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Antibody-mediated protection against pathogens is crucial to a healthy life. However, the recent SARS-CoV-2 pandemic has shown that pre-existing comorbid conditions including kidney disease account for compromised humoral immunity to infections. Individuals with kidney disease are not only susceptible to infections but also exhibit poor vaccine-induced antibody response. Using multiple mouse models of kidney disease, we demonstrate that renal dysfunction inhibits germinal center (GC) response against T-dependent antigens. GC B cells exhibit increased apoptosis in kidney disease. Uremic toxin hippuric acid drives loss of mitochondrial membrane potential, leading to increased apoptosis of GC B cells in a G-protein-coupled receptor 109A dependent manner. Finally, GC B cells and antibody titer are diminished in mice with kidney disease following influenza virus infection, a major cause of mortality in individuals with renal disorders. These results provide a mechanistic understanding of how renal dysfunction suppresses humoral immunity in patients with kidney disease., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Kidney disease represents a major medical and economic burden for which improved treatments are urgently needed. Emerging data have implicated Th17 cells and IL-17 signaling in the underlying pathogenesis of autoantibody-induced glomerulonephritis (AGN). However, the downstream transduction pathways mediated by IL-17 in autoimmunity are not well defined. In this article, we show that CCAAT/enhancer-binding protein (C/EBP) δ is elevated in kidney biopsies from multiple manifestations of human AGN. C/EBPδ is similarly upregulated in a mouse model of anti-glomerular basement membrane protein-mediated kidney disease, and Cebpd-/- mice were fully refractory to disease. Although C/EBPδ is expressed in a variety of cell types, C/EBPδ was required only in the radioresistant compartment to drive GN pathology. C/EBPδ induced expression of several IL-17-induced kidney injury markers and cytokines implicated in disease, including Il6 and Lcn2. Because mouse AGN models do not progress to fibrosis, we employed a nephrotoxic injury model using aristolochic acid I to assess the contribution of the IL-17-C/EBPδ pathway to renal fibrotic events. Surprisingly, deficiency of either C/EBPδ or the IL-17 receptor caused kidney fibrosis to be enhanced. Thus, C/EBPδ and IL-17 play divergent and apparently stage-specific roles in the pathogenesis of kidney disease., (Copyright © 2024 by The American Association of Immunologists, Inc.)

Autoantibody-mediated glomerulonephritis (AGN) arises from dysregulated renal inflammation, with urgent need for improved treatments. IL-17 is implicated in AGN and drives pathology in a kidney-intrinsic manner via renal tubular epithelial cells (RTECs). Nonetheless, downstream signaling mechanisms provoking kidney pathology are poorly understood. A noncanonical RNA binding protein (RBP), Arid5a, was upregulated in human and mouse AGN. Arid5a-/- mice were refractory to AGN, with attenuated myeloid infiltration and impaired expression of IL-17-dependent cytokines and transcription factors (C/EBPβ, C/EBPδ). Transcriptome-wide RIP-Seq revealed that Arid5a inducibly interacts with conventional IL-17 target mRNAs, including CEBPB and CEBPD. Unexpectedly, many Arid5a RNA targets corresponded to translational regulation and RNA processing pathways, including rRNAs. Indeed, global protein synthesis was repressed in Arid5a-deficient cells, and C/EBPs were controlled at the level of protein rather than RNA accumulation. IL-17 prompted Arid5a nuclear export and association with 18S rRNA, a 40S ribosome constituent. Accordingly, IL-17-dependent renal autoimmunity is driven by Arid5a at the level of ribosome interactions and translation., (© 2024 Li et al.)

The kidneys are life-sustaining organs that are vital to removing waste from our bodies. Because of their anatomic position and high blood flow, the kidneys are vulnerable to damage due to infections and autoinflammatory conditions. Even now, our knowledge of immune responses in the kidney is surprisingly rudimentary. Studying kidney-specific immune events is challenging because of the poor regenerative capacity of the nephrons, accumulation of uremic toxins, and hypoxia- and arterial blood pressure-mediated changes, all of which have unexpected positive or negative impacts on the immune response in the kidney. Kidney-specific defense confers protection against pathogens. On the other hand, unresolved inflammation leads to kidney damage and fibrosis. Interleukin-17 is a proinflammatory cytokine that has been linked to immunity against pathogens and pathogenesis of autoinflammatory diseases. In this review, we discuss current knowledge of IL-17 activities in the kidney in the context of infections, autoinflammatory diseases, and renal fibrosis.

Objectives: There is a paucity of available biomarkers of disease activity in idiopathic inflammatory myopathies (IIM), and serum cytokines/chemokines hold potential as candidate biomarkers. We aimed to determine serum cytokine profiles of IIM patients with active disease as compared to patients in remission and healthy controls., Methods: The IIM patients with active disease (included patients enrolled in repository corticotropin injection trial), in remission, and healthy controls were enrolled in this cross-sectional observational study. Serum concentrations of 51 cytokines/chemokines were obtained by utilising a bead-based multiplex cytokine assay (Luminex®). The myositis core set measures were obtained for all the patients. Cytokines with the best predictive ability to differentiate these clinical groups were assessed with three methods: 1) Least Absolute Shrinkage and Selection Operator modelling, 2) stepwise approach, and 3) logistic regression model., Results: Twenty-one IIM patients with active disease, 11 IIM patients in remission and 10 healthy controls were enrolled. Myositis patients had elevated levels of chemokines that attract eosinophils (eotaxin) and dendritic cells, NK cells, cytotoxic T-cells and monocytes/macrophages (CXCL-9, IP-10), cytokines that drive T-helper 1 responses (TNF-a, lymphotoxin-a), matrix degrading enzymes (MMP-3 and -9), and IGFBP-2 compared to healthy controls. Myositis patients with active disease had higher levels of lymphotoxin-a, CXCL-9, MIP-1a, MIP-1b and MMP-3 than patients in remission., Conclusions: This study demonstrated differences in cytokine profiles of IIM patients (active and inactive disease) compared to healthy controls and identified some cytokines that could potentially be used as biomarkers. Larger longitudinal studies are needed to validate our findings.

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., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pregnancy is a physiological state. During pregnancy increased physiological changes may lead to many biochemical and anatomical alterations. The biochemical changes that seen in blood of the pregnant mother are exaggerated in various complications of pregnancy like preeclampsia. Preeclampsia is a dangerous complication that may leads to maternal and neonatal mortality. Globally it affects 3.0-5.0% of pregnant women. The study was done to analyze the changes in serum phosphorus level in pre-eclamsia compared with normal pregnancy. The study was cross sectional and was performed from July 2016 to June 2017 in the department of Biochemistry, Mymensingh Medical College, Mymensingh, Bangladesh. Total 100 subjects were included in this study. Among them 50 preeclamptic patients were taken as case and another 50 normal pregnant women were taken as control. Statistical difference was calculated by Student's unpaired 't' test. Biochemical values were expressed as mean±SD. The mean±SD of serum phosphorus levels in case and control group were 2.81±0.79 and 3.40±0.87mg/dl respectively. The difference in mean±SD of serum phosphorus were highly significant (p<0.001) when compared between case and control.

Increasing selection differential and decreasing cycle time, the rate of genetic improvement can be accelerated. Creating and capturing higher genetic with higher accuracy within the shortest possible time is the prerequisite for enhancing genetic gain for any trait. Comprehensive yield testing at multi-locations at early generations together with the shortest line fixation time can expedite the rapid recycling of parents in the breeding program through recurrent selection. Genomic selection is efficient in capturing high breeding value individuals taking additive genetic effects of all genes into account with and without extensive field testing, thus reducing breeding cycle time enhances genetic gain. In the Bangladesh Rice Research Institute, GS technology together with the trait-specific marker-assisted selection at the early generation of RGA-derived breeding lines showed a prediction accuracy of 0.454-0.701 with 0.989-2.623 relative efficiency over the four consecutive years of exercise. This study reports that the application of GS together with trait-specific MAS has expedited the yield improvement by 117 kg ha -1 ·year -1 , which is around seven-fold larger than the baseline annual genetic gain and shortened the breeding cycle by around 1.5 years from the existing 4.5 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Biswas, Ahmed, Afrin, Rahman, Shalahuddin, Islam, Akter, Syed, Sarker, Ifterkharuddaula and Islam.)

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., (© 2023. The Author(s).)

IL-17 contributes to the pathogenesis of certain autoimmune diseases, but conversely is essential for host defense against fungi. Ab-based biologic drugs that neutralize IL-17 are effective in autoimmunity but can be accompanied by adverse side effects. Candida albicans is a commensal fungus that is the primary causative agent of oropharyngeal and disseminated candidiasis. Defects in IL-17 signaling cause susceptibility to candidiasis in mice and humans. A key facet of IL-17 receptor signaling involves RNA-binding proteins, which orchestrate the fate of target mRNA transcripts. In tissue culture models we showed that the RNA-binding protein AT-rich interaction domain 5A (Arid5a) promotes the stability and/or translation of multiple IL-17-dependent mRNAs. Moreover, during oropharyngeal candidiasis, Arid5a is elevated within the oral mucosa in an IL-17-dependent manner. However, the contribution of Arid5a to IL-17-driven events in vivo is poorly defined. In this study, we used CRISPR-Cas9 to generate mice lacking Arid5a. Arid5a -/- mice were fully resistant to experimental autoimmune encephalomyelitis, an autoimmune setting in which IL-17 signaling drives pathology. Surprisingly, Arid5a -/- mice were resistant to oropharyngeal candidiasis and systemic candidiasis, similar to immunocompetent wild-type mice and contrasting with mice defective in IL-17 signaling. Therefore, Arid5a-dependent signals mediate pathology in autoimmunity and yet are not required for immunity to candidiasis, indicating that selective targeting of IL-17 signaling pathway components may be a viable strategy for development of therapeutics that spare IL-17-driven host defense., (Copyright © 2022 by The American Association of Immunologists, Inc.)

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., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology.)

Aim: To share clinical pattern of presentation, the modalities of surgical intervention and the one month post-surgical outcome of rhino-orbito-mucormycosis (ROCM) cases., Methods: All COVID associated mucormycosis (CAM) patients underwent comprehensive multidisciplinary examination by ophthalmologist, otorhinolaryngologist and physician. Patients with clinical and radiological evidence of orbital apex involvement were included in the study. Appropriate medical and surgical intervention were done to each patient. Patients were followed up one-month post intervention., Results: Out of 89 CAM patients, 31 (34.8%) had orbital apex syndrome. Sixty-six (74.2%) of such patients had pre-existing diabetes mellitus, 18 (58%) patients had prior documented use of steroid use, and 55 (61.8%) had no light perception (LP) presenting vision. Blepharoptosis, proptosis, complete ophthalmoplegia were common clinical findings. Seventeen (19.1%) of such patients had variable amount of cavernous sinus involvement. Endoscopic debridement of paranasal sinuses and orbit with or without eyelid sparing limited orbital exenteration was done in most cases, 34 (38.2%) patients could retain vision in the affected eye., Conclusion: Orbital apex involvement in CAM patients occur very fast. It not only leads to loss of vision but also sacrifice of the eyeball, orbital contents and eyelids. Early diagnosis and prompt intervention can preserve life, vision and spare mutilating surgeries., (International Journal of Ophthalmology Press.)

Combating fungal pathogens poses metabolic challenges for neutrophils, key innate cells in anti-Candida albicans immunity, yet how host-pathogen interactions cause remodeling of the neutrophil metabolism is unclear. We show that neutrophils mediate renal immunity to disseminated candidiasis by upregulating glucose uptake via selective expression of glucose transporter 1 (Glut1). Mechanistically, dectin-1-mediated recognition of β-glucan leads to activation of PKCδ, which triggers phosphorylation, localization, and early glucose transport by a pool of pre-formed Glut1 in neutrophils. These events are followed by increased Glut1 gene transcription, leading to more sustained Glut1 accumulation, which is also dependent on the β-glucan/dectin-1/CARD9 axis. Card9-deficient neutrophils show diminished glucose incorporation in candidiasis. Neutrophil-specific Glut1-ablated mice exhibit increased mortality in candidiasis caused by compromised neutrophil phagocytosis, reactive oxygen species (ROS), and neutrophil extracellular trap (NET) formation. In human neutrophils, β-glucan triggers metabolic remodeling and enhances candidacidal function. Our data show that the host-pathogen interface increases glycolytic activity in neutrophils by regulating Glut1 expression, localization, and function., Competing Interests: Declaration of interests The authors declare no competing interests, (Copyright © 2022 Elsevier Inc. All rights reserved.)

In a recent Cell study, Leonardi et al. show that commensal mucosa-associated gut fungi profoundly impact host immunity, epithelial barrier function, and, unexpectedly, neuroimmune modulation of social behavior. All of these events are controlled by fungal-induced activation of type 17 cytokines that act on both epithelial cells and neurons., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The IL-17 family is structurally distinct from other cytokine subclasses. IL-17A and IL-17F, the most closely related of this family, form homodimers and an IL-17AF heterodimer. While IL-17A and IL-17F exhibit similar activities in many settings, in others their functions are divergent. To better understand the function of IL-17F in vivo, we created mice harboring a mutation in Il17f originally described in humans with unexplained chronic mucosal candidiasis (Ser-65-Leu). We evaluated Il17f S65L/S65L mice in DSS-colitis, as this is one of the few settings where IL-17A and IL-17F exhibit opposing activities. Specifically, IL-17A is protective of the gut epithelium, a finding that was revealed when trials of anti-IL-17A biologics in Crohn's disease failed and recapitulated in many mouse models of colitis. In contrast, mice lacking IL-17F are resistant to DSS-colitis, partly attributable to alterations in intestinal microbiota that mobilize Tregs. Here we report that Il17f S65L/S65L mice do not phenocopy Il17f -/- mice in DSS colitis, but rather exhibited a worsening disease phenotype much like Il17a -/- mice. Gut inflammation in Il17f S65L/S65L mice correlated with reduced Treg accumulation and lowered intestinal levels of Clostridium cluster XIV. Unexpectedly, the protective DSS-colitis phenotype in Il17f -/- mice could be reversed upon co-housing with Il17f S65L/S65L mice, also correlating with Clostridium cluster XIV levels in gut. Thus, the Il17f S65L/S65L phenotype resembles an IL-17A deficiency more closely than IL-17F deficiency in the setting of DSS colitis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Rice genetic improvement is a key component of achieving and maintaining food security in Asia and Africa in the face of growing populations and climate change. In this effort, the International Rice Research Institute (IRRI) continues to play a critical role in creating and disseminating rice varieties with higher productivity. Due to increasing demand for rice, especially in Africa, there is a strong need to accelerate the rate of genetic improvement for grain yield. In an effort to identify and characterize the elite breeding pool of IRRI's irrigated rice breeding program, we analyzed 102 historical yield trials conducted in the Philippines during the period 2012-2016 and representing 15,286 breeding lines (including released varieties). A mixed model approach based on the pedigree relationship matrix was used to estimate breeding values for grain yield, which ranged from 2.12 to 6.27 t·ha -1 . The rate of genetic gain for grain yield was estimated at 8.75 kg·ha -1  year -1 (0.23%) for crosses made in the period from 1964 to 2014. Reducing the data to only IRRI released varieties, the rate doubled to 17.36 kg·ha -1  year -1 (0.46%). Regressed against breeding cycle the rate of gain for grain yield was 185 kg·ha -1  cycle -1 (4.95%). We selected 72 top performing lines based on breeding values for grain yield to create an elite core panel (ECP) representing the genetic diversity in the breeding program with the highest heritable yield values from which new products can be derived. The ECP closely aligns with the indica 1B sub-group of Oryza sativa that includes most modern varieties for irrigated systems. Agronomic performance of the ECP under multiple environments in Asia and Africa confirmed its high yield potential. We found that the rate of genetic gain for grain yield found in this study was limited primarily by long cycle times and the direct introduction of non-improved material into the elite pool. Consequently, the current breeding scheme for irrigated rice at IRRI is based on rapid recurrent selection among highly elite lines. In this context, the ECP constitutes an important resource for IRRI and NAREs breeders to carefully characterize and manage that elite diversity., (© 2021. The Author(s).)

Objectives: COVID-19 pandemic has led to unprecedented increase in rates of stress and burn out among healthcare workers (HCWs). Heart rate variability (HRV) has been shown to be reflective of stress and burnout. The present study evaluated the prevalence of burnout and attempted to develop a HRV based predictive machine learning (ML) model to detect burnout among HCWs during COVID-19 pandemic., Methods: Mini-Z 1.0 survey was collected from 1615 HCWs, of whom 664, 512 and 439 were frontline, second-line and non-COVID HCWs respectively. Burnout was defined as score ≥3 on Mini-Z-burnout-item. A 12-lead digitized ECG recording was performed and ECG features of HRV were obtained using feature extraction. A ML model comprising demographic and HRV features was developed to detect burnout., Results: Burnout rates were higher among second-line workers 20.5% than frontline 14.9% and non-COVID 13.2% workers. In multivariable analyses, features associated with higher likelihood of burnout were feeling stressed (OR = 6.02), feeling dissatisfied with current job (OR = 5.15), working in a chaotic, hectic environment (OR = 2.09) and feeling that COVID has significantly impacted the mental wellbeing (OR = 6.02). HCWs with burnout had a significantly lower HRV parameters like root mean square of successive RR intervals differences (RMSSD) [p < 0.0001] and standard deviation of the time interval between successive RR intervals (SDNN) [p < 0.001]) as compared to normal subjects. Extra tree classifier was the best performing ML model (sensitivity: 84%) CONCLUSION: In this study of HCWs from India, burnout prevalence was lower than reports from developed nations, and was higher among second-line versus frontline workers. Incorporation of HRV based ML model predicted burnout among HCWs with a good accuracy., Competing Interests: Declaration of competing interest Dr. Jha has received contract research grants from Acadia Pharmaceuticals and Janssen Research & Development, educational grant to serve as Section Editor of the Psychiatry & Behavioral Health Learning Network, consultant fees from Eleusis Therapeutics US, Inc, and honoraria for CME presentations from North American Center for Continuing Medical Education and Global Medical Education. Dr Qamar is supported by institutional grant support from the North Shore Auxiliary research scholar fund and has received funding from Daiichi-Sankyo, American Heart Association and fees for educational activities from the American College of Cardiology, Society for Vascular Medicine, Society for Cardiovascular Angiography and Interventions, Janssen and Janssen, Pfizer, Medscape, and Clinical Exercise Physiology Association. The remaining authors have no disclosures to report., (Copyright © 2021 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

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.

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., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors.)

Aims: 1: Describe the epidemiology and determine risk factors for COVID-19 associated mucormycosis. 2: Elaborate the clinical spectrum of Rhino-Orbital-Cerebral Mucormycosis (ROCM), pattern of neuroaxis involvement and it's radiological correlates., Methods: Observational study. Consecutive, confirmed cases of mucormycosis (N = 55) were included. A case of mucormycosis was defined as one who had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological examination (HPE). Data pertaining to epidemiology, risk factors, clinico-radiological features were analysed using percentage of total cases., Results: Middle aged, diabetic males with recent COVID-19 infection were most affected. New onset upper jaw toothache was a striking observation in several cases. Among neurological manifestations headache, proptosis, vision loss, extraocular movement restriction; cavernous sinus, meningeal and parenchymal involvement were common. Stroke in ROCM followed a definitive pattern with watershed infarction., Conclusions: New onset upper jaw toothache and loosening of teeth should prompt an immediate search for mucormycosis in backdrop of diabetic patients with recent COVID-19 disease, aiding earlier diagnosis and treatment initiation. Neuroaxis involvement was characterized by a multitude of features pertaining to involvement of optic nerve, extraocular muscles, meninges, brain parenchyma and internal carotid artery., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Disseminated candidiasis is a hospital-acquired infection that results in high degree of mortality despite antifungal treatment. Autopsy studies revealed that kidneys are the major target organs in disseminated candidiasis and death due to kidney damage is a frequent outcome in these patients. Thus, the need for effective therapeutic strategies to mitigate kidney damage in disseminated candidiasis is compelling. Recent studies have highlighted the essential contribution of kidney-specific immune response in host defense against systemic infection. Crosstalk between kidney-resident and infiltrating immune cells aid in the clearance of fungi and prevent tissue damage in disseminated candidiasis. In this review, we provide our recent understanding on antifungal immunity in the kidney with an emphasis on IL-17-mediated renal defense in disseminated candidiasis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Antibody-mediated glomerulonephritis (AGN) is a clinical manifestation of many autoimmune kidney diseases for which few effective treatments exist. Chronic inflammatory circuits in renal glomerular and tubular cells lead to tissue damage in AGN. These cells are targeted by the cytokine IL-17, which has recently been shown to be a central driver of the pathogenesis of AGN. However, surprisingly little is known about the regulation of pathogenic IL-17 signaling in the kidney. Here, using a well-characterized mouse model of AGN, we show that IL-17 signaling in renal tubular epithelial cells (RTECs) is necessary for AGN development. We also show that Regnase-1, an RNA binding protein with endoribonuclease activity, is a negative regulator of IL-17 signaling in RTECs. Accordingly, mice with a selective Regnase-1 deficiency in RTECs exhibited exacerbated kidney dysfunction in AGN. Mechanistically, Regnase-1 inhibits IL-17-driven expression of the transcription factor IκBξ and, consequently, its downstream gene targets, including Il6 and Lcn2. Moreover, deletion of Regnase-1 in human RTECs reduced inflammatory gene expression in a IκBξ-dependent manner. Overall, these data identify an IL-17-driven inflammatory circuit in RTECs during AGN that is constrained by Regnase-1.

Excessive cytokine activity underlies many autoimmune conditions, particularly through the interleukin-17 (IL-17) and tumor necrosis factor-α (TNFα) signaling axis. Both cytokines activate nuclear factor κB, but appropriate induction of downstream effector genes requires coordinated activation of other transcription factors, notably, CCAAT/enhancer binding proteins (C/EBPs). Here, we demonstrate the unexpected involvement of a posttranscriptional "epitranscriptomic" mRNA modification [N6-methyladenosine (m 6 A)] in regulating C/EBPβ and C/EBPδ in response to IL-17A, as well as IL-17F and TNFα. Prompted by the observation that C/EBPβ/δ-encoding transcripts contain m 6 A consensus sites, we show that Cebpd and Cebpb mRNAs are subject to m 6 A modification. Induction of C/EBPs is enhanced by an m 6 A methylase "writer" and suppressed by a demethylase "eraser." The only m 6 A "reader" found to be involved in this pathway was IGF2BP2 (IMP2), and IMP2 occupancy of Cebpd and Cebpb mRNA was enhanced by m 6 A modification. IMP2 facilitated IL-17-mediated Cebpd mRNA stabilization and promoted translation of C/EBPβ/δ in response to IL-17A, IL-17F, and TNFα. RNA sequencing revealed transcriptome-wide IL-17-induced transcripts that are IMP2 influenced, and RNA immunoprecipitation sequencing identified the subset of mRNAs that are directly occupied by IMP2, which included Cebpb and Cebpd Lipocalin-2 ( Lcn2 ), a hallmark of autoimmune kidney injury, was strongly dependent on IL-17, IMP2, and C/EBPβ/δ. Imp2 -/- mice were resistant to autoantibody-induced glomerulonephritis (AGN), showing impaired renal expression of C/EBPs and Lcn2 Moreover, IMP2 deletion initiated only after AGN onset ameliorated disease. Thus, posttranscriptional regulation of C/EBPs through m 6 A/IMP2 represents a previously unidentified paradigm of cytokine-driven autoimmune inflammation., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Objectives: To determine the associations of epilepsy spectrum disorder (ESD) with brain insult and certain quantitative electroencephalographic (QEEG) and clinico-demographic parameters in patients with depression., Methods: 21 right-handed patients aged 18 to 50 years with the diagnosis of depression and ESD (scored ≥70 in Iowa Interview for Partial seizure-like symptoms) were compared with 21 patients with depression but without ESD (scored <70) and 21 normal subjects with <3 positive scores on the 12-Item General Health Questionnaire. Their QEEG parameters such as power spectrum and coherence of five frequency bands in 11 regions were compared., Results: Patients with ESD had more minor traumatic brain injury along with more severe and multiple depressive episodes. Patients with ESD had significantly higher beta1 power over all regions on the left scalp than did normal subjects. Patients with ESD had significantly higher beta2 power over the left central region than did patients with no ESD and normal subjects., Conclusions: For patients with severe recurrent depression, clinicians should systematically check for episodic partial seizure-like phenomena, especially when QEEG shows electrical disorganisation in the left side in those with mild traumatic brain injury., Competing Interests: No funding received for this work from any of the organizations or so. There is no commercial or proprietary interest in any device, or equipment mentioned in the submitted article. There is no financial interest any author might have (as a consultant, stock owner, employee, evaluator, etc.) in any item mentioned in the article. All authors reported no biomedical financial interests or potential conflicts of interest.

The invasive fungal infections (IFIs) are a major cause of mortality due to infectious disease worldwide. Majority of the IFIs are caused by opportunistic fungi including Candida , Aspergillus and Cryptococcus species. Lack of approved antifungal vaccines and the emergence of antifungal drug-resistant strains pose major constraints in controlling IFIs. A comprehensive understanding of the host immune response is required to develop novel fungal vaccines to prevent death from IFIs. In this review, we have discussed the challenges associated with the development of antifungal vaccines. We mentioned how host-pathogen interactions shape immunological memory and development of long-term protective immunity to IFIs. Furthermore, we underscored the contribution of long-lived innate and adaptive memory cells in protection against IFIs and summarized the current vaccine strategies., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a past co-authorship with the author., (Copyright © 2021 Biswas.)

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 I 2 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., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Vitamin A deficiency remains a common public health problem among the rice-dependent poor people in the developing countries of Asia. Conventional milled rice does not contain provitamin A (β-carotene) in is edible part (endosperm) and is also deficient in essential minerals, such as iron and zinc. Transgenic Golden Rice event GR2E, which produces β-carotene in its endosperm, was used as a parent to introgress the transgene locus conferring β-carotene biosynthesis into a widely grown rice variety, BRRI dhan29, which covers around 26.1% of the irrigated rice area (4.901 Mha) of Bangladesh in the dry season. The current study reports the introgression process and field performance of GR2E BRRI dhan29 Golden Rice. The background recovery of GR2E BRRI dhan29 lines at BC 5 F 2 generation was more than 98% with a 6K SNP-chip set. The transgenic GR2E BRRI dhan29 yielded 6.2 t/ha to 7.7 t/ha with an average of 7.0 ± 0.38 t/ha, while the non-transgenic BRRI dhan29 yielded 7.0 t/ha under confined field conditions in Bangladesh. Moreover, no significant difference between GR2-E BRRI dhan29 Golden Rice and non-transgenic BRRI dhan29 in any measured trait was observed in the multi-location trials conducted at five locations across the country. Furthermore, the appearance of cooked and uncooked rice was similar to that of BRRI dhan29 except for the yellow color indicating the presence of carotenoids. Total carotenoid content in the selected introgression lines ranged from 8.5 to 12.5 μg/g with an average of 10.6 ± 1.16 μg/g. This amount is sufficient to deliver approximately 66 and 80% of the recommended daily intake of vitamin A for children and women, respectively, assuming complete substitution of white rice in the diet with Golden Rice. However, the lead selected line(s) need further evaluation at open field conditions before deciding for commercial cultivation. A large-scale feeding trial among the malnourished community with this newly developed GR2-E BRRI dhan29 Golden Rice is also required to validate its efficacy in alleviating vitamin A deficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Biswas, Swamy, Kader, Hossain, Boncodin, Samia, Hassan, Wazuddin, MacKenzie and Reinke.)

Excessive inflammation can cause tissue damage and autoimmunity, sometimes accompanied by severe morbidity or mortality. Numerous negative feedback mechanisms exist to prevent unchecked inflammation, but this restraint may come at the cost of suboptimal infection control. Regnase-1 (MCPIP1), a feedback regulator of IL-17 and LPS signaling, binds and degrades target mRNAs. Consequently, Reg1 deficiency exacerbates autoimmunity in multiple models. However, the role of Reg1 in bacterial immunity remains poorly defined. Here, we show that mice deficient in Reg1 are resistant to Klebsiella pneumoniae (KP). Reg1 deficiency did not accelerate bacterial eradication. Rather, Reg1-deficient alveolar macrophages had elevated Ifnb1 and enrichment of type I IFN genes. Blockade of IFNR during KP infection reversed disease improvement. Reg1 did not impact Ifnb1 stability directly, but Irf7 expression was affected. Thus, Reg1 suppresses type I IFN signaling restricting resistance to KP, suggesting that Reg1 could potentially be a target in severe bacterial infections. IMPORTANCE Klebsiella pneumoniae (KP) can cause life-threatening bacterial pneumonia and is the third most common cause of ventilator-associated pneumonia in the United States. Host inflammatory responses to infection are necessary to control disease, yet at the same time can cause collateral damage or immunopathology. During immune responses, many events are established within the infected tissue to limit unchecked inflammation. However, this restraint of immunity can impair infection control, and it is not fully understood how this balance is maintained during different infection settings. In this study we explored the possibility that a host-derived negative regulator of RNA, Regnase-1, limits immunity to KP by dampening inflammation. Indeed, mice with reduced Regnase-1 levels showed improved survival to KP infection, linked to regulation of type I interferons. Therefore, although restraint of Reg1 is beneficial to prevent immunopathology, temporary blockade of Reg1 could potentially be exploited to improve host defense during infectious settings such as KP.

Golden Rice with β-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.

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., (Copyright © 2021 The Authors.)

Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Background and Aims: The implementation of safety measures during airway management is a major concern to prevent COVID-19 transmission during pandemic. Various guidelines and advisories are in vogue to ensure safe practices. However, their success depends on the caregivers' knowledge and understanding. This survey was conducted to assess the knowledge and safety concerns amongst physicians towards airway management in the background of COVID-19 pandemic., Material and Methods: A survey instrument of thirty questions covering three timelines of airway management viz. 'before', 'during' and 'after' airway intervention was created. The questionnaire was electronically mailed to the eligible physicians over a period of one month via a web-based platform and the responses were analyzed. The responses were depicted numerically as percentage. A multiple discriminant analysis was used to test the accuracy of responses after adjusting for common variables., Results: Out of 407 responses, 300 were eligible for analysis. The respondents with correct answers to questions with single correct response were 46%, 69% and 57.3%, along the three timelines and the respondents with more than 75% correct responses in questions with multiple correct responses were 49%, 58% and 31% along the same timelines. About 75% of the participants became aware of transmission through aerosols aftermath pandemic. About two-third of the participants had knowledge about the safety guidelines and recommendations. Majority of the respondents were aware of the safety measures 'during airway intervention'., Conclusion: Our study found satisfactory knowledge and appreciable concern among the practicing physicians regarding airway safety measures in the wake of COVID-19 pandemic. However, more physicians were aware about the measures required to be adopted 'during' airway intervention. The survey highlights the need for a more focused training of the caregivers about safety measures 'before' and 'after' airway intervention., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Anaesthesiology Clinical Pharmacology.)

Disseminated candidiasis caused by the fungus Candida albicans is a major clinical problem in individuals with kidney disease and accompanying uremia; disseminated candidiasis fatality is twice as common in patients with uremia as those with normal kidney function. Many antifungal drugs are nephrotoxic, making treatment of these patients particularly challenging. The underlying basis for this impaired capacity to control infections in uremic individuals is poorly understood. Here, we show in multiple models that uremic mice exhibit an increased susceptibility to systemic fungal infection. Uremia inhibits Glut1-mediated uptake of glucose in neutrophils by causing aberrant activation of GSK3β, resulting in reduced ROS generation and hence impaired killing of C. albicans in mice. Consequently, pharmacological inhibition of GSK3β restored glucose uptake and rescued ROS production and candidacidal function of neutrophils in uremic mice. Similarly, neutrophils isolated from patients with kidney disease and undergoing hemodialysis showed similar defect in the fungal killing activity, a phenotype rescued in the presence of a GSK3β inhibitor. These findings reveal a mechanism of neutrophil dysfunction during uremia and suggest a potentially translatable therapeutic avenue for treatment of disseminated candidiasis., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Oropharyngeal candidiasis (OPC; thrush) is an opportunistic infection caused by the commensal fungus Candida albicans Interleukin-17 (IL-17) and IL-22 are cytokines produced by type 17 lymphocytes. Both cytokines mediate antifungal immunity yet activate quite distinct downstream signaling pathways. While much is now understood about how IL-17 promotes immunity in OPC, the activities of IL-22 are far less well delineated. We show that, despite having similar requirements for induction from type 17 cells, IL-22 and IL-17 function nonredundantly during OPC. We find that the IL-22 and IL-17 receptors are required in anatomically distinct locations within the oral mucosa; loss of IL-22RA1 or signal transducer and activator of transcription 3 (STAT3) in the oral basal epithelial layer (BEL) causes susceptibility to OPC, whereas IL-17RA is needed in the suprabasal epithelial layer (SEL). Transcriptional profiling of the tongue linked IL-22/STAT3 not only to oral epithelial cell proliferation and survival but also, unexpectedly, to driving an IL-17-specific gene signature. We show that IL-22 mediates regenerative signals on the BEL that replenish the IL-17RA-expressing SEL, thereby restoring the ability of the oral epithelium to respond to IL-17 and thus to mediate antifungal events. Consequently, IL-22 signaling in BEL "licenses" IL-17 signaling in the oral mucosa, revealing spatially distinct yet cooperative activities of IL-22 and IL-17 in oral candidiasis., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Introduction: The prediction of mortality in acute pancreatitis (AP) is a useful estimate for effective treatment. Scoring systems such as acute physiology and chronic health evaluation (APACHE) II, computed tomography (CT) severity index (CTSI), bedside index of severity in acute pancreatitis (BISAP), etc., are used for prediction. Biomarkers like C-reactive protein (CRP) and procalcitonin (PCT) are also considered useful for prognostication. The aim of this retrospective study was to correlate the changes in serum PCT level with APACHE II score between admission and 48 hours as mortality predictor in AP., Materials and Methods: The observational study was conducted in a cohort of 42 patients admitted consecutively in the seven-bedded general intensive care unit (ICU) of our institute between June 2016 and May 2018, with the diagnosis of AP. The APACHE II score and serum PCT level at admission and 48 hours were retrieved from the hospital database. The change in APACHE II and PCT level was compared between ICU "survivors" and "nonsurvivors." The predictive accuracy of APACHE II and PCT was measured using area under receiver-operator characteristics (ROC) curve. A p value <0.05 was considered as significant., Results: Of the 42 patients enrolled, 30 patients (71.42%) were survivors and 12 (28.58%) were nonsurvivors. The median APACHE II score in nonsurvivors increased from 16 (7-19) to 23 (11-29) and remained unchanged at 16 (9-19 at admission; 10-22 at 48 hours) in survivors. The median PCT levels increased from 3.8 (1.2-5.6) to 6.2 (1.9-12.5) in nonsurvivors and decreased from 3.8 (1.2-5.6) to 2.2 (0.6-2.9) in survivors. Serum PCT change compared better than the APACHE II score change among survivors ( r = 0.455, p = 0.011) with a mean (±standard deviation SD) change of 1.41 (±1.59)., Conclusion: The change in serum PCT and APACHE II between admission and 48 hours correlates well and is useful for mortality prediction in AP. Serum PCT change compares better than APACHE II score change in survivors., How to Cite This Article: Choudhuri AH, Duggal S, Biswas PS, Uppal R. A Comparison of Acute Physiology and Chronic Health Evaluation II Score and Serum Procalcitonin Change for Predicting Mortality in Acute Pancreatitis. Indian J Crit Care Med 2020;24(3):190-194., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2020; Jaypee Brothers Medical Publishers (P) Ltd.)

Fibrosis affects all vital organs accounting for a staggering 45% of deaths worldwide and no effective therapies are currently available. Unresolved inflammation triggers downstream signaling events that lead to organ fibrosis. In recent years, proinflammatory cytokine Interleukin-17 (IL-17) has been implicated in several chronic inflammatory diseases that often culminate in organ damage followed by impaired wound healing and fibrosis. In this review, we outline the contribution of the IL-17 in mediating fibrotic diseases in various organs. A comprehensive understanding of the inflammatory events, and particularly the details of IL-17 signaling in vivo, could be beneficial in designing new therapeutic or preventive approaches to treat fibrosis. Additionally, understanding organ-specific differences in IL-17 activity could lead to targeted therapies and help spare other organs from unwanted side effects., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Lymph-node (LN) stromal cell populations expand during the inflammation that accompanies T cell activation. Interleukin-17 (IL-17)-producing helper T cells (T H 17 cells) promote inflammation through the induction of cytokines and chemokines in peripheral tissues. We demonstrate a critical requirement for IL-17 in the proliferation of LN and splenic stromal cells, particularly fibroblastic reticular cells (FRCs), during experimental autoimmune encephalomyelitis and colitis. Without signaling via the IL-17 receptor, activated FRCs underwent cell cycle arrest and apoptosis, accompanied by signs of nutrient stress in vivo. IL-17 signaling in FRCs was not required for the development of T H 17 cells, but failed FRC proliferation impaired germinal center formation and antigen-specific antibody production. Induction of the transcriptional co-activator IκBζ via IL-17 signaling mediated increased glucose uptake and expression of the gene Cpt1a, encoding CPT1A, a rate-limiting enzyme of mitochondrial fatty acid oxidation. Hence, IL-17 produced by locally differentiating T H 17 cells is an important driver of the activation of inflamed LN stromal cells, through metabolic reprogramming required to support proliferation and survival.

Key Message: New models for integration of major gene MAS with modern breeding approaches stand to greatly enhance the reliability and efficiency of breeding, facilitating the leveraging of traditional genetic diversity. Genetic diversity is well recognised as contributing essential variation to crop breeding processes, and marker-assisted selection is cited as the primary tool to bring this diversity into breeding programs without the associated genetic drag from otherwise poor-quality genomes of donor varieties. However, implementation of marker-assisted selection techniques remains a challenge in many breeding programs worldwide. Many factors contribute to this lack of adoption, such as uncertainty in how to integrate MAS with traditional breeding processes, lack of confidence in MAS as a tool, and the expense of the process. However, developments in genomics tools, locus validation techniques, and new models for how to utilise QTLs in breeding programs stand to address these issues. Marker-assisted forward breeding needs to be enabled through the identification of robust QTLs, the design of reliable marker systems to select for these QTLs, and the delivery of these QTLs into elite genomic backgrounds to enable their use without associated genetic drag. To enhance the adoption and effectiveness of MAS, rice is used as an example of how to integrate new developments and processes into a coherent, efficient strategy for utilising genetic variation. When processes are instituted to address these issues, new genes can be rolled out into a breeding program rapidly and completely with a minimum of expense.

Key Message: The integration of new technologies into public plant breeding programs can make a powerful step change in agricultural productivity when aligned with principles of quantitative and Mendelian genetics. The breeder's equation is the foundational application of quantitative genetics to crop improvement. Guided by the variables that describe response to selection, emerging breeding technologies can make a powerful step change in the effectiveness of public breeding programs. The most promising innovations for increasing the rate of genetic gain without greatly increasing program size appear to be related to reducing breeding cycle time, which is likely to require the implementation of parent selection on non-inbred progeny, rapid generation advance, and genomic selection. These are complex processes and will require breeding organizations to adopt a culture of continuous optimization and improvement. To enable this, research managers will need to consider and proactively manage the, accountability, strategy, and resource allocations of breeding teams. This must be combined with thoughtful management of elite genetic variation and a clear separation between the parental selection process and product development and advancement process. With an abundance of new technologies available, breeding teams need to evaluate carefully the impact of any new technology on selection intensity, selection accuracy, and breeding cycle length relative to its cost of deployment. Finally breeding data management systems need to be well designed to support selection decisions and novel approaches to accelerate breeding cycles need to be routinely evaluated and deployed.

Background and Aims: The patients in the intensive care unit (ICU) are often infected with multidrug resistant (MDR) organisms. When they are transferred to other ICUs, they can expand the reservoir of MDR organisms and pose a threat to the infection control program. The present observational study was undertaken to describe the epidemiology and compare the outcome of MDR and non-MDR infections after inter ICU patient transfer., Materials and Methods: A retrospective study was conducted in a cohort of 134 consecutive admitted patients in a tertiary care ICU from other ICUs. The primary objective was to measure the prevalence of MDR and non-MDR infections. The secondary objective was to compare the outcome between MDR and non-MDR group and identify the factors independently associated with mortality for each group., Results: Among 134 patients, 89 had infections (66.4%) and in 29 (21.6%) were due to MDR organisms. The most common organism was Klebsiella in the MDR and E. coli in the non-MDR group. There was no difference between the groups in mortality, duration of mechanical ventilation and length of ICU stay. The duration of mechanical ventilation and ICU stay >7 days was independently associated with mortality in the MDR group. No association was found in the non-MDR group., Conclusion: The study demonstrates a high prevalence of MDR infections after inter ICU transfer. There is no difference in outcome between the groups, but the mortality in the MDR group is independently associated with a longer duration of mechanical ventilation and ICU stay., How to Cite This Article: Choudhuri AH, Ahuja B, Biswas PS, Uppal R. Epidemiology of Multidrug Resistant Infections after Inter-ICU Transfer in India. Indian Journal of Critical Care Medicine, January 2019;23(1):1-6., Competing Interests: Source of support: Nil Conflict of interest: None

The kidney is an organ particularly susceptible to damage caused by infections and autoimmune conditions. Renal inflammation confers protection against microbial infections. However, if unchecked, unresolved inflammation may lead to kidney damage. Although proinflammatory cytokine IL-17 is required for immunity against extracellular pathogens, dysregulated IL-17 response is also linked to autoimmunity. In this review, we will discuss the current knowledge of IL-17 activity in the kidney in context to renal immunity and autoimmunity and raise the intriguing question to what extent neutralization of IL-17 is beneficial or harmful to renal inflammation., (Copyright © 2018 by The American Association of Immunologists, Inc.)

Chronic inflammation has an important role in the development and progression of most fibrotic diseases, for which no effective treatments exist. Tubulointerstitial fibrosis (TF) is characterized by irreversible deposition of fibrous tissue in chronic kidney diseases. Prolonged injurious stimuli and chronic inflammation regulate downstream events that lead to TF. In recent years, interleukin-17 (IL-17) has been strongly linked to organ fibrosis. However, the role of IL-17 receptor signaling in TF is an active area of debate. Using the unilateral ureteral obstruction (UUO) mouse model of TF, we show that IL-17 receptor A-deficient mice ( Il17ra -/- ) exhibit increased TF in the obstructed kidney. Consequently, overexpression of IL-17 restored protection in mice with UUO. Reduced renal expression of matrix-degrading enzymes results in failure to degrade ECM proteins, thus contributing to the exaggerated TF phenotype in Il17ra -/- mice. We demonstrate that the antifibrotic kallikrein-kinin system (KKS) is activated in the obstructed kidney in an IL-17-dependent manner. Accordingly, Il17ra -/- mice receiving bradykinin, the major end-product of KKS activation, prevents TF development by upregulating the expression of matrix-degrading enzymes. Finally, we show that treatment with specific agonists for bradykinin receptor 1 or 2 confers renal protection against TF. Overall, our results highlight an intriguing link between IL-17 and activation of KKS in protection against TF, the common final outcome of chronic kidney conditions leading to devastating end-stage renal diseases.

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., Competing Interests: There are no conflicts of interest.

Kidney injury is a frequent outcome in patients with disseminated Candida albicans fungal infections. IL-17 receptor (IL-17R) signaling is critical for renal protection against disseminated candidiasis, but the identity and function of IL-17-responsive cells in mediating renal defense remains an active area of debate. Using BM chimeras, we found that IL-17R signaling is required only in nonhematopoietic cells for immunity to systemic C. albicans infection. Since renal tubular epithelial cells (RTEC) are highly responsive to IL-17 in vitro, we hypothesized that RTEC might be the dominant target of IL-17 activity in the infected kidney. We generated mice with a conditional deletion of IL-17 receptor A (Il17ra) in RTEC (Il17raΔRTEC). Strikingly, Il17raΔRTEC mice showed enhanced kidney damage and early mortality following systemic infection, very similar to Il17ra-/- animals. Increased susceptibility to candidiasis in Il17raΔRTEC mice was associated with diminished activation of the renal protective Kallikrein-kinin system (KKS), resulting in reduced apoptosis of kidney-resident cells during hyphal invasion. Moreover, protection was restored by treatment with bradykinin, the major end-product of KKS activation, which was mediated dominantly via bradykinin receptor b1. These data show that IL-17R signaling in RTEC is necessary and likely sufficient for IL-17-mediated renal defense against fatal systemic C. albicans infection.

Yellowing, stunting, and seedling death associated with cold stress is a common problem in many Asian countries for winter rice cultivation. Improvement of cultivars through marker-assisted selection of QTLs for cold tolerance at seedling stage from locally adapted germplasm/cultivar is the most effective and sustainable strategy to resolve this problem. A study was undertaken to map QTLs from 151 F 2:3 progenies of a cross between a cold susceptible variety, BR1 and a locally adapted traditional indica cultivar, Hbj.BVI. A total of six significant QTLs were identified for two cold tolerance indices-cold-induced leaf discoloration and survival rate after a recovery period of seven days on chromosomes 6, 8, 11, and 12. Among these QTLs, qCTSL - 8 - 1 and qCTSS - 8 - 1 being co-localized into RM7027-RM339 on chromosome 8 and qCTSL - 12 - 1 and qCTSS - 12 - 1 into RM247-RM2529 on chromosome 12 showed 12.78 and 14.96% contribution, respectively, to the total phenotypic variation for cold tolerance. Validation of QTL effect in BC 1 F 3 population derived a cross between a cold susceptible BRRI dhan28 and Hbj.BVI showed dominating effect of qCTSL - 12 - 1 on cold tolerance at seedling stage and it became stronger when one or more other QTLs were co-segregated with it. These results suggest that the QTLs identified in this study are stable and effective on other genetic background also, which warrant the use of these QTLs for further study aiming to cultivar development for seedling stage cold tolerance.

Candida albicans is a dimorphic commensal fungus that causes severe oral infections in immunodeficient patients. Invasion of C. albicans hyphae into oral epithelium is an essential virulence trait. Interleukin-17 (IL-17) signaling is required for both innate and adaptive immunity to C. albicans During the innate response, IL-17 is produced by γδ T cells and a poorly understood population of innate-acting CD4 + αβ T cell receptor (TCRαβ) + cells, but only the TCRαβ + cells expand during acute infection. Confirming the innate nature of these cells, the TCR was not detectably activated during the primary response, as evidenced by Nur77 eGFP mice that report antigen-specific signaling through the TCR. Rather, the expansion of innate TCRαβ + cells was driven by both intrinsic and extrinsic IL-1R signaling. Unexpectedly, there was no requirement for CCR6/CCL20-dependent recruitment or prototypical fungal pattern recognition receptors. However, C. albicans mutants that cannot switch from yeast to hyphae showed impaired TCRαβ + cell proliferation and Il17a expression. This prompted us to assess the role of candidalysin, a hyphal-associated peptide that damages oral epithelial cells and triggers production of inflammatory cytokines including IL-1. Candidalysin-deficient strains failed to up-regulate Il17a or drive the proliferation of innate TCRαβ + cells. Moreover, candidalysin signaled synergistically with IL-17, which further augmented the expression of IL-1α/β and other cytokines. Thus, IL-17 and C. albicans , via secreted candidalysin, amplify inflammation in a self-reinforcing feed-forward loop. These findings challenge the paradigm that hyphal formation per se is required for the oral innate response and demonstrate that establishment of IL-1- and IL-17-dependent innate immunity is induced by tissue-damaging hyphae., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)