Efficacy and safety of chloroquine and hydroxychloroquine for COVID-19 : A comprehensive evidence synthesis of clinical, animal, and in vitro studies

This study was financially supported by the Deputy of Research and Technology of Iran University of Medical Sciences, Tehran, Iran (Grant no. 17668).Peer reviewedPublisher PD

Nonsteroidal anti-inflammatory drugs in acute viral respiratory tract infections : An updated systematic review

Peer reviewedPublisher PD

Global systematic review of primary immunodeficiency registries

Introduction During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear. Areas covered Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus. Additionally, the reference list of all studies was hand-searched for additional studies. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients. Expert opinion Although these data suggest some progress in the identification and documentation of PID patients worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.Peer reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

A belief network for prediction of extra cash withdrawals for Y2K

grantor: University of TorontoThe Y2K problem was one of the world's greatest technological challenges in the 1990s, but especially for the developed nations. In addition to the technical challenges, the Y2K problem could have brought in psychological issues for the banking system. The public's lack of knowledge of Y2K might have resulted in the wrong perception of its consequences. As a result of this ignorance, there could have been emotionally driven irrational behavior from the public resulting in a run on the banks. Since the banking system relies on public confidence, it is vulnerable to such unpredictable reactions. Belief Networks (BNs), expert systems for decision-making under uncertainty, makes an ideal tool for predicting the public's reaction towards the Y2K problem because they can address the inherent uncertainty and volatility of the public's response to the Y2K issue. A belief network model was developed to predict the amount of cash the citizenry would require to deal with the real or imagined emergencies resulting from the Y2K problem as we were approaching January 1, 2000. The final (practical) BN model proved to be a good predictor of the amount of cash withdrawals Canadians might make to deal with the Y2K. This technique might be used as a decision-making tool for future events affecting the banking system or any other situation where the public's reactions must be predicted in some way.M.A.Sc

The course and outcome of renal failure due to human leptospirosis referred to a hospital in North of Iran A follow-up study

Background: Renal complication of leptospirosis is common and its clinical manifestations vary from urinary sediment changes to acute renal failure. The aim of this study was to determine the final outcome of renal involvement in leptospirosis. Methods: This longitudinal prospective study included all serologically confirmed cases of leptospirosis with evidence of renal failure. All patients were followed for three months while all patients with renal failure were followed-up for one year. Results: Fifty-one patients, 53.5±14.8 years (82.4% males) with acute renal failure were studied. Over the hospitalization period, 28 patients recovered, and seven (13.72%) patients died of multiple organ failure. At the time of discharge, 16 patients had mild renal failure. Over the follow-up period, all patients recovered but in two patients renal failure persisted at creatinine level of 1.5 mg/dl. Conclusion: Development of renal failure in leptospirosis is not rare. Recovery of renal function may last several months. However, most patients recover completely at least after one year

Progressive changes in detrusor function and micturition patterns with chroinc bladder ischemia

Purpose: Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia. Materials and Methods: Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy. Results: Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively. Conclusions: Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers

Microbial production of platform chemicals from glycerol

The chemical industry is primarily dependent on fossil oil and gas as raw materials. With increasing demands on reducing the greenhouse gas emissions and carbon footprint attributed to fossil based production, the industry looks for alternative renewable cleaner resources to secure the supplies for future chemical and material products. The current trend in the shift to bio-based economy aims at using the residues and wastes from agricultural-, forest- and marine biomass and related industries as industrial feedstocks. In order to match the efficiency of the petrochemical industry, the biobased industry requires a set of platform chemicals from which a vast range of products can be derived. Organic acids and diols are among the important platform chemicals, many of which are found as intermediates or end products of metabolic pathways in several microbes. In a project sponsored by the Swedish Governmental Agency for Innovation Systems at Lund University, glycerol obtained as a byproduct of biodiesel production, was used as a feedstock for the production of propionic acid (PA), 3-hydroxypropionaldehyde (3HPA), 3-hydroxypropionic acid (3HP) and 1,3-propanediol (1,3PDO), which are potential platforms for important chemicals like methacrylic acid, acrylic acid as well as polymers used in coatings, adhesives, automotive, construction, food, pharmaceuticals, and other industries. PA was produced using Propionibacterium acidipropionici cells. Different strategies for high cell density fermentations have been studied using immobilized cells, sequential batch fermentation and continuous fermentation with cell recycle, resulting in considerable enhancement in volumetric productivities. Heat-treated potato juice turned out to be an inexpensive and efficient nitrogen source for the fermentation. Glycerol is used as an electron acceptor by Lactobacillus reuteri and is metabolized through propanediol-utilization (Pdu) pathway involving initial dehydration to 3HPA, which is subsequently oxidized into 3HP and simultaneously reduced into 1,3PDO. Production of 3HPA by the resting L. reuteri cells was possible by in situ removal of the inhibitory product. Flux analysis of the Pdu pathway was done to determine the optimal conditions for production of 3HPA, and co-production of 3HP and 1,3PDO by the cells. Furthermore, an integrated system for the conversion of glycerol to 3HP and then to acrylic acid was demonstrated.The pdu pathway enzymes catalysing the oxidation of 3HPA were also expressed in Escherichia coli for the production of 3HP. Use of the resting cells led to the quantitative conversion of 3HPA to 3HP while the growing cells gave a mixture of 3HP and 1,3PDO due to the intrinsic 1,3-PD oxidoreductase activity of the E. coli cells. Copexpression of L. reuteri NADH oxidase allowed regeneration of NADH to allow continuous production of 3HP by the resting E. coli cells.ReferencesDishisha T, Alvarez MT, Hatti-Kaul R (2012) Bioresour. Technol. 118, 553-562 Dishisha T, Ståhl Å, Lundmark S, Hatti-Kaul R (2013) Bioresour. Technol. 135, 504-512 Sardari RRR, Dishisha T, Pyo S-H, Hatti-Kaul R (2013) J. Biotechnol. 168, 534-542 Sardari RRR, Dishisha T, Pyo S-H, Hatti-Kaul R (2014) J. Biotechnol. 192, 223-230 Dishisha T, Pereyra LP, Pyo S-H, Britton RA, Hatti-Kaul R (2014) Microb. Cell Fact. 13, 76 Sabet-Azad R, Sardari RRR, Linares-Pastén JA, Hatti-Kaul R (2015) Bioresource Technology 180, 214-22