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Despite the availability of multiple therapies for chronic kidney disease (CKD), there still exists an unmet need for better options to slow down disease progression and prevent complications. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial, which demonstrated the renoprotective effects of the sodium-glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin, independent of diabetes, with improved survival, even in patients with CKD with estimated glomerular filtration rate (eGFR) as low as 25 mL/min/1.73 m2 , has highlighted the potential beneficial role of SGLT2i in patients with CKD. These benefits were also achieved in patients who were already receiving optimal therapies for slowing the progression of CKD. The potential candidature of SGLT2i for CKD therapy is now being widely discussed in the nephrology community. Therefore, a consensus meeting was held in September 2020 with a group of expert nephrologists from India, to discuss the need to improve CKD management and assess the position of SGLT2i, based on compelling evidence from recent studies. This document summarizes the expert opinions and views on the position of SGLT2i in CKD management and aims to enhance the current understanding of the applicability of SGLT2i in patients with CKD. This will aid nephrologists and physicians across the country in decision-making on the management of patients with CKD using SGLT2i. Keywords: Chronic kidney disease, Dapagliflozin, Estimated glomerular filtration rate, SGLT2i inhibitors, Type 2 diabetes mellitus.

Food grains in India achieved an all-time high production (310.74 mt) during 2020-21. Varietal and seed replacement rates played an important role in achieving this milestone. A total of 1646 varieties of food crops comprising 1273 of cereals and 373 of pulses were released from 2011 to 2022. Of these 977 varieties consisting of cereals (667) and pulses (310) have been inducted into the seed chain during 2020-21. New breeding technonologies such as bio-fortification of food crops and marker-assisted breeding were applied to improve crop varieties with respect to specific desirable traits. A total of 65 bio-fortified varieties comprising rice (8), wheat (28), maize (14), pearl millet (9), finger millet (3), little millet (1) and lentil (2) have been released with improved levels of proteins, essential amino acids (lysine, tryptophan), vitamins (pro-vitamin A) and micro/macro-nutrients (zinc, iron, calcium). Marker-assisted breeding adopting foreground and background selections with targeted gene(s) utilizing molecular markers such as RFLPs, SSRs, CAPs, STS and INDEL resulted in to the development and release of 66 cultivars comprising rice (43), wheat (5), maize (10), pearl millet (2) and chickpea (6) with one/and or combination of traits such as tolerance to biotic/abiotic stresses, herbicide tolerance, nutrient use efficiency, earliness, nutritional and other quality traits. These non-genetically modified crop varieties are expected to play vital role in achieving food and nutrition security in India. The paper also provides insight in to the maintenance breeding of food crops. The analysis of seed requirement and availability during 2010-11 to 2020-21 revealed that seed requirements for cereals and pulses have increased consistently by 31.6% and 62.3%, from 186.8 to 245.8 lakh q and 22.3 to 36.2 lakh q, respectively. The production of rice, wheat, maize, pearl millet and pulses during 2020-21 increased over that of 2010-11 by 27.4%, 26.0%, 45.2%, 4.4% and 41.3%, respectively. The productivity of sorghum was higher by 18.9% over that of 2010-11 but production decreased by 31.7% on account of a reduction in acreage by 42.5% during the corresponding period. The net per capita availability of food grains increased, by 17.2% from 159.5 kg to 187.0 kg during this period. The cereals and pulses production needs to be up-scaled by 5.3% and 24.4% to meet the demand by 2030 from 285.28 mt and 25.46 mt, respectively, in 2020-21, with almost the similar acreage, degrading and depleting natural resources, thus, requiring a greater focus on enhancing yield/ha. Crop-specific breeding programmes should be accelerated with the adoption of new technologies like GM, gene editing, marker-assisted selection and speed breeding to address the challenges of climate change and degrading natural sources.

Aim: To systematically investigate the timing of encapsulation of necrotic collections in acute necrotizing pancreatitis (ANP) using contrast-enhanced computed tomography (CECT). Methods: This retrospective study comprised consecutive patients of ANP who underwent CECT of the abdomen between the second and fourth weeks of illness. Number and site of collections and presence and completeness of the wall (defined as a thin smooth enhancing rim more than 1 mm in thickness) were documented. Results: A total of 195 patients of ANP were included. Seven hundred seventy-three collections were evaluated in 284 CECT scans. The most common site of the collection was anterior pararenal space (n=290, 37.5%). The mean maximum dimension of the collection was 8.1 cm (range, 3.1-16 cm). Two hundred twentytwo (28.7%) collections had a complete wall. The mean interval to complete wall maturation was 18 days (range, 8-28). Overall, 13.3%, 37.1%, and 56.2% of the collections showed complete encapsulation in the second, third, and fourth weeks, respectively. Conclusions: Our study suggests that a significant proportion of necrotic collections show complete encapsulation within 4 weeks of the onset of ANP.

The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different basolateral amygdala (BLA) projections are potentiated following reward or punishment learning(1–7). However, we do not yet understand how valence specific information is routed to the BLA neurons with the appropriate downstream projections. Nor do we understand how to reconcile the subsecond timescales of synaptic plasticity(8–11) with the longer timescales separating the predictive cues from their outcomes. Here, we demonstrate that neurotensin (NT) neurons in the paraventricular nucleus of the thalamus (PVT) projecting to the BLA (PVT-BLA:NT) mediate valence assignment by exerting concentration-dependent modulation in BLA during associative learning. We found that optogenetic activation of the PVT-BLA:NT projection promotes reward learning, while PVT-BLA projection-specific Nt gene knockout augments punishment learning. Using genetically encoded calcium and NT sensors, we further revealed that both calcium dynamics within the PVT-BLA:NT projection and NT concentrations in the BLA are enhanced after reward learning and reduced after punishment learning. Finally, we showed that CRISPR-mediated knockout of the Nt gene in the PVT-BLA pathway blunts BLA neural dynamics and attenuates the preference to active behavioral strategies to reward and punishment predictive cues. Taken together, we have identified NT as a neuropeptide that signals valence in the BLA, and showed that NT is a critical neuromodulator that orchestrates positive and negative valence assignment in amygdala neurons by extending valence-specific plasticity to behaviorally-relevant timescales.

Fecal sludge management (FSM) stakeholders have hitherto been unable to benefit from analytical approaches based on systems thinking principles, as studies utilizing theoretical frameworks to analyze governance structures remain in a nascent stage. One such prominent framework is the Systems Theoretic Process Analysis (STPA), which has no FSM-related applications in the literature. Relying on official documents such as ministerial ordinances, this study conducts a multistage STPA for a well-established and sustainable FSM system, that is, the Johkasou system in Japan. The analysis maps the key stakeholders and their interactions to comprehensively identify potential risks and corresponding novel indicators to help manage risks within the Johkasou system. The features of governance structure thus obtained also highlight the steps necessary to address governance issues for Japan and other countries attempting to establish sustainable FSM. The study extends the STPA literature by providing a substantial validity of STPA’s capability for analyzing the FSM governance structure against robust and independent criteria that define the objectives of a “good” governance structure, that is, efficiency, accountability, and legitimacy. The STPA results identify novel leading indicators to guide Japanese policymakers to improve FSM management. The results from STPA also effectively provide valuable insights for other countries by highlighting the various features contributing to an effective governance structure of the Johkasou, such as centralized decision-making in a combination of a hierarchy of goals to establish a clear division of responsibility across various actors. The study also notes potential challenges for field implementation of STPA and discusses directions that future work could explore.

Herein, we report a Pd(0)-catalyzed cascade reaction with multifunction of isocyanide as a nucleophile promoter for rearrangement and a hydride source.

Paracetamol is a popular and safe drug preferred by victims of pain or pyrexia; however, its overdose or abuse is a growing concern worldwide. Here the hepatoprotective effect of an ethnomedicinal plant Drynaria quercifolia against paracetamol‑induced toxicity in murine model is demonstrated. This fern, native to tropical countries including the Northeast India, is used by local tribes to treat inflammatory conditions. Paracetamol 500 mg/kg body weight was orally administered on alternate days for a period of 21days to mimic a chronic overdose. Drynaria quercifolia acetone extract (DQA) treatment interspaced with paracetamol significantly decreased serum biomarkers of hepatotoxicity (ALT, AST and ALP) renal toxicity (urea, creatinine), lipid peroxidation level, histological damage in liver and kidney. The protein and mRNA expressions of the transcription factor, Nrf2, and its target antioxidant genes (SOD1, CAT and GST) as well as activities of these antioxidant enzymes were downregulated by paracetamol administration but significantly recovered following the DQA treatment (Tab. 3, Fig. 5, Ref. 31). Keywords: acetaminophen/paracetamol, Drynaria quercifolia, renal toxicity, hepatotoxicity, Nrf-2.