Effectiveness of blended happy age education program (B-HAEP) on active aging promotion among pre-disable community dwelling older adults in Pakistan.

BACKGROUND: Addressing aging related functional declines in older adults has become a top priority for countries around the world. The aim of this study was to investigate the effectiveness of a blended happy age education program in promoting active aging among community-based pre-disable older adults. METHODS: We conducted a two-arm trial study in Khyber Pakhtunkhwa, Pakistan. Participants were randomly assigned into two groups using a computer-generated random sequence of 150 participants. RESULTS: Blended Happy Age Education Program (BHAEP) reduced time for 3 m walk (Estimated mean 19.5 ± 3.4 to 13.7 ± 1.3, effect size ηp² = 0.98, (P < 0.001). The current level of happiness improved in B-HAEP group from 4.7 ± 1.05 scores to 7.8 ± 1.6, P < 0.001, effect size (ηp² = 0.540). Healthy lifestyle significantly improved (P < 0.001, ηp² = 0.4). CONCLUSIONS: B-HAEP can be an effective intervention strategy to promote active aging in older adults with risk for immobility.

Clinical outcomes after total excision of transobturator tape inserted for treatment of stress urinary incontinence.

INTRODUCTION: Midurethral tapes (MUTs) were the most common surgical treatment for stress urinary incontinence (SUI) between 2008 and 2017. Transobturator tapes were introduced as a novel way to insert MUTs. Some women have experienced life-changing complications, and opt to undergo a total excision of transobturator tape (TETOT). There is a paucity in evidence about the outcomes of TETOT, which is a complex operation. This study aims to report clinical outcomes of all women who underwent TETOT in a specialist mesh center. METHODS: All women between 2017 and 2022 who underwent TETOT in one mesh center were reviewed. Background demographics and preoperative symptoms were recorded retrospectively. Outcome data were collected using patient global impression of improvement (PGI-I) scales via telephone review and analyzed using SPSS 25. RESULTS: Forty-five women underwent telephone review in May 2022, on average 27.9 months (range: 3-60) after TETOT. Mean age was 55 and body mass index (BMI): 30; 82% were postmenopausal, 20% were smokers, and 73.3% had recurrent SUI before excision. Indications for excision were infection (4%), vaginal exposure (24%), urethral perforation (9%), and chronic pain not associated with other complications (60%). Two women with recurrent SUI opted for a concomitant fascial sling; both reported a PGI of "very much improved" regarding SUI postoperatively. Only 12 women (26.5%) did not have SUI before excision; of these 9 (75%) reported new SUI postoperatively. Pain improved for 57.8%, but worsened for 24.4%. Although not statistically significant (p = 0.055), more women who underwent TETOT for pain alone reported worsening pain than those with pain with an additional complication (37% vs. 5.55%). Overall, 62.2% women felt "better" after their excision, 17.8% felt "worse." DISCUSSION: After TETOT, 62% of women felt better. Improvement in pain was reported by 58%-those with chronic pain without another complication reported improvement in pain less frequently (48% vs. 72%) and worsening pain more frequently (37% vs. 6%). Existing SUI worsened in 65% of women and 75% developed new SUI. There appears to be discordance between reporting global improvement with worsening of commonly measured clinical outcomes. CONCLUSION: Outcome data are important for counseling women about the risks and benefits of TETOT. Women and clinicians may have different attitudes to the possible benefits of TETOT, as evidenced by women reporting feeling better despite continuing pain or SUI. Conventional outcome measures do not adequately capture all outcomes that are important to patients.

Bioinformatics and genetic variants analysis of FGF10 gene promoter with their association at carcass quality and body measurement traits in Qinchuan beef cattle.

The fibroblast growth factor 10 (FGF10) gene regulates adipogenesis and myogensis. In this study, sequencing of FGF10 prompter region identified three SNPs at loci g.78G > A, g.116C > T and g.201A > T. Each SNP yields three genotypes as GG, GA and AA at loci g.78G > A, CC, CT and TT at loci g.116C > T and AA, AT and TT at loci g.201A > T. Allelic and genotypic frequencies of all three SNPs deviated from the Hardy-Weinberg equilibrium (HWE) (P < 0.05) and were found highly polymorphic as PIC (0.25 < PIC < 0.50). Moreover, we found highest LD (D'/γ2) between SNP2 and SNP3 (0.989/0.909), followed by SNP1 and SNP3 (0.944/0.796). Moreover, three variants of FGF10 gene promoter exhibited significant (P < 0.05) association with body measurement and carcass quality traits in Qinchuan beef cattle. At loci g.78G > A, the genotype GG showed significantly (P < 0.01) larger body length (BL), rump length (RL), chest depth (CD), chest circumference (CC) and ultrasound loin area (ULA). The genotype TC at loci g.116C > T showed significantly (P < 0.01 and 0.05) larger body measurement and intramuscular fat, and ultrasound loin area (ULA). In addition to that, at loci g.201A > T, genotype TT showed significantly (P < 0.01 and P < 0.05) larger body length (BL), rump length (RL), hip width (HW), chest circumference (CC) and ultrasound loin area (ULA). Additionally, screening of promoter sequence of FGF10 gene explored loss of four TFs binding sites (KLF3, ZNF37α, GLIS2 and BCL11A) at g.116C > T because of SNP2. However, a single TF binding site was lost at g.202A > T due to SNP3. Interestingly, none of TF binding site was lost at g.78G > A in SNP1; however, one new TF binding site was gained at this location due to SNP1. These findings conclude that genotype GG, TC and TT could be used as genetic markers of FGF10 gene for body measurement and carcass quality traits in Qinchuan beef cattle.

Photocatalytic assessed adsorptive removal of tinidazole from aqueous environment using reduced magnetic graphene oxide-bismuth oxychloride and its silver composite.

Antibiotics (tinidazole (TNZ)) in wastewater, exhibit adverse effects on humans and ecosystem. The current study was aimed to synthesize photocatalysts mrGO/BiOCl and mrGO/BiOCl/Ag. mrGO was coupled with BiOCl by hydrothermal method and Ag was deposited over it. The synthesized mrGO/BiOCl and mrGO/BiOCl/Ag were confirmed by Pzc analysis (5.5 and 4.4 for mrGO/BiOCl and mrGO/BiOCl/Ag, respectively), surface area analysis (380 m2 g-1, 227.7 m2 g-1, 220 m2 g-1 for mrGO, mrGO/BiOCl and mrGO/BiOCl/Ag respectively), elemental analysis (Ag, O, Bi, Fe), surface morphology (rough ball like sphere of mrGO/BiOCl and cubic Ag nanoparticles in mrGO/BiOCl/Ag), functional groups and band gap (Eg) determination. The Eg was determined using Kubelka-Munk equation as 3.5 and 2.8 eV for mrGO/BiOCl and mrGO/BiOCl/Ag respectively. During the adsorption study, the best experimental conditions for various operating parameters such as pH (2), contact time (5 min for mrGO/BiOCl and 10 min for mrGO/BiOCl/Ag under UV irradiation), TNZ concentration (18 µgL-1) and catalyst dosage (0.001 g) were achieved. Kinetic study revealed that both composites followed pseudo second order kinetics (R2 = 0.9979 and 0.9986, respectively). Data of rGO/BiOCl was fitted to Freundlich adsorption model (R2 = 0.9687) and rGO/BiOCl/Ag fitted to Langmuir adsorption model (R2 = 0.9994). Moreover, thermodynamic parameters confirmed that a photodegradation phenomenon was spontaneous and exothermic. The results confirmed that rGO/BiOCl and rGO/BiOCl/Ag are appropriate composites for TNZ removal from the aqueous environment with removal efficiency of 97 and 24%, respectively.

Core-shell magnetic molecularly imprinted polymer for selective recognition and detection of sunset yellow in aqueous environment and real samples.

Magnetic Molecularly imprinted polymers (MMIPs) have been recently recognized as an exceptional tool for monitoring and decontamination of environmental and biological samples of diverse nature. Based on the potential applications as sorbents and biomimetic sensors, herein, a core-shell magnetic-molecularly imprinted polymer (MMIP) was developed as a selective material for separation and sensing of sunset yellow (SY) dye in an aqueous environment and real samples. The MMIP was synthesized via precipitation polymerization using SY as a template, MAA as a functional monomer (chosen based on simulation studies), EGDMA as a cross-linking agent, and AIBN as an initiator. To elaborate the specificity of MMIP, a comparative agent, magnetic non-imprinted polymer (MNIP) was also synthesized. The XRD results showed that the MMIP showed both crystalline and amorphous structure attributed to the presence and polymeric and non-polymeric groups. The FTIR spectra confirmed synthesis of intermediate and final MMIP product. The SEM results showed spherical morphology and porous structure of the MMIP with an average particle size of 0.636 µm in diameter. The MMIP was first employed as a sorbent for the removal of SY from the aqueous environment. The binding experiments performed at optimized operating conditions (pH 2; time 30 min; sorbent dosage 3 mg; sorbate concentration 80 ppm) showed more selectivity when compared with MNIP. The data fitted best to Langmuir's sorption isotherm (Qo 359.8 mg/g) and followed the pseudo-second-order kinetic model. The synthesized MMIP was also used as an electrochemical sensor for detection of SY dye in the aqueous environment, which exhibited a linear range of detection as (1.51 × 10-6 - 1.5 × 10-3 M). The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.00413 M and 0.0137 M, respectively. While the R2 value was found to be 0.997 at optimized analytical conditions. These results suggested that the synthesized MMIP can be applied for the selective separation and quantification of SY dye in sample of diverse nature.

Designing, characterization, and evaluation of chitosan-zinc selenide nanoparticles for visible-light-induced degradation of tartrazine and sunset yellow dyes.

Employing dyes in different industrial sectors has produced a serious threat to the environment and living organisms of water bodies and land. For the decontamination of such toxic dyes, efforts have been made to develop an efficient, feasible, and low maintenance processes. In this context, chitosan-zinc selenide (CS-ZnSe) nanoparticles were prepared through chemical reduction method as the efficient photocatalysts for the decontamination of toxic dyes through photocatalysis. Photocatalyst's synthesis was confirmed with the help of FTIR spectroscopy. XRD indicated the hexagonal crystal structure of the CS-ZnSe with a crystallite size of 12 nm. SEM micrographs showed the average nano photocatalyst size as 25 nm. EDX analysis was employed to determine the elemental composition of the CS-ZnSe. An excellent photocatalytic degradation efficiency for tartrazine and sunset yellow dyes was obtained using CS-ZnSe. The results showed a 98% and 97% degradation efficiency for tartrazine dye and sunset yellow (SY) dye at optimized conditions of time (3 h), pH (5), dye concentration (30 ppm), catalyst dosage (0.09 g and 0.01 g) , and at a temperature of 35 °C. Findings of the photocatalytic degradation process fitted well with first-order kinetics for both the dyes. Rate constant, 'K' value was found to be 0.001362 min-1 and 0.001257 min-1 for tartrazine and SY dyes, respectively. While value for (correlation coefficient, R2) was 0.99307 and 0.99277 for tartrazine and sunset yellow dyes, respectively. Recyclability of the photocatalyst was confirmed using it for consecutive cycles to degrade organic dyes. Results showed that the CH-ZnS possesses excellent efficiency in decontaminating organic dyes from industrial wastewater.

Effect of supplementation of oilseeds co-products on production performance and fatty acids composition of Beetal goats.

This study evaluated the effect of different oilseed co-product supplementations on feed intake, nutrient digestibility, N retention, yields of milk and milk constituents, and milk fatty acid (FA) profile of Beetal goats. In the lactation trial, thirty-six lactating multiparous Beetal goats (45 ± 2.04 kg; 15 ± 2.3 days in milk) were assigned to four experimental rations according to randomized complete block design. The blocks were balanced for daily milk yield, parity, and body weight. The goats were either fed a maize silage and wheat straw-based basal ration ad libitum (control) or the control ration was supplemented with cotton seed cake, mustard seed cake, or maize oil cake on an iso-N basis. At the end of lactation trial, four goats (44 ± 0.8 kg BW; producing 1250 ± 110 g milk/day) were selected and moved to individual metabolism crates for a digestibility and N balance experiment, using a Latin square design (4 × 4). Supplementation of the co-products increased intakes of forage mixture (P = 0.002), total dry matter (DM; P < 0.001), neutral detergent fibre (NDF; P = 0.003), and crude protein (CP; P < 0.001). The additional N supplied by the co-products increased (P < 0.001) N retention, yields of milk, fat, protein, and lactose. Further comparison of the rations supplemented with the co-products revealed that the greatest (P < 0.05) increase in yields of milk (240 g/day), milk protein (11.6 g/day), fats (16.3 g/day), and lactose (11.2 g/day) was recorded for maize oil cake, as compared to the control. Except C8:0, supplementation of the co-products decreased (P < 0.01) the contents of all de novo-synthesized saturated FAs (SFAs) and increased (P < 0.001) the contents of health beneficial C18:1n-9, C18:1 tans-11, C18:2n-6, C18:3n-3, C20:2n-6, C20:5n3, and total unsaturated FAs in milk fat. Our findings demonstrated that the oilseed co-product inclusion in dairy goat rations significantly improves forage biomass utilization, yields of milk and milk constituents, and milk FAs' profile, with the largest impact being observed for maize oil cake.

Removal of Cd(II) from water using zero valent iron/copper functionalized spent tea.

Zero valent Fe/Cu functionalized spent tea adsorbent was prepared for the decontamination of Cd(II) contaminated water. The synthesized material was characterized for structural and morphological characteristics using various analytical techniques. The material was used as adsorbent for the adsorption of Cd(II) from aqueous solutions in batch study experiments. The effect of initial pH, adsorbent dosage, contact time and adsorbate concentration was investigated. The obtained data well followed the Langmuir adsorption isotherm model and pseudo-second order rate model with maximum adsorption capacity of 89.686 mg·g-1. Based on Langmuir separation factor (R), having a value of 0.706-0.194, the adsorption process was confirmed to be favorable. The adsorbent was used in the form of a column for the sorption of Cd(II) from a running solution with satisfactory results. The spent material was regenerated and reutilized with reduction of adsorption capacity by 1.48% only. Overall, the current adsorbent can be efficiently utilized for the removal of aqueous Cd(II).

Effect of feeding different levels of discarded date palm (Phoenix dactylifera) on digestibility, milk yield, and composition in Damani sheep.

Poor quality feed and lack of feed resource conservation in Pakistan are the major constraints influencing livestock production systems in the country. In the current study, we endeavored to ascertain the most favorable utilization of discarded date palm in sheep nutrition. Sixteen multiparous Damani sheep (average weight = 26 Kg) in the 2nd month of lactation were randomly distributed into four equal groups i.e., A, B, C, and D. They were fed with experimental rations supplemented with 0%, 10%, 20%, and 30% discarded date palm on dry matter (DM) basis, respectively, to investigate its impact on feed intake, digestibility coefficient, milk yield, and composition. The dry matter intake (DMI) significantly increased (P < 0.05) in groups C and D. Significant differences in dry matter digestibility (DMD) were noted among groups with mean values 50.2%, 56.4%, 65.2%, and 72.2%, respectively. Daily milk yield recorded for the groups was 842.00, 854.50, 921.00, and 960.00 (ml/day), respectively, showing a significant increase in groups C and D. However, investigating the mineral profile of milk, only calcium (Ca) and copper (Cu) were significantly (P < 0.05) increased in dates fed groups. In conclusion, significant utilization of discarded date palm can be achieved through incorporation of these wastes in small ruminant rations to get significant increases in DMI, DMD, and milk yield (MY), calcium (Ca) and copper (Cu) levels of milk.

Site-specific O-Glycosylation by Polypeptide N-Acetylgalactosaminyltransferase 2 (GalNAc-transferase T2) Co-regulates ß1-Adrenergic Receptor N-terminal Cleavage.

The ß1-adrenergic receptor (ß1AR) is a G protein-coupled receptor (GPCR) and the predominant adrenergic receptor subtype in the heart, where it mediates cardiac contractility and the force of contraction. Although it is the most important target for ß-adrenergic antagonists, such as ß-blockers, relatively little is yet known about its regulation. We have shown previously that ß1AR undergoes constitutive and regulated N-terminal cleavage participating in receptor down-regulation and, moreover, that the receptor is modified by O-glycosylation. Here we demonstrate that the polypeptide GalNAc-transferase 2 (GalNAc-T2) specifically O-glycosylates ß1AR at five residues in the extracellular N terminus, including the Ser-49 residue at the location of the common S49G single-nucleotide polymorphism. Using in vitro O-glycosylation and proteolytic cleavage assays, a cell line deficient in O-glycosylation, GalNAc-T-edited cell line model systems, and a GalNAc-T2 knock-out rat model, we show that GalNAc-T2 co-regulates the metalloproteinase-mediated limited proteolysis of ß1AR. Furthermore, we demonstrate that impaired O-glycosylation and enhanced proteolysis lead to attenuated receptor signaling, because the maximal response elicited by the ßAR agonist isoproterenol and its potency in a cAMP accumulation assay were decreased in HEK293 cells lacking GalNAc-T2. Our findings reveal, for the first time, a GPCR as a target for co-regulatory functions of site-specific O-glycosylation mediated by a unique GalNAc-T isoform. The results provide a new level of ß1AR regulation that may open up possibilities for new therapeutic strategies for cardiovascular diseases.

Mini review on photosensitization by plants in grazing herbivores.

Photosensitization is severe dermatitis or oxidative/chemical changes in the epidermal tissues activated by the light-induced excitation of molecules within the tissue. It is a series of reactions mediated through light receptors and is more common when the plant-produced metabolites are heterocyclic/polyphenols in nature. The areas affected are exposed body parts and mostly non-pigmented areas with least ultraviolet protection. Similarly, cellular alteration also occurs in the affected animal's dermal tissues and body parts and grazing animals by the accumulation and activation of photodynamic molecules. Photo-oxidation can also occur within the plant due to the generation of reactive oxygen species causing damage and degradation in the form of free radicals and DNA. During the last few decades, many new tropical grass species have been introduced in the grazing lands which are genetically modified, and the animals grazing on them are facing various forms of toxicity including photosensitization. The plant's secondary metabolites/drugs may cause toxicity when bacteria, viral agents, fungi (Pithomyces chartarum), or neoplasia injures the liver and prevents the phylloerythrin excretion. All these may disturb the liver enzymes and blood profile causing a decrease in weight and production (wool and milk etc.) with severe dermal, digestive, and nervous problems. Recent advancements in OMICS (cellomics, ethomics, metabolomics, metabonomics, and glycomics) have enabled us to detect and identify the plants' secondary metabolites and changes in the animal's physiology and histopathology as a causative of photosensitivity. The review focuses on types of photosensitization, reasons, secondary metabolic compounds, chemistry, and environmental effect on plants.

Short Communication - Study on quality and efficacy of commercial tylosin and doxycycline products against local isolates of mycoplasma in broilers.

The present study was conducted to investigate the quality and efficacy of commercially available preparations of tylosin and doxycycline available in the local market at Peshawar for poultry. In vitro and in vivo, tests were conducted to check the quality of these antimicrobial drugs. In vitro quality control test was performed by High performance liquid chromatographic (HPLC) and micro dilution method. In vivo, efficacy of the test drugs was checked in broilers infected with Mycoplasma gallisepticum. Results of HPLC indicated that test drug-2 contains doxycycline hydrochloride within specified limits but contain high quantity of active ingredient (Tylosin tartrate 120%). Recovery percentage of test drugs (3, 4, 5) were below the pharmacopoeial limit, which contained low quantity of tylosin tartrate (85%, 87.5%, 85%) respectively however, percent recovery of doxycycline were in the appropriate limits. All the tested drugs were effective against Mycoplasma gallisepticum and showed minimum inhibitory concentration (MIC) at 1.9µg/ml. The in vivo result indicated that all tested drugs decreased morbidity and mortality in infected chicks. The birds treated with test drugs (3 and 5) showed mortality of 9.5%, which was slightly higher than the other test groups. The current study suggested that there are incidences of substandard drugs in Pakistan and the drug regularity authorities should take strict actions against the manufacturing companies.

Effects of medetomidine on serum glucose in cattle calves.

An experimental study was carried out to compare physiological effects (serum glucose level) of medetomidine in Red Sindhi cattle calves at three different doses i.e. 8, 10 and 12µg/kg body weight intravenously. Medetomidine produced a dose dependent significant (P<0.01) increase in serum glucose level with a maximum increase observed at 30 minutes with 8µg/kg, 10µg/kg and 12µg/kg body weight respectively. Start of sedation, degree of sedation and total duration of sedation were all dose dependent and the values obtained were significantly (P<0.01) different from each other. It was observed that the sedation was rapid, deep and longer with the higher doses of medetomidine i.e. 12µg/kg. The results of the present study shows that medetomidine is a very effective and safest drug use as sedative for calves which in lower doses (8µg/kg) can be used as a pre-anesthetic and for restraining of the animal, while higher calculated doses (10µg/kg, 12µg/kg) can be used to execute the minor surgical procedures.

Characteristic patterns of maternal and fetal arterial construction in the rabbit placenta.

We studied vascular structure of the rabbit placenta, especially on three-dimensional morphological patterns and developmental process. Basic structure of maternal arterial system was re-constructed during day 13-18 of pregnancy, forming main routes for blood supply through the arterial sinuses and radial arteries. Intra-villous spaces were drastically developed showing as branches from the terminal radial arteries. Fetal arterial system was generated accompanied with maternal vascular development, showing characteristic features such as the perforating linear artery, hairpin flexion, and circular anastomoses in the capillaries. From the correlation of maternal and fetal blood currents, gas-exchange style in the rabbit placenta was considered as counter-current and pool mixed patterns. These data demonstrated an original feature for the placental arterial systems in rabbits, which differed from other animals having a property for discoid placenta.

ß-Adrenergic agonists mediate enhancement of ß1-adrenergic receptor N-terminal cleavage and stabilization in vivo and in vitro.

The ß(1)-adrenergic receptor (ß(1)AR) is the predominant ßAR in the heart and is the main target for ß-adrenergic antagonists, widely used in the treatment of cardiovascular diseases. Previously, we have shown that the human (h) ß(1)AR is cleaved in its N terminus by a metalloproteinase, both constitutively and in a receptor activation-dependent manner. In this study, we investigated the specific events involved in ß(1)AR regulation, focusing on the effects of long-term treatment with ß-adrenergic ligands on receptor processing in stably transfected human embryonic kidney 293(i) cells. The key findings were verified using the transiently transfected hß(1)AR and the endogenously expressed receptor in neonatal rat cardiomyocytes. By using flow cytometry and Western blotting, we demonstrated that isoproterenol, S-propranolol, CGP-12177 [4-[3-[(1,1-dimethylethyl)amino]2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one], pindolol, and timolol, which displayed agonistic properties toward the ß(1)AR in either the adenylyl cyclase or the mitogen-activated protein kinase signaling pathways, induced cleavage of the mature cell-surface receptor. In contrast, metoprolol, bisoprolol, and CGP-20712 [1-[2-((3-carbamoyl-4-hydroxy)phenoxy)ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol], which showed no agonistic activity, had only a marginal or no effect. Importantly, the agonists also stabilized intracellular receptor precursors, possibly via their pharmacological chaperone action, and they stabilized the receptor in vitro. The opposing effects on the two receptor forms thus led to an increase in the amount of cleaved receptor fragments at the plasma membrane. The results underscore the pluridimensionality of ß-adrenergic ligands and extend this property from receptor activation and signaling to the regulation of ß(1)AR levels. This phenomenon may contribute to the exceptional resistance of ß(1)ARs to downregulation and tendency toward upregulation following long-term ligand treatments.

Evaluation of Type 2 Diabetes Risk Variants (Alleles) in the Pashtun Ethnic Population of Pakistan.

Objective: To evaluate the Type 2 Diabetes (T2D) risk variants in the Pashtun ethnic population of Khyber Pakhtunkhwa using nascent whole-exome sequencing (WES) to better understand the pathogenesis of this complex polygenic disorder. Methodology: A total of 100 confirmed patients with T2D of Pashtun ethnicity were included in the study, DNA was extracted from whole blood samples, and paired-end libraries were prepared using the Illumina Nextera XT DNA library kit carefully following the manufacturer's instructions. Illumina HiSeq 2000 was used to obtain sequences of the prepared libraries followed by bioinformatics data analysis. Results: A total of n=11 pathogenic/likely pathogenic variants were reported in the CAP10, PAX4, IRS-2, NEUROD1, CDKL1 and WFS1. Among the reported variants CAP10/rs55878652 (c.1990-7T>C; p.Leu446Pro) and CAP10/rs2975766 (c.1996A>G; p.Ile666Val) identified were novel, and have not yet been reported for any disease in the database.The variants CAP10/rs7607759 (c.1510A>G, p.Thr504Ala), PAX4/rs712701 (c.962A>C; p.His321Pro), PAX4/rs772936097 (c.748-3delT; p.Arg325Trp), IRS-2/rs1805097 (c.3170G>A; p.Gly1057Asp), NEUROD1/rs1801262 (c.133A>G; p.Thr45Ala), CDKL1/rs77152992 (c.1226C>T; p.Pro409Leu), WFS1/rs1801212 (c.997G>A; p.Val333Ile), WFS1/rs1801208 (c.1367G>A; p.Arg456His), and WFS1/rs734312 (c.1832G>A; p.Arg611His) are previously identified in other ethnic populations. Our study reconfirms the associations of these variants with T2D in the Pakistani Pashtun population. Conclusion: In-silico analysis of exome sequencing data suggests a statistically substantial association of all (n=11) identified variants with T2D in the Pashtun ethnic population. This study may serve as a foundation for performing future molecular studies aimed at unraveling T2D associated genes.

Gender-based adjustment problems of divorcees in Hazara Division, Pakistan.

INTRODUCTION: Divorce is one of the harshest realities in Eastern societies worldwide because it is an intact component of the elementary social institution of the family. Grievously, divorce rates are escalating with profound ramifications for divorcees in Asia, including Pakistan. Therefore, exploring the challenges after divorce with gender-based dimensions in the Pakistani context was necessary, particularly in Hazara Division. RESEARCH METHODOLOGY: The study followed a pragmatic approach through snowball sampling and recruited 75 respondents. The data were collected through a semi-structured questionnaire and analysed using IBM SPSS 25. For descriptive statistics, frequencies of quantitative responses were determined using percentages, means, and standard deviations. Then Chi-Square Test of Independence, Principal Component Analysis, and Multivariate Analysis of Covariance were performed to find an association between the dependent and independent variables. RESULTS: Results demonstrated that most divorcees face children-related issues followed by economic, social, and psychological issues that impede post-divorce adjustment of divorcees. Results showed that the immaturity of divorcees and gender-specific violence specifically for women make it challenging for them to cope with the situation and impede their growth after divorce. Results revealed that more than half of women and a few of men have custody of children after divorce; however, fight over custody of children is another major cause of delayed adjustment. Results presented that gender significantly influences women's intensity of post-divorce adjustment constraints. CONCLUSION: Therefore, it is concluded that regardless of gender, ongoing conflicts with ex-spouses or in-laws made the post-divorce adjustment of divorcees difficult. Divorcees are in a constant tug-of-war between fighting internal dilemmas, pursuing individualistic ideals, and fulfilling societal norms, values, and expectations. This battle complicates and prolongs their adjustments after divorce. The study suggests that institutional, psychosocial, and family support is critical to proactively relieve divorcees from resources and their children.

Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study.

Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention.

Zinc Ortho Methyl Carbonodithioate Improved Pre and Post-Synapse Memory Impairment via SIRT1/p-JNK Pathway against Scopolamine in Adult Mice.

Alzheimer's disease (AD) is globally recognized as a prominent cause of dementia for which efficient treatment is still lacking. New candidate compounds that are biologically potent are regularly tested. We, therefore, hypothesized to study the neuroprotective potential of Zinc Ortho Methyl Carbonodithioate (thereafter called ZOMEC) against Scopolamine (SCOP) induced Alzheimer's disease (AD) model using adult albino mice. We post-administered ZOMEC (30 mg/Kg) into two group of mice for three weeks on daily basis that received either 0.9% saline or SCOP (1 mg/Kg) for initial two weeks. The other two groups of mice received 0.9% saline and SCOP (1 mg/Kg) respectively. After memory related behavioral analysis the brain homogenates were evaluated for the antioxidant potential of ZOMEC and multiple protein markers were examined through western blotting. Our results provide enough evidences that ZOMEC decrease oxidative stress by increasing catalase (CAT) and glutathione S transferase (GST) and decreasing the lipid peroxidation (LPO). The SIRT1 and pre and post synaptic marker proteins, synaptophysin (SYP) as well as post synaptic density protein (PSD-95) expression were also enhanced upon ZOMEC treatment. Furthermore, memory impairment was rescued and ZOMEC appreciably abrogated the Aß accumulation, BACE1 expression C and the p-JNK pathway. The inflammatory protein markers, NF-kß and IL-1ß in ZOMEC treated mice were also comparable with control group. The predicted interaction of ZOMEC with SIRT1 was further confirmed by molecular docking. These findings thus provide initial reports on efficacy of ZOMEC in SCOP induced AD model.