The role of sildenafil citrate in the treatment of fetal growth restriction: a randomized controlled trial

Background: This study was aimed to evaluate the effect of sildenafil citrate on Doppler velocity indices in patients with fetal growth restriction (FGR) associated with impaired placental circulation.Methods: A double-blinded, parallel group randomized clinical trial (clinicaltrials.gov NCT02590536) was conducted in Ain Shams Maternity Hospital, in the period between October 2015 and June 2017. Ninety pregnant women with documented intrauterine growth retardation at 24-37 weeks of gestation were randomized to either sildenafil citrate 25 mg orally every 8 hours or placebo visually-identical placebo tablets with the same regimen. The primary outcome of the study was the change in umbilical artery and fetal middle cerebral artery indices.Results: There was a significant improvement in umbilical and middle cerebral artery indices after sildenafil administration p<0.001. Present study observed that, sildenafil group, in comparison to placebo, has a significantly higher mean neonatal birth weight. 1783±241g vs 1570±455g (p<0.001). There was a significantly higher mean gestational age at delivery in women in sildenafil group 35.3±1.67 weeks, whereas it was lower in the placebo group 33.5±1.7 weeks. The side effects as headache, palpitation and facial flushing were significantly higher in sildenafil group compared to placebo group.Conclusions: The use sildenafil citrate in pregnancies with fetal growth restriction (FGR) improved the feto-placental Doppler indices (pulsatility index of umbilical artery and middle cerebral artery) and improved neonatal outcomes

The neurotoxic effects of Methotrexate (MTX) on rat hippocampus and to explore the neuroprotective role of Alpha Lipoic Acid (ALA): Review article

Background: The hippocampus is a major component of the mammalian brains and the brains of other vertebrates. It belongs to the limbic system and plays important roles in memory consolidation. Methotrexate (MTX) belongs to the antimetabolite group, which is an antineoplastic group of drugs. MTX has a wide range of therapeutic effects: e.g. at high doses in many malignancies and at low doses in autoimmune diseases such as rheumatoid arthritis and psoriasis, due to its anti-inflammatory and immunosuppressive effects. The therapeutic actions of Alpha Lipoic Acid (ALA) is based on its antioxidant properties including its capacity in regenerating endogenous antioxidants, its metal chelating abilities, its action as a scavenger of reactive oxygen species (ROS) and its capability to repair oxidative damage.Objective: This work aimed to study the neurotoxic effects of methotrxate (MTX) on rat hippocampus and to explore the neuroprotective role of alpha lipoic acid (ALA).Methods: The databases were searched for articles published in English in 4 data bases [PubMed – Google scholar- Science direct and Egyptian bank of knowledge] and Boolean operators (and, or, not) had been used such as neurotoxic effects of methotrxate and rat hippocampus OR alpha lipoic acid and in reviewed articles.Conclusion: So, from this review article, it can be concluded that, alpha lipoic acid administration along with methotrxate therapy can ameliorate the harmfull effects of methotrxate on hippocampus

Effect of Gut Microbiota Biotransformation on Dietary Tannins and Human Health Implications

Tannins represent a heterogeneous group of high-molecular-weight polyphenols that are ubiquitous among plant families, especially in cereals, as well as in many fruits and vegetables. Hydrolysable and condensed tannins, in addition to phlorotannins from marine algae, are the main classes of these bioactive compounds. Despite their low bioavailability, tannins have many beneficial pharmacological effects, such as anti-inflammatory, antioxidant, antidiabetic, anticancer, and cardioprotective effects. Microbiota-mediated hydrolysis of tannins produces highly bioaccessible metabolites, which have been extensively studied and account for most of the health effects attributed to tannins. This review article summarises the effect of the human microbiota on the metabolism of different tannin groups and the expected health benefits that may be induced by such mutual interactions. Microbial metabolism of tannins yields highly bioaccessible microbial metabolites that account for most of the systemic effects of tannins. This article also uses explainable artificial intelligence to define the molecular signatures of gut-biotransformed tannin metabolites that are correlated with chemical and biological activity. An understanding of microbiota–tannin interactions, tannin metabolism-related phenotypes (metabotypes) and chemical tannin-metabolites motifs is of great importance for harnessing the biological effects of tannins for drug discovery and other health benefits

Metabolomic profile, anti-trypanosomal potential and molecular docking studies of <i>Thunbergia grandifolia</i>

Trypanosomiasis is a protozoan disease transmitted via Trypanosoma brucei. This study aimed to examine the metabolic profile and anti-trypanosomal effect of methanol extract of Thunbergia grandifolia leaves. The liquid chromatography-high resolution electrospray ionisation mass spectrometry (LC-HRESIMS) revealed the identification of fifteen compounds of iridoid, flavonoid, lignan, phenolic acid, and alkaloid classes. The extract displayed a promising inhibitory activity against T. brucei TC 221 with MIC value of 1.90 μg/mL within 72 h. A subsequent in silico analysis of the dereplicated compounds (i.e. inverse docking, molecular dynamic simulation, and absolute binding free energy) suggested both rhodesain and farnesyl diphosphate synthase as probable targets for two compounds among those dereplicated ones in the plant extract (i.e. diphyllin and avacennone B). The absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of diphyllin and avacennone were calculated accordingly, where both compounds showed acceptable drug-like properties. This study highlighted the antiparasitic potential of T. grandifolia leaves

New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth

Purpose: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity. Methods: Docetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated. Results: We show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia. Conclusions: We show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer treatment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Trends in obesity and diabetes across Africa from 1980 to 2014: an analysis of pooled population-based studies

Background: The 2016 Dar Es Salaam Call to Action on Diabetes and Other non-communicable diseases (NCDs) advocates national multi-sectoral NCD strategies and action plans based on available data and information from countries of sub-Saharan Africa and beyond. We estimated trends from 1980 to 2014 in age-standardized mean body mass index (BMI) and diabetes prevalence in these countries, in order to assess the co-progression and assist policy formulation. Methods: We pooled data from African and worldwide population-based studies which measured height, weight and biomarkers to assess diabetes status in adults aged ≥ 18 years. A Bayesian hierarchical model was used to estimate trends by sex for 200 countries and territories including 53 countries across five African regions (central, eastern, northern, southern and western), in mean BMI and diabetes prevalence (defined as either fasting plasma glucose of ≥ 7.0 mmol/l, history of diabetes diagnosis, or use of insulin or oral glucose control agents). Results: African data came from 245 population-based surveys (1.2 million participants) for BMI and 76 surveys (182 000 participants) for diabetes prevalence estimates. Countries with the highest number of data sources for BMI were South Africa (n = 17), Nigeria (n = 15) and Egypt (n = 13); and for diabetes estimates, Tanzania (n = 8), Tunisia (n = 7), and Cameroon, Egypt and South Africa (all n = 6). The age-standardized mean BMI increased from 21.0 kg/m2 (95% credible interval: 20.3–21.7) to 23.0 kg/m2 (22.7–23.3) in men, and from 21.9 kg/m2 (21.3–22.5) to 24.9 kg/m2 (24.6–25.1) in women. The age-standardized prevalence of diabetes increased from 3.4% (1.5–6.3) to 8.5% (6.5–10.8) in men, and from 4.1% (2.0–7.5) to 8.9% (6.9–11.2) in women. Estimates in northern and southern regions were mostly higher than the global average; those in central, eastern and western regions were lower than global averages. A positive association (correlation coefficient ≃ 0.9) was observed between mean BMI and diabetes prevalence in both sexes in 1980 and 2014. Conclusions: These estimates, based on limited data sources, confirm the rapidly increasing burden of diabetes in Africa. This rise is being driven, at least in part, by increasing adiposity, with regional variations in observed trends. African countries’ efforts to prevent and control diabetes and obesity should integrate the setting up of reliable monitoring systems, consistent with the World Health Organization’s Global Monitoring System Framework

Prognostic tools and candidate drugs based on plasma proteomics of patients with severe COVID-19 complications

COVID-19 complications still present a huge burden on healthcare systems and warrant predictive risk models to triage patients and inform early intervention. Here, we profile 893 plasma proteins from 50 severe and 50 mild-moderate COVID-19 patients, and 50 healthy controls, and show that 375 proteins are differentially expressed in the plasma of severe COVID-19 patients. These differentially expressed plasma proteins are implicated in the pathogenesis of COVID-19 and present targets for candidate drugs to prevent or treat severe complications. Based on the plasma proteomics and clinical lab tests, we also report a 12-plasma protein signature and a model of seven routine clinical tests that validate in an independent cohort as early risk predictors of COVID-19 severity and patient survival. The risk predictors and candidate drugs described in our study can be used and developed for personalized management of SARS-CoV-2 infected patients. 2022, The Author(s).The authors would like to thank all the patients, volunteers, and the healthcare co-workers from Allergy and Immunology Section-HMC, and Dr. Mohamed G.H. Mohamedali, Mr. Hassen Maatoug, and Mr. Ahmed Soliman from Hezm Mebairek General Hospital-HMC for developing disposable racks for samples transportation, tubes labeling, blood collection, and handling. We thank the support provided by Qatar University Biomedical Research Centre, Biosafety Level 3, and Associate Professor Hadi M. Yassine (M.Sc., Ph.D.). We also acknowledge the help of the Anti-Doping Lab-Qatar (ADLQ) and Qatar Red Crescent (QRC) for recruiting control samples. This work was supported by a grant fund from Hamad Medical Corporation (fund number MRC-05-003) and core funding from Qatar Biomedical Research Institute (QBRI).Scopu

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