aspects that affect the efficacy and persistence of CAR T-cell therapy for ALL treatment and provide a widespread overview regarding the practical approaches capable of elevating the effectiveness and lessening the relative toxicities attributed to it.
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3,312 |
Evaluation and Management Coding Initiative
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3,313 |
Implementation of virtual focus groups for qualitative data collection in a global pandemic
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3,314 |
Biomarker testing in oncology – Requirements for organizing external quality assessment programs to improve the performance of laboratory testing: revision of an expert opinion paper on behalf of IQNPath ABSL
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In personalized medicine, predictive biomarker testing is the basis for an appropriate choice of therapy for patients with cancer. An important tool for laboratories to ensure accurate results is participation in external quality assurance (EQA) programs. Several providers offer predictive EQA programs for different cancer types, test methods, and sample types. In 2013, a guideline was published on the requirements for organizing high-quality EQA programs in molecular pathology. Now, after six years, steps were taken to further harmonize these EQA programs as an initiative by IQNPath ABSL, an umbrella organization founded by various EQA providers. This revision is based on current knowledge, adds recommendations for programs developed for predictive biomarkers by in situ methodologies (immunohistochemistry and in situ hybridization), and emphasized transparency and an evidence-based approach. In addition, this updated version also has the aim to give an overview of current practices from various EQA providers. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02928-z) contains supplementary material, which is available to authorized users.
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3,315 |
Kawasaki-Erkrankung oder Hyperinflammations-Syndrom?
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3,316 |
Schulbeginn für Kinder mit Asthma: Anfang September startete wieder der Alltag
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3,317 |
Update from the Editor in Chief
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3,318 |
DGSM-Jahrestagung und Abstractband 2020
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3,319 |
Correction to: A matched case-control study of risk factors associated with multiple sclerosis in Kuwait
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3,320 |
Lungenbeteiligung bei Tumorkrankheiten
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The lungs are often involved in tumors and are affected in a wide variety of ways. Lung cancer comprises one of the most common cancer entities and has been characterized by a vast expansion of treatment approaches in recent years. Moreover, the lungs are a common metastatic site of multiple other cancer entities. Various treatment modalities, such as tyrosine kinase inhibitors, checkpoint inhibitors, chimeric antigen receptor cell therapy, and radiotherapy approaches can cause pulmonary side effects. Finally, many patients suffer from pulmonary comorbidities which may mutually impact the clinical course and prognosis of the cancer disease. As examples, various aspects, such as pulmonary veno-occlusive disease, chronic obstructive pulmonary disease, and idiopathic pulmonary fibrosis are discussed.
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3,321 |
Dante Gatteschi: on the Occasion of His 75th Birthday
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3,322 |
Eine kritische Weihnachtsgeschichte: Essay über Anämie, Ersticken, Verhungern und andere Behandlungsverfahren der Intensivmedizin – im Stil von Dickens
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Somewhere in the USA, shortly before Christmas, tipsy Charlie Cratchit intends to cross a street but is hit by an oncoming city bus und suffers severe trauma: serial rib fracture, femoral fracture, fibula fracture, splenic, pancreatic and bowel ruptures. He is operated on in a maximum care hospital and then transferred to the critical care unit. From then on, an anonymous, very experienced physician continuously takes care of him. Four nights before Christmas, the ghost of the famous British physiologist Ernest Henry Starling appears at the patient’s bed. The ghost involves the anonymous physician in a dialogue and is very interested in the inserted Swan-Ganz catheter, then he disappears. He repeats his visits the next 3 nights. On the first occasion he is displeased with Cratchit’s low haematocrit, the second time he dislikes the mechanical ventilator settings, and on his final visit he is concerned with Cratchit’s clinical nutrition. At first, the anonymous physician is indignant with the ghost’s criticism and indoctrinations, but then recognizes that ultimately they are the key to Cratchit’s convalescence and acts accordingly. Successfully! Following the ghost’s proposals, he changes the ventilator settings, transfuses 3 units of packed red blood cells, and starts clinical nutrition. Shortly thereafter, Cratchit’s trachea is extubated, and on New Year’s Day he is ready to be discharged from the critical care unit. In this essay, Robert Bartlett transposed Charles Dickens’ “Christmas Carol” into the world of critical care. Its intention is to encourage the intensivist to scrutinize common therapeutic measures, such as mechanical ventilation, haemodynamic interventions and transfusion of blood products. Background information and comments on the addressed problems of modern intensive care are provided subsequent to the essay.
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3,323 |
Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial
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PURPOSE: Contemporary trauma resuscitation prioritizes control of bleeding and uses major haemorrhage protocols (MHPs) to prevent and treat coagulopathy. We aimed to determine whether augmenting MHPs with Viscoelastic Haemostatic Assays (VHA) would improve outcomes compared to Conventional Coagulation Tests (CCTs). METHODS: This was a multi-centre, randomized controlled trial comparing outcomes in trauma patients who received empiric MHPs, augmented by either VHA or CCT-guided interventions. Primary outcome was the proportion of subjects who, at 24 h after injury, were alive and free of massive transfusion (10 or more red cell transfusions). Secondary outcomes included 28-day mortality. Pre-specified subgroups included patients with severe traumatic brain injury (TBI). RESULTS: Of 396 patients in the intention to treat analysis, 201 were allocated to VHA and 195 to CCT-guided therapy. At 24 h, there was no difference in the proportion of patients who were alive and free of massive transfusion (VHA: 67%, CCT: 64%, OR 1.15, 95% CI 0.76–1.73). 28-day mortality was not different overall (VHA: 25%, CCT: 28%, OR 0.84, 95% CI 0.54–1.31), nor were there differences in other secondary outcomes or serious adverse events. In pre-specified subgroups, there were no differences in primary outcomes. In the pre-specified subgroup of 74 patients with TBI, 64% were alive and free of massive transfusion at 24 h compared to 46% in the CCT arm (OR 2.12, 95% CI 0.84–5.34). CONCLUSION: There was no difference in overall outcomes between VHA- and CCT-augmented-major haemorrhage protocols. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06266-1) contains supplementary material, which is available to authorized users.
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3,324 |
The threads of history: why record your pandemic experiences for the RCPI archive?
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3,325 |
Response to “Registry reports in COVID-19 patients: juggling with big data, poor data, and no data”
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3,326 |
Analysis of Amino Acid Mutations of the Foot-and-Mouth Disease Virus Serotype O Using both Heparan Sulfate and JMJD6 Receptors
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Foot-and-mouth disease (FMD) is an economically devastating animal disease. Adapting the field virus to cells is critical to the vaccine production of FMD viruses (FMDV), and heparan sulfate (HS) and Jumonji C-domain-containing protein 6 (JMJD6) are alternative receptors of cell-adapted FMDV. We performed serial passages of FMDV O/SKR/Andong/2010, classified as the O/Mya-98 topotype/lineage and known as a highly virulent strain, to develop a vaccine seed virus. We traced changes in the amino acid sequences of the P1 region, plaque phenotypes, and the receptor usage of the viruses, and then structurally analyzed the mutations. VP3 H56R and D60G mutations were observed in viruses using the HS receptor and led to changes in the hydrogen bonding between VP3 56 and 60. A VP1 P208L mutation was observed in the virus using the JMJD6 receptor during cell adaptation, enabling the interaction with JMJD6 through the formation of a new hydrogen bond with JMJD6 residue 300. Furthermore, VP1 208 was near the VP1 95/96 amino acids, previously reported as critical mutations for JMJD6 receptor interactions. Thus, the mutation at VP1 208 could be critical for cell adaptation related to the JMJD6 receptor and may serve as a basis for mechanism studies on FMDV cell adaptation.
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3,327 |
The Impact of Diet, Nutrition and Nutraceuticals on Oral and Periodontal Health
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Oral and periodontal diseases can determine severe functional, phonatory and aesthetic impairments and are the main cause of adult tooth loss. They are caused by some specific bacteria that provoke an intense local inflammatory response and affect—with particular gravity—susceptible subjects, because of reasons related to genetics and lifestyles (e.g., smoking and home oral hygiene habits). They are more frequent in the disadvantaged segments of society and, in particular, in subjects who have difficulty accessing preventive services and dental care. Some systemic diseases, such as uncontrolled diabetes, can increase their risk of development and progression. Recently, in addition to the obvious considerations of severe alterations and impairments for oral health and well-being, it has been noted that periodontitis can cause changes in the whole organism. Numerous clinical and experimental studies have highlighted the presence of a strong association between periodontitis and some systemic diseases, in particular, cardiovascular diseases, diabetes, lung diseases and complications of pregnancy. The purpose of this editorial is to provide a current and thoughtful perspective on the relationship of diet and natural agents on oral, periodontal diseases, and chewing disorder preventions which may reflect good systemic conditions and related quality of life or to analyze indirect effects through the contribution of diet and nutrition to systemic health in order to obtain a modern diagnostic–therapeutic approach.
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3,328 |
Exploring Language Learning as a Potential Tool against Cognitive Impairment in Late-Life Depression: Two Meta-Analyses and Suggestions for Future Research
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Late-life depression (LLD) affects about an eighth of community-dwelling seniors. LLD impacts well-being, with loneliness and small social networks being typical. It has also been linked to cognitive dysfunction and an increased risk of developing dementia. Safety and efficacy of pharmacological treatments for LLD have been debated, and cognitive dysfunction often persists even after remission. Various cognitive interventions have been proposed for LLD. Among these, one has received special attention: foreign language learning could serve as a social intervention that simultaneously targets brain structures affected in LLD. Lifelong bilingualism may significantly delay the onset of cognitive impairment symptoms by boosting cognitive reserve. Even late-life foreign language learning without lifelong bilingualism can train cognitive flexibility. It is then counterintuitive that the effects of language learning on LLD have never been examined. In order to create a theoretical basis for further interdisciplinary research, this paper presents a status quo of current work through two meta-analyses investigating cognitive functioning in LLD on the one hand and in senior bilinguals or seniors following a language course on the other hand. While LLD was consistently associated with cognitive dysfunction, inconsistent results were found for bilingualism and language learners. Possible reasons for this and suggestions for future research are subsequently discussed.
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3,329 |
STAU1 selectively regulates the expression of inflammatory and immune response genes and alternative splicing of the nerve growth factor receptor signaling pathway
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Double-stranded RNA-binding protein Staufen homolog 1 (STAU1) is a highly conserved multifunctional double-stranded RNA-binding protein, and is a key factor in neuronal differentiation. RNA sequencing was used to analyze the overall transcriptional levels of the upregulated cells by STAU1 and control cells, and select alternative splicing (AS). It was determined that the high expression of STAU1 led to changes in the expression levels of a variety of inflammatory and immune response genes, including IFIT2, IFIT3, OASL, and CCL2. Furthermore, STAU1 was revealed to exert a significant regulatory effect on the AS of genes related to the ‘nerve growth factor receptor signaling pathway’. This is of significant importance for neuronal survival, differentiation, growth, post-damage repair, and regeneration. In conclusion, overexpression of STAU1 was associated with immune response and regulated AS of pathways related to neuronal growth and repair. In the present study, the whole transcriptome of STAU1 expression was first analyzed, which laid a foundation for further understanding the key functions of STAU1.
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3,330 |
An overview of moonlighting proteins in Staphylococcus aureus infection
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Staphylococcus aureus is responsible for numerous instances of superficial, toxin-mediated, and invasive infections. The emergence of methicillin-resistant (MRSA), as well as vancomycin-resistant (VRSA) strains of S. aureus, poses a massive threat to human health. The tenacity of S. aureus to acquire resistance against numerous antibiotics in a very short duration makes the effort towards developing new antibiotics almost futile. S. aureus owes its destructive pathogenicity to the plethora of virulent factors it produces among which a majority of them are moonlighting proteins. Moonlighting proteins are the multifunctional proteins in which a single protein, with different oligomeric conformations, perform multiple independent functions in different cell compartments. Peculiarly, proteins involved in key ancestral functions and metabolic pathways typically exhibit moonlighting functions. Pathogens mainly employ those proteins as virulent factors which exhibit high structural conservation towards their host counterparts. Consequentially, the host immune system counteracts these invading bacterial virulent factors with minimal protective action. Additionally, many moonlighting proteins also play multiple roles in various stages of pathogenicity while augmenting the virulence of the bacterium. This has necessitated elaborative studies to be conducted on moonlighting proteins of S. aureus that can serve as drug targets. This review is a small effort towards understanding the role of various moonlighting proteins in the pathogenicity of S. aureus.
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3,331 |
Discoveries of Exoribonuclease-Resistant Structures of Insect-Specific Flaviviruses Isolated in Zambia
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To monitor the arthropod-borne virus transmission in mosquitoes, we have attempted both to detect and isolate viruses from 3304 wild-caught female mosquitoes in the Livingstone (Southern Province) and Mongu (Western Province) regions in Zambia in 2017. A pan-flavivirus RT-PCR assay was performed to identify flavivirus genomes in total RNA extracted from mosquito lysates, followed by virus isolation and full genome sequence analysis using next-generation sequencing and rapid amplification of cDNA ends. We isolated a newly identified Barkedji virus (BJV Zambia) (10,899 nt) and a novel flavivirus, tentatively termed Barkedji-like virus (BJLV) (10,885 nt) from Culex spp. mosquitoes which shared 96% and 75% nucleotide identity with BJV which has been isolated in Israel, respectively. These viruses could replicate in C6/36 cells but not in mammalian and avian cell lines. In parallel, a comparative genomics screening was conducted to study evolutionary traits of the 5′- and 3′-untranslated regions (UTRs) of isolated viruses. Bioinformatic analyses of the secondary structures in the UTRs of both viruses revealed that the 5′-UTRs exhibit canonical stem-loop structures, while the 3′-UTRs contain structural homologs to exoribonuclease-resistant RNAs (xrRNAs), SL-III, dumbbell, and terminal stem-loop (3′SL) structures. The function of predicted xrRNA structures to stop RNA degradation by Xrn1 exoribonuclease was further proved by the in vitro Xrn1 resistance assay.
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3,332 |
Infection Dynamics of Swine Influenza Virus in a Danish Pig Herd Reveals Recurrent Infections with Different Variants of the H1N2 Swine Influenza A Virus Subtype
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Influenza A virus (IAV) in swine, so-called swine influenza A virus (swIAV), causes respiratory illness in pigs around the globe. In Danish pig herds, a H1N2 subtype named H1N2dk is one of the main circulating swIAV. In this cohort study, the infection dynamic of swIAV was evaluated in a Danish pig herd by sampling and PCR testing of pigs from two weeks of age until slaughter at 22 weeks of age. In addition, next generation sequencing (NGS) was used to identify and characterize the complete genome of swIAV circulating in the herd, and to examine the antigenic variability in the antigenic sites of the virus hemagglutinin (HA) and neuraminidase (NA) proteins. Overall, 76.6% of the pigs became PCR positive for swIAV during the study, with the highest prevalence at four weeks of age. Detailed analysis of the virus sequences obtained showed that the majority of mutations occurred at antigenic sites in the HA and NA proteins of the virus. At least two different H1N2 variants were found to be circulating in the herd; one H1N2 variant was circulating at the sow and nursery sites, while another H1N2 variant was circulating at the finisher site. Furthermore, it was demonstrated that individual pigs had recurrent swIAV infections with the two different H1N2 variants, but re-infection with the same H1N2 variant was also observed. Better understandings of the epidemiology, genetic and antigenic diversity of swIAV may help to design better health interventions for the prevention and control of swIAV infections in the herds.
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3,333 |
Age-Related Changes and Sex-Related Differences in Brain Iron Metabolism
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Iron is an essential element that participates in numerous cellular processes. Any disruption of iron homeostasis leads to either iron deficiency or iron overload, which can be detrimental for humans’ health, especially in elderly. Each of these changes contributes to the faster development of many neurological disorders or stimulates progression of already present diseases. Age-related cellular and molecular alterations in iron metabolism can also lead to iron dyshomeostasis and deposition. Iron deposits can contribute to the development of inflammation, abnormal protein aggregation, and degeneration in the central nervous system (CNS), leading to the progressive decline in cognitive processes, contributing to pathophysiology of stroke and dysfunctions of body metabolism. Besides, since iron plays an important role in both neuroprotection and neurodegeneration, dietary iron homeostasis should be considered with caution. Recently, there has been increased interest in sex-related differences in iron metabolism and iron homeostasis. These differences have not yet been fully elucidated. In this review we will discuss the latest discoveries in iron metabolism, age-related changes, along with the sex differences in iron content in serum and brain, within the healthy aging population and in neurological disorders such as multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and stroke.
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3,334 |
Antiviral Properties of Flavonoids and Delivery Strategies
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This review summarizes the latest advancements in phytochemicals as functional antiviral agents. We focused on flavonoids, like apigenin, vitexin, quercetin, rutin and naringenin, which have shown a wide range of biological effects including antiviral activities. The molecular mechanisms of their antiviral effects mainly consist in the inhibition of viral neuraminidase, proteases and DNA/RNA polymerases, as well as in the modification of various viral proteins. Mixtures of different flavonoids or combination of flavonoids with antiviral synthetic drugs provide an enhancement of their antiviral effects. Recent strategies in drug delivery significantly contribute to overcoming the low bioavailability of flavonoids. Frequent viral infections worldwide have led to the need for new effective antiviral agents, which can be identified among the various phytochemicals. In this light, screening the antiviral activities of a cocktail of flavonoids would be advantageous in order to prevent viral infections and improve current antiviral therapies.
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The Husavirus Posa-Like Viruses in China, and a New Group of Picornavirales
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Novel posa-like viral genomes were first identified in swine fecal samples using metagenomics and were designated as unclassified viruses in the order Picornavirales. In the present study, nine husavirus strains were identified in China. Their genomes share 94.1–99.9% similarity, and alignment of these nine husavirus strains identified 697 nucleotide polymorphism sites across their full-length genomes. These nine strains were directly clustered with the Husavirus 1 lineage, and their genomic arrangement showed similar characteristics. These posa-like viruses have undergone a complex evolutionary process, and have a wide geographic distribution, complex host spectrum, deep phylogenetic divergence, and diverse genomic organizations. The clade of posa-like viruses forms a single group, which is evolutionarily distinct from other known families and could represent a distinct family within the Picornavirales. The genomic arrangement of Picornavirales and the new posa-like viruses are different, whereas the posa-like viruses have genomic modules similar to the families Dicistroviridae and Marnaviridae. The present study provides valuable genetic evidence of husaviruses in China, and clarifies the phylogenetic dynamics and the evolutionary characteristics of Picornavirales.
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The Monoclonal Antibody Recognized the Open Reading Frame Protein in Porcine Circovirus Type 2-Infected Peripheral Blood Mononuclear Cells
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The purpose of this study in the context of the open reading frame 3 (ORF3) protein of porcine circovirus type 2 (PCV2) was especially its location and its relation to the capsid protein and the apoptosis protein in PCV2-infected porcine peripheral blood mononuclear cells (PBMCs). To detect the ORF3 protein, monoclonal antibodies (mAbs) were generated in this study. The mAb 7D3 binds to the ORF3 peptide (residues 35–66) and the native ORF3 protein in PCV2-infected PBMCs, as shown by immunofluorescence assay (IFA). The data show that 3–5% of PBMCs were positive for ORF3 protein or p53 protein. Further, 78–82% of PBMCs were positive for the capsid. This study confirmed the ORF3 protein not only colocalized with the capsid protein but also colocalized with the p53 protein in PBMCs. Immunoassays were conducted in this study to detect the capsid protein, the ORF3 protein, anti-capsid IgG, and anti-ORF3 IgG. The data show the correlation (r = 0.758) of the ORF3 protein and the capsid protein in the blood samples from the PCV2-infected herd. However, each anti-viral protein IgG had a different curve of the profile in the same herd after vaccination. Overall, this study provides a blueprint to explore the ORF3 protein in PCV2-infected PBMCs.
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Induction of the Unfolded Protein Response during Bovine Alphaherpesvirus 1 Infection
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Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus that causes great economic losses in the cattle industry. Herpesvirus infection generally induces endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) in infected cells. However, it is not clear whether ER stress and UPR can be induced by BoHV-1 infection. Here, we found that ER stress induced by BoHV-1 infection could activate all three UPR sensors (the activating transcription factor 6 (ATF6), the inositol-requiring enzyme 1 (IRE1), and the protein kinase RNA-like ER kinase (PERK)) in MDBK cells. During BoHV-1 infection, the ATF6 pathway of UPR did not affect viral replication. However, both knockdown and specific chemical inhibition of PERK attenuated the BoHV-1 proliferation, and chemical inhibition of PERK significantly reduced the viral replication at the post-entry step of the BoHV-1 life cycle. Furthermore, knockdown of IRE1 inhibits BoHV-1 replication, indicating that the IRE1 pathway may promote viral replication. Further study revealed that BoHV-1 replication was enhanced by IRE1 RNase activity inhibition at the stage of virus post-entry in MDBK cells. Furthermore, IRE1 kinase activity inhibition and RNase activity enhancement decrease BoHV1 replication via affecting the virus post-entry step. Our study revealed that BoHV-1 infection activated all three UPR signaling pathways in MDBK cells, and BoHV-1-induced PERK and IRE1 pathways may promote viral replication. This study provides a new perspective for the interactions of BoHV-1 and UPR, which is helpful to further elucidate the mechanism of BoHV-1 pathogenesis.
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Diagnostic Challenges in Canine Parvovirus 2c in Vaccine Failure Cases
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In this study, three different diagnostic tests for parvovirus were compared with vaccination status and parvovirus genotype in suspected canine parvovirus cases. Faecal samples from vaccinated (N17) and unvaccinated or unknown vaccination status (N41) dogs that had clinical signs of parvovirus infection were tested using three different assays of antigen tests, conventional and quantitative PCR tests. The genotype of each sample was determined by sequencing. In addition to the suspected parvovirus samples, 21 faecal samples from apparently healthy dogs were tested in three diagnostic tests to evaluate the sensitivity and specificity of the tests. The antigen test was positive in 41.2% of vaccinated dogs and 73.2% of unvaccinated diseased dogs. Conventional PCR and qPCR were positive for canine parvovirus (CPV) in 82.4% of vaccinated dogs and 92.7% of unvaccinated dogs. CPV type-2c (CPV-2c) was detected in 82.75% of dogs (12 vaccinated and 36 unvaccinated dogs), CPV-2b was detected in 5.17% dogs (one vaccinated and two unvaccinated) and CPV-2a in 1.72% vaccinated dog. Mean Ct values in qPCR for vaccinated dogs were higher than the unvaccinated dogs (p = 0.049), suggesting that vaccinated dogs shed less virus, even in clinical forms of CPV. CPV-2c was the dominant subtype infecting dogs in both vaccinated and unvaccinated cases. Faecal antigen testing failed to identify a substantial proportion of CPV-2c infected dogs, likely due to low sensitivity. The faecal samples from apparently healthy dogs (n = 21) showed negative results in all three tests. Negative CPV faecal antigen results should be viewed with caution until they are confirmed by molecular methods.
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Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses
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Arthropod-borne viruses contribute significantly to global mortality and morbidity in humans and animals. These viruses are mainly transmitted between susceptible vertebrate hosts by hematophagous arthropod vectors, especially mosquitoes. Recently, there has been substantial attention for a novel group of viruses, referred to as insect-specific viruses (ISVs) which are exclusively maintained in mosquito populations. Recent discoveries of novel insect-specific viruses over the past years generated a great interest not only in their potential use as vaccine and diagnostic platforms but also as novel biological control agents due to their ability to modulate arbovirus transmission. While arboviruses infect both vertebrate and invertebrate hosts, the replication of insect-specific viruses is restricted in vertebrates at multiple stages of virus replication. The vertebrate restriction factors include the genetic elements of ISVs (structural and non-structural genes and the untranslated terminal regions), vertebrate host factors (agonists and antagonists), and the temperature-dependent microenvironment. A better understanding of these bottlenecks is thus warranted. In this review, we explore these factors and the complex interplay between ISVs and their hosts contributing to this host restriction phenomenon.
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N-glycosylation in the Pre-Membrane Protein Is Essential for the Zika Virus Life Cycle
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Asparagine (N)-linked protein glycosylation plays an important role in protein synthesis and modification. Two Zika virus (ZIKV) structural proteins, the pre-membrane (prM) and envelope (E) protein are N-glycosylated. The prM protein of all ZIKV strains contains a single N-linked glycosylation site, while not all strains contain an N-linked site in the E protein. Our aim was to examine the impact of prM and E N-linked glycosylation on ZIKV infectivity and cell trafficking. Using a ZIKV infectious clone, we found that when the N-glycan sites were removed, the prM- and the prM/E-double mutants did not produce an infectious virus in the supernatant. Further, by using ZIKV prME constructs, we found that N-glycosylation was necessary for effective secretion of ZIKV virions. The absence of the N-glycan on prM or E caused protein aggregation in the rough endoplasmatic reticulum (ER) compartment. The aggregation was more pronounced for the prM-mutation, and the mutant virus lost the ER-Golgi intermediate compartment (ERGIC) localization. In addition, lack of the N-glycan on prM induced nuclear translocation of CCAAT-enhancer-binding protein homologous protein (CHOP), an ER stress marker. To conclude, we show that the prM N-glycan is essential for the ZIKV infectious cycle, and plays an important role in viral protein trafficking, protein folding, and virion assembly.
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Inflammatory Correlated Response in Two Lines of Rabbit Selected Divergently for Litter Size Environmental Variability
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SIMPLE SUMMARY: Animal welfare is a priority objective for the livestock industry. Litter size environmental variability has been related to environmental sensitivity. A divergent selection experiment for environmental variance of litter size variance was carried out successfully in rabbits over thirteen generations. The low line showed a lower inflammatory response and susceptibility to infectious disorders than the high line. In conclusion, the decrease of environmental sensitivity seems to increase the adaptation of the animal to the environment, and thus, its welfare. ABSTRACT: A divergent selection experiment for environmental variance of litter size variance was carried out in rabbits over thirteen generations. The aim of this study was to evaluate the inflammatory response in the two lines of the experiment, in order to analyse the effect of selection on susceptibility to diseases after challenging to stressful situations, such as 24 h after the first delivery. A total of 78 females were used in this study, 39 from each line. The line selected for litter size heterogeneity (the high line) showed lower white blood leukocyte count (WBC; −0.87 × 10(3)/µL), lower percentage of basophils (−0.11%), higher concentration of TNF-α (+13.8 pg/mL), and greater concentration of CRP (+38.1 µg/mL) than the line selected for litter size homogeneity (the low line). The high line had also higher concentrations of bilirubin, cholesterol, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) compared to the low line (difference between lines were +0.08 µmol/L, +0.14 µmol/L, +0.35 U/L and +2.4 U/L, respectively). The high line showed higher inflammatory response than the low line, in accordance with a larger susceptibility to infectious disorders. In conclusion, the line selected to increase litter size environmental variability seems to have poor capacity coping with environmental stressors. Therefore, selection for litter size environmental variability can be a useful way to improve animal welfare.
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Dietary Supplementation of Probiotic Lactobacillus acidophilus Modulates Cholesterol Levels, Immune Response, and Productive Performance of Laying Hens
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SIMPLE SUMMARY: Chicken eggs provide a considerable source of high-quality nutrients for human food and health. However, egg consumption may harm some people for its high contents of cholesterol and association with cardiovascular disease risk. Therefore, we investigated the possible effect of using Lactobacillus acidophilus (LA) as a probiotic additive in the laying hens’ diets on lowering egg-yolk cholesterol and also evaluated the immune responses and the productive performance of laying hens. The obtained results display the ability of LA, when supplemented in hen diets, to decrease the plasma triglycerides and cholesterol levels and the liver and egg yolk cholesterols in the hen. The beneficial effects of LA were also explored on some important humoral and cell-mediated immune responses in the laying hens. These positive effects led to an improvement in the productive performance of laying hens. Therefore, dietary LA supplementation could be recommended as a nutritional strategy for commercial lower-cholesterol egg production in addition to positive impacts on the performance and health of laying hens. ABSTRACT: This study examines the effect of dietary supplementation with Lactobacillus acidophilus (LA) on the cholesterol levels, immune response, and productive performance of laying hens. A total of 216, 40-week-old, commercial Hy-Line brown chicken layers were randomly assigned into four treatment groups (18 birds × three replicates per group) and fed diet supplemented with 0 (control), 1 × 10(9), 21 × 10(9), and 31 × 10(9) colony forming units (CFUs) of Lactobacillus acidophilus (LA) per kg of feed for six consecutive weeks. Results show that plasma triglycerides, low-density lipoprotein (LDL) and total cholesterols became lesser, while high-density lipoprotein (HDL) cholesterol became higher in LA-supplemented groups compared to the control. In addition, a significant reduction occurred in the liver and egg yolk cholesterol by LA supplementation. Moreover, the immunological parameters including antibody titer against sheep red blood cells (SRBCs), phytohemagglutinin (PHA)-wattle swelling test, and T- & B-lymphocyte proliferation were enhanced in laying hens supplemented with LA compared to the control hens. While the heterophil to lymphocyte (H/L) ratio decreased with LA supplementation, indicating low stress conditions in the treated hens. These positive effects for LA were further reflected on the productive performance of laying hens and improved egg production, egg weight, egg mass, and feed efficiency. Our findings indicate that LA probiotic could be recommended in laying hens’ diets for lowering egg yolk cholesterol with positive impacts on health and performance.
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Prevalence of ticks (Acari: Ixodidae) and Theileria lestoquardi in sheep at El Huda and El Nuhud animals production research stations, Sudan
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A cross-sectional study was performed 200 blood samples and 314 tick samples in El Huda and El Nuhud animals production research stations, Sudan, in May (summer) and December (winter) in 2016, to determine the prevalence of Theileria lestoquardi in sheep and the potential risk factors associated with the infection. A total of 200 blood samples and 314 tick samples were collected from El Huda (n = 103 blood, 97 tick) and El Nuhud (n = 97 blood, 217 tick) stations. Data on the risk factors, such as age, sex, ecotype of sheep, body condition score and seasons were recorded. The overall prevalence of Theileria lestoquardi was 13% (26/200) using PCR. A significant variation in the prevalence of Theileria lestoquardi was observed between the stations and the ecotype of sheep (p ≤ 0.05), whereas the highest prevalence was recorded in El-Huda station (19.4%) as well as in Shugor (22.8%). Other risk factors, like age, sex, body condition, and seasons were not found to be significantly associated with infection. However, the highest prevalence rate was recorded in old animals (21.6%) than the other, in males (17.9%) than females (12.2%), in animals with poor body condition (26.1%) than the other, and in winter (16%) than summer (10%). Four tick species i.e. Rhipicephalus evertsi evertsi (63.1%), Hyalomma anatolicum (13.8%), Hyalomma dromedarii (8.8%), and Hyalomma impeltatum (14.3%) were recorded in El Nuhud station. While in El Huda station, only Rhipicephalus evertsi evertsi (79.4%), Hyalomma anatolicum (20.6%) were recorded. This study revealed that 13% of sheep were suffering from Theileria lestoquardi which is a considerable number at the stations. Therefore, further epidemiological investigations on disease throughout the year are required in order to set a well-coordinated control program.
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A Randomized, Placebo-Controlled Clinical Trial of Famciclovir in Shelter Cats with Naturally Occurring Upper Respiratory Tract Disease
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SIMPLE SUMMARY: Upper respiratory tract disease (URTD) impacts the health and welfare of shelter cats. Mitigation strategies include stress reduction and population-level approaches; effective treatment plans focus on reducing the clinical signs in cats affected by URTD. This study evaluated the use of famciclovir, an antiviral therapy, in reducing clinical signs in shelter cats with URTD when administered at a target dose range of 40–90 mg/kg twice daily for up to 21 days. Cats were randomized into either a famciclovir treatment group (n = 11) or placebo group (n = 11). Testing for viral pathogen identification was performed at enrollment in the study, and clinical scoring was completed daily to evaluate the severity of signs. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, cats in the famciclovir treatment group had a significantly lower risk of worsening clinical signs with each day compared to the placebo group. Feline herpesvirus, a common pathogen causing URTD, was identified in 11/21 cats. The results of this small study justify the need for further research to determine the utility of famciclovir as part of treatment protocols for improving clinical signs and overall impacts of URTD in shelter cats. ABSTRACT: Upper respiratory tract disease (URTD) is a clinically relevant infectious disease in shelter cats, with individual and population-level welfare implications. The purpose of this study was to evaluate the effectiveness of famciclovir in reducing clinical signs of URTD in shelter cats during a therapeutic period of up to 21 days. Cats at two Northeastern United States animal shelters with URTD clinical signs were enrolled in a pragmatic, prospective, randomized, placebo-controlled clinical trial. Cats received either famciclovir (n = 11, target dose range 40–90 mg/kg) or placebo (n = 11), administered orally twice daily for up to 21 days with once-daily clinical scoring. At enrollment, conjunctival and oropharyngeal samples were collected for respiratory pathogen identification by RT-PCR. Zero-inflated Poisson regression was used to evaluate the treatment group effects and changes in clinical scoring over time. With each day of treatment, cats in both groups were less likely to experience worsening clinical scores; however, the risk of worsening scores with each day of treatment was significantly less in the famciclovir group compared to placebo (p = 0.006). Feline herpesvirus (FHV-1) DNA was detected in 11/21 cats. The findings justify further pragmatic studies to determine whether famciclovir treatment can contribute to a clinically relevant reduction in URTD morbidity in shelter cats.
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Elementary Classroom Teachers’ Self-Reported Use of Movement Integration Products and Perceived Facilitators and Barriers Related to Product Use
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Movement integration (MI) products are designed to provide children with physical activity during general education classroom time. The purpose of this study was to examine elementary classroom teachers’ self-reported use of MI products and subsequent perceptions of the facilitators of and barriers to MI product use. This study utilized a mixed-methods design. Elementary classroom teachers (n = 40) at four schools each tested four of six common MI products in their classroom for one week. Teachers completed a daily diary, documenting duration and frequency of product use. Following each product test, focus groups were conducted with teachers to assess facilitators and barriers. MI product use lasted for 11.2 (Standard Deviation (SD) = 7.5) min/occasion and MI products were used 4.1 (SD = 3.5) times/week on average. Activity Bursts in the Classroom for Fitness, GoNoodle, and Physical Activity Across the Curriculum were most frequently used. Facilitators of and barriers to MI product use were identified within three central areas—logistics, alignment with teaching goals, and student needs and interests. Teachers were receptive to MI products and used them frequently throughout the week. When considering the adoption of MI products, teachers, administrators, and policy makers should consider products that are readily usable, align with teaching goals, and are consistent with student needs and interests.
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Anmerkung zu OVG Niedersachsen, Beschl. v. 3.3.2020 – 13 LA 51/19 (VG – Braunschweig)
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3,347 |
Red cell volume measurement: using technetium as a replacement for chromium
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3,348 |
Clinical leadership training: a clinician's perspective
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3,349 |
We’ve never seen a patient with ARDS!
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3,350 |
Decision making processes underlying avoidance of mandatory child vaccination in Croatia – a qualitative study
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Despite extensive research evidencing child vaccination is safe and effective, we are witnessing a trend of increasing vaccine hesitancy which is listed among the top ten global health threats. Although some countries incorporate mandatory vaccination programs, no particularly efficient strategies for addressing vaccine avoidance have so far been identified. Within this study we investigated perceptions and reasoning of vaccine hesitant parents from Croatia where child vaccination is mandatory. The aims were to reveal different strategies by which they avoid mandatory vaccination schedules and hypothetical situations in which they would reconsider vaccinating, as well as to identify features of related decision-making. We conducted 25 semi-structured interviews with vaccine hesitant parents and analyzed the data using the framework of thematic analyses. The identified themes were related to the parents’ decision-making process, reflection as well as justification of their decision, avoidance behavior of mandatory vaccination schedules and related consequences, dealing with outcomes of the decision and reconsidering vaccinating. The results support and extend previous findings regarding vaccine reasoning, linking hesitancy with the experientially intuitive thinking style and social intuitionist model of moral reasoning. The findings provide important insights into vaccination avoidance and potential for reconsideration, as well as dealing with related risks. Furthermore, we offer a general framework as well as practical guidelines that may help the development of strategies aimed at increasing vaccination rates. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12144-020-01110-7) contains supplementary material, which is available to authorized users.
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A pilot study for smartphone photography to assess bleb morphology and vasculature post-trabeculectomy
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PURPOSE: The current grading systems used for bleb morphology assessment in patients post-trabeculectomy are based on standardized slit-lamp photographs and anterior segment imaging devices. The lack of availability of these expensive and non-portable devices in resource-deficient settings is a significant deterrent in their widespread utilization for proper post-operative management. The rapidly evolving utilization of smartphone photography has significantly benefited diagnostics of posterior segment disorders and is now being increasingly utilized for monitoring anterior segment pathologies as well as post-surgical course. In this study, we study a novel use of smartphones for bleb photography for assessing the morphological characteristics as vascularity and microcysts. METHODS: In this pilot, observational study, we compared the trabeculectomy bleb images of five subjects, obtained by iPhone X (dual lens) and iPhone 6S (single lens). We captured two image sets with both smartphones first with a focussed torchlight and then with a built-in flash video light. RESULTS: The images resulting from the newer iPhone X were substantially superior than those from iPhone 6S. For the 12-megapixel dual-camera set-up on the iPhone X, the 1 × lens resulted in better images than the 2 × lens with contrast and overall clarity of the area of interest. While the macro-lens attachment had promising results at 1 × zoom, there is no added advantage of the macro-lens attachment as it resulted in considerable loss of image quality at twice the zoom. Using a 20 D lens helped attain higher magnification and better framing as it reduced the focussing distance needed to get sharp images. The images obtained from both smartphones were of higher quality when illuminated from an external source when compared to the native iPhone flash due to even exposure and fewer autofocus artefacts. CONCLUSION: Analyses of all image sets showed that the current generation in-built camera app on IOS and newer iPhone camera optics resulted in high-quality images of the ocular surface with high magnification without any loss in clarity. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10792-020-01598-9) contains supplementary material, which is available to authorized users.
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Correction to Lancet Diabetes Endocrinol 2020; 8: 782–92
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Maternal and child mortality worsens in Latin America and the Caribbean
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3,354 |
Nursing's seat at the research roundtable
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3,355 |
First human efficacy study of a plant-derived influenza vaccine
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3,356 |
Toto, I’ve a Feeling We’re Not in Kansas Anymore: Navigating the Mid-career Transition to Academic Medicine
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When physicians, nurse practitioners, and physician assistants transition from a community setting to a university-based academic environment during mid-career, it can be challenging. Strategic planning is needed to ensure success. Institutions can assist experienced providers making such a transition, and there are steps the provider can take to self-advocate. As a group of four medical professionals who began their careers in patient care community practices for up to 18 years before transitioning to an academic medical center, we have had to navigate an unfamiliar landscape. We collectively offer our tips for a successful mid-career transition to academic medicine.
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Tracheostomy in Pediatric Intensive Care Unit: Experience from Eastern India
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OBJECTIVE: Tracheostomy is one of the most commonly used surgical intervention in sick children in the intensive care unit. The literature in the pediatric population is limited, therefore, we conducted this study to evaluate the indications, timing, complications, and outcomes of tracheostomy among the children at our center. METHODS: This retrospective study was conducted from January 2016 through December 2019. Data was collected from the patients’ records and analyzed. RESULTS: During this study period, 283 children were ventilated, of which 26 (9.1%) required tracheostomy. Among this 73% were boys. The median age of the children who underwent tracheostomy was 6.32 y. The most common indication for tracheostomy was prolonged mechanical ventilation [24 cases (92%)] followed by upper airway obstruction [2 cases (8%)]. The average time of tracheostomy was 11.65 d, range (1–21 d). Complications were seen in 14 patients (55%). The most common complications were accidental decannulation, occlusion, pneumothorax, and granulation tissue. Twenty one (80%) patients were successfully discharged, out of which 16 (61%) patients were discharged after decannulation and 5 (21%) were sent home with a tracheostomy tube in situ. Overall mortality in present study was 11.5%; none was directly related to tracheostomy. CONCLUSIONS: The indication for tracheostomy has been changed from emergency to more elective one. Prolonged mechanical ventilation is the most common indication for tracheostomy. Although the timing of tracheostomy is not fixed, two weeks time is reasonable and it can be done safely at the bedside in pediatric intensive care.
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Reflecting on the Impact of Cardiovascular Nurses in Australia and New Zealand in the International Year of the Nurse and Midwife
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3,359 |
Emergency laparoscopic treated the spontaneous bleeding and cystobiliary communication of multiple liver cysts
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3,360 |
Erratum regarding previously published articles
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Conceptual Physical Education: A course for the future
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The conceptual physical education (CPE) innovation began in the mid-20th century as an alternative approach to college-level, activity-only basic instruction classes. In addition to physical activity sessions, CPE courses (classes) use text material and classroom sessions to teach kinesiology concepts and principles of health-related fitness and health-enhancing physical activity. CPE courses are now offered in nearly all college programs as either required or electives classes. Two decades later, the high school CPE innovation began, and Kindergarten-8 programs followed. In this commentary, I argue that historian Roberta Park was correct in her assessment that physical education has the potential to be the renaissance field of the 21st century. Scientific contributions of researchers in kinesiology will lead the way, but science-based CPE and companion fitness education (FE) programs that align with physical education content standards and FE benchmarks will play a significant role. CPE courses have been shown to be effective in promoting knowledge, attitudes, and out-of-school physical activity and have the potential to elevate physical education as we chart the course of our future.
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3,362 |
From Mouse to Man and Back: Closing the Correlation Gap between Imaging and Histopathology for Lung Diseases
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Lung diseases such as fibrosis, asthma, cystic fibrosis, infection and cancer are life-threatening conditions that slowly deteriorate quality of life and for which our diagnostic power is high, but our knowledge on etiology and/or effective treatment options still contains important gaps. In the context of day-to-day practice, clinical and preclinical studies, clinicians and basic researchers team up and continuously strive to increase insights into lung disease progression, diagnostic and treatment options. To unravel disease processes and to test novel therapeutic approaches, investigators typically rely on end-stage procedures such as serum analysis, cyto-/chemokine profiles and selective tissue histology from animal models. These techniques are useful but provide only a snapshot of disease processes that are essentially dynamic in time and space. Technology allowing evaluation of live animals repeatedly is indispensable to gain a better insight into the dynamics of lung disease progression and treatment effects. Computed tomography (CT) is a clinical diagnostic imaging technique that can have enormous benefits in a research context too. Yet, the implementation of imaging techniques in laboratories lags behind. In this review we want to showcase the integrated approaches and novel developments in imaging, lung functional testing and pathological techniques that are used to assess, diagnose, quantify and treat lung disease and that may be employed in research on patients and animals. Imaging approaches result in often novel anatomical and functional biomarkers, resulting in many advantages, such as better insight in disease progression and a reduction in the numbers of animals necessary. We here showcase integrated assessment of lung disease with imaging and histopathological technologies, applied to the example of lung fibrosis. Better integration of clinical and preclinical imaging technologies with pathology will ultimately result in improved clinical translation of (therapy) study results.
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State of the Art Review on Genetics and Precision Medicine in Arrhythmogenic Cardiomyopathy
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Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterised by ventricular arrhythmia and an increased risk of sudden cardiac death (SCD). Numerous genetic determinants and phenotypic manifestations have been discovered in ACM, posing a significant clinical challenge. Further to this, wider evaluation of family members has revealed incomplete penetrance and variable expressivity in ACM, suggesting a complex genotype-phenotype relationship. This review details the genetic basis of ACM with specific genotype-phenotype associations, providing the reader with a nuanced perspective of this condition; whilst also proposing a future roadmap to delivering precision medicine-based management in ACM.
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Effects of p-Cresol on Senescence, Survival, Inflammation, and Odontoblast Differentiation in Canine Dental Pulp Stem Cells
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Aging, defined by a decrease in the physical and functional integrity of the tissues, leads to age-associated degenerative diseases. There is a relation between aged dental pulp and the senescence of dental pulp stem cells (DPSCs). Therefore, it is important to investigate the molecular processes underlying the senescence of DPSCs to elucidate the dental pulp aging mechanisms. p-Cresol (PC), a uremic toxin, is strongly related to cellular senescence. Here, age-related phenotypic changes including senescence, apoptosis, inflammation, and declining odontoblast differentiation in PC-treated canine DPSCs were investigated. Under the PC condition, cellular senescence was induced by decreased proliferation capacity and increased cell size, senescence-associated β-galactosidase (SA-β-gal) activity, and senescence markers p21, IL-1β, IL-8, and p53. Exposure to PC could stimulate inflammation by the increased expression of IL-6 and cause the distraction of the cell cycle by the increased level of Bax protein and decreased Bcl-2. The levels of odontoblast differentiation markers, dentin sialophosphoprotein (DSPP), dentin matrix protein 1, and osterix, were decreased. Consistent with those findings, the alizarin red staining, alkaline phosphatase, and DSPP protein level were decreased during the odontoblast differentiation process. Taken together, these findings indicate that PC could induce cellular senescence in DPSCs, which may demonstrate the changes in aging dental pulp.
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Identification of Gastritis Subtypes by Convolutional Neuronal Networks on Histological Images of Antrum and Corpus Biopsies
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Background: Gastritis is a prevalent disease and commonly classified into autoimmune (A), bacterial (B), and chemical (C) type gastritis. While the former two subtypes are associated with an increased risk of developing gastric intestinal adenocarcinoma, the latter subtype is not. In this study, we evaluated the capability to classify common gastritis subtypes using convolutional neuronal networks on a small dataset of antrum and corpus biopsies. Methods: 1230 representative 500 × 500 µm images of 135 patients with type A, type B, and type C gastritis were extracted from scanned histological slides. Patients were allocated randomly into a training set (60%), a validation set (20%), and a test set (20%). One classifier for antrum and one classifier for corpus were trained and optimized. After optimization, the test set was analyzed using a joint result from both classifiers. Results: Overall accuracy in the test set was 84% and was particularly high for type B gastritis with a sensitivity of 100% and a specificity of 93%. Conclusions: Classification of gastritis subtypes is possible using convolutional neural networks on a small dataset of histopathological images of antrum and corpus biopsies. Deep learning strategies to support routine diagnostic pathology merit further evaluation.
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Signalling Pathways Implicated in Alzheimer′s Disease Neurodegeneration in Individuals with and without Down Syndrome
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Down syndrome (DS), the most common cause of intellectual disability of genetic origin, is characterized by alterations in central nervous system morphology and function that appear from early prenatal stages. However, by the fourth decade of life, all individuals with DS develop neuropathology identical to that found in sporadic Alzheimer’s disease (AD), including the development of amyloid plaques and neurofibrillary tangles due to hyperphosphorylation of tau protein, loss of neurons and synapses, reduced neurogenesis, enhanced oxidative stress, and mitochondrial dysfunction and neuroinflammation. It has been proposed that DS could be a useful model for studying the etiopathology of AD and to search for therapeutic targets. There is increasing evidence that the neuropathological events associated with AD are interrelated and that many of them not only are implicated in the onset of this pathology but are also a consequence of other alterations. Thus, a feedback mechanism exists between them. In this review, we summarize the signalling pathways implicated in each of the main neuropathological aspects of AD in individuals with and without DS as well as the interrelation of these pathways.
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Improving Phylogenetic Signals of Mitochondrial Genes Using a New Method of Codon Degeneration
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Recovering deep phylogeny is challenging with animal mitochondrial genes because of their rapid evolution. Codon degeneration decreases the phylogenetic noise and bias by aiming to achieve two objectives: (1) alleviate the bias associated with nucleotide composition, which may lead to homoplasy and long-branch attraction, and (2) reduce differences in the phylogenetic results between nucleotide-based and amino acid (AA)-based analyses. The discrepancy between nucleotide-based analysis and AA-based analysis is partially caused by some synonymous codons that differ more from each other at the nucleotide level than from some nonsynonymous codons, e.g., Leu codon TTR in the standard genetic code is more similar to Phe codon TTY than to synonymous CTN codons. Thus, nucleotide similarity conflicts with AA similarity. There are many such examples involving other codon families in various mitochondrial genetic codes. Proper codon degeneration will make synonymous codons more similar to each other at the nucleotide level than they are to nonsynonymous codons. Here, I illustrate a “principled” codon degeneration method that achieves these objectives. The method was applied to resolving the mammalian basal lineage and phylogenetic position of rheas among ratites. The codon degeneration method was implemented in the user-friendly and freely available DAMBE software for all known genetic codes (genetic codes 1 to 33).
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3,368 |
Databases and Bioinformatic Tools for Glycobiology and Glycoproteomics
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Glycosylation plays critical roles in various biological processes and is closely related to diseases. Deciphering the glycocode in diverse cells and tissues offers opportunities to develop new disease biomarkers and more effective recombinant therapeutics. In the past few decades, with the development of glycobiology, glycomics, and glycoproteomics technologies, a large amount of glycoscience data has been generated. Subsequently, a number of glycobiology databases covering glycan structure, the glycosylation sites, the protein scaffolds, and related glycogenes have been developed to store, analyze, and integrate these data. However, these databases and tools are not well known or widely used by the public, including clinicians and other researchers who are not in the field of glycobiology, but are interested in glycoproteins. In this study, the representative databases of glycan structure, glycoprotein, glycan–protein interactions, glycogenes, and the newly developed bioinformatic tools and integrated portal for glycoproteomics are reviewed. We hope this overview could assist readers in searching for information on glycoproteins of interest, and promote further clinical application of glycobiology.
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3,369 |
ERRATUM
| null |
3,370 |
Reply to GASTRO-D-20-01179
| null |
3,371 |
Assessing the public perceptions of treated wastewater reuse: opportunities and implications for urban communities in developing countries
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Wastewater reuse has become an integral part of Integrated Water Resources Management and thus plays a role in securing the water needs for future generations. This study aimed at determining the perceptions of Canaanland, an emerging urban community in Ogun State, Nigeria, on treated wastewater reuse for several purposes. Data were collected through questionnaires administered to the city residents (n = 244). Findings revealed that the city was aware of the economic and environmental benefits of wastewater reuse but would prefer reuse schemes that involved less human contact such as flushing toilets, electricity generation, building construction, and car wash. The least preferred option was for potable purposes. The community also revealed that they would be willing to accept wastewater reuse as long as it is endorsed by medical doctors, university professors, and experts. However, 45.5% of the respondents were from the Covenant University academic environment. Also, an assessment was carried out to ascertain the implications and opportunities for wastewater reuse in the city. Findings indicated that wastewater reuse involves several complexities and interlinkages, which revolve around political and decisional factors, economic and social factors, environmental factors, and technological factors. From the study, policy and decisional suggestions and a wastewater process flow were developed for more efficient wastewater management within developing cities. A study was carried out on eight cities from developing nations that have created a framework for wastewater management using several approaches. Also, a summary of findings reveals that if adequately researched, cheap and alternative means of wastewater treatment and reuse could be developed for electricity generation, carwash, and firefighting for developing nations. The result of this research can be used to address public anxieties regarding wastewater-reuse practices. Additionally, this study hopes to aid successful wastewater management schemes in the foreseeable future.
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3,372 |
Complex Family Planning: a newly accredited, landmark fellowship
| null |
3,373 |
Do we have a new drug for heart rate control in patients with permanent atrial fibrillation? Response
| null |
3,374 |
Intensive care accessibility and outcomes in pandemics
| null |
3,375 |
Treating postpartum depression in rural veterans using internet delivered CBT: program evaluation of MomMoodBooster
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Depression in the postpartum period impacts approximately 13–26% of the general population. This number can be much higher for rural veteran women who face additional barriers to accessing specialized mental health services due to isolation and cultural factors. This study reports on a program evaluation of MomMoodBooster, a coach-supported internet-delivered CBT program for the treatment of maternal depression in veteran women. Repeated measures ANOVA, run with this sample of 326 women, demonstrated an overall positive effect size across outcome measures and engagement with no differences found between rural women and their urban counterparts. Some differences between urban and rural participants were found in total and average time spent with coaches as well as ratings of coach helpfulness, possibly indicating some cultural differences between coaches and rural women that need to be addressed. These results and the results of earlier trials suggest that MomMoodBooster can be a valid and efficacious option for reaching under-served veteran populations with specialized postpartum mental health support and is as effective with rural women as with urban women
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3,376 |
Non-invasive indirect monitoring of intra-abdominal pressure using microwave reflectometry: system design and proof-of-concept clinical trial
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Monitoring intra-abdominal pressure (IAP) has become a standard in intensive care units. Correlation between the abdominal wall’s thickness (AWTh) and IAP has been reported previously. The abdominal wall can be modeled as a compound of parallel dielectric slabs; changes in their width have a direct effect on the reflection coefficient of the abdominal wall at microwave frequencies. This work describes the design of a reflectometry system and its proof-of-concept trial on five patients during laparoscopic surgery. The system complies with IEEE Std. C95.1-2005 concerning exposure of humans to microwave electromagnetic fields in controlled environments. The results putatively show an inverse correlation between IAP and the reflection coefficient, and a strong dependence on the body mass index. A better understanding of the dynamics in the changes of the AWTh (during intra-abdominal hypertension) will allow further development of a microwave-based technique for the continuous non-invasive indirect monitoring of IAP in critical patients.
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3,377 |
Gerontologie, Geriatrie und Robotikforschung: Blick zurück nach vorn
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Assistive robotics as a gerontological geriatric field of research so far seem to be perceived more as “recalcitrant”. Predominant is a reserved attitude as to whether this should be considered a research topic to be taken seriously. The reliability of research results and the scientific half-life period are questioned as digital technique generations change exceedingly rapidly and also only a few sustainable standards and guidelines are established. In this context there is a danger that essential developments will be missed in gerontology and geriatrics, then the momentum is active right now and can now be shaped. In the scientific gerontology and geriatrics these developments should not be missed out on but must be grasped with pioneering spirit and proactively co-created. This can be achieved by further research endeavors, public activities and the utilization of knowledge from clinical and nursing practice with each having feedback into development and research.
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3,378 |
The contribution of the network “Health Behavior in School-aged Children” to the health of young people in Central and Eastern Europe
| null |
3,379 |
Dramatic presentation of acquired thrombotic thrombocytopenic purpura associated with COVID-19
| null |
3,380 |
Thromboinflammatory mechanisms in sickle cell disease – challenging the hemostatic balance
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Sickle cell disease (SCD) is an inherited hemoglobinopathy that is caused by the presence of abnormal hemoglobin S (HbS) in red blood cells, leading to alterations in red cell properties and shape, as the result of HbS dexoygenation and subsequent polymerization. The pathophysiology of SCD is characterized by chronic inflammatory processes, triggered by hemolytic and vaso-occlusive events, which lead to the va - ried complications, organ damage and elevated mortality seen in individuals with the disease. In association with activation of the endothelium and leukocytes, hemostatic alterations and thrombotic events are welldocumented in SCD. Here, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet activation in SCD, due to tissue factor activation, adhesion molecule expression, inflammatory mediator production and the induction of innate immune responses, among other mechanisms. Thromboinflammatory pathways may play a significant role in some of the major complications of SCD, such as stroke, venous thromboembolism and possibly acute chest syndrome, besides exacerbating the chronic inflammation and cellular interactions that trigger vaso-occlusion, ischemia-reperfusion processes, and eventually organ damage.
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3,381 |
Emerging role of bacterial extracellular vesicles in cancer
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Shedding of microbial extracellular vesicles constitutes a universal mechanism for inter-kingdom and intra-kingdom communication that is conserved among prokaryotic and eukaryotic microbes. In this review we delineate fundamental aspects of bacterial extracellular vesicles (BEVs) including their biogenesis, cargo composition, and interactions with host cells. We critically examine the evidence that BEVs from the host gut microbiome can enter the circulatory system to disseminate to distant organs and tissues. The potential involvement of BEVs in carcinogenesis is evaluated and future research ideas explored. We further discuss the potential of BEVs in microbiome-based liquid biopsies for cancer diagnostics and bioengineering strategies for cancer therapy.
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3,382 |
The economics of long work hours: how economic incentives influence workplace practice
| null |
3,383 |
Biomarkers in the ICU: less is more? No
| null |
3,384 |
From the Editor's Desk…
| null |
3,385 |
Epithor
| null |
3,386 |
Approval of oliceridine (TRV130) for intravenous use in moderate to severe pain in adults
| null |
3,387 |
Adapting to ensure brachytherapy remains a vital component of our future
| null |
3,388 |
In Patients with ARDS, Optimal PEEP Should Not Be Determined Using the Intersection of Relative Collapse and Relative Overdistention
| null |
3,389 |
Reply to van den Berg and van der Hoeven: In Patients with ARDS, Optimal PEEP Should Not Be Determined Using the Intersection of Relative Collapse and Relative Overdistention
| null |
3,390 |
Mental health matters
| null |
3,391 |
Insights Into Addressing Structural Barriers and Building Specialty Diversity Through a Successful Pipeline Pathway Program
| null |
3,392 |
Correction to Lancet Psychiatry 7: e60
| null |
3,393 |
Global health: time for radical change?
| null |
3,394 |
Broadening the Tent with Intentional Spaces
| null |
3,395 |
Psychiatry in Lebanon
| null |
3,396 |
The USA and its discontents
| null |
3,397 |
Geospatial analysis: a new frontier in humanitarian health research?
| null |
3,398 |
India–China border standoff raises concerns on drug supplies
| null |
3,399 |
Bollywood on the brain: gender and mental health in Hindi cinema
| null |
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