Frequency of side effects of sofosbuvir and daclatsavir in patients of chronic Hepatitis C

Objective: To evaluate side effects of direct acting antivirals for hepatitis C patients.Study Design: Descriptive case series.Setting: Hepatitis Clinic, Medical Unit II, Jinnah Hospital Lahore.Duration Of Study: three months starting from 1st Dec 2018 to 28th Feb 2019. Subjects And Methods: Forty patients meeting the inclusion criteria were included in the study. All patients were then given direct anti-virals for a period of three months. Patients were called after every four weeks and observed for the presence of side effects like fever, fatigue, malaise, generalized weakness, myalgia, nausea and vomiting. Data was entered and analyzed in SPSS version ver.21.0. Frequency and percentages were calculated for demographic and clinical profile and side effects. Mean and Standard deviation was calculated for biochemical values at base line and end of therapy. Chi-square test was used to assess side effects among age, gender and duration of disease and paired t test for biochemical parameters with p < .05 as statistical significance. Results: Mean age of the patients was 39 years + 11.6. Fever was recorded in 72.5% fatigue was seen in 52.5%, malaise was recorded in 37.5% and generalized weakness was noticed in 37.5. Myalgia was recorded in 12.5% and nausea and vomiting were reported in 2.5% of patients. . (p> .05). There was a statistically significant difference between mean baseline and at end treatment values for AST, ALT, AP and TLC. ( P< .05). Conclusion: Our study concluded that along with efficacy advantage of DAA therapy, their safety profile is acceptable in terms of adverse drug reaction of immediate or during treatment however long term follow up is needed to ascertain and apprehend the safety matters linked with the utilization of DAAs. Key Words: Direct acting antivirals (DAAs), side effects, chronic hepatitis C

Detection of aflatoxins and zearalenone contamination in wheat derived products

In present study the natural occurrence of aflatoxins (AFs) and zearalenone (ZEN) has determined in 147 samples of wheat derived products i.e. spaghetti (25), noodles (34), macaroni (29), lasagne (37), and bucatini (22), collected from major districts of Punjab, Pakistan. The mean of AFs was found 9.12 in spaghetti, 7.35 in noodles, 5.91 in macaroni, 8.39 in lasagne, and 9.61 μg/kg in bucatini and 28, 18, 17, 22 and 27% of samples were found above the European Union's legal limit (i.e. 4 μg/kg) for total AFs, respectively. However, mean value of ZEN was found 7.36 in spaghetti, 6.80 in noodles, 4.98 in macaroni, 6.90 in lasagne, and 8.89 μg/kg in bucatini samples and 16, 15, 21, 19 and 36% of samples were found to be above the recommended limit. The study urged the need to focus more comprehensive survey for these toxins in wheat derived products from Punjab, Pakistan

Comparison of transgenic plant production for bacterial blight resistance in Pakistani local rice (Oryza sativa L.) cultivars

The study was carried out to improve bacterial leaf blight resistance in three rice cultivars (Basmati - 370, DR - 82 and IR - 6) by Agrobacterium mediated transformation system. Three week-old scutellum derived calli were infected with Agrobacterium strain EHA101, containing binary vector pTCL5 which has Xa 21 gene. Different levels of acetosyringone were tested to enhance transformation efficiency. Acetosyringone at 300 ìM showed 56.6% GUS expression with 100 and 200 ìM acetosyringone showing 13.3 and 30.0% GUS expression, respectively. Maximum transformation efficiency was obtained using DR - 82 with calli exposed to 300 ìM acetosyringone for 2 min. Direct hygromycin selection with 48 h ofco-cultivation was superior to pre-selection in all three cultivars. Transient GUS expression was 51.4% while stable GUS expression in calli was 18.8%. PCR analysis confirmed the presence of the Xa 21 gene in transformed regenerated plants. Stable varietal transformation efficiency was DR - 82 > Basmati-370 > IR - 6. Resistance of transgenic plants against Xanthomonas oryzae pathovar oryzae was evaluated with various strains/isolates at the seedling stage. All PCR positive transgenic plants of DR - 82 and Basmati - 370 were resistant with lesion areas less than 5% of the inoculated leaf area. The tested transgenic plants were resistant to all the indigenous and exotic strains tested due to the broad spectrum protection provided by the Xa 21 gene

Sequence and phylogenetic analysis of virulent Newcastle disease virus isolates from Pakistan during 2009–2013 reveals circulation of new sub genotype

AbstractDespite observing the standard bio-security measures at commercial poultry farms and extensive use of Newcastle disease vaccines, a new genotype VII-f of Newcastle disease virus (NDV) got introduced in Pakistan during 2011. In this regard 300 ND outbreaks recorded so far have resulted into huge losses of approximately USD 200 million during 2011–2013. A total of 33 NDV isolates recovered during 2009–2013 throughout Pakistan were characterized biologically and phylogenetically. The phylogenetic analysis revealed a new velogenic sub genotype VII-f circulating in commercial and domestic poultry along with the earlier reported sub genotype VII-b. Partial sequencing of Fusion gene revealed two types of cleavage site motifs; lentogenic 112GRQGRL117 and velogenic 112RRQKRF117 along with some point mutations indicative of genetic diversity. We report here a new sub genotype of virulent NDV circulating in commercial and backyard poultry in Pakistan and provide evidence for the possible genetic diversity which may be causing new NDV out breaks

Global review of the H5N8 avian influenza virus subtype

Orthomyxoviruses are negative-sense, RNA viruses with segmented genomes that are highly unstable due to reassortment. The highly pathogenic avian influenza (HPAI) subtype H5N8 emerged in wild birds in China. Since its emergence, it has posed a significant threat to poultry and human health. Poultry meat is considered an inexpensive source of protein, but due to outbreaks of HPAI H5N8 from migratory birds in commercial flocks, the poultry meat industry has been facing severe financial crises. This review focuses on occasional epidemics that have damaged food security and poultry production across Europe, Eurasia, the Middle East, Africa, and America. HPAI H5N8 viral sequences have been retrieved from GISAID and analyzed. Virulent HPAI H5N8 belongs to clade 2.3.4.4b, Gs/GD lineage, and has been a threat to the poultry industry and the public in several countries since its first introduction. Continent-wide outbreaks have revealed that this virus is spreading globally. Thus, continuous sero- and viro-surveillance both in commercial and wild birds, and strict biosecurity reduces the risk of the HPAI virus appearing. Furthermore, homologous vaccination practices in commercial poultry need to be introduced to overcome the introduction of emergent strains. This review clearly indicates that HPAI H5N8 is a continuous threat to poultry and people and that further regional epidemiological studies are needed

Benchmarking carbon fluxes of the ISIMIP2a biome models

The purpose of this study is to evaluate the eight ISIMIP2a biome models against independent estimates of long-term net carbon fluxes (i.e. Net Biome Productivity, NBP) over terrestrial ecosystems for the recent four decades (1971–2010). We evaluate modeled global NBP against 1) the updated global residual land sink (RLS) plus land use emissions (E LUC) from the Global Carbon Project (GCP), presented as R + L in this study by Le Quéré et al (2015), and 2) the land CO2 fluxes from two atmospheric inversion systems: Jena CarboScope s81_v3.8 and CAMS v15r2, referred to as F Jena and F CAMS respectively. The model ensemble-mean NBP (that includes seven models with land-use change) is higher than but within the uncertainty of R + L, while the simulated positive NBP trend over the last 30 yr is lower than that from R + L and from the two inversion systems. ISIMIP2a biome models well capture the interannual variation of global net terrestrial ecosystem carbon fluxes. Tropical NBP represents 31 ± 17% of global total NBP during the past decades, and the year-to-year variation of tropical NBP contributes most of the interannual variation of global NBP. According to the models, increasing Net Primary Productivity (NPP) was the main cause for the generally increasing NBP. Significant global NBP anomalies from the long-term mean between the two phases of El Niño Southern Oscillation (ENSO) events are simulated by all models (p < 0.05), which is consistent with the R + L estimate (p = 0.06), also mainly attributed to NPP anomalies, rather than to changes in heterotrophic respiration (Rh). The global NPP and NBP anomalies during ENSO events are dominated by their anomalies in tropical regions impacted by tropical climate variability. Multiple regressions between R + L, F Jena and F CAMS interannual variations and tropical climate variations reveal a significant negative response of global net terrestrial ecosystem carbon fluxes to tropical mean annual temperature variation, and a non-significant response to tropical annual precipitation variation. According to the models, tropical precipitation is a more important driver, suggesting that some models do not capture the roles of precipitation and temperature changes adequately

Increasing access to integrated ESKD care as part of Universal Health Coverage

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle–income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed