Effectiveness of Ivermectin among COVID-19 patients: A Randomized Controlled Trial

Objectives: To determine the effectiveness of Ivermectin among COVID-19 patients in terms of mortality and biochemical / hematological attributes. Materials and Methods:  A Randomized Controlled Trial (RCT) was carried out in Department of Infectious Diseases (DID) of Holy Family Hospital Rawalpindi during March 2021 through concurrent parallel study design. Apart from seeking Ethical approval for this research, DID was also licensed from Drug Regulatory Authority of Pakistan (DRAP) for this trial. Total 90 PCR positive COVID-19 patients were enrolled in this study via 1:1 randomization in experimental and control group without blinding. The control group received Standard of Care (SOC) starting from day 1 while experimental group was given SOC along with Ivermectin (200µg/kg) for 5 days. Study participants were assessed on day 0, 4, 7 and 10 for general symptoms through physical examination, blood oxygen saturation and diverse hematological and biochemical indicators in addition to adverse events. Data analysis was done by means of SPSS version 25.0. and Microsoft Excel 2010. Mean ± SD for age, length of hospital stay and time to PCR negativity were calculated. Independent sample t-test was applied to determine the mean difference in age, duration of hospital stay, time to PCR negativity, SpO2, oxygen supply, serum Hemoglobin, TLC, platelet count, Clinical Severity Score (CSS), urea and creatinine levels of both groups. The difference in secondary outcome (expiry / discharge) of both groups was compared by means of chi-square test. P-value ≤ 0.05 was considered significant. 95% Confidence Interval was also computed. Relative Risk (RR) was also measured to verify the effectiveness of Ivermectin in COVID patients Results: Males constituted the majority (56.7%) of our study participants. Statistically insignificant difference in mean age (P = 0.42) and mean length of hospital stay (P= 0.32) between experimental and control group subjects was observed. Mean time to PCR negativity was reported to be significantly less (P= 0.002) in experimental group. Significant improvement was seen in PCR negativity (P<0.05), mean Clinical Severity Score (CSS) (P0.02), mean hemoglobin level (P=0.03) and mean platelet count (P=0.03). Difference in health outcome of both groups was determined to be statistically insignificant (P<0.2, 95% CI (-0.20 – 0.12)). Relative Risk of 0.8 proved the protective effect of Ivermectin in COVID. Conclusion: Ivermectin was quite effective in reducing mortality and improving the health outcome in COVID-19 patients

Effectiveness of Ivermectin among COVID-19 patients: A Randomized Controlled Trial

Objectives: To determine the effectiveness of Ivermectin among COVID-19 patients in terms of mortality and biochemical / hematological attributes. Materials and Methods:  A Randomized Controlled Trial (RCT) was carried out in Department of Infectious Diseases (DID) of Holy Family Hospital Rawalpindi during March 2021 through concurrent parallel study design. Apart from seeking Ethical approval for this research, DID was also licensed from Drug Regulatory Authority of Pakistan (DRAP) for this trial. Total 90 PCR positive COVID-19 patients were enrolled in this study via 1:1 randomization in experimental and control group without blinding. The control group received Standard of Care (SOC) starting from day 1 while experimental group was given SOC along with Ivermectin (200µg/kg) for 5 days. Study participants were assessed on day 0, 4, 7 and 10 for general symptoms through physical examination, blood oxygen saturation and diverse hematological and biochemical indicators in addition to adverse events. Data analysis was done by means of SPSS version 25.0. and Microsoft Excel 2010. Mean ± SD for age, length of hospital stay and time to PCR negativity were calculated. Independent sample t-test was applied to determine the mean difference in age, duration of hospital stay, time to PCR negativity, SpO2, oxygen supply, serum Hemoglobin, TLC, platelet count, Clinical Severity Score (CSS), urea and creatinine levels of both groups. The difference in secondary outcome (expiry / discharge) of both groups was compared by means of chi-square test. P-value ≤ 0.05 was considered significant. 95% Confidence Interval was also computed. Relative Risk (RR) was also measured to verify the effectiveness of Ivermectin in COVID patients Results: Males constituted the majority (56.7%) of our study participants. Statistically insignificant difference in mean age (P = 0.42) and mean length of hospital stay (P= 0.32) between experimental and control group subjects was observed. Mean time to PCR negativity was reported to be significantly less (P= 0.002) in experimental group. Significant improvement was seen in PCR negativity (P<0.05), mean Clinical Severity Score (CSS) (P0.02), mean hemoglobin level (P=0.03) and mean platelet count (P=0.03). Difference in health outcome of both groups was determined to be statistically insignificant (P<0.2, 95% CI (-0.20 – 0.12)). Relative Risk of 0.8 proved the protective effect of Ivermectin in COVID. Conclusion: Ivermectin was quite effective in reducing mortality and improving the health outcome in COVID-19 patients

MicroRNA-145 replacement as a therapeutic tool to Improve TRAIL therapy

Pancreatic cancer (PanCa) is a third leading cause of cancer related deaths in US. Unlike other cancers, PanCa is highly resistant to TNF-related apoptosis-inducing ligand (TRAIL) that emerges as one of the most-promising therapy in clinical trials. Our group has previously identified microRNA-145 (miR-145) is downregulated in PanCa, the restoration of which inhibits tumor growth and enhances gemcitabine sensitivity. In this study, we have observed that miR-145 restoration in PanCa cells renders them sensitive to TRAIL treatment. Therefore, we have engineered unique superparamagnetic nanoparticles (SPs) for co-delivering miR-145 and TRAIL in PanCa for improving their therapeutic response to TRAIL. The results in this study demonstrate that acquired resistance to TRAIL in PanCa cells can overcome with the replacement of lost levels of miR-145 expression. Our SP nanoparticles were engineered to co-deliver miR-145 and TRAIL to PanCa cells, which resulted in simultaneous restoration of miR-145 and inhibition of acquired resistance to TRAIL. Combined actions of miR-145 and TRAIL markedly improve TRAIL-induced apoptotic effects in PanCa cells through the activation of an extrinsic apoptosis pathway pathway as indicated by activation of DR5, FLIP, FADD and enhanced expression of caspase-8/3. The co-delivery of miR-145 and TRAIL using SP nanoparticles inhibited tumorigenic characteristics of PanCa cells, which include proliferation, invasion, migration and clonogenicity. The results were reciprocated and got further confirmed with the inhibition of tumorsphere formation and in vivo tumorigencity in xenograft mice. Immunohistochemical staining of excised tumor tissues demonstrate an activation of death receptor pathway and subsequent expression of apoptotic markers. The study provides novel insights on two facades- how resistance of cancer cells to TRAIL-based pro-apoptotic therapies can be tackled, and how efficient intracellular delivery of TRAIL can be achieved. Our results suggest that acquired resistance to TRAIL can be overcome by co-delivery of miR-145 and pEGFP-TRAIL using SP nanoparticles

Further Decoding the Molecular Relationship Between Pancreatic Ductal Adenocarcinoma and Diabetes Mellitus

Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy, especially as there are no current reliable methods of screening. A significant relationship between PDAC and Diabetes Mellitus (DM), specifically a new onset of diabetes mellitus (NOD). The molecular network of PDAC and new onset DM is not completely understood. We sought to investigate the molecular network of these two diseases with the ultimate goal of identifying potential biomarkers to aid in the screening of PDAC. Methods: We conducted a review for relevant articles concerning the molecular relationship between PDAC and DM. We compiled a list of 74 genes which have been implicated in the relationship between PDAC and DM. These genes were used for the construction of gene interaction network (GIN) by using GeneMANIA on the bases of genetic interactions, co-expression, co-localization, pathway, physical interactions, predicted interaction and shared protein domains. The GIN input file was imported in the cytoscape for the pathways enrichment analyses by using KEGG plugin. The cytoscape was used for the construction of the final GIN of both normal and cancer genes separately. Results: GIN and pathways enrichment analyses of genes known to be altered during NOD/DM and PDAC indicate their association with different pathways. in this study we have mentioned around 20 enriched pathways in the associated tables and figures which promptly show the direct and indirect association with pancreatic cancer. The major signaling pathways that were observed to be upregulated include NABA Matrisome, protein phosphorylation, metabolic processes and proteins upregulated a s a result of hormone response. Out of all pathways, proteins that are more involved in metabolic processes were found most influenced. Conclusion: In conclusion, we have contributed to identifying the molecular network relating PDAC and DM. Our future aim is to investigate the genes associated in this pathway. We will use this data to design a panel for next generation sequencing in tissue samples of patients diagnosed with PDAC

Disparities and Microbiome Affecting Liver Disease Progression

Non-alcoholic fatty liver disease (NAFLD) is a metabolic illness that encompasses a wide range of pathological states, from simple steatosis to steatohepatitis (NASH) to cirrhosis and hepatocellular carcinoma. NAFLD is the most prevalent liver disease in the world, accounting for 25% of all liver diseases cases. A high-fat diet, smoking, and alcohol consumption have all been proven to disrupt the balance of beneficial and possibly pathogenic bacterial species, resulting in intestinal dysbiosis. The prevalence of liver cancer (LC) among Latinos in South Texas remains greater than elsewhere in the United States, necessitating further research on population-specific risk factors and aggressive mortality. Incidence rates among Hispanics are three to four times greater than among non-Hispanic whites. There are no precise molecular markers or imaging modalities that have the sensitivity or specificity to identify NAFLD patients at an early stage of illness or at a high risk of developing NASH/Cirrhosis or HCC and consider them candidates for early surgical intervention. Therefore, there is a need for the creation of non-invasive, selective molecular markers for detecting precursor lesions with dysplasia that advance to HCC. The makeup of the human gut microbiota, which is made up of hundreds of microbial species, can change with chronic illnesses that underpin health inequities that disproportionately afflict ethnic minorities. In this study, we explored the incidence and mortality rates of liver cancer in different ethnicities, Hispanics, African Americans, and non-Hispanic whites (NHW). Hispanics have the highest microbial richness and evenness in both study groups, followed by Non-Hispanic whites and Asian Pacific Islanders. Obesity, diabetes, and lifestyle changes, among other factors, have contributed to an increase in the number of instances of NAFLD in Hispanics. An increase in the number of Enterobacteriaceae, Veillonellaceae, and Streptococcaceae, as well as a reduction in the abundance of Lachnospiracea is witnessed in cirrhosis patients. There are different microbial fingerprints and interspecies interactions in several liver disorders that are susceptible to develop in HCC across ethnicities. Future studies are warranted to investigate the role of microbiota in conversion of NAFLD patients, role of microbiota in mediating HC

Prevalence of active hepatitis c virus infection in district mansehra pakistan

Prevalence of active hepatitis C virus (HCV) infection in apparently healthy inhabitants of District Mansehra, Pakistan was surveyed during September, 2009 to May, 2010. Subjects of different age and gender groups were analyzed through random blood sampling from people of three areas viz; Tehsil Mansehra, Tehsil Balakot and Tehsil Oghi. Sum of 400 individuals, 300 male and 100 females with age groups from 10 years to 50 and above were included in the study. All the individuals were screened for antibodies against HCV. The positive samples thus screened, were subjected to polymerase chain reaction (PCR) analysis for detection of HCV-RNA. The results showed that 3.5% of the people of District Mansehra are actively infected with HCV whereas 7% of the population in general, has the presence of antibodies against HCV in their blood. It was also concluded that the prevalence of active HCV infection was high 4% in males as compared to females (2%). The prevalence of HCV proportionality increases with the increase in age of the people. Its incidence was highest (7.69%) in the people of the age group of 51 years and above, whereas no sign of infection was recorded for the age group of 10-20 years

Analysis of cervical smears in a muslim population

Background: Screening for cancer of the cervix remains a neglected health care issue in Pakistan. To provide baseline data for future efforts to improve screening, we conducted a retrospective analysis of cervical smears taken in the obstetrics and gynaecological clinics of the Aga Khan University Hospital, Karachi, Pakistan.Method: We collected data on cervical smear cytology for cervical smears taken from January 1, 1990 to December 31,1996. We assessed risk factors for dysplasia, including age, age at first marriage, and number of pregnancies.Results: The overall prevalence of abnormal smears in our study was 0.5%. Of 20,995 cervical smears, 12,451 (59.3%) smears showed non-specific inflammation, 7302 (34.8%) were reported as normal, 809 (3.85%) showed monillial infection, 148 (0.71%) showed atypia, 105 (0.5%) had dysplastic cytology, and 52 (0.25%) samples were inadequate. The highest incidence of dysplastic smears was seen in the age group 35 to 44 years. Of 105 patients with dysplasia, 12 were pregnant, and all were asymptomatic, while in 93 non-pregnant women, 33 were symptomatic.Conclusion: The low prevalence of abnormal smears, compared with data from Western populations, could be due to the inherent bias of health awareness in the women who attended our hospital. The results of this study may serve as a baseline for future comparisons. A larger community-based study may establish the exact prevalence of malignant and premalignant lesions so as to plan for future screening

Organizational Performance and Entrepreneurial Orientation: The Intervening Role of Organizational Learning

Many past studies have examined the association between entrepreneurial orientation (E.O.) and organizational performance (O.P.). However, these studies have not adequately addressed the mediating roles of acquisition learning (A.L.) and experiential learning (E.L.) on organizational performance. Given this gap, we have developed a new model that contains six direct relationships, three mediating relationships, and one multi-mediating relationship. The focus of the study was on Indonesian Pharmaceutical SMEs. We have collected a sample of 365 respondents non-randomly. For statistical analysis, we have used Smart PLS version 3.2. The statistical analysis includes reliability, validity, and descriptive statistics. The results confirm that acquisition learning (A.L.), experiential learning (E.L.), and entrepreneurial orientation (E.O.) promote organizational performance (O.P.). We also found that entrepreneurial orientation (E.O.) impacts acquisition learning (A.L.) and innovative performance (I.P.) but does not affect organizational performance (O.P.). However, the results suggest that acquisition learning (A.L.) and experiential learning (E.L.) are positively linked. Our results also support all the mediating relationships