Intensifying spatially compound heatwaves: Global implications to crop production and human population.

Recent research has provided crucial insights on regional heatwaves, including their causal mechanisms and changes under global warming. However, detailed research on global-scale spatially compound heatwaves (SCHs) (concurrent heatwaves over multiple regions) is lacking. Here, we find statistically significant teleconnections in heatwaves and show that the frequency of global-scale SCHs and their areal extent have increased significantly, which has led to 50 % increase in the population exposed to extreme heat stresses in the two most recent decades. Crop yields were reduced in most of the years of anomalous heatwaves, which often happen during El-Niños. The internal climate variability appears to significantly influence the inter-annual variability of regional and global heatwave extents. Insights gained here are critical in better quantifying heat stress risks inflicted on socioecological systems.

A case report of coexisting multinodular goiter with carotid body tumor.

INTRODUCTION: Carotid body tumor (CBT), a neuroendocrine neoplasm, and benign multinodular goiter (BMNG) are distinct pathologies affecting the neck region. Although rare, they can occur concurrently. This case contributes to the limited evidence regarding the association between these distinct pathologies and their operative management. CASE PRESENTATION: The patient was a 45-year-old female with a palpable mass on the right side of her neck. She was diagnosed with Shamblin type III non-secretory CBT alongside BMNG. The surgical intervention included resection of the CBT, carotid artery bypass, and Dunhill thyroidectomy. DISCUSSION: This case is the third reported instance of coexisting CBT and BMNG. Their causative relationship is evident in the literature without a clear explanation of the underlying mechanism. Both conditions are treated surgically. Dunhill thyroidectomy for BMNG is a safer option, offering more flexibility and advantages over other thyroidectomies. CONCLUSION: This case highlights the complexity of managing such dual pathologies and may provide further evidence of their association.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

OBJECTIVE: To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. METHODOLOGY: OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and ß -Globin gene primers was performed. RESULTS: GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)] and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. CONCLUSION: The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. KEY WORDS: Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.

Genomic analysis and biodesulfurization potential of a new carbon-sulfur bond cleaving Tsukamurella sp. 3OW.

Direct combustion of sulfur-enriched liquid fuel oil causes sulfur oxide emission, which is one of the main contributors to air pollution. Biodesulfurization is a promising and eco-friendly method to desulfurize a wide range of thiophenic compounds present in fuel oil. Previously, numerous bacterial strains from genera such as Rhodococcus, Corynebacterium, Gordonia, Nocardia, Mycobacterium, Mycolicibacterium, Paenibacillus, Shewanella, Sphingomonas, Halothiobacillus, and Bacillus have been reported to be capable of desulfurizing model thiophenic compounds or fossil fuels. In the present study, we report a new desulfurizing bacterium, Tsukamurella sp. 3OW, capable of desulfurization of dibenzothiophene through the carbon-sulfur bond cleavage 4S pathway. The bacterium showed a high affinity for the hydrocarbon phase and broad substrate specificity towards various thiophenic compounds. The overall genome-related index analysis revealed that the bacterium is closely related to Tsukamurella paurometabola species. The genomic pool of strain 3OW contains 57 genes related to sulfur metabolism, including the key dszABC genes responsible for dibenzothiophene desulfurization. The DBT-adapted cells of the strain 3OW displayed significant resilience and viability in elevated concentrations of crude oil. The bacterium showed a 19 and 37% reduction in the total sulfur present in crude and diesel oil, respectively. Furthermore, FTIR analysis indicates that the oil's overall chemistry remained unaltered following biodesulfurization. This study implies that Tsukamurella paurometabola species, previously undocumented in the context of biodesulfurization, has good potential for application in the biodesulfurization of petroleum oils.

Concomitant Pulmonary Aspergillosis Following Severe COVID-19.

This case report discusses an atypical complication of COVID-19 pneumonia in a 68-year-old male patient, distinguished by the development of cavitary lung disease and a subsequent incidence of invasive pulmonary aspergillosis (IPA). This adverse development transpired following a prolonged hospitalization and an extensive course of corticosteroid therapy post-COVID-19 pneumonia. This case accentuates the importance of vigilance in observing patients with severe COVID-19 pneumonia for potential opportunistic infections, particularly given the inherent risks associated with prolonged corticosteroid therapy. Prompt diagnosis and initiation of treatment are key to enhancing patient outcomes in such presentations.

Association of MSX1 Gene Variants with Nonsyndromic Cleft Lip and/or Palate in the Pakistani Population.

OBJECTIVES: This study investigated the association of MSX1 gene variants rs3821949 and rs12532 with nonsyndromic cleft lip and/or palate (NSCL/P) in the Pakistani population. DESIGN: Comparative cross-sectional study.Setting: Multicenter of CL/P malformation.Patients/Participants: Unrelated Non-Syndromic cleft Lip/Palate patients and healthy controls were enrolled. METHODS: One hundred (n = 100) subjects with NSCL/P and n = 50 unrelated healthy controls were enrolled in a multicenter comparative cross-sectional study. A tetra amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) was performed to analyze MSXI gene single nucleotide variants (SNVs). RESULTS: Among 100 NSCL/P subjects, the majority were males (56%; male: female = 1.27: 1). Most of the cases (74%) had cleft lip and palate (CLP) compared to isolated clefts. Genotyping of MSX1 gene variant rs3821949 showed an increased risk for NSCL/P in various genetic models (P < 0.0001), and the A allele exhibited a more than 4-fold increased risk among cases (OR = 4.22: 95% CI = 2.16-8.22; P < 0.0001). Our investigation found no significant difference between the rs12532 variation and NSCL/P. CONCLUSION: Our study findings suggest that MSX1 gene variants may increase predisposition to NSCL/P in the Pakistani population. Further studies comprising large samples are required to identify the genetic aetiology of NSCL/P among our people.

Gut microbiome therapeutic modulation to alleviate drug-induced hepatic damage in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) infection caused by the severe acute respiratory syndrome coronavirus 2 virus, its symptoms, treatment, and post-COVID-19 effects have been a major focus of research since 2020. In addition to respiratory symptoms, different clinical variants of the virus have been associated with dynamic symptoms and multiorgan diseases, including liver abnormalities. The release of cytokines by the activation of innate immune cells during viral infection and the high doses of drugs used for COVID-19 treatment are considered major drivers of liver injury in COVID-19 patients. The degree of hepatic inflammation in patients suffering from chronic liver disease and having COVID-19 could be severe and can be estimated through different liver chemistry abnormality markers. Gut microbiota influences liver chemistry through its metabolites. Gut dysbiosis during COVID-19 treatment can promote liver inflammation. Here, we highlighted the bidirectional association of liver physiology and gut microbiota (gut-liver axis) and its potential to manipulate drug-induced chemical abnormalities in the livers of COVID-19 patients.

Post-Transcatheter Aortic Valve Replacement Infective Endocarditis Leading to Mitral Anterior Leaflet Perforation: A Case Report.

Transcatheter aortic valve replacement(TAVR)-related infective endocarditis is a rare but fatal complication that can lead to mitral valve perforation. The clinical presentation usually includes rapidly progressive heart failure and mitral regurgitation. Transesophageal echocardiogram (TEE) is considered superior to transthoracic echocardiogram (TTE) in delineating the diagnosis of mitral valve perforation. We present a case of a 75-year-old female who had a TAVR for severe aortic stenosis three years ago and presented with new-onset atrial fibrillation and developed rapidly progressive acute decompensated heart failure. A TTE showed echogenic vegetation of the mitral valve with a perforated mitral anterior leaflet and mitral regurgitation. The blood cultures grew Group B Streptococcus, and our patient lacked the risk factors for infective endocarditis, including alcoholism, chronic liver disease, pregnancy, immunosuppression, or malignancy. This article highlights infective endocarditis with an uncommon pathogen in a patient with a prior TAVR that leads to the fatal complication of mitral valve perforation.

Dietary Supplementation of Microbial Dextran and Inulin Exerts Hypocholesterolemic Effects and Modulates Gut Microbiota in BALB/c Mice Models.

Microbial exopolysaccharides (EPSs), having great structural diversity, have gained tremendous interest for their prebiotic effects. In the present study, mice models were used to investigate if microbial dextran and inulin-type EPSs could also play role in the modulation of microbiomics and metabolomics by improving certain biochemical parameters, such as blood cholesterol and glucose levels and weight gain. Feeding the mice for 21 days on EPS-supplemented feed resulted in only 7.6 ± 0.8% weight gain in the inulin-fed mice group, while the dextran-fed group also showed a low weight gain trend as compared to the control group. Blood glucose levels of the dextran- and inulin-fed groups did not change significantly in comparison with the control where it increased by 22 ± 5%. Moreover, the dextran and inulin exerted pronounced hypocholesterolemic effects by reducing the serum cholesterol levels by 23% and 13%, respectively. The control group was found to be mainly populated with Enterococcus faecalis, Staphylococcus gallinarum, Mammaliicoccus lentus and Klebsiella aerogenes. The colonization of E. faecalis was inhibited by 59-65% while the intestinal release of Escherichia fergusonii was increased by 85-95% in the EPS-supplemented groups, respectively, along with the complete inhibition of growth of other enteropathogens. Additionally, higher populations of lactic acid bacteria were detected in the intestine of EPS-fed mice as compared to controls.

Identification of RdRp inhibitors against SARS-CoV-2 through E-pharmacophore-based virtual screening, molecular docking and MD simulations approaches.

The outbreak of novel Coronavirus, an enduring pandemic declared by WHO, has consequences to an alarming ongoing public health menace which has already claimed several million human lives. In addition to numerous vaccinations and medications for mild to moderate COVID-19 infection, lack of promising medication or therapeutic pharmaceuticals remains a serious concern to counter the ongoing coronavirus infections and to hinder its dreadful spread. Global health emergencies have called for urgency for potential drug discovery and time is the biggest constraint apart from the financial and human resources required for the high throughput drug screening. However, computational screening or in-silico approaches appeared to be an effective and faster approach to discover potential molecules without sacrificing the model animals. Accumulated shreds of evidence on computational studies against viral diseases have revealed significance of in-silico drug discovery approaches especially in the time of urgency. The central role of RdRp in SARS-CoV-2 replication makes it promising drug target to curtain on going infection and its spread. The present study aimed to employ E-pharmacophore-based virtual screening to reveal potent inhibitors of RdRp as potential leads to block the viral replication. An energy-optimised pharmacophore model was generated to screen the Enamine REAL DataBase (RDB). Then, ADME/T profiles were determined to validate the pharmacokinetics and pharmacodynamics properties of the hit compounds. Moreover, High Throughput Virtual Screening (HTVS) and molecular docking (SP & XP) were employed to screen the top hits from pharmacophore-based virtual screening and ADME/T screen. The binding free energies of the top hits were calculated by conducting MM-GBSA analysis followed by MD simulations to determine the stability of molecular interactions between top hits and RdRp protein. These virtual investigations revealed six compounds having binding free energies of -57.498, -45.776, -46.248, -35.67, -25.15 and -24.90 kcal/mol respectively as calculated by the MM-GBSA method. The MD simulation studies confirmed the stability of protein ligand complexes, hence, indicating as potent RdRp inhibitors and are promising candidate drugs to be further validated and translated into clinics in future.

Identification of NS2B-NS3 Protease Inhibitors for Therapeutic Application in ZIKV Infection: A Pharmacophore-Based High-Throughput Virtual Screening and MD Simulations Approaches.

Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with -64.28, -55.15 and -50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.

Jejunogastric Intussusception: A Rare Case Report Study.

Jejunogastric intussusception (JGI) is a rare, potentially fatal complication of gastrojejunostomy following any gastric resection or gastric bypass surgery. Very less no of cases have been reported to date in the literature, with a very low incidence of <0.1%. Early recognition of JGI followed by prompt intervention is necessary to avoid any serious complications of gut gangrene or even possible death. It carries a mortality rate of approx. 10% of patients subjected to early intervention within 24 hours as compared to 50% in cases where surgery was delayed for more than 48 hours. The usual presenting complaints include a triad of palpable epigastric mass, hematemesis, and epigastric pain with only 50% of patients having this classical presentation. We here, report a middle-aged male with JGI which was diagnosed and managed at our center with emergency surgical intervention. How to cite this article: Haq MFU, Wagay BA, Malik AA, et al. Jejunogastric Intussusception: A Rare Case Report Study. Euroasian J Hepato-Gastroenterol 2023;13(2):163-165.

Relationship Between Upper Respiratory Tract Symptoms And Treatment-Seeking Behaviour In Healthy Attendants Of Patients Presenting To Opd Clinics Of Bbs Teaching Hospital Abbottabad.

Background: Indiscriminate use of antibiotics is a well-known reason for increasing antimicrobial resistance. Upper respiratory tract infection presents with similar symptoms and signs irrespective of its bacterial or viral causes and is either ignored or managed aggressively by the primary care physicians. The objective was to determine the relationship between upper respiratory tract infections and treatment-seeking behaviour in healthy individuals attending the OPD clinics of BBS Teaching Hospital with their sick family members. Methods: Six hundred and eighty-five healthy individuals who accompanied patients to the OPD clinics of BBS Teaching Hospital, Abbottabad were enrolled in this cross-sectional survey. They were given a modified questionnaire to respond to and their replies were analyzed for assessment. Results: In a survey of 685 individuals, 98.2% were aware of antibiotics, but only 28.6% correctly understood their use against infections. Misconceptions about antibiotic resistance were common, with 54.5% believing it arises from human immunity. Only 31.53% consulted a doctor for upper respiratory symptoms and 72.6% of those expected antibiotics. Women showed higher antibiotic knowledge than men, but education level was a stronger predictor of both knowledge and attitudes. Conclusion: This study highlights a critical gap in public understanding and responsible usage of antibiotics, particularly in the context of upper respiratory tract infections. This study reveals that increased awareness and more informed attitudes about antibiotic resistance correlate with a decreased likelihood of inappropriate antibiotic prescription.

Complete Recovery of an Occluded Coronary Artery Secondary to Spontaneous Coronary Artery Dissection With Medical Management in a Young Patient Presenting With Acute Coronary Syndrome.

Spontaneous coronary artery dissection (SCAD) is defined as a tear in the coronary arterial wall. The clinical presentation is similar to acute coronary syndrome (ACS); however, most of the patients are usually younger and do not have typical risk factors such as atherosclerosis. In addition, the management of SCAD varies from case to case unlike that of ACS due to atherosclerotic plaque rupture; therefore, recognizing and treating it appropriately is crucial. We present a case of a 47-year-old female who presented with typical clinical findings of ACS and was diagnosed with occlusion of the left anterior descending coronary artery due to SCAD on emergent coronary angiography. The patient was treated with medical management only, and a repeat coronary angiography showed complete healing of the vessel wall after six weeks. This article highlights that early diagnosis, recognition, and medical management of SCAD can prevent unnecessary invasive intervention.

Spectrum of EGFR mutation and its relation with high-risk predictors in thyroid cancer in Kashmiri population: 2 years prospective study at a tertiary care hospital.

BACKGROUND: EGFR mutation has not been extensively studied in thyroid cancer. This study was conducted to study spectrum of EGFR mutation in thyroid cancer in Kashmiri population for possible therapeutic purpose. METHODS: It was 2 years prospective cross-sectional study conducted at a tertiary care center in which histologically confirmed, untreated thyroid cancers were included. These specimens were subjected to EGFR mutation analysis by AS-PCR method. RESULTS: There were a total 60 patients with preponderance of females [44(73%) vs 16(27%)]. Most were in the age group of less than 45 years (75%). Most of these patients were non-smokers [50(83.3%) vs 10 (17.3%)]. Papillary thyroid carcinoma (PTC) was the commonest type 48(80%), rest was follicular type (FTC) 12(20%). Well-differentiated carcinoma (WDC) was common than poorly differentiated (PDC) [41(68.4%) vs 19 (31.6%)]. Lymph node metastasis and vascular invasion were present in 32 (53.4%) and 17 (28.4%) respectively. Thirty-two (53.3%) patients were having 15 bp deletion in exon 19 of EGFR. These deletions were common in PTC than FTC, 29(60.5%) vs 3(25%) which was statistically significant (p = 0.04, CI = 0.2). The total mutational rate of T790M in EGFR tyrosine kinase domain (exon 20) was found to be only 8.4% (5 of 60). Only 4 (8.3%) of these mutations were detected in PTC and rest in FTC (1 of 12). Twenty-six (43.3%) of exon 21 were positive for L858R mutation in EGFR tyrosine kinase domain. Married persons and PDC were significant predictors of L858R mutation in EGFR tyrosine kinase domain in thyroid cancer as this was statistically significant in them with p = 0.04, 0.03 respectively. CONCLUSION: In our population, PTC is common in females with half of population harboring EGFR mutation and it is statistically significant in poorly differentiated carcinoma and in married individuals. It implies that EGFR may be used in thyroid cancer as a possible therapeutic agent in our set of population.

Mycobacterium chimaera lung infection and empyema in a patient without cardiopulmonary bypass.

Mycobacterium chimaera is a nontuberculous mycobacterium that belongs to the Mycobacterium avium complex. Invasive infections are very rare and have been associated with contaminated heater-cooler water systems used during cardiopulmonary bypass. There is usually a long latency period and patients have nonspecific symptoms that can result in a delayed diagnosis or misdiagnosis. We report a case of M. chimaera infection in a man who presented with worsening shortness of breath and was found to have pleural effusion. The patient did not have any history of cardiopulmonary bypass surgery, which raises concerns about community spread of this rare infection and needs further investigation in the general population. Furthermore, he had a history of sarcoidosis and was on immunosuppressive medications, which might suggest that immunosuppressed patients can acquire this infection without the described risk factors.

High-Molecular-Weight Dextran-Type Exopolysaccharide Produced by the Novel Apilactobacillus waqarii Improves Metabolic Syndrome: In Vitro and In Vivo Analyses.

Metabolic syndrome is a leading medical concern that affects one billion people worldwide. Metabolic syndrome is defined by a clustering of risk factors that predispose an individual to cardiovascular disease, diabetes and stroke. In recent years, the apparent role of the gut microbiota in metabolic syndrome has drawn attention to microbiome-engineered therapeutics. Specifically, lactic acid bacteria (LAB) harbors beneficial metabolic characteristics, including the production of exopolysaccharides and other microbial byproducts. We recently isolated a novel fructophilic lactic acid bacterium (FLAB), Apilactobacillus waqarii strain HBW1, from honeybee gut and found it produces a dextran-type exopolysaccharide (EPS). The objective of this study was to explore the therapeutic potential of the new dextran in relation to metabolic syndrome. Findings revealed the dextran's ability to improve the viability of damaged HT-29 intestinal epithelial cells and exhibit antioxidant properties. In vivo analyses demonstrated reductions in body weight gain and serum cholesterol levels in mice supplemented with the dextran, compared to control (5% and 17.2%, respectively). Additionally, blood glucose levels decreased by 16.26% following dextran supplementation, while increasing by 15.2% in non-treated mice. Overall, this study displays biotherapeutic potential of a novel EPS to improve metabolic syndrome and its individual components, warranting further investigation.

A cross-sectional study to assess the epidemiological situation and associated risk factors of dengue fever; knowledge, attitudes, and practices about dengue prevention in Khyber Pakhtunkhwa Province, Pakistan.

Background: Dengue fever has been responsible for around 12 countrywide large outbreaks in Pakistan, resulting in 286,262 morbidities and 1,108 deaths. Khyber Pakhtunkhwa (KP) is the most recently impacted province. This study aimed to investigate the molecular, epidemiological, and potential elements that contribute to increasing dengue transmission patterns, and knowledge, attitude, and practice (KAP) toward dengue in KP province. Method: This cross-sectional community-based study was conducted (June-December, 2021) in two phases. Phase I involved the epidemiological (n = 5,242) and molecular analysis of DENV in 500 randomly collected blood samples of the 2021 dengue outbreak in KP. Phase II focused on assessing dengue-KAP levels in healthy communities (n = 14,745, aged >18 years), adopting a cross-sectional clustered multistage sampling in eight districts (dengue-hotspot vs. non-hotspot) of KP. Chi-square tests and logistic regression analysis were applied. Results: Peshawar district had the highest dengue cases (60.0%) associated with the predominant co-circulation of DENV-2 (45.8%) and DENV-3 (50.4%) serotypes. A rise in cases was reported in October (41.8%) followed by September (27.9%) and August (14.4%; p < 0.001). Males (63.7%, p < 0.001) and individuals aged 16-30 years (37.0%, p < 0.001) were highly affected. General workers (18.0%), families with a monthly income of 10,000-20,000 Pak rupees (50.5%), unmarried (71.0%), uneducated (31%), families with higher human density (>10 individuals per household), and those (29.0%) who faced power outages for more than 7/24 h were the most affected. Moreover, co-morbidities like renal failure and bronchial asthma were associated with disease severity. A community survey on KAP revealed that an average of 74, 60, and 43% of the participants demonstrated good knowledge, attitudes, and dengue preventive practices, respectively. Conclusion: Multiple poor socioeconomic elements are influencing dengue fever transmission in the province. Higher KAP levels may explain the low frequency of dengue in non-hotspot districts. Our study emphasizes the need for effective and long-term public health education, strengthened vector surveillance, and expanded laboratory capacity for better diagnosis and management of dengue cases to better predict the burden and seasonality of disease in the country.

Revealing Genome-Based Biosynthetic Potential of Streptomyces sp. BR123 Isolated from Sunflower Rhizosphere with Broad Spectrum Antimicrobial Activity.

Actinomycetes, most notably the genus Streptomyces, have great importance due to their role in the discovery of new natural products, especially for finding antimicrobial secondary metabolites that are useful in the medicinal science and biotechnology industries. In the current study, a genome-based evaluation of Streptomyces sp. isolate BR123 was analyzed to determine its biosynthetic potential, based on its in vitro antimicrobial activity against a broad range of microbial pathogens, including gram-positive and gram-negative bacteria and fungi. A draft genome sequence of 8.15 Mb of Streptomyces sp. isolate BR123 was attained, containing a GC content of 72.63% and 8103 protein coding genes. Many antimicrobial, antiparasitic, and anticancerous compounds were detected by the presence of multiple biosynthetic gene clusters, which was predicted by in silico analysis. A novel metabolite with a molecular mass of 1271.7773 in positive ion mode was detected through a high-performance liquid chromatography linked with mass spectrometry (HPLC-MS) analysis. In addition, another compound, meridamycin, was also identified through a HPLC-MS analysis. The current study reveals the biosynthetic potential of Streptomyces sp. isolate BR123, with respect to the synthesis of bioactive secondary metabolites through genomic and spectrometric analysis. Moreover, the comparative genome study compared the isolate BR123 with other Streptomyces strains, which may expand the knowledge concerning the mechanism involved in novel antimicrobial metabolite synthesis.

PNPLA3 and TM6SF2 genetic variants and hepatic fibrosis and cirrhosis in Pakistani chronic hepatitis C patients: a genetic association study.

BACKGROUND: The present study investigates if common missense functional variants p.I148M and p.E167K in PNPLA3 and TM6SF2 genes, respectively, associate with development of hepatic fibrosis and cirrhosis in a geographically novel cohort of Pakistani chronic hepatitis C (CHC) patients. METHODS: In total, 502 Pakistani CHC patients [242 males, median age 40 years, 220 with significant hepatic fibrosis, including 114 with cirrhosis] were genotyped for PNPLA3 and TM6SF2 variants using TaqMan genotyping assays. Associations between genotypes, biochemical and clinical parameters were evaluated. RESULTS: Genotypic distributions for PNPLA3 and TM6SF2 polymorphisms conformed to Hardy-Weinberg equilibrium and did not associate with fibrosis grades ≥ F2 or cirrhosis in any of the genetic models tested (all p = > 0.05). PNPLA3 and TM6SF2 variants did not modulate baseline characteristics and serum markers of liver injury in CHC patients. Similarly, increasing number of risk alleles of PNPLA3 and TM6SF2 polymorphisms had no trend effect on serum liver enzyme activities or proportion of CHC patients with significant or advanced fibrosis or cirrhosis (p = > 0.05). The same trend of no association with hepatic fibrosis or cirrhosis persisted in the multivariate logistic regression models adjusting for age, gender, body mass index and HCV viral load (p = > 0.05). CONCLUSIONS: PNPLA3 and TM6SF2 variants do not appear to modulate development of hepatic fibrosis or cirrhosis in present CHC patients of Pakistani origin, and may be of more relevance in liver pathology involving abnormalities in hepatic fat accumulation. These results also reflect the divergent associations observed for different genetic modifiers of hepatic fibrosis and cirrhosis in distinct ethnicities.