Genomic epidemiology of SARS-CoV-2 is imperative to explore the transmission, evolution, and also pathogenicity of viruses. The emergence of SARS-CoV-2 variants of concern posed a severe threat to the global public health efforts. To assess the potential consequence of these emerging variants on public health, continuous molecular epidemiology is of vital importance. The current study has been designed to investigate the major SARS-CoV-2 variants and emerging mutations in virus structural and non-structural proteins (NSP) during the fourth wave in September 2021 from the Punjab province of Pakistan. Twenty SARS-CoV-2 positive samples have been collected from major cities were subjected to next-generation sequencing. Among the 20 whole genomes (GenBank Accession SRR16294858-SRR16294877), 2 samples failed to be completely sequenced. These genome sequences harbored 207 non-synonymous mutations, among which 19 were unique to GISAID. The genome sequences were detected: Delta 21I, 21J variants (B.1.617.2). Mutation’s spike_F157del, spike_P681R, spike_T478K, spike_T19R, spike_L452R, spike_D614G, spike_G142D, spike_E156G, and spike_R158del have been detected in all samples where K1086Q, E554K, and C1250W were unique in spike protein. These genomic sequences also harbored 129 non-synonymous mutations in NSP. The most common were NSP3_P1469S (N = 17), NSP3_A488S (N = 17), NSP3_P1228L (N = 17), NSP4_V167L (N = 17), NSP4_T492I (N = 17), NSP6_T77A (N = 17), NSP14_A394V (N = 17), NSP12_G671S (N = 18), and NSP13_P77L (N = 18). The mutation, F313Y in NSP12, detected in the current study, was found in a single isolate from Belgium. Numerous other unique mutations have been detected in the virus papain-like protease (NSP3), main protease (NSP5), and RNA-dependent RNA polymerase (NSP12). The most common non-synonymous mutations in the spike protein were subjected to stability analysis, exhibiting a stabilizing effect on structures. The presence of Delta variants may affect therapeutic efforts and vaccine efficacy. Continuous genomic epidemiology of SARS-CoV-2 in Pakistan may be useful for better management of SARS-CoV-2 infections.
Objective This study investigates the association of preventive measures with coronavirus disease (COVID-19) seropositivity. Methods This cross-sectional study was conducted at the Combined Military Hospital Kharian Medical College, Pakistan, in September 2020. A total of 442 participants from three different strata (faculty, students, and administration/technical staff) were enrolled using a convenient sampling technique. A rapid antibody testing method was used to detect antibodies. The Ichroma™ COVID-19 Ab test is an in vitro diagnostic device that helps in the rapid identification of COVID-19 by measuring the levels of IgG and IgM antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the blood. An automated fluorescent immunoassay system (AFIAS-6), with a clinical sensitivity of 95.8% and specificity of 96.7%, was used for qualitative analysis. A self-administered questionnaire was used to collect data, and data analysis was performed using SPSS version 25. Results In total, 442 participants were included in the study: 40 (9%) faculty members, 299 (67%) students, and 103 (23.3%) administrative/technical staff. As many as 14.9% of the participants were symptomatic; 32.4% always used masks, and 14% never wore masks. Furthermore, 69.7% of participants frequently washed their hands for 20 s, and 75.6% were aware of social distancing. A total of 16.96% of participants tested positive for IgG antibodies. Moreover, most of the administration/technical staff who tested positive for IgG were asymptomatic (68.42%). A significant association ( p < 0.001) was found between following the safety guidelines (wearing masks, handwashing, and social distancing) and the occurrence of COVID-19. Conclusion This study showed a higher seroprevalence rate than other studies as it was conducted toward the end of the first wave of the COVID-19 pandemic. However, we are still far from achieving herd immunity. Furthermore, strict compliance with preventive measures is the only way to ensure safety until an effective vaccine is developed.
Background Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance and is due to variants in WFS1 and CISD2. Methods We evaluated the underlying molecular etiology of three affected members of a consanguineous family with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical and imaging data with the genetic findings and their associated phenotypes. Results We identified a homozygous missense variant p.(Asn1097Lys) in CDK13, a gene previously associated with autosomal dominant congenital heart defects, dysmorphic facial features, clinodactyly, gastrointestinal tract abnormalities, intellectual developmental disorder, and seizures with variable phenotypic features. Conclusion We report a homozygous variant in CDK13 and suggest that this gene causes an autosomal recessive disorder with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities.
Cardiovascular disease (CVD) have multifactorial nature, and owing to their disparate etiological roots, it is difficult to ascertain exact determinants of CVD. In the current study, primary objective was to determine association of single nucleotide polymorphisms (SNP) in folate pathway genes, homocysteine, antihypertensive medication, and of known risk factors in relation to CVD outcomes. The participants numbered 477 (controls, n = 201, ischemic heart disease patients, n = 95, and myocardial infarction cases, n = 181, respectively). SNPs that were queried for homocysteine pathway genes included, “methylene tetrahydrofolate reductase (MTHFR)” gene SNPs rs1801133 and rs1801131, “methyltransferase (MTR)” SNP rs1805087, “paraoxonase 1 (PON1)” SNP rs662, and angiotensin-converting enzyme (ACE) gene polymorphisms rs4646994. Medication data were collected through questionnaire, and serum-based parameters were analyzed through commercial kits. The analysis of variance and multiple comparison scrutiny revealed that age, gender, family history, cholesterol, creatinine, triglyceride, high density lipoproteins (HDL), homocysteine, beta-blocker, ACE inhibitors, MTHFR and PON1 SNPs related to coronary artery disease (CAD). On regression, rs662 SNPs and C-reactive protein had nonsignificant odds ratio, whereas age, gender, creatinine, and HDL were nonsignificant. Family history, cholesterol, homocysteine, beta blocker, and ACE inhibitors, homocysteine, rs1801133 and rs1801131 SNP maintained significance/significant odds for CAD. The current study indicates an intricate relationship between genetic variants, traditional factors, and drug usage in etiogenesis of arterial disease. Differences in SNPs, their modulated effects in consensus with medicinal usage may be related to ailment outcomes affecting coronary vasculature.
Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.
Purpose Systemic auto-inflammatory diseases are a diverse group of heterogeneous disorders resulting in development of the systemic inflammation in absence of the inflammatory induction. Sequence variants in the OTULIN gene, which disrupts its ubiquitination activity lead to auto-inflammation, panniculitis, and dermatosis syndrome. To date, only few disease-causing variants in the OTULIN have been reported.In the study, presented here, sequence analysis of the OTULIN gene in a patient, exhibiting features of OTULIN-related auto-inflammatory syndrome (ORAS), revealed a novel disease-causing missense variant p.(Thr312Met). Further, effect of the variant on structure and function of the OTULIN protein has been examined using in silico OTULINWT and OTULINT312M. Methods Cells, collected from the patient blood, were examined by flow cytometry. Search for the disease-causing variants was carried out using exome followed by Sanger sequencing. Effect of the sequence variant on structure of the mutated protein was studied using in-silico analyses. Results Flow cytometry analysis revealed slightly reduced number of lymphocytes, marked leukocytosis, and mildly increased levels of IgG. Whole exome sequencing coupled with Sanger sequencing revealed a homozygous missense variant [c.935C>T; p.(Thr312Met)] in the OTULIN gene. In-silico analyses revealed that the missense variant reduces OTULIN’s expression and promotes accumulation of LUBAC-linked UB chains leading to auto-inflammation.Conclusion Taken together, OTULIN may act as a novel therapeutic target for the development of immunomodulatory drugs that may potentially increase or stabilize their expression. Targeting more components of the Ub-proteasome pathway may provide new opportunities for therapeutic exploitation and drug discovery.
Background: Drug drug interactions (DDIs), being one of the most preventable drug related hazards having serious life threatening adverse consequences or at least results in therapeutic failure . Aim : T o confirm the drug drug interactions among medical patients at private and public sector hospitals of Jhelum and Kharian . Study d esign: Comparative study. Methodology: The collected data was analyzed for drug interactions. P atients who were being prescribed less than two drugs along with topical drugs (ointments, creams, ear drops and eye drops) were excluded. Information on prescriptions was retrieved from the hospital prescription. SPSS for windows version 20.0 was used to analyze the data. Results were presented as frequency and percen tage. Results: The results showed that the public sector showed 1640 drug interactions, that is 75%; on the other hand, the private sector showed 260 drug interactions, that is 41%. Conclusions: We concluded that frequency of drug interactions were more in public sector hospitals. Hence, a possible reason for such a result could be the greater patient load on public sector hospitals and less number of appointed doctors in such facilities. Keywords: Adverse Drug I nte raction, Drug Related Problems and Drug Drug Interaction.
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