Nuclear pore complex acetylation regulates mRNA export and cell cycle commitment in budding yeast.

Nuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm, and regulate gene expression by interacting with transcription and mRNA export factors. Lysine acetyltransferases (KATs) promote transcription through acetylation of chromatin-associated proteins. We find that Esa1, the KAT subunit of the yeast NuA4 complex, also acetylates the nuclear pore basket component Nup60 to promote mRNA export. Acetylation of Nup60 recruits the mRNA export factor Sac3, the scaffolding subunit of the Transcription and Export 2 (TREX-2) complex, to the nuclear basket. The Esa1-mediated nuclear export of mRNAs in turn promotes entry into S phase, which is inhibited by the Hos3 deacetylase in G1 daughter cells to restrain their premature commitment to a new cell division cycle. This mechanism is not only limited to G1/S-expressed genes but also inhibits the expression of the nutrient-regulated GAL1 gene specifically in daughter cells. Overall, these results reveal how acetylation can contribute to the functional plasticity of NPCs in mother and daughter yeast cells. In addition, our work demonstrates dual gene expression regulation by the evolutionarily conserved NuA4 complex, at the level of transcription and at the stage of mRNA export by modifying the nucleoplasmic entrance to nuclear pores.

Identification and optimization of pyridine carboxamide-based scaffold as a drug lead for Mycobacterium tuberculosis.

New drugs with novel mechanisms of action are urgently needed to tackle the issue of drug-resistant tuberculosis. Here, we have performed phenotypic screening using the Pathogen Box library obtained from the Medicines for Malaria Venture against Mycobacterium tuberculosis in vitro. We have identified a pyridine carboxamide derivative, MMV687254, as a promising hit. This molecule is specifically active against M. tuberculosis and Mycobacterium bovis Bacillus Calmette-Guérin (M. bovis BCG) but inactive against Enterococcus faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Escherichia coli pathogens. We demonstrate that MMV687254 inhibits M. tuberculosis growth in liquid cultures in a bacteriostatic manner. Surprisingly, MMV687254 was as active as isoniazid in macrophages and inhibited M. tuberculosis growth in a bactericidal manner. Mechanistic studies revealed that MMV687254 is a prodrug and that its anti-mycobacterial activity requires AmiC-dependent hydrolysis. We further demonstrate that MMV687254 inhibits M. tuberculosis growth in macrophages by inducing autophagy. In the present study, we have also carried out a detailed structure-activity relationship study and identified a promising novel lead candidate. The identified novel series of compounds also showed activity against drug-resistant M. bovis BCG and M. tuberculosis clinical strains. Finally, we demonstrate that in contrast to MMV687254, the lead molecule was able to inhibit M. tuberculosis growth in a chronic mouse model of infection. Taken together, we have identified a novel lead molecule with a dual mechanism of action that can be further optimized to design more potent anti-tubercular agents.

WS2 Nanotube Transistor for Photodetection and Optoelectronic Memory Applications.

Nanotube and nanowire transistors hold great promises for future electronic and optoelectronic devices owing to their downscaling possibilities. In this work, a single multi-walled tungsten disulfide (WS2) nanotube is utilized as the channel of a back-gated field-effect transistor. The device exhibits a p-type behavior in ambient conditions, with a hole mobility µp ≈  1.4 cm2V-1s-1 and a subthreshold swing SS ≈ 10 V dec-1. Current-voltage characterization at different temperatures reveals that the device presents two slightly different asymmetric Schottky barriers at drain and source contacts. Self-powered photoconduction driven by the photovoltaic effect is demonstrated, and a photoresponsivity R ≈ 10 mAW-1 at 2 V drain bias and room temperature. Moreover, the transistor is tested for data storage applications. A two-state memory is reported, where positive and negative gate pulses drive the switching between two different current states, separated by a window of 130%. Finally, gate and light pulses are combined to demonstrate an optoelectronic memory with four well-separated states. The results herein presented are promising for data storage, Boolean logic, and neural network applications.

Turning up the heat on essential E. coli genes.

Temperature-sensitive (TS) alleles create tunable thermoswitches to deplete essential cellular activities and are used to dissect gene function. In their recent study, Link and colleagues (Schramm et al 2023) use a CRISPR-based approach to systematically create TS alleles across essential genes in E. coli.

Adjusting for subsequent therapies in the TOURMALINE-MM1 study shows clinically meaningful improvement in overall survival with addition of ixazomib to lenalidomide and dexamethasone.

TOURMALINE-MM1, the only blinded randomized study in patients with relapsed and/or refractory multiple myeloma (RRMM; ≥1 prior therapy) in the last 10 years, investigated ixazomib + lenalidomide + dexamethasone (IRd) versus lenalidomide + dexamethasone (Rd). Final overall survival (OS) data were based on a median follow-up of 85 months. In RRMM trials where patients have had 1-3 relapses after initial treatment, a high proportion receive subsequent therapy. Application of salvage therapies in blinded trials and newer modes of therapy can increasingly complicate the interpretation of OS. This analysis explores the impact of subsequent therapies on OS outcomes in TOURMALINE-MM1. The inverse probability of censoring weights (IPCW) method, marginal structural model (MSM), and rank-preserving structural failure time model (RPSFTM) were utilized to adjust for confounding on OS, introduced by subsequent therapies. Analyses were conducted for the intent-totreat (ITT) population and ≥2 prior lines subgroup. Unadjusted hazard ratio (HR) for IRd versus Rd was 0.94 (95% confidence interval [CI]: 0.78-1.13) in the ITT population. After adjusting for the impact of subsequent therapies by the RPSFTM method, estimated HR for IRd versus Rd in the ITT population was 0.89 (95% CI: 0.74-1.07). Adjusting with IPCW and MSM methods also showed an improvement in HR, favoring IRd. IRd may be particularly beneficial in patients with ≥2 prior lines of therapy (IPCW and MSM HR=0.52, 95% CI: 0.30-0.88; RPSFTM HR=0.68, 95% CI: 0.51-0.91). These analyses highlight the growing challenge of demonstrating OS benefit in MM patients and the importance of assessing confounding introduced by subsequent therapies when interpreting OS.

Molecular aspects of BRAF and HER2 in prognosis of periampullary carcinoma.

BACKGROUND: Biological behaviour of Periampullary cancers (PACS) differs from pancreatic head cancer, and analysis of molecular alteration is needed. BRAF and HER2 are keys members of the RAS/RAF and EGFR pathway, playing roles in prognostic markers and therapeutic targets. METHODS: A study on 89 PACS patients, undergoing Whipple Pancreaticoduodenectomy, PCR-RFLP, and qPCR methods used for SNP and mRNA expression studies. Clinicopathological and survival data collected. Molecular changes were correlated with Clinicopathological parameters. Survival outcomes were assessed by Kaplan Meir Log rank test. RESULTS: The study revealed that homozygous mutant BRAF V600E was significantly higher in PAC compared to a healthy control (p = 0.0012). Whereas the genotype frequency of HER2 I1655V was similar among PAC and healthy control. The A > G change in HER2 was associated with tumor arising from duodenum (p = 0.004) and showed poor survival outcome (p = 0.001). Upregulation of BRAF and HER2 was found in 43 % of patients with synergistic effect, the median overall survival (OS) being 50.5 ± 13 months. The increased expression of HER2 was higher in early stage (p = 0.04) PAC. The gene expression did not impact the OS, whereas female gender, G3 tumors, T3-T4 depth of tumour, advanced stage, LN metastasis, LVI and PNI were poor predictors of OS. CONCLUSIONS: BRAF V600E SNP was associated with disease susceptibility, and had increased mRNA expression while HER2 I1655V SNP was associated with poor survival outcome in PAC. The increased expression of BRAF and HER2 in early tumors and their co-expression in PAC exhibit cross talk between RAS/RAF and EGFR pathway in PAC.

Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.

Response to BH3 mimetics in multiple myeloma (MM) correlates with CCND1-rearrangement or expression of anti-apoptotic molecules, particularly Bcl-2 and Mcl-1. Our study investigates the relationship between cytogenetic abnormalities (CGAs) and intracellular Bcl-2 and Mcl-1 expression in myeloma plasma cells (MPCs) using flow cytometry (FCM). We measured median fluorescence intensity (MFI) of Bcl-2 and Mcl-1 in 163 bone marrow samples (143 MM, 20 controls) across various cell types. Both Bcl-2MFI and Mcl-1MFI were significantly higher in MPCs compared to other cells, with Bcl-2 MFI exceeding Mcl-1 MFI in MPCs. Bcl-2 expression peaked in CCND1-rearranged cases, while Mcl-1 expression was highest in cases with 1q21 gain/amplification. Notably, 65-74% of cases with other CGAs exhibited moderate to strong Bcl-2 or Mcl-1 expression, indicating potential utility of BH3 mimetics in this group, while 25% showed dim to absent expression of one or both markers, suggesting potential futility in these patients. Our study highlights FCM's potential for rapid Bcl-2 and Mcl-1 quantification, surpassing traditional methods. We propose that direct measurement of Bcl-2 and Mcl-1 expression in PCs by FCM, combined with cytogenetic characterization, could improve therapeutic decision-making regarding the use of BH3 mimetics in MM, potentially enhancing outcomes and overcoming resistance.

Tribological and Rheological Study of Thixotropic Gels of 2D Nanoparticles.

A thixotropic colloidal gel constituting an aqueous dispersion of synthetic clay Laponite with varying concentrations of salt has been studied for its rheological and tribological performance as a lubricant. We observed that the incorporation of NaCl induces notable enhancements in the colloidal gel's relaxation time, elastic modulus, and yield stress. Although an increase in NaCl concentration decreases the material's relaxation time dependence on waiting time (tw), overall, the strength of its thixotropic character has been observed to increase with an increase in salt concentration. The analysis of friction and wear indicated that the utilization of a thixotropic colloidal gel of Laponite with a higher concentration of NaCl resulted in progressively greater reductions in both the coefficient of friction and specific wear rates under various load-speed conditions. Severe abrasive wear on disc surface under dry test, gradually mitigated upon the introduction of these lubricants. Two simultaneous lubricating mechanisms, first, the smooth sliding of the friction pair, facilitated by the alignment of Laponite particles in the direction of shear forces, and second, the stable structure of Laponite, coupled with the addition of NaCl, enabling continuous replenishment of the wear track with lubricant, are attributed to lubrication effectiveness.

Indolo[3,2-a]carbazoles as Engineered Materials for Optoelectronic Applications: Synthesis, Structural Insights, and Computational Screening.

The biological and medicinal importance of indolocarbazoles has been known for the past several decades. However, in recent times, these compounds have been emerging as potential candidates for optoelectronic applications, although several challenges are associated with their synthesis. We report here a Pd(II)-catalyzed process for the synthesis of indolo[3,2-a]carbazoles. The reaction proceeded under neat conditions and in the presence of aqueous nonmetallic oxidant TBHP, and the products were purified directly after the completion of the reaction. Also, the possibility of employing the present method for reaction with gram-scale feed was investigated. A detailed single-crystal analysis of several indolo[3,2-a]carbazoles revealed how the molecular arrangement can be tuned by altering the functionalization. Finally, the developed molecules were screened computationally to assess their potential for possible use as hole transport materials (HTMs) for organic light-emitting diodes (OLEDs).

Organosulphur and organoselenium compounds as ligands for catalytic systems in the Sonogashira coupling.

Sonogashira coupling is a reaction of aryl/vinyl halides with terminal alkynes. It is used for the synthesis of conjugated enynes. Generally, copper (Cu) is required as a mediator for this reaction. It requires a long reaction time, high catalyst loading, or expensive ligands. Recently, homogeneous, heterogeneous, and nanocatalysts have been developed using organosulphur and organoselenium compounds as building blocks. Preformed complexes of metals with organosulphur and organoselenium ligands are used for homogeneous catalysis. Heterogeneous catalytic systems have also been developed using Cu, Pd, and Ni as metals. The nanocatalytic systems (synthesized using such ligands) include copper selenides and stabilized palladium(0) nanospecies. This article aims to cover the developments in the field of the processes and techniques used so far to generate catalytically relevant organic ligands having sulphur or selenium donor sites, the utility of such ligands in the syntheses of homogeneous, heterogeneous, and nanocatalytic systems, and critical analysis of their application in the catalysis of this coupling reaction. The results of catalysis are analyzed in terms of the effects of the S/Se donor, halogen atom of aryl halide, the effect of the presence/absence of electron-withdrawing or electron-donating groups or substituents on the aromatic ring of haloarenes/substituted phenylacetylenes, as well as the position (ortho or para) of the substitution. Substrate scope is discussed for all the kinds of catalysis. The supremacy of heterogeneous and nanocatalytic systems indicates promising future prospects.

Assessment of prevalence of elevated blood lead levels and risk factors among children and pregnant women in Bihar, India.

BACKGROUND: While modeled estimates and studies in contaminated areas indicate high lead exposure among children in Bihar, India, local data on lead exposure in the child population is limited. OBJECTIVES: To characterize lead exposure, and assess potential sources of lead exposure among a state-representative sample of children and their pregnant mothers residing in Bihar. METHODS: Blood samples were collected from 697 children under five and 55 pregnant women from eight districts in Bihar. Blood lead levels were determined using capillary blood and a portable lead analyzer. Household demographics, home environment, behavior, and nutrition information were collected through computer-assisted personal interviews with primary caregivers. Logistic regression was used to assess associations between potential risk factors and elevated blood lead levels. RESULTS: More than 90% of children and 80% of pregnant women reported blood lead levels ≥5 µg/dL. Living near a lead-related industry and pica behavior of eating soil were significantly associated with increased odds of having elevated blood lead levels. Additional risk factors for having a blood level ≥5 µg/dL included the use of skin lightning cream (aOR = 5.11, 95%CI: 1.62, 16.16) and the use of eyeliners (aOR = 2.81, 95%CI: 1.14, 6.93). Having blood lead levels ≥10 µg/dL was also significantly associated with the household member who had an occupation or hobby involving the use of lead (aOR = 1.75, 95%CI: 1.13, 2.72). DISCUSSION: Elevated blood lead levels were prevalent among children and pregnant women in Bihar, indicating the urgent need for a comprehensive lead poisoning prevention strategy.

Heat-killed probiotic Levilactobacillus brevis MKAK9 and its exopolysaccharide promote longevity by modulating aging hallmarks and enhancing immune responses in Caenorhabditis elegans.

BACKGROUND: Proteostasis is a critical aging hallmark responsible for removing damaged or misfolded proteins and their aggregates by improving proteasomal degradation through the autophagy-lysosome pathway (ALP) and the ubiquitin-proteasome system (UPS). Research on the impact of heat-killed probiotic bacteria and their structural components on aging hallmarks and innate immune responses is scarce, yet enhancing these effects could potentially delay age-related diseases. RESULTS: This study introduces a novel heat-killed Levilactobacillus brevis strain MKAK9 (HK MKAK9), along with its exopolysaccharide (EPS), demonstrating their ability to extend longevity by improving proteostasis and immune responses in wild-type Caenorhabditis elegans. We elucidate the underlying mechanisms through a comprehensive approach involving mRNA- and small RNA sequencing, proteomic analysis, lifespan assays on loss-of-function mutants, and quantitative RT-PCR. Mechanistically, HK MKAK9 and its EPS resulted in downregulation of the insulin-like signaling pathway in a DAF-16-dependent manner, enhancing protein ubiquitination and subsequent proteasomal degradation through activation of the ALP pathway, which is partially mediated by microRNA mir-243. Importantly, autophagosomes engulf ubiquitinylated proteins, as evidenced by increased expression of the autophagy receptor sqst-3, and subsequently fuse with lysosomes, facilitated by increased levels of the lysosome-associated membrane protein (LAMP) lmp-1, suggesting the formation of autolysosomes for degradation of the selected cargo. Moreover, HK MKAK9 and its EPS activated the p38 MAPK pathway and its downstream SKN-1 transcription factor, which are known to regulate genes involved in innate immune response (thn-1, ilys-1, cnc-2, spp-9, spp-21, clec-47, and clec-266) and antioxidation (sod-3 and gst-44), thereby reducing the accumulation of reactive oxygen species (ROS) at both cellular and mitochondrial levels. Notably, SOD-3 emerged as a transcriptional target of both DAF-16 and SKN-1 transcription factors. CONCLUSION: Our research sets a benchmark for future investigations by demonstrating that heat-killed probiotic and its specific cellular component, EPS, can downregulate the insulin-signaling pathway, potentially improving the autophagy-lysosome pathway (ALP) for degrading ubiquitinylated proteins and promoting organismal longevity. Additionally, we discovered that increased expression of microRNA mir-243 regulates insulin-like signaling and its downstream ALP pathway. Our findings also indicate that postbiotic treatment may bolster antioxidative and innate immune responses, offering a promising avenue for interventions in aging-related diseases.

Revision Total Knee Arthroplasty Achieves Minimal Clinically Important Difference Faster than Primary Total Knee Arthroplasty.

INTRODUCTION: Revision total knee arthroplasty (rTKA) remains underexplored regarding patient-reported outcome measures (PROMs), particularly in terms of time to reach Minimal Clinically Important Difference (MCID). This study addresses this gap by comparing the time to achieve MCID between primary TKA (pTKA) and rTKA patients, providing valuable insights into their recovery trajectories. METHODS: A total of 8,266 TKAs (7,618 pTKA and 648 rTKA) were retrospectively studied in a multi-institutional arthroplasty registry. Patients who completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Global Physical, PROMIS Physical Function Short Form 10a (PF-10a), and Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form (KOOS-PS) questionnaires were identified by Current Procedural Terminology (CPT) codes. Survival curves with and without interval-censoring were utilized to evaluate the time to achieve MCID. RESULTS: Comparing the time to achieve MCID, rTKAs were significantly faster than pTKA for PROMIS Global Physical (3.5 versus 3.7 months, P = 0.004) and KOOS-PS (3.3 versus 4.2 months, P < 0.001), but similar for PROMIS PF-10a (4.4 versus 4.8 months, P = 0.057). Interval-censoring also showed similar trends with earlier times to achieve MCID for rTKAs for PROMIS Global Physical (0.6 to 0.61 versus 0.97 to 0.97 months, P = 0.009) and KOOS-PS (0.97 to 0.97 versus 1.47 to 1.47 months, P < 0.001), but not for PROMIS PF-10a (2.43 to 2.54 versus 1.90 to 1.91 months, P = 0.92). CONCLUSION: The present study revealed that the time to achieve MCID was faster in patients undergoing rTKA compared to those undergoing pTKA. These findings allow surgeons to reassure preoperative revision TKA patients that their recovery to a minimal clinically important difference postoperatively may be quicker than expected, especially when compared to their initial recovery after primary TKA.

Prediction of Drivers' Subjective Evaluation of Vehicle Reaction Under Aerodynamic Excitations.

OBJECTIVE: The objectives are to determine which quantities are important to measure to determine how drivers perceive vehicle stability, and to develop a regression model to predict which induced external disturbances drivers are able to feel. BACKGROUND: Driver experience of a vehicle's dynamic performance is important to auto manufacturers. Test engineers and test drivers perform several on-road assessments to evaluate the vehicle's dynamic performance before sign-off for production. The presence of external disturbances such as aerodynamic forces and moments play a significant role in the overall vehicle assessment. As a result, it is important to understand the relation between the subjective experience of the drivers and these external disturbances acting on the vehicle. METHOD: A sequence of external yaw and roll moment disturbances of varying amplitudes and frequencies is added to a straight-line high-speed stability simulation test in a driving simulator. The tests are performed with both common and professional test drivers, and their evaluations to these external disturbances are recorded. The sampled data from these tests are used to generate the needed regression model. RESULTS: A model is derived for predicting which disturbances drivers can feel. It quantifies difference in sensitivity between driver types and between yaw and roll disturbances. CONCLUSION: The model shows a relationship between steering input and driver sensitivity to external disturbances in a straight-line drive. Drivers are more sensitive to yaw disturbance than roll disturbance and increased steering input lowers sensitivity. APPLICATION: Identify the threshold above which unexpected disturbances such as aerodynamic excitations can potentially create unstable vehicle behaviour.

Embracing nutritional, physical, pasting, textural, sensory and phenolic profile of functional muffins prepared by partial incorporation of lyophilized wheatgrass, fenugreek and basil microgreens juice powder.

BACKGROUND: Muffins are delightful baked food products that have earned a prominent place in the daily diet of a majority of people around the world. The incorporation of microgreens juice powder (MJP) into muffins boosts their nutritional value. The influence of the incorporation of wheatgrass, fenugreek and basil MJP at 1.5% and 3.0% levels on the nutritional composition, physical properties, pasting, sensory, textural and phenolic profile of functional muffins was evaluated. RESULTS: The results indicated a significant increase in the protein content, ash content, dietary fiber and total phenolic content of MJP incorporated muffins. The incorporation of MJP to the muffins led to a gradual reduction in the L*, a* and b* values. Baking characteristic such as bake loss decreased significantly as a result of MJP incorporation. Furthermore, the incorporation of various MJPs resulted in a significant decrease in the peak viscosity of the flour-MJP blends. Regarding texture, the hardness and chewiness of the muffins increased progressively with an increase in the level of MJP incorporation. The highest hardness (10.15 N) and chewiness (24.45 mJ) were noted for 3% fenugreek MJP incorporated muffins (FK 3.0). The sensory score of MJP incorporated muffins was acceptable and satisfactory. Additionally, 3% basil MJP incorporated muffins (BL 3.0) marked the dominant presence of majority of the detected phenolic acids such as ferulic acid, sinapic acid, chlorogenic acid, caffeic acid, quercetin, cinnamic acid, isothymosin and rosamarinic acid. The highest concentration of p-coumaric acid (11.95 mg kg-1), vanillic acid (26.07 mg kg-1) and kaempferol (8.04 mg kg-1) was recorded for FK 3.0 muffin. CONCLUSION: MJP incorporated muffins revealed the pool of phenolic acids and the reduced bake loss is of industrial interest. The present study concludes that wheatgrass, fenugreek and basil MJP can be incorporated by up to 3% into baked products as a source of functional ingredients for health benefits. © 2024 Society of Chemical Industry.

Postoperative pain management after abdominal transplantations.

PURPOSE OF REVIEW: The aim of this review article is to present current recommendations as well as knowledge gaps and controversies pertaining to commonly utilized postoperative pain management after solid organ transplantation in the abdominal cavity. RECENT FINDINGS: Postsurgical pain has been identified as one of the major challenges in recovery and treatment after solid organ transplants. Many perioperative interventions and management strategies are available for reducing and managing postoperative pain. Management should be tailored to the individual needs, taking an interdisciplinary and holistic approach and following enhanced recovery after surgery guidelines. Many centers currently utilize peripheral and neuraxial blocks during transplantation surgery, but these techniques are far from standardized practices. The utilization of these procedures is often dependent on transplantation centers' historical methods and perioperative cultures. SUMMARY: The optimal pain management regimen has not yet been definitively established, and current scientific evidence does not yet support the endorsement of a certain analgesic approach. This objective necessitates the need for high-quality randomized controlled trials.

Fine mapping of interspecific secondary CSSL populations revealed key regulators for grain weight at qTGW3.1 locus from Oryza nivara.

Grain weight (GW) is the most important stable trait that directly contributes to crop yield in case of cereals. A total of 105 backcross introgression lines (BC2F10 BILs) derived from Swarna/O. nivara IRGC81848 (NPS) and 90 BILs from Swarna/O. nivara IRGC81832 (NPK) were evaluated for thousand-grain weight (TGW) across four years (wet seasons 2014, 2015, 2016 and 2018) and chromosome segment substitution lines (CSSLs) were selected. From significant pair- wise mean comparison with Swarna, a total of 77 positively and 29 negatively significant NPS lines and 62 positively and 29 negatively significant NPK lines were identified. In all 4 years, 14 NPS lines and 9 NPK lines were positively significant and one-line NPS69 (IET22161) was negatively significant for TGW over Swarna consistently. NPS lines and NPK lines were genotyped using 111 and 140 polymorphic SSRs respectively. Quantitative trait locus (QTL) mapping using ICIM v4.2 software showed 13 QTLs for TGW in NPS. Three major effect QTLs qTGW2.1, qTGW8.1 and qTGW11.1 were identified in NPS for two or more years with PVE ranging from 8 to 14%. Likewise, 10 QTLs were identified in NPK and including two major effect QTL qTGW3.1 and qTGW12.1 with 6 to 32% PVE. In all QTLs, O. nivara alleles increased TGW. These consistent QTLs are very suitable for fine mapping and functional analysis of grain weight. Further in this study, CSSLs NPS1 (10-2S) and NPK61 (158 K) with significantly higher grain weight than the recurrent parent, Swarna cv. Oryza sativa were selected from each population and secondary F2 mapping populations were developed. Using Bulked Segregant QTL sequencing, a grain weight QTL, designated as qTGW3.1 was fine mapped from the cross between NPK61 and Swarna. This QTL explained 48% (logarithm of odds = 32.2) of the phenotypic variations and was fine mapped to a 31 kb interval using recombinant analysis. GRAS transcription factor gene (OS03go103400) involved in plant growth and development located at this genomic locus might be the candidate gene for qTGW3.1. The results of this study will help in further functional studies and improving the knowledge related to the molecular mechanism of grain weight in Oryza and lays a solid foundation for the breeding for high yield. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01483-0.

Outcomes following reoperative bariatric surgery following laparoscopic sleeve gastrectomy at a tertiary care centre.

INTRODUCTION: Laparoscopic sleeve gastrectomy (SG) is the most common bariatric surgical procedure worldwide. Approximately 20%-30% of patients present with weight loss failure or reflux following SG, which might require reoperative surgery. We present the surgical outcomes and complications following reoperative bariatric surgery at a tertiary care centre. PATIENTS AND METHODS: Prospectively collected data of all patients undergoing reoperative bariatric surgery from 2008 to 2021 were analysed retrospectively. Weight loss, resolution of comorbidities and complications following reoperative surgery were evaluated. RESULTS: Twenty-six patients were included in the study. The mean age was 38.8 (10.8) years. The primary procedure performed was laparoscopic SG in all cases. Nine patients underwent Roux en Y gastric bypass (RYGB) (one banded RYGB) and 14 underwent one anastomosis gastric bypass (OAGB) (three-banded OAGB). Three patients underwent resleeve. The most common indication was weight loss failure (65.3%). Fifteen patients were diagnosed to have hiatal hernia intraoperatively and concomitant repair was performed. The mean body mass index before revision surgery was 42.7 (9.8). It was 32.6 (5.7) kg/m2 and 33.0 (6.1) kg/m2 at 1 and 3 years, respectively. Age and pre-revision surgery excess weight correlated with weight loss (r = -0.79 and r = 0.99, respectively). Leak and bleeding occurred in one and two patients, respectively. There were two band-related complications and one 30-day mortality. CONCLUSION: Re-operative bariatric surgery following SG has adequate weight loss with acceptable complication rates. Band placement in re-operative surgery might lead to a higher complication rate.

Terminal Extubation or Terminal Weaning: Is it Feasible in Indian Intensive Care Units?

Terminal extubation (TE) and weaning have long been suggested as a modality of intervention when the continuation of mechanical ventilation is not expected to achieve its therapeutic aim and is merely prolonging the dying process. The decision, however, is complex considering limited evidence regarding the best practices and is often defied due to inherent ethical, legal, and medical dilemmas. The article attempts a brief overview of available literature on this subject and discusses its feasibility in Indian intensive care units (ICUs). How to cite this article: Kumar A, Bhat RS, Mani RK. Terminal Extubation or Terminal Weaning: Is it Feasible in Indian Intensive Care Units? Indian J Crit Care Med 2024;28(2):103-105.

Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit.

End-of-life care (EOLC) exemplifies the joint mission of intensive and palliative care (PC) in their human-centeredness. The explosion of technological advances in medicine must be balanced with the culture of holistic care. Inevitably, it brings together the science and the art of medicine in their full expression. High-quality EOLC in the ICU is grounded in evidence, ethical principles, and professionalism within the framework of the Law. Expert professional statements over the last two decades in India were developed while the law was evolving. Recent landmark Supreme Court judgments have necessitated a review of the clinical pathway for EOLC outlined in the previous statements. Much empirical and interventional evidence has accumulated since the position statement in 2014. This iteration of the joint Indian Society of Critical Care Medicine-Indian Association of Palliative Care (ISCCM-IAPC) Position Statement for EOLC combines contemporary evidence, ethics, and law for decision support by the bedside in Indian ICUs. How to cite this article: Mani RK, Bhatnagar S, Butola S, Gursahani R, Mehta D, Simha S, et al. Indian Society of Critical Care Medicine and Indian Association of Palliative Care Expert Consensus and Position Statements for End-of-life and Palliative Care in the Intensive Care Unit. Indian J Crit Care Med 2024;28(3):200-250.