Fractionation of Boswellia serrata oleogum resin essential oil by short-path molecular vacuum distillation: Unveiling potent biological activities and chemical composition.

Boswellia serrata produces oleo gum resin, a rich source of essential oil (EO). EOs, produced as secondary metabolites by medicinal plants, are employed for medicinal and therapeutic purposes. The present study aimed to investigate the yield, chemical composition, antioxidant (AO), antimicrobial, and hemolytic activity of B. serrata EO and its fractions and sub-fractions (SFs). The EO was extracted using the superheated steam extraction (SHSE) method at 140°C. Short-path molecular vacuum distillation was used to separate the EO into fractions and SFs. Gas chromatography-mass spectrometry analysis showed α-pinene, α-thujene, trans verbenol, and linalool as major components of EO. The AO potential was evaluated using a 2,2-diphenyl-1-picrylhydrazyl assay, % inhibition in a linoleic acid assay, H2O2 scavenging assay, and total AO content (TAOC) using a ferric reducing AO power assay. F2b SF exhibited the highest scavenging activity, with percentages of 95.77%, 96.20%, and 83.54%, respectively, whereas EO revealed the highest TAOC value of 115.94%. Antimicrobial activity was evaluated by disc diffusion, resazurin microtiter plate, and microdilution broth assays. F1c SF showed maximum antibacterial potential (high inhibition zone 17.65-38.28 mm and low minimum inhibitory concentration [MIC] 2.20-84.44 µg/mL). The EO showed the highest antifungal activity (high inhibition zone 12.58-25.81 mm and low MIC 35.18-225.17 µg/mL). Cytotoxicity was assessed by hemolytic assay, with the F1c SF showing the highest activity at 10.89%. It is concluded that SHSE is an effective technique for B. serrata EO extraction, and this EO can be utilized for various medicinal purposes.

Techno-economic and environmental analysis of hybrid energy system for industrial sector of Pakistan.

The industrial sector of Pakistan is currently facing severe load-shedding, which ultimately affects its unit production. The greater dependency on conventional energy resources (Thermal, Nuclear, etc.) results in higher production costs and environmental pollution. A sustainable, cost-effective, and environment-friendly solution can help the industrial growth of Pakistan. This article proposes an optimal hybrid energy system (HES) for the industrial sector of Pakistan to overcome the mentioned challenges. The proposed HES is developed in HOMER Pro. Three different energy cases (Case I: Existing energy system including a utility grid and diesel generator, Case II: On-grid Biogas system, and Case III: On-grid PV system with batteries) are considered for the Gourmet food Industry in the Sundar Industrial estate, Pakistan. The Load profile of the selected site was calculated through on-site visits and data provided by the designated utility grid feeder. The analysis shows that Case III is more effective than other cases, indicating reduced Net Present Cost (NPC), Cost of Energy (COE), and Operating Cost (OC) to $ 19.2 million, $0.034/kWh, and $ 573,371/year respectively. Moreover, the On-grid PV system with batteries (Case III) provides an environmentally friendly solution by reducing 63.82% [Formula: see text] by and 62.22% [Formula: see text]. Comparing the sensitivity analysis for various grid sell-back prices ($0/kWh, $0.043/kWh, $0.061/kWh, and $0.09/kWh), Case III is more cost-effective than Case II. The revenue generation in Case III is $128,499.41/yr, considering the supply of excess electricity into nearby small industrial loads at $0.065/kWh, this indicates that installing optimal HES in industries will not only help in overall cost reduction but also support in mitigating environmental pollution and load shedding.

Combined left atrial appendage occlusion and catheter ablation procedure for left atrial arrhythmias: A real-world, propensity-matched analysis.

INTRODUCTION: Real-world studies comparing safety and efficacy of combined percutaneous left atrial appendage occlusion (LAAO) and catheter ablation (CA) to LAAO alone are limited. METHODS: Patients from a large US hospital system undergoing combined LAAO and left-atrial CA from 8/2020 to 2/2024 were retrospectively analyzed and compared to a control group undergoing LAAO alone. Controls were identified using a 1:2 propensity score match based on LAAO device type (Watchman FLX vs. Amulet), CHA2D2-VASc and Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio [INR], Elderly, Drugs/alcohol (HAS-BLED) scores and compared for safety, sealing performance and clinical outcomes at 6 months. RESULTS: Patients were younger in the combined (n = 72) than in the control group (n = 144, 70.2 ± 7.3 vs. 76.7 ± 6.9 years, p < 0.001) but otherwise comparable with a mean CHA2D2-VASc score of 4.2 ± 1.1 and 4.4 ± 1.2 (p = 0.26) and HAS-BLED score of 2.2 ± 0.8 and 2.3 ± 0.7 (p = 0.34). Successful LAAO implantation rates were the same (95.8% vs. 95.8%, p = 0.99) with longer procedure times seen in the combined group (156.5 ± 53 vs. 56 ± 26 min, p < 0.001). Both major (1.4% vs. 2.1%, p = 0.72) and minor (27.8% vs. 19.4%, p = 0.17) in-hospital complications were similar between the combined and control group, respectively. At 45 days, presence of peri-device leak (18.3% vs. 30.4%, p = 0.07) and device related thrombosis (4.5% vs. 4.5%, p = 0.96) on transesophageal echocardiogram did not differ. Finally, all-cause mortality (0% vs. 1.4%, p = 0.99), thromboembolic (0% vs. 0%, p = 0.99) and bleeding (6.1% vs. 4.4%, p = 0.73) events during follow-up were comparable. CONCLUSION: This large, real-world analysis indicates comparable safety and efficiency of combined LAAO and CA when compared with LAAO alone.

Unraveling the impact of high arsenic, fluoride and microbial population in community tubewell water around coal mines in a semiarid region: Insight from health hazards, and geographic information systems.

High arsenic (As), fluoride (F-), and microbial pathogens coexist in semiarid conditions afflicting > 240 million people worldwide including Pakistan. Groundwater quality has declined due to geogenic and manmade activities providing suitable ground for ubiquity, bioavailability, and toxicity of contaminants. We tested the health hazard, distribution, and apportionment of As, F-, and microbes in groundwater around coal mines in Quetta, Pakistan. The range of As, and F- concentrations in groundwater were 0.2-16.6 µg/L, 0.4-18.5 mg/L. Both, As and F- correlate with high HCO3-, pH, Na+, SO42-, Fe, and Mn, and negatively with Ca2+ water. The coalfield showed many folds higher As 15.8-28.5 µg/L, and F- 10.8-34.5 mg/L compared to groundwater-wells. Geochemical phases revealed saturation of groundwater with calcite, dolomite, fluorite, gypsum, and undersaturation with halite-mirabilite, and arsenopyrite minerals. The positive matrix factorization (PMF) model assessed five-factor solutions: geogenic, industrial, coal mining, sulfide & fluoride-bearing mineral-dissolution, and agriculture pollution delivered As, F-, and microbial contamination. About 24.6 % and 64.4 % of groundwater samples exceeded the WHO guidelines of As 10 µg/L, F- 1.5 mg/L. The carcinogenicity, and non-carcinogenicity of As, and F- were higher in children than adults. Therefore, health hazards in children are of great concern in achieving sustainable management goals.

Dataset factors associated with age-related changes in brain structure and function in neurodevelopmental conditions.

With brain structure and function undergoing complex changes throughout childhood and adolescence, age is a critical consideration in neuroimaging studies, particularly for those of individuals with neurodevelopmental conditions. However, despite the increasing use of large, consortium-based datasets to examine brain structure and function in neurotypical and neurodivergent populations, it is unclear whether age-related changes are consistent between datasets and whether inconsistencies related to differences in sample characteristics, such as demographics and phenotypic features, exist. To address this, we built models of age-related changes of brain structure (regional cortical thickness and regional surface area; N = 1218) and function (resting-state functional connectivity strength; N = 1254) in two neurodiverse datasets: the Province of Ontario Neurodevelopmental Network and the Healthy Brain Network. We examined whether deviations from these models differed between the datasets, and explored whether these deviations were associated with demographic and clinical variables. We found significant differences between the two datasets for measures of cortical surface area and functional connectivity strength throughout the brain. For regional measures of cortical surface area, the patterns of differences were associated with race/ethnicity, while for functional connectivity strength, positive associations were observed with head motion. Our findings highlight that patterns of age-related changes in the brain may be influenced by demographic and phenotypic characteristics, and thus future studies should consider these when examining or controlling for age effects in analyses.

Hydrogeochemical properties, source provenance, distribution, and health risk of high fluoride groundwater: Geochemical control, and source apportionment.

This study evaluated high fluoride (F-) levels, source distribution, provenance, health risk, and source apportionment in the groundwater of Sargodha, Pakistan. Therefore, 48 groundwater samples were collected and analyzed by ion-chromatography (DX-120, Dionex). The lowest concentration of F- was 0.1, and the highest was 5.8 mg/L in the aquifers. In this study, 43.76% of the samples had exceeded the World Health Organization's allowable limit of 1.5 mg/L. The hydrogeochemical facies in Na-rich and Ca-poor aquifers showed NaCl (66.6%), NaHCO3 (14.5%), mixed CaNaHCO3 (8.3%), CaCl2 (8.3%), mixed CaMgCl2 (2%), and CaHCO3 (2%) type water. Alkaline pH, high Na+, HCO3- concentrations, and poor Ca-aquifers promoted F- dissolution in aquifer. The significant positive correlations between Na⁺ and F- suggested cation exchange, where elevated Na⁺ occurs in Ca-poor aquifers. The cation exchange reduces the availability of Ca2+ would lead to higher F- concentrations. Meanwhile, the correlation between HCO3- and F- indicates that carbonate minerals dissolution helps in increasing pH and HCO3- as a result F- triggers in aquifers. Groundwater chemistry is primarily governed by the weathering of rock, water-rock interaction, ion-exchange, and mineral dissolution significantly control groundwater compositions. Cluster analysis (CA) determined three potential clusters: less polluted (10.4%), moderately polluted (39.5%), and severely polluted (50%) revealing fluoride toxicity and vulnerability in groundwater wells. Mineral phases showed undersaturation and saturation determining dissolution of minerals and precipitation of minerals in the aquifer. PCAMLR model determined that high fluoride groundwater takes its genesis from F-bearing minerals, ion exchange, rock-water interaction, and industrial, and agricultural practices. The health risk assessment model revealed that children are at higher risk to F- toxicity than adults. Thus, groundwater of the area is unsuitable for drinking, domestic, and agricultural needs.

Chemistry, biosynthesis, and theranostics of antioxidant flavonoids and polyphenolics of genus Rhododendron: an overview.

The genus Rhododendron is an ancient and most widely distributed genus of the family Ericaceae consisting of evergreen plant species that have been utilized as traditional medicine since a very long time for the treatment of various ailments including pain, asthma, inflammation, cold, and acute bronchitis. The chemistry of polyphenolics isolated from a number of species of the genus Rhododendron has been investigated. During the currently designed study, an in-depth study on the phytochemistry, natural distribution, biosynthesis, and pharmacological properties including their potential capability as free radical scavengers has been conducted. This work provides structural characteristics of phenolic compounds isolated from the species of Rhododendron with remarkable antioxidant potential. In addition, biosynthesis and theranostic study have also been encompassed with the aims to furnish a wide platform of valuable information for designing of new drug entities. The detailed information including names, structural features, origins, classification, biosynthetic pathways, theranostics, and pharmacological effects of about 171 phenolics and flavonoids isolated from the 36 plant species of the genus Rhododendron with the antioxidant potential has been covered in this manuscript. This study demonstrated that species of Rhododendron genus have excellent antioxidant activities and great potential as a source for natural health products. This comprehensive review might serve as a foundation for more investigation into the Rhododendron genus.

Health risk assessment of bread wheat grown under cadmium and nickel stress and impact of silicic acid application on its growth, physiology, and metal uptake.

Heavy metal stress poses a significant threat to the productivity of agricultural systems and human health. Silicon (Si) is widely reported to be very effective against the different heavy metal stresses in crops. According to reports, it can help plants that are under cadmium (Cd) and nickel (Ni) stress. The presented work investigated how silicon interacted in Cd- and Ni-stressed wheat and mitigated metal toxicity. A pot experiment was carried out in which wheat crop was irrigated with Cd- and Ni-contaminated water. Application of Cd and Ni-contaminated water to wheat significantly reduced the root and shoot growth parameters and physiological and biochemical factors while increasing the antioxidant enzymatic activity and bioaccumulation of Cd and Ni metal in shoot and root as compared to the control. Application of Si led to an improvement in physiological parameters, i.e., greenness of leaves, i.e., SPAD values (17% and 26%), membrane stability (26% and 25%), and growth parameters i.e., root surface area (42% and 23%), root length (81% and 79%), root dry weight (456% and 190%), root volume (64% and 32%), shoot length (41% and 35%), shoot dry weight of shoot (111% and 117%), and overall grain weight (62% and 72%) under Cd and Ni stress, respectively. It increased the activity of antioxidant activity (max. up to 20%) whereas decreased the metal bioaccumulation of Cd and Ni in the roots and shoot (max. up to 62%) of wheat. It was concluded that the application of Si potentially increases antioxidant activity and metal chelation resulting in decreased oxidative damage and reducing the effect of Cd and Ni stress on wheat which improves growth and physiological parameters as well as inhibits Cd and Ni inclusion in food chain under Cd and Ni toxicity reducing health risks associated with these metals.

All the king's men (and women): Fluoro-less leadless pacemaker implant in a severely obese patient.

INTRODUCTION: Severe obesity presents significant challenges in imaging and delivery of therapy, including pacemaker implant. METHODS AND RESULT: We present our experience implanting a leadless pacemaker (LP) in a severely obese man presenting with heart block. We describe our multidisciplinary approach using right internal jugular venous access and transesophageal imaging in lieu of fluoroscopy which failed to provide workable images in this instance. CONCLUSION: Ultrasound guided LP placement may have wider application in the midst of an ongoing obesity epidemic where fluoroscopy imaging is both limited and unsafe.

The Role of Platelet Rich Plasma in Vertebrogenic and Discogenic Pain: A Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: The present investigation evaluates clinical uses and roles of platelet rich plasma in the management of vetrebrogenic and discogenic mediated pain states. RECENT FINDINGS: Back pain is a common and significant condition that affects millions of people around the world. The cause of back pain is often complex and multifactorial, with discogenic and vertebrogenic pain being two subtypes of back pain. Currently, there are numerous methods and modalities in which back pain is managed and treated such as physical therapy, electrical nerve stimulation, pharmacotherapies, and platelet-rich plasma. To conduct this systematic review, the authors used the keywords "platelet-rich plasma", "vertebrogenic pain", and "discogenic pain", on PubMed, EuroPMC, Who ICTRP, and clinicaltrials.gov to better elucidate the role of this treatment method for combating vertebrogenic and discogenic back pain. In recent decades, there has been a rise in popularity of the use of platelet-rich plasma for the treatment of numerous musculoskeletal conditions. Related to high concentration of platelets, growth factors, cytokines, and chemokines, platelet-rich plasma is effective in reducing pain related symptoms and in the treatment of back pain. Platelet-rich plasma use has evolved and gained popularity for pain related conditions, including vertebrogenic and discogenic back pain. Additional well-designed studies are warranted in the future to better determine best practice strategies to provide future clinicians with a solid foundation of evidence to make advancements with regenerative medical therapies such as platelet-rich plasma.

Concomitant Occurrence of Peripheral Neuropathy and Vision Loss Due to Multivitamin Deficiency After Bariatric Surgery.

Vitamin deficiencies, especially after Bariatric surgery, are common and, when not properly addressed, can lead to debilitating complications. Bariatric procedures, to variable degrees, alter the anatomy and physiology of the gastrointestinal; this alteration makes these patients more susceptible to developing nutritional deficiencies. Peripheral neuropathy is one of the complications that can arise from nutritional deficiencies, and it can cause severe functional impairment. Vision loss is a relatively uncommon complication after weight loss procedure. Changes in the retinal nerve fiber layer, choroidal thickness, and visual fields due to hypovitaminosis result in nutritional optic neuropathy and retinopathy. The main retinal complication is nyctalopia (night blindness), which is caused by vitamin A deficiency. We present a case of concomitant peripheral neuropathy and vision loss secondary to reduced levels of multiple vitamins following gastric bypass surgery. This case highlights the need for regular vitamin level monitoring and appropriate replenishment in patients after bariatric surgery to prevent significant morbidities.

Immune Checkpoint Inhibitors and Cardiotoxicity: A Comparative Meta-Analysis of Observational Studies and Randomized Controlled Trials.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have uncommon associations with cardiotoxicity, yet these cardiotoxic effects are associated with high mortality. An accurate assessment of risk for cardiotoxicity is essential for clinical decision-making, but data from randomized controlled trials often differ from real-world observational studies. METHODS AND RESULTS: A systematic search of PubMed, Embase, Cochrane Library, and Scopus was performed, including phase II and III randomized controlled trials (RCTs) and observational studies (OSs) reporting myocarditis or pericardial disease, myocardial infarction, or stroke with an immunotherapy. Odds ratios (ORs) were used to pool results between ICIs and other cancer therapy in RCTs and OSs. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline was followed. In total, 54 RCTs (N=38 264) and 24 OSs (N=12 561 455) were included. In RCTs, ICI use resulted in higher risk of myocarditis (OR, 3.55 [95% CI, 2.10-5.98]), pericardial disease (OR, 2.73 [95% CI, 1.57-4.77]), and myocardial infarction (OR, 1.83 [95% CI, 1.03-3.25]), compared with non-ICI (placebo or chemotherapy). In OSs, ICI use was not associated with myocarditis, pericardial disease, or myocardial infarction compared with controls; however, combination ICIs demonstrated higher risk of myocarditis compared with single ICI use (OR, 3.07 [95% CI, 1.28-7.39]). Stroke risk was not increased with use of ICIs in RCTs. CONCLUSIONS: We demonstrated increased risk of ICI myocarditis, pericardial disease, and myocardial infarction in RCTs but not OSs. Results of this study suggest there are differences between ICI cardiotoxicity risk, possibly suggesting differences in diagnoses and management, in clinical trials versus the OSs.

Uterine artery embolization versus myomectomy: a systematic review and meta-analysis.

Introduction: Uterine fibroids are the commonest benign tumors of the reproductive tract in women of childbearing age. They are usually asymptomatic but can cause menorrhagia. Treatments include myomectomy and uterine artery embolization (UAE). The latter is a relatively new procedure, therefore of special interest. Objectives: We conducted a systematic review and meta-analysis of all published studies to provide a comprehensive outlook on the effectiveness of UAE by comparing its outcomes to those of myomectomy. Electronic databases (PubMed and Cochrane Central) were systematically searched from January 2000 to March 2022 for published randomized control trials, observational studies, and meta-analyses that compared UAE to myomectomy for at least one of the pre-specified outcomes, namely re-intervention rates, length of hospital stay, and complications. Methods: We shortlisted nine studies for the final analysis. For continuous outcomes, results from random-effects meta-analysis were presented as mean differences (MDs) and corresponding 95% confidence intervals (CIs). Risk ratios (RRs) for dichotomous outcomes were pooled using a random-effects model. Results: The final analysis consisted of nine studies. Factors like re-intervention, hospitalization, and complications, each with its unique follow-up duration were assessed. Pooled analysis demonstrated significant results for greater re-intervention rates with UAE as compared to myomectomy (RR: 2.16, 95% CI: (1.27-3.66), p-value 0.004, heterogeneity I2 = 85%). UAE holds a greater but statistically insignificant risk for major complications (RR: 0.62, 95% CI: (0.29-1.33), p-value 0.22, heterogeneity I2 = 0%) and myomectomy shows a statistically insignificant greater risk for minor complications (RR: 1.72, 95% CI: (0.92-3.22), p-value 0.09, heterogeneity I2 = 0%). UAE had a shorter but statistically insignificant duration of hospital stay (MD: -1.12, 95% CI: (-2.50 to 0.27), p-value 0.11, heterogeneity I2 = 96%) (p-value for subgroup differences = 0.005). Conclusion: Our meta-analysis of approximately 196,595 patients demonstrates that myomectomy results in a significant reduction in re-intervention rate compared to UAE.

Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder.

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.

Behaviour-correlated profiles of cerebellar-cerebral functional connectivity observed in independent neurodevelopmental disorder cohorts.

The cerebellum, through its connectivity with the cerebral cortex, plays an integral role in regulating cognitive and affective processes, and its dysregulation can result in neurodevelopmental disorder (NDD)-related behavioural deficits. Identifying cerebellar-cerebral functional connectivity (FC) profiles in children with NDDs can provide insight into common connectivity profiles and their correlation to NDD-related behaviours. 479 participants from the Province of Ontario Neurodevelopmental Disorders (POND) network (typically developing = 93, Autism Spectrum Disorder = 172, Attention Deficit/Hyperactivity Disorder = 161, Obsessive-Compulsive Disorder = 53, mean age = 12.2) underwent resting-state functional magnetic resonance imaging and behaviour testing (Social Communication Questionnaire, Toronto Obsessive-Compulsive Scale, and Child Behaviour Checklist - Attentional Problems Subscale). FC components maximally correlated to behaviour were identified using canonical correlation analysis. Results were then validated by repeating the investigation in 556 participants from an independent NDD cohort provided from a separate consortium (Healthy Brain Network (HBN)). Replication of canonical components was quantified by correlating the feature vectors between the two cohorts. The two cerebellar-cerebral FC components that replicated to the greatest extent were correlated to, respectively, obsessive-compulsive behaviour (behaviour feature vectors, rPOND-HBN = -0.97; FC feature vectors, rPOND-HBN = -0.68) and social communication deficit contrasted against attention deficit behaviour (behaviour feature vectors, rPOND-HBN = -0.99; FC feature vectors, rPOND-HBN = -0.78). The statistically stable (|z| > 1.96) features of the FC feature vectors, measured via bootstrap re-sampling, predominantly comprised of correlations between cerebellar attentional and control network regions and cerebral attentional, default mode, and control network regions. In both cohorts, spectral clustering on FC loading values resulted in subject clusters mixed across diagnostic categories, but no cluster was significantly enriched for any given diagnosis as measured via chi-squared test (p > 0.05). Overall, two behaviour-correlated components of cerebellar-cerebral functional connectivity were observed in two independent cohorts. This suggests the existence of generalizable cerebellar network differences that span across NDD diagnostic boundaries.

Gender diversity is correlated with dimensional neurodivergent traits but not categorical neurodevelopmental diagnoses in children.

BACKGROUND: Gender clinic and single-item questionnaire-based data report increased co-occurrence of gender diversity and neurodevelopmental conditions. The nuances of these associations are under-studied. We used a transdiagnostic approach, combining categorical and dimensional characterization of neurodiversity, to further the understanding of its associations with gender diversity in identity and expression in children. METHODS: Data from 291 children (Autism N = 104, ADHD N = 104, Autism + ADHD N = 17, neurotypical N = 66) aged 4-12 years enrolled in the Province of Ontario Neurodevelopmental Network were analyzed. Gender diversity was measured multi-dimensionally using a well-validated parent-report instrument, the Gender Identity Questionnaire for Children (GIQC). We used gamma regression models to determine the significant correlates of gender diversity among age, puberty, sex-assigned-at-birth, categorical neurodevelopmental diagnoses, and dimensional neurodivergent traits (using the Social Communication Questionnaire and the Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Rating Scales). Internalizing and externalizing problems were included as covariates. RESULTS: Neither a categorical diagnosis of autism nor ADHD significantly correlated with current GIQC-derived scores. Instead, higher early-childhood dimensional autistic social-communication traits correlated with higher current overall gender incongruence (as defined by GIQC-14 score). This correlation was potentially moderated by sex-assigned-at-birth: greater early-childhood autistic social-communication traits were associated with higher current overall gender incongruence in assigned-males-at-birth, but not assigned-females-at-birth. For fine-grained gender diversity domains, greater autistic restricted-repetitive behavior traits were associated with greater diversity in gender identity across sexes-assigned-at-birth; greater autistic social-communication traits were associated with lower stereotypical male expression across sexes-assigned-at-birth. CONCLUSIONS: Dimensional autistic traits, rather than ADHD traits or categorical neurodevelopmental diagnoses, were associated with gender diversity domains across neurodivergent and neurotypical children. The association between early-childhood autistic social-communication traits and overall current gender diversity was most evident in assigned-males-at-birth. Nuanced interrelationships between neurodivergence and gender diversity should be better understood to clarify developmental links and to offer tailored support for neurodivergent and gender-diverse populations.

Early Intervention in Psychosis and Management of First Episode Psychosis in Low- and Lower-Middle-Income Countries: A Systematic Review.

BACKGROUND AND HYPOTHESIS: People with first-episode psychosis (FEP) in low- and lower-middle-income countries (LMIC) experience delays in receiving treatment, resulting in poorer outcomes and higher mortality. There is robust evidence for effective and cost-effective early intervention in psychosis (EIP) services for FEP, but the evidence for EIP in LMIC has not been reviewed. We aim to review the evidence on early intervention for the management of FEP in LMIC. STUDY DESIGN: We searched 4 electronic databases (Medline, Embase, PsycINFO, and CINAHL) to identify studies describing EIP services and interventions to treat FEP in LMIC published from 1980 onward. The bibliography of relevant articles was hand-searched. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. STUDY RESULTS: The search strategy produced 5074 records; we included 18 studies with 2294 participants from 6 LMIC countries. Thirteen studies (1553 participants) described different approaches for EIP. Pharmacological intervention studies (n = 4; 433 participants) found a high prevalence of metabolic syndrome among FEP receiving antipsychotics (P ≤ .005). One study found a better quality of life in patients using injectables compared to oral antipsychotics (P = .023). Among the non-pharmacological interventions (n = 3; 308 participants), SMS reminders improved treatment engagement (OR = 1.80, CI = 1.02-3.19). The methodological quality of studies evidence was relatively low. CONCLUSIONS: The limited evidence showed that EIP can be provided in LMIC with adaptations for cultural factors and limited resources. Adaptations included collaboration with traditional healers, involving nonspecialist healthcare professionals, using mobile technology, considering the optimum use of long-acting antipsychotics, and monitoring antipsychotic side effects.

Hydrogeochemical characteristics, stable isotopes, positive matrix factorization, source apportionment, and health risk of high fluoride groundwater in semiarid region.

Chronic exposure to high fluoride (F-) levels in groundwater causes community fluorosis and non-carcinogenic health concerns in local people. This study described occurrence, dental fluorosis, and origin of high F-groundwater using δ2H and δ18O isotopes at semiarid Gilgit, Pakistan. Therefore, groundwater (n = 85) was collected and analyzed for F- concentrations using ion-chromatography. The lowest F- concentration was 0.4 mg/L and the highest 6.8 mg/L. F- enrichment is linked with higher pH, NaHCO3, NaCl, δ18O, Na+, HCO3-, and depleted Ca+2 aquifers. The depleted δ2H and δ18O values indicated precipitation and higher values represented the evaporation effect. Thermodynamic considerations of fluorite minerals showed undersaturation, revealing that other F-bearing minerals viz. biotite and muscovite were essential in F- enrichment in groundwater. Positive matrix factorization (PMF) and principal component analysis multilinear regression (PCAMLR) models were used to determine four-factor solutions for groundwater contamination. The PMF model results were accurate and reliable compared with those of the PCAMLR model, which compiled the overlapping results. Therefore, 28.3% exceeded the WHO permissible limit of 1.5 mg/L F-. Photomicrographs of granite rocks showed enriched F-bearing minerals that trigger F- in groundwater. The community fluorosis index values were recorded at > 0.6, revealing community fluorosis and unsuitability of groundwater for drinking.

A novel in-frame deletion in KIF5C gene causes infantile onset epilepsy and psychomotor retardation.

Motor proteins, encoded by Kinesin superfamily (KIF) genes, are critical for brain development and plasticity. Increasing studies reported KIF's roles in neurodevelopmental disorders. Here, a 6 years and 3 months-old Chinese boy with markedly symptomatic epilepsy, intellectual disability, brain atrophy, and psychomotor retardation was investigated. His parents and younger sister were phenotypically normal and had no disease-related family history. Whole exome sequencing identified a novel heterozygous in-frame deletion (c.265_267delTCA) in exon 3 of the KIF5C in the proband, resulting in the removal of evolutionarily highly conserved p.Ser90, located in its ATP-binding domain. Sanger sequencing excluded the proband's parents and family members from harboring this variant. The activity of ATP hydrolysis in vitro was significantly reduced as predicted. Immunofluorescence studies showed wild-type KIF5C was widely distributed throughout the cytoplasm, while mutant KIF5C was colocalized with microtubules. The live-cell imaging of the cargo-trafficking assay revealed that mutant KIF5C lost the peroxisome-transporting ability. Drosophila models also confirmed p.Ser90del's essential role in nervous system development. This study emphasized the importance of the KIF5C gene in intracellular cargo-transport as well as germline variants that lead to neurodevelopmental disorders and might enable clinicians for timely and accurate diagnosis and disease management in the future.