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Objectives: Both superficial (s) and deep (d) serratus anterior plane (SAP) blocks are effective for anterior chest wall surgeries, but there is little clarity on which is more effective. Hence, we conducted a systematic review and meta-analysis of randomized control trials (RCT) to evaluate the comparative efficacy of the two approaches for SAP block after anterior chest wall surgery., Materials and Methods: A systematic literature search was performed using PubMed, Embase, Scopus, and Cochrane Central Registers of Controlled Trials for eligible RCTs from inception until August 2023. The primary outcome was opioid consumption during the first 24 hours of the postoperative period. The secondary outcomes included pain scores at various intervals, intraoperative opioid consumption, time to first analgesic request, block-related complications, opioid-related side effects, and patient satisfaction scores. Statistical analysis of the pooled data was performed using Review Manager Version 5.3., Results: We identified seven RCTs published between 2020 and 2022, enrolling 371 patients (186 in the sSAP block and 187 in the dSAP block). Moderate certainty of evidence suggests that both the approaches (deep and superficial) of SAP block were comparable for 24-hour oral morphine equivalent consumption with a mean difference (MD) of 3.78 mg (95% CI -1.70 to 9.29; P=0.18; I2=87%). The results of other secondary outcomes were comparable, including resting pain scores with an MD of 0.08 (95% CI -0.27 to 0.43; P=0.67; I2=87%) for early pain and MD of 0.63 (95% CI -1.28 to 0.01; P=0.05; I2=95%) for late pain scores, time to first analgesic request with MD of -0.41 hour (95% CI -1.40 to 0.59; P=0.42; I2=90%), and incidence of PONV (OR, 1.45 (95% CI 0.72 to 2.90; P=0.30; I2=0%)., Discussion: Current evidence does not support the preference for one approach of SAP block over the other for postoperative pain. Based on the available data, we recommend further future trials to determine any differences between these interventions., Competing Interests: Conflict of interest: None, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The emergence of hypervirulent strains of Acinetobacter baumannii poses a significant threat in intensive care units (ICU). This study aimed to molecularly characterize hypervirulent A. baumannii strains isolated from ICU patients with respiratory infections. Six strains were isolated from ICU patients over one month. Isolates were identified by phenotypic characterization biochemical properties and 16s RNA sequencing. Antibiotic susceptibility testing was conducted followed by resistance genes detection by PCR. MLST, and PFGE were employed to analyse clonal relationships among strains. Plasmid replicon typing and plasmid transmission frequencies were determined. The isolated strains exhibited diverse clinical manifestations, including acute respiratory distress syndrome (ARDS). Antibiotic susceptibility testing revealed multidrug-resistance phenotype. Molecular analysis revealed a complex genetic landscape of antibiotic resistance genes, including ESBLs and carbapenemases, as well as virulence genes such as omp A, csu E, and exo S. The multiple sequence types indicating genetic diversity among the strains as ST1512, ST622, and ST149 (each type two isolates). Plasmid characterization revealed the presence of diverse replicon types associated with multidrug resistance. This study provides comprehensive insights into the phenotypic, molecular, and epidemiological characteristics of hypervirulent A. baumannii outbark in ICU., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Jinjun Qiu et al.)

Background: Vagal schwannomas are well-documented, but cervical sympathetic chain schwannomas (CSCS) are rare, with most knowledge from case reports. This study aims to identify radiological predictors of misdiagnosis and factors guiding surgical approaches based on tumor size and extent., Methods: An ambispective analysis was conducted on 21 cases of CSCS, examining preoperative data, intraoperative findings and the questionnaire to identify the potential predictors. Tumors were classified into three types based on their relationship with the carotid sheath, and this classification was correlated with vessel ligation and postoperative neural outcomes., Results: An excellent agreement was found between radiologist on new classification system(Kappa:0.89). Tumor classification revealed a diverse distribution, with 6 cases identified as Type 1, 6 as Type 2, 5 as Type 3, and 4 as Type 3S. The necessity of external carotid artery (ECA) ligation correlated with the tumor type. Type 3 tumors required ECA ligation in 50% of cases, while Type 1 and Type 2 tumors predominantly involved vascular preservation. Postoperative complications included vagal palsy in 28.5% of cases and first bite syndrome in 71.4%., Conclusion: Accurate preoperative planning and a novel staging system can enhance surgical outcomes and reduce postoperative complications as validated by our study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Neuroendocrine breast cancers (NEBCs) are a rare and distinct subtype of breast tumors, characterized by their neuroendocrine differentiation. Despite accounting for less than 1% of all breast cancers, NEBCs present unique diagnostic and therapeutic challenges due to their heterogeneous nature and variable prognosis. Accurate imaging plays a crucial role in the diagnosis, treatment planning, and follow-up of NEBCs, yet remains a complex area due to the rarity of these tumors and overlapping features with more common breast cancers. We present a series of 4 cases of primary NEBC, emphasizing the imaging features and their histopathological correlations. All patients presented with breast lump. Diagnostic Mammography followed by Ultrasound was performed in each case. All 4 cases were categorized as Breast Imaging- Reporting and Data System (BI-RADS)-4. Trucut biopsy was performed and histopathological analysis revealed the diagnosis of NEBC. Patients underwent Surgery followed by Chemotherapy, Hormonal Therapy or Radiation therapy alone or in combination with each other depending upon the histopathological characteristics., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Introduction: Blood request form (BRF) stands as a pivotal document in ensuring safe and effective blood transfusions within healthcare settings. Incomplete or erroneous data on BRF can heighten risk of adverse reactions and compromise patient safety. Aim of study was to assess level of completion of BRFs by clinicians and to evaluate root cause analysis (RCA) of incompleteness of BRFs and factors leading to their rejection., Materials and Methods: This prospective study was carried out from February 2024 to April 2024 on BRFs received in the blood centre. They were audited and RCA for factors leading to their incompleteness and rejection were analysed., Results: Total number of BRFs received in blood centre was 14,468. 13,358 (92.3%) BRFs were accepted and 1,110 (7.7%) BRFs were rejected. 12,804 (95.85%) of accepted BRFs were incomplete. Weight was the most common missing parameter (89% {n = 11403}) while name of the requesting clinician was least common (2.5% {n-318}). 3.52% n = 510) BRFs were rejected due to mismatch in name and patient registration number on BRF and samples. 0.14% n = 21) BRFs were rejected due to hemolysed samples. RCA for incompleteness of BRFs showed that main reason was manpower (61-83%) while environment was least common (17-67%). RCA for rejection of BRFs showed that environment was most common cause (13.3-80.15%) while manpower was least common (9-19.85%)., Conclusion: Regular audits and personnel training, and quality assurance measures can help identify and address deficiencies in BRF completion to enhance patient safety and reduce incidence of transfusion-related errors and complications., (Copyright © 2024 Society francophone de transfusion sanguine (SFTS). Published by Elsevier Masson SAS. All rights reserved.)

Background: Multidisciplinary teams (MDT) aid the diagnosis and management of patients with inflammatory bowel disease (IBD) and improve patient outcomes. The direct impact of a gastrointestinal expert pathologist on MDT care of IBD patients is unknown., Methods: A retrospective chart review was conducted evaluating all cases (N = 289) discussed at the IBD MDT conference at Carilion Roanoke Memorial Hospital from June 1, 2013, through December 31, 2019. Cases were discussed between 1 and 6 times at the conference. Data collected included demographics, diagnosis before and after conference, reason for diagnostic change, endoscopy findings, medications, surgeries, and clinical follow-up., Results: Approximately 15% to 42% of patients had a change in diagnosis after the first 3 conferences. The majority of diagnostic changes after the first (84%), second (73%), and third (67%) conferences were due to expert pathologist interpretation. Indeterminate colitis was the most frequently changed diagnosis, and Crohn's disease was the most common new diagnosis after conference. Among patients with a diagnostic change, 28.6% to 38.5% of patients had a change in their IBD medication regimen, and 7.7% to 10.9% had a surgical intervention after the first 2 conferences. Approximately 54.2% to 60% of patients reported clinical improvement or remission within 6 months of the first 3 conferences., Conclusion: The majority of diagnostic changes made at the multidisciplinary IBD conference were due to histopathologic re-interpretation. A change in diagnosis at times led to significant modifications in medical or surgical management. An expert gastrointestinal pathologist is an essential MDT member for IBD management., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

To study the clinical, laboratory profile and outcome of juvenile Systemic Lupus Erythematosus (jSLE) patients at a tertiary care centre in South India. A retrospective review of the medical records of all jSLE patients visiting the Pediatric Immunology and Rheumatology Unit, Aster CMI Hospital, India from February 2017 to December 2023 was performed. The clinical characteristics, treatment and outcomes were recorded and tabulated. Seventy patients diagnosed with jSLE were included in the study. The female-to-male ratio was 4.4:1. Mean age at onset and delay in diagnosis were 120.1 (+/- 56.8) and 11.7 (+/- 22.7) months respectively. The median follow-up period was 13 months (range 4, 29 months). Nine patients presented with early onset SLE (< 5 years). Most common manifestations were constitutional symptoms (n = 56), followed by haematologic (n = 55), and mucocutaneous(n = 50) involvement. Immunological workup showed SLE-specific antibody positivity in 38 patients, hypocomplementemia in 40 patients, and anti-phospholipid antibody positivity in 13 patients. Mortality was observed in five patients with LN while there was no mortality in the non-nephritis group (p 0.004). C1q deficiency was the most common cause of monogenic lupus seen in 5/9 patients; protein kinase C delta (PRKCD) defect and chronic granulomatous disease (CYBB mutation) were seen in one patient each. We describe a large cohort of jSLE from Southern India. Lupus nephritis was noted in 35.7% of our cohort and had a direct correlation with mortality. 10% of patients had monogenic lupus. Serious infections were more frequent in patients with monogenic lupus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study investigates the toxic effects of the insecticide spinetoram on the model organism Bombyx mori (Linnaeus) and explores the potential ameliorative properties of O-Vanillin. Sub-lethal concentrations of spinetoram were given to silkworm larvae via oral feed, resulting in reduced body weight, larval length, and impaired cocoon characteristics. A study of the enzymatic and non-enzymatic antioxidants revealed oxidative stress in the gut, fat body, and silk gland tissues, characterized by decreased antioxidants and increased lipid peroxidation. However, post-treatment with O-Vanillin effectively mitigated these toxic effects, preserving antioxidant capacities and preventing lipid peroxidation. Additionally, O-Vanillin prevented the loss of body weight and improved cocoon characteristics. At the histological level, spinetoram exposure caused mild histological damage in the gut, fat body, and silk gland. However, O-Vanillin post-treatment had ameliorative effects and mitigated the histological damages. To delve deeper into the mechanism of amelioration of O-Vanillin, in silico studies were used to study the interaction between an important xenobiotic metabolism protein of the Bombyx mori, i.e., Cytochrome p450, specifically CYP9A19, and O-Vanillin. We performed blind molecular docking followed by molecular dynamic simulation, and the results demonstrated stable binding interactions between O-Vanillin and CYP9A19, a cytochrome P450 protein in silkworm, belonging to the subfamily CYP9A, suggesting a potential role for O-vanillin in modulating xenobiotic metabolism., (© 2024. Sociedade Entomológica do Brasil.)

Introduction: Childhood cancers are a significant global health concern, particularly in low- and middle-income countries (LMICs), where over 80% of childhood cancer patients reside. In India, acute myeloid leukemia (AML) constitutes a significant portion of childhood cancers; however, the data on the cost-effectiveness of childhood AML treatment in India and other LMICs remain limited., Methods: The study focused on children (<15 years of age) diagnosed with AML at a tertiary care cancer center in North India. Data, including treatment outcome, treatment-related morbidity, mortality, and costs were retrospectively collected from the electronic medical record and hospital database. Cost-effectiveness was assessed using disability-adjusted life years (DALY) averted in relation to the country-specific cost-effectiveness threshold., Results: Among 59 AML patients, treatment-related high mortality rates, abandonment, and limited access to bone marrow transplantation were notable challenges. Intensive chemotherapy resulted in substantial sepsis-related complications, with treatment-related mortality reaching 30%. The 3-year event-free survival and overall survival of the 43 patients who received intensive therapy were 24.5% ± 7.6% and 27.9% ± 8.3%, respectively. Despite these challenges, treating childhood AML was still found to be cost-effective. The total cost per newly diagnosed patient treated with curative intent was $4454. Cost per DALY averted accounted for 24% of the gross domestic product (GDP) per capita, rendering the treatment to be cost-effective with a stringent cost-effectiveness threshold utilized., Conclusion: The study underscores the challenges faced while treating childhood AML in LMICs, including treatment-induced high sepsis-related mortality and abandonment. Despite these challenges, it remains cost-effective to treat childhood AML in India. Future efforts should focus on reducing treatment-related morbidity and mortality to further improve outcomes and cost-effectiveness., (© 2024 The Author(s). Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Biopolymers are highly desirable alternatives to petrochemical-based plastics owing to their biodegradable nature. The production of bioplastics, such as polyhydroxyalkanoates (PHAs), has been widely reported using various bacterial cultures with substrates ranging from pure to biowaste-derived sugars. However, large-scale production and economic feasibility are major limiting factors. Now, using algal biomass for PHA production offers a potential solution to these challenges with a significant environmental benefit. Algae, with their unique ability to utilize carbon dioxide as a greenhouse gas (GHG) and wastewater as feed for growth, can produce value-added products in the process and, thereby, play a crucial role in promoting environmental sustainability. The sugar recovery efficiency from algal biomass is highly variable depending on pretreatment procedures due to inherent compositional variability among their cell walls. Additionally, the yields, composition, and properties of synthesized PHA vary significantly among various microbial PHA producers from algal-derived sugars. Therefore, the microalgal biomass pretreatments and synthesis of PHA copolymers still require considerable investigation to develop an efficient commercial-scale process. This review provides an overview of the microbial potential for PHA production from algal biomass and discusses strategies to enhance PHA production and its properties, focusing on managing GHGs and promoting a sustainable future.

Background: In 2021, Nigeria had an estimated 1.9 million people living with the human immunodeficiency virus (PLHIV) and 1.7 million (90%) on antiretroviral therapy (ART). Study Design: A systematic review and meta-analysis., Methods: This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. We searched PubMed, Embase, PsychINFO, CINAHL, Global Index Medicus, and Cochrane Library. Studies were included if they reported on ART retention in care among PLHIV in Nigeria. The random-effects meta-analyses were used to combine the studies that had complete retention data. The I 2 statistic was used to assess the heterogeneity of the studies. A sensitivity analysis was then done by conducting a leave-one-out analysis. Afterward, data were analyzed using STATA version 18., Results: The search yielded 966 unique articles, of which 52 studies met the inclusion criteria for the meta-analysis, and four experimental studies were split into their component arms. The total number of study participants was 563,410, and the pooled retention rate was 72% (95% CI: 67%, 76%; I 2 =99.9%; n=57). Sub-analysis showed that the Southeast region of Nigeria had the highest retention of 86% (95% CI: 78%, 92%), and the South-South had the lowest retention (58%; 95% CI: 38%, 79%)., Conclusion: In Nigeria, the pooled ART retention rate is less than optimal to achieve the UNAIDS goal of 95%, thus developing new models for ART retention is needed., (© 2024 The Author(s); Published by Hamadan University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Diabetes Mellitus (DM) is the sixth leading cause of mortality and morbidity in the world. Early diagnosis and periodic monitoring are mandatory to prevent complications. The custom of noninvasive exfoliative cytology diagnostic technique is the need of the hour in diabetes, where the invasive methods lose viability. The purpose of this meta-analysis is to analyze the cytomorphometric changes in the exfoliated cells of the oral mucosa, as an adjunct to the diagnosis of type II diabetes. A thorough search was made by using PubMed, Google Scholar, and Cochrane Library databases. Original research articles, that evaluated cytomorphometric parameters (nuclear area, cytoplasmic area, cytoplasmic nuclear ratio) in type II diabetes patients were included in this review. Risk of bias was analysed for each study using Joanna Briggs Institute and Review Manager was used for meta-analysis. All nine subgroups included for qualitative and quantitative data synthesis revealed that there was a significant increase in nuclear area and a decrease in cytoplasmic nuclear ratio in diabetic patients as compared to non-diabetics. Random-effects model also confirmed cytologically altered (nuclear area and cytoplasmic nuclear ratio) parameters to have a significantly increased risk of association with diabetes. Furthermore, these morphometry parameters were also associated with glycemic control and there was no gender disparity among them. Mounting evidence authenticate that cytomorphometric analysis of oral mucosal cells using exfoliative cytology might be aid as an adjunct non-invasive diagnostic tool for type II diabetes., Competing Interests: Conflict of interestThe authors report there are no competing interests to declare., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Folate and vitamin B12 deficiencies in pregnant women are associated with increased risk for adverse maternal and infant health outcomes, including neural tube defects (NTDs)., Methods: A population-based cross-sectional survey was conducted in two rural areas in Ambala District, Haryana, India in 2017 to assess baseline folate and vitamin B12 status among women of reproductive age (WRA) and predict the prevalence of NTDs. We calculated the prevalence of folate and vitamin B12 deficiency and insufficiency by demographic characteristics among 775 non-pregnant, non-lactating WRA (18-49 years). Using red blood cell (RBC) folate distributions and an established Bayesian model, we predicted NTD prevalence. All analyses were conducted using SAS-callable SUDAAN Version 11.0.4 to account for complex survey design., Results: Among WRA, 10.1% (95% CI: 7.9, 12.7) and 9.3% (95% CI: 7.4, 11.6) had serum (<7 nmol/L) and RBC folate (<305 nmol/L) deficiency, respectively. The prevalence of RBC folate insufficiency (<748 nmol/L) was 78.3% (95% CI: 75.0, 81.3) and the predicted NTD prevalence was 21.0 (95% uncertainly interval: 16.9, 25.9) per 10,000 live births. Prevalences of vitamin B12 deficiency (<200 pg/mL) and marginal deficiency (≥200 pg/mL and ≤300 pg/mL) were 57.7% (95% CI: 53.9, 61.4) and 23.5% (95% CI: 20.4, 26.9), respectively., Conclusions: The magnitude of folate insufficiency and vitamin B12 deficiency in this Northern Indian population is a substantial public health concern. The findings from the survey help establish the baseline against which results from future post-fortification surveys can be compared., (© 2024 Wiley Periodicals LLC.)

Background: Midbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), observed in PSP-Richardson's syndrome (PSP-RS) and to a lesser extent PSP-parkinsonism (PSP-P)., Objective: Our aim was to critically evaluate the utility of manual magnetic resonance imaging measurements of the midbrain tectal plate as a diagnostic biomarker in PSP., Methods: Length of the tectal plate and width of the superior and inferior colliculi were measured in 40 PSP (20 PSP-RS and 20 PSP-P) patients and compared with 20 Parkinson's disease and 20 healthy control subjects., Results: Tectal plate length was reduced in both PSP groups compared with Parkinson's disease and control subjects and was most abnormal in PSP-RS followed by PSP-P. Reduced tectal plate length was associated with worse PSP Rating Scale scores., Conclusions: Simple manual measurements of tectal plate length show utility as a diagnostic biomarker in PSP, particularly for PSP-RS., (© 2024 International Parkinson and Movement Disorder Society.)

Pediatric regional anesthesia (RA) has emerged as a rapidly advancing dimension within pediatric anesthesia, demanding a continual commitment to knowledge acquisition. This review underscores the contemporary significance of this specialty, focusing on its application in neonates and infants. The primary objective of RA is to address perioperative pain effectively while preserving the delicate physiological balance, thereby enhancing overall patient care. This review explores the advantages offered by RA in this age group. Furthermore, conventional, and recently introduced techniques of RA are examined by exploring the advantages and disadvantages of these methods. The aim is to provide clinicians with a nuanced understanding of their applicability in different clinical scenarios. Additionally, the review elucidates the unique considerations associated with pediatric RA, acknowledging pediatric patients' distinctive anatomical and physiological characteristics. The exceptional cases of congenital anomalies and their implications for the choice of RA are considered. An aspect of the review is its focus on dosages of local anesthetics and the volumes required for various blocks in neonates and infants. The dosages for continuous infusion and practical issues with infusions are considered. Complications due to RA are described with their prevention and treatment. The review offers pragmatic insights into the selection criteria for various regional blocks, aiding anesthesiologists in making informed decisions tailored to individual patient needs.

Interfacial electron transport in multicomponent systems plays a crucial role in controlling electrical conductivity. Organic-inorganic heterostructures electronic devices where all the entities are covalently bonded to each other can reduce interfacial electrical resistance, thus suitable for low-power consumption electronic operations. Programmed heterostructures of covalently bonded interfaces between ITO-ethynylbenzene (EB) and EB-zinc ferrite (ZF) nanoparticles, a programmed structure showing 67 978-fold enhancement of electrical current as compared to pristine NPs-based two terminal devices are created. An electrochemical approach is adopted to prepare nearly π-conjugated EB oligomer films of thickness ≈26 nm on ITO-electrode on which ZF NPs are chemically attached. A "flip-chip" method is employed to combine two EB-ZnFe 2 O 4 NPs-ITO to probe electrical conductivity and charge conduction mechanism. The EB-ZnFe 2 O 4 NPs exhibit strong electronic coupling at ITO-EB and EB-NPs with an energy barrier of 0.13 eV between the ITO Fermi level and the LUMO of EB-ZF NPs for efficient charge transport. Both the DC and AC-based electrical measurements manifest a low resistance at ITO-EB and EB-ZF NPs, revealing enhanced electrical current at ± 1.5 V. The programmed heterostructure devices can meet a strategy to create well-controlled molecular layers for electronic applications toward miniaturized components that shorten charge carrier distance, and interfacial resistance., (© 2024 Wiley‐VCH GmbH.)

This study investigates the efficacy of rosemary extract (RE) in stabilizing structured lipids (SL) developed using perilla seed oil (PSO) and palmolein (PO) under accelerated storage conditions. The oil samples, comprising PSO, Blend, and SL formulations with and without RE (1500 ppm) and BHT (200 ppm), were studied for their storage stability during a 30 day storage period at 65 °C, with the analysis carried out at 6 day intervals. Oxidative properties were comprehensively assessed, including both physical attributes (color, viscosity, and refractive index) and chemical parameters (peroxide value, free fatty acid (FFA), p -anisidine value, TOTOX value, conjugated dienes, and trienes). The results demonstrated that RE-enriched oil samples exhibited significantly higher oxidative stability ( p < 0.05) compared to the control group. SL added with 1500 ppm of RE exhibited notable enhancements in quality parameters, showcasing reductions in FFA, TOTOX value, conjugated diene, and triene value by 44.01%, 35.42, 39.03, and 47.36, respectively, when compared to SL without any antioxidant. The RE at 1500 ppm concentration showed a similar effect as the synthetic antioxidant BHT at 200 ppm. Also, the RE demonstrated potent inhibition of the oxidation of polyunsaturated fatty acids, thereby contributing to the improved oxidative stability of the SLs. Furthermore, SL with RE also exhibited reduced degradation of the tocopherol content and total phenolic content during the storage period. Principal component analysis demonstrated that SL and blend followed similar oxidative characteristics as they fell within the same quadrant. These findings underscore RE as a potent source of antioxidants capable of scavenging free radicals and enhancing the oxidative stability of omega-3 fatty acid-rich SLs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Basal cell carcinoma (BCC) is the most common malignant skin tumor, constituting 80% of nonmelanocytic skin tumors. Intermittent exposure to ultraviolet radiation is considered a major risk factor for BCC. This study was done in 2023 at a tertiary care cancer centre in North India. Pigmented BCC is a rare entity, a histopathological and clinical variant of BCC. This entity belongs to the category of nonmelanocytic skin tumors but exhibits increased pigmentation. Increased pigmentation also creates suspicion of melanocytic tumors, seborrheic keratosis, and Discoid Lupus Erythematosus DLE. However, this diagnostic dilemma can be elicited with histopathological analysis and clinical correlation. However, to prevent basal cell carcinoma, the best is to avoid direct sunlight; if it cannot be avoided, use sunscreen., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Education and Health Promotion.)

Despite global progress in childhood vaccination coverage, fragile and humanitarian countries, with high burden of infectious diseases, continue to report a significant number of zero-dose and under-vaccinated children. Efforts to equitably reach zero-dose children remain thus critical. This study assesses the prevalence and determinants of zero-dose children in fragile context of Somalia. We used secondary data from 2020 Somali Health and Demographic Survey (SHDS) to determine status of unvaccinated children aged between 12 to 23 months. Variables related to socio-demographic, household, health seeking, and community level factors were extracted from the SHDS data. Variables that were shown to be significantly associated with zero-dose children at p< 0.05 in the single logistic regression analysis were identified and included in a final multiple logistic regression analysis. A total of 2,304 women and their children aged between 12-23 months were used to determine the prevalence and determinants of zero dose children in Somalia. Approximately 60.2% of the children were zero dose children and did not receive any dose of the four basic routine vaccines. Children living in rural and nomadic areas were more likely to be zero dose (aOR 1.515, 95% CI: 1.189-1.93). Mother with primary education and above (aOR 0.519, 95% CI: 0.371-0.725), those who attended antenatal care (aOR 0.161, 95% CI: 0.124-0.209) and postnatal care (aOR 0.145, 95% CI: 0.085-0.245) and listen frequently to radio (aOR 2.212, 95% CI: 1.106-4.424) were less likely to have children with zero dose than with their counterparts. Majority of children under two years of age in Somalia are reported to be zero dose children. Context and population specific interventions that target vulnerable mothers and their children, in rural and nomadic areas, and from lower wealth quintile index families with no education and adequate access to antenatal and postnatal care remain critical., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Mohamoud 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.)

Activation of Gasdermin D (GSDMD) results in its cleavage, oligomerization, and subsequent formation of plasma membrane pores, leading to a form of inflammatory cell death denoted as pyroptosis. The roles of GSDMD in inflammation and immune responses to infection are well documented. However, whether GSDMD also plays a role in sporadic cancer development, especially that in the gut epithelium, remains unknown. Here, we show that GSDMD is activated in colorectal tumors of both human and mouse origins. Ablation of GSDMD in a mouse model of sporadic colorectal cancer resulted in reduced tumor formation in the colon and rectum, suggesting a tumor-promoting role of the protein in the gut. Both antibiotic-mediated depletion of gut microbiota and pharmacological inhibition of NLRP3 inflammasome reduced the activation of GSDMD. Loss of GSDMD resulted in reduced infiltration of immature myeloid cells, and increased numbers of macrophages in colorectal tumors. Activation of GSDMD is also accompanied by the aggregation of the endosomal sorting complex required for transport (ESCRT) membrane repair proteins on the membrane of colorectal tumor cells, suggesting that active membrane repairment may prevent pyroptosis induced by the formation of GSDMD pore in tumor cells. Our results show that gut microbiota/NLRP3-mediated activation of GSDMD promotes the development of colorectal tumors, and supports the use of NLRP3 inhibitors to treat colon cancer., (© 2024. The Author(s).)

Introduction: Corticobasal syndrome (CBS) can result from underlying Alzheimer's disease (AD) pathologies. Little is known about the utility of blood plasma metrics to predict positron emission tomography (PET) biomarker-confirmed AD in CBS., Methods: A cohort of eighteen CBS patients (8 amyloid beta [Aβ]+; 10 Aβ-) and 8 cognitively unimpaired (CU) individuals underwent PET imaging and plasma analysis. Plasma concentrations were compared using a Kruskal-Wallis test. Spearman correlations assessed relationships between plasma concentrations and PET uptake., Results: CBS Aβ+ group showed a reduced Aβ42/40 ratio, with elevated phosphorylated tau (p-tau)181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) concentrations, while CBS Aβ- group only showed elevated NfL concentration compared to CU. Both p-tau181 and GFAP were able to differentiate CBS Aβ- from CBS Aβ+ and showed positive associations with Aβ and tau PET uptake., Discussion: This study supports use of plasma p-tau181 and GFAP to detect AD in CBS. NfL shows potential as a non-specific disease biomarker of CBS regardless of underlying pathology., Highlights: Plasma phosphorylated tau (p-tau)181 and glial fibrillary acidic protein (GFAP) concentrations differentiate corticobasal syndrome (CBS) amyloid beta (Aβ)- from CBS Aβ+. Plasma neurofilament light concentrations are elevated in CBS Aβ- and Aβ+ compared to controls. Plasma p-tau181 and GFAP concentrations were associated with Aβ and tau positron emission tomography (PET) uptake. Aβ42/40 ratio showed a negative correlation with Aβ PET uptake., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

In this investigation, three medicinal plant powders and a composite flour developed from them were analyzed. FESEM/EDS illustrated irregularly shaped particles in the plant powders except for Withania, which had round to oval shape particles. XRD analysis displayed a semi-crystalline nature of powders, except for Asparagus, which showed amorphous behavior. Both methanol and ethanol plant extracts exhibited significantly higher antioxidants, total phenols, and cell viability. Amongst, optimized composite flour (OCF) methanolic extract demonstrated the highest total phenolic content (69.2 ± 0.11 μg GAE/ml), potent cell viability against A549 cells (3.35 ± 0.15% at 50 μg/ml), and strong free-radical scavenging activity (48.89 ± 0.67 at 200 μg/ml). GCMS and FTIR analyses of the methanolic extracts demonstrated the presence of essential phytoconstituents and functional groups. In silico studies of the phytocomponents, ethyl isoallocholate, 3-Deoxy-d-mannoic lactone, and 4,5-Diamino-2-hydroxypyrimidine suggested good binding affinity against BAX, P53, and EGFR proteins with no toxicity and a good drug score., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Meenakshi Garg has patent #A composition of optimized composite flour manufactured using medicinal plants or application no. 202311014262 pending to Office of Controller General of Patents, Designs, & Trademarks (Indian Patent Office). 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., (Copyright © 2023. Published by Elsevier Ltd.)

The amount of apically extruded debris following glide-path preparation of mesial root of 120 freshly extracted human mandibular molar teeth using Senseus ProFinder files, PathFile, G-Files, Scout-RaCe files, HyFlex glidepath files and V glide-path two file system is of interest. The Eppendorf tubes were used as test equipment for collecting debris and the average weight of the debris was measured using an electronic micro-balancing system. It was observed that regardless of the file system utilized, debris was expelled from the apex. The G files resulted in a lower quantity of debris being extruded (0.070 ± 0.002 mg). In contrast, the V glide-path two file system exhibited the highest amount of debris extrusion (0.110 ± 0.004 mg) compared to all other file systems., (© 2024 Biomedical Informatics.)

Forcibly displaced populations experience an increased burden of mental illness. Scaling up mental health (MH) services places new resource demands on health systems in crises-affected settings and raises questions about how to provide equitable MH services for refugee and host populations. Our study investigates barriers, facilitators, and proposed solutions to MH financing and access for Lebanese populations and Syrian refugees in Lebanon, a protracted crisis setting. We collected qualitative data via 73 interviews and 3 focus group discussions. Participants were purposively selected from: (i) national, United Nations and NGO stakeholders; (ii) frontline MH service providers; (iii) insurance company representatives; (iv) Lebanese and Syrian adults and parents of children aged 12-17 years using MH services. Data were analysed using inductive and deductive approaches. Our results highlight challenges facing Lebanon's system of financing MH care in the face of ongoing multiple crises, including inequitable coverage, dependence on external humanitarian funds, and risks associated with short-term funding and their impact on sustainability of services. The built environment presents additional challenges to individuals trying to navigate, access and use existing MH services, and the social environment and service provider factors enable or hinder individuals accessing MH care. Registered Syrian refugees have better financial coverage to secondary MH care than Lebanese populations. However, given the economic crisis, both populations are facing similar challenges in paying for and accessing MH care at primary health care (PHC) level. Multiple crises in Lebanon have exacerbated challenges in financing MH care, dependence on external humanitarian funds, and risks and sustainability issues associated with short-term funding. Urgent reforms are needed to Lebanon's health financing system, working with government and external donors to equitably and efficiently finance and scale up MH care with a focus on PHC, and to reduce inequities in MH service coverage between Lebanese and Syrian refugee populations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 El Masri 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.)

In this study, we have proposed a novel approach that combines hyaluronic acid (HA), folic acid (FA), and celastrol (CLS) within a polymeric micelle system (CLS-HF/MLs), offering a dual-action strategy against breast cancer. Polymeric mixed micelles were prepared through the thin-film hydration method, and comprehensive quality control parameters were established, encompassing particle size, polydispersity index, zeta potential, surface morphology, encapsulation efficiency, drug content, in vitro drug release, and storage stability assessment. The average particle size of CLS-HF/MLs micelles was found to be 120 nm and their drug loading and encapsulation efficiencies were 15.9 % and 89.52 %, respectively. The in vitro release data showed that the CLS-HF/MLs targeted mixed micelles displayed a prolonged release profile compared to the free drug. Additionally, the stability of the developed polymeric mixed micelles was maintained for up to 8 weeks of storage in terms of particle size and drug content. Furthermore, both flow cytometry and confocal laser scanning microscopy studies indicated a significant enhancement in the cellular uptake efficiency and cytotoxicity of CLS-HF/MLs mixed micelles against MCF-7 cell line. In terms of pharmacokinetic analysis, the half-life and AUC values of CLS-HF/MLs mixed micelles were found to be approximately 4.71- and 7.36-folds higher than the values of free drug (CLS), respectively. The CLS-HF/MLs micelles exhibited remarkable antitumor efficacy (almost complete ablation of the 4 T1-cell bearing tumor xenografts mouse model) due to the dual receptor (CD44 and folate) targeting effects with minimal side effects. When considering the cumulative findings of our present research, it becomes evident that mixed micelles designed for chemotherapy offer a promising and potentially effective therapeutic avenue for the treatment of breast cancer., 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 B.V. All rights reserved.)

Gastrointestinal stromal tumors (GISTs) are rare tumors of the gastrointestinal (GI) tract. Intermittent GI bleeding is the most common manifestation. Massive GI bleeding leading to syncopal episodes and hemorrhagic shock is a rare presentation of these tumors. Herein, we describe a case of a jejunal GIST presenting as massive bleeding., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Wadhwa et al.)

Background & Aims: Coconut water (CW) is anti-inflammatory, can manipulate the gut microbiome, and is a rich source of potassium. Gut microbiome modulation improves outcomes in ulcerative colitis (UC), and potassium possesses in vitro anti-inflammatory property. We evaluated the effect of CW as an adjunct therapy for patients with mild-moderate UC., Methods: This single-center, double-blind, placebo-controlled trial randomized patients with mild to moderate (Simple Clinical Colitis Activity Index [SCCAI]: 3-9) endoscopically active UC (Ulcerative Colitis Endoscopic Index of Severity [UCEIS] >1) in 1:1 ratio to CW + standard medical therapy (SMT) vs placebo + SMT. Four hundred mL of CW was administered for 8 weeks. Primary outcome measure was clinical remission (SCCAI ≤2), and secondary outcome measures were clinical response (SCCAI decline ≥3) and adverse events at 8 weeks. Microbiome was analyzed at baseline and 8 weeks., Results: Of 121 patients screened, 95 were included for modified intention to treat analysis (CW, n = 49; placebo, n = 46) (mean age, 37.2 ± 11.2 years; males, 54.1%; disease duration, 48 months [interquartile range (IQR), 24-90 months]; pancolitis, 26.1%; SCCAI, 5 [IQR, 4-6]; UCEIS, 4 [IQR, 3-5]). Clinical response (57.1% vs 28.3%; odds ratio [OR], 3.4; 95% confidence interval [CI], 1.4-7.9; P = .01), remission (53.1% vs 28.3%; OR, 2.9; 95% CI, 1.2-6.7; P = .02), and proportion of patients with fecal calprotectin (FCP) <150 μg/g (30.6% vs 6.5%; OR, 6.3; 95% CI, 1.7-23.6; P = .003) were significantly higher in CW. The relative abundance of bacterial taxa that had a significant or trend towards negative correlation with SCCAI, UCEIS, or FCP increased at 8 weeks in CW, and this effect was independent of disease activity and dietary fiber. Adverse events were comparable, and no patient developed hyperkalemia., Conclusions: CW was more effective than placebo for induction of clinical remission in patients with mild to moderate UC. The trial was prospectively registered on Clinical Trials Registry of India (ctri.nic.in, Number: CTRI/2019/03/01827)., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: Avascular necrosis (AVN) is a devastating complication often necessitating arthroplasty, particularly common in systemic lupus erythematosus (SLE). Limited research exists on arthroplasty trends since new steroid-sparing agents. We analyzed trends and characteristics associated with AVN and AVN-related arthroplasties among SLE and RA hospitalizations using two decades of data from the U.S. National Inpatient Sample (NIS)., Methods: This cross-sectional study used NIS (2000-2019) to identify hospitalized adults with SLE and RA, with or without AVN, using ICD codes. AVN was further grouped by arthroplasty status. Primary outcomes were AVN and AVN-related arthroplasty rates and time trends in SLE and RA. Baseline sociodemographics and comorbidities were compared. Analyses used STATA and Joinpoint regression to calculate annual percent change (APC)., Results: Overall, 42,728 (1.3 %) SLE and 43,600 (0.5 %) RA hospitalizations had concomitant AVN (SLE-AVN and RA-AVN). Of these, 16,724 (39 %) and 25,210 (58 %) underwent arthroplasties, respectively. RA-AVN increased (APC: 0.98*), with a decrease in arthroplasties (APC: -0.82*). In contrast, SLE-AVN initially increased with a breakpoint in 2011 (APC 2000-2011: 1.94* APC 2011-2019 -2.03), with declining arthroplasties (APC -2.03*). AVN hospitalizations consisted of individuals who were younger and of Black race; while arthroplasties were less likely in individuals of Black race or Medicaid coverage., Conclusion: We report a breakpoint in rising SLE-AVN after 2011, which may relate to newer steroid-sparing therapies (i.e., belimumab). AVN-associated arthroplasties decreased in SLE and RA. Fewer AVN-associated arthroplasties were noted for Black patients and those with Medicaid, indicating potential disparities. Further research should examine treatment differences impacting AVN and arthroplasty rates., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In this paper, we developed a series of piperic acid (PA) analogs with the aim of overcoming the limitations associated with the natural products for the management of Alzheimer's disease (AD). A comprehensive SAR study was performed to enhance cholinesterase inhibition of PA. The acetylcholinesterase inhibition and its kinetic data suggested 6j as the lead molecule (AChE IC 50  = 2.13 ± 0.015 µM, BChE = 28.19 ± 0.20%), in comparison to PA (AChE = 7.14 ± 0.98%) which was further selected for various biological studies in AD models. 6j, exhibited interaction with the peripheral anionic site of AChE, BBB permeability (Pe = 7.98), and antioxidant property (% radical scavenging activity = 35.41 ± 1.09, 2.43 ± 1.65, for 6j and PA at 20 M μ , respectively). The result from the metal chelation study suggests that 6j did not effectively chelate iron. The molecular modeling studies suggested that 6j could effectively interact with Ser293, Phe295, Arg296, and Tyr34 of AChE. In the cell-based cytotoxicity studies, 6j exhibited cytocompatibility at the different tested concentrations. The acute toxicity data on mice suggested that compound 6j had no renal and hepatotoxicity at 500 mg/kg. Moreover, 6j could effectively reverse scopolamine-induced amnesia by improving spatial and cognitive memory in mice. The above results strongly suggest that compound 6j may act as a novel multi-targeted lead for AD therapy., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Overlap between language and visual variants of atypical Alzheimer's disease (AD) has been reported. However, the extent, frequency of overlap, and its neuroanatomical underpinnings remain unclear. Eighty-two biomarker-confirmed AD patients who presented with either predominant language (n = 34) or visuospatial/perceptual (n = 48) deficits underwent detailed clinical examinations, MRI, and [ 18 F]flortaucipir-PET. Subgroups were defined based on language/visual testing and patterns of volume loss and tau uptake were assessed. 28% of the language group had visual dysfunction (marked in 8%), and 47% of the visual group had language impairment (marked in 26%). Progressive involvement of the parieto-occipital and frontal lobes was noted with greater visual impairment in the language group, and greater left parieto-temporal and frontal involvement with worsening language impairment in the visual group. Only 25% of our cohort showed a pure language or visual presentation, highlighting the high frequency of syndromic overlap in atypical AD and the diagnostic challenge of categorical phenotyping., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Objective: Oral submucous fibrosis is a frequently reported potentially malignant disorder characterized by fibrosis and a malignant transformation rate of 7-30%. The role of hypoxia-inducible factor-1/2α in malignant transformation mechanisms of oral submucous fibrosis remains uncharted territory owing to a scarcity of studies. Thus the present systematic review and meta-analysis aimed to determine the role of hypoxia-inducible factor-1/2α in the progression of fibrosis of oral submucous fibrosis and its malignant transformation., Material and Methods: Using PubMed, Google Scholar, and Cochrane Library databases, full-text articles that investigated hypoxia-inducible factor-1/2α in oral submucous fibrosis were entailed for review. A modified Newcastle-Ottawa scale was employed to evaluate risk of bias in all articles and Review Manager was utilized for meta-analysis., Results: Eighteen and eight qualified articles respectively were included for qualitative and quantitative data synthesis. Progressive upregulation of hypoxia-inducible factor-1/2α in oral submucous fibrosis is associated with fibrosis-induced carcinogenesis. A Random-effects model uncloaked that oral submucous fibrosis cases with significantly increased expression of hypoxia-inducible factor-1α had an increased associated risk of malignant transformation compared with controls (combined odds ratio 523.83, 95% confidence interval 125.74- 2182.28, p < 0.00001)., Conclusion: The existing evidence substantiates the notion that hypoxia-inducible factor-1/2α, a fundamental pathogenetic mechanism of progression and malignant transformation of oral submucous fibrosis in the background of fibrosis., Competing Interests: Declaration of Competing Interest Regarding the content of the article, none of the authors have any conflict of interest to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: A library of Virtual Reality (VR) tasks has been developed for targeted post-stroke rehabilitation of distal upper extremities. The objective of this pilot study was to evaluate the clinical potential of the targeted VR-based therapeutic intervention in a small cohort of patients specifically with chronic stroke. Furthermore, our aim was to explore the possible neuronal reorganizations in corticospinal pathways in response to the distal upper limb targeted VR-intervention., Methodology: Five patients with chronic stroke were enrolled in this study and were given VR-intervention of 20 sessions of 45 min each. Clinical Scales, cortical-excitability measures (using Transcranial Magnetic Stimulation): Resting Motor Threshold (RMT), and Motor Evoked Potential (MEP) amplitude, task-specific performance metrics i.e., Time taken to complete the task (TCT), smoothness of trajectory, relative % error were evaluated pre- and post-intervention to evaluate the intervention-induced improvements., Results: Pre-to post-intervention improvements were observed in Fugl-Meyer Assessment (both total and wrist/hand component), Modified Barthel Index, Stroke Impact Scale, Motor Assessment Scale, active range of motion at wrist, and task-specific outcome metrics. Pre-to post-intervention ipsilesional RMT reduced (mean ∼9%) and MEP amplitude increased (mean ∼29µV), indicating increased cortical excitability at post-intervention., Conclusion: VR-training exhibited improved motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes observed in terms of improved cortical-excitability might be a consequence of plastic reorganization induced by VR-intervention.

Introduction: Mixed connective tissue disease (MCTD) is a rare entity in children. There is a paucity of studies on juvenile-onset MCTD (jMCTD) worldwide especially from Southeast Asia., Objectives: To describe clinical and laboratory features of jMCTD diagnosed at pediatric rheumatology centers across India., Methods: A predesigned detailed case proforma in an excel format was prepared and was sent to all the Pediatric Rheumatology centers in India. Eleven centers provided the clinical and laboratory data of their jMCTD patients, which was then compiled and analyzed in detail., Results: Thirty-one jMCTD patients from 11 centers were included in the study. Our cohort had 27 females and four male patients over 12 months (August 2021 to July 2022). The median age at presentation was 12 years (range 5-18 years) and the median duration of symptoms was 24 months at diagnosis (range 2-96 months). The common features included arthritis (90%), malar rash (70.9%), and Raynaud's phenomenon (70.9%). At a mean follow-up of 43 months (range 1-168 months), 45% of them were in remission. There were two deaths reported, due to macrophage activation syndrome and sepsis respectively., Conclusion: We present the largest multicenter experience on jMCTD from the Indian subcontinent. The study's findings serve as a crucial stepping stone toward unraveling the complexities of jMCTD and improving patient care and management strategies., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Purpose: We sought to examine the incidence of severe postoperative pain in patients with cerebral palsy (CP) in the first 48 hr after surgery performed under combined regional and general anesthesia and its association with patient and surgical factors., Methods: In a historical cohort study, we reviewed the electronic records of 452 patients with spastic CP who underwent orthopedic surgeries of the upper and lower extremities from April 2016 to February 2020. Collected data included patient characteristics, American Society of Anesthesiologists Physical Status, details of anesthesia and surgery, types of regional anesthesia applied, success rate of anesthesia, incidence of severe pain, and adverse events., Results: We analyzed data from 440 patients; 404 patients underwent lower extremity surgery, 20 upper extremity surgery, and 15 both, and one patient required stem cell injection. All patients received general anesthesia before block performance. Single-injection neuraxial anesthesia was performed in 241 (54.8%) patients, brachial plexus block in 27 (6.1%) patients, and femoral/sciatic nerve blocks in 17 (3.9%) patients. Continuous neuraxial, brachial plexus, and femoral/sciatic nerve blocks were performed in 149 (33.9%), four (0.9%), and seven (1.6%) of the patients, respectively. Major and complex major surgeries were performed in 161 (36.6%) and 72 (16.4%) patients, respectively and continuous catheters were inserted in 50.3% of patients undergoing major surgery and in 91.7% of patients undergoing complex major surgery. Severe pain was reported by the caregivers of 68 (15.5%) patients who received nonopioid analgesic interventions., Conclusion: Despite the use of regional anesthesia, approximately 15% of patients with spastic CP undergoing orthopedic surgery for spastic cerebral palsy experienced severe pain that responded to treatment adjustments., Study Registration: CTRI.nic.in (027002); registered 5 August 2020., (© 2023. Canadian Anesthesiologists' Society.)

Current standard-of-care systemic therapy options for locally advanced and metastatic bladder cancer (BC), which are predominantly based on cisplatin-gemcitabine combinations, are limited by significant treatment failure rates and frailty-based patient ineligibility. We previously addressed the urgent clinical need for better-tolerated BC therapeutic strategies using a drug screening approach, which identified outstanding antineoplastic activity of clofarabine in preclinical models of BC. To further assess clofarabine as a potential BC therapy component, we conducted head-to-head comparisons of responses to clofarabine versus gemcitabine in preclinical in vitro and in vivo models of BC, complemented by in silico analyses. In vitro data suggest a distinct correlation between the two antimetabolites, with higher cytotoxicity of gemcitabine, especially against several nonmalignant cell types, including keratinocytes and endothelial cells. Accordingly, tolerance of clofarabine (oral or intraperitoneal application) was distinctly better than for gemcitabine (intraperitoneal) in patient-derived xenograft models of BC. Clofarabine also exhibited distinctly superior anticancer efficacy, even at dosing regimens optimized for gemcitabine. Neither complete remission nor cure, both of which were observed with clofarabine, were achieved with any tolerable gemcitabine regimen. Taken together, our findings demonstrate that clofarabine has a better therapeutic window than gemcitabine, further emphasizing its potential as a candidate for drug repurposing in BC. PATIENT SUMMARY: We compared the anticancer activity of clofarabine, a drug used for treatment of leukemia but not bladder cancer, and gemcitabine, a drug currently used for chemotherapy against bladder cancer. Using cell cultures and mouse models, we found that clofarabine was better tolerated and more efficacious than gemcitabine, and even cured implanted tumors in mouse models. Our results suggest that clofarabine, alone or in combination schemes, might be superior to gemcitabine for the treatment of bladder cancer., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Breast lymphomas are a rare group of malignancies that are further subdivided into primary and secondary. AIMS: To study the pathological and clinical course of breast lymphomas., Materials and Methods: This is a retrospective analysis of patients treated at our institute over a period of 4.5 years from September 2018 to February 2023. The details of all the patients diagnosed with breast lymphoma were reviewed and analysed for the histomorphological, immunohistochemical, clinical, and treatment details. Appropriate statistical analysis including Kaplan-Meier methods was used., Results: Out of 11 cases of breast lymphoma, five were primary and six were secondary. It was seen predominantly in females (82%) and the age range was 31 to 73 years. Diffuse large B cell lymphoma (DLBCL) was the predominant morphology (73%), along with single rare cases of ALK-negative anaplastic large cell lymphoma, Burkitt lymphoma, and small lymphocytic lymphoma. The treatment details were analyzed for 7 patients. The median follow-up was 28 months. Rituximab along with CHOP regimen or its variants was commonly used as first-line treatment with initial response rates of 71%. The median progression-free survival was 5 months. The median overall survival was 15 months., Conclusion: Lymphomas of the breast are rare but it is crucial to differentiate them from the commoner breast carcinomas as the treatment and prognosis vary vastly., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Competing Interests: Competing interests: None declared.

Introduction: The most crucial factor in improving animal reproduction efficiency is early pregnancy diagnosis. Early diagnosis not only reduces the time interval between two calvings but also aids farmers in identifying open animals, thereby preventing significant milk production losses. Therefore, the objective of this study was to discover circulatory miRNAs that would be useful for early pregnancy diagnosis in buffalo. Material and methods: Blood samples were taken on 0, 6 th , 12 th , and 18 th day after artificial insemination from pregnant animals (n = 30) and non-pregnant animals (n = 20). During these stages of pregnancy, total RNA was extracted, and a small RNA library was subsequently generated and sequenced on the Illumina platform. Subsequently, Real-time PCR was used to validate the findings. Results and discussion: There were 4,022 miRNAs found during the pregnancy, with 15 of those lacking sequences and 4,007 having sequences already in the database. From the beginning of pregnancy until the 18 th day, 25 of these miRNAs showed a substantial shift in expression levels in the maternal blood, with a change more than two logs. Furthermore, based on qPCR results, 19 miRNAs were found to be more abundant in pregnant animals than in non-pregnant animals. We used target prediction analysis to learn how maternally expressed miRNAs relate to fetal-maternal communication. In conclusion, miRNA based biomarkers that could be associated with the diagnosis of pregnancy were identified including miR-181a and miR-486 highly upregulated on the 18 th day of pregnancy. This study also provides a comprehensive profile of the entire miRNA population in maternal buffalo blood during the early stages of pregnancy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Batra, Sehrawat, Kumar, Singh, Kaur, Yadav, Singh and Maan.)

The complexity and multifaceted nature of Alzheimer's disease (AD) have driven us to further explore quinazoline scaffolds as multi-targeting agents for AD treatment. The lead optimization strategy was utilized in designing of new series of derivatives (AK-1 to AK-14) followed by synthesis, characterization, and pharmacological evaluation against human cholinesterase's (hChE) and β-secretase (hBACE-1) enzymes. Amongst them, compounds AK-1, AK-2, and AK-3 showed good and significant inhibitory activity against both hAChE and hBACE-1 enzymes with favorable permeation across the blood-brain barrier. The most active compound AK-2 revealed significant propidium iodide (PI) displacement from the AChE-PAS region and was non-neurotoxic against SH-SY5Y cell lines. The lead molecule (AK-2) also showed Aβ aggregation inhibition in a self- and AChE-induced Aβ aggregation, Thioflavin-T assay. Further, compound AK-2 significantly ameliorated Aβ-induced cognitive deficits in the Aβ-induced Morris water maze rat model and demonstrated a significant rescue in eye phenotype in the Aꞵ-phenotypic drosophila model of AD. Ex-vivo immunohistochemistry (IHC) analysis on hippocampal rat brains showed reduced Aβ and BACE-1 protein levels. Compound AK-2 suggested good oral absorption via pharmacokinetic studies and displayed a good and stable ligand-protein interaction in in-silico molecular modeling analysis. Thus, the compound AK-2 can be regarded as a lead molecule and should be investigated further for the treatment of AD., 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 Masson SAS. All rights reserved.)

In recent years, Onco-immunotherapies (OIMTs) have been shown to be a potential therapy option for cancer. Several immunotherapies have received regulatory approval, while many others are now undergoing clinical testing or are in the early stages of development. Despite this progress, a large number of challenges to the broad use of immunotherapies to treat cancer persists. To make immunotherapy more useful as a treatment while reducing its potentially harmful side effects, we need to know more about how to improve response rates to different types of immunotherapies. Nanocarriers (NCs) have the potential to harness immunotherapies efficiently, enhance the efficiency of these treatments, and reduce the severe adverse reactions that are associated with them. This article discusses the necessity to incorporate nanomedicines in OIMTs and the challenges we confront with current anti-OIMT approaches. In addition, it examines the most important considerations for building nanomedicines for OIMT, which may improve upon current immunotherapy methods. Finally, it highlights the applications and future scenarios of using nanotechnology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A blend of organic municipal solid waste, slaughterhouse waste, fecal sludge, and landfill leachate was selected in different mixing ratios to formulate the best substrate mixture for biomethanation. Individual substrates were characterized, and the mixing ratio was optimized with the help of a response surface methodology tool to a value of 1:1:1:1 (with a C/N ratio of 28±0.769 and total volatile fatty acid (VFA) concentration of 2500±10.53 mg/L) to improve the overall biomethanation. The optimized blend (C/N ratio: 28.6, VFA: 2538 mg/L) was characterized for physicochemical, biological, and microbial properties and subjected to anaerobic digestion in lab-scale reactors of 1000 mL capacity with and without the addition of inoculum. The biogas yield of individual substrates and blends was ascertained separately. The observed cumulative biogas yield over 21 days from the non-inoculated substrates varied between 142±1.95 mL (24.6±0.3 ml/gVS) and 1974.5±21.72 mL (270.4±3.1 ml/gVS). In comparison, the addition of external inoculation at a 5% rate (w/w) of the substrate uplifted the minimum and maximum cumulative gas yield values to 203±9.9 mL (35.0±1.6 mL/gVS) and 3394±13.4 mL (315.3±1.2 mL/gVS), respectively. The inoculum procured from the Defence Research and Development Organisation (DRDO) was screened in advance, considering factors such as maximizing VFA production and consumption rate, biogas yield, and digestate quality. A similar outcome regarding biogas yield and digestate quality was observed for the equivalent blend. The cumulative gas yield increased from 2673±14.5 mL (373.7±2.2 mL/gVS) to 4284±111.02 mL (391.47±20.02 mL/gVS) over 21 days post-application of a similar dosage of DRDO inoculum. The 16S rRNA genomic analysis revealed that the predominant bacterial population belonged to the phylum Firmicutes, with the majority falling within the orders Clostridiales and Lactobacillales. Ultimately, the study advocates the potential of the blend mentioned above for biomethanation and concomitant enrichment of both biogas yield and digestate quality., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Glial fibrillary acidic protein (GFAP) in plasma is a proxy for astrocytic activity and is elevated in amyloid-β (Aβ)-positive individuals, making GFAP a potential blood-based biomarker for Alzheimer's disease (AD)., Methods: We assessed plasma GFAP in 72 Aβ-positive participants diagnosed with the visual or language variant of AD who underwent Aβ- and tau-PET. Fifty-nine participants had follow-up imaging. Linear regression was applied on GFAP and imaging quantities., Results: GFAP did not correlate with Aβ- or tau-PET cross-sectionally. There was a limited positive correlation between GFAP and rates of tau accumulation, particularly in the language variant of AD, although associations were weaker after removing one outlier patient with the highest GFAP level., Discussion: Among Aβ-positive AD participants with atypical presentations, plasma GFAP did not correlate with levels of AD pathology on PET, suggesting that the associations between GFAP and AD pathology might plateau during the advanced phase of the disease., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Comprehensive and proper management of fecal sludge (FS) is an ongoing concern in many nations. Decentralized fecal sludge treatment plants (FSTPs) are effective in this regard; however, many have experienced strong public opposition based partly on suspicion of malodor. Fecal sludge and freshly generated fecal matter (FM) samples from various FSTPs were collected, characterized, and investigated for biomethane potential. The homogenized samples were anaerobically digested for 28 days. Digestion successfully reduced total suspended solids, biochemical oxygen demand, and threshold odor number values of 97,350-97,420 mg/l, 43,230-43,260 mg/l, and 130-150 for FM, to 49,500-49,650 mg/l, 23,760-23,850 mg/l, and 3338, respectively, for FS samples. The comprehensive gas yield from Bhongir, Boduppal, and Shadnagar FS samples was 40, 55, and 31 ml, respectively. In contrast, cumulative gas generation from the FM was 26,361 ml. Digestion of FS samples also reduced concentrations of volatile solids and coliforms by 66-72% and 99%, respectively. Characterization of gas samples revealed methane and carbon dioxide concentrations as 56% and 22% for FM, and 0.4% and 61% for FS samples, respectively. Hydrogen sulfide and ammonia gas were absent in FS samples, dispelling common societal misconceptions of FSTPs being associated with malodor., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [ 18 F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum., Competing Interests: Declaration of competing interest Dr. Singh, Dr. Carlos, Dr. Sintini, Dr. Reid, Carling Robinson and Austin Goodrich have no disclosures to report. Dr. Whitwell, Dr. Machulda and Dr. Josephs reported receiving research funding from the NIH. Dr. Graff-Radford reported receiving research support from the NIH and he also serves as an editorial board member for Neurology. Dr. Jack receives no personal compensation from any commercial entity and has no conflicts. He receives research support from NIH, the GHR foundation and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic. Dr. Lowe reported consulting for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receiving research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, Elli Lilly and Company and the NIH (NIA, NCI). Dr. Peterson reported serving on scientific advisory boards for Elan Pharmaceuticals and GE Healthcare, he receives royalties from publishing mild cognitive impairment (Oxford University Press, 2003) and receives research support from NIH. Dr. Kantarci receives research support from the NIH (K23 AG030935 [PI], P50 AG16574/P1 [PI], and R01 AG11378 [Co-]). Dr. Boeve has served as a consultant to GE Healthcare; receives royalties from the publication of Behavioral Neurology of Dementia (Cambridge Medicine, 2009); and receives research support from Myriad Genetics Inc., Cephalon, Inc., the NIH (P50 AG16574 [Co-I], UO1 AG06786 [Co-I, and RO1 AG15866 [Co-I]), the Alzheimer's Association, and the Center for Inherited Disease Research (U24 AG026395 [Co-I])., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To evaluate diagnostic performance of ganglion cell inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) parameters measured with Cirrus high-definition optical coherence tomography (OCT) in patients with preperimetric glaucoma., Methods: In this multicenter cross-sectional study, 150 eyes of 83 patients with preperimetric glaucoma were compared with 200 eyes of age and sex matched healthy subjects. All patients had visual field testing and OCT scanning of GCIPL and RNFL in all quadrants. The independent Samples t -test was used to determine if a difference exists between the means of two independent groups on a continuous dependent variable. The area under the receiver operating characteristic (ROC) curve (AUC) of each parameter was calculated for discriminatory ability between normal controls and preperimetric glaucoma. The sensitivity and specificity were estimated by point coordinates on ROC curve., Results: The best parameters for distinguishing preperimetric glaucoma from healthy eyes were the combined average GCIPL + average RNFL, followed by average RNFL + GCIPL (inferotemporal), and average RNFL + GCIPL (minimum). The GCIPL parameters with the highest to lowest AUC (in decreasing order) were inferotemporal, followed by average, minimum, superior, inferior, superonasal, inferonasal, superotemporal, and quadrants. The RNFL parameters with the highest to lowest AUC (in decreasing order) were average, followed by nasal, temporal, superior, and inferior quadrants. The sensitivity of combined GCIPL + RNFL parameters ranged 85%-88% and the specificity ranged 76%-88%. The sensitivity for RNFL parameters ranged 80%-90% and the specificity ranged 64%-88%., Conclusion: GCIPL and RNFL have good discriminatory ability; the sensitivity and specificity increase when both parameters are combined for early detection of glaucoma., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Current Ophthalmology.)

Introduction: Progress related to sexual, reproductive, maternal, newborn, child and adolescent health (SRMNCAH) has stalled. COVID-19, conflict and climate change threaten to reverse decades of progress and to ensure the health and well-being of vulnerable populations in humanitarian and fragile settings (HFS) going forward, there is a need for tailored guidance for women, children and adolescents (WCA). This review seeks to map and appraise current resources on SRMNCAH in HFS., Methods: In line with the updated Joanna Briggs Institute guidance and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews framework, a manual literature review was conducted of global and regional guidance published between January 2008 and May 2023 from members of the Global Health Cluster, the Global Nutrition Cluster and the Inter-Agency Working Group on Reproductive Health in Crises. A content analysis was conducted. Scores were then calculated according to the Appraisal of Guidelines for Research and Evaluation II scoring tool and subsequently categorised as high quality or low quality., Results: A total of 730 documents were identified. Of these, 141 met the selection criteria and were analysed. Available guidance for delivering SRMNCH services exists, which can inform policy and programming for the general population and WCA. Important gaps related to beneficiaries, health services and health system strengthening strategies were identified., Conclusion: The review revealed there is evidence-based guidance available to support interventions targeting WCA in HFS, including: pregnant and lactating women, women of reproductive age, adolescents, newborns, small vulnerable newborns, stillbirths, refugees and internally displaced persons and WCA with disabilities. However, gaps related to beneficiaries, health services and health system strengthening strategies must be addressed in updated guidance that is created, disseminated and monitored in a standardised way that is mindful of the need to respond rapidly in HFS., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)