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Introduction: Palliative stenting fur relieving malignant obstruction of the gastrointestinal tract is routinely practical in western world. Obstructing advanced 67 malignancy requires bypass or exteriorization of proximal gut before NACT or as a bridge to definite surgery. The aim of the study was to review the experience at tertiary cancer hospital and short-term outcome with endoscopic stalling in lieu of palliative bypass surgery for advanced and obstracting GI malignancy. Materials and Methods: This observation study was carried out in the surgical out-patient department of NICRH where all therapeutic endoscopic facilities were available. All patients treated with stenting in a 2 years period from 2018- 2020 were studied. Results: Fifty-six patients received 60 stents. No case of perforation occurred. In fifteen cases (26.78%) clogging with food occurred: in 5 cases (8.92%) displacement occur. Tumour overgrowth was noted in 7(12.66%) cases. Four patients (6.72%) received a second stent. Mean survival of patients with esophageal stent was 221 days. Four patients received 4 stents in their colon or rectum. The stents were placed in the sigmoid (n=2), the descending colon (n=l), and the transverse colon (n=1). Mean survival of colonic stent patients was 331 days. No perforation, no clogging by stool and no tumour ingrowth among patients with colonic stent but one (25%) had displacement. Eighteen patients received a total of IS stents because of obstructing stomach cancer. 12 (61.22%) patients had tumour at cardia. Mean survival after gastric stent placement was 176 days. There was no perforation, one case of clogging (8.33%), and two cases of tumour ingrowth (16.66%). 5 patients underwent duodenal stenting. Remaining one at Billroth II anastomotic site. Single patients (20%) required laparotomy and stent extraction due to duodenal stent migration. Mean survival after duodenal stent placement was 242 days. No perforation, no clogging and no tumour ingrowth. Conclusions: The present series shows that placement of expandable metallic stents in the obstructing GI tract malignancy us an alternative to bypass surgery is safe, cost effective, low complications, short hospital stay and provides good palliation. [ABSTRACT FROM AUTHOR]

Numerous hydraulic structures are to be provided in canals and rivers for storage, diversion and transport of water. Some innovative, economic and improved hydraulic design has been discussed. Transitions are to be provided in all canal structures wherever the canal is flumed to achieve economy. Most popular transition in the USA and Europe is Hinds transition. The author performed large numbers of experiments to introduce short curved transitions at entry and straight expansion at exit to attain higher efficiency and better performance. Energy dissipaters are usually provided with parallel side walls followed by transition structures to connect the stilling basin with normal channel section, resulting in huge cost of the structure. For low value of inflow Froude's number (F1), the author introduced a new type of energy dissipater with straight diverging side walls starting from toe of the structure so that it functions as both energy dissipater and flow diffuser. Flow metering structures are needed for flow measurement in both rivers and canals. Parshall flumes may be free or submerged. The author invented a new proportional-type flow meter, by simultaneously fluming and raising the bed so that the flow remains free for all discharges in a given range. [ABSTRACT FROM AUTHOR]

The water wealth and terrain head of the Himalayas are nature's gift and a bounty. Whereas concentration of the sediments carried by the rivers Indus, Ganga, Brahmaputra and their tributaries exceeds 2,000 p.p.m. [Extracted from the article]

Background: The prevalence of caesarean sections (C-sections) has remarkably increased in the past few decades worldwide, especially in the lower and middle-income countries (LMICs). To our best knowledge, no studies focused on and compared the C-section scenarios of Bangladesh, Nepal, and Pakistan based on the latest demographic and health survey (DHS) data., Objectives: To assess the trends and factors associated with C-sections in the three South Asian countries., Study Population: Mothers aged 15-49 years participated in DHS 1990 to 2017-2018 and gave birth within three years of each of the surveys in Bangladesh, Nepal, and Pakistan., Materials and Methods: This study analyzed data from five recent DHS rounds in Bangladesh and four in Nepal and Pakistan. Multivariable logistic regression was used to assess the association between C-sections and sociodemographic characteristics., Results: The results show that institutional delivery and C-sections have increased throughout the period in all three countries. In Bangladesh, the hospital birth rate increased from 10.0% in 2004 to 49.9% in 2017, and the corresponding figures [S1 Appendix: Figure A1 and Figure A2] for C-sections increased from 3.5% to 32.8%. In Nepal, the hospital birth rate increased from 11.0% in 2001 to 58.6% in 2016, and the C-sections from 0.8% to 11.0%. Pakistan observed a sharp increase from 13.7% to 66.3% and 2.7% to 22.3% in the respective cases from 1990 to 2017. Results from regression reveal that the mother's age, place of residence, education, partner's education, wealth status, birth order, number of antenatal care visits, and body mass index are associated with C-section deliveries in all three countries., Conclusions: Our findings regarding the association of sociodemographic factors with increased C-sections may help identify subgroups of women susceptible to C-sections and offer better support regarding C-sections plans. However, the substantial increase in C-sections across the three countries warrants further investigation to identify the reasons., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Enantioselective catalytic reactions have a significant impact on chemical synthesis, and they are important components in an experimental chemist's toolbox. However, development of asymmetric catalysts often relies on the chemical intuition and experience of a synthetic chemist, making the process both time-consuming and resource-intensive. The machine-learning-assisted reaction discovery can serve as a very efficient platform for obtaining high-performing catalysts in a time-economical manner without extensive experimentation. Herein, we report a data-driven and machine learning method for reliably predicting enantiomeric excess (%ee) of 211 asymmetric Pauson-Khand reactions (PKR 1-PKR 211) between a variety of 45 unique 1,6-enyne substrates and 12 unique axially chiral biaryl ligands in the presence of different reaction conditions like varying CO gas pressure, temperature, and solvent polarity. Four different machine learning algorithms have been studied: extreme gradient boosting (XGBoost), random forest (RF), light gradient boosting machine (LGBM), and neural network (NN). A fivefold cross validation method was applied to our k-means SMOTE-augmented data set to obtain the optimized hyperparameters for the training set, and subsequently, these parameters were used in the test data set. In the case of the out-of-box set, the XGBoost method is found to be superior among all four machine learning methods investigated. Our out-of-box samples contain a total of 12 unique asymmetric Pauson-Khand reactions (PKR 212-PKR 223) arising from three new 1,3-benzodioxole-based SEGPHOS catalysts, which were never included in the training set. The XGBoost algorithm shows an impressive root mean square error (RMSE) of 7.06 (±1.11) in predicting %ee. The XGBoost-predicted %ee values match reasonably well with the experimental results. The absolute difference between the experimental and XGBoost-calculated %ee values ranges from 0.9 to 7.6 for the majority of the out-of-box Pauson-Khand reactions. The reactions with fluoro-substituted-SEGPHOS ligand L14 shows smaller deviations from the experimental %ee values compared to the reactions with L13 and L15 catalysts where the benzodioxole units do not have fluorine atoms. Finally, we have discovered a library of 3357 lead reactions with excellent %ee (≥99) by engaging the experimentally unknown combinations of the catalysts, substrates, and reaction conditions. The axially chiral biaryl catalysts and enyne substrates present in the library are synthetically accessible. The ligand space in the library is dominated by the presence of tol-BINAP and the DTBM-OMe-BIPHEP ligands. The substrate space is predominantly occupied by NTs-tethered, O-tethered, NBn-tethered, and C(CO 2 Me) 2 -tethered 1,6-enynes that have an H or methyl functional group present in the alkyne unit. Our newly discovered library assists a synthetic chemist to develop a highly enantioselective PKR by starting with a priori knowledge without extensive trial-and-error experimentation.

India is dealing with both nutritional and agricultural issues. The maximum area of agricultural land with irrigation capabilities has been largely utilized, while the amount of dry land is expanding. The influence is distinct on farmer's livelihoods and earnings, which ultimately affects nutritional security. In order to attain nutritional security and the goal of SDG (Sustainable Development Goals), millets are sustainable solutions, with respect to high nutritional content, bioactive and medicinal properties, and climate resilience. The nutrient profile of millet includes 60%-70% carbohydrate content, 3.5%-5.2% fat, and 7.52%-12.1% protein sources. A wide spectrum of amino acids, including cysteine, isoleucine, arginine, leucine, tryptophan, lysine, histidine, methionine, tyrosine, phenylalanine, threonine, and valine are generally present in millets. Mineral content in millets includes calcium, phosphorus, potassium, sodium, and magnesium. Additionally, millets are an excellent source of bioactive molecules such as polyphenol, phenolic acid, flavonoids, active peptides, and soluble fiber, which have a wide range of therapeutic applications, including the prevention of free radical damage, diabetes, anti-microbial, anti- biofilm, and anti-cancer effects. This review will focus on the nutritional profile and health benefits of millet considering the present-day food security problems.

Non-steroidal anti-inflammatory drugs (NSAIDs) are most extensively used over-the-counter FDA-approved analgesic medicines for treating inflammation, musculoskeletal pain, arthritis, pyrexia and menstrual cramps. Moreover, aspirin is widely used against cardiovascular complications. Owing to their non-addictive nature, NSAIDs are also commissioned as safer opioid-sparing alternatives in acute trauma and post-surgical treatments. In fact, therapeutic spectrum of NSAIDs is expanding. These "wonder-drugs" are now repurposed against lung diseases, diabetes, neurodegenerative disorders, fungal infections and most notably cancer, due to their efficacy against chemoresistance, radio-resistance and cancer stem cells. However, prolonged NSAID treatment accompany several adverse effects. Mechanistically, apart from cyclooxygenase inhibition, NSAIDs directly target mitochondria to induce cell death. Interestingly, there are also incidences of dose-dependent effects where NSAIDs are found to improve mitochondrial health thereby suggesting plausible mitohormesis. While mitochondria-targeted effects of NSAIDs are discretely studied, a comprehensive account emphasizing the multiple dimensions in which NSAIDs affect mitochondrial structure-function integrity, leading to cell death, is lacking. This review discusses the current understanding of NSAID-mitochondria interactions in the pathophysiological background. This is essential for assessing the risk-benefit trade-offs of NSAIDs for judiciously strategizing NSAID-based approaches to manage pain and inflammation as well as formulating effective anti-cancer strategies. We also discuss recent developments constituting selective mitochondria-targeted NSAIDs including theranostics, mitocans, chimeric small molecules, prodrugs and nanomedicines that rationally optimize safer application of NSAIDs. Thus, we present a comprehensive understanding of therapeutic merits and demerits of NSAIDs with mitochondria at its cross roads. This would help in NSAID-based disease management research and drug development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Non-canonical nucleotides, generated as oxidative metabolic by-products, significantly threaten the genome integrity of Plasmodium falciparum and thereby, their survival, owing to their mutagenic effects. PfHAM1, an evolutionarily conserved inosine/xanthosine triphosphate pyrophosphohydrolase, maintains nucleotide homeostasis in the malaria parasite by removing non-canonical nucleotides, although structure-function intricacies are hitherto poorly reported. Here, we report the X-ray crystal structure of PfHAM1, which revealed a homodimeric structure, additionally validated by size-exclusion chromatography-multi-angle light scattering analysis. The two monomeric units in the dimer were aligned in a parallel fashion, and critical residues associated with substrate and metal binding were identified, wherein a notable structural difference was observed in the β-sheet main frame compared to human inosine triphosphate pyrophosphatase. PfHAM1 exhibited Mg ++ -dependent pyrophosphohydrolase activity and the highest binding affinity to dITP compared to other non-canonical nucleotides as measured by isothermal titration calorimetry. Modifying the pfham1 genomic locus followed by live-cell imaging of expressed mNeonGreen-tagged PfHAM1 demonstrated its ubiquitous presence in the cytoplasm across erythrocytic stages with greater expression in trophozoites and schizonts. Interestingly, CRISPR-Cas9/DiCre recombinase-guided pfham1-null P. falciparum survived in culture under standard growth conditions, indicating its assistive role in non-canonical nucleotide clearance during intra-erythrocytic stages. This is the first comprehensive structural and functional report of PfHAM1, an atypical nucleotide-cleansing enzyme in P. falciparum., (© 2024 Federation of European Biochemical Societies.)

Palladium-catalyzed regiocontrolled intramolecular oxypalladation-initiated cascades of multifunctional internal alkyne bearing an N -tosyl tether deliver functionalized benzazepine as an exclusive product via 6- endo-dig pathway in 1,4-dioxane solvent and tetrahydroquinoline scaffold as a major product via the 5- exo-dig pathway in the DMSO solvent. The role of the solvent in controlling the regioselectivity is still unknown which can be a major hurdle for further reaction development. Moreover, the reaction in DMSO suffered from having a mixture of products, and no exclusive formation of tetrahydroquinoline was achieved. Herein, we report a concerted computational and experimental study, revealing the role of the solvent in controlling the reaction outcome. DFT study revealed that the formation of the σ-vinylpalladium intermediate is reversible for the 5- exo-dig pathway while it is irreversible for the 6- endo-dig mechanism in 1,4-dioxane and consequently, the 5- exo-dig pathway is difficult to proceed. In contrast, both the 5- exo-dig and 6- endo-dig pathways are irreversible in DMSO. We predicted an exclusive formation of isobenzofuranone-fused chromane via the 5 -exo-dig pathway when the N -tosyl tether is replaced by the O -tether in the internal alkyne in DMSO. The experimental study confirms the theoretical hypothesis and provides a highly chemo-divergent approach for the synthesis of biologically significant chromane with a large substrate scope and up to 95% yield at room temperature.

In the Western Pacific Region, the prevalence of dementia is expected to increase, however, the diversity of the region is expected to present unique challenges. The region has varying levels of preparedness, with a limited number of countries having a specific national dementia plan and awareness campaigns. Diversity of risk and healthcare services within the region is exerting impact on diagnosis, treatment, care, and support, with most countries being under resourced. Similarly, the ability to monitor dementia-related indicators and progress research, particularly relating to treatment and clinical trial access needs to be addressed. Countries require comprehensive national plans that lay out how resources will be allocated to improve dementia literacy, train, and support carers, mobilise resources to reduce risk factors and improve research capabilities. These plans need to be informed by consumers and tailored to the region to develop an inclusive society for people living with dementia and their families., Competing Interests: ST's research is supported by an NHMRC Ideas Grant (APP2029871), FightMND, and Lenity Australia. SHK was supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center (KDRC), funded by the Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea (RS-2024-00348451)”. SW is the Clinical Lead/steering committee co-chair of the ADNeT Registry and received an honorium from ROCHE and Eisai for attendance at an advisory meeting. KJA received a speaker honorarium from Roche in 2023 and is supported by ARC FL19010001. CO is supported by a University of Sydney Robinson Fellowship and an Australian National Health and Medical Research Council EL2 Fellowship (2016866). CSYL is supported by the Sydney Medical School Foundation, University of Sydney. DF is supported by the Edwards Fund for Dementia Research and has received research grants from the Dementia Australia Research Foundation, outside the work submitted. OP is supported in part by an NHMRC Leadership Fellowship and has received research grants from the NHMRC and the Australian Research Council, outside the submitted work. JCM received a speaker honorarium; investigator-initiated research grant to institution from Eisai Australia. Y-HJ has received research grants from the National Health and Medical Research Council (NHMRC) and Arcare in Australia and travel support for invited talks from Singapore Sing Health, Northern Ireland Queen’s University Belfast, Hong Kong Jockey Club, and Korea National Health Insurance Service: Long-term Care, all outside the submitted work. MCK was supported by a NHMRC Practitioner Fellowship (1156093) and National Health and Medical Research Council of Australia Partnership Project (1153439). RHT is supported by a FightMND Mid-Career Fellowship and her research is supported by NSW Health and MNDRA. GS is supported by the Japan Agency for Medical Research and Development. SN received a speaker honorarium HT, SP, DT, SM, SA, VCTM, NS, JYS, have no conflict of interests to declare., (© 2024 The Authors.)

The agricultural sector in Bangladesh is a cornerstone of the nation's economy, with key crops such as rice, corn, wheat, potato, and tomato playing vital roles. However, these crops are highly vulnerable to various leaf diseases, which pose significant threats to crop yields and food security if not promptly addressed. Consequently, there is an urgent need for an automated system that can accurately identify and categorize leaf diseases, enabling early intervention and management. This study explores the efficacy of the latest state-of-the-art object detection model, YOLOv8 (You Only Look Once), in surpassing previous models for the automated detection and categorization of leaf diseases in these five major crops. By leveraging modern computer vision techniques, the goal is to enhance the efficiency of disease detection and management. A dataset comprising 19 classes, each with 150 images, totaling 2850 images, was meticulously curated and annotated for training and evaluation. The YOLOv8 framework, known for its capability to detect multiple objects simultaneously, was employed to train a deep neural network. The system's performance was evaluated using standard metrics such as mean Average Precision (mAP) and F1 score. The findings demonstrate that the YOLOv8 framework successfully identifies leaf diseases, achieving a high mAP of 98% and an F1 score of 97%. These results underscore the significant potential of this approach to enhance crop disease management, thereby improving food security and promoting agricultural sustainability in Bangladesh., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Md. Jakir Hossen reports financial support was provided by 10.13039/100012024Multimedia University. Dr. Md. Jakir Hossen reports a relationship with Multimedia University that includes: employment and funding grants. Dr. Md. Jakir Hossen has patent pending to Patent is not applied yet. No conflict of interest If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Producing alternative staple foods like millet will be essential to feeding ten billion people by 2050. The increased demand for millet is driving researchers to improve its genetic variation. Millets include protein, dietary fiber, phenolic substances, and flavonoid components. Its climate resilience makes millet an appealing crop for agronomic sustainability. Integrative omics technologies could potentially identify and develop millets with desirable phenotypes that may have high agronomic value. Millets' salinity and drought tolerance have been enhanced using transcriptomics. In foxtail, finger, and pearl millet, proteomics has discovered salt-tolerant protein, phytohormone-focused protein, and drought tolerance. Metabolomics studies have revealed that certain metabolic pathways including those involving lignin, flavonoids, phenylpropanoid, and lysophospholipids are critical for many processes, including seed germination, photosynthesis, energy metabolism, and the synthesis of bioactive chemicals necessary for drought tolerance. Metabolomics integration with other omics revealed metabolome engineering and trait-specific metabolite creation. Integrated metabolomics and ionomics are still in the development stage, but they could potentially assist in comprehending the pathway of ionomers to control nutrient levels and biofortify millet. Epigenomic analysis has shown alterations in DNA methylation patterns and chromatin structure in foxtail and pearl millets in response to abiotic stress. Whole-genome sequencing utilizing next-generation sequencing is the most proficient method for finding stress-induced phytoconstituent genes. New genome sequencing enables novel biotechnological interventions including genome-wide association, mutation-based research, and other omics approaches. Millets can breed more effectively by employing next-generation sequencing and genotyping by sequencing, which may mitigate climate change. Millet marker-assisted breeding has advanced with high-throughput markers and combined genotyping technologies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: Antibiotic misuse represent a significant global health challenge, with medical students positioned as key figures in promoting responsible antibiotic usage. This study investigates the knowledge, attitudes, and practices (KAP) regarding antibiotic use among medical students in Bangladesh, aiming to identify areas for targeted educational and policy interventions., Methods: This cross-sectional survey was conducted among 501 medical students across various years of study in Bangladesh, collecting data over a 3-month period. The survey assessed antibiotic knowledge, usage practices, and attitudes towards misuse, employing descriptive statistics and multiple logistic regression analyses to explore associations between students' demographic characteristics and their KAP towards antibiotics. Significance was assigned at p -value < 0.05., Results: In our study involving 501 medical students from four medical colleges in Bangladesh, we achieved a 76% response rate. Among the participants, 78.24% correctly identified antibiotics' effectiveness against bacterial infections, but 45.71% were uncertain about their efficacy against viral infections. Notably, 21.20% reported self-prescribing antibiotics, predominantly sourced from physician prescriptions (54.89%). The most common reason for antibiotic use was fever (19.02%). Senior students were less likely to have good knowledge compared to junior students, and urban students demonstrated a higher likelihood of good knowledge and positive attitude towards antibiotic resistance., Conclusion: This study highlights the critical need for educational reforms and antimicrobial stewardship among medical students in Bangladesh to combat antibiotic misuse and mitigate antimicrobial resistance., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Background: Experiences of delayed conception and infertility have been reported among women. However, the concept of intersectionality is rarely utilised in studies of infertility, and it is particularly uncommon in research from low- and middle- income countries., Research Question: What are the lived experiences of women with delayed conception in low to -middle income neighbourhoods of Delhi, India?, Methods: This was a qualitative study (n = 35) that recruited women who had failed to conceive after 18 months of regular unprotected sexual intercourse. Data were collected between February and July 2021. Data were collected through focus group discussions in low income to middle income neighbourhoods of Delhi, India. Analysis identified themes related to intersecting axes of inequality., Results: The results showed that gender intersected with economics, masculinity, patriarchal norms and class to influence the experiences of women. The intersection of gender, economics and patriarchal norms compromised women's agency to be active generators of family income, and this dynamic was exacerbated by patrilocal residence. In addition, masculinity contributed to stigmatisation and blaming of women, due to the inaccurate perception that men did not contribute to a couple's infertility. The intersection of gender and social class in medical settings created barriers to women's access to medical information., Conclusion: Findings from this study provide representative examples of the variety of axes of inequality that shape women's experiences in the study setting. Although these findings may not be generalisable to all women who are experiencing delayed conception, they highlight a need for improved awareness and education on infertility, as well as a need to ensure the availability and accessibility of fertility care for couples in need., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Adhikary et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The fifth edition of the WHO classification of tumors of the central nervous system (WHO CNS5) was published in 2021 which is the sixth version of the international standard for the diagnostics of CNS tumors. Regular updates of the consortium to inform molecular and practical approaches to CNS tumor taxonomy (cIMPACT-NOW) shaped the WHO CNS5 which continues the trend of incorporating the molecular characteristics of tumors into the histological and immunohistochemical findings. The various updates can be classified into general changes across all tumors and specific changes within the tumor groups. This mini-review highlights the general changes and the major changes in adult diffuse gliomas., (Copyright © 2024 Copyright: © 2024 Annals of African Medicine.)

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.33-1.55) and a risk allele frequency of ∼18% in Hispanic/Latino populations and <0.5% in European populations. This risk allele was positively associated with Indigenous American ancestry, showed evidence of selection in human history, and was associated with reduced IKZF1 expression. We identified a putative causal variant in a downstream enhancer that is most active in pro-B cells and interacts with the IKZF1 promoter. This variant disrupts IKZF1 autoregulation at this enhancer and results in reduced enhancer activity in B cell progenitors. Our study reveals a genetic basis for the increased ALL risk in Hispanic/Latino children., Competing Interests: Declaration of interests V.G.S. serves as an advisor to and/or has equity in Branch Biosciences, Ensoma, and Cellarity, all unrelated to the present work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Macrophages restrain microbial infection and reinstate tissue homeostasis. The mitochondria govern macrophage metabolism and serve as pivot in innate immunity, thus acting as immunometabolic regulon. Metabolic pathways produce electron flows that end up in mitochondrial electron transport chain (mtETC), made of super-complexes regulating multitude of molecular and biochemical processes. Cell-intrinsic and extrinsic factors influence mtETC structure and function, impacting several aspects of macrophage immunity. These factors provide the macrophages with alternate fuel sources and metabolites, critical to gain functional competence and overcoming pathogenic stress. Mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS) generated through the mtETC are important innate immune attributes, which help macrophages in mounting antibacterial responses. Recent studies have demonstrated the role of mtETC in governing mitochondrial dynamics and macrophage polarization (M1/M2). M1 macrophages are important for containing bacterial pathogens and M2 macrophages promote tissue repair and wound healing. Thus, mitochondrial bioenergetics and metabolism are intimately coupled with innate immunity. In this review, we have addressed mtETC function as innate rheostats that regulate macrophage reprogramming and innate immune responses. Advancement in this field encourages further exploration and provides potential novel macrophage-based therapeutic targets to control unsolicited inflammation., Competing Interests: The authors declare that they have no known commercial, financial interests or personal relationships that could be construed as a potential conflict of interest., (© 2024 The Authors.)

Alba domain proteins, owing to their functional plasticity, play a significant role in organisms. Here, we report an intrinsic DNase activity of PfAlba6 from Plasmodium falciparum , an etiological agent responsible for human malignant malaria. We identified that tyrosine28 plays a critical role in the Mg 2+ driven 5'-3' DNase activity of PfAlba6. PfAlba6 cleaves both dsDNA as well as ssDNA. We also characterized PfAlba6-DNA interaction and observed concentration-dependent oligomerization in the presence of DNA, which is evident from size exclusion chromatography and single molecule AFM-imaging. PfAlba6 mRNA expression level is up-regulated several folds following heat stress and treatment with artemisinin, indicating a possible role in stress response. PfAlba6 has no human orthologs and is expressed in all intra-erythrocytic stages; thus, this protein can potentially be a new anti-malarial drug target., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Gastric cancer (GC) is a deadly malignancy that demands effective therapeutic intervention capitalizing unique drug target/s. Here, we report that indomethacin, a cyclooxygenase non-selective non-steroidal anti-inflammatory drug, arrests GC cell growth by targeting mitochondrial deacetylase Sirtuin 3 (SIRT3). Interaction study revealed that indomethacin competitively inhibited SIRT3 by binding to nicotinamide adenine dinucleotide (NAD)-binding site. The Cancer Genome Atlas data meta-analysis indicated poor prognosis associated with high SIRT3 expression in GC. Further, transcriptome sequencing data of human gastric adenocarcinoma cells revealed that indomethacin treatment severely downregulated SIRT3. Indomethacin-induced SIRT3 downregulation augmented SOD2 and OGG1 acetylation, leading to mitochondrial redox dyshomeostasis, mtDNA damage, respiratory chain failure, bioenergetic crisis, mitochondrial fragmentation, and apoptosis via blocking the AMPK/PGC1α/SIRT3 axis. Indomethacin also downregulated SIRT3 regulators ERRα and PGC1α. Further, SIRT3 knockdown aggravated indomethacin-induced mitochondrial dysfunction as well as blocked cell-cycle progression to increase cell death. Thus, we reveal how indomethacin induces GC cell death by disrupting SIRT3 signaling., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Weed management is an important aspect of crop production, as weeds cause significant losses in terms of yield and quality. Various approaches to weed management are commonly practiced by crop growers. Due to limitations in other control methods, farmers often choose herbicides as a cost-effective, rapid and highly efficient weed control strategy. Although herbicides are highly effective on most weeds, they are not a complete solution for weed management because of the genetic diversity and evolving flexibility of weed communities. The excessive and indiscriminate use of herbicides and their dominance in weed control have triggered the rapid generation of herbicide-resistant weed species. Moreover, environmental losses of active ingredients in the herbicides cause serious damage to the environment and pose a serious threat to living organisms. Scientific advances have enabled nanotechnology to emerge as an innovation with real potential in modern agriculture, adding a new dimension in the preparation of controlled release formulations (CRF) of herbicides. Here the required amount of active ingredients is released over longer periods of time to obtain the desired biological efficacy whilst reducing the harmful effects of these chemicals. Various organic and inorganic carrier materials have been utilised in CRF and researchers have a wide range of options for the synthesis of eco-friendly carrier materials, especially those with less or no toxicity to living organisms. This manuscript addresses the history, progress, and consequences of herbicide application, and discusses potential ways to reduce eco-toxicity due to herbicide application, along with directions for future research areas using the benefits of nanotechnology., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Disease and therapy-related hypoproliferative thrombocytopenia is a significant barrier to managing acute lymphoblastic leukaemia (ALL) patients. To reduce the risk of haemorrhage, apheretic platelet transfusion is a modern, effective, and expensive option. Since most ALL patients in Bangladesh have financial constraints, this study can shed light on the magnitude of benefit regarding the effectiveness of apheretic platelet prophylactically and therapeutically in children of ALL receiving induction chemotherapy., Materials and Methods: This observational cross-sectional study was conducted in the department of transfusion medicine and the department of paediatric haematology and oncology at a tertiary level hospital in Bangladesh from June 2020 to June 2021. A total of 33 cases of ALL were enroled in this study according to inclusion and exclusion criteria. After receiving written informed consent, relevant data were collected using a face-to-face interview with the guardian of the patients, thorough clinical examination, and relevant investigation. After the collection of all the required data, analysis was done by Stata (v.16)., Results: Mean age of the patients was 7.39±4.46 (SD), ranging from 1 to 18 years. The majority of children were aged younger than or equal to 10 years (69.70%). Male children were slightly predominant (51.5%). Significant post-transfusion platelet increment (Median pre-transfusion count 16×10 3 /μl vs. Median post-transfusion count 133×10 3 /μl, P <0.001) was observed. WHO bleeding grades also improved after apheretic platelet transfusion ( P <0.05). Age was a significant factor associated with corrected count increment (CCI) in both univariate and multivariate analysis. In subgroup analysis, age and gender were significant predictors of CCI in therapeutic transfusion group but not in prophylactic transfusion group., Conclusions: Significant improvement in bleeding status and platelet count was observed following apheretic platelet transfusion., Competing Interests: The authors have declared that they have no competing interests.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Substance abuse by adolescents and young adults is a major public health issue. This study aimed to (i) show the transition of sociodemographic and substance abuse characteristics from 1992 to 2017 among US adolescents and young adults, (ii) evaluate the likelihood of co-occurrence of substances, and (iii) identify significant sociodemographic characteristics in association with polysubstance abuse., Methods: This study extracted data for adolescents and young adults from 1992 and 2017 Treatment Episode Data Set-Admission (TEDS-A) datasets. The extracted sample included 337858 admissions in 1992 and 333322 in 2017., Findings: Both years experienced significant admissions. A significant transition in 2017 compared to 1992 was evident in education, living status, and ethnicity. Substance-specific transition showed alcohol was dominant in 1992, while marijuana/ hashish was dominant in 2017. Also, heroin, other opiates/synthetics, and methamphetamine experienced an increase, while cocaine/crack decreased. The pairwise co-occurrences exhibited a considerable variation in the likelihood of using one substance given another one. The odds ratios (ORs) obtained from generalized ordered logit models showed significantly higher odds of one or more substances with age, while education showed the opposite scenario. A mixed effect of gender was evident in 1992, whereas females were significantly less likely with one or more substances than males in 2017. Other significant vulnerable groups were those not in the labor force, homeless, white, and Mexican Americans., Conclusion: The findings may help to understand the overall changes between 1992 and 2017 and take necessary measures to reduce the burden of this public health problem., Competing Interests: Competing Interests The authors report no conflict of interest., (© 2024 Kerman University of Medical Sciences.)

Introduction: The outcome of recurrent/metastatic gynaecological malignancy has drastically improved with the introduction of poly(ADP-ribose) polymerase inhibitors and immunotherapy, but the use of these drugs in routine practice is complicated due to access barriers and their high cost in developing countries. The purpose of this study is to present the clinical response, outcome and safety of oral metronomic chemotherapy (OMCT) in resource-limited, financially constrained populations., Methods: This is a retrospective study on patients with advanced gynaecological cancer treated at Chittaranjan National Cancer Institute, Kolkata, India, from 2021 to 2023. The patients were treated with one of these two regimens: a split-dose course of cyclophosphamide (50 mg orally once daily for 21 days) and capecitabine (500 mg twice daily continuous) or a fixed-dose combination (capecitabine 1800 mg and cyclophosphamide 80 mg orally for 14 days in every 21 days) until disease progression or unacceptable toxicities occurred. All data was captured from the hospital's medical records until June 2023. Toxicity data was reported per the Common Terminology Criteria for Adverse Events (CTCAE) v5.1, and progression-free survival (PFS) was estimated using Kaplan-Meier methods., Results: Among 34 screened patients, 10 were excluded due to noncompliance. This study analysed 24 patients with a median age at diagnosis of 56 years (IQ range 44-75). Sixteen (67%) patients were at stage IV disease with an Eastern Cooperative Oncology Group (ECOG) performance status of 3. Ovarian and cervical cancers were 80% and 20%, respectively; among them, 16 (67%) patients were platinum-refractory. Forty-two per cent of patients received three lines of chemotherapy before OMCT. A split course versus fixed dose was given to 67% versus 33% of the population; the best responses per the Response Evaluation Criteria in Solid Tumours v1.1 were complete response in 12%, partial response in 67% and stable disease in 21%. The most common toxicities were grade I anaemia (54%), grade I chemotherapy-induced nausea and vomiting (46%), grade I fatigue (42%) and grade I neutropenia (21%). Twenty-five per cent of patients were offered next-line systemic therapy after progression. The entire cohort had a median PFS of nine months (95%, CI: 5.2-12.7). Cox regression analysis identified a median PFS of 12 months (95%, CI: 6.2-17.7) among platinum-refractory groups., Conclusion: OMCT was a well-tolerated, affordable regimen with durable clinical response and survival outcome (median PFS of nine months) in recurrent, refractory advanced gynaecological cancer and can be offered to patients at resource-limited centres., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ghosh et al.)

Aim: This study aimed to investigate the career preferences among Bangladeshi medical students, identify the factors that influence their present choices, and additionally report the role of gender and academic year behind their decisions., Methods: This cross-sectional study conducted in Bangladesh from August 2022 to April 2023 included 801 medical students conveniently selected from medical colleges in eight divisions. Data were collected using a web-based survey and analysed using STATA version 16.0. Statistical tests included the Kolmogorov-Smirnov test, arithmetic mean, standard deviation, frequency, and Kruskal-Wallis H test. The response rate was 94.6%, and the CHERRIES guideline was followed for reporting the results., Result: The majority of the participants were female (64.42%) and under the age of 23 years (58.8%). The study revealed that medicine was the preferred career choice for the majority of students (65%), with surgery being the most popular first choice (30.21%) among them. Female medical students showed a significantly higher preference for gynaecology & obstetrics (p < 0.001), while male students had a significantly higher tendency to choose general practice (p = 0.002). There is a significant gender difference (p < 0.05) in the career preference factors, including professional prestige, role model influence, easy money, family time, promotion opportunities, income for lifestyle, and research opportunities. Academic year differences were also observed, with increasing interest in medicine and public health (p < 0.001), a decrease in interest in surgery (p < 0.001), and a decline in preference for non-medical careers as students progressed through their MBBS life (p < 0.05)., Conclusion: Overall, medicine was the most popular speciality choice, however, male students preferred general practice and female students preferred gynaecology and obstetrics more. Personal passion, opportunities for contribution to society, professional prestige, having a direct dealing with patients, and income will allow an enjoyable lifestyle were the most important factors in the choice of their career., (© 2024. The Author(s).)

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions., Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment., Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022., Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods., Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool., Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group., Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation., Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

Objectives: This study aims at exploring the effects of physicians' communication behaviors on patients' satisfaction in primary care medical consultations in Chattogram, Bangladesh. The study used a quantitative research approach designed with a cross-sectional survey., Methods: Data were collected using post-consultation and facilitator administered questionnaire from the patients who visited the physician for medical consultation in different hospitals and clinics in Chattogram city. Seven hundred patients were included as the study participants. A hierarchical linear regression analysis was performed to examine the factors contributing to the outcome variables., Results: A statistically significant difference ( P  < .001) appeared regarding patients' perception of adequate consultation, physicians' nonverbal behavior, inhibiting behavior and patients' participating behavior in private and public settings. However, R 2 value shows that physicians' patient-centered behaviors appeared as the stronger predictors of patient satisfaction toward medical interviews, followed by socioeconomic variables of patients and physicians and patients' participation during the consultation. Presence of a third person with patients during consultation (β = -.05, P  = .040), physicians' private setting of consultation (β = .16, P  < .001), physicians' seniority (β = .05, P  = .042), patients' participating behavior during consultation (β = .20, P  < .001), physicians' nonverbal behavior (β = .10, P  < .001), physicians' inhibiting behavior (β = -.39, P  < .001), and physicians' facilitating behavior with patients (β = .32, P  < .001) were reported as the influencing factors of patients' satisfaction with medical consultation., Conclusion: This study suggests the profound impact of physicians' patient-centered communication behaviors on patient satisfaction in primary care settings, overshadowing even socioeconomic factors and patient participation., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Posterior reversible encephalopathy syndrome (PRES) is a pathology seen not only in precelampsia with severe symptoms and eclampsia but in a varicty of diseases/ conditions. With the availability of neuroimaging, it is possible to know the exact underlying Central nervous system (CNS) pathology in preeclampsia with severe symptoms and eclampsia and thus therapy can be targeted. Preeclampsia with severe symptoms and eclampsia remains to be an important cause of maternal morbidity and mortality in both the developing and developed world. The objective of this study was to evaluate the association of Posterior reversible encephalopathy syndrome (PRES) by MRI (Magnetic resonance imaging) with preeclampsia with severe symptoms and eclampsia in south east part of Bangladesh. This cross-sectional observational study was performed among women suffering from preeclampsia with severe symptoms and eclampsia who attended at Obstetrics & Gynaecology department of Chittagong Medical College Hospital (CMCH), Bangladesh from January 2021 to June 2021. According to inclusion/exclusion criteria 50 samples were taken by convenient sampling for this study. A detail history was taken and complete general physical and gynecological examination was performed. Required data was collected through preset questionnaire. Neuroimaging reports were reviewed by both neurologist and radiologist. Data was analyzed by using windows based computer software device, SPSS 25.0. Results obtained from this study will be used to make a statement regarding aggressive management for cerebral vasospasm in severe preeclampsia and eclamptia related PRES. PRES has been reported to be reversible but late recognition or incorrect treatment can cause irreversible brain damage. Institution of early treatment leads to resolution of symptoms without any neurologic deficit and thus reduces maternal morbidity and mortality. PRES is a cliniconeuroradiologic entity. This study can aware doctors regarding prompt diagnosis of PRES in peripartum period among patient suffering from preeclampsia with severe symptoms and eclampsia by imaging aside clinical findings. A conclusive decision can be made to improve the outcome in this potentially life threatening but reversible condition.

Fewer than 30 cases of Mycobacterium senegalense infection have been reported. We report a complicated case of M. senegalense infection in Memphis, Tennessee, in the southeastern United States. The patient's comorbidities of past organ transplant and insulin-dependent diabetes required delicate consideration of those health conditions to guide treatment.

Importance: Cellulose diacetate (CDA) is a promising alternative to conventional plastics due to its versatility in manufacturing and low environmental persistence. Previously, our group demonstrated that CDA is susceptible to biodegradation in the ocean on timescales of months. In this study, we report the composition of microorganisms driving CDA degradation in the coastal ocean. We found that the coastal ocean harbors distinct bacterial taxa implicated in CDA degradation and these taxa have not been previously identified in prior CDA degradation studies, indicating an unexplored diversity of CDA-degrading bacteria in the ocean. Moreover, the shape of the plastic article (e.g., a fabric, film, or foam) and plasticizer in the plastic matrix selected for different microbial communities. Our findings pave the way for future studies to identify the specific species and enzymes that drive CDA degradation in the marine environment, ultimately yielding a more predictive understanding of CDA biodegradation across space and time., Competing Interests: The authors declare no conflict of interest.

Patients with multiple myeloma (MM), an age-dependent neoplasm of antibody-producing plasma cells, have compromised immune systems and might be at increased risk for severe COVID-19 outcomes. This study characterizes risk factors associated with clinical indicators of COVID-19 severity and all-cause mortality in myeloma patients utilizing NCATS' National COVID Cohort Collaborative (N3C) database. The N3C consortium is a large, centralized data resource representing the largest multi-center cohort of COVID-19 cases and controls nationwide (>16 million total patients, and >6 million confirmed COVID-19+ cases to date). Our cohort included myeloma patients (both inpatients and outpatients) within the N3C consortium who have been diagnosed with COVID-19 based on positive PCR or antigen tests or ICD-10-CM diagnosis code. The outcomes of interest include all-cause mortality (including discharge to hospice) during the index encounter and clinical indicators of severity (i.e., hospitalization/emergency department/ED visit, use of mechanical ventilation, or extracorporeal membrane oxygenation (ECMO)). Finally, causal inference analysis was performed using the Coarsened Exact Matching (CEM) and Propensity Score Matching (PSM) methods. As of 05/16/2022, the N3C consortium included 1,061,748 cancer patients, out of which 26,064 were MM patients (8,588 were COVID-19 positive). The mean age at COVID-19 diagnosis was 65.89 years, 46.8% were females, and 20.2% were of black race. 4.47% of patients died within 30 days of COVID-19 hospitalization. Overall, the survival probability was 90.7% across the course of the study. Multivariate logistic regression analysis showed histories of pulmonary and renal disease, dexamethasone, proteasome inhibitor/PI, immunomodulatory/IMiD therapies, and severe Charlson Comorbidity Index/CCI were significantly associated with higher risks of severe COVID-19 outcomes. Protective associations were observed with blood-or-marrow transplant/BMT and COVID-19 vaccination. Further, multivariate Cox proportional hazard analysis showed that high and moderate CCI levels, International Staging System (ISS) moderate or severe stage, and PI therapy were associated with worse survival, while BMT and COVID-19 vaccination were associated with lower risk of death. Finally, matched sample average treatment effect on the treated (SATT) confirmed the causal effect of BMT and vaccination status as top protective factors associated with COVID-19 risk among US patients suffering from multiple myeloma. To the best of our knowledge, this is the largest nationwide study on myeloma patients with COVID-19., (© 2023. The Author(s).)

Cobalt-chromium-molybdenum (CoCrMo) alloys are widely used in orthopedic implants due to their excellent corrosion and wear resistance and superior mechanical properties. However, their limited capability to promote cell adhesion and new bone tissue formation, poor blood compatibility, and risk of microbial infection can lead to implant failure or reduced implant lifespan. Surface structure modification has been used to improve the cytocompatibility and blood compatibility of implant materials and reduce the risk of infection. In this study, we prepared CoCrMo alloys with surface nanostructures of various aspect ratios (AR) using laser-directed energy deposition (L-DED) and biocorrosion. Our results showed that medium and high AR nanostructures reduced platelet adhesion, while all of the alloys demonstrated good blood compatibility and antibacterial properties. Moreover, the medium and high AR nanostructures promoted cell adhesion and spreading of both preosteoblast MC3T3 cells and human bone marrow mesenchymal stem cells (hMSCs). Furthermore, the nanostructure promoted the osteogenic differentiation of both cell types compared with the flat control surface, with a substantial enhancing effect for the medium and high ARs. Our study proposes a promising approach for developing implant materials with improved clinical outcomes., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Oral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) is the most common cancer among men in India, and is associated with poor prognosis and frequent recurrence. Cellular heterogeneity in OSCC-GB was investigated by single-cell RNA sequencing of tumors derived from the oral cavity of 12 OSCC-GB patients, 3 of whom had concomitant presence of a precancerous lesion (oral submucous fibrosis [OSMF]). Unique malignant cell types, features, and phenotypic shifts in the stromal cell population were identified in oral tumors with associated submucous fibrosis. Expression levels of FOS, ATP1A, and DUSP1 provided robust discrimination between tumors with or without the concomitant presence of OSMF. Malignant cell populations shared between tumors with and without OSMF were enriched with the expression of partial epithelial-mesenchymal transition (pEMT) or fetal cell type signatures indicative of two dominant cellular programs in OSCC-GB-pEMT and fetal cellular reprogramming. Malignant cells exhibiting fetal cellular and pEMT programs were enriched with the expression of immune-related pathway genes known to be involved in antitumor immune response. In the tumor microenvironment, higher infiltration of immune cells than the stromal cells was observed. The T cell population was large in tumors and diverse subtypes of T cells with varying levels of infiltration were found. We also detected double-negative PLCG2 + T cells and cells with intermediate M1-M2 macrophage polarization. Our findings shed light on unique aspects of cellular heterogeneity and cell states in OSCC-GB., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: Sarcopenia refers to a reduction in skeletal muscle mass and strength. Despite the known association between single-slice muscle measurements on lumbar computed tomography and poor outcomes in various clinical settings, studies using thoracic muscle measurements on cardiac magnetic resonance imaging (CMR) have been limited., Methods: Patients undergoing surgical aortic valve replacement (SAVR) between 2010 and 2020 were included if they were ≥ 50 years of age with preoperative CMR. Manual unilateral pectoralis major and minor skeletal muscle area measurements were made at the carina and normalized for body size by height to obtain skeletal muscle index (SMI). Sarcopenia was defined as the lowest sex-stratified SMI tertile and higher-risk as the highest fiftieth percentile Society of Thoracic Surgeons' (STS) mortality score., Results: A total of 133 patients were included, 35 (26.3%) females. The average age was 64 ± 9 years, with most Caucasian (93.2%). Compared to non-sarcopenic patients, sarcopenic patients were older with lower body mass index. During a median follow-up of 27.3 (7.6-60.4) months, 10 (22.2%) deaths occurred in the sarcopenic group and 8 (9.1%) in the non-sarcopenic group (p = 0.039 by log-rank test). On subgroup analysis (66 patients), higher-risk sarcopenic patients had 10 (37.0%) deaths compared to 8 (20.5%) in higher-risk non-sarcopenic patients (p = 0.011 by log-rank test)., Conclusions: Simple unilateral pectoralis muscle measurements on preoperative CMR can be used as an adjunct to traditional risk scores for predicting mortality post-SAVR., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients with concomitant frontotemporal dementia (FTD)., Objective: In order to improve current understanding of the presence and relevance of pathological pTDP-43 subtypes in ALS, the present study examined the pattern of cortical pTDP-43 aggregates in 61 ALS cases without FTD., Results: Based on the presence, morphology and composition of pTDP-43 pathology, three distinct ALS-TDP subtypes were delineated: (1) A predominant pattern of pTDP-43 granulofilamentous neuronal inclusions (GFNIs) and grains that were immuno-negative for p62 was identified in 18% of cases designated ALS-TDP type E; (2) neuronal cytoplasmic inclusions (NCIs) that were immuno-positive for both pTDP-43 and p62 were observed in 67% of cases assigned ALS-TDP type B; and (3) scarce cortical pTDP-43 and p62 aggregates were identified in 15% of cases coined ALS-TDP type SC (scarce cortical). Quantitative analyses revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E. Principal component analysis demonstrated significant relationships between GFNIs, grains and ALS-TDP subtypes to support the distinction of subtypes E and B. No significant difference in age at death or disease duration was found between ALS-TDP subgroups to suggest that these subtypes represent earlier or later stages of the same disease process. Instead, a significantly higher ALS-TDP stage, indicating greater topographical spread of pTDP-43, was identified in ALS-TDP type E. Alzheimer's disease neuropathological change (ABC score ≥ intermediate) and Lewy body disease (Braak stage ≥ IV) was more prevalent in the ALS-TDP type SC cohort, which also demonstrated a significantly lower overall cognitive score., Conclusion: In summary, the present study demonstrates that ALS-TDP does not represent a single homogenous neuropathology. We propose the subclassification of ALS-TDP into three distinct subtypes using standard immuno-stains for pTDP-43 and p62 in the motor cortex, which is routinely sampled and evaluated for diagnostic neuropathological characterisation of ALS. We propose that future studies specify both clinicopathological group and pTDP-43 subtype to advance current understanding of the pathogenesis of clinical phenotypes in pTDP-43 proteinopathies, which will have significant relevance to the development of targeted therapies for this heterogeneous disorder., (© 2023. The Author(s).)

Background and Purpose: Mitochondrial oxidative stress, inflammation and apoptosis primarily underlie gastric mucosal injury caused by the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Alternative gastroprotective strategies are therefore needed. Sirtuin-3 pivotally maintains mitochondrial structural integrity and metabolism while preventing oxidative stress; however, its relevance to gastric injury was never explored. Here, we have investigated whether and how sirtuin-3 stimulation by the phytochemical, honokiol, could rescue NSAID-induced gastric injury., Experimental Approach: Gastric injury in rats induced by indomethacin was used to assess the effects of honokiol. Next-generation sequencing-based transcriptomics followed by functional validation identified the gastroprotective function of sirtuin-3. Flow cytometry, immunoblotting, qRT-PCR and immunohistochemistry were used measure effects on oxidative stress, mitochondrial dynamics, electron transport chain function, and markers of inflammation and apoptosis. Sirtuin-3 deacetylase activity was also estimated and gastric luminal pH was measured., Key Results: Indomethacin down-regulated sirtuin-3 to induce oxidative stress, mitochondrial hyperacetylation, 8-oxoguanine DNA glycosylase 1 depletion, mitochondrial DNA damage, respiratory chain defect and mitochondrial fragmentation leading to severe mucosal injury. Indomethacin dose-dependently inhibited sirtuin-3 deacetylase activity. Honokiol prevented mitochondrial oxidative damage and inflammatory tissue injury by attenuating indomethacin-induced depletion of both sirtuin-3 and its transcriptional regulators PGC1α and ERRα. Honokiol also accelerated gastric wound healing but did not alter gastric acid secretion, unlike lansoprazole., Conclusions and Implications: Sirtuin-3 stimulation by honokiol prevented and reversed NSAID-induced gastric injury through maintaining mitochondrial integrity. Honokiol did not affect gastric acid secretion. Sirtuin-3 stimulation by honokiol may be utilized as a mitochondria-based, acid-independent novel gastroprotective strategy against NSAIDs., (© 2023 British Pharmacological Society.)