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Background: Benign prostatic hyperplasia affects about 210 million males as of 2010 (6% of the population). BPH is the most common disease of men above 50 years of age. BPH is a major cause of morbidity in the ageing men. Lower urinary tract symptoms, are a collective term for the symptoms of disrupted voiding in males, which has long been associated with BPH. Materials and Methods: Study was descriptive cross-sectional study conducted in Department of Urology, Nobel medical college, Biratnagar, Nepal over a period from January 2022 to December 2022. The entire Patient with visiting urology clinic of the provisionally diagnosed as BEP was enrolled in the study with approval of institutional review committee. Results: We enrolled a cohort of 75 patients who had been diagnosed with BEP. The mean age was 51.31 years. The mean prostate size among these individuals was measured to be 45.63 grams, and their mean Prostate-Specific Antigen level was determined to be 3.57.We observed a moderate positive correlation (r = 0.536) with statistical significance (p < 0.01) between VPSS total and IPSS total. Out of total, 35 (47%) completed VPSS alone without any assistance while filling IPSS only 9 (12%) could complete one. Median time for completing VPSS versus IPSS was 60sec and 300 sec respectively. Conclusion: In assessment of symptom severity visual prostate symptom score is equally effective as International prostate symptom score in cases of benign prostatic hyperplasia presenting with Lower urinary tract symptoms. All parameters of visual prostate symptom score is significantly correlated with International prostate symptom score.

Abstract Hybrid molecules maintain their stronghold in the drug market, with over 60% of drug candidates in pharmaceutical industries. The substantial expenses for developing and producing biologically privileged drugs are expected to create opportunities for producing hybrid molecule-based drugs. Therefore, we have developed a simple and efficient copper-catalyzed approach for synthesizing a wide range of triazole-linked glycohybrids derived from pyrazolo[1,5-a]pyrimidines. Employing a microwave-assisted copper-catalyzed approach, we developed a concise route using various 7-O-propargylated pyrazolo[1,5-a]pyrimidines and 1-azidoglycosides. This strategy afforded a series of twenty-seven glycohybrids up to 98% yield with diverse stereochemistry. All were achieved within a remarkably shortened time frame. Our investigation extends to evaluating the anticancer potential of these synthesized triazole-linked pyrazolo[1,5-a] pyrimidine-based glycohybrids. In-vitro assays against MCF-7, MDA-MB231, and MDA-MB453 cell lines reveal intriguing findings. (2R,3S,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate emerges as a standout with better anticancer activity against MDA-MB231 cells (IC50 = 29.1 µM), while (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-(((5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)tetrahydro-2H-pyran-3,4,5-triyl triacetate demonstrates the best inhibitory effects against MCF-7 cells (IC50 = 15.3 µM) in all derived compounds. These results align with our docking analysis and structure–activity relationship (SAR) investigations, further validating the in-vitro outcomes. This work not only underscores the synthetic utility of our devised protocol but also highlights the promising potential of these glycohybrids as candidates for further anticancer therapeutic exploration.

Background: Amongst all the modalities of treatment for renal stones, percutaneous nephrolithotomy is preferred treatment for large volume renal stone disease. However, percutaneous nephrolithotomy is associated with the risk of postoperative complications and the problem of stone free status. So, a preoperative classification is necessary to grade the complexity of percutaneous nephrolithotomy and STONE (stone size, tract length, degree of obstruction, number of involved calices, and stone essence) nephrolithometry score is one of such kind. Materials and Methods: This is analytical study conducted at the Department of Urology and Kidney Transplant, Nobel Medical College and Teaching Hospital, Biratnagar, Nepal from January 2020 to July 2020. Total 115 patients were included in the study. These patients were subjected for percutaneous nephrolithotomy. Stone clearance was documented at the end of the surgery; on first postoperative day and at 4 weeks. Results: In our study the stone – free rate was 89.6%. 32 patients experienced complications (27.8%). The STONE (stone size, tract length, degree of obstruction, number of involved calices, and stone essence) score correlated with the postoperative stone – free status (P=0.001). The patients rendered stone free had statistically significant lower scores than the patients with residual stones (6.83 ± 1.83 vs 9.83 ± 2.08, P = 0.001). Conclusion: The STONE (stone size, tract length, degree of obstruction, number of involved calices, and stone essence) nephrolithometry score is a simple and easy tool to apply system for predicting complexity in stone clearance with percutaneous nephrolithotomy.

Background: Laparoscopic Cholecystectomy is considered as a gold standard treatment for symptomatic cholelithiasis. The timing of surgery for acute Cholecystitis is still controversial, weather to go early surgery or wait for six to eight weeks after conservative management. Therefore, the aim of this study is to compare the clinical outcomes of early versus delayed laparoscopic cholecystectomy for acute Cholecystitis. Materials and Methods: A prospective study was conducted in Nobel Medical College Teaching Hospital, Biratnagar, Nepal. Total of 80 patients with the diagnosis of acute Cholecystitis were enrolled in the study. The patients were equally divided in two groups: 40 underwent early laparoscopic cholecystectomy within 72 hours of admission (Group A) and next 40 underwent delayed laparoscopic cholecystectomy after 6-8 weeks of conservative management (Group B). Results: Out of 80 patients of acute Cholecystitis, mean age of the patients in Group A was 43.40±13.45 years and that in Group B was 44.80±14.36 years. The mean operative time in Group A was 90.22±2.81 minutes whereas in Group B it was 80.97±4.47 minutes. Mean duration of Hospital stay in Group A was 2.02±0.15 days whereas in Group B it was 2.15±0.36 days. Two patients in Group A and one patient in Group B converted to open cholecystectomy. Three patients of Group A and one patient of Group B landed in outpatient department with superficial surgical site infection. Group B patients underwent second hospital admission compared to Group A patients. Conclusion: Early Laparoscopic cholecystectomy for acute cholecystitis is almost comparable with delayedLaparoscopic cholecystectomy. However, early laparoscopic cholecystectomy reduces the morbidity of patients as well as it is cost-effectiveness.

Active galactic nuclei (AGN) feedback and its impact on their host galaxies are critical to our understanding of galaxy evolution. Here, we present a combined analysis of new high resolution ultraviolet (UV) data from the Ultraviolet Imaging Telescope (UVIT) on AstroSat and archival optical spectroscopic data from the Very Large Telescope/MUSE, for the Seyfert galaxy, NGC 1365. Concentrating on the central 5 kpc region, the UVIT images in the far- and near-UV show bright star-forming knots in the circumnuclear ring as well as a faint central source. After correcting for extinction, we found the star formation rate (SFR) surface density of the circumnuclear 2 kpc ring to be similar to other starbursts, despite the presence of an AGN outflow, as seen in [O iii ] 5007 Å. On the other hand, we found fainter UV and thus lower SFR in the direction southeast of the AGN relative to northwest in agreement with observations at other wavelengths from JWST and Atacama Large Millimeter/submillimeter Array. The AGN outflow velocity is found to be lesser than the escape velocity, suggesting that the outflowing gas will rain back into the galaxy. The deep UV data have also revealed diffuse UV emission in the direction of the AGN outflow. By combining [O iii ] and UV data, we found the diffuse emission to be of AGN origin.

We present a detailed near-infrared study of an embedded cluster located in the hub of the giant molecular cloud G148.24+00.41 of mass ∼10 ^5 M _⊙ , with the TANSPEC instrument mounted on the 3.6 m Devasthal Optical Telescope. The hub is located near the geometric center of the cloud and represents its most massive clump. We studied the central 2 pc × 2 pc area of the hub with 5 σ limiting magnitudes of 20.5, 20.1, and 18.6 mag in the J , H , and K _s bands, respectively. Using the K _s - band luminosity function and comparing it with the synthetic clusters, we obtained the age of the cluster as ∼0.5 Myr, which was found to corroborate well with the visual extinction versus the age of nearby embedded clusters. We find that the present mass of the cluster is around ∼180 M _⊙ , and the cluster is currently forming stars at a rate of ∼330 M _⊙ Myr ^−1 , with an efficiency of ∼20%. The cluster is connected to an extended gas reservoir through a filamentary network; thus, we hypothesize that the cluster has the potential to become a richer cluster in a few Myr of time.

We present the study of four far-ultraviolet (FUV) bright stars in the field of the open cluster NGC 2420 using the Ultra Violet Imaging Telescope mounted on AstroSat. The three stars 525, 527, and 560 are members, while star 646 is a nonmember of the cluster. To characterize and determine the parameters of these stars, multiwavelength spectral energy distributions (SEDs) are analyzed using UV, optical, and IR data sets. For all four FUV bright stars, a two-component SED model fits well. Our findings indicate that two stars, 525 and 560, are binary blue straggler star (BSS) systems. These BSS systems may have formed in a tertiary system due to mass transfer from an evolved outer tertiary companion. Star 527 is a binary system of a BSS and an extremely low-mass (ELM) white dwarf, while star 646 is a binary system of a horizontal branch star and an ELM white dwarf. The effective temperatures, radii, luminosities, and masses of the two ELMs are (10250, 11500) K (0.42, 0.12) R _⊙ , (1.61, 0.23) L _⊙ , and (0.186, 0.170) M _⊙ , respectively. The star 527 could be a post-mass-transfer system and may have originated through the Case A/B mass-transfer process in a low-density environment. The cooling age of the ELMs is < 1 Myr, indicating that they have only recently formed.

Agitation is one of the most eminent characteristics of neuropsychiatric symptoms (NPS) affecting people living with Alzheimer’s and Dementia and has serious consequences for patients and caregivers. The current consensus is that agitation results, in part, from the disruption of ascending monoamine regulators of cortical circuits, especially the loss of serotonergic activity. It is believed that the first line of treatment for these conditions is selective serotonin reuptake inhibitors (SSRIs), but these are effective in only about 40% of patients. Person-specific biomarkers, for example, ones based on in vitro iPSC-derived models of serotonin activity, which predict who with Agitation responds to an SSRI, are a major clinical priority. Here, we report the generation of human-induced pluripotent stem cells (iPSCs) from a 74-year-old AD patient, the homozygous APOE ε4/ε4 carrier, who developed Agitation. His iPSCs were reprogrammed from peripheral blood mononuclear cells (PBMCs) using the transient expression of pluripotency genes. These display typical iPSC characteristics that are karyotypically normal and attain the capacity to differentiate into three germ layers. The newly patient-derived iPSC line offers a unique resource to investigate the underlying mechanisms associated with neuropsychiatric symptom progression in AD.

The recent advances in creating pluripotent stem cells from somatic cells and differentiating them into a variety of cell types is allowing us to study them without the caveats associated with disease-related changes. We generated induced Pluripotent Stem Cells (iPSCs) from eight Alzheimer’s disease (AD) patients and six controls and used lentiviral delivery to differentiate them into excitatory glutamatergic neurons. We then performed RNA sequencing on these neurons and compared the Alzheimer’s and control transcriptomes. We found that 621 genes show differences in expression levels at adjusted p < 0.05 between the case and control derived neurons. These genes show significant overlap and directional concordance with genes reported from a single-cell transcriptome study of AD patients; they include five genes implicated in AD from genome-wide association studies and they appear to be part of a larger functional network as indicated by an excess of interactions between them observed in the protein–protein interaction database STRING. Exploratory analysis with Uniform Manifold Approximation and Projection (UMAP) suggests distinct clusters of patients, based on gene expression, who may be clinically different. Our research outcomes will enable the precise identification of distinct biological subtypes among individuals with Alzheimer’s disease, facilitating the implementation of tailored precision medicine strategies.

Abstract The conversion of NIR light into visible light has been studied in Ho3+/Yb3+/Bi3+ co-doped ZnGa2O4 phosphor for the first time. The crystallinity and particles size of the phosphor increase through Bi3+ doping. The absorption characteristics of Ho3+, Yb3+ and Bi3+ ions are identified by the UV–vis-NIR measurements. The Ho3+ doped phosphor produces intense green upconversion (UC) emission under 980 nm excitations. The emission intensity ~ excitation power density plots show contribution of two photons for the UC emissions. The UC intensity of green emission is weak in the Ho3+ doped phosphor, which enhances upto 128 and 228 times through co-doping of Yb3+ and Yb3+/Bi3+ ions, respectively. The relative and absolute temperature sensing sensitivities of Ho3+/Yb3+/5Bi3+ co-doped ZnGa2O4 phosphor are calculated to be 13.6 × 10−4 and 14.3 × 10−4 K−1, respectively. The variation in concentration of Bi3+ ion and power density produces excellent color tunability from green to red via yellow regions. The CCT also varies with concentration of Bi3+ ion and power density from cool to warm light. The color purity of phosphor is achieved to 98.6% through Bi3+ doping. Therefore, the Ho3+/Yb3+/Bi3+:ZnGa2O4 phosphors can be suitable for UC-based color tunable devices, green light emitting diodes and temperature sensing.

Abstract Hijacking of host metabolic status by a pathogen for its regulated dissemination from the host is prerequisite for the propagation of infection. M. tuberculosis secretes an NAD+-glycohydrolase, TNT, to induce host necroptosis by hydrolyzing Nicotinamide adenine dinucleotide (NAD+). Herein, we expressed TNT in macrophages and erythrocytes; the host cells for M. tuberculosis and the malaria parasite respectively, and found that it reduced the NAD+ levels and thereby induced necroptosis and eryptosis resulting in premature dissemination of pathogen. Targeting TNT in M. tuberculosis or induced eryptosis in malaria parasite interferes with pathogen dissemination and reduction in the propagation of infection. Building upon our discovery that inhibition of pathogen-mediated host NAD+ modulation is a way forward for regulation of infection, we synthesized and screened some novel compounds that showed inhibition of NAD+-glycohydrolase activity and pathogen infection in the nanomolar range. Overall this study highlights the fundamental importance of pathogen-mediated modulation of host NAD+ homeostasis for its infection propagation and novel inhibitors as leads for host-targeted therapeutics.

Precision medicine (PM) in public health offers a new paradigm. Over a past few decades, there has been very rapid development in science and technology, especially in medical-clinical research to enhance the likelihood of preventive treatment which is personalized to an individual. This combined with digital health and accessibility of environmental and behavioral data offers a unique opportunity for specific prevention advice to individuals and thus to population at large. Indian with its 1.3 billion population and its ethnic diversity with high burden of disease offers a unique opportunity for the role of PM in public health. The article further explores the status and way forward for PM in India.

Visceral leishmaniasis (VL) and post kala-azar dermal leishmaniasis (PKDL) affect most of the poor populations worldwide. The current treatment modalities include liposomal formulation or deoxycholate salt of amphotericin B, which has been associated with various complications and severe side effects. Encouraged from the recent marked antimalarial effects from plant-derived glycosides, in this study, we have exploited a green chemistry-based approach to chemically synthesize a library of diverse glycoside derivatives (Gly1–12) and evaluated their inhibitory efficacy against the AG83 strain of Leishmania donovani. Among the synthesized glycosides, the in vitro inhibitory activity of Glycoside-2 (Gly2) (1.13 µM IC50 value) on L. donovani promastigote demonstrated maximum cytotoxicity with ~94% promastigote death as compared to amphotericin B that was taken as a positive control. The antiproliferative effect of Gly2 on promastigote encouraged us to analyze the structure–activity relationship of Gly2 with Gp63, a zinc metalloprotease that majorly localizes at the surface of the promastigote and has a role in its development and multiplication. The result demonstrated the exceptional binding affinity of Gly2 toward the catalytic domain of Gp63. These data were thereafter validated through cellular thermal shift assay in a physiologically relevant cellular environment. Mechanistically, reduced multiplication of promastigotes on treatment with Gly2 induces the destabilization of redox homeostasis in promastigotes by enhancing reactive oxygen species (ROS), coupled with depolarization of the mitochondrial membrane. Additionally, Gly2 displayed strong lethal effects on infectivity and multiplication of amastigote inside the macrophage in the amastigote–macrophage infection model in vitro as compared to amphotericin B treatment. Gp63 is also known to bestow protection against complement-mediated lysis of parasites. Interestingly, Gly2 treatment enhances the complement-mediated lysis of L. donovani promastigotes in serum physiological conditions. In addition, Gly2 was found to be equally effective against the clinical promastigote forms of PKDL strain (IC50 value of 1.97 µM); hence, it could target both VL and PKDL simultaneously. Taken together, this study reports the serendipitous discovery of Gly2 with potent antileishmanial activity and proves to be a novel chemotherapeutic prototype against VL and PKDL.

Background: Benign prostatic hyperplasia is regarded as non-malignant growth of prostatic tissueIt is the most common benign tumor in men, and the incidence is age related. In men aged more than 50 years, it is the fourth most prevalent disease. This study aim to determine the association of benign prostatic hyperplasia with diabetes mellitus and/or hypertension and this may help to bring out new dimensions in management of benign prostatic hyperplasia, hypertension and diabetes mellitus. Materials and Methods: Five hundred forty patients, diagnosed as benign enlargement of prostate with control group 270 at Urology out patient door between May 2018 to February 2019 with approval of Institutional review committee, were included. Patient with history of prostate cancer, neurogenic bladder, those who had undergone surgical intervention for prostate, not willing to take part in study were excluded. Results: Age range in cases and control were from 41–94 years. Diabetes was present in 14.63% of cases and 11.85% of controls. The positive association was established between prostatic hyperplasia and Diabetes (P-0.27). Hypertension was present in 37.96% of cases and 29.63% of controls (P-0.019). Diabetes and Hypertension were present in 56.48% in cases and 43.33% in control (P-0.000). Conclusion: Study suggests that benign prostatic hyperplasia is associated with diabetes mellitus and hypertension and may help to bring out new dimensions in management of benign prostatic hyperplasia.

Introduction: Patients of COVID-19 patients while in a hospital may have stigma, fear, and guilt among them. However, the data on anxiety among the admitted COVID-19 patients are lacking in India and elsewhere. Hence, the study was conducted among the admitted patient of COVID-19 to describe their anxiety status. Methods: The study was conducted as a cross-sectional study in a designated COVID-19 hospital in Delhi. The data were collected from October 22, 2020, to November 21, 2020. All patients who were admitted to the hospital for more than 72 h were eligible for participation. The data collection was done using a questionnaire. The questionnaire consists of two parts. One part was sociodemographic variables, and the other part was the Anxiety Scale. The anxiety score was collected on the Zung Self-Rating Anxiety Scale. Results: A total of 132 eligible patients were admitted during the period. The questionnaire was answered by 122 (92.4%) patients. All patients were male. The patients' mean age was 33.5 years (standard deviation = 8.9 years), with a range of 21 years–65 years. The mean score of the Zung Self-Rating Scale was 29.5 (7.2), with an interquartile range of 24–33. There were only five patients (4.4%; 95% confidence interval: 1.3%–9.3%) whose scores were 45 or more, indicating mild-to-moderate anxiety. There was no statistically significant association between any sociodemographic variable and Anxiety Rating Scale. Conclusion: The anxiety level in the specialized population was low due to social security. The level of anxiety among health-care workers may be further explored.

Black-hole-driven outflows in galaxies hosting active galactic nuclei (AGN) may interact with their interstellar medium (ISM) affecting star formation (SF). Such feedback processes, reminiscent of those seen in massive galaxies, have been reported recently in some dwarf galaxies. However, such studies have usually been on kiloparsec and larger scales and our knowledge of the smallest spatial scales to which these feedback processes can operate is unclear. Here we demonstrate radio jet−ISM interaction on the scale of an asymmetric triple radio structure of ∼10 pc size in NGC 4395. This triple radio structure is seen in the 15 GHz continuum image and the two asymmetric jet-like structures are situated on either side of the radio core that coincides with the optical Gaia position. The high-resolution radio image and the extended [O iii ] λ 5007 emission, indicative of an outflow, are spatially coincident and are consistent with the interpretation of a low-power radio jet interacting with the ISM. Modelling of the spectral lines using MAPPINGS , and estimation of temperature using optical integral field spectroscopic data suggest shock ionization of the gas. The continuum emission at 237 GHz, though weak, was found to spatially coincide with the AGN. However, the CO(2−1) line emission was found to be displaced by around 20 pc northward of the AGN core. The spatial coincidence of molecular H _2 λ 2.4085 along the jet direction, the morphology of ionized [O iii ] λ 5007, and displacement of the CO(2−1) emission argues for conditions less favorable for SF in the central ∼10 pc region.

Please note, following publication of the original article [1], the authors have advised of two errors that are present in the published article.

Abstract Background Malaria is one of the deadliest infectious diseases caused by protozoan parasite of Plasmodium spp. Increasing resistance to anti-malarials has become global threat in control of the disease and demands for novel anti-malarial interventions. Naturally-occurring coumarins, which belong to a class of benzo-α-pyrones, found in higher plants and some essential oils, exhibit therapeutic potential against various diseases. However, their limited uptake and non-specificity has restricted their wide spread use as potential drug candidates. Methods Two series of carbohydrate fused pyrano[3,2-c]pyranone carbohybrids which were synthesized by combination of 2-C-formyl galactal and 2-C-formyl glucal, with various freshly prepared 4-hydroxycoumarins were screened against Plasmodium falciparum. The anti-malarial activity of these carbohybrids was determined by growth inhibition assay on P. falciparum 3D7 strain using SYBR green based fluorescence assay. Haemolytic activity of carbohybrid 12, which showed maximal anti-malarial activity, was determined by haemocompatibility assay. The uptake of the carbohybrid 12 by parasitized erythrocytes was determined using confocal microscopy. Growth progression assays were performed to determine the stage specific effect of carbohybrid 12 treatment on Pf3D7. In silico studies were conducted to explore the mechanism of action of carbohybrid 12 on parasite microtubule dynamics. These findings were further validated by immunofluorescence assay and drug combination assay. Results 2-C-formyl galactal fused pyrano[3,2-c]pyranone carbohybrid 12 exhibited maximum growth inhibitory potential against Plasmodium with IC50 value of 5.861 µM and no toxicity on HepG2 cells as well as no haemolysis of erythrocytes. An enhanced uptake of this carbohybrid compound was observed by parasitized erythrocytes as compared to uninfected erythrocytes. Further study revealed that carbohybrid 12 arrests the growth of parasite at trophozoite and schizonts stage during course of progression through asexual blood stages. Mechanistically, it was shown that the carbohybrid 12 binds to α,β-heterodimer of tubulin and affects microtubule dynamics. Conclusion These findings show carbohydrate group fusion to 4-hydroxycoumarin precursor resulted in pyrano-pyranones derivatives with better solubility, enhanced uptake and improved selectivity. This data confirms that, carbohydrate fused pyrano[3,2-c]pyranones carbohybrids are effective candidates for anti-malarial interventions against P. falciparum.

A new central nervous system (CNS) depressant cardenolide glycoside named nerioleanderoside (1) was isolated from active n-butanol fraction of the aqueous- ethanolic (5:95 v/v) extract of the fresh dried roots of Nerium oleander. The chemical structure of nerioleanderoside was elucidated as 3β-O-(d-diginosyl)-15 β-O-(d-glucopyranosyl)-14 β -hydroxy-card-20(22)-enolide, through spectroscopic methods including IR, HRMS, NMR spectroscopy and acidic hydrolysis. One more new cardinolide glycoside (2), fully characterized stereochemically as 3 β-O-(d-diginosyl)-(1 → 4) β-(d-glucopyranosyl)-14 β-hydroxy-card-20(22)-enolide was isolated from same n-butanol fraction. The pure nerioleanderoside (1) exhibited CNS depressant activity in Swiss mice at the dose of 15 mg/kg.

The treatment of complex and multifactorial diseases constitutes a big challenge in day-to-day clinical practice. As many parameters influence clinical phenotypes, accurate diagnosis and prompt therapeutic management is often difficult. Significant research and investment focuses on state-of-the-art genomic and metagenomic analyses in the burgeoning field of Precision (or Personalized) Medicine with genome-wide-association-studies (GWAS) helping in this direction by linking patient genotypes at specific polymorphic sites (single-nucleotide polymorphisms, SNPs) to the specific phenotype. The generation of polygenic risk scores (PRSs) is a relatively novel statistical method that associates the collective genotypes at many of a person’s SNPs to a trait or disease. As GWAS sample sizes increase, PRSs may become a powerful tool for prevention, early diagnosis and treatment. However, the complexity and multidimensionality of genetic and environmental contributions to phenotypes continue to pose significant challenges for the clinical, broad-scale use of PRSs. To improve the value of PRS measures, we propose a novel pipeline which might better utilize GWAS results and improve the utility of PRS when applied to Alzheimer’s Disease (AD), as a paradigm of multifactorial disease with existing large GWAS datasets that have not yet achieved significant clinical impact. We propose a refined approach for the construction of AD PRS improved by (1), taking into consideration the genetic loci where the SNPs are located, (2) evaluating the post-translational impact of SNPs on coding and non-coding regions by focusing on overlap with open chromatin data and SNPs that are expression quantitative trait loci (QTLs), and (3) scoring and annotating the severity of the associated clinical phenotype into the PRS. Open chromatin and eQTL data need to be carefully selected based on tissue/cell type of origin (e.g., brain, excitatory neurons). Applying such filters to traditional PRS on GWAS studies of complex diseases like AD, can produce a set of SNPs weighted according to our algorithm and a more useful PRS. Our proposed methodology may pave the way for new applications of genomic machine and deep learning pipelines to GWAS datasets in an effort to identify novel clinically useful genetic biomarkers for complex diseases like AD.

Clostridium perfringens epsilon toxin (Etx) is categorized as the third most lethal bioterrorism agent by the Centers for Disease Control and Prevention (CDC), with no therapeutic counter measures available for humans. Here, we have developed a high-affinity inhibitory compound by synthesizing and evaluating the structure activity relationship (SAR) of a library of diverse glycosides (numbered 1-12). SAR of glycoside-Etx heptamers revealed exceptionally strong H-bond interactions of glycoside-4 with a druggable pocket in the oligomerization and β-hairpin region of Etx. Analysis of its structure suggested that glycoside-4 might self-aggregate to form a robust micelle-like supra-molecular complex due to its linear side-chain architecture, which was authenticated by fluorescence spectroscopy. Further, this micelle hinders the Etx monomer-monomer interaction required for oligomerization, validated by both surface plasmon resonance (SPR) and immunoblotting. This phenomenon in turn leads to blockage of pore formation. Downstream evaluation revealed that glycoside-4 effectively blocked cell death of Etx-treated cultured primary cells and maintained cellular homeostasis via disrupting oligomerization, blocking pore formation, restoring calcium homeostasis, stabilizing the mitochondrial membrane and impairing high mobility group box 1 (HMGB1) translocation from nucleus to cytoplasm. Furthermore, a single dosage of glycoside-4 protected the Etx-challenged mice and restored normal function to multiple organs. This work reports for the first time a potent, nontoxic glycoside with strong ability to occlude toxin lethality, representing it as a bio-arm therapeutic against Etx-based biological threat.

Objective: The aim of the present case–control study was to determine the association between methylene tetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene polymorphism and risk of ischemic stroke (IS) in North Indian population. Methods: Patients with IS and age-sex matched controls were recruited from Neurology Outpatient Department and Ward of All India Institute of Medical Sciences, New Delhi, India. Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method. PCR–RFLP results of nine randomly selected samples were confirmed by DNA sequencing. Genotypic and allelic distributions were compared between cases and controls. Statistical analysis was done by STATA, version 13.0 software. Results: Hypertension, diabetes, dyslipidemia, low socioeconomic status and family history of stroke were found to have an independent association with the risk of IS after adjusting for potential confounding factors. Mean age of cases and controls were 52.83 ± 12.59 and 50.97 ± 12.70 years. Multivariate logistic regression analysis showed an independent association between MTHFR C677T gene polymorphism and risk of IS (OR 1.91; 95% CI 1.07–3.41; p = 0.028) under dominant model [CT + TT vs. CC]. MTHFR C677T gene polymorphism was found to be independently associated with risk of small vessel disease (SVD) after adjustment for potential confounding factors [OR 2.51; 95% CI 1.30–4.85; p = 0.006] under the dominant model. Conclusion: Findings of the present study suggest that MTHFR C677T gene polymorphism might be a risk factor of IS mainly for SVD subtypes of IS in North Indian population. Further large prospective studies are required to confirm these findings.

Sugarcane is an important tropical cash crop meeting 75% of world sugar demand and it is fast becoming an energy crop for the production of bio-fuel ethanol. A considerable area under sugarcane is prone to waterlogging which adversely affects both cane productivity and quality. In an effort to elucidate the genes underlying plant responses to waterlogging, a subtractive cDNA library was prepared from leaf tissue. cDNA clones were sequenced and annotated for their putative functions. Major groups of ESTs were related to stress (15%), catalytic activity (13%), cell growth (10%) and transport related proteins (6%). A few stress-related genes were identified, including senescence-associated protein, dehydration-responsive family protein, and heat shock cognate 70 kDa protein. A bioinformatics search was carried out to discover novel microRNAs (miRNAs) that can be regulated in sugarcane plants subjected to waterlogging stress. Taking advantage of the presence of miRNA precursors in the related sorghum genome, seven candidate mature miRNAs were identified in sugarcane. The application of subtraction technology allowed the identification of differentially expressed sequences and novel miRNAs in sugarcane under waterlogging stress. The comparative global transcript profiling in sugarcane plants undertaken in this study suggests that proteins associated with stress response, signal transduction, metabolic activity and ion transport play important role in conferring waterlogging tolerance in sugarcane.

Context: Teeth and restorations are subjected continuously to degradation in hostile physical and chemical environments, resulting in corrosion. Component of liquid or solid is an important factor influencing the corrosion of metallic appliances placed in the oral cavity. Aims: To study in vitro corrosion of titanium wires immersed in solutions of toothpaste and chocolate in artificial saliva. Materials and Methods: Immersion test and electrochemical studies using different parameters, including corrosion potential (E corr ), cathodic Tafel constant (βc), anodic Tafel constant (βa), corrosion current (I corr ), polarization resistance (R p ), and corrosion rate of titanium wires, were done in solutions of artificial saliva containing Colgate™ toothpaste and Amul™ chocolate. Photomicrographs were also taken. Results: The results showed degradation of titanium wires by electrochemical attack when they were placed in the hostile electrolytic environments provided in the experiments. Surface analysis of titanium wires showed pitting and localized attacks on the surface. Pitting corrosion was found in the titanium wires.

Background: Childhood obesity is a global health challenge. Socioeconomic factors play a significant role in influencing obesity rates, with distinct variations observed between urban and rural communities. Objective: To investigate the influence of socioeconomic factors on childhood obesity rates in urban versus rural communities using an observational approach. Material and Methods: The study sampled 100 children aged 5-15 years, equally divided between urban and rural areas. Childhood obesity prevalence was determined through BMI classification. Data on socioeconomic status (SES), parental education levels, access to nutritional food, and physical activity levels were collected through questionnaires and surveys. Descriptive statistics were used to identify correlations between these factors and obesity prevalence. Results: Obesity Prevalence: Urban children had a higher obesity prevalence (36%) than rural children (28%). Socioeconomic Status: In urban communities, children from lower SES households had a 40% obesity rate compared to 32% in higher SES households. In rural communities, these rates were 36% (lower SES) and 20% (higher SES). Parental Education Levels: Urban children with parents having a high school education or less had a 45% obesity prevalence versus 20% for those with college-educated parents. In rural communities, these rates were 32% and 25%, respectively. Nutritional Food Access: Urban children with limited access to nutritional food had a 40% obesity prevalence compared to 24% for those with good access. Physical Activity Levels: Urban children with less than 60 minutes of daily activity had a 48% obesity prevalence versus 28% for those exceeding 60 minutes. Rural communities showed similar trends. Conclusion: The study highlights the significant impact of socioeconomic factors on childhood obesity rates. Tailored interventions addressing SES disparities, education, food access, and physical activity are crucial for managing obesity in urban and rural settings. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to obtain the morphological and morphometric variations of the glenoid cavity of the scapula in the population of Bihar and compare it to that of the study done in different races by the previous author. Method: A total of 120 dry adult human scapulae of unknown age and sex in which 60 belong to the right side and 60 belonging to the left side were obtained from the Department of Anatomy and forensic medicine of Indira Gandhi Institute of Medical Sciences, Patna and also from other medical colleges of Bihar. Results: The most common shape of the glenoid cavity recorded in this study was pearshaped followed by inverted comma-shaped. The least common shape was oval. The mean scapular length was observed as 137.11±8.72 mm, the mean breadth of scapula was 98.73±10.92 mm, the mean supero-inferior glenoid diameter was 36.34±3.91 mm, the mean anteroposterior glenoid diameter was 24.95±4.58 mm and mean glenoid cavity index was 68.82±10.33. Conclusion: Morphological and morphometric analysis of the glenoid cavity of the scapula is very important during designing and fitting of glenoid components in total shoulder arthroplasty and its associated shoulder pathology. [ABSTRACT FROM AUTHOR]