Sustained virological response to antiviral drugs in treatment of different genotypes of HCV cirrhotic patients.

Cirrhosis and liver cancer are both caused by hepatitis C virus (HCV) infection of the liver. Patients with HCV cirrhosis may be treated with one of many antiviral medications, depending on their specific genotype. Samples of cirrhotic HCV were obtained from 190 people at the Khyber Teaching Hospital and the Hayatabad Medical Complex in Peshawar, Pakistan. Multiplex and real-time PCR were used to assess the genotypes and viral loads of the samples, respectively. Sixty patients were given sofosbuvir plus daclatasvir with ribavirin, while the remaining 56 patients were given sofosbuvir with ribavirin for a period of 12-24 weeks. LFTs were also tracked both before and after therapy. Group I (sofosbuvir + daclatasvir) had a sustained virological response of 82.70 percent. Group II (sofosbuvir + daclatasvir with ribavirin) had an 86% sustained virological response, whereas group III (84% sustained virological response) received only ribavirin. When compared to other genotypes, genotype 3 showed the most impressive sustained virologic response (SVR) to the antiviral medicines. Based on the results of this trial, we propose sofosbuvir + daclatasvir ribavirin for the treatment of cirrhotic patients with various HCV genotypes since it produces the greatest sustained virological response.

Evaluation of therapeutic potential and anti-hyperchlostrolemic effects of prunes in albino rats: An experimental study.

Hyperlipidemia is a global epidemic that causes various cardiovascular diseases (CVDs). Prunes include fiber and numerous phenolic compounds that decrease cholesterol by decreasing LDL oxidation and supporting heart health. This study examined the therapeutic effects of Prunus domestica prunes on plasma fatty acids in albino rats after ingesting prune pulp. After chemical examination, prunes were proximately examined for nutritional content. Prunus domestica pulp was given to hyperlipidemic rats for two months in a clinical trial. 12 albino rates and divide into 3 groups. First group was controlled, others experimental. The study's 15th, 30th and 60th days evaluated lipid profile. The following study was analyzed using 2 way anova. Prunes have enough fiber, minerals and polyphenols to affect hyperlipidemic rats. GIII rats lower LDL, weight, and HDL more than GI and GII.

Investigating the effect of selenium nano-particles on microbial activity and cancerous cell line of MCF-7 and MDA-MB-231.

Selenium is a mineral that is essential to human health and is widely recognized for its responsibilities as a powerful anticancer vitamin and antibacterial vitamin. Selenium also plays a critical part in the production of vitamin D. The purpose of this research was to evaluate the particular effects that selenium nano-particles (SeNPs') had on the infectious agent Staphylococcus aureus as well as the breast cancer cell lines MCF-7 and MDA-MB-231. The proportion of MDA-MB-231 and MCF-7 cells that underwent late apoptosis was dramatically increased by selenium nanoparticles, whereas the number of cells that underwent cell expansion was significantly reduced. There was a wide range of variability in the effects of selenium nanoparticle treatment on cell growth apoptosis, apoptosis rates and patterns of cell cycle arrest. After 2, 4 and 6 hours, researchers found that the development of S. aureus was significantly reduced by selenium nanoparticles at doses of 8.0, 16.0 and 32g/mL. In addition to this, the presence of selenium nanoparticles resulted in a reduced percentage of bacteria that were still alive. According to the findings of the study, there is a need for more research into selenium nanoparticles with the intention of preventing and treating infections caused by S. aureus.

SARS-CoV-2: big seroprevalence data from Pakistan-is herd immunity at hand?

PURPOSE: Seroprevalence surveys from different countries have reported SARS CoV-2 antibodies below 20% even in the most adversely affected areas and herd immunity cannot be predicted till more than half of the population gets the disease. The purpose of this survey was to estimate the magnitude of community-based spread of the infection, associated immunity, and the future prospects and proximity to a 'herd community'. METHODS: The study was undertaken as a cluster randomized, cross-sectional countrywide survey. This largest community-based seroprevalence data of SARS-CoV-2 were collected between 15th and 31st July, 2020 from seven randomly selected cities belonging to the three most populous provinces of Pakistan. The FDA approved kit of ROCHE was used for detection of SARS-CoV-2 antibodies. RESULTS: Serum samples of 15,390 participants were tested for SARS CoV-2 antibodies with an overall seroprevalence of 42.4%. The seroprevalence ranged from 31.1% to 48.1% in different cities with the highest in Punjab province (44.5%). In univariable analysis, the odds of seropositivity was higher in men compared to women (OR: 1.10, 95% CI: 1.01-1.19, P < 0.05). In multivariable analysis, the risk of being seropositive was lower (OR 0.72, 95% CI: 0.60-0.87, P < 0.01) in younger group (≤ 20 years) than in those aged above 60 years. CONCLUSION: The study concluded that despite a reasonable seroprevalence, the country is yet to reach the base minimum of estimations for herd immunity. The durability of immunity though debated at the moment, has shown an evidenced informed shift towards longer side.

Serum p53 antibodies detection in oral squamous cell carcinoma, oral potentially malignant disorders and healthy individuals: A multicentre study.

OBJECTIVE: To detect antibodies against p53 in serum of patients of oral squamous cell carcinoma and oral potentially malignant disorders compared to healthy individuals. METHODS: The descriptive cross-sectional study was conducted at the departments of Oral and Maxillofacial Surgery, Peshawar Dental College, Peshawar, Khyber College of Dentistry, Peshawar, and the Pakistan Institute of Medical Sciences, Islamabad, Pakistan, from April, 2016 to March, 2017, and comprised serum of oral squamous cell carcinoma patients in group A, oral potentially malignant disorder patients in group B and healthy individuals in group C. Serum concentrations of anti-p53 antibodies were determined by enzyme-linked immunosorbent assay. Data was analysed using SPSS 20. RESULTS: Of the180 subjects, there were 60(33.3%) in each of the three groups. Circulating serum p53 antibodies were detected in 59(98.3%) cases in group A, 58(96.6%) in group B and in 20(33.3%) individuals in group C (p=0.001). CONCLUSIONS: The expression of circulating p53 antibodies in serum samples of squamous cell carcinoma and oral potentially malignant disorders patients indicates the potential to be a probable candidate for being taken as a diagnostic or prognostic biomarker.

Genome wide association study and phylogenetic analysis of novel SARS-COV-2 virus among different countries.

Corona Virus (COVID-19) outbreak has threatened the world, since it has become pandemic and spread all over the world. The causative agent SARS-COV2 has proved lethal caused serious public health concern worldwide. Our aims were to describe the SARS-COV-2 genetic connections and check for recombination of all genome. The recombination was investigated by RDP5 and conflicting phylogenetic clustering in individual genomic fragments was established by phylogenetic study by maximum likelihood and Bayesian methods. Our analysis suggests that the available sequences from currently genomes of various strain were retrieved from different countries including Japan, French Republic, Spain, Peru, China, Vietnam, Taiwan, Brazil, U.S.A., South Korea, Sweden, Australia, Nepal, India, Iran, and Italy. The phylogeny of SARS-COV-2 observed the largest number of genome is Vietnam 29891-bp, while France is the smallest member identified with 29679-bp. Using Recombination Detection program5 (RDP5) the china strains was taken as parental strain but there were no recombination in the all strains. In our study we identified the mutation in Pakistani strains in high conserved region of Corona nucleoca super family domain at the nucleotide position (394: C replace with T, Position: 858: C replace with T and Position: 997 G replace A).

Anti-nucleocapsid IgG antibodies in SARS-CoV-2 recovered health care workers: One year follow-up study.

Objective: The objective of this study was to evaluate the magnitude and durability of the anti-nucleocapsid-IgG antibody titer in healthcare workers previously infected with SARS-CoV-2 for a period of 12 months.Methods: This study examined blood samples for SARS-CoV-2-specific IgG collected periodically from 120 healthcare workers previously infected with SARS-CoV-2 (confirmed by RT-PCR) and followed longitudinally up to 12 months from their enrolment into the study.Results: The median anti-N-IgG antibody level identified at 3 months was 23.7 CO-index (IQR: 9.13-50.27) and increased to 32.9 CO-index (IQR: 11.8-84.4) at 6 months. At 9 months, the median anti-N-IgG antibody level started to wane in the subsequent time and was dropped to 14 CO-index (IQR: 3.4-37.6) and declined further to 9.8 CO-index at 12 months (IQR: 2.8-9.8). When classified by age groups, the only statistically significant difference in anti-N-IgG between the two age groups (≤30 years and >30 years) was identified at 12 month time point (median difference 8.06, p = 0.035). Spearman correlation coefficient was negatively associated between anti-N-IgG and time interval (r = -0.255, p = 0.000) but was not statistically significant with age of a patient (p > 0.05).Conclusions: In conclusion, SARS-CoV-2 antibody levels started declining after 6 months but remained detectable in the majority of patients up to 12 months.

Predictive Potential Of Il28b Gene In Hcv Patients, Resistant To Daclatasvir And Sofosbuvir In KPK Population.

Background: Recently various combinations of direct acting antivirals (DAAs) have been tried successfully. The Sofosbuvir + Daclatasvir combination has been used with promising results. Recently, resistance has been noticed against DAAs. Therefore, polymorphism at particular sites in the interleukin 28B gene are under study to find possible association with resistance. This study was aimed at finding out any association of SNPs rs8099917 and rs12979860 (IL28B gene) with response and resistance to treatment in HCV genotype 3 patients in Khyber Pakhtunkhwa. Methods: This cross sectional, Analytical study was conducted at Gastroenterology/hepatology OPD of Prime Teaching Hospital, Peshawar Medical College. Collected Samples were stored at -20o C in PCR Lab of the College. DNA extraction and genotyping was carried out at BJ Molecular Biology Lab in Rawalpindi. Data was analyzed by using SPSS version 21. Chi-Square Test was used to see the statistically significant differences between rs8099917 T/G and rs12979860 T/C model. Results: In the IL28-B gene, single nucleotide polymorphism at rs12979860 T/C model, we observed that there are 37.5% CC homozygous, 12.5% TT homozygous and 50% CT heterozygous genotypes in resistant patients and 42.85% CC homozygous, 28.57% TT and 28.57% CT genotype in responder group. In rs12979860 T/C model, genotype of IL28-B in the responder and resistant group significantly varies at p-value =0.00572. Conclusion: We conclude that in SNP at rs12979860, CC genotype is associated with clearance of HCV, while CT genotype was more prevalent in the resistant group and associated with chronicity.

Incidence of SARS-CoV-2 re-infection in anti-nucleocapsid IgG-positive healthcare workers: a prospective cohort study.

BACKGROUND : Since the pandemic of SARS-CoV-2 began, our understanding of the pathogenesis and immune responses to this virus has continued to evolve. It has been shown that this infection produces natural detectable immune responses in many cases. However, the duration and durability of immunity and its effect on the severity of the illness are still under investigation. Moreover, the protective effects of antibodies against new SARS-CoV-2 variants still remain unclear. OBJECTIVES: To assess the incidence and associated demographic features of SARS-CoV-2 infection in anti-nucleocapsid IgG-positive and anti-nucleocapsid IgG-negative healthcare workers. MATERIAL AND METHODS: This prospective longitudinal cohort study was conducted in Peshawar Medical College group of hospitals of Prime Foundation. Anti-nucleocapsid IgG sero-positive and anti-nucleocapsid IgG sero-negative healthcare workers were followed for a period of 6 months (from 1 Aug 2020 to 31 Jan 2021), and the incidence of SARS-CoV-2 was confirmed by RT-PCR. RESULTS: A total number of 555 cohorts were followed for a period of 6 months; of them 365 (65.7%) were anti-nucleocapsid-negative (group A) and 190 (34.3%) were anti-nucleocapsid-positive (group B) healthcare workers. The mean age of the study cohort was 33.85 ± 9.80 (anti-N (-), 34.2 ± 10.58; anti-N ( +), 33.5 ± 9.50). The median antibody level in anti-nucleocapsid-positive HCWs was 15.95 (IQR: 5.24-53.4). Male gender was the majority in both groups (group A, 246 (67%), group B, 143 (48%)) with statistically significant difference (P < 0.05). Majority of the HCWs were blood group B in both groups (34% each). None of the 190 anti-nucleocapsid-positive HCWs developed subsequent SARS-CoV-2 re-infection, while 17% (n = 65) HCWs developed infection in anti-nucleocapsid-negative group during the 6-month follow-up period. CONCLUSION: In conclusion, none of the anti-nucleocapsid-positive HCWs developed SARS-CoV-2 re-infection in this study, and the presence of IgG anti-nucleocapsid antibodies substantially reduce the risk of re-infection for a period of 6 months.

Predictors of Mortality in Patients With Dengue Fever: Insights From a Comparative Analysis.

Objective To determine the clinical and biochemical predictors of mortality in patients with dengue fever. Methods This was an analytical, cross-sectional study conducted at Hayatabad Medical Complex, Peshawar, Pakistan. The study participants were patients admitted to the hospital for the management of dengue fever. Clinical parameters (age, gender, duration of hospital stay, and the presence of complications) and biochemical parameters [white blood cells count (WBC), platelet count, serum c-reactive protein (CRP) level, serum alanine aminotransferase (ALT) level, and serum creatinine] were recorded. These parameters were compared between the survivors and non-survivors of dengue fever. Results Out of 115 patients, the majority (n=82, 71.3%) were up to 45 years and the mean age was 38.40 ± 18.1 years. Most of the patients (n=105, 91.3%) survived. On univariate logistic regression analysis, age more than 45 years [odds ratio (OR) 0.141, 95% confidence interval (CI) 0.034 - 0.585, p = 0.007), leukocytosis (> 11,000/mcL) (OR 0.187, 95% CI 0.049 - 0.719, p = 0.015), and acute kidney injury (creatinine > 1.5 mg/dL) (OR 0.124, 95% CI 0.029 - 0.531, p = 0.005)] at the time of admission reduced the likelihood to survive. Leukocytosis and acute kidney injury remained significant independent predictors of mortality on multivariate logistic regression analysis. [(OR 0.201, 95% CI 0.042 - 0.960, p = 0.044) and (OR 0.148, 95% CI 0.026 - 0.857, p = 0.033) for survival, respectively]. Gender, duration of inpatient stay, thrombocytopenia (platelets < 30,000/mcL), and acute liver injury (ALT > 200 IU/L) were not associated with mortality from dengue fever. Conclusion Age over 45 years, leukocytosis, and acute kidney injury at presentation increased the likelihood of mortality from dengue fever in this study. Gender, duration of hospital stay, thrombocytopenia, and acute liver injury did not affect the odds of mortality.

Description of clinicopathological characteristics of oral potentially malignant disorders with special focus on two histopathologic grading systems and subepithelial inflammatory infiltrate.

OBJECTIVE: This study was conducted to evaluate the clinicopathological features of oral potentially malignant disorders (OPMDs) with a focus on two histologic grading systems and subepithelial inflammatory infiltrates. MATERIALS AND METHODS: This cross-sectional and multicenter study was conducted from April 2016 to September 2021 and comprised patients diagnosed with OPMDs. Hematoxylin and eosin-stained slides of 127 cases were assessed based on the World Health Organization (WHO) 2005 classification system, namely, epithelial precursor lesions and binary system of oral epithelial dysplasia (OED). Chi-square test and Fisher's exact test were used to compare different categorical variables related to OPMDs. RESULTS: The mean age of OPMD cases at presentation was 54.72 13.30 (P < 0.01) with a male to female ratio of 1.6:1. Oral leukoplakia (52.8%) was the most commonly diagnosed form of OPMD. Most OPMDs were classified as oral epithelial hyperplasia (59.1%) and the remaining (40.9%) as OED (P < 0.01). Of the 52 OPMDs with OED, all cases of mild dysplasia (36.5%) and carcinoma in situ (9.6%) were categorized as low-risk and high-risk lesions, respectively. Chronic inflammatory infiltrate (79.5%) was the most common subepithelial inflammatory alteration observed among OPMDs. CONCLUSIONS: Early detection of OPMDs is vital due to increased risk of developing into oral cancer. Timely clinicopathological risk assessment of OPMD is desirable for improving the prognosis and preventing the malignant transformation in oral premalignancy. Besides the epithelial precursor lesions' classification by the WHO, binary system of grading OED use can be encouraged. Also, subepithelial inflammatory infiltrate can be of importance in future research regarding OPMDs.

Predictive value of tissue p53 protein expression and serum p53 antibodies in oral potentially malignant disorders: Relative to oral squamous cell carcinoma.

Objective: This study aims to assess and report the predictive value of tissue p53 protein expression and serum p53 antibodies as a screening tool for oral potentially malignant disorders (OPMDs) cases with risk of malignant transformation. Methods: A case-control study was jointly conducted at the Department of Pathology and Oral and Maxillofacial Surgery in several dental institutes in the country from April 2016 to March 2017. A total of 180 eligible subjects (60 cases of OPMDs, 60 cases of oral squamous cell carcinoma, and 60 controls) were included in the study. Tissue p53 immunoreactivity was determined by immunohistochemistry, and serum concentrations of p53 antibodies were determined by enzyme-linked immunosorbent assay. Specimens were collected for laboratory investigations after obtaining written consent from both patients and controls. Results: Among the study participants, the recorded male to female ratio was close to 2:1, and most participants fell in the age range of 41-60 years and above. Of the 60 cases of OPMDs, the observed tissue p53 immunopositivity was 73.3% (n = 44) while for the p53 antibody, the seropositivity was 96.7% (n = 58). The sensitivity for p53 immunoreactivity was 73%, and specificity was 98.3% between OPMDs and healthy individuals. Conclusion: The present study provides evidence (for OPMDs) that serum p53 antibodies and p53 immunoreactivity could be used as a sensitivity test and a specific test, respectively, and may contribute to determining the potential of OPMD for malignant transformation risk.

Identifying higher risk subgroups of health care workers for priority vaccination against COVID-19.

Background: Health care workers (HCWs) are exposed to high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to close contact with infected patients in hospital. The objective of this study was to estimate the seroprevalence and to identify the exposure risk of various subgroups among HCWs to prioritize them for early vaccination. Methods: This was a multicentre cross-sectional study conducted between 15 and 29 June 2020. A total of 987 HCWs were recruited randomly from two major tertiary-care hospitals of Peshawar city, Pakistan. The HCWs included doctors, nurses, paramedics and hospital support staff. The US Food and Drug Administration (FDA)-approved kit was used for the detection of SARS-CoV-2 antibodies. Results: Overall, 310 (31.4%) HCWs were seropositive for SARS-CoV-2 antibodies (95% confidence interval, CI: 28.5-34.4). Seroprevalence was higher in males (33.5%) and in age group 51-60 years (40.9%). Seropositivity increased with increasing age from 8.3% in age group ⩽20 to 40.9% in 51-60 years of age group (p < 0.05). The highest seroprevalence was identified in paramedical staff (42·5%, 95% CI: 36.6-48.6) followed by nursing staff (38·8%, 95% CI: 32.1-45.7). In logistic regression, being a male HCW led to higher risk of seropositivity (odds ratio, OR: 1.50, 95% CI: 1·06-2.13. p < 0.05) compared with female staff members. The odds of seropositivity was higher in nurses (OR: 3·47, 95% CI: 1.99-6.05. p < 0.01), paramedical staff (OR: 3·19, 95% CI: 1.93-5.28. p < 0.01) and hospital support staff (OR: 2·47, 95% CI: 1.29-4.7. p < 0.01) compared with consultants. Conclusion: Overall, our results concluded that nursing and paramedical staff are at higher risk and should be vaccinated on priority.

Incidence of Dengue fever, serotypes, clinical features, and laboratory markers: a case study of 2019 outbreak at district Shangla, KP, Pakistan.

Background: Dengue is a widely spread mosquito-borne infection in humans, which in recent decades declared is public health problem globally. The dengue virus contains 4 different serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) which belong to the genus Flavivirus. Aims: A descriptive experimental study was conducted to determine the epidemiology, types of Dengue serotypes, clinical features, laboratory probe, and markers for primary diagnosis of dengue virus infection in hospitalized patients. Methodology: A total of 691 suspects were diagnosed from August to October 2019 in district Shangla KP, Pakistan. Serological tests were used for nonstructural protein-1 antigen (NS1), and antibodies (immunoglobulin-M (IgM) & Immunoglobulin-G (IgG)) while real-time PCR was used to confirm the cases. The data was statistically analyzed using IBM-SPSS Statistics 20 version. Results: The dengue virus infection was more prevalent in the male group (68.09%) than the female group (31.1%). A large number of patients were from rural areas (63.5%) while from urban areas were (36.4%), whereas Besham tehsil was found the most affected compared to other regions. The most prevalent serotype observed in our study was DENV-3 (56.60%) while DENV-4 was the least prevalent serotype (1.88%). Among the age-wise analysis of dengue-virus-infected individuals, the age group of 19-37 years (64.07%) was found the most affected group. The month-wise analysis revealed that the highest number of infections (49.8%) were recorded in September. Significant differences were noticed among blood parameters. Conclusion: The possible reasons for the dengue overwhelming in the study area could be less or lack of awareness particularly regarding the transmission of viral infections, improper sewage management, and no effective vector control strategies that lead the dengue outbreaks in the study population.

Does Working in a COVID-19 Receiving Health Facility Influence Seroprevalence to SARS-CoV-2?

Objective In this study, we aimed at comparing the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in healthcare workers (HCWs) in coronavirus disease 2019 (COVID-19) receiving and non-COVID-19 receiving hospitals in Peshawar, Pakistan. Methods This cross-sectional analytical study was conducted in a COVID-19 receiving hospital (hospital 'A') and a non-COVID-19 receiving hospital (hospital 'B'). Using stratified random sampling, 1,011 HCWs (439 from hospital 'A' and 572 from hospital 'B') were recruited to participate in the study. Immunoglobulin G/immunoglobulin M (IgG/IgM) antibodies were checked using Elecsys® (Roche, Basel, Switzerland) Anti-SARS-CoV-2 immunoassay. The chi-squared test was used to compare frequencies, and the binary logistic regression model was used to predict the association between study variables' seropositivity to SARS-CoV-2. A p-value of <0.05 was considered statistically significant. Results The overall seroprevalence to SARS-CoV-2 antibodies in the two hospitals was 30.76%. It was 28.2% in hospital 'A' and 32.7% in hospital 'B' (p=0.129). The seroprevalence in HCWs having direct contact with COVID-19 patients was higher (33.1%) in non-COVID-19 receiving hospital versus 23.8% in COVID-19 receiving hospital (p=0.034). Seroprevalence was highest among administrative staff (44.0%), followed by nurses (30.8%), residents (19.8%), and consultants (17.8%) (p=0.001). As compared to consultants, the administrative and nursing staff were 3.398 and 3.116 times more likely to have positive antibodies, respectively. There were no significant differences in the seroprevalence between the respective categories of staff of the two hospitals. Conclusions The non-COVID-19 receiving hospital had a higher proportion of seropositive HCWs than the COVID-19 receiving hospital. The HCWs in the non-COVID-19 receiving hospital who had direct contact with patients had significantly higher seroprevalence. Seroprevalence was highest for administrative staff followed by nursing staff, residents, and consultants. Regardless of the COVID-19 status of the healthcare facility, all HCWs shall be trained on, and consistently follow, the proper protocols for donning and doffing of personal protective equipment (PPE).