Abscisic Acid Supplementation Rescues High Fat Diet-Induced Alterations in Hippocampal Inflammation and IRSs Expression

Accumulated evidence indicates that neuroinflammation induces insulin resistance in the brain. Moreover, both processes are intimately linked to neurodegenerative disorders, including Alzheimer’s disease. Potential mechanisms underlying insulin resistance include serine phosphorylation of the insulin receptor substrate (IRS) or insulin receptor (IR) misallocation. However, only a few studies have focused on IRS expression in the brain and its modulation in neuroinflammatory processes. This study used the high-fat diet (HFD) model of neuroinflammation to study the alterations of IR, an insulin-like growth factor receptor (IGF1R) and IRS expressions in the hippocampus. We observed that HFD effectively reduced mRNA and protein IRS2 expression. In contrast, a HFD induced the upregulation of the IRS1 mRNA levels, but did not alter an IR and IGF1R expression. As expected, we observed that a HFD increased hippocampal tumor necrosis factor alpha (TNFα) and amyloid precursor protein (APP) levels while reducing brain-derived neurotrophic factor (BDNF) expression and neurogenesis. Interestingly, we found that TNFα correlated positively with IRS1 and negatively with IRS2, whereas APP levels correlated positively only with IRS1 but not IRS2. These results indicate that IRS1 and IRS2 hippocampal expression can be affected differently by HFD-induced neuroinflammation. In addition, we aimed to establish whether abscisic acid (ABA) can rescue hippocampal IRS1 and IRS2 expression, as we had previously shown that ABA supplementation prevents memory impairments and improves neuroinflammation induced by a HFD. In this study, ABA restored HFD-induced hippocampal alterations, including IRS1 and IRS2 expression, TNFα, APP, and BDNF levels and neurogenesis. In conclusion, this study highlights different regulations of hippocampal IRS1 and IRS2 expression using a HFD, indicating the important differences of these scaffolding proteins, and strongly supports ABA therapeutic effects

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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Clitoral Therapy Device for Alleviating Sexual Dysfunction After Female Genital Mutilation: Randomized Controlled Trial

BackgroundFemale genital mutilation is considered a crime but is still practiced today in Africa and the Middle East, despite all the laws that make this procedure illegal due to the long-term physical and psychological harm it causes to women. Millions of girls and women living today have undergone genital mutilation, which involves removing the external female genitalia either partially or totally, based on the belief that it restricts feminine sexuality, thereby “saving” a girl for marriage. For girls and women, the surgery offers no health advantages. Girls’ right to control critical decisions regarding their sexual and reproductive health is violated because genital mutilation is frequently done against their will and frequently without their consent, leading to lifelong psychic trauma in addition to sexual dysfunction and lack of satisfaction due to distortion of the genitalia that threatens marital stability. ObjectiveTo determine the effect of a clitoral therapy device on improving sexual domains in women suffering from sexual dysfunction after female genital mutilation. MethodsThis study examined 80 married women aged from 20 to 45 years who were referred from the gynecology outpatient clinic of the Faculty of Medicine, Suez University, for sexual dysfunction resulting from female genital mutilation. The women were divided into 2 equal groups: the study group received a clitoral therapy device and traditional psychosexual education and were closely followed for 3 months, while the control group received only traditional psychosexual education for 3 months. The Arabic version of the Female Sexual Function Index (FSFI) questionnaire was used to assess sexual outcomes pre- and posttreatment in the 2 groups. ResultsOur findings revealed a significant increase in the 6 domains of the FSFI pretreatment in both groups compared to posttreatment (P>.001), except the orgasm domain in the control group, which showed only a nonsignificant increase (P=.16). ConclusionsClitoral therapy devices may be an effective, safe, noninvasive rehabilitation method for sexual dysfunction following female genital mutilation. Trial RegistrationClinicalTrials.gov NCT05039775; https://clinicaltrials.gov/ct2/show/NCT0503977

A comprehensive iso-octane combustion model with improved thermochemistry and chemical kinetics

Iso-Octane (2,2,4-trimethylpentane) is a primary reference fuel and an important component of gasoline fuels. Moreover, it is a key component used in surrogates to study the ignition and burning characteristics of gasoline fuels. This paper presents an updated chemical kinetic model for iso-octane combustion. Specifically, the thermodynamic data and reaction kinetics of iso-octane have been re-assessed based on new thermodynamic group values and recently evaluated rate coefficients from the literature. The adopted rate coefficients were either experimentally measured or determined by analogy to theoretically calculated values. Furthermore, new alternative isomerization pathways for peroxy-alkyl hydroperoxide (OOQOOH) radicals were added to the reaction mechanism. The updated kinetic model was compared against new ignition delay data measured in rapid compression machines (RCM) and a high-pressure shock tube. These experiments were conducted at pressures of 20 and 40 atm, at equivalence ratios of 0.4 and 1.0, and at temperatures in the range of 632-1060 K. The updated model was further compared against shock tube ignition delay times, jet-stirred reactor oxidation speciation data, premixed laminar flame speeds, counterflow diffusion flame ignition, and shock tube pyrolysis speciation data available in the literature. Finally, the updated model was used to investigate the importance of alternative isomerization pathways in the low temperature oxidation of highly branched alkanes. When compared to available models in the literature, the present model represents the current state-of-the-art in fundamental thermochemistry and reaction kinetics of iso-octane; and thus provides the best prediction of wide ranging experimental data and fundamental insights into iso-octane combustion chemistry. (C) 2016 The Combustion Institute. Published by Elsevier Inc. All rights reserved.The presented work was supported by Saudi Aramco under the FUELCOM program and by the King Abdullah University of Science and Technology (KAUST) with competitive research funding given to the Clean Combustion Research Center (CCRC). The work at UCONN was supported by the National Science Foundation under Grant No. CBET-1402231. The work at LLNL was supported by the U.S. Department of Energy, Vehicle Technologies Office, program managers Gurpreet Singh and Leo Breton and was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratories under contract DE-AC52-07NA273442019-02-0

Evaluating knowledge, attitude, and physical activity levels related to cardiovascular disease in Egyptian adults with and without cardiovascular disease: a community-based cross-sectional study

Background: Cardiovascular disease (CVD) represents a significant health challenge in Egypt, yet there exists limited understanding regarding the knowledge, attitudes, and physical activity levels associated with CVD. These factors play a pivotal role in developing effective prevention and management strategies. Hence, this cross-sectional study aimed to evaluate Egyptian adults’ knowledge, attitudes, and physical activity (KAP) levels. Methods: Data were collected using a previously validated questionnaire encompassing demographic characteristics, CVD knowledge (including risk factors and symptoms), attitudes toward CVD, and self-reported physical activity levels. The survey was distributed among social media channels, and trained researchers administered the questionnaire via face-to-face interviews with adult patients with and without CVD admitted to Cairo University Hospital clinics. Results: The study involved 591 participants, of whom 21.7% had CVD. Overall, participants exhibited poor knowledge regarding CVD, with a mean score of 21 ± 7 out of 40, equivalent to 52.5%. Attitudes toward CVD were moderate, with a mean score of 66.38 ± 8.7 out of 85, approximately 78%. Physical activity levels per week were also moderate, averaging 1188 MET-min with a range of 1121–18,761. Subgroup analysis revealed that individuals with CVD had lower average knowledge, attitude, and physical activity levels than those without CVD. Working in the healthcare field was a predictor of higher knowledge score (standard error (SE) 5.89, 95% confidence interval (CI) 4.61 to 7.17, P < 0.001), while those with CVD and smokers were predictors of lower attitude score (SE -4.08, 95% CI -6.43 to -1.73, P < 0.001) and (SE -2.54, 95% CI -4.69 to -0.40, P = 0.02), respectively. Conclusion: The study findings highlight a significant disparity in knowledge, attitudes, and physical activity levels related to CVD in Egypt. Targeted interventions aimed at improving awareness, fostering positive attitudes, and promoting physical activity among individuals at risk for CVD are crucial for effective prevention and management

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially