A DFT approach to correlate the physical characteristics of novel chalcopyrites ASbN2(A = Li, Na) for green technology.

Semiconductor chalcopyrite compounds have been a subject of research interest due to their diverse range of physical properties that have captured the attention of scientists. In this ongoing research, we have examined the physical characteristics of LiSbN2 and NaSbN2 chalcopyrites using DFT. The modified Becke-Johnson (mBJ) potential is utilized for the computation of electronic structures. The stability is attained with negative formation energies and optimization curves. A bandgap of 2.60 eV in LiSbN2 and 3.15 eV in NaSbN2 has been achieved, which is further endorsed by the density of states. An in-depth analysis of the optical properties unveils the potential utility of LiSbN2 and NaSbN2 in various photovoltaic devices, attributed to its pronounced absorption in the UV spectrum. The transport characteristics are also assessed through various transport characteristics. The large electrical conductivity and ZT values for both chalcopyrite compounds are attained. Due to their remarkable capability to convert heat into electricity, these materials display potential for use in thermoelectric devices.

Long COVID in Pakistan: a cross-sectional analysis of health and psychosocial outcomes.

According to the World Health Organization-led Delphi consensus, long COVID corresponds to the occurrence of symptoms beyond twelve weeks after the onset of acute COVID-19 illness that cannot be explained by alternate diagnosis. This cross-sectional study aimed to analyse the impacts of long COVID on general health and psychosocial well-being. For this study, the participants were interviewed either face to face or via telephone, and their responses were recorded on a questionnaire capturing information on demographics, COVID-19 status, duration of symptoms and long COVID symptoms. The psychosocial impacts of the pandemic were assessed using scales like Short Mood and feeling questionnaire (sMFQ), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Generalized Anxiety Disorder Assessment (GAD-7) and Perceived Stress Scale (PSS). Regression analysis was conducted to analyse the predictors of long COVID. A total of 300 participants were interviewed, of which 155 (52%) had COVID-19 illness. Of these 54 (35%) had persistent symptoms for a period of more than 12 weeks classified as long COVID. Muscle problems and fatigue were the most frequent (14.7%) symptoms encountered, followed by breathing problems (12.6%) and cognitive issues (12.6%). The symptoms of decrease in appetite and confusion or disorientation during the initial phase of the infection were associated with long COVID. The majority of the participants (83.3%) had moderate level of perceived stress, while moderate to severe levels of stress were observed in 17.3% of the individuals. Moreover, a high level of positive mental well-being was also observed. This study highlights the need for further research into the clinical aspects and implications of long COVID in Pakistan and emphasizes the importance of ongoing support for affected individuals.

Knowledge, Attitude, and Practices Regarding Vitamin D in Middle-Aged Pakistani Population and the Impact of Sun Exposure on Their Serum Vitamin D Levels.

OBJECTIVE: This study aimed to assess the knowledge, attitude, and practices regarding vitamin D (D-KAP) among middle-aged individuals in Pakistan and examine the impact of sun exposure on their serum vitamin D levels. METHODOLOGY: A cross-sectional study was conducted, involving 80 middle-aged individuals from Lahore, Pakistan. Data on demographics, sun exposure, and D-KAP were collected. Serum vitamin D levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: The study revealed inadequate knowledge and awareness of vitamin D among the participants. There was a positive correlation between sun exposure duration and serum vitamin D levels, indicating the importance of sun exposure for maintaining optimal vitamin D status. However, there was no significant difference in practice scores between groups, highlighting the need for interventions to bridge the gap between knowledge and practice. CONCLUSION: The study emphasizes the need to improve D-KAP in the middle-aged Pakistani population. Public health initiatives should focus on promoting accurate information, addressing cultural beliefs, and encouraging responsible sun exposure practices. Collaborative efforts are crucial to address vitamin D deficiency and its associated health consequences.

A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1G93A model of ALS.

BACKGROUND: Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function. METHODS: We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases. RESULTS: We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway. CONCLUSIONS: We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention.

Mapping of familial hypercholesterolemia and dyslipidemias basic management infrastructure in Pakistan: a cross-sectional study.

Background: Familial hypercholesterolemia (FH) is an autosomal inherited disorder characterised by elevated low-density lipoprotein cholesterol and premature cardiovascular events. Despite being declared as a public health priority, FH remains highly underdiagnosed, generally due to the lack of awareness and shortcomings in the available infrastructure, particularly in lower income countries. Methods: To map the existing infrastructure for the management of FH, a survey was conducted among 128 physicians (cardiologists, paediatricians, endocrinologists, and internal medicine specialists) from different regions of Pakistan. Findings: The respondents encountered a limited number of adults or children with diagnosed FH. A very small proportion of the population had access to free cholesterol and genetic testing even when indicated by a physician. In general, cascade screening of the relatives was not performed. Uniform diagnostic criteria for FH had not been established even within the same institution or province. The use of statins and ezetimibe in addition to lifestyle changes were the most common recommended treatment option for FH patients. The respondents considered lack of financial resources as a major barrier for the management of FH and stressed on taking relevant measures for a uniform FH screening programs around the country. Interpretation: National FH screening programmes are not in place worldwide hence FH is commonly undiagnosed, and many individuals are at a high risk for cardiovascular diseases. Timely screening of population for FH requires knowledge about FH among the clinicians and the availability of fundamental infrastructure coupled with sufficient financial resources. Funding: The authors confirm independence from the sponsor. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. FS received funding from Higher Education Commission, Pakistan (Grant 20-15760) and UG received grants from Slovenian Research Agency (J3-2536, P3-0343).

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Reviewing methods of deep learning for diagnosing COVID-19, its variants and synergistic medicine combinations.

The COVID-19 pandemic has necessitated the development of reliable diagnostic methods for accurately detecting the novel coronavirus and its variants. Deep learning (DL) techniques have shown promising potential as screening tools for COVID-19 detection. In this study, we explore the realistic development of DL-driven COVID-19 detection methods and focus on the fully automatic framework using available resources, which can effectively investigate various coronavirus variants through modalities. We conducted an exploration and comparison of several diagnostic techniques that are widely used and globally validated for the detection of COVID-19. Furthermore, we explore review-based studies that provide detailed information on synergistic medicine combinations for the treatment of COVID-19. We recommend DL methods that effectively reduce time, cost, and complexity, providing valuable guidance for utilizing available synergistic combinations in clinical and research settings. This study also highlights the implication of innovative diagnostic technical and instrumental strategies, exploring public datasets, and investigating synergistic medicines using optimised DL rules. By summarizing these findings, we aim to assist future researchers in their endeavours by providing a comprehensive overview of the implication of DL techniques in COVID-19 detection and treatment. Integrating DL methods with various diagnostic approaches holds great promise in improving the accuracy and efficiency of COVID-19 diagnostics, thus contributing to effective control and management of the ongoing pandemic.

Allelopathy: an alternative tool for sustainable agriculture.

Population increase, poverty, environmental degradation, and the use of synthetic herbicides are interdependent and closely linked and hence influence global food safety and stability of world agriculture. On the one hand, varied weeds, insects, and other pests have caused a tremendous loss in agricultural crop productivity annually. On the other hand, the use of synthetic insecticides, herbicides, fungicides, and other pesticides significantly disturbed the ecology of biotic communities in agricultural and natural ecosystems. Eventually, it destroyed the ecological balance in food chains. Interestingly, natural products released by the plants (allelochemicals) are secondary metabolites involved in ecological interactions and could be an important source of alternative agrochemicals. Mainly released by the plants as an outcome of acquaintances with other plants in their vicinity, these allelochemicals can also be used as eco-friendly substitutes for synthetic herbicides and other pesticides. Despite these facts, agrochemicals are either preferred over allelochemicals or the latter are not known in the direction of their use in achieving sustainability in agriculture. Given this, considering recent reports, this paper aims to: (1) emphasize allelochemicals; (2) overview the major biochemistry of allelochemicals; (3) critically discuss the role of allelopathy (and underlying major mechanisms) in the management of noxious weeds, insect pests, and major plant pathogens; and (4) enlighten the significant aspects so far not or least explored in the current context.

Amomum subulatum: A treasure trove of anti-cancer compounds targeting TP53 protein using in vitro and in silico techniques.

Cancer is a primary global health concern, and researchers seek innovative approaches to combat the disease. Clinical bioinformatics and high-throughput proteomics technologies provide powerful tools to explore cancer biology. Medicinal plants are considered effective therapeutic agents, and computer-aided drug design (CAAD) is used to identify novel drug candidates from plant extracts. The tumour suppressor protein TP53 is an attractive target for drug development, given its crucial role in cancer pathogenesis. This study used a dried extract of Amomum subulatum seeds to identify phytocompounds targeting TP53 in cancer. We apply qualitative tests to determine its phytochemicals (Alkaloid, Tannin, Saponin, Phlobatinin, and Cardic glycoside), and found that alkaloid composed of 9.4% ± 0.04% and Saponin 1.9% ± 0.05% crude chemical constituent. In the results of DPPH Analysis Amomum subulatum Seeds founded antioxidant activity, and then we verified via observing methanol extract (79.82%), BHT (81.73%), and n-hexane extract (51.31%) found to be positive. For Inhibition of oxidation, we observe BHT is 90.25%, and Methanol (83.42%) has the most significant proportion of linoleic acid oxidation suppression. We used diverse bioinformatics approaches to evaluate the effect of A. subulatum seeds and their natural components on TP53. Compound-1 had the best pharmacophore match value (53.92), with others ranging from 50.75 to 53.92. Our docking result shows the top three natural compounds had the highest binding energies (-11.10 to -10.3 kcal/mol). The highest binding energies (-10.9 to -9.2 kcal/mol) compound bonded to significant sections in the target protein's active domains with TP53. Based on virtual screening, we select top phytocompounds for targets which highly fit based on pharmacophore score and observe these compounds exhibited potent antioxidant activity and inhibited cancer cell inflammation in the TP53 pathway. Molecular Dynamics (MD) simulations indicated that the ligand was bound to the protein with some significant conformational changes in the protein structure. This study provides novel insights into the development of innovative drugs for the treatment of cancer disorders.

Treadmill Versus Overground Gait Training in Patients with Lower Limb Burn Injury: A Comparative Study.

The primary goal of the rehabilitation services offered to patients with lower limb burns is to enhance gait function. Exercise on a treadmill and conventional overground gait training are the two most widespread gait-training methods. Numerous studies have been published in the literature that claim treadmill training helps people walk more easily. Therefore, it would be intriguing to investigate whether treadmill gait training affects the progress made by post-lower limb burn patients compared to traditional overground gait training. The goal of the current study was to compare the effectiveness of treadmill training and traditional physical therapy therapies for improving gait after lower limb burn injury. A comparative study was conducted between January to August 2022 at a burns care unit, in Islamabad. All the participants were informed about the study procedure and consent was taken before initiating the study. All the participants received the set standard of Burn Rehabilitation by the American Burn Association (ABA). The program consists of ROM exercises, mobilization, functional mobility, stretching, balance training, and resisted exercises for enhancing muscle power. Statistical analyses were performed using IBM SPSS 24.0 software. The study subjects selected were 30 burn patients, aged above 18 years, vitally stable, and had lower limb burn injuries with an average TBSA (total burn surface area) of 20-30%. The mean for the Experimental is 18.86 and for the control group is 21.13. Patients were randomly either assigned to an experimental group or a control group. The Experimental group had a lower Time Up and Go test score of 11.86 ± 3.58 (9.50-24.07) as compared to the control group's TUG score (of 12.78 ± 4.41 (6.30-24.07). Functional mobility significantly improved as the P < 0.05. The total mean scores calculated on the Tampa Kinesiophobia scale for the Experimental group were 35.66 ± 6.32 which was less compared with those of the control group 37.93 ± 6.36. It demonstrates that fear of movement was reduced for treadmill training participants. Comparison of pre-distance (350.9 ± 86.82), pre-velocity (62.78 ± 20.20), and post-distance (385.02 ± 32.29), post-velocity 40.48 ± 21.91 of the experimental group with the control group pre-distance (339.26 ± 98.17), pre-velocity (55.07 ± 22.63), post-distance (383.07 ± 36.914), and post-velocity (40.57 ± 21.95) showed significant changes in results. In contrast to traditional gait training, treadmill training significantly improves walking ability in burn patients with lower limb damage.

High resistance of fluoroquinolone and macrolide reported in avian pathogenic Escherichia coli isolates from the humid subtropical regions of Pakistan.

OBJECTIVES: This study aimed to assess the antimicrobial resistance profile, virulence potential, and genetic characterization of avian pathogenic Escherichia coli (APEC) that cause colibacillosis in poultry. METHODS: Antibiotic susceptibility testing (AST) was measured via the Kirby-Bauer disc diffusion method against 27 commonly used antibiotics. Phylogrouping, virulence-associated gene detection, and hybrid strain detection via multiplex polymerase chain reaction (PCR) and genetic diversity were analysed via ERIC-PCR fingertyping method. RESULTS: AST analysis showed 100% of isolates were multidrug-resistant (MDR) and highest resistance was against penicillin, tetracycline, and macrolide classes of antibiotics. The mcr-1 gene was present in 40% of the isolates, though only 4% of isolates were showing phenotypic resistance. Despite the scarce use of fluoroquinolone, carbapenem, and cephalosporin in the poultry sector, resistance was evident because of the high prevalence of extended-spectrum ß-lactamase (ESBL) (53.7%) and other ß-lactamases in APEC isolates. ß-lactamase genotyping of APEC isolates revealed that 85.7% of isolates contained either blaCTX or blaTEM and around 38% of isolates were complement resistant. Growth in human urine was evident in 67.3% of isolates. Phylogroup B1 (51%) was the most prevalent group followed by phylogroups A (30.6%), D (13.61%), and B2 (4.76%). The most prevalent virulence-associated genes were fimH, iss, and tatT. Results showed that 26 isolates (17.69%) can be termed hybrid strains and APEC/EHEC (enterohemorrhagic E. coli) was the most prevalent hybrid E. coli pathotype. ERIC-PCR fingerprinting genotype analysis clustered APEC isolates in 40 groups (E1-E40). This study provides insights into the antibiotic resistance and virulence profiling of the APEC isolates in Pakistan. CONCLUSIONS: The findings of this study provide insights into that the antibiotic resistance and virulence profiling of the APEC isolates in Pakistan. This data can inform future studies designed to better estimate the severity of the colibacillosis in poultry farms.

Genomic and comparative clinico-pathological assessment of two Pakistani pigeon-derived newcastle disease virus sub-genotypes XXI.1.1 and XXI.1.2 isolated in 2017.

Pigeon paramyxovirus type-1 (PPMV-1) is an antigenic-variant of Newcastle disease virus (NDV) which is associated with infection in Columbidae family. In this study, we isolated two pigeon-derived strains pi/Pak/Lhr/SA_1/17 (designed as SA_1) and pi/Pak/Lhr/SA_2/17 (designed as SA_2) from diseased pigeons collected in Punjab province in 2017. We performed the whole genome, phylogenetic analysis and comparative clinico-pathological evaluation of two viruses in pigeons. Phylogenetic analysis based on fusion (F) gene and complete genome sequences showed that SA_1 belonged to sub-genotype XXI.1.1 and SA_2 clustered in sub-genotype XXI.1.2. SA_1 and SA_2 viruses contributed to morbidity and mortality in pigeons. Remarkably, although the two viruses resulted in comparatively similar pattern of pathogenesis and replication ability in various tissues of infected pigeons, SA_2 could cause more severe histopathological lesions and had comparatively high replication ability in pigeons than SA_1. Moreover, pigeons infected with SA_2 had higher shedding efficiency than that of pigeons infected with SA_1. Moreover, several aa substitutions in the major functional domains of the F and HN proteins might be contributed to the pathogenic differences between the two isolates in pigeons. Overall, these findings provide us with important insight into the epidemiology and evolution of PPMV-1 in Pakistan and laid the foundation for the further elucidation of the mechanism underlying the pathogenic difference of PPMV-1 in pigeons.

Does mainstream BRCA testing affect surgical decision-making in newly-diagnosed breast cancer patients?

BACKGROUND: Germline pathogenic variants mutations) in the BRCA1 and BRCA2 genes cause an increased risk of breast cancer and ovarian cancer. Mainstream cancer genetic testing (MCG) was introduced for breast cancer patients in our unit in 2013. Non-geneticist clinicians have been trained to offer genetic testing during initial treatment planning. We assessed the impact of timely test results on surgical decision-making. METHODS: Women who had undergone mainstream genetic testing for breast cancer between September 2013 and September 2018 were identified from a prospective database. Surgical data were collected retrospectively. RESULTS: 580 eligible women had mainstream genetic testing. For 474 this was their first breast cancer diagnosis. The median age was 46 years (interquartile range (IQR) 38-57). The indications were: age ≤45 years for 233 (49%); triple negative disease for 192 women (40.5%); bilateral breast cancer age <60 for 39 (8%) and other for 72 (14%) women. The median time for test initiation to result was 18 days (IQR 15-21). 302 (64% received results before surgery. 88% of those found to have a BRCA mutation before surgery opted for bilateral mastectomy (compared to 5% with BRCA wild type). An additional 106 patients had a new diagnosis on a background of previous treatment. Of these all with a pathogenic variant chose bilateral mastectomy. CONCLUSION: Timely BRCA gene testing influences surgeons' and patients' choice of surgery. It reassures women with a negative result and allows those with a positive result to take an active decision about the management of their future risk.

First Detection of Extensively Drug-Resistant Salmonella Typhi Isolates Harboring VIM and GES Genes for Carbapenem Resistance from Faisalabad, Pakistan.

Rapid emergence of resistance in Salmonella enterica serovar Typhi (Salmonella Typhi) against most of the available therapeutic options for typhoid has rendered its treatment more difficult. This study sought to determine the current scenario of antimicrobial resistance in local isolates of Faisalabad following several treatment failure reports. Out of 300 clinical specimens collected in 2018, 45 isolates were identified as Salmonella Typhi. To assess changes, we compared their antibiogram profile with 31 Salmonella Typhi strains isolated in 2005. The isolates collected during 2018 showed a significant rise in antimicrobial drug resistance as compared with isolates revived from the cultures of 2005, including 15 multidrug-resistant (MDR), 20 extensively drug-resistant, and 14 pan drug-resistant isolates compared with only 8 MDRs from 2005. Notably, in 2018 isolates, resistance to azithromycin was seen in 75% of the isolates. Extended-spectrum beta-lactamase production was detected in 47% of Salmonella Typhi isolates and 18% isolates showed resistance against carbapenems. The sequences of two carbapenemase genes, VIM and GES, found in Salmonella Typhi were submitted in NCBI. The carbapenem resistance is rare in Enterobacteriaceae and probably first time reported in Salmonella Typhi. H58 haplotype was identified in the 2018 Salmonella Typhi isolates and PCR-restriction fragment length polymorphism method identified 16.7% of H58 strains that belonged to lineage I, 19.4% of H58 strains that belonged to lineage II, and the remaining 63.9% that belonged to the node. The regional difference in the antimicrobial resistance trend needs effective epidemiological studies.

Impact of COVID-19 Vaccination on Menstrual Cycle: A Cross-Sectional Study From Karachi, Pakistan.

Background The coronavirus disease 2019 (COVID-19) disease triggered a worldwide health catastrophe. To deal with this deadly situation multiple vaccines were developed and a mass immunization program started globally. However, vaccine hesitancy was seen, especially among women of reproductive age, having concerns that the vaccine might affect their menstrual cycle. This study investigated the link between COVID-19 vaccination and menstrual abnormalities. It is essential for us to understand the effects of vaccines on menstruation as menstrual distress can have effects on everyday life, and mental and reproductive health. Methods A cross-sectional study was performed using self-administered online forms to collect data from all over Karachi. The sample included 384 females aged 18 years and above. The data were collected from November 2021 to February 2022. Results Majority of the participants were aged 21 years and had a normal body mass index (BMI). Most were moderately stressed (n=245) with 146 reporting menstrual changes post-vaccination. The difference between the post-vaccine menstruation affected (n=146) and the unaffected cohort (n=238) was significant. Other factors which likely contributed to the post-vaccine menstrual changes included Perceived Stress Scale (PSS) score, strenuous physical activity, and the pre-vaccine menstrual flow. Conclusions Among the women vaccinated for COVID-19, strenuous physical activity and high perceived stress levels affected the menstrual cycle. There is no denying that existing data are inadequate, which is one of the grounds for vaccination apprehension, particularly among menstruating women. To minimize this hesitation, the spread of disinformation about the vaccine's influence on the menstrual cycle must be avoided. In future research and clinical trials, menstruation-related side effects should also be investigated when developing vaccines.

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma.

IQ motif-containing GTPase-activating proteins (IQGAPs) are a class of scaffolding proteins, including IQGAP1, IQGAP2, and IQGAP3, which govern multiple cellular activities by facilitating cytoskeletal remodeling and cellular signal transduction. The role of IQGAPs in cancer initiation and progression has received increasing attention in recent years, especially in hepatocellular carcinoma (HCC), where the aberrant expression of IQGAPs is closely related to patient prognosis. IQGAP1 and 3 are upregulated and are considered oncogenes in HCC, while IQGAP2 is downregulated and functions as a tumor suppressor. This review details the three IQGAP isoforms and their respective structures. The expression and role of each protein in different liver diseases and mainly in HCC, as well as the underlying mechanisms, are also presented. This review also provides a reference for further studies on IQGAPs in HCC.

Demographic factors associated with length of stay in hospital and histological diagnosis in adults undergoing appendicectomy.

Objectives: Appendicectomy remains of the most common emergency operations in the United Kingdom. The exact etiologies of appendicitis remain unclear with only potential causes suggested in the literature. Social deprivation and ethnicity have both been demonstrated to influence outcomes following many operations. There are currently no studies evaluating their roles with regards to severity and outcomes following appendicectomy. Material and Methods: Demographic data were retrieved from health records for adult patients who underwent appendicectomy between 2010-2016 within a single NHS trust. To measure social deprivation, Indices of Multiple Deprivation (IMD) rankings were used. Histology reports were reviewed and diagnosis classified into predefined categories: non-inflamed appendix, uncomplicated appendicitis, complicated appendicitis and gangrenous appendicitis. Results: Three thousand four hundred and forty-four patients were identified. Mean age was 37.8 years (range 73 years). Using a generalized linear model, South Asian ethnicity specifically was found to be independently predictive of increased length of stay following appendicectomy (p <0.001). Amongst South Asian patients, social deprivation was found to be further predictive of longer hospital stay (p= 0.005). Deprivation was found to be a predictor of complicated appendicitis but not of gangrenous appendicitis (p= 0.01). Male gender and age were also independent predictors of positive histology for appendicitis (p <0.001 and p= 0.021 respectively). Conclusion: This study is the first to report an independent association between South Asian ethnicity and increased length of stay for patients undergoing appendicectomy in a single NHS trust. The associations reported in this study may be a result of differences in the pathophysiology of acute appendicitis or represent inequalities in healthcare provision across ethnic and socioeconomic groups.

Morpho-anatomical characters of family Oscillatoriaceae (algae) identified using primitive (LM) and advance technique (SEM) from Punjab, Pakistan.

In this study, 34 species belonging to the class Nostocophyceae order Nostocales and family Oscillatoriaceae were identified based on light microscopy (LM) and scanning electron microscopy (SEM). All species belong to nine genera of which two species belong to Arthrospira, six species to Lyngbya, ten species belongs to Oscillatoria, six species belong to Spirulina, seven species to Phormidium, three species to Microcoleus. The morpho-anatomical characters were identified among different species using LM and SEM. These studies highlighted that north-eastern area of Punjab was blessed with the diversity of algae. These outcomes also indicated that for internal examination along with LM, SEM was necessary for correct identification of algal sample up to specie level. RESEARCH HIGHLIGHTS: The different Oscillatoria species abundance in waste-water of four different areas. The sampling was carried out randomly in different seasons from the water bodies especially from waste-water. The morpho-anatomical characters were recognized using light microscopy (LM) and scanning electron microscopy (SEM). Thirty-four species belonging to the class Nostocophyceae order Nostocales and family Oscillatoriaceae were identified based on LM and SEM.

Discovery and characterization of dual inhibitors of human Vanin-1 and Vanin-2 enzymes through molecular docking and dynamic simulation-based approach.

The vanins are ectoenzymes with pantetheinase activity and are involved in recycling pantothenic acid (vitamin B5) from pantetheine. Elevated levels of vanin have been linked with the development and severity of several diseases, including steatosis, diabetes, skin diseases, cancer, inflammatory diseases etc. Therefore, vanins have previously been used as a potential drug target to combat related diseases. In this study, we used a molecular docking and molecular dynamic simulation-based approach to screen dual inhibitors of hVnn1, and hVnn2 from a library of 120 chemical candidates. Molecular docking of drug candidates with hVnn1, and hVnn2 using GOLD and MOE revealed that the chemical compound "methotrexate (CID: 126941)" has the highest binding affinity against both the target enzymes which was further validated through molecular dynamic simulation. Toxicity profiling of drug candidates evaluated using Lipinski's rule of five and Molsoft tool, and AdmetSar 2.0 confirms the drug suitability of methotrexate, therefore, suggesting its use as a potential therapeutic agent to inhibit the activity of vainin enzyme in related disease conditions.

Immunological characterization of chitosan adjuvanted outer membrane proteins of Salmonella enterica serovar Typhi as multi-epitope typhoid vaccine candidate.

BACKGROUND: Outer membrane proteins (OMPs) of Gram-negative bacteria have been known as potential vaccine targets due to their antigenic properties and host specificity. Here, we focused on the exploration of the immunogenic potential and protective efficacy of total OMPs of Salmonella enterica serovar Typhi due to their multi epitope properties, adjuvanted with nanoporous chitosan particles (NPCPs). The study was designed to extrapolate an effective, low cost prophylactic approach for typhoid fever being getting uncontrolled in Pakistan due to emergence of extensively drug resistant (XDR) strains. METHODS & RESULTS: The OMPs of two S. Typhi variants (with and without Vi capsule) alone and with nanoporous chitosan particles as adjuvant were comparatively analyzed for immunogenic potential in mice. Adaptive immunity was evaluated by ELISA and relative quantification of cytokine gene expression (IL4, IL6, IL9, IL17, IL10, TNF, INF and PPIA as house keeping gene) using RT-qPCR. Statistical analysis was done using Welch's test. The protection was recorded by challenging the immunized mice with 50% ×LD50 of S. Typhi. The Vi + ve-OMPs of S. Typhi showed the most promising results by ELISA and significantly high expression of IL-6, IL-10 and IL-17 and 92.5% protective efficacy with no detectable side effects. CONCLUSION: We can conclude that the OMPs of Vi + ve S. Typhi are the most promising candidates for future typhoid vaccines because of cost effective preparation without expensive purification steps and multi-epitope properties. Chitosan adjuvant may have applications for oral protein based vaccines but found less effective in injectable preparations.