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Although most lumbar lesions associated with spinal tuberculosis can be satisfactorily resolved with nonoperative treatment, there are cases in which surgery is indicated. Between July 1982 and December 2003 we retrospectively reviewed 51 patients who were operated by anterior débridement and fusion. Twelve patients were lost to followup and one died due to inferior vena cava tear. Followup of 38 patients ranged from 2 to 10 years (average 4 years). There were 22 male and 16 female patients, average age 35 years (range, 8-65 years); upper lumbar area (L1-L3) was involved in 17 cases, lower lumbar (L3-L5) in 19 and lumbosacral area in two patients; 28 patients had two-body and 10 had three-body involvement. In 35 patients we performed single stage débridement and fusion. More recently three patients had two stage (instrumentation plus débridement and fusion) procedure. Followup was based on subjective relief, recovery of neural deficit and consolidation at fusion site. Thirty-six out of 38 patients had complete relief from pain and discomfort along with radiographic fusion. Five patients who had neural deficit recovered completely. Surgical treatment of lumbar spinal tuberculosis in selected cases gives satisfactory results. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa, an opportunistic bacterial pathogen of public health concern, is known for its metabolic versatility, adaptability in harsh environment, and pathogenic aggressiveness. P. aeruginosa relies on various regulatory networks modulated by small non-coding RNAs, which in turn influence different physiological traits such as metabolism, stress response, and pathogenesis. In this study, srbA sRNA has been shown to play a diverse role in regulating cellular metabolism and the production of different virulence factors in P. aeruginosa. srbA was found to control the TCA cycle, a key regulatory pathway for cellular metabolism and energy production, by regulating three main enzymes: citrate synthase (gltA), isocitrate dehydrogenase (icd), and α-ketoglutarate dehydrogenase E1 subunit (sucA) at both the transcriptional and translational levels. By modulating the TCA cycle, srbA could help the bacteria to adapt nutritional stress by lowering energy consumption. Additionally, srbA has been found to differentially regulate production of various virulence factors such as rhamnolipid, elastase, LasA protease, and pyocyanin under both nutrient-rich and nutrient-limiting conditions. It could also influence motilities in P. aeruginosa, linked to biofilm formation and pathogenicity. Thus, srbA might hold a promise in the research area for identifying virulence pathways and developing novel therapeutic targets to combat the global pathogenic threat of P. aeruginosa., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

An emerging hypothesis linking arsenic toxicity involves altered epigenetic mechanisms, such as DNA methylation. In this study, we examined the relationship between parents' arsenic exposure and DNA methylation in tissues obtained from 28 infants with spina bifida from Bangladesh. We analyzed arsenic in parents' toenails using inductively coupled plasma mass spectrometry (ICP-MS). DNA methylation was measured in infants' dural tissue, buccal swabs, and whole blood using the Illumina Infinium MethylationEPIC BeadChip. We performed epigenome-wide association analyses (EWAS) and tested differentially methylated regions (DMRs). In EWAS, DNA methylation at cg24039697 in dural tissue was positively associated (β = 0.59, p  = 7.6 × 10 -9 ) with father's toenail arsenic concentrations, adjusting for covariates. We did not identify any CpG sites related to father's arsenic exposure in the other tissues, or any CpG sites related to mother's arsenic exposure. Gene ontology analysis identified many biological pathways of interest, including the Wnt signaling pathways. We identified several DMRs across the tissues related to arsenic exposure that included probes mapping to genes that have previously been identified in studies of neural tube defects. This study emphasizes the potential impact of arsenic exposure in fathers, often understudied in epidemiological studies, on DNA methylation in a unique neurological tissue specific to spina bifida.

Objectives: Prevalence of irregular menstrual cycle ranges from 81.7% to 96.3%. Recent research suggested that homeopathy is one of the most popular choices for women with various gynecological disorders. This trial was aimed at differentiating individualized homeopathic medicinal products (IHMPs) from identical-looking placebos in the treatment of menstrual irregularities in early reproductive women. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled trial. Setting: D. N. De Homoeopathic Medical College & Hospital, Kolkata, West Bengal, India. Subjects: Ninety-two females with menstrual irregularities. Interventions: Group verum ( n = 46; IHMPs plus concomitant care) versus group control ( n = 46; placebos plus concomitant care). Outcome Measures: Primary-The proportion of early reproductive females in whom menstrual irregularities can be corrected for consecutive three cycles; Secondary-Menstrual Distress Questionnaire (MDQ) total score; all of them were measured at baseline and every month, up to 4 months. Results: Intention-to-treat sample ( n = 92) was analyzed. Group differences were examined by chi-squared tests with categorical outcomes, two-way repeated measure analysis of variance accounting for the time-effect interactions, and unpaired t -tests comparing the mean estimates obtained individually every month. The level of significance was set at p < 0.05 two-tailed. After 4 months of intervention, the group difference in the primary outcome was nonsignificant statistically-IHMPs: 22/46 v/s placebo: 24/46, chi-square (Yates corrected) = 0.043, p = 0.835. The improvement observed in the MDQ total score ( F 1 , 90 = 0.054, p = 0.816) and subscales scores were higher in the IHMPs group than in placebos, however statistically nonsignificant in most of the occasions, except for the behavioral change subscale ( F 1 , 90 = 0.029, p < 0.001). Pulsatilla nigricans was the most frequently prescribed medicine. Kent's Repertory and Zandvoort's Complete Repertory were the most frequently used repertories. No harm or serious adverse events were reported from either group. Conclusions: The analysis failed to demonstrate clearly that IHMPs were effective beyond placebos in all but one of the outcomes. More appropriate outcome measures may be sought for future trials. Clinical Trial Registration Number: CTRI/2022/04/041659.

Background: Spina bifida is a type of neural tube defect (NTD); NTDs are developmental malformations of the spinal cord that result from failure of neural tube closure during embryogenesis and are likely caused by interactions between genetic and environmental factors. Arsenic induces NTDs in animal models, and studies demonstrate that mice with genetic defects related to folate metabolism are more susceptible to arsenic's effects. We sought to determine whether 25 single-nucleotide polymorphisms (SNPs) in genes involved in folate and arsenic metabolism modified the associations between maternal arsenic exposure and risk of spina bifida (a common NTD) among a hospital-based case-control study population in Bangladesh., Methods: We used data from 262 mothers and 220 infants who participated in a case‒control study at the National Institutes of Neurosciences & Hospital and Dhaka Shishu Hospital in Dhaka, Bangladesh. Neurosurgeons assessed infants using physical examinations, review of imaging, and we collected histories using questionnaires. We assessed arsenic from mothers' toenails using inductively coupled plasma mass spectrometry (ICP-MS), and we genotyped participants using the Illumina Global Screening Array v1.0. We chose candidate genes and SNPs through a review of the literature. We assessed SNP-environment interactions using interaction terms and stratified models, and we assessed gene-environment interactions using interaction sequence/SNP-set kernel association tests (iSKAT)., Results: The median toenail arsenic concentration was 0.42 μg/g (interquartile range [IQR]: 0.27-0.86) among mothers of cases and 0.47 μg/g (IQR: 0.30-0.97) among mothers of controls. We found an two SNPs in the infants' AS3MT gene (rs11191454 and rs7085104) and one SNP in mothers' DNMT1 gene (rs2228611) were associated with increased odds of spina bifida in the setting of high arsenic exposure (rs11191454, OR 3.01, 95% CI: 1.28-7.09; rs7085104, OR 2.33, 95% CI: 1.20-4.and rs2228611, OR 2.11, 95% CI: 1.11-4.01), along with significant SNP-arsenic interactions. iSKAT analyses revealed significant interactions between mothers' toenail concentrations and infants' AS3MT and MTR genes (p = 0.02), and mothers' CBS gene (p = 0.05)., Conclusions: Our results support the hypothesis that arsenic increases spina bifida risk via interactions with folate and arsenic metabolic pathways and suggests that individuals in the population who have certain genetic polymorphisms in genes involved with arsenic and folate metabolism may be more susceptible than others to the arsenic teratogenicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Nocturnal enuresis (NE) is a very common problem in childhood. The prevalence rate varies from 3.5% to 56.4% in different geographical regions and countries., Objective: Homeopathy is claimed to be a safe and effective mode of complementary and alternative therapy; however, robust research evidence supporting the efficacy or effectiveness of homeopathy in NE is scarce. This trial aimed at detecting the group differences between homeopathy and placebo in the treatment of NE in children., Design: Three-month, double-blind, randomized (1:1), placebo-controlled trial., Setting: Pediatric outpatient department of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal., Patients: One hundred and forty children suffering from NE., Interventions: Active treatment (individualized homeopathic medicinal products, IHMPs plus concomitant care, CC; n = 70) versus control (identical-looking placebos, plus CC; n = 70)., Main Outcome Measures: Primary - the frequency of bedwetting events between groups; secondary - the pediatric quality of life inventory (PedsQL, version 4.0) questionnaire and its subscales - child-rated and parent-rated versions; all were measured at baseline, and every month, up to 3 months., Results: After 3 months of intervention, group differences were statistically significant in the primary outcome favoring IHMPs against placebo (median difference: 2.4, interquartile range -4 to 9.7, Mann Whitney U = 1956.5, p = 0.039). Although the intra-group median reductions were higher in the IHMPs group than in placebos, the differences were statistically non-significant in the secondary outcome - PedsQL total child report version (p = 0.224) and PedsQL total parent report version (p = 0.942). Sulphur (n = 26, 18.6%), Calcarea phosphorica (n = 20, 14.3%), Calcarea carbonica and Kreosotum (n = 9 each, 6.4%), and Mercurius solubilis (n = 8, 5.7%) were the most frequently prescribed medicines. Thus, IHMPs were found superior to placebos in reducing the frequency of bedwetting events in children. Independent replications are warranted to substantiate the findings. Clinical Trials Registry - India CTRI/2022/04/042009., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Small RNA (sRNA) in bacteria serve as the key messengers in regulating genes associated with quorum sensing controlled bacterial virulence. This study was aimed to unveil the regulatory role of sRNA PA0730.1 on the expression of various traits of Pseudomonas aeruginosa linked to pathogenicity, with special emphasis on the growth, colony morphology, cell motility, biofilm formation, and the expression of diverse virulence factors. PA0730.1 sRNA was found to be upregulated both during planktonic stationary growth phase and at biofilm state of P. aeruginosa PAO1. PA0730.1 deleted strain showed significant growth retardation with increased doubling time. Overexpression of PA0730.1 led to enhanced motility and biofilm formation, while the ∆PA0730.1 strain displayed significant inhibition in motility and biofilm formation. Furthermore, PA0730.1 was found to regulate the synthesis of selected virulence factors of P. aeruginosa. These observations in PA0730.1 + and ∆PA0730.1 were found to be correlated with the PA0730.1-mediated repression of transcription regulators, mucA and rpoS, both at transcriptional and translational levels. The results suggest that PA0730.1 sRNA might be a promising target for developing new drug to counter P. aeruginosa pathogenesis, and could also help in RNA oligonucleotide based therapeutic research for formulating a novel therapeutant., 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.)

Objectives: Evidence suggests that post-coronavirus disease 2019 (COVID-19) is associated with reduced health-related quality of life, and up to 80% of those infected with COVID-19 may experience these symptoms. The objective of the present study was to identify the effects of individualized homeopathic medicinal products (IHMPs) against placebos in postCOVID-19 conditions. Design: Double-blind, randomized (1:1), two parallel arms, placebo-controlled, feasibility trial. Setting: D. N. De Homoeopathic Medical College & Hospital, Kolkata, West Bengal, India. Subjects: Sixty participants with post-COVID-19 conditions. Interventions: Group verum ( n = 30; IHMPs plus concomitant care) versus group control ( n = 30; placebos plus concomitant care). Outcome Measures: Feasibility issues; primary-post-COVID-19 symptoms checklist; secondary-Measure Yourself Medical Outcomes Profile version 2 (MYMOP-2); all of them were measured at baseline, and monthly intervals, up to 3 months. The intention-to-treat sample was analyzed; group differences were reported using descriptive statistics: means, 95% confidence intervals (CIs), and between group effect sizes (Cohen's d ). Results: Feasibility concerns showed promise; recruitment, retention, and attrition rates were 34.2%, 95%, and 5%, respectively. Group differences in both primary and secondary outcomes favored IHMPs against placebos: symptoms checklist score mean difference after 3 months: -4.2, 95% CI -4.9 to -3.4, d = 2.854 and MYMOP-2 mean difference after 3 months: -2.2, 95% CI -2.8 to -1.7, d = 2.082, respectively. Natrum muriaticum (11.7%), Pulsatilla nigricans (10%), Rhus toxicodendron (8.3%), and Calcarea carbonica (8.3%) were the most frequently prescribed remedies. Conclusions: IHMPs produced better results than placebos in reducing symptoms checklist scores and MYMOP-2 scores in the treatment of post-COVID-19 conditions. Definitive trials are warranted to confirm the findings.

Context: Pre-diabetes is a significant public health problem worldwide. India has a very high rate of progression from pre-diabetes to diabetes, 75-78 per thousand persons per year., Objective: To study the efficacy of individualized homeopathic medicinal products (HMPs) against placebos in preventing the progression from pre-diabetes to diabetes., Design: Six-month, double-blind, randomized (1:1), two parallel arms, placebo-controlled trial., Setting: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India., Patients: Sixty participants with pre-diabetes., Interventions: Verum: HMPs plus yoga therapy (YT; n = 30); control: identical-looking placebos plus YT (n = 30)., Main Outcome Measures: The primary efficacy endpoint was the proportion of participants progressing from pre-diabetes to diabetes, measured after three and six months. Secondary outcomes comprised of fasting blood glucose (FBS), oral glucose tolerance test (OGTT), glycated hemoglobin percentage (HbA1c%), lipid profile, liver enzymes (alanine transaminase, aspartate transaminase), urea and creatinine, and Measure Yourself Medical Outcome Profile version 2 (MYMOP-2); all measured after 3 and 6 months., Results: The proportion of participants converted from pre-diabetics to diabetics (n/N; n = diabetics, N = prediabetics) was significantly less in the verum group than control: HbA1C% (month 3: verum - 2/30 versus control - 11/30, p = 0.003; month 6: 3/30 vs. 2/30, p = 0.008), OGTT (month 3: 0/30 vs. 8/30, p = 0.015; month 6: 0/30 vs. 1/30, p = 0.008), but not according to FBS (month 3: 1/30 vs. 1/30, p = 0.779; month 6: 1/30 vs. 3/30, p = 0.469). Several secondary outcomes also revealed significant improvements in the verum group than in placebo: HbA1C% (p < 0.001), OGTT (p = 0.001), serum ALT (p = 0.031), creatinine (p = 0.012), and MYMOP-2 profile scores (p < 0.001). Sulphur, Bryonia alba, and Thuja occidentalis were the most frequently indicated medicines. Thus, HMPs outperformed placebos by successfully preventing the progression of pre-diabetes to diabetes., Trial Registration: Clinical Trials Registry - India CTRI/2022/04/042,026; UTN: U1111-1277-0021., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Guidelines for surgical correction of patients with ascending thoracic aortic aneurysm (ATAA) with a bicuspid aortic valve (BAV) have oscillated over the years. In this study, we outline the natural history of the ascending aorta in patients with BAV and trileaflet aortic valve (TAV) ATAA followed over time, to ascertain if their behavior differs and to determine if a different threshold for intervention is required., Methods: Aortic diameters and long-term complications (ie, adverse aortic events) of 2428 patients (554 BAV and 1874 TAV) with ATAA before operative repair were reviewed. Growth rates, yearly complication rates, event-free survival, and risk of complications as a function of aortic size were calculated. Long-term follow-up and precise cause of death granularity was achieved via a comprehensive 6-pronged approach., Results: Aortic growth rate in patients with BAV vs TAV ATAA was 0.20 and 0.17 cm/year, respectively (P = .009), with the rate increasing with increasing aortic size. Yearly adverse aortic events rates increased with ATAA size and were lower for patients with BAV. The relative risk of adverse aortic events exhibited an exponential increase with aortic diameter. Patients with BAV had a lower all-cause and ascending aorta-specific adverse aortic events hazard. Age-adjusted 10-year event-free survival was significantly better for patients with BAV, and BAV emerged as a protective factor against type A dissection, rupture, and ascending aortic death., Conclusions: The threshold for surgical repair of ascending aneurysm with BAV should not differ from that of TAV. Prophylactic surgery should be considered at 5.0 cm for patients with TAV (and BAV) at expert centers., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed at examining the feasibility issues of comparing individualized homeopathic medicines (IHMs) with identical-looking placebos for treating knee osteoarthritis (OA)., Methods: Forty eligible patients participated in this double-blind, randomized (1:1), placebo-controlled feasibility trial in the outpatient clinics of a homeopathic hospital in West Bengal, India. Either IHMs or identical-looking placebos were administered, along with mutually agreed-upon concomitant care guidelines. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was the primary outcome measure, along with derived Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores from KOOS. The EQ-5D-5L questionnaire and Visual Analog Scale (VAS) were the secondary outcomes. All were measured at baseline and after 2 months. Group differences and effect sizes (Cohen's d ) were estimated using an intention-to-treat approach. p -Values less than 0.05 (two-tailed) were considered statistically significant., Results: Enrolment/screening and trial retention rates were 43% and 85% respectively. Recruitment was difficult owing to the coronavirus disease 2019 (COVID-19) lockdown. Group differences were statistically significant, favoring IHMs against placebos in all the KOOS sub-scales: symptoms ( p  < 0.001), pain ( p  = 0.002), activities of daily living ( p  < 0.001), sports or recreation ( p  = 0.016), and quality of life ( p  = 0.002). Derived WOMAC scores from KOOS favored IHMs against placebos: stiffness ( p  < 0.001) and pain ( p  < 0.001). The EQ-5D-5L questionnaire score ( p  < 0.001) and EQ-5D-5L VAS scores ( p  < 0.001) also yielded significant results, favoring IHMs over placebos. All the effect sizes ranged from moderate to large. Sulphur was the most frequently prescribed homeopathic medication. Neither group reported any harm or serious adverse events., Conclusion: Although recruitment was sub-optimal due to prevailing COVID-19 conditions during the trial, the action of IHMs was found to be superior to that of placebos in the treatment of knee OA. Larger and more definitive studies, with independent replications, are warranted in order to substantiate the findings., Trial Registration: CTRI/2021/02/031453., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Background:   Arsenicum album , Causticum , Nux vomica , Pulsatilla nigricans , Rhus toxicodendron and Sulphur are frequently prescribed homeopathic medicines; however, their symptoms, as mentioned in different homeopathic literature works, have rarely been investigated systematically. Likelihood ratio (LR), based on Bayesian statistics, may reflect a better estimation of the strengths of symptoms than the existing entries in the homeopathic literature., Methods:  A prospective, longitudinal, analytical patient outcome study was conducted in the outpatient departments of D. N. De Homeopathic Medical College and Hospital, Kolkata, on 1,954 patients over 21 months. The outcomes were recorded at each follow-up using the Outcome Related to Impact on Daily Living (ORIDL) +4 to -4 scale. The average period of treatment for each participant was 3 months. The LRs of four symptoms for each of the six selected medicines were calculated., Results:  One hundred and two different remedies were prescribed. The prevalence, LR + , and LR - , with respective 95% confidence intervals, of different symptoms were reported. The study found that the following symptoms had particularly high LR+ scores: "intense sympathy for the suffering of others" ( Causticum , LR+ = 12.0); "dyspepsia from business anxiety" ( Nux vomica , LR+ = 27.4); "burning pain relieved by heat" ( Arsenicum album , LR+ = 29.6); "envy" ( Pulsatilla nigricans , LR+ = 13.2); "desire for milk" ( Rhus toxicodendron , LR+ = 7.5); "very selfish, no regard for others" ( Sulphur , LR+ = 20.6). The findings corroborated well with the presentation of the symptoms in different homeopathic materia medica and repertories. ORIDL scores of +2 or greater were identified most prominently for Pulsatilla nigricans ( n  = 138) and Sulphur ( n  = 119)., Conclusion:  There was adequate evidence to attribute all the assessed symptoms to the medicines investigated. Further studies with a larger population are warranted to tackle the possible confirmation bias., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Objective: Reports on the management and survival of children with myelomeningocele defects in Bangladesh are limited. This study describes the characteristics and outcomes of these children, focusing on the timing of surgical repair and factors affecting survival., Methods: We enrolled patients with myelomeningoceles in a case-control study on arsenic exposure and spina bifida in Bangladesh. Cases were subsequently followed at regular intervals to assess survival. Demographic, clinical, and surgical characteristics were reviewed. Univariate tests identified factors affecting survival., Results: Between 2016 and 2022, we enrolled 272 patients with myelomeningocele. Postnatal surgical repair was performed in 63% of cases. However, surgery within 5 days after birth was infrequent (<10%) due to delayed presentation, and there was a high rate (29%) of preoperative deaths. Surgical repair significantly improved patient survival (P < 0.0001). Older age at time of surgery was also associated with improved survival rates, which most likely represents that those who survived to older ages prior to surgery accommodated better with their lesions. Patients who presented with ruptured lesions had lower survival rates., Conclusions: Timely neurosurgical repair of myelomeningoceles in Bangladesh is hindered by late patient presentation, resulting in a high preoperative patient death rate. Neurosurgical intervention remains a significant predictor of survival. Increased access to neurosurgical care and education of families and non-neurosurgical providers on the need for timely surgical intervention are important for improving the survival of infants with myelomeningoceles., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Spina bifida, a developmental malformation of the spinal cord, is associated with high rates of mortality and disability. Although folic acid-based preventive strategies have been successful in reducing rates of spina bifida, some areas continue to be at higher risk because of chemical exposures. Bangladesh has high arsenic exposures through contaminated drinking water and high rates of spina bifida. This study examines the relationships between mother's arsenic exposure, folic acid, and spina bifida risk in Bangladesh., Methods: We conducted a hospital-based case-control study at the National Institute of Neurosciences & Hospital (NINS&H) in Dhaka, Bangladesh, between December 2016 and December 2022. Cases were infants under age one year with spina bifida and further classified by a neurosurgeon and imaging. Controls were drawn from children seen at NINS&H and nearby Dhaka Shishu Hospital. Mothers reported folic acid use during pregnancy, and we assessed folate status with serum assays. Arsenic exposure was estimated in drinking water using graphite furnace atomic absorption spectrophotometry (GF-AAS) and in toenails using inductively coupled plasma mass spectrometry (ICP-MS). We used logistic regression to examine the associations between arsenic and spina bifida. We used stratified models to examine the associations between folic acid and spina bifida at different levels of arsenic exposure., Results: We evaluated data from 294 cases of spina bifida and 163 controls. We did not find a main effect of mother's arsenic exposure on spina bifida risk. However, in stratified analyses, folic acid use was associated with lower odds of spina bifida (adjusted odds ratio [OR]: 0.50, 95% confidence interval [CI]: 0.25-1.00, p = 0.05) among women with toenail arsenic concentrations below the median value of 0.46 µg/g, and no association was seen among mothers with toenail arsenic concentrations higher than 0.46 µg/g (adjusted OR: 1.09, 95% CI: 0.52-2.29, p = 0.82)., Conclusions: Mother's arsenic exposure modified the protective association of folic acid with spina bifida. Increased surveillance and additional preventive strategies, such as folic acid fortification and reduction of arsenic, are needed in areas of high arsenic exposure., (© 2024. The Author(s).)

Expanding possibilities for foreign gene expression in cucurbits, we present a novel approach utilising a bipartite vector system based on the cucumber green mottle mosaic virus (CGMMV) genome. Traditional full-length CGMMV vectors face limitations such as a restricted cargo capacity and unstable foreign gene expression. To address these challenges, we developed two 'deconstructed' CGMMV genomes, DG-1 and DG-2. DG-1 features a major internal deletion, resulting in the loss of crucial replicase enzyme domains, rendering it incapable of self-replication. However, a staggered infiltration of DG-1 in CGMMV-infected plants enabled successful replication and movement, facilitating gene-silencing experiments. Conversely, DG-2 was engineered to enhance replication rates and provide multiple cloning sites. Although it exhibited higher replication rates, DG-2 remained localised within infiltrated tissue, displaying trans-replication and restricted movement. Notably, DG-2 demonstrated utility in expressing GFP, with a peak expression observed between 6 and 10 days post-infiltration. Overall, our bipartite system represents a significant advancement in functional genomics, offering a robust tool for foreign gene expression in Nicotiana benthamiana .

The structural, optoelectronics, and transport properties of TlTaO 3 compounds were determined utilizing the full potential augmented plane wave approach using first-principle method. We have considered the generalized gradient approximation for structural optimization and modified Becke-Johnson for electronic properties. The electronic properties reveal that the studied TlTaO 3 possesses direct bandgap of magnitude 1.52 eV. Between 0 and 12 eV, optical spectra calculations are made, taking into account the real and imaginary parts of the dielectric function, refractive index, and loss function. The transport properties are estimated considering Boltzmann transport theory. The Seebeck coefficient, electrical conductivity, thermal conductivity, and power factor are all assessed using the Boltzmann transport theory. The optimized thermoelectric response of the examined TlTaO 3 is produced by the improved carrier mobility, which also improves the thermoelectric efficiency of the TlTaO 3 . The obtained results will act as a theoretical road map for upcoming experimental and commercial TlTaO 3 applications., (© 2024 Wiley Periodicals LLC.)

Objectives: Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area and aneurysm location (root versus ascending)., Methods: Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analysed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age and body surface area, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with 'hinge points' of steep risk, constructed separately for the aortic root and mid-ascending aorta., Results: A total of 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root and z = 5 for the mid-ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75-year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented, which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size., Conclusions: This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Human studies of genetic risk factors for neural tube defects, severe birth defects associated with long-term health consequences in surviving children, have predominantly been restricted to a subset of candidate genes in specific biological pathways including folate metabolism., Methods: In this study, we investigated the association of genetic variants spanning the genome with risk of spina bifida (i.e., myelomeningocele and meningocele) in a subset of families enrolled from December 2016 through December 2022 in a case-control study in Bangladesh, a population often underrepresented in genetic studies. Saliva DNA samples were analyzed using the Illumina Global Screening Array. We performed genetic association analyses to compare allele frequencies between 112 case and 121 control children, 272 mothers, and 128 trios., Results: In the transmission disequilibrium test analyses with trios only, we identified three novel exonic spina bifida risk loci, including rs140199800 (SULT1C2, p = 1.9 × 10 -7 ), rs45580033 (ASB2, p = 4.2 × 10 -10 ), and rs75426652 (LHPP, p = 7.2 × 10 -14 ), after adjusting for multiple hypothesis testing. Association analyses comparing cases and controls, as well as models that included their mothers, did not identify genome-wide significant variants., Conclusions: This study identified three novel single nucleotide polymorphisms involved in biological pathways not previously associated with neural tube defects. The study warrants replication in larger groups to validate findings and to inform targeted prevention strategies., (© 2024 Wiley Periodicals LLC.)

Pseudomonas aeruginosa , a vivid biofilm-producing bacterium, is considered a dreadful opportunistic pathogen, and thus, management of biofilm-associated infections due to multidrug resistant strains by traditional drugs currently is of great concern. This study was aimed to assess the impact of trigonelline hydrochloride, a pyridine alkaloid, on P. aeruginosa PAO1, in search of an alternative therapeutant. The effect of trigonelline on colony morphology and motility was studied along with its role on biofilm and expression virulence factors. Trigonelline influenced the colony structure, motility, biofilm architecture, and the production of virulence factors in a dose-dependent manner. Alterations in quorum sending (QS)-regulated gene expression after treatment and molecular docking analysis for certain regulator proteins confirmed its effect on the QS-system network by affecting Las, Rhl, and Pqs signaling pathways and as possible molecular targets. Thus, trigonelline might be considered as a potential chemical lead to manage biofilm-associated pathogenesis or to develop other analogues with enhanced pharmacokinetic actions.

Background Objectives: Discovery of new antibiotics is the need of the hour to treat infectious diseases. An ever-increasing repertoire of multidrug-resistant pathogens poses an imminent threat to human lives across the globe. However, the low success rate of the existing approaches and technologies for antibiotic discovery remains a major bottleneck. In silico methods like machine learning (ML) deem more promising to meet the above challenges compared with the conventional experimental approaches. The goal of this study was to create ML models that may be used to successfully predict new antimicrobial compounds., Methods: In this article, we employed eight different ML algorithms namely, extreme gradient boosting, random forest, gradient boosting classifier, deep neural network, support vector machine, multilayer perceptron, decision tree, and logistic regression. These models were trained using a dataset comprising 312 antibiotic drugs and a negative set of 936 non-antibiotic drugs in a five-fold cross validation approach., Results: The top four ML classifiers (extreme gradient boosting, random forest, gradient boosting classifier and deep neural network) were able to achieve an accuracy of 80 per cent and above during the evaluation of testing and blind datasets., Interpretation Conclusions: We aggregated the top performing four models through a soft-voting technique to develop an ensemble-based ML method and incorporated it into a freely accessible online prediction server named ABDpred ( http://clinicalmedicinessd.com.in/abdpred/ )., (Copyright © 2024 Copyright: © 2024 Indian Journal of Medical Research.)

The double perovskites are become the emerging aspirant to fulfill the demand of energy. Therefore, the optoelectronic, elastic and transport characteristics of Ba 2 XMoO 6 (X = Zn, Cd) are addressed systemically. The elastic constants show the mechanical stability. The nature of Ba 2 ZnMoO 6 is brittle and Ba 2 CdMoO 6 is ductile with large values of Debye temperature covalent bonding. The electronic band structures exhibit band gaps of 2.81 and 2.98 eV, which increase their importance for optoelectronic applications. The absorption of light energy, optical loss, refractive index, polarization of light energy are addressed in the energy range zero to 14 eV. Furthermore, thermoelectric characteristics are computed against chemical potentials at 300, 600, and 900 K. The chemical potential decides the p-type nature, with holes as majority carriers. The increasing temperature increases the power factor and figure of merit. Therefore, the optoelectronic and thermoelectric characteristics reveals the importance of studied DPs for energy applications., (© 2023 Wiley Periodicals LLC.)

Molecular cloning, a crucial prerequisite for engineering plasmid constructs intended for functional genomic studies, relies on successful restriction and ligation processes. However, the lack of unique restriction sites often hinders construct preparation, necessitating multiple modifications. Moreover, achieving the successful ligation of large plasmid constructs is frequently challenging. To address these limitations, we present a novel PCR strategy in this study, termed 'long-fragment circular-efficient PCR' (LC-PCR). This technique involves one or two rounds of PCR with an additional third-long primer that complements both ends of the newly synthesized strand of a plasmid construct. This results in self-circularization with a nick-gap in each newly formed strand. The LC-PCR technique was successfully employed to insert a partial sequence (210 nucleotides) of the phytoene desaturase gene from Nicotiana benthamiana and a full capsid protein gene (770 nucleotides) of a begomovirus (tomato leaf curl New Delhi virus) into a 16.4 kb infectious construct of a tobamovirus , cucumber green mottle mosaic virus (CGMMV), cloned in pCambia. This was done to develop the virus-induced gene silencing vector (VIGS) and an expression vector for a foreign protein in plants, respectively. Furthermore, the LC-PCR could be applied for the deletion of a large region (replicase enzyme) and the substitution of a single amino acid in the CGMMV genome. Various in planta assays of these constructs validate their biological functionality, highlighting the utility of the LC-PCR technique in deciphering plant-virus functional genomics. The LC-PCR is not only suitable for modifying plant viral genomes but also applicable to a wide range of plant, animal, and human gene engineering under in-vitro conditions. Additionally, the LC-PCR technique provides an alternative to expensive kits, enabling quick introduction of modifications in any part of the nucleotide within a couple of days. Thus, the LC-PCR proves to be a suitable 'all in one' technique for modifying large plasmid constructs through site-directed gene insertion, deletion, and mutation, eliminating the need for restriction and ligation.

Aims: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention., Methods and Results: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression., Conclusion: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention., Competing Interests: Conflict of interest J.E. serves as the principal of CoolSpine and consultant for Tissium. All other authors report no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Trichomonas vaginalis is a human infective parasite responsible for trichomoniasis-the most common, non-viral, sexually transmitted infection worldwide. T. vaginalis resides exclusively in the urogenital tract of both men and women. In women, T. vaginalis has been found colonizing the cervix and vaginal tract while in men it has been identified in the upper and lower urogenital tract and in secreted fluids such as semen, urethral discharge, urine, and prostatic fluid. Despite the over 270 million cases of trichomoniasis annually worldwide, T. vaginalis continues to be a highly neglected organism and thus poorly studied. Here we have developed a male mouse model for studying T. vaginalis pathogenesis in vivo by delivering parasites into the murine urogenital tract (MUT) via transurethral catheterization. Parasite burden was assessed ex-vivo using a nanoluciferase-based gene expression assay which allowed quantification of parasites pre- and post-inoculation. Using this model and read-out approach, we show that T. vaginalis can be found within MUT tissue up to 72 hrs post-inoculation. Furthermore, we also demonstrate that parasites that exhibit increased parasite adherence in vitro also have higher parasite burden in mice in vivo. These data provide evidence that parasite adherence to host cells aids in parasite persistence in vivo and molecular determinants found to correlate with host cell adherence in vitro are applicable to infection in vivo. Finally, we show that co-inoculation of T. vaginalis extracellular vesicles (TvEVs) and parasites results in higher parasite burden in vivo. These findings confirm our previous in vitro-based predictions that TvEVs assist the parasite in colonizing the host. The establishment of this pathogenesis model for T. vaginalis sets the stage for identifying and examining parasite factors that contribute to and influence infection outcomes., Competing Interests: The authors disclose no competing interests that could be perceived to bias this work., (Copyright: © 2023 Molgora 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.)

Introduction: Screening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency., Methods and Findings: Data from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with <30% activity and 77% (95% CI 66.8%-85.4%) for females with intermediate activity between 30%-70%. Specificity was 98.1% (95% CI 97.6%-98.5%) and 92.8% (95% CI 91.6%-93.9%) for G6PD deficient individuals and intermediate females, respectively. Out of 20 G6PD intermediate females with false normal results, 12 had activity levels >60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test., Conclusions: The STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Adissu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The structural, magnetic, electronic, elastic, vibrational, optical, thermodynamic as well as thermoelectric properties of newly predicted quaternary LiZrCoX (X = Ge, Sn) Heusler compounds are evaluated intricately with the aid of ab initio techniques developed under the framework of density functional theory. The computed structural properties are found to be in tandem with the existing analogous theoretical and experimental facts. Structural optimization has been carried out in three different structural arrangements, i.e. , Type-1, Type-2, and Type-3. Further analysis of the optimization curves reveals that the Type-3 phase, which has the least amount of energy, is the most stable structure for the compounds under consideration. The tabulated cohesive energy and formation energy of these compounds depict their chemical as well as thermodynamic stability. The absence of negative phonon frequencies in the phonon band spectrum of the studied compounds depicts their dynamic stability. Similarly, the tabulated second-order elastic constants ( C ij ) and the linked elastic moduli show their stability in the cubic phase. The calculated value of Pugh's ratio and Cauchy pressure reveal that LiZrCoGe is brittle whereas LiZrCoSn is ductile. Additionally, the optical characteristics of the compounds are studied in terms of the dielectric function, refractive index, extinction coefficient, absorption coefficient, reflectivity, energy loss function, and optical conductivity. The obtained high value of power factor and figure of merit of the studied lithium-based quaternary compounds predict good thermoelectric behavior in these compounds. Thus, LiZrCoX (X = Ge, Sn) compounds can therefore be used to create innovative and intriguing thermoelectric materials as well as optoelectronic and energy-harvesting equipment., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (This journal is © The Royal Society of Chemistry.)

Objective: To use machine learning to predict rupture, dissection, and all-cause mortality for patients with descending and thoracoabdominal aortic aneurysms in an effort to improve on diameter-based surgical intervention criteria., Methods: Retrospective data from 1083 patients with descending aortic diameters 3.0 cm or greater were collected, with a mean follow-up time of 3.52 years and an average descending diameter of 4.13 cm. Six machine learning classifiers were trained using 44 variables to predict the occurrence of dissection, rupture, or all-cause mortality within 1, 2, or 5 years of initial patient encounter for a total of 54 (6 × 3 × 3) separate classifiers. Classifier performance was measured using area under the receiver operator curve., Results: Machine learning models achieved area under the receiver operator curves of 0.842 to 0.872 when predicting type B dissection, 0.847 to 0.856 when predicting type B dissection or rupture, and 0.820 to 0.845 when predicting type B dissection, rupture, or all-cause mortality. All models consistently outperformed descending aortic diameter across all end points (area under the receiver operator curve = 0.713-0.733). Feature importance inspection showed that other features beyond aortic diameter, such as a history of myocardial infarction, hypertension, and patient sex, play an important role in improving risk prediction., Conclusions: This study provides surgeons with a more accurate, machine learning-based, risk-stratification metric to predict complications for patients with descending aortic aneurysms., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Key Message: We report the size dependent uptake of dsRNA loaded MSNPs into the leaves and roots of Nicotiana benthamiana plants and accessed for their relative reduction in Tomato leaf curl New Delhi viral load. A non-GMO method of RNA interference (RNAi) has been recently in practice through direct delivery of double stranded RNA into the plant cells. Tomato leaf curl New Delhi virus (ToLCNDV), a bipartitie begomovirus, is a significant viral pathogen of many crops in the Indian subcontinent. Conventional RNAi cargo delivery strategies for instance uses viral vectors and Agrobacterium-facilitated delivery, exhibiting specific host responses from the plant system. In the present study, we synthesized three different sizes of amine-functionalized mesoporous silica nanoparticles (amino-MSNPs) to mediate the delivery of dsRNA derived from the AC2 (dsAC2) gene of ToLCNDV and showed that these dsRNA loaded nanoparticles enabled effective reduction in viral load. Furthermore, we demonstrate that amino-MSNPs protected the dsRNA molecules from nuclease degradation, while the complex was efficiently taken up by the leaves and roots of Nicotiana benthamiana. The real time gene expression evaluation showed that plants treated with nanoparticles of different sizes ~ 10 nm (MSNP DEA ), ~ 32 nm (MSNP TEA ) and ~ 66 nm (MSNP NH3 ) showed five-, eleven- and threefold reduction of ToLCNDV in N. benthamiana, respectively compared to the plants treated with naked dsRNA. This work clearly demonstrates the size dependent internalization of amino-MSNPs and relative efficacy in transporting dsRNA into the plant system, which will be useful in convenient topical treatment to protect plants against their pathogens including viruses. Mesoporous silica nanoparticles loaded with FITC, checked for its uptake into Nicotiana benthamiana., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This issue of the Yale Journal of Biology and Medicine ( YJBM ) focuses on Big Data and precision analytics in medical research. At the Aortic Institute at Yale New Haven Hospital, the vast majority of our investigations have emanated from our large, prospective clinical database of patients with thoracic aortic aneurysm (TAA), supplemented by ultra-large genetic sequencing files. Among the fundamental clinical and scientific discoveries enabled by application of advanced statistical and artificial intelligence techniques on these clinical and genetic databases are the following: From analysis of Traditional "Big Data" (Large data sets) . 1. Ascending aortic aneurysms should be resected at 5 cm to prevent dissection and rupture. 2. Indexing aortic size to height improves aortic risk prognostication. 3. Aortic root dilatation is more malignant than mid-ascending aortic dilatation. 4. Ascending aortic aneurysm patients with bicuspid aortic valves do not carry the poorer prognosis previously postulated. 5. The descending and thoracoabdominal aorta are capable of rupture without dissection. 6. Female patients with TAA do more poorly than male patients. 7. Ascending aortic length is even better than aortic diameter at predicting dissection. 8. A "silver lining" of TAA disease is the profound, lifelong protection from atherosclerosis. From Modern "Big Data" Machine Learning/Artificial Intelligence analysis : 1. Machine learning models for TAA: outperforming traditional anatomic criteria. 2. Genetic testing for TAA and dissection and discovery of novel causative genes. 3. Phenotypic genetic characterization by Artificial Intelligence. 4. Panel of RNAs "detects" TAA. Such findings, based on (a) long-standing application of advanced conventional statistical analysis to large clinical data sets, and (b) recent application of advanced machine learning/artificial intelligence to large genetic data sets at the Yale Aortic Institute have advanced the diagnosis and medical and surgical treatment of TAA., (Copyright ©2023, Yale Journal of Biology and Medicine.)

At high pressure, the pressure dependencies of the structural, electronic, optical, and thermoelectric properties of Fe 2 HfSi Heusler were calculated using the FP-LAPW method within the framework of the density functional theory. The calculations were carried out using the modified Becke-Johnson (mBJ) scheme. Our calculations showed that the Born mechanical stability criteria confirmed the mechanical stability in the cubic phase. Further, through Poisson and Pugh's ratios critical limits, the findings of the ductile strength were computed. At a pressure of 0 GPa, the indirect nature of the material may be deduced from the electronic band structures of Fe 2 HfSi as well as the estimations for its density of states. Under pressure, the real and imaginary dielectric function responses, optical conductivity, absorption coefficient, energy loss function, refractive index, reflectivity, and extinction coefficient were computed in the 0-12 eV range. Using semi-classical Boltzmann theory, a thermal response is also studied. As the pressure rises, the Seebeck coefficient decreases, while the electrical conductivity rises. The figure of merit ( ZT ) and Seebeck coefficients were determined at temperatures of 300 K, 600 K, 900 K, and 1200 K in order to better understand the thermoelectric properties of a material at these different temperatures. Despite the fact that the ideal Seebeck coefficient for Fe 2 HfSi was discovered at 300 K and was determined to be superior to that reported previously. Materials with a thermoelectric reaction has been shown to be suitable for reusing waste heat in systems. As a result, Fe 2 HfSi functional material may aid in the development of new energy harvesting and optoelectronic technologies., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Introduction: Hyperuricemia (HU) is a major health issue in India and across the globe. It increases the disease burden and hampers quality of life. This study was aimed at exploring the effects of individualized homeopathic medicines (IHMs) against placebo in the treatment of HU., Methods: This double-blind, randomized, placebo-controlled trial was conducted on 60 patients suffering from HU in the outpatient department of D. N. De Homoeopathic Medical College and Hospital, Kolkata. Each patient received either IHMs or identical-looking placebos, along with advice on dietary modifications irrespective of codes. Serum uric acid (SUA) level was the primary outcome measure; the HU quality of life questionnaire (HUQLQ) and the Measure Yourself Medical Outcome Profile version 2 (MYMOP-2) were the secondary outcomes; all measured at baseline, and every month, up to 3 months. Group differences were examined by two-way (split-half) repeated-measures analysis of variance after adjusting for baseline differences. Significance level was set at p ≤0.05, two-tailed., Results: The intention-to-treat sample ( n  = 58) was analyzed. Between-group differences in SUA levels ( F 1, 56  = 13.833, p <0.001), HUQLQ scores ( F 1, 56  = 32.982, p <0.001) and MYMOP-2 profile scores ( F 1, 56  = 23.873, p <0.001) were statistically significant, favoring IHMs against placebos, with medium to large effect sizes. Calcarea carbonica and Pulsatilla nigricans were the most frequently prescribed medicines. No serious adverse events were reported from either of the groups., Conclusion: IHMs showed significantly better results than placebos in reducing SUA levels and improving quality of life in patients suffering from HU., Trial Registration: CTRI/2019/10/021503; UTN: U1111-1241-1431., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

A significant number of SARS-CoV-2-infected individuals naturally overcome viral infection, suggesting the existence of a potent endogenous antiviral mechanism. As an innate defense mechanism, microRNA (miRNA) pathways in mammals have evolved to restrict viruses, besides regulating endogenous mRNAs. In this study, we systematically examined the complete repertoire of human miRNAs for potential binding sites on SARS-CoV-2 Wuhan-Hu-1, Beta, Delta, and Omicron. Human miRNA and viral genome interaction were analyzed using RNAhybrid 2.2 with stringent parameters to identify highly bonafide miRNA targets. Using publicly available data, we filtered for miRNAs expressed in lung epithelial cells/tissue and oral keratinocytes, concentrating on the miRNAs that target SARS-CoV-2 S protein mRNAs. Our results show a significant loss of human miRNA and SARS-CoV-2 interactions in Omicron (130 miRNAs) compared to Wuhan-Hu-1 (271 miRNAs), Beta (279 miRNAs), and Delta (275 miRNAs). In particular, hsa-miR-3150b-3p and hsa-miR-4784 show binding affinity for S protein of Wuhan strain but not Beta, Delta, and Omicron. Loss of miRNA binding sites on N protein was also observed for Omicron. Through Ingenuity Pathway Analysis (IPA), we examined the experimentally validated and highly predicted functional role of these miRNAs. We found that hsa-miR-3150b-3p and hsa-miR-4784 have several experimentally validated or highly predicted target genes in the Toll-like receptor, IL-17, Th1, Th2, interferon, and coronavirus pathogenesis pathways. Focusing on the coronavirus pathogenesis pathway, we found that hsa-miR-3150b-3p and hsa-miR-4784 are highly predicted to target MAPK13. Exploring miRNAs to manipulate viral genome/gene expression can provide a promising strategy with successful outcomes by targeting specific VOCs., 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 © 2022 Elsevier B.V. All rights reserved.)

Background: Copper nanoparticle (CuNP) has well-established antimicrobial activity. Instability in an aqueous medium due to aggregation into larger particles, conversion into metal ions, and oxidation into metal oxides are the major limitations of its practical use against bacterial infections., Objective: Development of CuNP Conjugated Chitosan Microparticles as a reservoir that will release CuNP effective against notorious bacteria like Methicillin-resistant Staphylococcus aureus., Methods: CuNP conjugated chitosan microparticles (CNCCM) were synthesized using a simple twostep process. In the first step, a solution of chitosan in 2% (w/v) ascorbic acid was added dropwise in copper sulphate solution to prepare Cu ion conjugated chitosan beads. In the second step, these beads were soaked in sodium hydroxide solution to get the CNCCM. The dried CNCCM were characterized thoroughly for surface conjugation of CuNP, and the release of CuNP in a suitable medium. The physicochemical properties of release CuNP were further verified with the in silico modelled CuNP. The Antimicrobial and antibiofilm activities of released CuNp were evaluated against methicillin-resistant Staphylococcus aureus (MRSA)., Results: 2% (w/v) ascorbic acid solution (pH 3.5) was the optimum medium for the release of ~2 nm CuNP from CNCCM. The CuNP had an optical band gap of ~ 2 eV. It inhibited the cell wall synthesis of MRSA. The minimum inhibitory concentration was 200 nM. At 100 nM dose, the CuNP caused ~73% reduction in biofilm development after 24 h of growth. The cytotoxic effect of CuNP on the human cell line (HEK 293) was significantly less than that on MRSA. The 48 h IC 50 value against HEK 293 was 3.45-fold higher than the MIC value against MRSA after 24 h treatment., Conclusion: CuNP Conjugated Chitosan Microparticle has been developed. It works as a stable reservoir of ~2 nm CuNP. The CuNP is released in an aqueous medium containing 2% (w/v) ascorbic acid (pH 3.5). The released CuNP has a bacteriostatic effect against MRSA at a concentration safe for human cells., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Thrips palmi (Thysanoptera: Thripidae) is an important pest of vegetables, legumes, and ornamentals. In addition, it transmits several plant viruses. T. palmi genes associated with innate immunity, endocytosis-related pathways, and cuticular development are highly enriched in response to Groundnut bud necrosis orthotospovirus (GBNV, genus Orthotospovirus, family Tospoviridae) infection. As the previous transcriptomic study suggested the involvement of T. palmi UHRF1BP1 and PFAS in GBNV infection, these two genes were targeted for silencing using antisense oligonucleotides (ASOs), and the effects on thrips’ fitness and virus acquisition were observed. Phosphorothioate modification of ASOs was carried out by replacing the nonbridging oxygen atom with a sulfur atom at the 3′ position to increase nuclease stability. The modified ASOs were delivered orally through an artificial diet. Exposure to ASOs reduced the target mRNA expression up to 2.70-fold optimally. Silencing of T. palmi UHRF1BP1 and PFAS induced 93.33% mortality that further increased up to 100% with an increase in exposure. Silencing of T. palmi UHRF1BP1 and PFAS also produced morphological deformities in the treated T. palmi. GBNV titer in T. palmi significantly declined post-exposure to ASOs. This is the first-ever report of silencing T. palmi UHRF1BP1 and PFAS using modified ASO to induce mortality and impair virus transmission in T. palmi. T. palmi UHRF1BP1 and PFAS would be novel genetic targets to manage thrips and restrict the spread of tospovirus.

Multiple begomovirus species are known to cause leaf curl disease in tomato in India. In order to develop specific and generic PCR based diagnostics for the tomato-infecting begomoviruses, in this study, we attempted to design primers initially based on the multiple alignment of the complete genome sequence of DNA-A component. However, the specific nucleotide stretches adequate for preparing specific primers could not be obtained. Alternatively, the online Primer-BLAST tool that offers designing of target-specific PCR primers was attempted to prepare specific primers targeting three clones (DNA-A) of tomato-infecting begomovirus species ( Tomato leaf curl New Delhi virus , Tomato leaf curl Palampur virus and Tomato leaf curl Joydebpur virus ) selected based on their sequence identity and phylogenetic relatedness. The primers derived from Primer-BLAST tool showed high level of cross-reaction among these begomovirus species and therefore were not able to differentiate these target begomovirus species. In order to understand the reason of cross-reactivity further sequence analysis revealed the high occurrence of single nucleotide variations (SNVs) compared to the multi-nucleotide stretches. There was no SNV hot-spot in the genome, rather the SNVs were randomly distributed throughout the genome of these begomovirus species. This pattern of nucleotide diversities among these tomato-infecting begomoviruses seriously implicated on developing specific PCR diagnostics. On the contrary, sequence analysis showed high sequence conservancy, which enabled to develop a generic PCR diagnostic for these begomoviruses. Our study, thus showed that the genome sequence diversity pattern among the tomato-infecting begomoviruses in India poses challenges in developing PCR based specific diagnostics., Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-022-00785-9., (© The Author(s), under exclusive licence to Indian Virological Society 2022, Springer Nature or its licensor 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.)

Purpose: To describe the design, implementation, and adoption of a simplified electronic medical record (EMR) and its use in documenting pediatric central nervous system (CNS) tumors at a tertiary care referral hospital in South-East Asia., Methods: A novel EMR, cataloguing pediatric CNS tumors was used to collect data from August 2017 to March 2020 at National Institute of Neurosciences and Hospital (NINS&H) in Dhaka, Bangladesh., Results: Two hundred forty-nine pediatric patients with a CNS tumor were admitted to NINS&H. Fifty-eight percent of patients were male, and the median age was 8 years. A total of 188/249 patients (76%) underwent surgery during their index admission. Radiographic locations were known for 212/249 (85%) of cases; the most common radiographic locations were infratentorial (81/212; 38%), suprasellar (45/212; 21%), and supratentorial (29/212; 14%). A histopathological classification was reported on 156/249 (63%) of patients' cytology. The most common infratentorial pathologies were medulloblastoma (22/47; 47%) and pilocytic astrocytoma (14/47; 30%). The median time between admission and surgery was 36 days, while the median post-operation stay was 19.5 days., Conclusions: The feasibility of a basic EMR platform for a busy pediatric neurosurgery department in a lower-middle income country is demonstrated, and preliminary clinical data is reviewed. A wide variety of pediatric CNS tumors were observed, spanning the spectrum of anatomic locations and histopathologic subtypes. Surgical intervention was performed for the majority of patients. Barriers to care include limited molecular diagnostics and unavailable data on adjuvant therapy. Future targets include improvement of clinical documentation in the pre-operative and post-operative period., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

High pressure deep subsurface environments of Mars may harbor high concentrations of dissolved salts, such as perchlorates, yet we know little about how these salts influence the conditions for life, particularly in combination with high hydrostatic pressure. We investigated the effects of high magnesium perchlorate concentrations compared to sodium and magnesium chloride salts and high pressure on the conformational dynamics and stability of double-stranded B-DNA and, as a representative of a non-canonical DNA structure, a DNA-hairpin (HP), whose structure is known to be rather pressure-sensitive. To this end, fluorescence spectroscopies including single-molecule FRET methodology were applied. Our results show that the stability both of the B-DNA as well as the DNA-HP is largely preserved at high pressures and high salt concentrations, including the presence of chaotropic perchlorates. The perchlorate anion has a small destabilizing effect compared to chloride, however. These results show that high pressures at the kbar level and perchlorate anions can modify the stability of nucleic acids, but that they do not represent a barrier to the gross stability of such molecules in conditions associated with the deep subsurface of Mars.

Competing Interests: None declared.

Context: Pre-hypertension remains a significant public health challenge and appropriate intervention is required to stop its progression to hypertension and/or cardiovascular diseases., Objective: To study the effects of individualized homeopathic medicines (IH) against placebo in intervening with the progression of pre-hypertension to hypertension., Design: Double-blind, randomized, two parallel arms, placebo-controlled trial., Setting: Outpatient departments of D. N. De Homoeopathic Medical College and Hospital, Kolkata, West Bengal, India., Patients: Ninety-two patients suffering from pre-hypertension; randomized to receive either IH (n = 46) or identical-looking placebo (n = 46)., Interventions: IH or placebo in the mutual context of lifestyle modification (LSM) advices including dietary approaches to stop hypertension (DASH) and brisk exercises., Main Outcome Measures: Primary - systolic and diastolic blood pressure (SBP and DBP); secondary - Measure Yourself Medical Outcome Profile version 2.0 (MYMOP-2) scores; all measured at baseline, and every month, up to 3 months., Results: After 3 months of intervention, the number of patients having progression from pre-hypertension to hypertension between groups were similar without any significant differences in between (all P>0.05). Reduction in BP and MYMOP-2 scores were non-significantly higher (all P>0.05) in the IH group than placebo with small effect sizes. Lycopodium clavatum, Thuja occidentalis and Natrum muriaticum were the most frequently prescribed medicines. No harms or serious adverse events were reported from either group. Thus, there was a small, but non-significant direction of effect favoring homeopathy, which ultimately rendered the trial as inconclusive. [Trial registration: CTRI/2018/10/016,026; UTN: U1111-1221-8251]., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: There is some evidence that homeopathic treatment has been used successfully in previous epidemics, and currently some countries are testing homeoprophylaxis for the coronavirus disease 2019 (COVID-19) pandemic. There is a strong tradition of homeopathic treatment in India: therefore, we decided to compare three different homeopathic medicines against placebo in prevention of COVID-19 infections., Methods: In this double-blind, cluster-randomized, placebo-controlled, four parallel arms, community-based, clinical trial, a 20,000-person sample of the population residing in Ward Number 57 of the Tangra area, Kolkata, was randomized in a 1:1:1:1 ratio of clusters to receive one of three homeopathic medicines ( Bryonia alba 30cH, Gelsemium sempervirens 30cH, Phosphorus 30cH) or identical-looking placebo, for 3 (children) or 6 (adults) days. All the participants, who were aged 5 to 75 years, received ascorbic acid (vitamin C) tablets of 500 mg, once per day for 6 days. In addition, instructions on healthy diet and general hygienic measures, including hand washing, social distancing and proper use of mask and gloves, were given to all the participants., Results: No new confirmed COVID-19 cases were diagnosed in the target population during the follow-up timeframe of 1 month-December 20, 2020 to January 19, 2021-thus making the trial inconclusive. The Phosphorus group had the least exposure to COVID-19 compared with the other groups. In comparison with placebo, the occurrence of unconfirmed COVID-19 cases was significantly less in the Phosphorus group (week 1: odds ratio [OR], 0.1; 95% confidence interval [CI], 0.06 to 0.16; week 2: OR, 0.004; 95% CI, 0.0002 to 0.06; week 3: OR, 0.007; 95% CI, 0.0004 to 0.11; week 4: OR, 0.009; 95% CI, 0.0006 to 0.14), but not in the Bryonia or Gelsemium groups., Conclusion: Overall, the trial was inconclusive. The possible effect exerted by Phosphorus necessitates further investigation., Trial Registration: CTRI/2020/11/029265., Competing Interests: None declared., (Faculty of Homeopathy. This article is published by Thieme.)

Given the emergence of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), which particularly threatens older people with comorbidities such as diabetes mellitus and dementia, understanding the relationship between Covid-19 and other diseases is an important factor for treatment. Possible targets for medical intervention include G-quadruplexes (G4Qs) and their protein interaction partners. We investigated the stability and conformational space of the RG-1 RNA-G-quadruplex of the SARS-CoV-2 N-gene in the presence of salts, cosolutes, crowders and intrinsically disordered peptides, focusing on α-Synuclein and the human islet amyloid polypeptide, which are involved in Parkinson's disease (PD) and type-II diabetes mellitus (T2DM), respectively. We found that the conformational dynamics of the RG-1 G4Q is strongly affected by the various solution conditions. Further, the amyloidogenic peptides were found to strongly modulate the conformational equilibrium of the RG-1. Considerable changes are observed with respect to their interaction with human telomeric G4Qs, which adopt different topologies. These results may therefore shed more light on the relationship between PD as well as T2DM and the SARS-CoV-2 disease and their molecular underpinnings. Since dysregulation of G4Q formation by rationally designed targeting compounds affects the control of cellular processes, this study should contribute to the development of specific ligands for intervention., (© 2021 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background: Arsenic exposure has been associated with gestational diabetes mellitus. However, the extent to which arsenic exposure during pregnancy is associated with postpartum glucose intolerance is unknown., Methods: We studied 323 women in Bangladesh. We assessed arsenic exposure in early pregnancy via toenail and water samples. We measured fasting glucose and insulin in serum at a mean (SD) of 4.0 (3.5) weeks post-delivery. We ran covariate-adjusted, linear regression models to examine associations of arsenic concentrations with HOMA-IR, a marker of insulin resistance, and HOMA-β, a marker of beta cell function., Results: Median (IQR) arsenic concentration was 0.45 (0.67) μg/g in toenails and 2.0 (6.5) μg/L in drinking water. Arsenic concentrations during pregnancy were not associated with insulin resistance or beta cell function postpartum. HOMA-IR was 0.07% (- 3.13, 3.37) higher and HOMA-β was 0.96% (- 3.83, 1.99) lower per IQR increment in toenail arsenic, but effect estimates were small and confidence intervals crossed the null., Conclusions: Although arsenic exposure during pregnancy has been consistently associated with gestational diabetes mellitus, we found no clear evidence for an adverse effect on postpartum insulin resistance or beta cell function., (© 2021. The Author(s).)