Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Sensory and motor deficits as contributors to early cognitive impairment.

INTRODUCTION: Age-related sensory and motor impairment are associated with risk of dementia. No study has examined the joint associations of multiple sensory and motor measures on prevalence of early cognitive impairment (ECI). METHODS: Six hundred fifty participants in the Baltimore Longitudinal Study of Aging completed sensory and motor function tests. The association between sensory and motor function and ECI was examined using structural equation modeling with three latent factors corresponding to multisensory, fine motor, and gross motor function. RESULTS: The multisensory, fine, and gross motor factors were all correlated (r = 0.74 to 0.81). The odds of ECI were lower for each additional unit improvement in the multisensory (32%), fine motor (30%), and gross motor factors (12%). DISCUSSION: The relationship between sensory and motor impairment and emerging cognitive impairment may guide future intervention studies aimed at preventing and/or treating ECI. HIGHLIGHTS: Sensorimotor function and early cognitive impairment (ECI) prevalence were assessed via structural equation modeling. The degree of fine and gross motor function is associated with indicators of ECI. The degree of multisensory impairment is also associated with indicators of ECI.

Pneumocystis jirovecii pneumonia in people living with HIV: a review.

Pneumocystis jirovecii is a ubiquitous opportunistic fungus that can cause life-threatening pneumonia. People with HIV (PWH) who have low CD4 counts are one of the populations at the greatest risk of Pneumocystis jirovecii pneumonia (PCP). While guidelines have approached the diagnosis, prophylaxis, and management of PCP, the numerous studies of PCP in PWH are dominated by the 1980s and 1990s. As such, most studies have included younger male populations, despite PCP affecting both sexes and a broad age range. Many studies have been small and observational in nature, with an overall lack of randomized controlled trials. In many jurisdictions, and especially in low- and middle-income countries, the diagnosis can be challenging due to lack of access to advanced and/or invasive diagnostics. Worldwide, most patients will be treated with 21 days of high-dose trimethoprim sulfamethoxazole, although both the dose and the duration are primarily based on historical practice. Whether treatment with a lower dose is as effective and less toxic is gaining interest based on observational studies. Similarly, a 21-day tapering regimen of prednisone is used for patients with more severe disease, yet other doses, other steroids, or shorter durations of treatment with corticosteroids have not been evaluated. Now with the widespread availability of antiretroviral therapy, improved and less invasive PCP diagnostic techniques, and interest in novel treatment strategies, this review consolidates the scientific body of literature on the diagnosis and management of PCP in PWH, as well as identifies areas in need of more study and thoughtfully designed clinical trials.

Ameliorative effects of Lactobacillus against Aflatoxin B1 / Efeitos benéficos do Lactobacillus contra a Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P<0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p<0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P < 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p < 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Ameliorative effects of Lactobacillus against Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P 0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p 0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Local spatial navigation or "steering" in patients with vestibular loss in a virtual reality environment.

BACKGROUND: Patients with vestibular loss have reduced wayfinding ability, but the association between vestibular loss and impaired steering spatial navigation is unclear. OBJECTIVE: To evaluate whether vestibular loss is associated with reduced steering navigation performance in a virtual reality (VR) environment containing obstacles. METHODS: 17 ambulatory adults with vestibular loss were age/sex-matched to healthy controls. Participants traversed a VR hallway with obstacles, and their navigation performance was compared using metrics such as collisions, time, total distance travelled, and speed in single and multivariate analysis. RESULTS: In univariate analysis there was no significant difference in collisions between vestibular patients and controls (1.84 vs. 2.24, p = 0.974). However, vestibular patients took more time, longer routes, and had lower speeds to complete the task (56.9 vs. 43.9 seconds, p < 0.001; 23.1 vs. 22.0 meters, p = 0.0312; 0.417 vs. 0.544 m/s, p < 0.001). These results were confirmed in multivariate analysis. CONCLUSIONS: This study found that patients with vestibular loss displayed slower gait speeds and traveled longer distances, though did not make more collisions, during a VR steering navigation task. Beyond the known influence of vestibular function on gait speed, vestibular loss may also contribute to less efficient steering navigation through an obstacle-laden environment, through neural mechanisms that remain to be elucidated.

Association Between Retinal Pathology and Hearing in Older Adults.

We investigated the association between retinal microvascular changes and hearing loss based on the hypothesis that both may result from shared microvascular pathology. Data from 536 older adults from the National Health and Nutritional Examination Survey 2005 to 2006 including sociodemographic and health characteristics, pure-tone hearing thresholds, and retinal pathologies were collected and analyzed. Associations between retinal and hearing pathologies were modeled with multivariable-adjusted linear regressions. 75% of participants had hearing loss and 15% of participants had retinopathy. The association between retinopathy, microaneurysms, and blot hemorrhages with better speech-frequency pure tone average was -2.81 (95% confidence interval [CI]: -5.72 to 0.10), -4.75 (95% CI: -8.73 to -0.78), and -5.34 (95% CI: -8.68 to -2.00), respectively. The presence of retinopathy, microaneurysms, and blot hemorrhages was inversely associated with hearing loss. Further studies are needed to better understand the potential relationship between microvascular pathologies of the eye and ear.

Acoustic Noise Levels in High-field Magnetic Resonance Imaging Scanners.

7-Tesla (T) magnetic resonance imaging may allow for higher resolution images but may produce greater acoustic noise than 1.5- and 3-T scanners. We sought to characterize the intensity of acoustic noise from 7- versus 3-T scanners. A-weighted sound pressure levels from 5 types of pulse sequences used for brain and inner ear imaging in 3- and 7-T scanners were measured. Time-averaged sound level and maximum sound levels generated for each sequence were compared. Time-averaged sound levels exceeded 95 dB and reached maximums above 105 dB on the majority of 3- and 7-T scans. The mean time-averaged sound level and maximum sound level across pulse sequences were greater in 7- than 3-T (105.6 vs 91.4, P = .01; 114.0 vs. 96.5 dB, P < .01). 7- and 3-T magnetic resonance imaging scanners produce high levels of acoustic noise that exceed acceptable safety limits, emphasizing the need for active and passive noise protection.

Sex Differences in the Effectiveness of Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Blockers, and Sacubitril-Valsartan for the Treatment of Heart Failure.

Background PARAGON-HF (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction) suggested a potential benefit of sacubitril-valsartan in women with preserved ejection fraction. Among patients with heart failure previously treated with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), we studied whether effectiveness of treatment with sacubitril-valsartan compared with ACEI/ARB monotherapy differed between men and women for both preserved and reduced ejection fraction. Methods and Results Data were derived from the Truven Health MarketScan Databases between January 1, 2011, and December 31, 2018. We included patients with a primary diagnosis of heart failure on treatment with ACEIs, ARBs, or sacubitril-valsartan on the basis of the first prescription after diagnosis. A total of 7181 patients treated with sacubitril-valsartan, 25 408 patients using an ACEI, and 16 177 patients treated with ARBs were included. A total of 790 readmissions or deaths occurred among 7181 patients in the sacubitril-valsartan group and 11 901 events in 41 585 patients treated with an ACEI/ARB. Adjusted for covariates, the hazard ratio (HR) for treatment with sacubitril-valsartan compared with an ACEI or ARB was 0.74 (95% CI, 0.68-0.80). The protective effect of sacubitril-valsartan was evident for men and women (women: HR, 0.75 [95% CI, 0.66-0.86]; P<0.01; men: HR, 0.71 [95% CI, 0.64-0.79]; P<0.01; P interaction 0.03). A protective effect for both sexes was seen only among those with systolic dysfunction. Conclusions Treatment with sacubitril-valsartan is more effective at reducing death and admission to the hospital for heart failure compared with ACEIs/ARBs similarly among men and women with systolic dysfunction; sex differences in the effectiveness of sacubitril-valsartan in diastolic dysfunction requires further investigation.

Growth, physiological, biochemical and molecular changes in plants induced by magnetic fields: A review.

The Earth's geomagnetic field (GMF) is an inescapable environmental factor for plants that affects all growth and yield parameters. Both strong and weak magnetic fields (MF), as compared to the GMF, have specific roles in plant growth and development. MF technology is an eco-friendly technique that does not emit waste or generate harmful radiation, nor require any external power supply, so it can be used in sustainable modern agriculture. Thus, exposure of plants to MF is a potential affordable, reusable and safe practice for enhancing crop productivity by changing physiological and biochemical processes. However, the effect of MF on plant physiological and biochemical processes is not yet well understood. This review describes the effects of altering MF conditions (higher or lower values than the GMF) on physiological and biochemical processes of plants. The current contradictory and inconsistent outcomes from studies on varying effects of MF on plants could be related to species and/or MF exposure time and intensity. The reviewed literature suggests MF have a role in changing physiological processes, such as respiration, photosynthesis, nutrient uptake, water relations and biochemical attributes, including genes involved in ROS, antioxidants, enzymes, proteins and secondary metabolites. MF application might efficiently increase growth and yield of many crops, and as such, should be the focus for future research.

Natural History of Cystic Vestibular Schwannomas.

OBJECTIVE: To determine the natural history of cystic vestibular schwannomas (VS). STUDY DESIGN: Retrospective cohort. SETTING: Single tertiary academic hospital. PATIENTS: Adults diagnosed with cystic VS who had at least 2 MRIs performed at least 6 months apart between 2008 and 2016 with no intervening treatment. MAIN OUTCOME MEASURES: Volumetric growth rates of both the entire tumor and individual cystic and solid components were measured. Linear growth rate of the entire tumor was assessed using the largest diameter parallel to the petrous face at the cerebellopontine angle (CPA). RESULTS: Twenty-one patients met inclusion criteria. The average volumetric growth rate of the tumor was 1.1 ± 2 (range: -1.2 to 7.8), while the average growth rate of the cystic component was 0.8 ± 1.6 (range: -0.5 to 5.3) cm3/year. The CPA diameter of the tumor demonstrated an average linear growth rate of was 1.2 ± 4.4 (range: -8to 13.5) mm/year. With regards to tumor diameter, 9/21 (42.9%) remained stable, 3/21 (14.2%) decreased in size, while 9/21 (42.9%) increased in size. CONCLUSIONS: Cystic tumors demonstrate a wide variability in growth rate. Larger, multi-center studies will be required to further compare this relationship to solid tumors.

Low-dose trimethoprim-sulfamethoxazole for the treatment of Pneumocystis jirovecii pneumonia (LOW-TMP): protocol for a phase III randomised, placebo-controlled, dose-comparison trial.

INTRODUCTION: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection of immunocompromised hosts with significant morbidity and mortality. The current standard of care, trimethoprim-sulfamethoxazole (TMP-SMX) at a dose of 15-20 mg/kg/day, is associated with serious adverse drug events (ADE) in 20%-60% of patients. ADEs include hypersensitivity reactions, drug-induced liver injury, cytopenias and renal failure, all of which can be treatment limiting. In a recent meta-analysis of observational studies, reduced dose TMP-SMX for the treatment of PJP was associated with fewer ADEs, without increased mortality. METHODS AND ANALYSIS: A phase III randomised, placebo-controlled, trial to directly compare the efficacy and safety of low-dose TMP-SMX (10 mg/kg/day of TMP) with the standard of care (15 mg/kg/day of TMP) among patients with PJP, for a composite primary outcome of change of treatment, new mechanical ventilation, or death. The trial will be undertaken at 16 Canadian hospitals. Data will be analysed as intention to treat. Primary and secondary outcomes will be compared using logistic regression adjusting for stratification and presented with 95% CI. ETHICS AND DISSEMINATION: This study has been conditionally approved by the McGill University Health Centre; Ethics approval will be obtained from all participating centres. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04851015.

Remdesivir for the treatment of COVID-19: a systematic review and meta-analysis.

BACKGROUND: The benefits of remdesivir in the treatment of hospitalized patients with COVID-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use. OBJECTIVES: To evaluate the role of remdesivir for hospitalized inpatients as a function of oxygen requirements. DATA SOURCES: Beginning with our prior systematic review, we searched MEDLINE using PubMed from 15 January 2021 through 5 May 2022. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials; all languages. PARTICIPANTS: All hospitalized adults with COVID-19. INTERVENTIONS: Remdesivir, in comparison to either placebo, or standard of care. ASSESSMENT OF RISK OF BIAS: We used the ROB-2 criteria. METHODS OF DATA SYNTHESIS: The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio scale and, to contextualize the probabilistic benefits, we also performed a Bayesian random effects meta-analysis on the risk difference scale. A ≥1% absolute risk reduction was considered clinically important. RESULTS: We identified eight randomized trials, totaling 10 751 participants. The risk ratio for mortality comparing remdesivir vs. control was 0.77 (95% CI, 0.5-1.19) in the patients who did not require supplemental oxygen; 0.89 (95% CI, 0.79-0.99) for nonventilated patients requiring oxygen; and 1.08 (95% CI, 0.88-1.31) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 76.8%, 93.8%, and 14.7%, respectively. The probability that remdesivir reduced mortality by ≥ 1% was 77.4% for nonventilated patients requiring oxygen. CONCLUSIONS: Based on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy. Treatment guidelines should be re-evaluated.

Repair of surviving hair cells in the damaged mouse utricle.

Sensory hair cells (HCs) in the utricle are mechanoreceptors required to detect linear acceleration. After damage, the mammalian utricle partially restores the HC population and organ function, although regenerated HCs are primarily type II and immature. Whether native, surviving HCs can repair and contribute to this recovery is unclear. Here, we generated the Pou4f3DTR/+; Atoh1CreERTM/+; Rosa26RtdTomato/+ mouse to fate map HCs prior to ablation. After HC ablation, vestibular evoked potentials were abolished in all animals, with ∼57% later recovering responses. Relative to nonrecovery mice, recovery animals harbored more Atoh1-tdTomato+ surviving HCs. In both groups, surviving HCs displayed markers of both type I and type II subtypes and afferent synapses, despite distorted lamination and morphology. Surviving type II HCs remained innervated in both groups, whereas surviving type I HCs first lacked and later regained calyces in the recovery, but not the nonrecovery, group. Finally, surviving HCs initially displayed immature and subsequently mature-appearing bundles in the recovery group. These results demonstrate that surviving HCs are capable of self-repair and may contribute to the recovery of vestibular function.

Remdesivir for the Treatment of COVID-19: An Updated Systematic Review and Meta-Analysis

BackgroundThe benefits of remdesivir in the treatment of hospitalized patients with Covid-19 remain debated with the National Institutes of Health and the World Health Organization providing contradictory recommendations for and against use. MethodsWe performed a systematic review of randomized controlled trials (RCTs) of remdesivir for the treatment of hospitalized patients with COVID-19. The primary outcome was mortality, stratified by oxygen use (none, supplemental oxygen without mechanical ventilation, and mechanical ventilation). We conducted a frequentist random effects meta-analysis on the risk ratio (RR) scale and, to better contextualize the probabilistic benefits, we also performed a bayesian random effects meta-analysis on the risk difference scale. ResultsWe identified 8 randomized trials, totaling 9157 participants. The RR for mortality comparing remdesivir versus control was 0.71 (95% confidence interval [CI] 0.42-1.22; I2=0.0%) in the patients who did not require supplemental oxygen; 0.83 (95%CI 0.73-0.95; I2=0.0%) for nonventilated patients requiring oxygen; and 1.19 (95%CI 0.98-1.44 I2=0.0%) in the setting of mechanical ventilation. Using neutral priors, the probabilities that remdesivir reduces mortality were 74.7%, 96.9% and 8.9%, respectively. The probability that remdesivir reduced mortality by more than 1% was 88.1% for nonventilated patients requiring oxygen. ConclusionBased on this meta-analysis, there is a high probability that remdesivir reduces mortality for nonventilated patients with COVID-19 requiring supplemental oxygen therapy.

Hydrogen sulfide: an emerging component against abiotic stress in plants.

As a result of climate change, abiotic stresses are the most common cause of crop losses worldwide. Abiotic stresses significantly impair plants' physiological, biochemical, molecular and cellular mechanisms, limiting crop productivity under adverse climate conditions. However, plants can implement essential mechanisms against abiotic stressors to maintain their growth and persistence under such stressful environments. In nature, plants have developed several adaptations and defence mechanisms to mitigate abiotic stress. Moreover, recent research has revealed that signalling molecules like hydrogen sulfide (H2 S) play a crucial role in mitigating the adverse effects of environmental stresses in plants by implementing several physiological and biochemical mechanisms. Mainly, H2 S helps to implement antioxidant defence systems, and interacts with other molecules like nitric oxide (NO), reactive oxygen species (ROS), phytohormones, etc. These molecules are well-known as the key players that moderate the adverse effects of abiotic stresses. Currently, little progress has been made in understanding the molecular basis of the protective role of H2 S; however, it is imperative to understand the molecular basis using the state-of-the-art CRISPR-Cas gene-editing tool. Subsequently, genetic engineering could provide a promising approach to unravelling the molecular basis of stress tolerance mediated by exogenous/endogenous H2 S. Here, we review recent advances in understanding the beneficial roles of H2 S in conferring multiple abiotic stress tolerance in plants. Further, we also discuss the interaction and crosstalk between H2 S and other signal molecules; as well as highlighting some genetic engineering-based current and future directions.

Ameliorative effects of Lactobacillus against Aflatoxin B1.

Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P<0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p<0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Antimicrobial susceptibility of Neisseria gonorrhoeae isolates and syndromic treatment of men with urethral discharge in Kingston, Jamaica, 2018-19.

OBJECTIVES: To quantitatively determine the antimicrobial susceptibility of clinical Neisseria gonorrhoeae isolates from men with urethral discharge in Jamaica and to describe the syndromic treatment therapies administered. METHODS: Urethral eSwabs (Copan) were collected from 175 men presenting with urethral discharge to the Comprehensive Health Centre STI Clinic, Kingston, Jamaica. Clinical information was collected and MICs of eight antimicrobials were determined for N. gonorrhoeae isolates (n = 96) using Etest and interpreted using CLSI criteria. RESULTS: The median age of the subjects was 28 years (range: 18-73 years) with a median of 2 sexual partners (range: 1-25) per male in the previous 3 months. All examined N. gonorrhoeae isolates were susceptible to ceftriaxone (96/96), azithromycin (91/91), cefixime (91/91) and spectinomycin (91/91). For ciprofloxacin and gentamicin, respectively, 98.9% (91/92) and 91.3% (84/92) of the isolates were susceptible and 1.1% (1/92) and 8.7% (8/92) showed intermediate susceptibility/resistance. For tetracycline and benzylpenicillin, respectively, 38.0% (35/92) and 22.0% (20/91) of the isolates were susceptible, 52.2% (48/92) and 74.7% (68/91) showed intermediate susceptibility/resistance and 9.8% (9/92) and 3.3% (3/91) were resistant. Syndromic treatment was administered as follows: 93.1% received 250 mg of ceftriaxone intramuscularly plus 100 mg of doxycycline orally q12h for 1-2 weeks and 6.9% received 500 mg of ciprofloxacin orally plus 100 mg of doxycycline orally q12h for 1 week. CONCLUSIONS: Ceftriaxone (250 mg) remains appropriate for gonorrhoea treatment in the examined population of men in Kingston, Jamaica. Surveillance of N. gonorrhoeae AMR should be expanded in Jamaica and other Caribbean countries to guide evidence-based treatment guidelines.

The forgotten oral microbial transplantation for improving the outcomes of COVID-19.

Ever since the uncovering of the severe discrepancy of COVID-19 manifestations, irrespective of viral load, scientists have raced to locate and manage factors contributing to the genesis of a critical state. Recent evidence delineates the role of oral dysbiosis in the development of low-grade inflammation, characterized by the increase of inflammatory cytokines common to those fundamental to the development of severe COVID. Furthermore, high periodontopathic bacteria were recorded in severe acute respiratory syndrome in COVID patients, as well as its common provoking comorbidities such as diabetes and hypertension. This can be explained by the immigration and elimination of oral bacteria into the airways, which, in the context of an injured lung, allows for their preferential overgrowth familiar to that, causing the progression to advanced lung diseases. This is why we indicate the promising usage of oral microbiome transplantation as a treatment of oral microbial dysbiosis, not only associated with the worst outcomes of COVID-19 but also in other disorders of low-grade inflammation.