BACKGROUND: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown. METHODS: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke). RESULTS: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (SD) baseline hemoglobin levels were similar in the two groups. The mean (SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.740.02 g per deciliter in the daprodustat group and 0.660.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups. CONCLUSIONS: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.).

Cardiorespiratory or aerobic exercise immediately after practice of an upper-extremity motor skill task can facilitate skill consolidation, as demonstrated by enhanced performances at 24 h and 7-day retention tests. The purpose of this study was to examine the effect of acute cardiorespiratory exercise on motor skill consolidation when skill practice involved low and high levels of contextual interference introduced through repetitive and interleaved practice schedules, respectively. Forty-eight young healthy adults were allocated to one of four groups who performed either repetitive or interleaved practice of a pinch grip motor sequence task, followed by either a period of seated rest or a bout of high-intensity interval cycling. At pre- and post-practice and 24 h and 7-day retention tests, we assessed motor skill performance and -band (15-35 Hz) intermuscular coherence using surface electromyography (EMG) collected from the abductor pollicis brevis and first dorsal interosseous. At the 7-day retention test, off-line consolidation was enhanced in the cardiorespiratory exercise relative to the rest group, but only among individuals who performed interleaved motor skill practice (p = 0.02). Similarly, at the 7-day retention test, -band intermuscular coherence increased to a greater extent in the exercise group than in the rest group for those who performed interleaved practice (p = 0.02). Under the present experimental conditions, cardiorespiratory exercise preferentially supported motor skill consolidation and change in intermuscular coherence when motor skill practice involved higher rather than lower levels of contextual interference.

BACKGROUND Interactions of Streptococcus pneumoniae with viruses feature in the pathogenesis of numerous respiratory illnesses. METHODS We undertook a case-control study among adults at Kaiser Permanente Southern California between 2015-2019. Cases were diagnosed with lower respiratory tract infection (LRTI; including pneumonia or non-pneumonia LRTI diagnoses) with viral infections detected by multiplex polymerase chain reaction testing. Controls without LRTI diagnoses were matched to cases by demographic and clinical attributes. We measured vaccine effectiveness (VE) for PCV13 against virus-associated LRTI via the adjusted odds ratio of PCV13 receipt, comparing cases to controls. RESULTS Primary analyses included 13,856 virus-associated LRTI cases and 227,887 matched controls. Receipt of PCV13 was associated with 24.9% (95% confidence interval: 18.4-30.9%) VE against virus-associated pneumonia and 21.5% (10.9-30.9%) VE against other (non-pneumonia) virus-associated LRTI. We estimated 26.8% (19.9-33.1%) and 18.6% (9.3-27.0%) VE against all virus-associated LRTI episodes diagnosed in inpatient and outpatient settings, respectively. We identified statistically-significant protection against LRTI episodes associated with influenza A and B viruses, endemic human coronaviruses, parainfluenza viruses, human metapneumovirus, and enteroviruses, but not respiratory syncytial virus or adenoviruses. CONCLUSIONS Among adults, PCV13 conferred moderate protection against virus-associated LRTI. Impacts of PCVs may be mediated, in part, by effects on polymicrobial interactions between pneumococci and respiratory viruses.

Purpose The COVID-19 pandemic represents a major global health burden, and an important cause of morbidity and mortality nowadays. Data remains scarce on COVID-19 in lung transplant recipients (LTR). The purpose of this study was to understand impact of infection with COVID-19 in this population, to investigate different variables that contributed to the prognosis, and to assess the long-term clinical outcomes. This represents the largest cohort of continuously followed LTR with COVID-19 to date. Methods We conducted an observational retrospective cohort study of LTRs infected with COVID 19 at a major transplant center between June 2020 and April 2021. Infection was defined by having a positive diagnostic polymerase chain reaction (PCR) test. Patients characteristics, COVID severity and management were retrieved. Changes in individual patient's FEV1, imaging and trans-bronchial lung biopsies (TBLB) performed at 3, 6, and 12 month intervals after infection were compared to the baseline prior to infection. Results Fifty-three LTRs were identified as having COVID infection. Median age was 64 years, 31 (58.5%) were males, and 48 (90.5%) were double-LTR. Average BMI was 26.71 and 9 patients had diabetes. 38 (71.7%) patients were on three immunosuppression agents, and 4 (7.5%) patients had an augmented immunosuppression prior to COVID infection. 7 (13.2%) patients had at least one dose of mRNA COVID vaccine. 29 (54.7%) patients were treated as outpatient. Among admitted patients, 13 (24.5%) were treated in the ICU, and 7 (13.2%) required mechanical ventilation. Mortality rate was 15.1%. 26 patients had follow up on their FEV1 in 3 months, 33 in 6 months, and 7 up to 12 months. 14 (26.4%) patients had at least >10% drop in their FEV1, of which 10 patients had >20% drop. 18 patients had TBLB in 3 months, 19 in 6 months, and 4 in 12 months. Overall, 7 (13.2%) patients had acute cellular rejections (ACR). 23 patients had chest imaging at time of infection, with CT scan available for 10. Out of these, 6 showed pure ground glass opacities (GGO), and 4 showed mixed GGO and nodular opacities. Conclusion Out of our 53 LTR with COVID infection, 24.5% had severe disease. Mortality was high in our cohort at 15.1%. PFT decline was common, with 26.4% having an FEV1 drop of over 10% at follow up, suggesting persistent complications are common.

Rigorous estimates of preference-based utilities are important inputs into economic evaluations of childhood obesity interventions, yet no published review currently exists examining utility by weight status in paediatric populations. A comprehensive systematic literature review and meta-analysis was therefore undertaken, pooling data on preference-based health state utilities by weight status in children using a random-effects model. Tests for heterogeneity were performed, and publication bias was assessed. Of 3,434 potentially relevant studies identified, 11 met our eligibility criteria. Estimates of Cohen's d statistic suggested a small effect of weight status on preference-based utilities. Mean utility values were estimated as 0.85 (95% uncertainty interval [UI] 0.84-0.87), 0.83 (95% UI 0.81-0.85), 0.82 (95% UI 0.79-0.84) and 0.83 (95% UI 0.80-0.86) for healthy weight, overweight, obese and overweight/obese states, respectively. Meta-analysis of studies reporting utility values for both healthy weight and overweight/obese participants found a statistically significant weighted mean difference (0.015, 95% UI 0.003-0.026). A small but statistically significant difference was also estimated between healthy weight and overweight participants (0.011, 95% UI 0.004-0.018). Study findings suggest that paediatric-specific benefits of obesity interventions may not be well reflected by available utility measures, potentially underestimating cost-effectiveness if weight loss in childhood/adolescence improves health or well-being.

This contribution analyzes the COVID-19 outbreak by comparably simple mathematical and numerical methods. The final goal is to predict the peak of the epidemic outbreak per country with a reliable technique. This is done by an algorithm motivated by standard SIR models and aligned with the standard data provided by the Johns Hopkins University. To reconstruct data for the unregistered Infected, the algorithm uses current values of the infection fatality rate and a data-driven estimation of a specific form of the recovery rate. All other ingredients are data-driven as well. Various examples of predictions are provided for illustration.

INTRODUCTION Mortality rates associated with COVID-19 vary widely between countries and, within countries, between regions. These differences might be explained by population susceptibility, environmental factors, transmission dynamics, containment strategies, and diagnostic approaches. We aimed to analyze if obesity and diabetes prevalence are associated with higher COVID-19 mortality rates in Mexico. METHODOLOGY We analyzed the mortality rate for each of the 2,457 municipalities in Mexico, one of the countries with highest COVID-19 mortality rate, during the first seven months of the pandemic to identify factors associated with higher mortality, including demographic, health-related characteristics (prevalence of obesity, diabetes, and hypertension in adults older than 20 years old), and altitude. RESULTS During the first seven months of the COVID-19 pandemic there were 85,666 deaths reported in Mexico, with a cumulative mortality rate of 67 per 100,000 population. The mean mortality rate for the 2,457 municipalities in Mexico was 33.9 per 100,000 population. At a municipal level, the prevalence of diabetes and obesity, as well as high human development index, and location at < 500 or > 2000 above sea level were associated with higher mortality rate. CONCLUSIONS Elevated obesity and diabetes prevalence explain, in part, high COVID-19 mortality rates registered in certain municipalities in Mexico. These results suggest that a regionalized approach should be considered to successfully limit the impact of SARS-CoV-2.

BACKGROUND: Healthcare workers (HCWs) treating patients with COVID-19 report psychological distress. We examined whether disturbed sleep was associated with psychological distress in New York City (NYC) HCWs during the initial peak of the COVID-19 pandemic (April-May 2020). METHODS: HCWs completed a survey screening for acute stress (4-item Primary Care PTSD screen), depressive (Patient Health Questionaire-2), and anxiety (2-item Generalized Anxiety Disorder scale) symptoms. Insomnia symptoms (modified item from the Insomnia Severity Index) and short sleep (SS, sleep duration <6 hours/day) were assessed. Poisson regression analyses predicting psychological distress from SS and insomnia symptoms, adjusting for demographics, clinical role/setting, redeployment status, shifts worked, and multiple comparisons were performed. RESULTS: Among 813 HCWs (80.6% female, 59.0% white) mean sleep duration was 5.81.2 hours/night. Prevalence of SS, insomnia, acute stress, depressive, and anxiety symptoms were 38.8%, 72.8%, 57.9%, 33.8%, and 48.2%, respectively. Insomnia symptoms was associated with acute stress (adjusted prevalence ratio [PR]: 1.51, 95% CI: 1.35, 1.69), depressive (PR: 2.04, 95% CI: 1.78, 2.33), and anxiety (PR: 1.74, 95% CI: 1.55, 1.94) symptoms. SS was also associated with acute stress (PR: 1.17, 95% CI: 1.07, 1.29), depressive (PR: 1.36, 95% CI: 1.233, 1.51), and anxiety (PR: 1.38, 95% CI: 1.26, 1.50) symptoms. LIMITATIONS: Our cross-sectional analysis may preclude the identification of temporal associations and limit causal claims. CONCLUSIONS: In our study, SS and insomnia were associated with psychological distress symptoms in NYC HCWs during the COVID-19 pandemic. Sleep may be a target for interventions to decrease psychological distress among HCWs.

Journalistic crisis responses have been object of critical research, based on the analyses of wartime and terror reporting, as well as the coverage of natural disasters. This research notes that news media consistently fail to adequately cover political action during such crises, focusing too much on a limited set of political elite actors. Following this line of thought, the current analysis is interested in identifying general patterns of political reporting in the first nine months of the coronavirus crisis. In a large-scale computational content analysis of news medias Facebook messages in Germany, we apply named entity recognition and network analysis in order to identify political actors: how they were connected to specific topics in the coverage, and how this has changed during the various phases of the pandemic. The analysis reveals a focus on governmental elite actors and a limited set of experts, while the parliamentary opposition did not receive much attention. In contrast, conspiracy theorists and some foreign actors were covered prominently. However, this focus was not uniform throughout the year, and in a later phase of the pandemic, the analysis reveals a normalization with a less reduced set of individualized political actors. ? 2022 selection and editorial matter, Peter Van Aelst and Jay G. Blumler.

SIMPLE SUMMARY: The rate of death and disease in young dairy calves is alarmingly high, with diarrhea accounting for over half of all disease incidence. The majority of diarrhea cases are treated with antimicrobials, which may not be warranted. There is increasing concern related to the use of antimicrobials in food animals due to the emanant development of antimicrobial resistance. Bovine colostrum is densely packed with hundreds of nutrients and bioactives specifically tailored to improve calf health and development. As such, colostrum may have potential to be used an alternative to antimicrobials for the treatment of diarrhea. The objective of this review is to outline the causation and implication of diarrhea in young dairy calves and to explore the benefits of colostrum and its potential use as a therapy and preventative for diarrhea in pre-weaned calves. ABSTRACT: Diarrhea is the leading cause of morbidity and mortality in pre-weaned dairy calves and, as such, represents a significant animal health and welfare concern. Furthermore, digestive disease early in life is associated with several long-term consequences such as reduced growth rate and decreased milk yield during the first lactation, thus generating severe economic losses. The majority of diarrheic cases in young calves are treated with antimicrobials; however, it is necessary to develop alternative treatments, as excessive antimicrobial usage can lead to antimicrobial resistance and can negatively impact the gut microflora of a calf. Bovine colostrum is abundant in immune and bioactive factors that improve immune function and development. This rich and natural combination of immunoglobulins, natural antimicrobial factors, growth factors, anti-inflammatories and nutrients may be an attractive alternative to antimicrobials in the treatment of diarrhea in young dairy calves. There is evidence that supports the use of colostrum as an early treatment for diarrhea in young calves. Future research should investigate its therapeutic and economic effectiveness.

Severe COVID-19 (coronavirus disease 2019) is associated with elevated inflammatory markers, consistent with cytokine release syndrome (CRS). Tocilizumab is an interleukin-6 (IL-6) inhibitor effective in treating CRS secondary to chimeric antigen receptor T-cell (CAR T-cell) therapy. The efficacy of tocilizumab in treating COVID-19 is unknown. This was a retrospective cohort study conducted at two hospitals in northern New Jersey (USA). All patients treated with tocilizumab for confirmed or suspected COVID-19 between 10 March 2020 and 9 April 2020 at the study sites were included. The primary endpoint was clinical improvement on Day 7 after treatment as assessed by respiratory status. Univariate analysis compared data between those who improved and those who did not. A total of 45 severe and critically ill patients treated with tocilizumab for COVID-19 were evaluated. Of the 45 patients, 11 (24.4%), 22 (48.9%) and 12 (26.7%) patients improved, had no change or worsened by Day 7 after treatment, respectively. Lower white blood cell count and lactate dehydrogenase at the time of drug administration as well as shorter time from supplemental oxygen initiation to dosing were significantly associated with clinical improvement in the univariate analysis. In conclusion, tocilizumab administration was associated with a low rate of clinical improvement within 7 days in this cohort of severe and critically ill patients with COVID-19.

When the SARS-CoV-2 pandemic started,[1] science came to the immediate attention of the broad public. People and politicians were hanging on every word of medical doctors, virologists, molecular biologists, data scientists and many others in the hope of finding other protective measures than those used for centuries such as basic hygiene, distance, or quarantine. Here, at the Institute of Chemistry and Biotechnology at the Zurich University of Applied Sciences (ZHAW) we were also willing to provide scientific solutions to overcome the pandemic. Together with our partners from industry, we contributed to the development of a Swiss vaccine, are working on filters for active ventilated full protective suits and are developing tests to show the efficacy and safety of an active antiviral textile that allows controlled virus inactivation through an electrochemical reaction by applying a small current.

BACKGROUND: SARS-CoV-2 nucleic acid testing (NAT) has been routinely used for COVID-19 diagnosis during this pandemic; however, there have been concerns about its high false negative rate. We dissected its detection efficiency with a large COVID-19 cohort study. METHODS: We analyzed SARS-CoV-2 NAT positive rates of 4,275 specimens from 532 COVID-19 patients in Sichuan Province with different disease severities, statuses, and stages, as well as different types and numbers of specimens. RESULTS: The total positive rate of the 4,275 specimens was 37.5%. Among seven specimen types, BALF generated a 77.8% positive rate, followed by URT specimens (38.5%), sputum (39.8%), and feces/rectal swabs (34.1%). Specimens from critical cases generated a 43.4% positive rate, which was significantly higher than that of other severities. With specimens from patients at stable status, the SARS-CoV-2 positive rate was 40.6%, which was significantly higher than that of improved status (17.1%), but lower than that of aggravated status (61.5%). Notably, the positive rate of specimens from COVID-19 patients varied significantly from 85 to 95% during 3 days before and after symptom onset, to 20% at around 18 days after symptom onset. In addition, the detection rate increased from 72.1% after testing one throat swab, to 93.2% after testing three consecutive respiratory specimens from each patient. CONCLUSIONS: SARS-CoV-2 NAT detection rates vary with patient disease severity and status, specimen type, number of specimens, and especially disease progression. Sampling as close to symptom onset as possible, and consecutively collecting more than one respiratory specimen could effectively improve SARS-CoV-2 NAT detection efficiency.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has kept the whole world in tenterhooks due to its severe life-threatening infectious disease, COVID-19. The virus is distinct from its cousins, SARS-CoV and MERS-CoV in terms of severity of the infection. The obligated killing properties of the SARS-CoV-2 virus is mediated by its unique structure. Efforts for developing vaccines for COVID-19 are ongoing, but it is unlikely to be available in the immediate future. Due to the absence of precise treatment, the investigators are discovering other effective, protective, and healing choices. However, the lower than a predictable number of SARS-CoV-2 cases in countries with fragile health systems is mystifying. Recently, there has been a buzz about the protective effect of Bacille Calmette-Gurin (BCG) vaccine in COVID-19 through long-term boosting of trained immunity. Based on epidemiological correlations, we link up that BCG vaccination adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated mortality through the vaccine's capacity to confer heterologous protection. A number of clinical studies are underway to investigate this possibility but even if they prove effective-many questions will remain. Moreover, responsible stewardship of the BCG vaccine in the context of the COVID-19 epidemic is directly needed.

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease affecting up to 6.5% of the general population. There is no simple definition of NASH, and the molecular mechanism underlying disease pathogenesis remains elusive. Studies applying single omics technologies have enabled a better understanding of the molecular profiles associated with steatosis and hepatic inflammationthe commonly accepted histologic features for diagnosing NASH, as well as the discovery of novel candidate biomarkers. Multi-omics analysis holds great potential to uncover new insights into disease mechanism through integrating multiple layers of molecular information. Despite the technical and computational challenges associated with such efforts, a few pioneering studies have successfully applied multi-omics technologies to investigate NASH. Here, we review the most recent technological developments in mass spectrometry (MS)-based proteomics, metabolomics, and lipidomics. We summarize multi-omics studies and emerging omics biomarkers in NASH and highlight the biological insights gained through these integrated analyses.

Coronavirus Disease 2019 (COVID-19) is a pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak began in Wuhan, China, and spread rapidly, with many cases confirmed in multiple countries. Usually, after viral pneumonia were clinical cured, the pulmonary lesions of majority patients will gradually be absorbed to complete dissipation, very few severe patients may retain pulmonary interstitial inflammation and fibrosis (1-3). In this case, we described one unique COVID-19 patient, the symptoms were: dry cough, fatigue, poor appetite and subjective fever, moreover, the patient was a non-smoker, had no pulmonary bullous, no history of tuberculosis, and also no hypertension or diabetes. The patient received antiviral therapy, antibacterial therapy, recombinant human interferon-&#945;2a, vitamin C and oxygen inhalation. After two weeks of treatment and observation, the patient was clinical cured and discharged. However, two days later, the patient had a sudden chest stuffiness, CT images indicted: his lung didn't heal like others, but developed a large pulmonary cavity in the lower lobe of right lung. In hospital, the patient showed no symptoms of infection for another 14 days, and the pulmonary cavity remain unchanged. This case suggested: it is important to follow convalescent COVID-19 patients, especially their lung CT images, to make sure a fully recovery.

This note introduces the POLITICIZE dataset which contains information on the characteristics of 105 Deliberative Mini-Publics (DMPs) that took place in Europe between 2000 and 2020. Based on coding of experts regarding cases of real-life deliberative experiments in 18 different European countries, the dataset describes the core features of DMPs in Europe. It comprises information on three crucial dimensions: their composition (who deliberates?), their format (how do they deliberate?) and their role (what do they deliberate about and what are their prerogatives?). Hence, the note presents the different variables included in the dataset and reports empirical variations across them, thereby presenting the main contribution of the POLITICIZE dataset: delivering the most systematic and comprehensive efforts of data collection on mini-publics in Europe.

With the COVID-19 pandemic the health system is facing dual burden of cases, one being the COVID-19 or Severe Acute Respiratory Illness (SARI) cases and the second being the other Non-COVID cases. The Non-COVID cases due to the burden of the SARI cases became almost neglected by the Health System increasing the sufferings of the Non-COVID cases. In the current COVID times All India Institute of Medical Sciences, Gorakhpur continued to provide the health care to the Non-COVID cases. The current manuscript provides the detailed strategy and results of the various strategies used to provide care to such Non-COVID patients with minimum risk to the healthcare staff. ? 2021, Indian Association of Preventive and Social Medicine. All rights reserved.

Since being identified as a key receptor for SARS-CoV-2, Angiotensin converting enzyme 2 (ACE2) has been studied as one of the potential targets for the development of preventative and/or treatment options. Tissue expression of ACE2 and the amino acids interacting with the spike protein of SARS-CoV-2 have been mapped. Furthermore, the recombinant soluble extracellular domain of ACE2 is already in phase 2 trials as a treatment for SARS-CoV-2 infection. Most studies have continued to focus on the ACE2 extracellular domain, which is known to play key roles in the renin angiotensin system and in amino acid uptake. However, few also found ACE2 to have an immune-modulatory function and its intracellular tail may be one of the signaling molecules in regulating cellular activation. The implication of its immune-modulatory role in preventing the cytokine-storm, observed in severe COVID-19 disease outcomes requires further investigation. This review focuses on the regulated proteolytic cleavage of ACE2 upon binding to inducer(s), such as the spike protein of SARS-CoV, the potential of cleaved ACE2 intracellular subdomain in regulating cellular function, and the ACE2s immune-modulatory function. This knowledge is critical for targeting ACE2 levels for developing prophylactic treatment or preventative measures in SARS-CoV infections.

Glycosphingolipids (GSLs) are a specialized class of membrane lipids composed of a ceramide backbone and a carbohydrate-rich head group. GSLs populate lipid rafts of the cell membrane of eukaryotic cells, and serve important cellular functions including control of cellCcell signaling, signal transduction and cell recognition. Of the hundreds of unique GSL structures, anionic gangliosides are the most heavily implicated in the pathogenesis of lysosomal storage diseases (LSDs) such as Tay-Sachs and Sandhoff disease. Each LSD is characterized by the accumulation of GSLs in the lysosomes of neurons, which negatively interact with other intracellular molecules to culminate in cell death. In this review, we summarize the biosynthesis and degradation pathways of GSLs, discuss how aberrant GSL metabolism contributes to key features of LSD pathophysiology, draw parallels between LSDs and neurodegenerative proteinopathies such as Alzheimers and Parkinsons disease and lastly, discuss possible therapies for patients.