Value of Matrix metalloproteinase-7and ‎Vimentin as Prognostic Biomarkers in Adenoid ‎Cystic Carcinoma (Immunohistochemical Study)‎

خلفية:MMP7 دورها الأساسي هو كسر المصفوفة خارج الخلية بما في ذلك الكازين، النوع الأول، الجيلاتين الثاني والرابع، والخامس. ويرتبط زيادة التعبير النسيجي ل MMP7 مع العديد من الأورام الخبيثة. Vim لها دور مهم في الأورام فيما يتعلق بالتصاق الخلية والهجرة. في الدراسة الحالية، نحاول تقييم تعبير  MMP7 و Vim كعلامات للسلوك العدواني البيولوجي ل AdCC. المواد والطرق: تسعة عشر نسيج مثبت بالفورمالين ومطمورة بشمع البارافيين مشخصة نسيجبا كسرطان كيسي شبيه بالغدة. استخدم تقنية المناعة الكيميائية النسيجية لتقيم تعبير MMP7 و Vim كمضادات احادية النسل. النتائج: أظهرت MMP7 علاقة ذات دلالة مع الاورام الكبيرة (P = 0.003) ، والمتباينة للغاية نسيجيا (P = 0.006). ارتبط Vim بشكل ملحوظ مع الغدة اللعابية الصغيرة  (P = 0.041) ، الاورام الكبيرة (P = 0.021)، والمتباينة للغاية نسيجيا (P = 0.040). كشفت كل من MMP7 و Vimعلامات ارتباط كبير للغاية مع المراحل المتقدمة نسيجيا (P <0.001) ، والعقدة الليمفاوية (P <0.001). وعلاوة على ذلك، كان هناك علاقة طردية ذات دلالة إحصائية بين MMP7و Vim ((P = 0.001.  الخلاصة: كل MMP 7 وVim مرتبطة بشكل إيجابي مع أورام ذات مستقبل مرضي سيء.Background: matrix metalloproteinase-7 (MMP7), its primary role is to break down extracellular matrix including casein, type I, II, IV, and V gelatins, fibronectin, and proteoglycan. The upregulation of MMP7 is associated with many malignant tumors. Vimentin (Vim) plays an important role in malignant tumors with regard to cellular adhesion, migration and signaling. In our current study, we have attempted to evaluate the expression of MMP7 and Vim as markers for aggressive biological behavior of AdCC.  Materials and Methods: Nineteen formalin fixed paraffin embedded blocks of AdCC were collected retrospectively were included in this study. An immunohistochemical (IHC) staining was performed using anti MMP7 and anti Vim monoclonal antibodies. Results: MMP7 showed significant relation with larger size tumor (P=0.003), higher grade (P=0.006). The Vim was significantly correlated with minor salivary gland (P=0.041), larger size tumor (P=0.021), high grade (P=0.040).   Both markers revealed highly significant correlation with advanced stage (P<0.001), and positive lymph node (LN) (P<0.001). There was a significant positive correlation between Vim and MMP7 (P=0.001).Conclusion: Both MMP7 and Vim are positively correlated with tumors of poor prognosis.&nbsp

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 years; 78.2% included were male with a median age of 37 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

Epidemiology of Chlamydia trachomatis in the Middle East and north Africa: a systematic review, meta-analysis, and meta-regression.

BACKGROUND: The epidemiology of Chlamydia trachomatis in the Middle East and north Africa is poorly understood. We aimed to provide a comprehensive epidemiological assessment of C trachomatis infection in the Middle East and north Africa. METHODS: We did a systematic review of C trachomatis infection as well as a meta-analysis and meta-regression of C trachomatis prevalence. We searched PubMed and Embase, as well as regional and national databases up to March 13, 2019, using broad search terms with no language or year restrictions. Any document or report including biological measures for C trachomatis prevalence or incidence was eligible for inclusion. We extracted all measures of current (genital or rectal), recent, and ever infection with C trachomatis. We estimated pooled average prevalence in different populations using random-effects meta-analysis. Factors associated with prevalence and sources of between-study heterogeneity were determined using meta-regression. FINDINGS: We identified a total of 1531 citations, of which 255 reports contributed to 552 C trachomatis prevalence measures from 20 countries. No incidence measures were identified. Pooled prevalence of current genital infection was 3·0% (95% CI 2·3-3·8) in general populations, 2·8% (1·0-5·2) in intermediate-risk populations, 13·2% (7·2-20·7) in female sex workers, 11·3% (9·0-13·7) in infertility clinic attendees, 12·4% (7·9-17·7) in women with miscarriage, 12·4% (9·4-15·7) in symptomatic women, and 17·4% (12·5-22·8) in symptomatic men. Pooled prevalence of current rectal infection was 7·7% (4·2-12·0) in men who have sex with men. Substantial between-study heterogeneity was found. Multivariable meta-regression explained 29·0% of variation. Population type was most strongly associated with prevalence. Additional associations were found with assay type, sample size, country, and sex, but not with sampling methodology or response rate (about 90% of studies used convenience sampling and >75% had unclear response rate). There was no evidence for temporal variation in prevalence between 1982 and 2018. INTERPRETATION: C trachomatis prevalence in the Middle East and north Africa is similar to other regions, but higher than expected given its sexually conservative norms. High prevalence in infertility clinic attendees and in women with miscarriage suggests a potential role for C trachomatis in poor reproductive health outcomes in this region. FUNDING: National Priorities Research Program from the Qatar National Research Fund (a member of Qatar Foundation)

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

New Alpha-Amylase Inhibitory Metabolites from Pericarps of <i>Garcinia mangostana</i>

Two new benzophenones: garcimangophenones A (6) and B (7) and five formerly reported metabolites were purified from the pericarps EtOAc fraction of Garcinia mangostana ((GM) Clusiaceae). Their structures were characterized by various spectral techniques and by comparing with the literature. The α-amylase inhibitory (AAI) potential of the isolated metabolites was assessed. Compounds 7 and 6 had significant AAI activity (IC50 9.3 and 12.2 µM, respectively) compared with acarbose (IC50 6.4 µM, reference α-amylase inhibitor). On the other hand, 5 had a moderate activity. Additionally, their activity towards the α-amylase was assessed utilizing docking studies and molecular dynamics (MD) simulations. The docking and predictive binding energy estimations were accomplished using reported crystal structure of the α-amylase (PDB ID: 5TD4). Compounds 7 and 6 possessed highly negative docking scores of −11.3 and −8.2 kcal/mol, when complexed with 5TD4, respectively while acarbose had a docking score of −16.1 kcal/mol, when complexed with 5TD4. By using molecular dynamics simulations, the compounds stability in the complexes with the α-amylase was analyzed, and it was found to be stable over the course of 50 ns. The results suggested that the benzophenone derivative 7 may be potential α-amylase inhibitors. However, further investigations to support these findings are required

Oral Health-Related Quality of Life in Patients with Chronic Oral Mucosal Diseases: Reliability and Validity of Urdu Version of Chronic Oral Mucosal Disease Questionnaire (COMDQ)

The aim of the study was to translate and validate the Urdu version of the Chronic Oral Mucosal Disease Questionnaire (COMDQ) and measure the oral health-related quality of life (OHRQoL) in Pakistani patients with chronic oral mucosal disease. One hundred and twenty patients with chronic oral mucosal diseases were recruited for this study. Two types of reliability of the COMDQ were tested. First, the internal consistency was calculated using Cronbach’s alpha, and second, test-retest reliability was calculated using intraclass correlation coefficients (ICC). Convergent validity was assessed for testing the validity of the COMDQ by examining the correlations with the Visual Analogue Scale (VAS) and OHIP-14 using Pearson’s correlations coefficient, and a t-test was used to compare the COMDQ domains and the socio-demographic characteristics. The most prevalent chronic oral mucosal disease (COMD) among the participants was recurrent aphthous stomatitis (47.5%), and the least prevalent was oral granulomatosis (6.6%). The total mean score for COMDQ was 43.5 (SD = 18.4). It showed a high level of internal consistency (Cronbach’s a = 0.81), and test-retest reliability was also good (r = 0.85). The total score of COMDQ was strongly correlated with the total score of OHIP-14 and VAS (r = 0.86 and r = 0.83), which indicated good convergent validity. The score of pain and the functional limitation domain reported a significant difference with age (p p < 0.034). The Urdu version of COMDQ is an accurate, valid, and reliable instrument that can be used to assess the OHRQoL in patients with chronic oral mucosal diseases in Pakistani and other Urdu-speaking populations of different age groups

Spontaneous preterm birth and single nucleotide gene polymorphisms: a recent update

Abstract Background Preterm birth (PTB), birth at <37 weeks of gestation, is a significant global public health problem. World-wide, about 15 million babies are born preterm each year resulting in more than a million deaths of children. Preterm neonates are more prone to problems and need intensive care hospitalization. Health issues may persist through early adulthood and even be carried on to the next generation. Majority (70 %) of PTBs are spontaneous with about a half without any apparent cause and the other half associated with a number of risk factors. Genetic factors are one of the significant risks for PTB. The focus of this review is on single nucleotide gene polymorphisms (SNPs) that are reported to be associated with PTB. Results A comprehensive evaluation of studies on SNPs known to confer potential risk of PTB was done by performing a targeted PubMed search for the years 2007–2015 and systematically reviewing all relevant studies. Evaluation of 92 studies identified 119 candidate genes with SNPs that had potential association with PTB. The genes were associated with functions of a wide spectrum of tissue and cell types such as endocrine, tissue remodeling, vascular, metabolic, and immune and inflammatory systems. Conclusions A number of potential functional candidate gene variants have been reported that predispose women for PTB. Understanding the complex genomic landscape of PTB needs high-throughput genome sequencing methods such as whole-exome sequencing and whole-genome sequencing approaches that will significantly enhance the understanding of PTB. Identification of high risk women, avoidance of possible risk factors, and provision of personalized health care are important to manage PTB