Inhibition of HCV 3a genotype entry through Host CD81 and HCV E2 antibodies

<p>Abstract</p> <p>Background</p> <p>HCV causes acute and chronic hepatitis which can eventually lead to permanent liver damage hepatocellular carcinoma and death. HCV glycoproteins play an important role in HCV entry by binding with CD81 receptors. Hence inhibition of virus at entry step is an important target to identify antiviral drugs against HCV.</p> <p>Methods and result</p> <p>The present study elaborated the role of CD81 and HCV glycoprotein E2 in HCV entry using retroviral pseudo-particles of 3a local genotype. Our results demonstrated that HCV specific antibody E2 and host antibody CD81 showed dose- dependent inhibition of HCV entry. HCV E2 antibody showed 50% reduction at a concentration of 1.5 ± 1 μg while CD81 exhibited 50% reduction at a concentration of 0.8 ± 1 μg. In addition, data obtained with HCVpp were also confirmed with the infection of whole virus of HCV genotype 3a in liver cells.</p> <p>Conclusion</p> <p>Our data suggest that HCV specific E2 and host CD81 antibodies reduce HCVpp entry and full length viral particle and combination of host and HCV specific antibodies showed synergistic effect in reducing the viral titer.</p

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Onlay Versus Sublay Technique of Repairing Ventral Abdominal Hernia

Background: To compare Onlay versus Sublay technique of repairing ventral abdominal hernia Methods: In this compatrative study patients of ventral abdominal hernia (n=150) were included. Seventy six were in onlay group (Group A) and 74 in sublay group (Group B). In group A patients (onlay) the hernial sac was not opened unless the contents were irreducible. In such conditions the sac was opened and the contents were dissected and reduced, sac was closed, inverted and sutured with vicryl 2/0. An onlay polypropylene mesh was inserted. In Group B(sublay) midline laprotomy incision was given and in cases of incisional hernias excision of the previous scar. Afterwards hernial sac was opened. After adhenolysis the bowels were covered with a towel to avoid any iatrogenic injury to the bowel. A sufficient mesh overlap with a subduction of healthy tissue of at least 6 cm in each direction was provided to avoid recurrence at the edges due to shrinkage of prosthesis. After preparation of the mesh bearing the peritoneal layer was closed with an absorbable running suture. The mesh was then placed into contact with the muscle fibres. Follow up in each group was done for the period of one month with the interval of 7days, 15 days and 30days. Results: The mean operative time in group A was 49.35 ± 8.29 minutes and in group B 63.15 ± 15.0 minutes (p&lt; 0.001). The patients with seroma in group A were 12 percent, 34.67percent and 0 percent on 7th , 15th and 30th day respectively .Superficial surgical site (SSI) in the same group was 17.33 percent , 6.67 percent and 0 percent in 7th, 15th and 30th day respectively. The patients who presented with seroma in group B were 6.3percent, 3.78percent and 0 percent on 7th , 15th and 30th day respectively .SSI in the same group B were 4.3percent , 2.9 percent and 0 percent on 7th, 15th and 30th day respectively. Conclusion: Sublay is better than onlay technique with less postoperative complications, but operative time is slightly greater in sublay technique

Prevalence and severity of temporomandibular disorders among university students in Riyadh

Objective: The aim of this study was to evaluate the prevalence and severity of temporomandibular disorders (TMDs) among male university students in Riyadh, Saudi Arabia. The role of relevant medical and dental histories in the assessment of TMD in this Arab population was also addressed. Methods: Required information was collected via a questionnaire. The first part of the questionnaire was used to obtain the medical and dental histories of participants. The second part included 10 questions regarding common TMD symptoms. Fonseca’s anamnestic index (FAI) was used to classify TMD severity as “no dysfunction”, “light dysfunction”, “moderate dysfunction”, or “severe dysfunction”. Results: Of the 600 distributed questionnaires, 400 questionnaires were completed (response rate: 66.6%). Mean age of eligible participants was 21.90 ± 1.79 years. Psychological stress (30.5%) and direct restorations (77%) were the most commonly reported items on the medical and dental histories respectively for the total number of participants. According to the FAI, 53.2% of participants were classified as having no dysfunction, followed by light (36.1%), moderate (9.6%), and severe dysfunction (1.1%). Conclusions: Based on the FAI, mild to moderate prevalence of TMD appears to exist among male university students in Riyadh. Histories of psychological stress and dental treatment were evident among these students. Information obtained from the FAI may be helpful in assessing the prevalence of TMD and has important implications for the early diagnosis of TMD and the prevention of future TMD-related complications. Keywords: Temporomandibular disorder, Temporomandibular joint, TMDs, Fonseca’s questionnaire, Fonseca’s anamnestic index, Cross-sectional surve

Development and characterisation of MMT-reinforced polyacrylonitrile-pullulan nanofibers for controlled permeation of isotretinoin

AbstractDrug nanofibers play a crucial role in ameliorating therapeutic effects, reducing toxicity, and increasing the bioavailability of drugs. This study was aimed at the fabrication of isotretinoin-loaded MMT-reinforced bi-polymeric (PAN/PU) nanofibers with varying concentrations of isotretinoin. In this study, montmorillonite (MMT)-reinforced cross-linked polyacrylonitrile and pullulan nanofibers combined with varying amounts of isotretinoin were fabricated through an electrospinning approach and investigated for their drug permeation potential. PAN-PU nanofibers were successfully integrated with the isotretinoin. The incorporation of isotretinoin into the nanofibrous structure was confirmed by FTIR and XRD. TGA study indicated the stability of the fabricated nanoparticles. The SEM results showed the beaded and smooth morphology of nanofibers. Formulation with a higher drug concentration had a non-significantly (p > 0.05) higher swelling ratio. Drug-loaded polymeric nanofiber erodes at a slower rate as compared to drug-free nanofibers. The ex-vivo permeation study of nanofibers revealed that the drug was not released all at once, but rather gradually and consistently over the period of 24 h, indicating a controlled release of the drug. In addition, the drug concentration in the nanofibers affected the permeation of the drug. According to the findings, isotretinoin-loaded MMT-reinforced bi-polymeric (PAN/PU) nanofibers with varying concentrations of isotretinoin were successfully fabricated. The fabricated nanofibers (PAN/PU) showed a promising potential for controlled permeation of drugs through rabbit skin