Similar and Additive Effects of Ovariectomy and Diabetes on Insulin Resistance and Lipid Metabolism

Type 2 diabetes mellitus (T2DM) is among the leading causes of death in postmenopausal women. The disruption of ovarian function may contribute to the incidence of T2DM. The purpose of this study was to investigate the effects of ovariectomy and T2DM on glucose and lipid homeostasis, perilipin levels in adipose tissues, as a lipolytic regulator, and levels of certain adipokines. Ovariectomized (OVX) rats were used as a model for postmenopausal women. The study was performed on sham, OVX, sham diabetic, and OVX diabetic female rats. The results indicated that ovariectomy alters adipose tissue metabolism through reducing perilipin content in white adipose tissue (WAT); however it has no effect on perilipin level in brown adipose tissue (BAT). OVX diabetic females suffer from serious metabolic disturbances, suggested by exacerbation of insulin resistance in terms of disrupted lipid profile, higher HOMA-IR, hyperinsulinemia, higher leptin, and lower adiponectin concentrations. These metabolic derangements may underlie the predisposition for cardiovascular disease in women after menopause. Therefore, for efficient treatment, the menopausal status of diabetic female should be addressed, and the order of events is of great importance because ovariectomy following development of diabetes has more serious complications compared to development of diabetes as result of menopause

The anti-obesity potential of superparamagnetic iron oxide nanoparticles against high-fat diet-induced obesity in rats: possible involvement of mitochondrial biogenesis in the adipose tissues

Obesity is a pandemic disease that is rapidly growing into a serious health problem and has economic impact on healthcare systems. This bleak image has elicited creative responses, and nanotechnology is a promising approach in obesity treatment. This study aimed to investigate the anti-obesity effect of superparamagnetic iron oxide nanoparticles (SPIONs) on a high-fat-diet rat model of obesity and compared their effect to a traditional anti-obesity drug (orlistat). Methods: The obese rats were treated daily with orlistat and/or SPIONs once per week for 8 weeks. At the end of the experiment, blood samples were collected for biochemical assays. Then, the animals were sacrificed to obtain white adipose tissues (WAT) and brown adipose tissues (BAT) for assessment of the expression of thermogenic genes and mitochondrial DNA copy number (mtDNA-CN). Results: For the first time, we reported promising ameliorating effects of SPIONs treatments against weight gain, hyperglycemia, adiponectin, leptin, and dyslipidemia in obese rats. At the molecular level, surprisingly, SPIONs treatments markedly corrected the disturbed expression and protein content of inflammatory markers and parameters controlling mitochondrial biogenesis and functions in BAT and WAT. Conclusions: SPIONs have a powerful anti-obesity effect by acting as an inducer of WAT browning and activator of BAT functions

Effect of superparamagnetic iron oxide nanoparticles on glucose homeostasis on type 2 diabetes experimental model

[Aims]: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment.[Main methods]: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins.[Key finding]: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better.[Significance]: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model.This work was partially supported by the Spanish Ministry of Science, Innovation and Universities (Grant PGC2018-095795-B-I00) and by the European Union's Horizon 2020 FET Open Programme (Grant no. 801305).Peer reviewe

A panel of circulating non-coding RNAs in the diagnosis and monitoring of therapy in Egyptian patients with breast cancer

Background: Non-coding RNAs (ncRNAs) have recently been identified to have a pivotal role in many diseases, including breast cancer (BC). This study aims to investigate the relative quantification of long non-coding RNA (lncRNA) H19, microRNA (miR) 675-5p, 675-3p, and miR-let 7 in breast cancer patients. Methods: The study was performed on three groups: Group 1: 30 non-intervened BC female patients about to undergo breast surgery; group 2: 30 postoperative female BC patients about to receive adjuvant anthracycline chemotherapy; and group 3: 30 apparently healthy female volunteers as the control group. Plasma samples were drawn before and after the intervention in groups 1 and 2, with a single sample drawn from group 3. The relative quantification levels were compared with healthy control subjects and were related with the clinicopathological statuses of these patients. Results: There was a statistically significant increase in H19, miR-675-5p, miR-675-3p, and miR-let 7 in the non-intervened BC patients when compared to the control group. Surgery resulted in a significant reduction in all four ncRNAs under investigation. Chemotherapy brought about a significant increase in the level of miR-let 7, with no significant effect on the remaining parameters measured. The assay discriminated normal from BC where a receiver operating characteristic for the area under the curve (ROCAUC) of miR-675-3p showed the maximal AUC of 1.000. The diagnostic sensitivity and specificity were also 100% when CA 15-3 and H19 were combined. Conclusion: The results strongly indicate that the panel of ncRNAs in this study can all potentially act as novel biomarkers whether alone or combined in the diagnosis of BC

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

BACKGROUND: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. METHODS: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. RESULTS: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien–Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. CONCLUSION: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761

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

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