Neuro Endoscopic Vs Craniotomy approach in Supratentorial hypertensive Intracerebral Hemorrhage: An updated Meta-analysis.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a serious medical condition associated with high mortality and disability rates. Surgical interventions, including neuro-endoscopic surgery (NES) and craniotomy, are employed to manage ICH and improve patient outcomes. This meta-analysis compares the effectiveness of NES versus craniotomy in treating ICH. METHODS: A systematic literature search was conducted to identify relevant studies comparing NES with craniotomy for ICH. Inclusion criteria encompassed primary or secondary results from randomized controlled trials (RCTs) or observational studies (OSs) with confirmed supratentorial ICH. Data were extracted, and methodological quality was assessed using appropriate tools. Statistical analysis was performed using Comprehensive Meta-Analysis. RESULTS: Twenty-six studies (n=3237 patients) were included in the analysis. NES was associated with significantly lower mortality compared to craniotomy (OR: 0.45, 95% CI 0.33 to 0.60, p < 0.00001). Hematoma evacuation rates were higher with NES (SDM: 1.505, 95% CI 0.835 to 2.160, p < 0.00001). NES also showed better functional outcomes (OR: 3.31, 95% CI 1.78 to 6.17, p = 0.0002) and reduced blood loss (SDM: -3.06, 95% CI -3.979 to -2.141, p = 0.000). Additionally, NES was associated with shorter hospital and ICU stays, shorter operative times, and fewer complications such as infection and rebleeding. CONCLUSION: NES emerges as a promising alternative to craniotomy for treating ICH, offering advantages in terms of mortality reduction, improved functional outcomes, and fewer complications. Future studies should explore advancements in neuro-endoscopic techniques to optimize patient outcomes further.

Systematic Review and Meta-Analysis Comparing Complete Versus Incomplete or Culprit-only Revascularization by Percutaneous Coronary Intervention in Elderly Patients with Acute Coronary Syndrome.

BACKGROUND: Complete revascularization (CR) is favored over culprit-only or incomplete revascularization (IR) for patients with acute coronary syndrome (ACS) and multi-vessel disease (MVD) due to better long-term outcomes. However, the optimal revascularization strategy is currently uncertain in elderly patients, where frailty, polypharmacy, multi-morbidity, inherent bleeding risk and presumed cognitive decline can often burden the decision-making process. METHODS: We searched Medline, PubMed, and Google Scholar from inception to April 2024. The search of databases identified relevant studies that reported the comparative effects of CR and IR in the elderly population undergoing percutaneous coronary intervention (PCI). Data was pooled for individual studies using random-effects models on Comprehensive Meta-Analysis software, with statistical significance set at p<0.05. RESULTS: The meta-analysis included 14 studies and 62577 patients. CR demonstrated a significant reduction in all-cause mortality [RR: 0.680; 95% CI: 0.57-0.82; p=<0.001], cardiovascular-related mortality [RR: 0.620; 95% CI: 0.478-0.805; p=<0.001], and myocardial infarction [RR: 0.675; 95% CI: 0.553-0.823; p=<0.001] rates. There was no difference between the risk of stroke [RR: 1.044; 95% CI: 0.733-1.486; p=0.81], major bleeding [RR: 1.001; 95% CI: 0.787-1.274; p=0.991], stent thrombosis [RR: 1.015; 95% CI: 0.538-1.916; p=0.936], and contrast-induced acute kidney injury [RR: 1.187; 95% CI: 0.963-1.464; p=0.109]. CONCLUSION: The meta-analysis suggests that CR may be a favorable revascularization strategy for elderly patients undergoing PCI, displaying a significant decrease in mortality and repeat myocardial infarction risk.

Precision medicine in peripartum cardiomyopathy: advancing diagnosis and management through genomic and phenotypic integration.

Peripartum cardiomyopathy (PPCM) is a rare and life-threatening cardiac condition characterized by heart failure due to left ventricular systolic dysfunction, often developing in late pregnancy or the early postpartum period. Despite being a leading cause of maternal morbidity and mortality, clinical presentation of PPCM frequently overlaps with normal pregnancy-related physiological changes, causing diagnostic delays and increased complications. Current management strategies, primarily derived from general heart failure protocols, are evolving to address the unique aspects of PPCM. This includes the development of personalized medicine approaches that integrate genetic profiling, biomarker evaluation, and clinical phenotyping. Notable genes such as titin (TTN), Bcl2-associated athanogene 3 (BAG3), and lamin A/C (LMNA) are implicated in PPCM, revealing a complex genetic landscape similar to other cardiomyopathies. Biomarkers like N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) are under investigation for their diagnostic and prognostic value, indicating that personalized treatments hold the promise of enhancing diagnostic precision and therapeutic outcomes by tailoring interventions to individual patient profiles. This review article aims to highlight how integrating genetic and phenotypic data can establish a novel framework for managing PPCM, potentially transforming treatment paradigms and improving long-term outcomes.

Revolutionary breakthrough: FDA approves CASGEVY, the first CRISPR/Cas9 gene therapy for sickle cell disease.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting from a ß-globin chain mutation that causes abnormal hemoglobin (HbS) polymerization and leads to severe complications. Current treatment options primarily focus on symptom management, with limited curative potential. Recently, Casgevy, the first CRISPR/Cas9-based gene therapy for SCD, has received breakthrough FDA approval. Clinical trials have shown that Casgevy administered to patients aged older than or equal to 12 years enables precise modifications in hematopoietic stem cells, resulting in elevated fetal hemoglobin (HbF) levels and a significant reduction in vaso-occlusive events. Unlike conventional treatments, this therapy offers a curative approach and eliminates the need for recurrent transfusions and transplants, thereby improving the quality of life of patients with SCD. Casgevy has emerged as a beacon of hope for SCD patients and signifies a potential paradigm shift in SCD management due to its safety, curative potential, and transformative impact, positioning it as a groundbreaking intervention. Nevertheless, ethical considerations surrounding CRISPR technology and regulatory frameworks must be addressed to ensure responsible application and equitable access to this one-time gene editing therapy. As the authors celebrate this scientific advancement, sustained interdisciplinary collaboration and ethical scrutiny are essential to navigating the evolving landscape of CRISPR technology in medicine. This review aims to provide a detailed insight into the application of Casgevy, challenges associated with its application, future prospects of this therapy, and its comparison with existing treatment options for SCD.

Redefining Management in Hypertrophic Cardiomyopathy: The Role and Challenges of Exercise Rehabilitation.

Hypertrophic cardiomyopathy (HCM), a common genetic heart condition, is characterized by thickening of the left ventricle, which can result in a range of health issues, such as arrhythmias, heart failure, and sudden death. Despite traditional cautions against exercise in HCM patients due to potential exacerbation of symptoms and risk of sudden death, recent evidence suggests a paradigm shift toward the benefits of structured exercise rehabilitation. The pathogenesis of HCM, the physical and psychological effects of the illness on patients, and changing views on exercise as a therapeutic intervention are all covered in this review. Recent research shows that modest physical activity can considerably enhance functional ability, psychological health, and overall quality of life in individuals with heart failure without increasing the risk of unfavorable cardiac events, challenging earlier recommendations. Moreover, exercise rehabilitation has been shown to induce favorable myocardial remodeling and enhance cardiovascular fitness, suggesting a revaluation of exercise prescriptions tailored to individual patient profiles. Despite the promising role of exercise in managing HCM, this review also acknowledges the complexities of implementing rehabilitation programs, including the need for comprehensive patient assessment, personalized exercise regimens, and monitoring for potential complications. Future research should focus on optimizing exercise recommendations, understanding long-term outcomes, and integrating exercise rehabilitation into standard care protocols for HCM to foster a more holistic approach to patient management. Underscoring the necessity of a multidisciplinary strategy that balances the benefits of physical activity with the unique risks associated with HCM with the aim of improving patient outcomes through evidence-based, patient-centered care.

Identification of Schizophrenia Susceptibility Loci in the Urban Taiwanese Population.

Background and Objectives: Genomic studies have identified several SNP loci associated with schizophrenia in East Asian populations. Environmental factors, particularly urbanization, play a significant role in schizophrenia development. This study aimed to identify schizophrenia susceptibility loci and characterize their biological functions and molecular pathways in Taiwanese urban Han individuals. Materials and Methods: Participants with schizophrenia were recruited from the Taiwan Precision Medicine Initiative at Tri-Service General Hospital. Genotype-phenotype association analysis was performed, with significant variants annotated and analyzed for functional relevance. Results: A total of 137 schizophrenia patients and 26,129 controls were enrolled. Ten significant variants (p < 1 × 10-5) and 15 expressed genes were identified, including rs1010840 (SOWAHC and RGPD6), rs11083963 (TRPM4), rs11619878 (LINC00355 and LINC01052), rs117010638 (AGBL1 and MIR548AP), rs1170702 (LINC01680 and LINC01720), rs12028521 (KAZN and PRDM2), rs12859097 (DMD), rs1556812 (ATP11A), rs78144262 (LINC00977), and rs9997349 (ENPEP). These variants and associated genes are involved in immune response, blood pressure regulation, muscle function, and the cytoskeleton. Conclusions: Identified variants and associated genes suggest a potential genetic predisposition to schizophrenia in the Taiwanese urban Han population, highlighting the importance of potential comorbidities, considering population-specific genetic and environmental interactions.

A novel nanoparticles spilled-over In2O3microcubes-enabled sustainable chemiresistor for environmental carbon dioxide monitoring.

Achieving sustainable future energy goals includes enhancing renewable energy production, optimizing daily energy consumption using feedback loops and minimizing/monitoring contributions to atmospheric carbon dioxide (CO2). Developing economic next-generation CO2sensors enables local monitoring of industrial CO2emissions, aiding energy management and climate monitoring. This study elucidates the efficacy of CO2chemiresistor based on indium oxide (In2O3) micro cubes with spilled-over nanoparticles. The investigation primarily focuses on fabricating and optimising In2O3-based CO2chemiresistors utilizing a hydrothermal technique, creating porous micro cubes essential for enhanced CO2monitoring. As revealed by various characterization techniques, the minimum crystallite size was found to be 24.92 nm with optimum porosity and a high surface-to-volume ratio comprising spilled-over nanoparticle morphology. The fabricated chemiresistor demonstrated excellent CO2 sensing efficacy with a maximum response of around 4.1% at room temperature with selectivity, repeatability, and reversible sensing behavior. The sensing mechanism has been revealed, which is supported by theoretical density functional theory evaluations. Notably, the sensing results reveal the capability of In2O3-based sensors to detect CO2at low concentrations as low as ⩽10 ppm, which enables the chemiresistor for practical implementation in diverse sectors to achieve sustainability.

Molecular Electrochemical Catalysis of CO-to-Formaldehyde Conversion with a Cobalt Complex.

Formox, a highly energy-intensive process, currently serves as the primary source of formaldehyde (HCHO), for which there is a crucial and steadily growing chemical demand. The alternative electrochemical production of HCHO from C1 carbon sources such as CO2 and CO is still in its early stages, with even the few identified cases lacking mechanistic rationalization. In this study, we demonstrate that cobalt phthalocyanine (CoPc) immobilized on multiwalled carbon nanotubes (MW-CNTs) constitutes an excellent electrocatalytic system for producing HCHO with productivity through the direct reduction of CO, the two-electron reduction product of CO2. By carefully adjusting both the pH and the applied potential, we identified conditions that enable the production of HCHO with a partial current density of 0.64 mA cm-2 (17.5% Faradaic efficiency, FE) and a total FE of 61.2% for the liquid products (formaldehyde and methanol). A reduction mechanism is proposed.

Repurposing FDA approved drugs against Sterol C-24 methyltransferase of Leishmania donovani: A dual in silico and in vitro approach.

Leishmaniasis is a disease caused by the parasite Leishmania donovani affecting populations belonging to developing countries. The present study explores drug repurposing as an innovative strategy to identify new uses for approved clinical drugs, reducing the time and cost required for drug discovery. The three-dimensional structure of Leishmania donovani Sterol C-24 methyltransferase (LdSMT) was modeled and 1615 FDA-approved drugs from the ZINC database were computationally screened to identify the potent leads. Fulvestrant, docetaxel, indocyanine green, and iohexol were shortlisted as potential leads with the highest binding affinity and fitness scores for the concerned pathogenic receptor. Molecular dynamic simulation studies showed that the macromolecular complexes of indocyanine green and iohexol with LdSMT remained stable throughout the simulation and can be further evaluated experimentally for developing an effective drug. The proposed leads have further demonstrated promising safety profiles during cytotoxicity analysis on the J774.A1 macrophage cell line. Mechanistic analysis with these two drugs also revealed significant morphological alterations in the parasite, along with reduced intracellular parasitic load. Overall, this study demonstrates the potential of drug repurposing in identifying new treatments for leishmaniasis and other diseases affecting developing countries, highlighting the importance of considering approved clinical drugs for new applications.

Neuroprotective Effects of Cannabispirenone A against NMDA-Induced Excitotoxicity in Differentiated N2a Cells.

The endocannabinoid system is found throughout the central nervous system, and its cannabinoids receptor 1 is critical in preventing neurotoxicity caused by N-methyl-D-aspartate receptor activation (NMDARs). The activity of NMDARs places demands on endogenous cannabinoids to regulate their calcium currents. Endocannabinoids keep NMDAR activity within safe limits, protecting neural cells from excitotoxicity. Cannabinoids are remembered to deliver this outcome by repressing presynaptic glutamate discharge or obstructing postsynaptic NMDAR-managed flagging pathways. The endocannabinoid system must exert a negative influence proportional to the strength of NMDAR signaling for such control to be effective. The goal of this paper is to draw the attention towards the neuroprotective mechanism of constituents of Cannabis sativa against NMDA-induced excitotoxic result. Phytochemical investigation of the cannabis flowers led to the isolation of nine secondary metabolites. A spiro-compound, Cannabispirenone A, which on treatment of the cells prior to NMDA exposure significantly increases cell survival while decreasing ROS production, lipid peroxidation, and intracellular calcium. Our findings showed that this compound showed neuroprotection against NMDA-induced excitotoxic insult, has antioxidative properties, and increased cannabinoid receptor 1 expression, which may be involved in the signaling pathway for this neuroprotection.

Toward Rational Design of Mononuclear Nickel Complexes as Water Oxidation Catalysts Exploring the Ligand Effects on the Rate-Determining Step.

The major impediment in realizing a carbon-neutral hydrogen fuel economy is the cost and inadequacy of contemporary electrochemical water splitting approaches towards the energy intensive oxygen evolution reaction (OER). The O-O bond formation in the water oxidation half-cell reaction is both kinetically and thermodynamically challenging and amplifies the overpotential requirement in most of the active water oxidation catalysts. Herein, density functional theory is employed to interrogate 20 Ni(II) complexes, out of which 17 are in silico designed molecular water oxidation catalysts, coordinated to electron-rich tetra-anionic redox non-innocent phenylenebis(oxamidate) and dibenzo-1,4,7,10-tetraazacyclododecane-2,3,8,9-tetraone parent ligands and their structural analogues, and identify the role of substituent changes or ligand effects in the order of their reactivity. Importantly, our computational mechanistic analyses predict that the activation free energy of the rate-determining O-O bond formation step obeys an inverse scaling relationship with the global electrophilicity index of the intermediate generated on two-electron oxidation of the starting complex. Additionally, the driving force is directly correlated with this OER descriptor which enables two-dimensional volcano representation and thereby extrapolation towards the ideal substitution with the chosen ligand. Our study, therefore, establish fundamental insights to overcome the imperative overpotential issue with simple and precise computational rationalization preceding experimental validation.

Co-occurrence of rhino-orbital mucormycosis and acute lymphoblastic leukemia post-COVID-19 infection in a young adolescent male: A case report from a low middle-income country.

Key Clinical Message: Immunosuppression from B-acute lymphoblastic leukemia (B-ALL) chemotherapy and a preceding COVID-19 infection may predispose patients to rare complications such as rhino-orbital mucormycosis. Hence, a high index of suspicion should be maintained by physicians (and oncologists) if patients undergoing B-ALL treatment present with orofacial symptoms and ophthalmological manifestations such as peri-orbital swelling, ophthalmoplegia, and loss of vision, suggestive of infection. Abstract: Mucormycosis is a severe fungal infection that poses significant mortality and morbidity risks, particularly in immunocompromised individuals. We present a rare case of a 16-year-old patient with rhino-orbital mucormycosis following B-acute lymphoblastic leukemia (B-ALL) treatment and concurrent COVID-19 infection. We describe the clinical presentation, diagnosis, treatment, and outcome of this patient, and discuss the possible interactions and implications of these three conditions. A young 16-year-old male patient without significant clinical history was admitted with complaints of low-grade intermittent fever, fatigue, malaise, restlessness, and unexplained weight loss for the past 2 months. A bone marrow biopsy confirmed the diagnosis of B-ALL. Following the diagnosis of B-ALL, the patient underwent initiation of chemotherapy. Following the initial two cycles of chemotherapy, the patient experienced fever and cough and tested positive for COVID-19 infection. Nearly a week later, the patient presented to the chemotherapy emergency department with a clinical picture characterized by a fever up to 39°C associated with left facial swelling, severe headache, purulent rhinorrhea, and foreign body sensation in the ipsilateral nostril. The following day, erythema and left eyelid edema were observed, with ocular opening limitation. The diagnosis was confirmed based on the positive result of polymerase chain reaction for left-sided mucormycosis. Initial administration of liposomal and lipid amphotericin B at 1-1.5 mg/kg/d doses for 4-6 weeks was followed by surgical debridement of necrotic tissue on the left side of the face and nose. Subsequent ophthalmological examinations showed normal conditions of the left eye. The case underscores the importance of heightened clinical suspicion, early diagnosis through imaging and molecular techniques, aggressive multimodal therapy, and close interdisciplinary collaboration for improved outcomes in such rare and challenging clinical scenarios.

Ultrafast Dynamics of Self-Trapped Excitons in Cs2AgInCl6:Al3+ Double Perovskite Nanocrystals.

It is a huge challenge to increase the photoluminescence (PL) of lead-free halide perovskites, and understanding the mechanism behind exciton dynamics can provide a valuable solution. Herein, we achieved enhanced broad-band emission at ambient conditions in Cs2AgInCl6 by tuning self-trapped excitons (STEs) through Al3+ doping. Cryogenic measurements showed an inhomogeneous nature of STE emission due to the presence of defect states and is subject to thermal quenching. An increased Huang-Rhys factor (S-factor) resulted in better electron-phonon coupling and high-density STE states post Al3+ doping. Femtosecond transient absorption (fs-TA) results provided insights into the distribution dynamics of excitons, which occurs through gradient energy levels from free excitons (FE) to STEs, where each STE state potentially possesses higher quantized energy states. Overall, this study aims to comprehend the origins of self-trapping and decay of STEs in Cs2AgInCl6:Al3+ and emphasizes the potential of compositional engineering to mitigate self-trapping in this material.

Exploring landscape of measles vaccination coverage: A step towards measles elimination goal in India.

INTRODUCTION: Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24-35 months. DATA SOURCES AND METHODOLOGY: The National Family Health Survey 2019-21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24-35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. RESULTS: The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. DISCUSSION: Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal.

Growth-regulated co-occupancy of Mediator and Lsm3 at intronic ribosomal protein genes.

Mediator is a well-known transcriptional co-regulator and serves as an adaptor between gene-specific regulatory proteins and RNA polymerase II. Studies on the chromatin-bound form of Mediator revealed interactions with additional protein complexes involved in various transcription-related processes, such as the Lsm2-8 complex that is part of the spliceosomal U6 small nuclear ribonucleoprotein complex. Here, we employ Chromatin Immunoprecipitation sequencing (ChIP-seq) of chromatin associated with the Lsm3 protein and the Med1 or Med15 Mediator subunits. We identify 86 genes co-occupied by both Lsm3 and Mediator, of which 73 were intron-containing ribosomal protein genes. In logarithmically growing cells, Mediator primarily binds to their promoter regions but also shows a second, less pronounced occupancy at their 3'-exons. During the late exponential phase, we observe a near-complete transition of Mediator from these promoters to a position in their 3'-ends, overlapping the Lsm3 binding sites ∼250 bp downstream of their last intron-exon boundaries. Using an unbiased RNA sequencing approach, we show that transition of Mediator from promoters to the last exon of these genes correlates to reduction of both their messenger RNA levels and splicing ratios, indicating that the Mediator and Lsm complexes cooperate to control growth-regulated expression of intron-containing ribosomal protein genes at the levels of transcription and splicing.