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BACKGROUND: Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition. METHODS: Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software. RESULTS: WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1. CONCLUSIONS: Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.

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Transcatheter aortic valve replacement (TAVR) continues to grow in the United States. There are limited data on recipients of solid organ transplant (SOT) and patients with liver cirrhosis who undergo aortic valve replacement (AVR). Our study aims to evaluate outcomes in these populations. Using the national readmission database (2016 to 2020), we identified recipients of SOT and patients with liver cirrhosis without previous liver transplants who were admitted for severe aortic stenosis and underwent either TAVR or surgical AVR (SAVR). We used multivariable regression for adjusted analysis and the propensity score matching model, implementing complete Mahalanobis distance matching within the Propensity Score Caliper (0.2) to match TAVR and SAVR cohorts for outcomes. Of 3,394 hospitalizations for AVR in recipients of SOT, 2,181 underwent TAVR, and 1,213 underwent SAVR. On propensity-matched analysis, SAVR was associated with more adverse events than was TAVR, including in-hospital mortality (5.2% vs 1.1%, adjusted odds ratio [aOR] 4.49, p <0.001), acute kidney injury (43.7% vs 10.2%, p <0.001), cardiogenic shock (9.0% vs 1.6%, p <0.001), sudden cardiac arrest (15.9 vs 6.0%, p <0.001), major adverse cardiac and cerebrovascular events (28% vs 10.4%, p <0.001), and net adverse events (72.8 vs 37.6%, p <0.001). A greater median length of stay (10 vs 2 days, p <0.001) and adjusted cost ($80,842 vs $57,014, p <0.001) were also observed. The readmission rates were the same for both cohorts after a 6-month follow-up. Similarly, in 14,763 hospitalizations for AVR in liver cirrhosis, 7,109 patients underwent TAVR, and 7,654 underwent SAVR. In propensity-matched cohorts (n = 2,341), SAVR was found to be associated with greater adverse events, including in-hospital mortality (19.8% vs 10%), stroke (6.7% vs 2%), acute kidney injury (67.7% vs 30.3%), cardiogenic shock (41.9% vs 19.9%), sudden cardiac arrest (31.8% vs 13.2%, aOR 2.89), major adverse cardiac and cerebrovascular events (66.2% vs 35.7%), and net adverse events (86% vs 59.5%) (p <0.001). A greater median length of stay (16 vs 3 days) and cost ($500,218 vs $263,383) were also observed (p <0.001). However, the rate of readmissions at 30-day (9% vs 11.1%) and 180-day intervals (33.4% vs 39.8%) was lower for the SAVR cohort (p <0.05). In recipients of SOT and patients with liver cirrhosis, SAVR is associated with greater short-term mortality, adverse events, and healthcare burden than is TAVR. TAVR is a relatively safer alternative to SAVR in these patient populations, although further studies are warranted to compare the long-term outcomes.

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There are many different applications of heterocyclic molecules in the pharmaceutical and materials science fields, which make them an important family of compounds. Among these heterocyclic compounds, nitrogen-containing heterocyclic (N-heterocyclic) compounds have attracted a lot of interest among researchers due to their various applications across a wide variety of fields. Many studies have been performed over the past few years to study the synthesis of N-heterocycles under different reaction conditions, such as solvent-free, catalytic, reactants immobilized on a solid support, one-pot synthesis, and microwave irradiation. It has been demonstrated by our research group that microwaves can be utilized for rapid and efficient synthesis of biologically active compounds. In this review, we provide an overview of the microwave-assisted non-catalytic and catalytic preparation of nitrogen-containing heterocycles, mostly polycyclic N-heterocycles, five-membered N-heterocycles, six-membered N-heterocycles, and fused N-heterocycles. Mostly in this article, we explore the microwave-assisted preparation of biologically important compounds, such as pyrimidines, thiazoles, imines, tetrazoles, steroidal derivatives, quinolines, indolizine, triazoles, beta-lactams, pyrroles and quinoxalines.

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Potato farming is a vital component of food security and the economic stability especially in the under developing countries but it faces many challenges in production, blackleg disease caused by Pectobacterium atrosepticum (Pa) is one of the main reason for damaging crop yield of the potato. Effective management strategies are essential to control these losses and to get sustainable potato crop yield. This study was focused on characterizing the Pa and the investigating new chemical options for its management. The research was involved a systematic survey across the three district of Punjab, Pakistan (Khanewal, Okara, and Multan) to collect samples exhibiting the black leg symptoms. These samples were analyzed in the laboratory where gram-negative bacteria were isolated and identified through biochemical and pathogenicity tests for Pa. DNA sequencing further confirmed these isolates of Pa strains. Six different chemicals were tested to control blackleg problem in both vitro and vivo at different concentrations. In vitro experiment, Cordate demonstrated the highest efficacy with a maximum inhibition zones of 17.139 mm, followed by Air One (13.778 mm), Profiler (10.167 mm), Blue Copper (7.7778 mm), Spot Fix (7.6689 mm), and Strider (7.0667 mm). In vivo, Cordate maintained its effectiveness with the lowest disease incidence of 14.76%, followed by Blue Copper (17.49%), Air One (16.98%), Spot Fix (20.67%), Profiler (21.45%), Strider (24.99%), and the control group (43.00%). The results highlight Cordate's potential as a most effective chemical against Pa, offering promising role for managing blackleg disease in potato and to improve overall productivity.

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Dragon fruit (Selenicereus undatus), known for its captivating appearance and remarkable nutritional profile, has garnered considerable attention in recent years. Despite its popularity, there's a dearth of research on optimal conditions for seed germination and early growth stages such as seedling shoot length, which are crucial for optimal crop yield. This study aims to bridge this gap by evaluating various growing media's performance on dragon fruit germination and early growth stages. Dragon fruit seeds were obtained from local markets in Pakistan and evaluated in five different growing media: cocopeat, peat moss, sand, vermiculite, and compost. Germination parameters were observed for 45 days, including seed germination percentage, mean germination time, and mean daily germination percentage, among others while early growth was monitored for 240 days. Statistical analysis was conducted using ANOVA and Tukey's HSD test. Significant differences were found among the growing media regarding germination percentage, mean germination time, and mean daily germination. Vermiculite exhibited the highest germination rate (93.33%), while compost showed the least (70%). Peat moss and sand media facilitated rapid germination, while compost showed slower rates. Stem length was significantly influenced by the growth media, with compost supporting the longest stems. Vermiculite emerged as the most effective medium for dragon fruit seed germination, while compost showed slower but steady growth. These findings provide valuable insights for optimizing dragon fruit cultivation, aiding commercial growers and enthusiasts in achieving higher yields and quality. Further research could explore additional factors influencing dragon fruit growth and development.

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Shigella dysenteriae has been recognized as the second most prevalent pathogen associated with diarrhea that contains blood, contributing to 12.9% of reported cases, and it is additionally responsible for approximately 200,000 deaths each year. Currently, there is no S. dysenteriae licensed vaccine. Multidrug resistance in all Shigella spp. is a growing concern. Current vaccines, such as O-polysaccharide (OPS) conjugates, are in clinical trials but are ineffective in children but protective in adults. Thus, innovative treatments and vaccines are needed to combat antibiotic resistance. In this study, we used immuno-informatics to design a new multiepitope vaccine and identified S. dysenteriae strain SD197's membrane protein targets using in-silico methods. The target protein was prioritized using membrane protein topology analysis to find membrane proteins. B and T-cell epitopes were predicted for vaccine formulation. The epitopes were shortlisted based on an IC50 value <50, antigenicity, allergenicity, and a toxicity analysis. In the final vaccine construct, a total of 8 B-cell epitopes, 12 MHC Class I epitopes, and 7 MHC Class II epitopes were identified for the Lipopolysaccharide export system permease protein LptF. Additionally, 17 MHC Class I epitopes and 14 MHC Class II epitopes were predicted for the Lipoprotein-releasing ABC transporter permease subunit LolE. These epitopes were selected and linked via KK, AAY, and GGGS linkers, respectively. To enhance the immunogenic response, RGD (arginine-glycine-aspartate) adjuvant was incorporated into the final vaccine construct. The refined vaccine structure exhibits a Ramachandran score of 91.5% and demonstrates stable interaction with TLR4. Normal Mode Analysis (NMA) reveals low eigenvalues (3.925996e-07), indicating steady and flexible molecular mobility of docked complexes. Codon optimization was carried out in an effective microbial expression system of the Escherichia coli K12 strain using the recombinant plasmid pET-28a (+). Finally, the entire in-silico analysis suggests that the suggested vaccine may induce a significant immune response against S. dysenteriae, making it a promising option for additional experimental trials.

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Saffron, the "golden spice" derived from Crocus sativus L., is renowned for its richness in secondary metabolites such as crocin and safranal, contributing to its unique properties. Facing challenges like decreasing global production, optimizing cultivation techniques becomes imperative for enhanced yields. Although the impact of factors like planting density, planting depth, spacing, and corm size on saffron growth has been studied, the interaction between corm size and planting depth remains underexplored. This study systematically investigates the interactive effects of corm size and planting depth on saffron growth and yield, providing evidence-based guidelines for optimizing cultivation. A factorial experiment, employing a completely randomized design, was conducted to assess the influence of corm size (05-10g, 10.1-15g, 15.1-20g) and planting depth (10cm, 15cm, 20cm) on saffron yield. Uniform-sized corms were obtained, and a suitable soil mixture was prepared for cultivation. Morphological and agronomic parameters were measured, and statistical analyses were performed using ANOVA and Tukey's HSD test. The study revealed that planting depth significantly affected saffron emergence. The corms sown under 15cm depth showed 100% emergence regardless of corm size (either 05-10g, 10.1-15g, 15.1-20g) followed by 10cm depth corms. Corm dry weight exhibited a complex interaction, where larger corms benefited from deeper planting, while intermediate-sized corms thrived at shallower depths. Similar patterns were observed in shoot fresh weight and dry weight. Specifically, the largest corm size (t3, 15.1-20g) produced the greatest fresh-weight biomass at the deepest planting depth of 20cm (T3), while intermediate-sized corms (t2, 10.1-15g) were superior at the shallowest 10cm depth (T1). The total plant biomass demonstrated that larger corms excelled in deeper planting, while intermediate-sized corms were optimal at moderate depths. This research highlights the intricate interplay between corm size and planting depth in influencing saffron growth. Larger corms generally promote higher biomass, but the interaction with planting depth is crucial. Understanding these dynamics can aid farmers in tailoring cultivation practices for optimal saffron yields. The study emphasizes the need for a coordinated approach to corm selection and depth placement, providing valuable insights for sustainable saffron production and economic growth.

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A 67-year-old female came to Tampa General Hospital with Philadelphia chromosome-positive (Ph+) acute myeloid leukemia (AML) featuring an intriguing combination of mutations, including NPM1 and IDH2 mutations. Novel combination therapy with azacitidine, venetoclax and ponatinib allowed her to successfully achieve a complete response (CR) and undergo an allogeneic hematopoietic stem cell transplant (HSCT). This case report provides an overview of her clinical course, emphasizing the significance of integrated therapy and the challenges associated with balancing treatment for AML. It also underscores the importance of a multidisciplinary approach and careful monitoring of patients with complex hematologic conditions.

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Land transportation is a major source of heavy metal contamination along the roadside, posing significant risks to human health through inhalation, oral ingestion, and dermal contact. Therefore, this study has been designed to determine the concentrations of vehicular released heavy metals (Cd, Pb, Ni, and Cu) in roadside soil and leaves of two commonly growing native plant species (Calotropis procera and Nerium oleander).Two busy roads i.e., Lahore-Okara road (N-5) and Okara-Faisalabad roads (OFR) in Punjab, Pakistan, were selected for the study. The data were collected from five sites along each road during four seasons. Control samples were collected ~ 50 m away from road. The metal content i.e. lead (Pb), cadmium (Cd) nickel (Ni) and copper (Cu) were determined in the plant leaves and soil by using Atomic Absorption Spectrophotometer (AAS). Significantly high amount of all studied heavy metals were observed in soil and plant leaves along both roads in contrast to control ones. The mean concentration of metals in soil ranged as Cd (2.20-6.83 mg/kg), Pb (4.53-15.29 mg/kg), Ni (29.78-101.26 mg/kg), and Cu (61.68-138.46 mg/kg) and in plant leaves Cd (0.093-0.53 mg/kg), Pb (4.31-16.34 mg/kg), Ni (4.13-16.34 mg/kg) and Cu (2.98-32.74 mg/kg). Among roads, higher metal contamination was noted along N-5 road. Significant temporal variations were also noted in metal contamination along both roads. The order of metal contamination in soil and plant leaves in different seasons was summer > autumn > spring > winter. Furthermore, the metal accumulation potential of Calotropis procera was higher than that of Nerium oleander. Therefore, for sustainable management of metal contamination, the plantation of Calotropis procera is recommended along roadsides.

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Green-synthesized metal oxide nanoparticles have garnered considerable attention due to their simple, sustainable, and eco-friendly attributes, coupled with their diverse applications in biomedicine and environmental context. The current study shows a sustainable approach for synthesizing molybdenum oxide nanoparticles (MoONPs) utilizing an extract from Anabaena sp. A-1. This novel approach marks a significant milestone as various spectral approaches were employed for characterization of the green-synthesized MoONPs. Ultraviolet-visible (UV-Vis) spectroscopic analysis revealed a surface plasmon resonance (SPR) peak of MoONPs at 538 nm. Fourier transform infrared (FTIR) spectral analysis facilitated the identification of functional groups responsible for both the stability and production of MoONPs. Scanning electron microscopy (SEM) was utilized revealing a rod shape morphology of the MoONPs. X-ray diffraction (XRD) analysis yielded a calculated crystal size of 31 nm, indicating the crystalline nature of MoONPs. Subsequently, biological assays were employed to ascertain the potential of the bioengineered MoONPs. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay was used to quantify free radical scavenging activity, revealing an antioxidant capacity of 68.1% at 200 µg/mL. To evaluate antibacterial and antifungal efficacy, the disc diffusion method was employed across varying concentrations of MoONPs (6.25, 12.5, 25, 50, 100, 150, 200 µg/mL). Quantification of cytotoxicity was performed via a brine shrimp assay, yielding an IC50 value of 552.3 µg/mL, a metric of moderate cytotoxicity. To assess the biocompatibility of MoONPs, an antihemolytic assay was conducted, confirming their safety profile. Additionally, MoONPs exhibited non-toxic attributes in an insecticidal assay. Notably, in anti-inflammatory assay MoONPs showed an inactive nature towards the reactive oxygen species. In conclusion, these findings highlight the potential versatility of MoONPs in various biological applications, extending beyond their recognized anti-inflammatory and insecticidal properties. RESEARCH HIGHLIGHTS: This study marks an advancement in nanotechnology, exploring ways for MoONPs fabrication, representing a unique and unexplored research domain. Green-synthesized MoONPs using Anabaena sp. A-1 extract offers a sustainable and eco-friendly approach. Characterized by UV-Vis, FTIR, SEM, and XRD, MoONPs demonstrate rod-shaped morphology and crystalline nature. Bioengineered MoONPs exhibit versatility in biological applications, demonstrating notable antioxidant, antibacterial and antifungal efficacy, moderate cytotoxicity, biocompatibility, and insecticidal properties, emphasizing their multifaceted utility. The research findings highlight the potential utilization of MoONPs across a spectrum of biological applications, thereby suggesting their promising role in the realm of biomedicine and environmental context.

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The aim of the current study was to map the genetic diversity in the haemagglutinin (HA) glycoprotein of influenza A viruses (IAVs) of the H9N2 subtype. Twenty-five H9N2 IAVs were isolated from broiler chickens from March to July 2019. The HA gene was amplified, and phylogenetic analysis was performed to determine the evolutionary relationship. Important antigenic amino acid residues of HA attributed to immune escape and zoonotic potential were compared among H9N2 IAVs. Phylogenetic analysis revealed that sublineage B2 under the G1 lineage in Pakistan was found to be diversified, and newly sequenced H9N2 isolates were nested into two clades (A and B). Mutations linked to the antigenic variation and potential immune escape were observed as G72E (1/25, 4%), A180T (3/25, 12%), and A180V (1/25, 4%). A twofold significant reduction (P < 0.01) in log2 hemagglutination inhibition titers was observed with H9N2 IAV naturally harboring amino acid V180 instead of A180 in HA protein. Moreover, in the last 20 years, complete substitution at residues (T127D, D135N, and L150N) and partial substitution at residues (72, 74, 131, 148, 180, 183, 188, 216, 217, and 249, mature H9 HA numbering) associated with changes in antigenicity were observed. The presence of L216 in all H9N2 IAV isolates and T/V180 in four isolates in the receptor-binding site reveals the potential of these viruses to cross the species barrier to infect human or mammals. The current study observed the circulation of antigenically diverse H9N2 IAV variants that possess potential mutations that can escape the host immune system.

Nota de investigación- Mapeo de marcadores genéticos asociados con la antigenicidad y el rango de huéspedes en los virus de la influenza tipo A subtipo H9N2 que infectan a la avicultura en Pakistán. El objetivo del presente estudio fue mapear la diversidad genética en la glicoproteína hemaglutinina (HA) de los virus de la influenza A (IAV) del subtipo H9N2. Se aislaron veinticinco virus de influenza H9N2 de pollos de engorde de marzo a julio del 2019. Se amplificó el gene HA y se realizó un análisis filogenético para determinar la relación evolutiva. Se compararon importantes residuos de aminoácidos antigénicos de la hemaglutinina atribuidos al escape inmunológico y al potencial zoonótico entre los virus de la influenza aviar H9N2. El análisis filogenético reveló que el sublinaje B2 bajo el linaje G1 en Pakistán estaba diversificado, y los aislados de H9N2 recién secuenciados se agruparon en dos clados (A y B). Se observaron mutaciones relacionadas con la variación antigénica y el posible escape inmunológico como los residuos de aminoácidos G72E (1/25, 4%), A180T (3/25, 12%) y A180V (1/25, 4%). Se observó una reducción significativa al doble (P < 0.01) en los títulos de inhibición de la hemaglutinación log2 cuando el virus de la influenza aviar H9N2 albergaba naturalmente el aminoácido V180 en lugar del A180 en la proteína HA. Además, en los últimos 20 años, sustitución completa en los residuos (T127D, D135N y L150N) y sustitución parcial en los residuos (72, 74, 131, 148, 180, 183, 188, 216, 217 y 249, de acuerdo con la numeración de la HA subtipo madura) asociados con cambios en la antigenicidad. La presencia del residuo L216 en todos los aislados de influenza aviar H9N2 y T/V180 en cuatro aislados en el sitio de unión al receptor revela el potencial de estos virus para cruzar la barrera de las especies para infectar a humanos o mamíferos. El estudio actual observó la circulación de variantes antigénicamente diversas del virus de influenza aviar H9N2 que poseen mutaciones potenciales que pueden escapar del sistema inmunológico del huésped.

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Ants belonging to the Monomorium indicum (Formicidae: Hymenoptera) species are ubiquitous insects that are commonly associated with household settings in Pakistan. Packaged foodstuffs are easily destroyed by household ants when packaging is made with materials that have a high susceptibility. This study evaluated the susceptibility of three common flexible plastic packaging materials namely: opaque polyethylene, transparent polyethylene and polypropylene, which were each tested at thicknesses of 0.02 mm for their susceptibility against M. indicum. Except opaque polyethylene which is only available at 0.02 mm thickness, both transparent polyethylene and polypropylene were tested at higher thickness of 0.04 mm and 0.06 mm also against M. indicum. In order to simulate household settings, experiments were conducted at the faculty building of the agriculture and environment department of The Islamia University of Bahawalpur, Pakistan during summer vacations when the building was quiet. Different corners were selected near water sources for maximum exposure to the largest number of ants. Experimental cages used for the experiment were built with wood and 2 mm iron gauze to allow only ants to enter the cages. Daily activity of ants was used as an infestation source in cages. Experiments were run over three time spans of fifteen days each from June 20th 2022 to August 15th 2022. Results showed all packaging materials were susceptible against M. indicum at the 0.02 mm thickness level. Polypropylene was susceptible at 0.04 mm thickness but resistant to ants at 0.06 mm thickness, whereas polyethylene was still susceptible to ants at the higher thickness of 0.06 mm. Correlation of packaging damage with weather factors showed that temperature had a positive relationship, while relative humidity had a negative association with M. indicum attack. Overall correlation of packaging damage with packaging thickness showed packaging thickness was negatively associated with packaging damage from the ants. Because major cutting role is performed by the mandibles, we studied mandibles of ants and three frequent pests of packaged foodstuff namely Rhyzopertha dominica, Tribolium castaneum and Trogoderma granarium. The results showed that ants had the largest mandible and frontal mandibular tooth lengths compared with the mandibles and frontal teeth of the common stored product pests, indicating M. indicum household ants have a higher pest status for packaged foodstuffs compared to common stored product pests. Although the thickness of the flexible plastic packaging was a major factor against household ants, the study results recommend the use of polypropylene with a thickness of at least 0.06 mm as foodstuff packaging against household ants compared with polyethylene packaging, which was found to be susceptible to ants even at 0.06 mm thickness.

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Hypertrophic pachymeningitis (HP) is a rare condition characterized by inflammation and thickening of the dura mater. It can be idiopathic or secondary to various causes, including infections, tumors, or systemic inflammatory diseases. Diagnosis is challenging due to its rarity and the overlap of symptoms with other conditions. We present the case of a 42-year-old Hispanic woman with diabetes mellitus type 2 and end-stage kidney disease who presented with chest pain, dry cough, mild dyspnea, and chronic occipital headaches. Physical examination revealed cranial VI nerve palsy. Imaging showed pulmonary cavitary lesions and mediastinal lymphadenopathy. Elevated inflammatory markers and positive autoimmune tests, including rheumatoid factor and antineutrophil cytoplasmic antibody (ANCA), led to further investigation. Brain imaging revealed dural thickening, confirming HP. The patient's medical history revealed double ANCA positivity and a lung biopsy confirmed granulomatous pneumonitis. A diagnosis of ANCA-associated vasculitis (granulomatosis with polyangiitis (GPA)) was established, and treatment with rituximab and high-dose corticosteroids led to symptom improvement. GPA rarely involves meningeal inflammation, but severe and persistent headaches are common early symptoms. Inflammatory markers are often elevated, and around two-thirds of HP cases related to GPA have positive serum ANCA. MRI is the primary diagnostic tool, with characteristic findings of dural thickening and contrast enhancement. This case highlights HP as a rare cause of chronic headaches and the importance of a comprehensive medical history in diagnosis. Early recognition and treatment are crucial for improving outcomes in GPA-related HP.

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BACKGROUND: Translation and validation of important scales in other languages reduce bias in reporting the functional status of the patient. OBJECTIVE: To translate the Back Pain Functional Scale into Urdu (BPFSu), adapt it for use in other cultures, and evaluate its psychometric properties. METHOD: According to Beaton guidelines, translation and cultural adaption was carried out. On 100 Urdu-literate men and women aged 18-60 years with lower back pain, the final BPFSu was assessed for psychometric qualities. First at baseline and again after 7 days, participants completed the BPFSu, the Functional Rating Index (FRI), and the Numeric Pain Rating Scale (NPRS). RESULTS: Internal consistency of the BPFSu was excellent (Cronbach's alpha: 0.937). No floor and ceiling effects were found Excellent test-retest reliability (ICC = 0.882, CI 95%; 0.830-0.919) was achieved. Spearman correlation coefficient showed criterion validity with the NPRS (rho =â⁢⁢0.701, p⩽ 0.001) and Pearson correlation coefficient showed construct validity with the FRI (r=â⁢⁢0.740, p⩽ 0.001). The minimum detectable changes were 9.96, while the standard error of measurement was 3.6. CONCLUSION: The BPFSu is a valid and reliable instrument for assessing physical function in individuals experiencing low back discomfort.

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Lumpy skin disease (LSD) is a contagious infection of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. In Pakistan, recent outbreaks have resulted in significant nationwide mortality and economic losses. A 20-day prospective cohort study was performed on sixty infected cattle with the aim to evaluate LSD-induced oxidative stress's genotoxic role and to determine the ameliorative effect of antioxidant therapy using principal component analysis (PCA) and a multivariable ordinal logistic regression model. LSDV was identified from scab samples and nodular lesions using RPO30-specific gene primers. The infected cattle were divided into control and treated groups. The animals were observed initially and finally on day 20 to evaluate the homeostatic, oxidative, and genotoxic changes. The animals in the treated group were administered a combination of selenium (Se) and vitamin E at the standard dose rate for five consecutive days. A substantial (p < 0.05) improvement in the hematological indices was observed in the treated group. The treated group also showed a significant (p < 0.05) reduction in levels of serum nitric oxide (NO) and malondialdehyde (MDA) post-therapy. The PCA at the final sampling data of the treated group showed that Principal Component (PC1 eigenvalue 1.429) was influenced by superoxide dismutase (SOD; 0.3632), catalase (CAT; 0.2906), and glutathione (GSH; 0.0816) and PC2 (eigenvalue 1.200) was influenced by CAT (0.4362), MDA (0.2056), and NO (0.0693). A significant correlation between serum NO (76%) and MDA levels (80%) was observed with genetic damage index (GDI) scores. The ordinal logistic regression model regarding the use of antioxidant therapy revealed 73.95-times (95%CI; 17.36-314.96) improvement in the GDI in treated animals. The multivariable ordinal logistic regression showed that each unit increase in NO and MDA resulted in a 13% increase in genotoxicity in infected individuals. In conclusion, our study revealed that LSD-induced oxidative stress and lipid peroxidation product causes genotoxicity in affected animals. Furthermore, the combined Se and vitamin E therapy significantly alleviated oxidative stress and genotoxicity in LSD-affected cattle.

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We present a unique case of a 42-year-old gentleman with alcohol use disorder who developed osmotic demyelination syndrome (ODS) despite appropriate hyponatremia correction. This patient initially presented with severe hyponatremia (Na 97 mEq/L) due to beer potomania, which was corrected gradually over eight days, resulting in no observed neurological deficits upon discharge. However, he was readmitted with respiratory failure from aspiration pneumonia, leading to endotracheal intubation. Laboratory findings revealed a sodium level of 134 mEq/L and serum osmolality (293 mOsm/kg). The patient had neurological exam findings of spontaneous eye opening with left gaze preference and decreased power ⅕ in all extremities. Following extubation, he experienced a relapse with evolving subacute central pontine myelinolysis and bulbar weakness necessitating reintubation. Subsequently, five sessions of plasmapheresis were conducted, resulting in stable clinical findings. Despite remaining non-verbal, the patient demonstrated gradual neurological motor improvement, progressing from 1/5 power in all extremities to 4/5 on the right side and 3/5 on the left side. He was discharged with ventilator support, tracheostomy, and PEG tube placement to a long-term care facility. This case underscores the importance of vigilant monitoring in high-risk individuals following hyponatremia treatment because ODS presentation can be delayed.

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Anthrax, a severe zoonotic disease, is infrequently reported in anthrax-endemic regions of Pakistan. Despite clinical reports indicating its presence, particularly cutaneous anthrax, there is insufficient laboratory evidence regarding disease occurrence and environmental persistence. The present study aimed to confirm Bacillus anthracis presence, accountable for animal mortality and human infection, while exploring environmental transmission factors. Between March 2019 and July 2021, a total of 19 outbreaks were documented. Of these, 11 affected sheep/goats in Zhob district and 8 affected cattle/sheep in Bajour Agency. Clinical signs suggestive of Bacillus anthracis outbreak were observed in 11 animals. Blood and swab samples were collected for confirmation. The study followed a One Health approach, analyzing animal, environmental (soil/plant), and human samples. Of the 19 outbreaks, 11 were confirmed positive for anthrax based on growth characteristics, colony morphology, and PCR. Soil and plant root samples from the outbreak areas were collected and analyzed microscopically and molecularly. Cutaneous anthrax was observed in six humans, and swab samples were taken from the lesions. Human serum samples (n = 156) were tested for IgG antibodies against PA toxin and quantitative analysis of anthrax toxin receptor 1 (ANTXR1). Bacillus anthracis was detected in 65 out of 570 (11.40%) soil samples and 19 out of 190 (10%) plant root samples from the outbreak areas. Four out of six human samples from cutaneous anthrax lesions tested positive for Bacillus anthracis. Human anthrax seroprevalence was found to be 11% and 9% in two districts, with the highest rates among butchers and meat consumers. The highest ANTXR1 levels were observed in butchers, followed by meat consumers, farm employees, meat vendors, veterinarians, and farm owners. These findings highlight the persistence of anthrax in the region and emphasize the potential public health risks.

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Glioblastoma multiforme (GBM) is one of the most aggressive cancers with a low overall survival rate. The treatment of GBM is challenging due to the presence of the blood-brain barrier (BBB), which hinders drug delivery. Invasive procedures alone are not effective at completely removing such tumors. Hence, identifying the crucial pathways and biomarkers for the treatment of GBM is of prime importance. We conducted this study to identify the pathways associated with GBM. We used The Cancer Genome Atlas (TCGA) GBM genomic dataset to identify differentially expressed genes (DEGs). We investigated the prognostic values of the guanine nucleotide-binding protein G(i) alpha subunit (GNAI) family of genes in GBM using a Chinese Glioma Genome Atlas (CGGA) dataset. Within this dataset, we observed the association in the tumor microenvironment between the gene expression of GNAI subunit 3 (GNAI3) and a poor prognosis. MetaCore and gene ontology (GO) analyses were conducted to explore the role of GNAI3 in co-expressed genes and associated signaling pathways using a transcript analysis. Notable pathways included "Cytoskeleton remodeling regulation of actin cytoskeleton organization by the kinase effectors of Rho GTPases" and "Immune response B cell antigen receptor (BCR) pathway". A single-cell analysis was used to assess GNAI3 expression in GBM. The results demonstrated that GNAI family genes, specifically GNAI3, were significantly associated with carcinogenesis and malignancy in GBM patients. Our findings suggest that the GNAI3 gene holds potential as a prognostic biomarker for GBM.