A Comprehensive Review: COVID-19 And Post-Covid Versus Thromboembolism

In spite of the fact that COVID-19 was previously predominantly believed to be a respiratory ailment, rapidly increasing data point to a significant prevalence of venous thromboembolic consequences in the disease. This review article's main goal was to determine if there was a requirement to raise knowledge of  PE (Pulmonary Embolism) in the aftermath of the COVID-19 outbreak given the still-weak epidemiologic data. The gathered studies were subjected to a critical evaluation and literature search. A digital search of Science Direct, Google Scholar, PubMed, and Scopus until June 2022. COVID-19’s lasting effects on health are yet mostly unknown. The pathophysiology of pulmonary embolism is highlighted in this review, along with the significance of being aware of the possible ways that enhanced the  risk of VTE (Venous Thromboembolism) in patients suffering from post- COVID-19, including those who have a moderate or asymptomatic illness. To define suitable clinical care recommendations for the avoidance of thromboembolic consequences in the critically sick and post-COVID-19 phase, further study is necessary.   &nbsp

Etravirine induced severe hypersensitivity reaction and fulminant hepatitis: A case report and review of the literature.

We report the first published case of etravirine induced hypersensitivity reaction leading to fulminant hepatic failure in a 49-year-old female patient with Human Immunodefi ciency Virus. She presented with a life threatening rash and end stage organ damage requiring intensive care unit supportive care. Liver biopsy supported the diagnosis of drug-induced hypersensitivity. The patient recovered after withdrawal of etravirine and the use of systemic corticosteroids. The authors describe etravirine drug hypersensitivity as a clinically important reaction and that early recognition can improve survival

Silica functionalized sulfonic acid catalyzed one-pot synthesis of 4,5,8a-triarylhex-ahydropyrimido[4,5-d]pyrimidine-2,7(1H,3 H)-diones under liquid phase catalysis

SiO2-SO3H catalyzed one-pot synthesis of 4,5,8a-triarylhexahydropyrimido[4,5-d]pyrimidine-2,7(1H,3 H)-diones (4a-k) is reported under liquid phase catalysis. The catalyst is easily prepared, highly stable, very simple to handle and recycled for five times without loss of significant activity

A randomized, controlled trial of initial anti-retroviral therapy with abacavir/lamivudine/zidovudine twice-daily compared to atazanavir once-daily with lamivudine/zidovudine twice-daily in HIV-infected patients over 48 weeks (ESS100327, the ACTION Study)

<p>Abstract</p> <p>Background</p> <p>Traditional first line regimens containing a non-nucleoside reverse transcriptase inhibitor or protease inhibitor may not be suitable for a subset of antiretroviral-naïve patients such as those with certain co-morbidities, women of child-bearing potential, and intolerability to components of standard first line therapy. This study was conducted to determine if alternate treatment options may meet the needs of both general and special patient populations. The ACTION study was a randomized, open-label, multicenter, 48-week trial that compared the safety and efficacy of a triple nucleoside regimen versus a protease inhibitor plus a dual nucleoside regimen in HIV-1 treatment-naïve subjects.</p> <p>Results</p> <p>279 HIV-infected subjects with HIV-1 RNA (VL) >5000 but < 200,000 copies/mL (c/mL) and CD4+ count ≥ 100 cells/mm³were randomized (1:1) to receive abacavir sulfate/lamivudine/zidovudine (ABC/3TC/ZDV) twice-daily or atazanavir (ATV) once-daily plus lamivudine/zidovudine (3TC/ZDV) twice-daily. Protocol-defined virologic failure was based on multiple failure criteria.</p> <p>Non-inferiority of ABC/3TC/ZDV to ATV+3TC/ZDV was established with 62% vs. 59% of subjects achieving a VL < 50 c/mL at week 48, [ITT(E), M/S = F, 95% CI: -5.9, 10.4]. Similar results were observed in the 230 (82%) subjects with baseline VL<100,000 c/mL (ABC/3TC/ZDV vs. ATV+3TC/ZDV), 66% vs. 59%; 95% CI: -5.6, 19.5. However, ABC/3TC/ZDV did not meet the non-inferiority criterion compared to ATV+3TC/ZDV in the 48 subjects with baseline VL ≥ 100,000 c/mL, 39% vs. 60%; 95% CI: -49.2, 7.4, respectively. Protocol-defined virologic failure was similar between groups.</p> <p>Conclusion</p> <p>ABC/3TC/ZDV demonstrated comparable virologic efficacy to ATV+3TC/ZDV in this population over 48 weeks. In those with a baseline VL ≥ 100,000 c/mL, subjects in the ATV+3TC/ZDV showed better virologic efficacy. Both regimens offer benefits in select therapy-naïve subjects.</p> <p>Trial Registration</p> <p>[Clinical Trials Identifier, NCT00082394].</p

Bezlotoxumab for prevention of recurrent Clostridium difficile infection in patients at increased risk for recurrence

Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II)

Whole genome expression profiles of yeast RNA polymerase II core subunit, Rpb4, in stress and nonstress conditions

Organisms respond to environmental stress by adopting changes in gene expression at the transcriptional level. Rpb4, a nonessential subunit of the core RNA polymerase II has been proposed to play a role in non-stress-specific transcription and in the regulation of stress response in yeast. We find that in addition to the temperature sensitivity of the null mutant of Rpb4, diploid null mutants are also compromised in sporulation and show morphological changes associated with nitrogen starvation. Using whole genome expression analysis, we report here the effects of Rpb4 on expression of genes during normal growth and following heat shock and nutritional starvation. Our analysis shows that Rpb4 affects expression of a small yet significant fraction of the genome in both stress and normal conditions. We found that genes involved in galactose metabolism were dependent on the presence of Rpb4 irrespective of the environmental condition. Rpb4 was also found to affect the expression of several other genes specifically in conditions of nutritional starvation. The general defect in the absence of Rpb4 is in the expression of metabolic genes, especially those involved in carbon metabolism and energy generation. We report that various stresses are affected byRPB4 and that on overexpression the stress-specific activators can partially rescue the corresponding defects

Virosome: A vector in vaccine delivery

These days vaccines are considered the best economical and effective technique for preventing and handling bacterial infections, like human papillomavirus (HPV) or meningitis, allergies, autoimmune Relevant Disorders, Microbial Infections, and many more viral diseases. Annually millions of lives are saved from death-causing infections and other relevant disorders with the help of proper immunization with the help of vaccines. But still, many diseases are not yet preventable by vaccines and there is a chance of the improvement of current vaccines with help of many approaches. One of these is a compound known as a virosome, which is produced when pure haemagglutinin and neuraminidase projections of the influenza virus surface are removed from viral envelope and deposited on the exterior of unilamellar liposomes.Studies have shown that in order to attain the desired therapeutic effect, a physical attachment between the target antigen and the virosomal carrier is necessary. A virosome can bind to and “infect” host cells and deliver the antigen directly into the processing pathway which is an Alternatively, the virosome may be phagocytosed by an APC. So Our review gives a novel idea of the vector technology for vaccine delivery, its properties, method of preparation, and importance as well as some applications of different virosomal vaccine discoveries

Multi-Level Considerations for Optimal Implementation of Long-Acting Injectable Antiretroviral Therapy to Treat People Living with HIV: Perspectives of Health Care Providers Participating in Phase 3 Trials

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings. METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M trial across 13 countries; and (2) in-depth interviews with 14 providers participating in FLAIR/ ATLAS/ATLAS-2 M trials in the United States and Spain. Both assessments explored provider views and clinic dynamics related to the introduction of LA ART and were analyzed using thematic content analysis. The Consolidated Framework for Implementation Research (CFIR) was drawn on as the conceptual framework underpinning development of a model depicting study findings. RESULTS: Barriers and proposed solutions to LA ART implementation were identified at the individual, clinic and health system levels. Provider perceptions of patient level barriers included challenges with adhering to frequent injection appointments and injection tolerability. Proposed solutions included patient education, having designated staff for clinic visit retention, and clinic flexibility with appointment scheduling. The main provider concern was identifying appropriate candidates for LA ART; proposed solutions focused on patient provider communication and decision making. Clinic level barriers included the need for additional skilled individuals to administer injections, shifts in workflow as demand increases and the logistics of cold-chain storage. Proposed solutions included staff hiring and training, strategic planning around workflow and logistics, and the possibility of offering injections in other settings, including the home. Health system level barriers included cost and approvals from national regulatory bodies. Potential solutions included governments subsidizing treatment, ensuring cost is competitive with oral ART, and offering co-pay assistance. CONCLUSIONS: Results suggest the importance of multi-level support systems to optimize patient-provider communication and treatment decision-making; clinic staffing, workflow, logistics protocols and infrastructure; and cost-related factors within a given health system

Long-term efficacy and safety of fostemsavir among subgroups of heavily treatment-experienced adults with HIV-1

Objectives: The aim of this study was to understand how demographic and treatment-related factors impact responses to fostemsavir-based regimens. Design: BRIGHTE is an ongoing phase 3 study evaluating twice-daily fostemsavir 600 mg and optimized background therapy (OBT) in heavily treatment-experienced individuals failing antiretroviral therapy with limited treatment options (Randomized Cohort 1-2 and Nonrandomized Cohort 0 fully active antiretroviral classes). Methods: Virologic response rates (HIV-1 RNA <40 copies/ml, Snapshot analysis) and CD4+ T-cell count increases in the Randomized Cohort were analysed by prespecified baseline characteristics (age, race, sex, region, HIV-1 RNA, CD4+ T-cell count) and viral susceptibility to OBT. Safety results were analysed by baseline characteristics for combined cohorts (post hoc). Results: In the Randomized Cohort, virologic response rates increased between Weeks 24 and 96 across most subgroups. Virologic response rates over time were most clearly associated with overall susceptibility scores for new OBT agents (OSS-new). CD4+ T-cell count increases were comparable across subgroups. Participants with baseline CD4+ T-cell counts less than 20 cells/μl had a mean increase of 240 cells/μl. In the safety population, more participants with baseline CD4+ T-cell counts less than 20 vs. at least 200 cells/μl had grade 3/4 adverse events [53/107 (50%) vs. 24/96 (25%)], serious adverse events [58/107 (54%) vs. 25/96 (26%)] and deaths [16/107 (15%) vs. 2/96 (2%)]. There were no safety differences by other subgroups. Conclusion: Week 96 results for BRIGHTE demonstrate comparable rates of virologic and immunologic response (Randomized Cohort) and safety (combined cohorts) across subgroups. OSS-new is an important consideration when constructing optimized antiretroviral regimens for heavily treatment-experienced individuals with limited remaining treatment options

Strategies and Programs for Improved Nutrient Use Efficiency, Doubling Farmer’s Income, and Sustainable Agriculture: Indian Context

Since the Green Revolution era, the farming sector exploited the soils for food, fiber, fodder, etc., with high input responsive varieties that excavated vast amounts of chemical fertilizers. The burgeoning population of the country calls for a commensurate increase in food production to satisfy the demands of its inhabitants. Further, due to innovative mechanization in agriculture, specialization, and government policy programs, the productivity of food has soared. Subsequently, it ensued greater productions and minimized food prizes. Regrettably, intensive agricultural operations degraded the soil quality and now reached such a stage where without external inputs, growers unable to achieve their targeted yields. India has lost 68% innate productive capacity of agricultural soils. This plunder of land’s quality continues unabated, further resulting in low nutrient use efficiency and insufficient yields of agroecosystems. Therefore, this is high time to realize the dreadful impacts of intensive crop production on the natural ecosystem. Irrefutably, both soil and its nutrients are the wondrous gifts of nature to humankind; utilizing them sustainably is imperative. The present chapter highlights the impacts of non-judicious nutrient management on soil productivity, nutrient use efficiency, and novel technologies required to promote sustainable agriculture and achieve the target of doubling farmer’s income in India