50 years of rice breeding in Bangladesh: genetic yield trends.

To assess the efficiency of genetic improvement programs, it is essential to assess the genetic trend in long-term data. The present study estimates the genetic trends for grain yield of rice varieties released between 1970 and 2020 by the Bangladesh Rice Research Institute. The yield of the varieties was assessed from 2001-2002 to 2020-2021 in multi-locations trials. In such a series of trials, yield may increase over time due to (i) genetic improvement (genetic trend) and (ii) improved management or favorable climate change (agronomic/non-genetic trend). In both the winter and monsoon seasons, we observed positive genetic and non-genetic trends. The annual genetic trend for grain yield in both winter and monsoon rice varieties was 0.01 t ha-1, while the non-genetic trend for both seasons was 0.02 t ha-1, corresponding to yearly genetic gains of 0.28% and 0.18% in winter and monsoon seasons, respectively. The overall percentage yield change from 1970 until 2020 for winter rice was 40.96%, of which 13.91% was genetic trend and 27.05% was non-genetic. For the monsoon season, the overall percentage change from 1973 until 2020 was 38.39%, of which genetic and non-genetic increases were 8.36% and 30.03%, respectively. Overall, the contribution of non-genetic trend is larger than genetic trend both for winter and monsoon seasons. These results suggest that limited progress has been made in improving yield in Bangladeshi rice breeding programs over the last 50 years. Breeding programs need to be modernized to deliver sufficient genetic gains in the future to sustain Bangladeshi food security.

Mental Health Impact of COVID-19 Infection on Postpartum Women from Lower and Middle-income Backgrounds in India and its Effects on Early Mother-infant Bonding: An Observational Study.

The study was designed to examine the mental health impact of COVID-19 infection in postpartum women and its effects on mother-infant bonding during the first eight weeks postpartum. Fifty-seven consenting eligible postpartum women were recruited for the study. They were assessed at two time points using standardized rating scales to measure distress and uniquely designed scales assessing COVID-19-specific outcome fears and bonding. Almost half [42%] of postpartum women with COVID-19 suffered from a probable anxiety disorder, and one-third [33.3%] suffered from probable depression. The overwhelming majority [91.2%] experienced COVID-19-specific fear. There was an inverse relationship between one dimension of maternal caregiving and self-report depression and anxiety scores, respectively. Additionally, despite discharge, 25% of the mothers had not breastfed the infants till the 8th-week postpartum period, which is in discordance with the World Health Organization (WHO) recommendation of exclusive breastfeeding up to 6 months of age that is widely practiced in India. The novel COVID-19 pandemic was associated with anxiety and depression, impacting mother-infant bonding. Therefore, there is a need for specialized mental health services and individualized breastfeeding interventions for this vulnerable population to ensure positive outcomes.

Safety and efficacy of convalescent plasma as a therapy for SARS-CoV-2: A systematic review and meta-analysis.

Background and Aims: The safety and efficacy of convalescent plasma therapy (CPT) in SARS-CoV-2 is promising but intriguing due to heterogeneity of published studies. We conducted this systematic review and meta-analysis of convalescent plasma use in COVID-19 to identify its safety and efficacy. Material and Methods: We comprehensively searched the databases - PubMed, Web of Science, Embase, and the Cochrane Library for journal papers published between December 2019 and January 2021 about the use of CPT in SARS-CoV-2, and performed a meta-analysis using random effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results: Of 1529 records, 11 studies were eligible (five RCTs, two nonrandomized intervention trials, three prospective observational, and one retrospective), and all were conducted in confirmed patients of SARS-CoV-2. Out of the 11 studies, four investigated the effect of CPT on mortality, three on symptom alleviation, five on duration of hospital stay, four on time to discharge, three on the effect on viral clearance, three on the improvement in antibody titers, two on oxygen requirement, and two on adverse events. The pooled estimate for relative risk of death from SARS-CoV-2 was no different after CPT than control (RR: 0.87, 95% CI: 0.69, 1.10), (p = 0.426) but the relative risk of clinical improvement of symptoms was better after CPT (RR: 1.61, 95% CI: 0.97. 2.70). There was earlier hospital discharge after CPT over control (RR: 1.49, 95% CI: 0.79, 2.80), improved viral clearance (RR: 1.95; 95% CI: 1.07, 3.53), and quicker detection of antibody titer (RR: 1.95; 95% CI: 1.07, 3.53). No difference was observed for adverse effects between CPT and control (RR: 0.92.; 95% CI: 0.63 1.35). Conclusion: CPT appears to be a safe and promising treatment in moderate to severe SARS-CoV-2 leading to faster clinical improvement, reduced oxygen requirement, early hospital discharge, and quicker emergence of protective antibodies despite having no mortality benefit.

The efficacy and safety of hydroxychloroquine (HCQ) in treatment of COVID19 -a systematic review and meta-analysis.

INTRODUCTION: The treatment of SARS CoV2 (Severe Acute Respiratory Syndrome corona virus 2) also known as COVID-19 (corona virus disease 2019) continues to remain an enigma even after six months of the pandemic. Hydroxychloroquine (HCQ) has been one of the most widely tested drugs for SARS CoV2 on account of its antiviral properties. However the results so far have been far from categorical. The meta-analyses conducted till date are also lacking in precision and appropriateness. This systematic review and meta-analysis addresses the efficacy and safety of HCQ in SARS CoV2 by overcoming the limitations of earlier meta-analysis. METHODS: A total of 5 prominent medical databases were searched and fourteen studies (n = 12455) were included in the systematic review and meta-analyses. The data on survival, alleviation of symptoms, conversion of RT PCR positivity to negativity, use and efficacy in presence of co-morbidities (Hypertension, diabetes and heart disease) and cardiac and gastrointestinal side effects were extracted. Meta-analysis was applied to calculate the pooled estimates. Fixed-effects model results were chosen since I2 was <25%.Meta-analysis was conducted using STATA version 13 (StataCorp LP, College Station, TX, USA). RESULTS: The pooled estimates showed that HCQ treatment did not significantly affect survival at 14 and 28 days in COVID-19 patients with respect to the control population (RR: 1.003, 95% CI: 0.983-1.022), alleviation of symptoms at day 10 (RR: 1.044, 95% CI: 0.911 1.196), success in presence of co-morbidities (RR: 1.058, 95% CI: 1.035-1.082) and conversion from RT PCR positive to RT PCR negative on day 6 (RR:1.123, 95% CI: 1.041 1.212). There was higher risk for cardiac side effects (RR: 2.012, 95% CI: 1.428 2.833) and gastrointestinal side effects (RR: 1.318, 95% CI: 0.730 2.380) in HCQ recipients. CONCLUSION: There is no evidence on the safety and efficacy of HCQ either alone or in combination with other drugs in SARS CoV2 infection.

Comparative study of the mental health impact of the COVID-19 pandemic on health care professionals in India.

Aims: This study aimed to investigate how the psychological health of health care professionals (HCP) on COVID duty was different from those who were not directly in contact. Methodology: Of 473 (76%) randomly selected respondents (doctors and nurses) to a WhatsApp request message, 450 subjects' data were finally analyzed. Result: The prevalence of stress, anxiety and depression among HCP was 33.8, 38.9 and 43.6%, respectively. Compared with nonexposed professionals, COVID-19-exposed professionals had roughly double the score of these morbidities (t = 6.3, p < 0.001; t = 6.9, p < 0.001; t = 6.0, p < 0.001). Most worry (71.11%) was about the health of their family, followed by themselves (35.55%). Conclusion: The level of exposure, feelings of uncertainty and fear of infection emerged in our study as possible risk factors for psychological morbidities among HCP.

Uremia Coupled with Mucosal Damage Predisposes Mice with Kidney Disease to Systemic Infection by Commensal Candida albicans.

Infections are the second major cause of mortality in patients with kidney disease and accompanying uremia. Both vascular access and non-access-related infections contribute equally to the infection-related deaths in patients with kidney disease. Dialysis is the most common cause of systemic infection by Candida albicans in these patients. C albicans also reside in the gastrointestinal tract as a commensal fungus. However, the contribution of gut-derived C albicans in non-access-related infections in kidney disease is unknown. Using a mouse model of kidney disease, we demonstrate that uremic animals showed increased gut barrier permeability, impaired mucosal defense, and dysbiosis. The disturbance in gut homeostasis is sufficient to drive the translocation of microbiota and intestinal pathogen Citrobacter rodentium to extraintestinal sites but not C albicans Interestingly, a majority of uremic animals showed fungal translocation only when the gut barrier integrity is disrupted. Our data demonstrate that uremia coupled with gut mucosal damage may aid in the translocation of C. albicans and cause systemic infection in kidney disease. Because most of the individuals with kidney disease suffer from some form of gut mucosal damage, these results have important implications in the risk stratification and control of non-access-related opportunistic fungal infections in these patients.

The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.

The kidney local microenvironment (KLM) plays a critical role in the pathogenesis of kidney fibrosis. However, the composition and regulation of a fibrotic KLM remain unclear. Through a multidisciplinary approach, we investigated the roles of the hepatocyte growth factor/c-met signaling pathway in regulating KLM formation in various chronic kidney disease (CKD) models. We performed a retrospective analysis of single-cell RNA sequencing data and determined that tubular epithelial cells and macrophages are two major cell populations in a fibrotic kidney. We then created a mathematical model that predicted loss of c-met in tubular cells would cause greater responses to injury than loss of c-met in macrophages. By generating c-met conditional knockout mice, we validated that loss of c-met influences epithelial plasticity, myofibroblast activation, and extracellular matrix synthesis/degradation, which ultimately determined the characteristics of the fibrotic KLM. Our findings open the possibility of designing effective therapeutic strategies to retard CKD.

Development and characterization of GR2E Golden rice introgression lines.

Golden Rice with ß-carotene in the grain helps to address the problem of vitamin A deficiency. Prior to commercialize Golden Rice, several performance and regulatory checkpoints must be achieved. We report results of marker assisted backcross breeding of the GR2E trait into three popular rice varieties followed by a series of confined field tests of event GR2E introgression lines to assess their agronomic performance and carotenoid expression. Results from confined tests in the Philippines and Bangladesh have shown that GR2E introgression lines matched the performance of the recurrent parents for agronomic and yield performance, and the key components of grain quality. Moreover, no differences were observed in terms of pest and disease reaction. The best performing lines identified in each genetic background had significant amounts of carotenoids in the milled grains. These lines can supply 30-50% of the estimated average requirements of vitamin A.

Epidemiology and risk factors for multidrug-resistant bacteria in critically ill patients with liver disease.

BACKGROUND AND AIMS: The critically ill patients with liver disease are vulnerable to infections in both community and hospital settings. The nosocomial infections are often caused by multidrug-resistant (MDR) bacteria. The present observational study was conducted to describe the epidemiology, course, and outcome of MDR bacterial infection and identify the risk factors of such infection in critically ill patients with liver disease. MATERIALS AND METHODS: A retrospective observational study was conducted on 106 consecutive critically patients with liver disease admitted in the Intensive Care Unit between March 2015 and February 2017. The MDR and non-MDR (non-MDR) groups were compared and the risk factors identified by multivariate analysis. RESULTS: Out of the 106 patients enrolled in the study, 23 patients had infections caused by MDR bacteria. The MDR-infected patients had severe liver disease (Child-Pugh score 11 ± 2.3 vs. 7 ± 3.9; P = 0.04), longer duration of antibiotic usage (6 ± 2.7 days vs. 2 ± 1.5 days; P = 0.04), greater use of total parenteral nutrition (TPN) (73.9% vs. 62.6%; P = 0.04), and more concurrent antifungal administration (60.8% vs. 38.5%; P = 0.04). The mortality was higher in MDR group (hazard ratio = 1.86; P < 0.05). The independent predictors of MDR bacterial infection were Child-Pugh score >10, prior carbapenem use, antibiotic use for more than 10 days, TPN use, and concurrent antifungal administration. CONCLUSION: The study demonstrated a high prevalence of MDR bacterial infection in critically ill patients with a higher mortality over non-MDR bacterial infection and also identified the independent predictors of such infections.

Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis.

Herpetic stromal keratitis (HSK) results in postinfection with Herpes simplex virus type 1 (HSV-1). The pathogenesis involves tissue damage by the host immune system, classifying HSK as an immunopathological disease. The crucial disease orchestrating cells is thought to be the T lymphocytes. The present study elucidates pathogenic and protective T cell subsets involved in the development of HSK using the gBT mice, which possess a monoclonal population of CD8+ T cells reactive to a HSV immunodominant epitope. Results show that HSV-reactive CD8+ T cells enter infected corneas during the acute but not the chronic phase of the disease during which the predominant population is CD4+ T cells. Adoptive transfer experiments in T and B cell-deficient recombination-activating gene knockout mice revealed that HSV-reactive CD8+ T cells are capable of ocular virus clearance, possibly through a combination of corneal and peripheral nervous system antiviral effects, but are not involved in lesion development. CD4+ T cells of the virus-specific or nonspecific species emerged as the pathogenic T cells capable of precipitating disease. These observations have the potential to yield important treatment strategies by targeting specific cell types in HSK.

Counteracting corneal immunoinflammatory lesion with interleukin-1 receptor antagonist protein.

Herpetic stromal keratitis (HSK) is a T cell-orchestrated, immunoinflammatory lesion that results from corneal Herpes simplex virus infection. Previous reports indicate an essential role for proinflammatory cytokine interleukin (IL)-1 in HSK pathogenesis. The present study evaluates the efficacy of IL-1 receptor antagonist (IL-1 ra) protein in the management of HSK. Mice receiving IL-1 ra had diminished disease severity. The administration of IL-1 ra was shown to reduce the influx into the cornea of cells of the innate and adaptive immune response. In addition, the treatment diminished corneal vascular endothelial growth factor levels, resulting in reduced angiogenic response. Our results show the importance of targeting early proinflammatory molecules such as IL-1 to counteract HSK and advocate IL-1 ra as an effective agent to achieve this.

Herpetic eye disease: immunopathogenesis and therapeutic measures.

Infection of the cornea with herpes simplex virus (HSV) can result in a chronic disease called herpetic stromal keratitis (HSK). The disease represents one of the leading causes of infectious blindness in the Western world. Immune-mediated cellular damage is suspected in the pathogenesis of human HSK. The murine model has been pivotal in further establishing HSK as an immunopathological disease. This article reviews understanding of HSK, both in humans and in the mouse model, with an emphasis on possible future therapeutic strategies to counteract this blinding immunoinflammatory disease.

Psychosis following chloroquine ingestion: a 10-year comparative study from a malaria-hyperendemic district of India.

OBJECTIVES: Serious adverse effects such as acute psychoses have been reported following treatment with chloroquine. Chloroquine can cause cell death, including neurons. We aimed to identify the most frequent type of psychiatric manifestation and symptomatological characteristics of psychosis following chloroquine ingestion (PFC). METHOD: Out of a total of 4471 randomly selected recent-onset psychosis patients, 3610 consecutive patients who had responded to standard treatment were screened for entry in the study. We compared background clinicodemographic profile information and psychopathology of 51 PFC patients, who were either drug free or drug naive, to 51 brief psychotic disorder (BPD) patients who were matched in terms of age, sex and education. Only those patients who remitted within 8 weeks (PFC patients) or 4 weeks (BPD patients) were included. Cranial computed tomography, electroencephalography and lumbar puncture of the entire experimental group were normal, and none had Mini Mental Status Examination score <22. Group difference and correlational statistics (parametric and nonparametric) have been used to test the hypotheses and explain the results. RESULTS: The most common (76.2%) type of psychiatric disturbance in PCF group was mood disorder (mixed episode) accompanied by predominant irritability with little blunting of affect. PFC patients characteristically had prominent positive symptoms with visual hallucination and derealization experiences. They were more restless, agitated and anxious and had more disturbed thought content and orientation, but better preserved insight. There was no linear relationship between the amount of chloroquine consumed and the severity of psychosis. CONCLUSION: Considering the large number of patients still receiving chloroquine especially in developing countries, this study has been presented to draw attention of the psychiatrists and other health professionals to the hazardous effect of chloroquine on mental health.

Pathogen-specific CD8 T cell responses are directly inhibited by IL-10.

Regulation of CD8 T cell expansion and contraction is essential for successful immune defense against intracellular pathogens. IL-10 is a regulatory cytokine that can restrict T cell responses by inhibiting APC functions. IL-10, however, can also have direct effects on T cells. Although blockade or genetic deletion of IL-10 enhances T cell-mediated resistance to infections, the extent to which IL-10 limits in vivo APC function or T cell activation/proliferation remains unknown. Herein, we demonstrate that primary and memory CD8 T cell responses following Listeria monocytogenes infection are enhanced by the absence of IL-10. Surface expression of the IL-10R is transiently up-regulated on CD8 T cells following activation, suggesting that activated T cells can respond to IL-10 directly. Consistent with this notion, CD8 T cells lacking IL-10R2 underwent greater expansion than wild-type T cells upon L. monocytogenes infection. The absence of IL-10R2 on APCs, in contrast, did not enhance T cell responses following infection. Our studies demonstrate that IL-10 produced during bacterial infection directly limits expansion of pathogen-specific CD8 T cells and reveal an extrinsic regulatory mechanism that modulates the magnitude of memory T cell responses.

Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection.

Following ocular HSV-1 infection, neovascularisation of the avascular cornea is a critical event in the pathogenesis of herpetic stromal keratitis. This present study evaluates the role of proinflammatory cytokines such as IL-6 in corneal angiogenesis following virus infection. Both in vivo and in vitro data indicate that IL-6 produced from virus-infected cells can stimulate noninfected resident corneal cells and other inflammatory cells in a paracrine manner to secrete VEGF, a potent angiogenic factor. Antibody neutralisation of IL-6 resulted in a significant decrease in the number of VEGF producing cells in the cornea. Thus, our results further demonstrate the close relationship between proinflammatory cytokines and VEGF-induced corneal neovascularisation.

Herpes keratitis in the absence of anterograde transport of virus from sensory ganglia to the cornea.

Herpes stromal keratitis is an immunopathologic disease in the corneal stroma leading to scarring, opacity, and blindness, and it is an important problem in common corneal surgeries. Paradoxically, virus antigens are largely focused in the epithelial layer of the cornea and not in the stromal layer, and viral antigens are eliminated before stromal inflammation develops. It is not clear what drives inflammation, whether viral antigens are necessary, or how viral antigens reach the stroma. It has been proposed that herpes simplex virus (HSV) travels from the corneal epithelium to sensory ganglia then returns to the stroma to cause disease. However, there is also evidence of HSV DNA and infectious virus persistent in corneas, and HSV can be transmitted to transplant recipients. To determine whether HSV resident in the cornea could cause herpes stromal keratitis, we constructed an HSV US9- mutant that had diminished capacity to move in neuronal axons. US9- HSV replicated and spread normally in the mouse corneal epithelium and to the trigeminal ganglia. However, US9- HSV was unable to return from ganglia to the cornea and failed to cause periocular skin disease, which requires zosteriform spread from neurons. Nevertheless, US9- HSV caused keratitis. Therefore, herpes keratitis can occur without anterograde transport from ganglia to the cornea, probably mediated by virus persistent in the cornea.

Protective and pathological roles of virus-specific and bystander CD8+ T cells in herpetic stromal keratitis.

Herpetic stromal keratitis (HSK), resulting from corneal HSV-1 infection, represents a T cell-mediated immunopathologic lesion. In T cell transgenic mice on a SCID or RAG knockout background, the T cells mediating lesions are unreactive to viral Ags. In these bystander models, animals develop ocular lesions but are unable to control infection. Transfer of HSV-immune cells into a CD8(+) T cell bystander model resulted in clearance of virus from eyes, animals survived, and lesions developed to greater severity. However, the adoptively transferred CD8(+) T cells were not evident in lesions, although they were readily detectable in the lymphoid tissues as well as in the peripheral and CNS. Our results indicate that viral-induced tissue damage can be caused by bystander cells, but these fail to control infection. Immune CD8(+) T cells trigger clearance of virus from the eye, but this appears to result by the T cells acting at sites distal to the cornea. A case is made that CD8(+) T cell control is expressed in the trigeminal ganglion, serving to curtail a source of virus to the cornea.