The nuclear effector ArPEC25 from the necrotrophic fungus Ascochyta rabiei targets the chickpea transcription factor CaßLIM1a and negatively modulates lignin biosynthesis, increasing host susceptibility.

Fungal pathogens deploy a barrage of secreted effectors to subvert host immunity, often by evading, disrupting, or altering key components of transcription, defense signaling, and metabolic pathways. However, the underlying mechanisms of effectors and their host targets are largely unexplored in necrotrophic fungal pathogens. Here, we describe the effector protein Ascochyta rabiei PEXEL-like Effector Candidate 25 (ArPEC25), which is secreted by the necrotroph A. rabiei, the causal agent of Ascochyta blight disease in chickpea (Cicer arietinum), and is indispensable for virulence. After entering host cells, ArPEC25 localizes to the nucleus and targets the host LIM transcription factor CaßLIM1a. CaßLIM1a is a transcriptional regulator of CaPAL1, which encodes phenylalanine ammonia lyase (PAL), the regulatory, gatekeeping enzyme of the phenylpropanoid pathway. ArPEC25 inhibits the transactivation of CaßLIM1a by interfering with its DNA-binding ability, resulting in negative regulation of the phenylpropanoid pathway and decreased levels of intermediates of lignin biosynthesis, thereby suppressing lignin production. Our findings illustrate the role of fungal effectors in enhancing virulence by targeting a key defense pathway that leads to the biosynthesis of various secondary metabolites and antifungal compounds. This study provides a template for the study of less explored necrotrophic effectors and their host target functions.

Endoscopic Ultrasound-Guided vs Endoscopic Retrograde Cholangiopancreatography-Guided Biliary Drainage as Primary Approach to Malignant Distal Biliary Obstruction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Endoscopic ultrasound-guided biliary drainage (EUS-BD) is an alternative to endoscopic retrograde cholangiopancreatography (ERCP)-guided transpapillary drainage in malignant distal biliary obstruction (MDBO). This meta-analysis of randomized controlled trials (RCTs) aims to compare the outcomes of these 2 approaches. METHODS: Electronic databases from January 2005 through December 2023 were searched for RCTs comparing outcomes of EUS-BD and ERCP for treating MDBO. Pooled proportions, risk ratio (RR), and odds ratio were calculated using random-effects models. RESULTS: Five RCTs comprising 519 patients were included in the final analysis. The pooled RR for overall technical success with EUS-BD compared with ERCP was 1.05 (95% confidence interval [CI] = 0.96-1.16, P = 0.246, I2 = 61%) and for clinical success was 0.99 (95% CI = 0.95-1.04, P = 0.850, I2 = 0%). The pooled rate of procedure-related pancreatitis was 7.20% (95% CI = 3.60-13.80, I2 = 34%) in the ERCP group compared with zero in the EUS-BD group. The pooled RR for stent dysfunction with EUS-BD compared with ERCP was 0.48 (95% CI = 0.28-0.83, P = 0.008, I2 = 7%). The weighted mean procedure time was 13.43 (SD = 10.12) minutes for EUS-BD compared with 21.06 (SD = 6.64) minutes for ERCP. The mean stent patency was 194.11 (SD = 52.12) days in the EUS-BD group and 187 (SD = 60.70) days in the ERCP group. DISCUSSION: EUS-BD is an efficient and safe alternative to ERCP in MDBO. An almost nonexistent risk of procedure-related pancreatitis, lower procedure time, and ease of use make this an attractive primary approach to biliary decompression in centers with expertise.

Do Patients With NASH-related Cirrhosis Have Better Overall Survival Compared With Other Etiologies of Cirrhosis? A Population-based Study.

GOALS AND BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. We aim to explore the clinical outcomes of NASH cirrhosis compared with other etiologies of cirrhosis. METHODS: We utilized an EHR-based database (TriNetX) to study the outcomes of NASH cirrhosis. Patients diagnosed with NAFLD or NASH and cirrhosis between January 2016 and December 2019 were identified utilizing appropriate ICD-10-CM codes. The primary outcome was 3-year overall survival. Secondary outcomes were decompensated cirrhosis, hepatocellular carcinoma, and liver transplantation. The Control group was patients with other etiologies of cirrhosis than NASH. Study and control groups were matched for demographic characters and comorbidities using propensity score matching. RESULTS: We identified 45,063 patients with NASH cirrhosis. The NASH cirrhosis cohort comprised older (61 vs. 59 y) White (78% vs. 64%) women (58% vs. 38%) with more comorbidities (diabetes mellitus, obesity, ischemic heart disease, history of cancer, chronic kidney disease). After propensity score matching, patients with NASH cirrhosis had a better 3-year survival (78% vs. 74%, HR 0.79, 95% CI 0.77-0.82) compared with patients with non-NASH cirrhosis. Hepatocellular carcinoma was diagnosed less commonly in patients with NASH cirrhosis (6.7% vs. 10.6%, P<0.001), and liver transplantation was performed more often for NASH cirrhosis compared with non-NASH cirrhosis [Risk ratio 1.13 (1.08-1.18)]. CONCLUSIONS: Patients with NASH cirrhosis probably have better 3-year overall survival than other etiologies of cirrhosis. This is an interesting finding, as patients with NASH are older and have more comorbidities. Improved survival can be partly explained by a higher probability of liver transplantation and improvements in cardiovascular outcomes.

Fabrication of novel glutathione-Fe3O4-loaded/activated carbon encapsulated sand bionanocomposites for enhanced removal of Diethyl phthalate from aqueous environment in a vertical flow reactor.

The extensive use of plasticizers in various industries has made Diethyl phthalate (DEP), a serious threat to the environment and ecological water security, owing to its complex-structure and low-biodegradability. Thus, the present study aimed to design a sustainable sand-coated nano glutathione (GSH) -Fe3O4-loaded/activated carbon (AC) bionanocomposite (AC-GSH-Fe3O4@sand bionanocomposite) for effective removal of DEP from water. Characterization results suggested bionanocomposites' rough and irregular texture due to the uneven distribution of AC and Fe3O4 nanoparticles over the sand. The XRD spectra indicated high crystallinity of bionanocomposites, while the FTIR spectra confirmed the presence of all individual components, i.e., GSH, AC, Fe3O4, and sand. EDX-mapping, AFM, and TGA further verified its elemental composition, topographical changes and thermal stability. The influence of pH (3, 7, 9), bed height (2, 4, 6) cm, and flow rate (2.5, 3.5, 4.5) mL min-1 were studied in a dynamic system with an initial DEP concentration of 50 mg L-1 to investigate the removal behavior of the bionanocomposites. The best DEP removal efficiency (90.18 %) was achieved over 28-hours at pH 9, bed-height-4 cm, and flow-rate-3.5 mL min-1, with an optimum qmax-200.25 mg g-1 as determined through Thomas-model. Breakthrough curves were predicted using various column models, and the corresponding parameters essential for column-reactor process design were calculated. The high reusability up to the 10th cycle (≥ 83.32%) and the effective treatment in complex matrices (tap-water: 90.11 %, river-water: 89.72 %, wastewater: 83.83%) demonstrated bionanocomposites' prominent sustainability. Additionally, the production cost at 6.64 USD per Kg, underscores its potentiality for industrial application. Phytotoxicity assessment on mung-bean revealed better root (5.02 ± 0.27) cm and shoot (17.64 ± 0.35) cm growth in the bionanocomposite-treated DEP samples over the untreated samples. Thus, AC-GSH-Fe3O4@sand bionanocomposites could be considered a highly-sustainable, low-cost technique for the effective removal of DEP and other phthalate-esters from contaminated matrices.

Chitosan anchored nZVI bionanocomposites for treatment of textile wastewater: Optimization, mechanism, and phytotoxic assessment.

In recent years, there has been a growing focus on treating textile wastewater due to its escalating threat to aquatic ecosystems and exposed communities. The present study investigates the adsorption efficacy of biopolymer functionalized nanoscale zero-valent iron (CS@nZVI) composite for the treatment of textile wastewater using the RSM-CCD model. The structure and morphology of CS@nZVI were characterized using XRD, FTIR, FESEM, and EDX. CS@nZVI was then evaluated for its adsorption potential in removing COD, color, and other physico-chemical parameters from textile wastewater. The results showed the high efficacy of CS@nZVI for COD and color removal from textile wastewater. Under optimal conditions (pH 6, contact time 60 min, and 1.84 g CS@nZVI), COD removal reached a maximum of 85.53%, and decolorization efficiency was found to be 89.73%. The coefficient of determination R2 (0.98) and AIC (269.75) values suggested quadratic model as the best-fitted model for optimizing the process parameters for COD removal. Additionally, the physico-chemical parameters were found to be within permissible limits after treatment with CS@nZVI. The influence of coexisting ions on COD removal followed the order PO43- > SO42- > Cl- >Na+ > Ca2+. The kinetics data fitted well with the pseudo-first-order reaction, indicating physisorption as the primary mechanism. The thermodynamic study revealed the endothermic nature of the removal process. Reusability tests demonstrated that great regeneration capacity of spent CS@nZVIafter five consecutive cycles. Furthermore, toxicological studies showed reduced toxicity in treated samples, leading to improved growth of Vigna radiata L. These findings suggest that CS@nZVI bionanocomposites could serve as an efficient, cost-effective, and eco-friendly remediation agent for the treatment of textile effluents, presenting significant prospects for commercial applications.

Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study.

Background: Traumatic brain injury (TBI) is a major cause of mortality among young individuals, accounting for 65% of deaths in road traffic accidents. Paroxysmal sympathetic hyperactivity (PSH) is a common syndrome associated with TBI. This study represents the first prospective investigation aimed at assessing the impact of gabapentin on TBI patients, focusing on the prevention of secondary brain injury and brain edema while enhancing the Glasgow Coma Scale (GCS). Materials and methods: The study was conducted from September 2019 to July 2021 after receiving ethical committee approval. It included adult ICU patients (≥18 years) with moderate and severe GCS. Patients below 18 years, death within 48 hours, non-consenting, pregnant females, and individuals allergic to gabapentin were excluded from the study. Patients were randomly allocated in two groups: study group received 300 mg of gabapentin orally twice daily and control group received multivitamin tablets twice daily. The treatment period spanned 2 weeks. Follow-up occurred in the ICU and continued for up to 3 months post-discharge, including telephonic conversations. Results: About 60 patients were involved for analysis. Significant differences were found in GCS change from admission to discharge, Glasgow Outcome Scale (GOS) at 30 and 90 days, PSH episodes, and sedation bolus per day. Glasgow Coma Scale change was 53% in the study group compared with 25% in the control group (p = 0.009). Mortality was significantly lower in the study group. Glasgow Outcome Scale change between 30 and 90 days showed a 25% improvement in cases and no change in controls (p = 0.001). Conclusion: This pioneering study underscores the potential of gabapentin in managing traumatic brain injuries. How to cite this article: Singh R, Ambasta S, Bais PS, Azim A, Kumar S, Upreti B, et al. Role of Gabapentin in Traumatic Brain Injury: A Prospective Comparative Study. Indian J Crit Care Med 2024;28(2):120-125.

Plant BBR/BPC transcription factors: unlocking multilayered regulation in development, stress and immunity.

MAIN CONCLUSION: This review provides a detailed structural and functional understanding of BBR/BPC TF, their conservation across the plant lineage, and their comparative study with animal GAFs. Plant-specific Barley B Recombinant/Basic PentaCysteine (BBR/BPC) transcription factor (TF) family binds to "GA" repeats similar to animal GAGA Factors (GAFs). These GAGA binding proteins are among the few TFs that regulate the genes at multiple steps by modulating the chromatin structure. The hallmark of the BBR/BPC TF family is the presence of a conserved C-terminal region with five cysteine residues. In this review, we present: first, the structural distinct yet functional similar relation of plant BBR/BPC TF with animal GAFs, second, the conservation of BBR/BPC across the plant lineage, third, their role in planta, fourth, their potential interacting partners and structural insights. We conclude that BBR/BPC TFs have multifaceted roles in plants. Besides the earliest identified function in homeotic gene regulation and developmental processes, presently BBR/BPC TFs were identified in hormone signaling, stress, circadian oscillation, and sex determination processes. Understanding how plants' development and stress processes are coordinated is central to divulging the growth-immunity trade-off regulation. The BBR/BPC TFs may hold keys to divulge the interactions between development and immunity. Moreover, the conservation of BBR/BPC across plant lineage makes it an evolutionary vital gene family. Consequently, BBR/BPCs are prospective to attract the increasing attention of the scientific communities as they are probably at the crossroads of diverse fundamental processes.

Real-world evidence of safety and effectiveness of Barrett's endoscopic therapy.

BACKGROUND AND AIMS: Real-world data on the adverse events and the survival benefit of Barrett's endoscopic therapy (BET) are limited. The aim of this study was to examine the safety and effectiveness (survival benefit) of BET in patients with neoplastic Barrett's esophagus (BE). METHODS: An electronic health record-based database (TriNetX) was used to select patients with BE with dysplasia and esophageal adenocarcinoma (EAC) from 2016 to 2020. Primary outcome was 3-year mortality among patients with high-grade dysplasia (HGD) or EAC who underwent BET versus 2 comparison cohorts: patients with HGD or EAC who had not undergone BET and patients with GERD but no BE/EAC. Secondary outcome was adverse events (esophageal perforation, upper GI bleeding, chest pain, and esophageal stricture) after BET. To control for confounding variables, 1:1 propensity score matching was performed. RESULTS: We identified 27,556 patients with BE and dysplasia, of whom 5295 underwent BET. After propensity score matching, patients with HGD and EAC who underwent BET had significantly lower 3-year mortality (HGD risk ratio [RR], .59; 95% CI, .49-.71; EAC RR, .53; 95% CI, .44-.65) compared with corresponding cohorts who did not undergo BET (P < .001). There was no difference in median 3-year mortality between control subjects (GERD without BE/EAC) compared with patients with HGD (RR, 1.04; 95% CI, .84-1.27) who underwent BET. Finally, there was no difference in median 3-year mortality between patients who underwent BET compared with patients who underwent esophagectomy among both HGD (RR, .67; 95% CI, .39-1.14; P =.14) and EAC (RR, .73; 95% CI, .47-1.13; P = .14). Esophageal stricture was the most common adverse event (6.5%) after BET. CONCLUSIONS: Real-world, population-based evidence from this large database shows that endoscopic therapy is safe and effective for patients with BE. Endoscopic therapy is associated with a significantly lower 3-year mortality; however, it leads to esophageal strictures in 6.5% of treated patients.

Cardiovascular and Renal Outcomes With Sodium-Glucose Cotransporter-2 Inhibitors and Dipeptidyl Peptidase-4 Inhibitors Combination Therapy: A Meta-Analysis of Randomized Cardiovascular Outcome Trials.

OBJECTIVE: The cardiovascular (CV) and renal benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in people with type 2 diabetes are well known. However, similar beneficial effects of SGLT2i in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) are unknown. It is of interest to explore a trial-level meta-analysis to fill this knowledge gap. METHODS: A literature search was conducted in the PubMed and Embase databases until January 31, 2023. All CV outcome trials (CVOTs) reporting the CV and renal outcomes of SGLT2i with or without background DPP4i therapy against the placebo were retrieved. A meta-analysis was subsequently conducted by applying the inverse variance-weighted averages of pooled logarithmic hazard ratio using primarily random-effects analysis. RESULTS: This meta-analysis showed that the beneficial 3-point major adverse cardiovascular events composite (3 CVOTs; N = 32 418), the composite of CV death or heart failure hospitalization (hHF) (4 CVOTs; N = 37 687), hHF (3 CVOTs; N = 27 545), CV death (4 CVOTs; N = 34 565), and renal outcomes (2 CVOTs; N = 25 406) with SGLT2i were similar with or without background DPP4i therapy against the placebo (Pheterogeneity = .71, .07, .87, .72, and .25; respectively). However, against the placebo, the summary estimates for the 3-point major adverse cardiovascular events composite, hHF, and renal outcomes were stronger with SGLT2i alone, whereas the summary estimates for CV death or hHF composite were larger with SGLT2i with background DPP4i therapy. CONCLUSION: Beneficial CV and renal effects of SGLT2i are similar against the placebo regardless of background DPP4i therapy.

Incidence and risk factors for recurrence of ampullary adenomas after endoscopic papillectomy: Comparative analysis of familial adenomatous polyposis and sporadic ampullary adenomas in an international multicenter cohort.

OBJECTIVES: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA. METHODS: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease. RESULTS: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence. CONCLUSION: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients.

A Non-Instrumental Green Analytical Method Based on Surfactant-Assisted Dispersive Liquid-Liquid Microextraction-Thin-Layer Chromatography-Smartphone-Based Digital Image Colorimetry(SA-DLLME-TLC-SDIC) for Determining Favipiravir in Biological Samples.

Favipiravir (FAV) has become a promising antiviral agent for the treatment of COVID-19. Herein, a green, fast, high-sample-throughput, non-instrumental, and affordable analytical method is proposed based on surfactant-assisted dispersive liquid-liquid microextraction (SA-DLLME) combined with thin-layer chromatography-digital image colourimetry (TLC-DIC) for determining favipiravir in biological and pharmaceutical samples. Triton X-100 and dichloromethane (DCM) were used as the disperser and extraction solvents, respectively. The extract obtained after DLLME procedure was spotted on a TLC plate and allowed to develop with a mobile phase of chloroform:methanol (8:2, v/v). The developed plate was photographed using a smartphone under UV irradiation at 254 nm. The quantification of FAV was performed by analysing the digital images' spots with open-source ImageJ software. Multivariate optimisation using Plackett-Burman design (PBD) and central composite design (CCD) was performed for the screening and optimisation of significant factors. Under the optimised conditions, the method was found to be linear, ranging from 5 to 100 µg/spot, with a correlation coefficient (R2) ranging from 0.991 to 0.994. The limit of detection (LOD) and limit of quantification (LOQ) were in the ranges of 1.2-1.5 µg/spot and 3.96-4.29 µg/spot, respectively. The developed approach was successfully applied for the determination of FAV in biological (i.e., human urine and plasma) and pharmaceutical samples. The results obtained using the proposed methodology were compared to those obtained using HPLC-UV analysis and found to be in close agreement with one another. Additionally, the green character of the developed method with previously reported protocols was evaluated using the ComplexGAPI, AGREE, and Eco-Scale greenness assessment tools. The proposed method is green in nature and does not require any sophisticated high-end analytical instruments, and it can therefore be routinely applied for the analysis of FAV in various resource-limited laboratories during the COVID-19 pandemic.

Collaborative Research in Critical Care Medicine: A Way Forward to High-impact Publications from India.

How to cite this article: Ravisankar NP, Singh R, Gurjar M. Collaborative Research in Critical Care Medicine: A Way Forward to High-impact Publications from India. Indian J Crit Care Med 2023;27(12):869-870.

Monitoring the Reversibility of GPCR Signaling by Combining Photochromic Ligands with Label-free Impedance Analysis.

G protein-coupled cell surface receptors (GPCR) trigger complex intracellular signaling cascades upon agonist binding. Classic pharmacological assays provide information about binding affinities, activation or blockade at different stages of the signaling cascade, but real time dynamics and reversibility of these processes remain often disguised. We show that combining photochromic NPY receptor ligands, which can be toggled in their receptor activation ability by irradiation with light of different wavelengths, with whole cell label-free impedance assays allows observing the cell response to receptor activation and its reversibility over time. The concept demonstrated on NPY receptors may be well applicable to many other GPCRs providing a deeper insight into the time course of intracellular signaling processes.

A Global Transcriptome and Co-expression Analysis Reveals Robust Host Defense Pathway Reprogramming and Identifies Key Regulators of Early Phases of Cicer-Ascochyta Interactions.

Ascochyta blight (AB) caused by the filamentous fungus Ascochyta rabiei is a major threat to global chickpea production. The mechanisms underlying chickpea response to A. rabiei remain elusive to date. Here, we investigated the comparative transcriptional dynamics of AB-resistant and -susceptible chickpea genotypes upon A. rabiei infection, to understand the early host defense response. Our findings revealed that AB-resistant plants underwent rapid and extensive transcriptional reprogramming compared with a susceptible host. At the early stage (24 h postinoculation [hpi]), mainly cell-wall remodeling and secondary metabolite pathways were highly activated, while differentially expressed genes related to signaling components, such as protein kinases, transcription factors, and hormonal pathways, show a remarkable upsurge at 72 hpi, especially in the resistant genotype. Notably, our data suggest an imperative role of jasmonic acid, ethylene, and abscisic acid signaling in providing immunity against A. rabiei. Furthermore, gene co-expression networks and modules corroborated the importance of cell-wall remodeling, signal transduction, and phytohormone pathways. Hub genes such as MYB14, PRE6, and MADS-SOC1 discovered in these modules might be the master regulators governing chickpea immunity. Overall, we not only provide novel insights for comprehensive understanding of immune signaling components mediating AB resistance and susceptibility at early Cicer-Ascochyta interactions but, also, offer a valuable resource for developing AB-resistant chickpea. [Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Design of imprinting matrix for dual template sensing via electropolymerized polythiophene films.

This work presents the design of 3-thiophene acetic acid (3-TAA) polymer matrix based molecularly imprinted polymer (MIP)/reduced graphene oxide (RGO) composite for sensitive and selective detection of antipyrine (AnP) and ethionamide (ETH) simultaneously. Dual drug embedded molecularly imprinted polymer (MIP) based electrochemical sensor was developed via electropolymerization of 3-TAA. AnP and ETH were embedded inside a polymer matrix based on their 3-D orientation and interaction(s) with functional monomer(s). Their extraction from polymeric matrix generates cavities complimentary to shape and size of AnP and ETH. The extraction of templates was confirmed by differential pulse voltammetry (DPV) as well as high-performance liquid chromatography (HPLC). The designed sensor selectively captures and produces the electrochemical signal for imprinted drugs. The electrochemical behaviour of AnP and ETH was investigated by DPV technique. The sensitivity for both drug molecules was commendable on a single polymeric composite with RGO on GC electrode (LOD of 0.117 µM for AnP and 0.15 µM for ETH). Also, the sensor exhibited excellent selectivity towards AnP and ETH in the presence of other analogous interferent molecules. Thus, the designed sensor showed high sensitivity as well as high selectivity for imprinted dual drug molecules on a single platform.

Broadening the horizon of crop research: a decade of advancements in plant molecular genetics to divulge phenotype governing genes.

MAIN CONCLUSION: Advancements in sequencing, genotyping, and computational technologies during the last decade (2011-2020) enabled new forward-genetic approaches, which subdue the impediments of precise gene mapping in varied crops. The modern crop improvement programs rely heavily on two major steps-trait-associated QTL/gene/marker's identification and molecular breeding. Thus, it is vital for basic and translational crop research to identify genomic regions that govern the phenotype of interest. Until the advent of next-generation sequencing, the forward-genetic techniques were laborious and time-consuming. Over the last 10 years, advancements in the area of genome assembly, genotyping, large-scale data analysis, and statistical algorithms have led faster identification of genomic variations regulating the complex agronomic traits and pathogen resistance. In this review, we describe the latest developments in genome sequencing and genotyping along with a comprehensive evaluation of the last 10-year headways in forward-genetic techniques that have shifted the focus of plant research from model plants to diverse crops. We have classified the available molecular genetic methods under bulk-segregant analysis-based (QTL-seq, GradedPool-Seq, QTG-Seq, Exome QTL-seq, and RapMap), target sequence enrichment-based (RenSeq, AgRenSeq, and TACCA), and mutation-based groups (MutMap, NIKS algorithm, MutRenSeq, MutChromSeq), alongside improvements in classical mapping and genome-wide association analyses. Newer methods for outcrossing, heterozygous, and polyploid plant genetics have also been discussed. The use of k-mers has enriched the nature of genetic variants which can be utilized to identify the phenotype-causing genes, independent of reference genomes. We envisage that the recent methods discussed herein will expand the repertoire of useful alleles and help in developing high-yielding and climate-resilient crops.

Does Hyperlipasemia Predict Worse Clinical Outcomes in COVID-19? A Multicenter Retrospective Cohort Study.

GOAL: We aim to perform a multicenter retrospective cohort study to determine if elevated serum lipase determines clinical outcomes in patients with coronavirus disease 2019 (COVID-19). BACKGROUND: Several cases of acute pancreatitis (AP) have recently been reported in association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Most of the evidence is based on elevated serum lipase values without objective demonstration of pancreatic inflammation or necrosis. MATERIALS AND METHODS: A population-based, multicenter, retrospective cohort study utilizing TriNetX was performed to obtain aggregated health records of ∼69 million patients from 49 health care organizations from January 1, 2020, to December 31, 2020. Adult patients (18 y and above) diagnosed with COVID-19 were identified using appropriate International Classification of Diseases, 10th Revision (ICD-10) codes and were stratified into 2 groups, with elevated (≥180 U/L) and with normal (≤80 U/L) serum lipase. The primary outcome was 30-day mortality; other outcomes were 30-day rehospitalization, need for mechanical ventilation, need for vasopressor use, acute kidney injury. RESULTS: A total of 435,731 adult patients with COVID-19 were identified, and 1406 of them had elevated serum lipase which was associated with higher 30-day mortality [risk ratio (RR)=1.53, P<0.001], risk of acute kidney injury (RR=1.5, P=0.003), and vasopressor use (RR=1.69, P<0.001) without any difference in 30-day rehospitalization (RR=0.98, P=0.54), or need for mechanical ventilation (RR=1.20, P=0.26). The negative predictive value of normal serum lipase for 3-month mortality in patients with COVID-19 was 91%. CONCLUSIONS: Patients with COVID-19 who have elevated serum lipase experience worse clinical outcomes even in the absence of AP. If these findings can be replicated in prospective studies, serum lipase can be utilized as a marker of disease severity in patients with COVID-19.

The outcomes of Clostridioides difficile infection in inpatient liver transplant population.

BACKGROUND: Chronic immunosuppression is a known cause of Clostridioides difficile, which presents with colon infection. It is associated with increased mortality and morbidity. Our aim is to determine the inpatient outcomes of liver transplant patients with Clostridioides difficile infection (CDI) and trends in the last few years. METHODS: We utilized the national re-admission data (2010-2017) to study the outcomes of CDI in liver transplant patients. Association of C. difficile with re-admission was computed in a multivariable model adjusted for age, sex, gastrointestinal bleeding, hypertension, diabetes, hyperlipidemia, congestive heart failure, cerebrovascular disease, obesity, cancer, insurance, chronic kidney disease, chronic obstructive pulmonary disease, dementia, peripheral vascular disease, smoking, hospital location, and teaching status. RESULTS: During 2010-2017, there were 310 222 liver transplant patients hospitalized. Out of these, 9826 had CDI. CDI infection in liver transplant patients was associated with higher 30-day re-admission (14.3% vs. 11.21%, hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.28, p = .02) and in-hospital mortality (odds ratio [OR]: 1.36, 95% CI: 1.14-1.61, p < .001). The most common causes of re-admission in the CDI group were recurrent CDI (41.1%), liver transplant complications (16.5%), and sepsis (11.6%). The median cost for liver transplant patients with C. difficile was significantly higher, $53 064 (IQR $24 970-$134 830) compared to patients that did not have C. difficile, $35 703 ($18 793-$73 871) (p < .001). The median length of stay was also longer for patients with CDI, 6 days (4-14) vs. 4 days (2-7) (p < .001). CONCLUSION: CDI in post-liver transplant patients was associated with higher mortality, re-admission, health care cost, and longer length of stay. The most common cause of re-admission was recurrent CDI, which raises the question of the efficacy of standard first-line therapy.

Association of Fasting Proinsulin Levels with Glycemic Profile in Indian Type 2 Diabetes Patients.

Type 2 diabetes mellitus is a major cause of cardiovascular disease and mortality, with mortality rate 27% higher in the diabetes cohort. Hyperproinsulinemia is a sign of beta cell dysfunction that is augmented by the increased demands placed on beta cell by chronic hyperglycemia. Hyperproinsulinaemia is the result of secretion of immature proinsulin-rich granules from beta cells, as a response to an increased demand for insulin i.e. an insulin resistant state According to previous studies intact proinsulin was a stronger predictor for type 2 diabetes than specific insulin. We plan to confirm this finding in the Indian demographic. MATERIAL: An observational cross-sectional study was carried out in LHMC with 150 subjects having type 2 diabetes aged between 35-80 years. The subjects taking insulin or any diabetogenic drugs; with history of chronic respiratory, cardiac or metabolic illness other than diabetes were excluded from the study. laboratory examination was conducted after drawing 10ml of venous blood and patients consent. 3 ml of the blood was stored after centrifugation at -20c for assay of fasting proinsulin level. Fasting blood glucose, HbA1c and lipid profile were analyzed. Co-relation between said parameters was established using spearman test of correlation and Wilcoxin-Mann-Whitney U test was used to make comparisons. OBSERVATION: Assessment of glycemic profile of the study population revealed half the subjects having FBS >150mg/dl (n=78, p= 52.0%). Mean HbA1c was 8.40 ± 2.26% with 61 subjects having a well-controlled HbA1c of <7.5%, 35 with 7.5-9.0 % and 54 with HbA1c >9.0%. Association of pro insulin with FBS and HbA1c was positive and strongly significant (rho=0.26 & p value= 0.001, rho=0.23& p value= 0.005 respectively). The mean values of proinsulin in normoglycemic and hyperglycemic subjects were 12.1ug/ml and 17.4 ug/ml respectively. Association of proinsulin with triglyceride levels was found to be positive and significant (rho= 0.22, p value= 0.008). The mean value of pro insulin in subjects with hypertriglyceridemia was 17.9ug/ml as compared to 12.7ug/ml in normal subjects. CONCLUSION: The results of the study demonstrated significant positive association between fasting proinsulin levels and glycemic indicators (p value FBS =0.001, HbA1c= 0.005, triglyceride =0.008). Proinsulin however has multiple associations with the diabetes pathophysiology which need to be studied further. Other studies have also demonstrated proinsulin to be an independent cardiovascular risk factor by stimulating plasminogen activator inhibitor-1 secretion and blocking fibrinolysis. Hence, proinsulin needs to be evaluated for use as a early marker for diabetes progression.

Depression and Anxiety among COVID-19 Indian Intensive Care Unit Survivors: A Prospective Observational Study.

Background: Long-lasting physical, cognitive, and mental health sequelae including depression and anxiety are common in intensive care unit (ICU) survivors. Aim: This study was aimed to assess the immediate and medium-term mental health sequelae-depression and anxiety among coronavirus disease-2019 (COVID-19) ICU survivors. Materials and methods: The COVID-19 ICU survivors of a tertiary level ICU were recruited into this study from 1 July 2020 to 31 October 2020. Willing participants were circulated with an electronic questionnaire. It consisted of demographics and questionnaires related to COVID-19 disease, comorbidities, and a patient health questionnaire (PHQ-9) scale for depression, and generalized anxiety disorder (GAD-7) scale for anxiety. Responses were collected at the time of discharge. Follow-up was done at 2 weeks and 6 months. Results: Among the 133 COVID-19 ICU survivors contacted, 91 survivors submitted the baseline data at the time of discharge. Fourteen and another 11 survivors were lost to follow-up at 2 weeks and at 6 months. The median age was 52.75 and 68.1% (n = 62/91) were male. The median PHQ-9 and GAD-7 scores showed a statistically significant decrease at 2 weeks and a non-significant decrease at 6 months compared to baseline scores. The GAD-7 score was the same or worse between baselines to 2 weeks, but it reduced between baseline to 6 months for all variables and their subgroups. Conclusion: This study revealed a high prevalence of anxiety and depression in the immediate post-discharge period. These findings suggest the need for better mental rehabilitation strategies to deal with the well-being of critically ill survivors in future pandemics. How to cite this article: Gunjiganvi M, Rai S, Awale RB, Mishra P, Gurjar M, Gupta D, et al. Depression and Anxiety among COVID-19 Indian Intensive Care Unit Survivors: A Prospective Observational Study. Indian J Crit Care Med 2022;26(12):1267-1274.