Evolution of waterborne diseases: A case study of Khyber Pakhtunkhwa, Pakistan.

Objectives: In Pakistan, the degradation of drinking water quality is exacerbated by the increasing population size and rapid industrialization. Contaminated water serves as the predominant source of numerous diseases, including diarrhea, gastroenteritis, and typhoid. This article explores the evolution of waterborne diseases across 21 districts of the Khyber Pakhtunkhwa province in Pakistan by monitoring changes in the clustering solutions. Methods: The data employed in this study were sourced from 21 districts of KP by the Director-General Health Services. Cluster analysis was utilized to uncover patterns in waterborne disease incidence, while principal component analysis was employed to reveal underlying patterns and reduce dimensionality. Additionally, the MONItoring Clusters (MONIC) framework was applied for change detection, facilitating the identification of significant shifts in disease patterns over time and aiding in the understanding of temporal dynamics. Results: Our analysis indicates that two clusters survived consistently over time, while other clusters exhibited inconsistency. Profiling of the surviving clusters (C12 → C24 → C32 → C43) suggests a gradual increase in cases of bloody diarrhea in the Swat Valley, Hangu, Karak, and Lakki Marwat regions. Similarly, profiling of the surviving clusters (⊙→ C22 → C34 → C44) suggests an increase in the acute watery diarrhea (non-cholera) and typhoid fever in the regions of Peshawar, Nowshera, and Swabi. Conclusion: The findings of this study hold significant importance as they pinpoint the most vulnerable regions for various waterborne diseases. These insights offer valuable guidance to policymakers and health officials, empowering them to implement effective measures for controlling waterborne diseases in the respective regions of Khyber Pakhtunkhwa, Pakistan.

Microstructural and mechanical characterization of electron beam welded low-nickel nitrogen-strengthened austenitic stainless steel.

In this paper, the Electron Beam Welding (EBW) was used to join thin plates of low-nickel nitrogen-strengthened austenitic stainless steel (LNiASS), a material valued for its superior mechanical properties and cost-effectiveness. Traditional welding techniques often lead to issues such as hot cracking, reduced toughness, and undesirable microstructures. The objective was to address these challenges using EB·W., which offers precise control, minimal heat input, and deeper penetration. Methodology included joining LNiASS plates with E.B.W. and analyzing the resulting microstructures and mechanical properties through optical microscopy, tensile testing, microhardness testing, and scanning electron microscopy (SEM). The findings indicated the presence of various ferrite morphologies without significant precipitation of deleterious phases like carbides and sigma phase. The weldment strength was ∼90 % of the base alloy, with fractures occurring near the weld cord due to nitrogen loss and grain coarsening in the (HAZ). Microhardness increased by ∼12.9 %, attributed to microstructural evolution and a fine-grained structure. Impact testing in Charpy V-Notch (CVN) configuration showed the weld absorbed ∼50 % more impact energy than the base material, due to refined Microstructure and enhanced hardness. Longitudinal residual stress analysis indicated compressive nature below mid-thickness, resulting from thermal expansion and contraction during welding. These results demonstrated E.B·W.'s effectiveness in preserving mechanical properties and enhancing the performance of nitrogen-strengthened stainless steel welds.

Effectiveness and safety of preoperative distraction using modified halo-pelvic Ilizarov distraction assembly in patients with severe kyphoscoliosis.

Study Design: A 2-year follow-up study. Purpose: To evaluate the effectiveness of modified halo-pelvic Ilizarov distraction assembly in the management of patients with severe kyphoscoliosis. Overview of Literature: Severe and rigid scoliosis curves are always a challenge for operating surgeons. Preoperative correction through halo-pelvic devices successfully minimizes the severity of the curve; however, cumbersome complications are also reported with its use. Modified assembly could be safe for these cases. Methods: Patients with severe kyphoscoliosis having coronal Cobb angle >90° were applied with modified halo-pelvic Ilizarov distraction assembly preoperatively. The modified assembly consisted of a pelvic component and halo ring, and distraction was given at the rate of 2-3 mm/day for 6-12 weeks. Complete clinical assessments along with pulmonary function tests were performed, and scoliosis series X-ray images were assessed for coronal and sagittal Cobb angle and other spinopelvic parameters before applying the assembly and during 2 years of follow-up. Results: Thirty-four patients (age, 9-27 years; male/female ratio of 18:16) were included. The coronal and sagittal Cobb angles were 116°±16.2° and 84°±28.3°, respectively. Correction rates obtained through modified halo-pelvic assembly were nearly 52% (p=0.001) in coronal and 40% (p=0.001) in sagittal Cobb angles, with improvement in height (p=0.001). Apical vertebral translation and coronal balance were also improved significantly (p=0.001). Further improvements in all the parameters were obtained after definitive surgery, with improvements in the forced expiratory volume in 1 second (p =0.002) and forced vital capacity (p=0.001). Conclusions: Our modified halo-pelvic Ilizarov distraction assembly can achieve good correction in severe spinal deformities without significant risk to neurology, has fewer complications, and promotes good patient compliance.

Removal of hydrocarbon pollutants from refinery wastewater using N-hexadecylchitosan as an efficient adsorptive platform.

The negative impact of refinery wastewater is of great concern to the aquatic, terrestrial, and aerial environment. In this study, N-hexadecylchitosan (NHDC) was successfully synthesized to deal with low mechanical strength, poor adsorption capacity, and limited selectivity of native chitosan. The NHDC was characterized by fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and X-Ray diffraction analysis (XRD) to study its composition, morphology, and structural attributes. The adsorption of hydrocarbon pollutants from refinery wastewater was studied in batch mode experiments. The results indicated that the removal of COD attained by chitosan and NHDC was 21 and 63%, respectively. COD removal was found to be maximal, i.e., 96% using 0.08 g of NHDC at 60 min in a solution of pH 6.5 maintained at 60 °C. Furthermore, kinetic data revealed that the adsorption system followed pseudo-second order kinetics, whereas equilibrium studies supported both monolayer and multilayer adsorption mechanisms. The designed adsorption platform was able to capture hydrocarbon pollutants under very mild optimized conditions. Furthermore, NHDC demonstrated long term stability when subjected to five successive cycles, which contributed to the sustainability of water treatment systems. On the basis of the outcome of this work, it is advocated that new biobased NHDC can be used as an efficient adsorbent for the remediation of organic contaminants laden wastewater streams generated from oil refineries.

Insights into Metabolites Profiling and Pharmacological Investigation of Aconitum heterophyllum wall ex. Royle Stem through Experimental and Bioinformatics Techniques.

The Aconitum genus is a leading source of a wide range of structurally diverse metabolites with significant pharmacological implications. The present study investigated metabolite profiling, pharmacological investigation, anticancer potential, and molecular docking analysis of the stem part of Aconitum heterophyllum (AHS). The metabolite profiling of the AHS extract was experimentally examined using LC-MS/MS-orbitrap in both modes (ESI+/ESI-) and GC-MS in EI mode. The in vitro MTT model was used to study the anticancer potential, while the in vivo animal model was used to study the anti-inflammatory and antinociceptive activities. The MOE software was used for the molecular docking study. A total of 118 novel and previously known metabolites, among 44 metabolites (26 in ESI+ positive mode and 18 in ESI- negative mode) in the MeOH extract, while 74 metabolites (46 in ESI+ and 28 in ESI- mode) were identified in the n-hexane extract via LCMS/MS. The identified metabolites include 24 phenolic compounds, 18 alkaloids, 10 flavonoids, 24 terpenoids, 2 coumarins, 2 lignans, and 38 other fatty acids and organic compounds. The major bioactive metabolites identified were hordenine, hernagine, formononetin, chrysin, N-methylhernagine, guineesine, shogaol, kauralexin, colneleate, zerumbone, medicarpin, boldine, miraxinthin-v, and lariciresinol-4-O-glucoside. Furthermore, the GC-MS study helped in the identification of volatile and nonvolatile chemical constituents based on the mass spectrum and retention indices. The methanol extract significantly inhibited tumor progression in H9c2 and MDCK cancer cells with IC50 values of 186.39 and 199.63 µg/mL. In comparison, the positive control aconitine exhibited potent IC50 values (132.32 and 141.58 µg/mL) against H9c2 and MDCK cell lines. The anti-inflammatory (carrageenan-induced hind paw edema) and antinociceptive (acetic acid-induced writhing) effects were significantly dose-dependent, (p < 0.001) and (p < 0.05), respectively. In addition, a molecular docking study was conducted on identified ligands against the anti-inflammatory enzyme (COX-2) (PDB ID: 5JVZ) and the cancer enzyme ADAM10 (PDB ID: 6BDZ) which confirmed the anti-inflammatory and anticancer effects in an in silico model. Among all ligands, L2, L3, and L7 exhibit the most potent potential for inhibiting COX-2 inflammation with binding energies of -7.3424, -7.0427, and -8.3562 kcal/mol. Conversely, against ADAM10 cancer protein, ligands L1, L4, L6, and L7, with binding energies of -8.0650, -7.7276, -7.0454, and -7.2080 kcal/mol, demonstrated notable effectiveness. Overall, the identified metabolites revealed in this AHS research study hold promise for discovering novel possibilities in the disciplines of chemotaxonomy and pharmacology.

A Novel Coated Suture Displays Antimicrobial Activity Without Compromising Structural Properties.

BACKGROUND: Treated or coated sutures promise to prevent contamination of wounds. PURPOSE: The purpose of the study was to coat surgical sutures with a new quaternary ammonium silane (QAS) antimicrobial compound at two different application temperatures and then to evaluate the resulting structural, physical, mechanical, and biological properties. STUDY DESIGN, SETTING, SAMPLE: In vitro and in vivo studies were conducted using male albino Wistar rats approved by the Joint Ethical Committee of IMU and Postgraduate Medical Institute, Lahore. Only suture samples, coated uniformly with verified presence of the compound and of adequate length were used. Samples which were not coated uniformly and with inadequate length or damaged were excluded. PREDICTOR VARIABLE: Predictor variables were sutures with and without QAS coatings and different temperatures. Sutures were coated with QAS at 0.5 and 1.0% wt/vol using the dip coating technique and sutures with and without QAS coating were tested at 25 and 40 °C temperatures. MAIN OUTCOME VARIABLE(S): Outcome variables of structural and physico-mechanical properties of QAS-coated and non-coated sutures were measured using Fourier transform infrared spectroscopy (for structural changes), confocal laser and scanning electron (for diameter changes), and tensile strength/modulus (for mechanical testing). Biologic outcome variables were tested (bacterial viability); macrophage cultures from Wistar rats were tested (M1/M2 polarization detecting IL-6 and IL-10). Macrophage cells were analyzed with CD80+ (M1) and CD163+ (M2). Chemotaxis index was calculated as a ratio of quantitative fluorescence of cells. COVARIATES: Not applicable. ANALYSES: Ordinal data among groups were compared using the Wilcoxon Mann-Whitney U test along with the comparison of histological analysis using the Wilcoxon Sign-rank test (P < .05). RESULTS: Fourier transform infrared spectroscopy peak at 1490 cm-1 confirmed the presence of QAS on suture's surfaces with a significant increase (P < .05) in diameter (0.99 ± 0.5-mm) and weight (0.77 ± 0.02-mg) observed for 1% QAS groups treated at 40 °C. Non-coated samples heated at 25 °C had significantly (P < .05) less diameters (0.22 ± 0.03-mm) and weights (0.26 ± 0.06-mg). Highest tensile strength/modulus was observed for 0.5% QAS-coated samples which also had significantly higher antibacterial characteristics than other sutures (P < .05). QAS-coated sutures significantly increased M1 and M2 markers. CONCLUSION AND RELEVANCE: QAS coating conferred antibacterial action properties without compromising the physical and mechanical properties of the suture.

Melamine-based hyper-cross-linked resin for efficient removal of total petroleum hydrocarbons (C10-C32) from aqueous solutions.

Petroleum hydrocarbons (PHCs) are produced from industrial discharges, storage leakages, accidental spills, and operational failures. The hazardous nature of PHCs causes serious health risks and threatens the entire aquatic habitat. In this research work, the investigation of the removal of total petroleum hydrocarbons (TPHs) from the contaminated water is carried out utilizing a novel hypercross-linked resin, MAICY, which is generated by condensation of commercially available precursors. The chemical structures of MAICY have been examined extensively by FESEM, FT-IR, solid (CP-MAS) 13C-NMR, and TGA. A comprehensive analysis for adsorption parameters of TPHs has been performed, and different models such as Langmuir and Freundlich isotherms have been employed where the Freundlich isotherm was found to be the best fit for removal of THPs (R2= 0.9991). The results revealed that the performance of MAICY for the adsorption of TPHs from contaminated water gives a maximum adsorption capacity (qe) of 146 mg.g-1. The results of various parameters hinted that the contact time (0.25-4 h), the dosage of adsorbent (0.17 g/L), pH (7), and concentration of TPHs (26.5 mg/L) have controlled the overall adsorptive performance. Moreover, the kinetic data of qe(expt.) and qe(calc.) for adsorption of TPHs disclosed the regression values (R2) for pseudo-first order (R2= 0.9921) and pseudo-second order (R2= 0.9891). Additionally, based on CHI factor (X2) error estimations, the data was shown to be more consistent with pseudo-first-order kinetics. Moreover, MAICY demonstrated excellent reusability and recycling properties for up to four consecutive adsorption-desorption cycles.

A novel variant in the FLNB gene associated with spondylocarpotarsal synostosis syndrome.

OBJECTIVES: Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. METHODS: The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. RESULTS: Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. CONCLUSIONS: The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Vertebral Endplate Defects Induced Mechanical Alterations and Disc Calcification.

STUDY DESIGN: Cross sectional comparative study. OBJECTIVES: The current study aims to explore the calcification potential (BMP2 expression) of intervertebral discs and its association with the presence of vertebral endplate defects visible on MRI. METHODS: Forty-seven herniated lumbar disc samples obtained from patients aged 20-76 (31 M/16F) undergoing surgery. Five-µm thin sections were stained with H&E in order to assign a histological degeneration score (HDS) from 0-15 on the basis of cell density (0-5), structural alterations (0-4), granular changes (0-3) and mucus degeneration (0-3). Sections were immuno-stained with anti BMP-2 antibodies to observe the calcification potential in these discs. In addition, pre-operativeT2-T1 W MRI images of the lumbar spine were analyzed for the presence and type (typical or atypical) of vertebral endplate defects, grade of disc degeneration (Pfirrmann grade I-V), presence of high intensity zones (HIZ), and Modic changes at the operated level. RESULTS: Vertebral endplate defects, Modic changes & HIZ were observed in 81%, 29% and 21% of patients respectively. Mean HDS & BMP-2 expression was 9 ± 2 and mean 71 ± 36 spots/mm2 respectively. Discs with adjacent vertebral endplate defects showed increased cell density (P = .004), mucus degeneration (P = .002), HDS (P = .01) and BMP-2 expression (P = .01). Discs with HIZ also had increased HDS, but significance was seen with increased BMP2 expression (P = .006). HDS showed a positive correlation with BMP 2 expression (r = .30, P = .04). CONCLUSION: These findings suggest that the altered mechanical environment of discs is strongly associated with BMP-2 expression which is an important marker of intervertebral disc calcification.

Eating Disorders and Disordered Eating Behaviors Among Undergraduate Students in Pakistan as Measured by Eating Disorder Examination Questionnaire (EDE-Q).

Objectives Eating disorders (ED) are an emerging public health issue globally, especially in young adults studying at the undergraduate level. This study aims to assess the frequency of eating disorders, their types, and disordered eating behaviors among such students. Moreover, it aims to identify factors like weight concern, shape concern, eating concern, and restraint, along with assessing the shifting trend of BMI impact on eating disorders using a standardized Eating Disorder Examination Questionnaire (EDE-Q). Methods In this cross-sectional study, 400 undergraduate students (aged 18-25) from four public universities participated from July 2022 to November 2023. Data was collected using the Eating Disorder Examination Questionnaire (EDE-Q). The frequency of eating disorders was computed using SPSS version 27. Results Among the participants, 21.75% (n=84) were identified as having a score surpassing the clinical cut-off. This group comprised 5.5% males (n=22) and 16% females (n=64). The highest prevalence among the four subscales was observed in the Shape Concern subscale (10.5%). Objective binge episodes (19.3%) emerged as the most notable disordered eating attitude. Atypical anorexia nervosa accounted for 13.8% of different eating disorders, while disordered eating was noted in 19.5% (n=78) of individuals. Discussion This study offers critical insights into eating disorders among Pakistan undergraduate students, utilizing the EDE-Q 6.0. Disordered eating behaviors, particularly shape concern and objective binge eating, exhibit significant correlations with these disorders. Weight dissatisfaction emerges as a prominent predictor, suggesting societal influence. The study also reveals a moderate correlation between BMI and eating disorders, challenging conventional assumptions. Furthermore, a changing trend in the prevalence of eating disorders is observed among the male population.

Cholesteryl Ester Transfer Protein Inhibitors and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy. METHODS: We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible. PRIMARY OUTCOMES: major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality. SECONDARY OUTCOMES: stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI). RESULTS: Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; p = 0.02; I2 = 0%); the same studies also reduced the risk of MI (RR = 0.92; 95% CI: 0.86-0.98; p = 0.01; I2 = 0%), which was primarily attributed to anacetrapib. The use of a CETPi did not reduce the likelihood any other outcomes. CONCLUSIONS: Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI.

Genome-wide association studies identifies genetic loci related to fatty acid and branched-chain amino acid metabolism and histone modifications under varying nitrogen treatments in safflower (Carthamus tinctorius).

Effective identification and usage of genetic variation are prerequisites for developing nutrient-efficient cultivars. A collection of 94 safflower (Carthamus tinctorius ) genotypes (G) was investigated for important morphological and photosynthetic traits at four nitrogen (N) treatments. We found significant variation for all the studied traits except chlorophyll b (chl b ) among safflower genotypes, nitrogen treatments and G×N interaction. The examined traits showed a 2.82-50.00% increase in response to N application. Biological yield (BY) reflected a significantly positive correlation with fresh shoot weight (FSW), root length (RL), fresh root weight (FRW) and number of leaves (NOL), while a significantly positive correlation was also observed among carotenoids (C), chlorophyll a (chl a ), chl b and total chlorophyll content (CT) under all treatments. Superior genotypes with respect to plant height (PH), FSW, NOL, RL, FRW and BY were clustered into Group 3, while genotypes with better mean performance regarding chl a , chl b C and CT were clustered into Group 2 as observed in principal component analysis. The identified eight best-performing genotypes could be useful to develop improved nitrogen efficient cultivars. Genome-wide association analysis resulted in 32 marker-trait associations (MTAs) under four treatments. Markers namely DArT-45481731 , DArT-17812864 , DArT-15670279 and DArT-45482737 were found consistent. Protein-protein interaction networks of loci associated with MTAs were related to fatty acid and branched-chain amino acid metabolism and histone modifications.

Color-switching hydrogels as integrated microfluidic pressure sensors.

Precisely measuring pressure in microfluidic flows is essential for flow control, fluid characterization, and monitoring, but faces specific challenges such as achieving sufficient resolution, non-invasiveness, or ease of use. Here, we demonstrate a fully integrated multiplexed optofluidic pressure sensor, entirely decoupled from the flow path, that enables local pressure measurements along any microfluidic channel without altering its flow geometry. The sensor itself relies on the compression of a soft mechano-actuated hydrogel, changing color in response to a pressure change. The hydrogel is separated from the fluid circulating in the channel by a thin membrane, allowing for the unrestricted use of different types of fluids. Imaging the gel through the transparent PDMS with a color camera provides a direct, easy, and contact-free determination of the fluid pressure at the sensing location for pressures as small as 20mbar with a resolution of around 10mbar. The sensitivity and accessible pressure range can be tuned via the mechanical properties of the sensing unit. The photonic gel can also be used to acquire 2D pressure or deformation maps, taking advantage of the fast response time and fine spatial resolution.

Assessing the health risks of heavy metals and seasonal minerals fluctuations in Camellia sinensis cultivars during their growth seasons.

The risk assessment of heavy metals in tea is extremely imperative for the health of tea consumers. However, the effects of varietal variations and seasonal fluctuations on heavy metals and minerals in tea plants remain unclear. Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to evaluate the contents of aluminum (Al), manganese (Mn), magnesium (Mg), boron (B), calcium (Ca), copper (Cu), cobalt (Co), iron (Fe), sodium (Na), zinc (Zn), arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), and antimony (Sb) in the two categories of young leaves (YL) and mature leaves (ML) of tea (Camellia sinensis) cultivars throughout the growing seasons. The results showed significant variations in the contents of the investigated nutrients both among the different cultivars and growing seasons as well. Furthermore, the average concentrations of Al, Mn, Mg, B, Ca, Cu, Co, Fe, Na, Zn, As, Cd, Cr, Ni, and Sb in YL ranged, from 671.58-2209.12, 1260.58-1902.21, 2290.56-2995.36, 91.18-164.68, 821.95-5708.20, 2.55-3.80, 3.96-25.22, 37.95-202.84, 81.79-205.05, 27.10-69.67, 0.028-0.053, 0.065-0.127, 2.40-3.73, 10.57-12.64, 0.11-0.14 mg kg-1, respectively. In ML, the concentrations were 2626.41-7834.60, 3980.82-6473.64, 3335.38-4537.48, 327.33-501.70, 9619.89-13153.68, 4.23-8.18, 17.23-34.20, 329.39-567.19, 145.36-248.69, 40.50-81.42, 0.089-0.169, 0.23-0.27, 5.24-7.89, 18.51-23.97, 0.15-0.19 mg kg-1, respectively. The contents of all analyzed nutrients were found to be higher in ML than in YL. Target hazard quotients (THQ) of As, Cd, Cr, Ni, and Sb, as well as the hazard index (HI), were all less than one, suggesting no risk to human health via tea consumption. This research might provide the groundwork for essential minerals recommendations, as well as a better understanding and management of heavy metal risks in tea.

Human mutations in SLITRK3 implicated in GABAergic synapse development in mice.

This study reports on biallelic homozygous and monoallelic de novo variants in SLITRK3 in three unrelated families presenting with epileptic encephalopathy associated with a broad neurological involvement characterized by microcephaly, intellectual disability, seizures, and global developmental delay. SLITRK3 encodes for a transmembrane protein that is involved in controlling neurite outgrowth and inhibitory synapse development and that has an important role in brain function and neurological diseases. Using primary cultures of hippocampal neurons carrying patients' SLITRK3 variants and in combination with electrophysiology, we demonstrate that recessive variants are loss-of-function alleles. Immunostaining experiments in HEK-293 cells showed that human variants C566R and E606X change SLITRK3 protein expression patterns on the cell surface, resulting in highly accumulating defective proteins in the Golgi apparatus. By analyzing the development and phenotype of SLITRK3 KO (SLITRK3-/-) mice, the study shows evidence of enhanced susceptibility to pentylenetetrazole-induced seizure with the appearance of spontaneous epileptiform EEG as well as developmental deficits such as higher motor activities and reduced parvalbumin interneurons. Taken together, the results exhibit impaired development of the peripheral and central nervous system and support a conserved role of this transmembrane protein in neurological function. The study delineates an emerging spectrum of human core synaptopathies caused by variants in genes that encode SLITRK proteins and essential regulatory components of the synaptic machinery. The hallmark of these disorders is impaired postsynaptic neurotransmission at nerve terminals; an impaired neurotransmission resulting in a wide array of (often overlapping) clinical features, including neurodevelopmental impairment, weakness, seizures, and abnormal movements. The genetic synaptopathy caused by SLITRK3 mutations highlights the key roles of this gene in human brain development and function.