Developing A Synthetic Composite Membrane For Cleft Palate Repair

An oronasal fistula is a passage between the oral and nasal cavity. Currently, surgical procedures use mucosal flaps or collagen grafts to make a barrier between oral and nasal cavities. Our aim was to develop a cell-free synthetic repair material for closure of nasal fistulas. We surface functionalized electrospun polyurethane (PU) and poly-L-lactic acid (PLLA) and composite polymer (PU-PLLA) membranes with acrylic acid through plasma polymerization. Membranes were treated in a layer-by-layer approach to develop highly charged electrostatic layer that could bind heparin as a pro-angiogenic glycosaminoglycan. The properties were evaluated through physical, chemical, and mechanical characterization techniques. Cytotoxicity was tested with MC3T3 pre-osteoblast cell lines for 3, 7, and 14 days, and vasculogenesis was assessed by implantation into the chorio-allantoic membrane in chick embryos for 7 days. In vivo biocompatibility was assessed by subcutaneous implantation in rats for 1, 3, and 6 weeks. The membranes consisted of random fibers of PLLA-PU with fiber diameters of 0.47 and 0.12 μm, respectively. Significantly higher cell proliferation and migration of MC3T3 cells at 3, 7, and 14 days were shown on plasma-coated membranes compared with uncoated membranes. Further, it was found that plasma-coated membranes were more angiogenic than controls. In vivo implantation of membranes in rats did not reveal any gross toxicity to the materials, and wound healing was comparable with the native tissue repair (sham group). We therefore present a plasma-functionalized electrospun composite polymer membrane for use in the treatment of fistulas. These membranes are flexible, non-cytotoxic, and angiogenic, and we hope it should lead to permanent closure of oronasal fistula

COVID-19: Third dose booster vaccine effectiveness against breakthrough coronavirus infection, hospitalisations and death in patients with cancer: A population-based study

Purpose: People living with cancer and haematological malignancies are at increased risk of hospitalisation and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus third dose vaccine boosters are proposed to boost waning immune responses in immunocompromised individuals and increase coronavirus protection; however, their effectiveness has not yet been systematically evaluated. Methods: This study is a population-scale real-world evaluation of the United Kingdom’s third dose vaccine booster programme for cancer patients from 8th December 2020 to 7th December 2021. The cancer cohort comprises individuals from Public Health England’s national cancer dataset, excluding individuals less than 18 years. A test-negative case-control design was used to assess third dose booster vaccine effectiveness. Multivariable logistic regression models were fitted to compare risk in the cancer cohort relative to the general population. Results: The cancer cohort comprised of 2,258,553 tests from 361,098 individuals. Third dose boosters were evaluated by reference to 87,039,743 polymerase chain reaction (PCR) coronavirus tests. Vaccine effectiveness against breakthrough infections, symptomatic infections, coronavirus hospitalisation and death in cancer patients were 59.1%, 62.8%, 80.5% and 94.5% respectively. Lower vaccine effectiveness was associated with a cancer diagnosis within 12 months, lymphoma, recent systemic anti-cancer therapy (SACT) or radiotherapy. Lymphoma patients had low levels of protection from symptomatic disease. In spite of third dose boosters, following multivariable adjustment, individuals with cancer remain at increased risk of coronavirus hospitalisation and death compared to the population control (OR 3.38, 3.01 respectively. p<0.001 for both). Conclusions: Third dose boosters are effective for most individuals with cancer, increasing protection from coronavirus. However, their effectiveness is heterogenous, and lower than the general population. Many patients with cancer will remain at increased risk of coronavirus infections, even after 3 doses. In the case of patients with lymphoma, there is a particularly strong disparity of vaccine effectiveness against breakthrough infection and severe disease. Breakthrough infections will disrupt cancer care and treatment with potentially adverse consequences on survival outcomes. The data support the role of vaccine boosters in preventing severe disease, and further pharmacological intervention to prevent transmission and aid viral clearance to limit disruption of cancer care as the delivery of care continues to evolve during the coronavirus pandemic

Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Developing a culture towards medical journalism

A letter to Editor Biomedica has been written to congratulate and highlight the importance of programs on journalistic writing among health professional. A disconnect between public and health delivery system and healthcare providers can be avoided if medical professionals become involved in writing for community and masses.&nbsp;</p

Agonists and antagonists of the orexinergic system: therapeutic molecules of the future - a narrative review

The orexinergic system involves orexin (OX) neurons, OX peptides, and OX receptors. OX neurons are located throughout the central nervous tissue (including many nuclei) and the peripheral nervous tissue and organs. These neurons are critically involved in the sleepwake transition, cardiorespiratory, and autonomic regulations. OX antagonists include selective OX type 1 receptor (OX1R) antagonists, selective OX type 2 receptor (OX2R) antagonists, and dual OX1/2R antagonists. Similarly, OX agonists include dual OX1/2R agonists and selective OX1R or OX2R agonists. Recent understandings of the therapeutic mechanism of OX have led to possible therapeutic options in diseases such as insomnia, narcolepsy, psychiatric disorders, and neurodegenerative diseases. This review focuses on the therapeutic roles of OXs as agonists or antagonists in animal models and human patients, which can lead to possible avenues related to their application in health and disease.</p

Commiphora wightii and molmol have therapeutic effects in oral cancers and COVID-19 disease by modulating anti-apoptotic proteins and inflammatory pathways

Oral Squamous Cell Carcinoma (OSCC) has become prevalent worldwide and is one of the leading cause of death. Derangement of anti-apoptotic proteins is important regarding OSCC development. Over-expression of these proteins lead to prolonged cellular survival, thus increasing the susceptibility of tumor formation. Commiphora wightii and molmol are the natural herbs with ability to down-regulate anti-apoptotic proteins by acting on Nuclear Factor-kappa B (NF-&kappa;B) pathway, p53 pathway, signal transducer and activator of transcription pathway, estrogen, cyclooxygenase 2 and mitogen activated protein kinase pathway. NF-&kappa;B pathway has been found to involve in the release of cytokine storm associated with COVID-19 disease. Commiphora wightii and molmol suppress the COVID-19 infection by their anti-inflammatory and anti-viral properties. This review sheds light on the effect of Commiphora wightii and molmol on suppression of oral cancer and COVID-19 infection by modulation of anti-apoptotic proteins and inflammatory pathway.</p