Objective: The study examined the efficacy of various generations of cephalosporins against biofilms developed by pathogenic S. aureus and E. coli. Methods: The development of biofilms by both bacteria was assessed using petri-plate and microplate methods. Biofilm hydrolysis and inhibition were tested using first to fourth generations of cephalosporins, and the effects were analyzed by crystal violet staining and phase contrast microscopy. Results: Both bacterial strains exhibited well-developed biofilms in petri-plate and microplate assays. Cefradine (first generation) showed 76.78% hydrolysis of S. aureus biofilm, while significant hydrolysis (59.86%) of E. coli biofilm was observed by cefipime (fourth generation). Similarly, cefuroxime, cefadroxil, cefepime, and cefradine caused 78.8%, 71.63%, 70.63%, and 70.51% inhibition of the S. aureus biofilms, respectively. In the case of E. coli, maximum biofilm inhibition (66.47%) was again shown by cefepime. All generations of cephalosporins were more effective against S. aureus than E. coli, which was confirmed by phase contrast microscopy. Conclusions and Relevance: Cephalosporins exhibit dual capabilities of hydrolyzing and inhibiting S. aureus and E. coli biofilms. First-generation cephalosporins exhibited the highest inhibitory activity against S. aureus, while the third and fourth generations significantly inhibited E. coli biofilms. This study highlights the importance of tailored antibiotic strategies based on the biofilm characteristics of specific bacterial strains.

Purpose: Infantile colic diagnostic criteria were established by Rome IV. A universally accepted management remains to be established. We aimed to evaluate diagnostic criteria, management strategies, and perceived regional prevalence of infantile colic in Pakistan, as well as its effect on physicians and parents. Methods: A questionnaire was distributed amongst 1,256 physicians. Results: We received 800 replies. Wessel and Rome IV criteria were used by most physicians for diagnosis; however, the response “any infant who cries a lot” was selected by older physicians (48% of those over 60 years), physicians in rural areas (32%), physicians practicing in private clinics (27%), and general physicians (30%). Estimated prevalence of infantile colic ranges from 21–40%. Reassurance was the most widely recommended management strategy followed by herbal teas (51%), switching to a different formula (49%), probiotics (28%) and antibiotics (26%), discontinuation of breastfeeding (14%), elimination of dairy products from the breastfeeding mothers’ diet (6%), and the administration of colic drops (1%). Most physicians considered the negative impact of colic on their personal lives and the parents as mild-to-moderate. Notably, 38% of percent of physicians routinely screened for maternal depression, and 45% of physicians were aware of the association between infantile colic and shaken baby syndrome. Conclusion Most physicians in Pakistan diagnose and manage infantile colic according to the established guidelines. However, the guidelines pertaining to treatment planning are not followed. Educational efforts directed toward general physicians and doctors practicing in rural areas and clinics must be implemented to avoid unnecessary testing and treatment burden.

Background: and Purpose There are reports of decline in the rates of acute emergency presentations during coronavirus disease 2019 (COVID-19) pandemic including stroke. We performed a meta-analysis of the impact of COVID-19 pandemic on rates of stroke presentations and on rates of reperfusion therapy. Methods: Following the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines, we systematically searched the literature for studies reporting changes in stroke presentations and treatment rates before and during the COVID-19 pandemic. Aggregated data were pooled using meta-analysis with random-effect models. Results: We identified 37 observational studies (n=375,657). Pooled analysis showed decline in rates of all strokes (26.0%; 95% confidence interval [CI], 22.4 to 29.7) and its subtypes; ischemic (25.3%; 95% CI, 21.0 to 30.0), hemorrhagic (27.6%; 95% CI, 20.4 to 35.5), transient ischemic attacks (41.9%; 95% CI, 34.8 to 49.3), and stroke mimics (45.6%; 95% CI, 33.5 to 58.0) during months of pandemic compared with the pre-pandemic period. The decline was most evident for mild symptoms (40% mild vs. 25%–29% moderate/severe). Although rates of intravenous thrombolytic (IVT) and endovascular thrombectomy (EVT) decreased during pandemic, the likelihood of being treated with IVT and EVT did not differ between the two periods, both in primary and in comprehensive stroke centers (odds ratio [OR], 1.08; 95% CI, 0.94 to 1.24 and OR, 0.95; 95% CI, 0.83 to 1.09, respectively). Conclusions Rates of all strokes types decreased significantly during pandemic. It is of paramount importance that general population should be educated to seek medical care immediately for stroke-like symptoms during COVID-19 pandemic. Whether delay in initiation of secondary prevention would affect eventual stroke outcomes in the long run needs further study.

Aims: Helicobacter pylori is a gastrointestinal bacterium that causes peptic ulcers and stomach cancer in nearly half of the world’s population. Many virulence factors influence the outcome of H. pylori related disorders. The purpose of this study was to see if there was a relationship between H. pylori virulence factors and histological and endoscopic findings in stomach biopsy specimens from Sudanese gastritis patients. Methodology and results: In the period between March 2018 and January 2020, a total of 290 gastric biopsies were taken from patients in Khartoum State hospitals. Histopathology and polymerase chain reaction (PCR) assays were performed on all specimens. Histological investigation revealed H. pylori in 103/290 (35.5%) samples, while PCR revealed H. pylori 16S rRNA positivity in 88/290 (30.3%) samples. Eighty-eight positive PCR specimens were subjected to PCR for genotypic detection of cagA, cagE, vacA, dupA and iceA1 genes. All of strains were vacA positive 100% (88/88) followed by dupA 50.0% (44/88), cagA 40.9% (36/88), cagE gene 38.6% (34/88) and iceA1 gene was detected in only 15.9% (14/88). The vacA s1/m1 68.2% (60/88) was the most prevalent vacA subtype. Conclusion, significance and impact of study Helicobacter pylori virulence genes were widespread and diversified in Sudanese gastritis patients. Helicobacter pylori cagA and iceA1 were significantly in association with gastric mucosa inflammation degree, whereas the dupA gene was found to be associated with the clinical outcomes.
Helicobacter pylori ; Gastritis

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Cystic Echinococcosis (CE) is one of the most important zoonotic parasitic diseases in human, livestock, and wildlife globally. The prevalence of CE depends upon human behavioral risk factors, the diversity and ecology of animal host interactions and the genetic diversity within Echinococcus species which differ in their zoonotic potential and pathogenicity. It is a neglected, economic and socio-cultural problem in Pakistan. The available data about the incidence of CE is very limited and no extensive study has been reported in Pakistan. The current study was aimed to analyze the hospital reported cases of CE and the associated risk factors related to the incidence of CE. The hospital-based data of CE for the time period of January 2012-December 2017 was collected from Islamabad, Rawalpindi and Peshawar. The data covered demographic characteristics including age, gender, and cyst localization of infected individuals and socioeconomic determinants. The data was analyzed based upon different risk factors along with the different socioeconomic parameters that has an important impact on the distribution of disease. A total of 228 cases were presented in the selected hospitals of different cities during the study period. Out of total 228 patients, 59.21% were males and 40.78% were females (P<0.001). Most infections have been recorded in young adults (>20-30) showing 22.8% of total infected individuals followed by children (0-10) showing 10.5% (n=24), respectively (P<0.001). Liver was the most vulnerable organ (58.77%, n=134) followed by lungs (14.47%, n=33) (P<0.001). The infection was higher among rural communities (84.2%) than urban (12.8%) (P<0.001). Socioeconomic and demographic factors had an important impact on the intensity of disease (P<0.001). The occurrence of cases in children and young adults was an important finding as it indicated an active transmission of the parasite in Pakistan along with the poverty index. Emergence of echinococcosis in Pakistan showed that emerging health issues in Pakistan could bring the disease to limelight for future research. This finding, together with the fact that 1 hospital reported 214 cases over 6 years 325 underlines the need for a program for prevention/control of this disease in Pakistan. The timely measure needs to be taken to hamper the disease development and establishment. In order to control the disease, complete surveillance should be done which in turn weighs down the disease progress.

INTRODUCTIONMetabolic heterogeneity among obese individuals is thought to translate into variations in cardiovascular risk. Identifying obese people with an unfavourable metabolic profile may allow preventive strategies to be targeted at high-risk groups. This study aimed to identify clinical, biochemical and immunological differences between insulin-sensitive and insulin-resistant obese subgroups, to understand the population-specific pathophysiological basis of the adverse cardiovascular risk profile in the latter group.

METHODSCardiovascular risk indicators, including anthropometric parameters, blood pressure, acanthosis nigricans area, and related biochemical, endocrine and inflammatory markers, were determined in 255 healthy South Asian volunteers aged 18-45 years, with a 2:1 ratio of obese/overweight to normal-weight individuals. Lifetime atherosclerotic cardiovascular disease (ASCVD) risk was also calculated.

RESULTSBody mass index (BMI) and insulin sensitivity-based tertiles independently showed incremental trends in waist-hip ratio, skinfold thickness, acanthosis nigricans area, blood pressure, serum lipids, hepatic enzymes, adipokines, inflammatory markers and ten-year ASCVD risk. The anthropometric, biochemical and inflammatory parameters of obese insulin-sensitive and obese insulin-resistant groups differed significantly. Extreme group analysis after excluding the middle tertiles of both insulin resistance and BMI also showed significant difference in anthropometric indicators of cardiovascular risk and estimated lifetime ASCVD risk between the two obese subgroups.

CONCLUSIONObese insulin-sensitive individuals had a favourable metabolic profile compared to the obese insulin-resistant group. The most consistent discriminative factor between these phenotypic classes was anthropometric parameters, which underscores the importance of clinical parameters as cardiovascular risk indicators in obesity.

Objective: To gather the fragmented literature on ethnobotany, phytochemistry and in-vitro activities of medicinal plants of Pakistan being used against common infections caused by Staphylococcus aureus (S. aureus). Methods: A large number of published and unpublished research studies related to the ethnomedicinal, phytochemical and anti-S. aureus activity of medicinal flora of Pakistan published from 1990-2018 were reviewed using online bibliographic databases such as PubMed, Web of Science, Science Direct, ResearchGate and libraries. Results: S. aureus can cause many human ailments including endocarditis, staphylococcal scalded skin syndrome, septic arthritis, respiratory problems with an estimated infection rate of 25%-35% across the globe. This review comprised of 86 medicinal plants. Data showed that people mostly used leaves (50%) for the preparation of traditional medicines. Correlation analysis on the reviewed data revealed that methanolic extract concentrations of medicinal plants was highly significantly positive correlated (r=0.8; P<0.01) with the S. aureus zone of inhibitions. S. aureus reportedly showed complete resistant to the commonly used antibiotic erythromycin. Isolated compounds like altheahexacosanyl lactone, cinnamaldehyde, niloticane, gobicusin A, asparacosin A, muzanzagenin, isoagatharesinol, friedelin, inophynone and eugenol were active against S. aureus. This study provided in-vitro proof for the flora of Pakistan used against different infections caused by S. aureus. Conclusions: Antibacterial agents from natural sources could be more effective against bacterial pathogens and will be helpful in minimizing the adverse effects of synthetic drugs, and hence provides a base for the pharmaceutical industries. http://www.apjtm.org/article.asp?issn=1995-7645;year=2018;volume=11;issue=6;spage=355;epage=368;aulast=Adnan;type=2.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the main component in hot peppers, including red chili peppers, jalapenos, and habanero, belonging to the genus Capsicum. Capsaicin is a potent antioxidant that interferes with free radical activities. In the present study, the possible protective effect of capsaicin was studied against methyl methanesulphonate (MMS) induced toxicity in third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ)Bg. The third instar was allowed to feed on the diet having different doses of capsaicin and MMS separately and in combination. The results suggested that the exposure of third instar larvae to the diet having MMS alone showed significant hsp70 expression as well as tissue DNA and oxidative damage, whereas the larvae feed on the diet having MMS and capsaicin showed a decrease in the toxic effects for 48-h of exposure. In conclusion, capsaicin showed a dose-dependent decrease in the toxic effects induced by MMS in the third instar larvae of transgenic Drosophila melanogaster.
Acetylcholinesterase ; metabolism ; Animals ; Animals, Genetically Modified ; Anticarcinogenic Agents ; pharmacology ; Capsaicin ; pharmacology ; DNA Damage ; drug effects ; Drosophila melanogaster ; drug effects ; Larva ; drug effects ; Methyl Methanesulfonate ; antagonists & inhibitors

Objective: Wharton jelly-derived mesenchymal stem cells (WJMSCs) exhibit multilineage differentiation potential and can be used to treat multiple organs. However, diabetes affects the repair capability of MSCs. The aim of this study was to evaluate the effect of diabetic patient-derived serum on WJMSC behavior. Methods: WJMSCs at passage 3 were treated with serum derived from type 2 diabetic patients. WJMSCs were characterized for surface markers expression by using immunocytochemistry technique. The effects on cell viability, proliferation, cell death rate, and vascular endothelial growth factor level were assessed by crystal violet staining, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphe-nyltetrazolium bromide (MTT) assay, lactate dehydrogenase assay, and enzyme-linked immuno-sorbent assay, respectively. Oxidative stress was assessed by the estimation of free radical species malondialdehyde (MDA) and enzymes glutathione (GSH), catalase, and superoxide dismutase (SOD). Results: WJMSCs isolated in this study were positive for CD29, CD49, CD73, CD90, CD105, and SSEA4 and negative for CD45 and CD34. Under diabetic stress conditions, WJMSCs showed low viability and high lactate dehydrogenase release. A low level of vascular endothelial growth factor was also observed after diabetic serum treatment. Antioxidant level was also lower in diabetic serum-treated WJMSCs compared to in normal serum-treated WJMSCs. Conclusion: The results of the present study suggest that pre-treatment of WJMSCs with type 2 diabetic serum decreases the survival of WJMSCs. The findings of this study provide insight into diabetes-induced harmful effects on WJMSCs.