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

Decoding Diabetes Biomarkers and Related Molecular Mechanisms by Using Machine Learning, Text Mining, and Gene Expression Analysis

The molecular basis of diabetes mellitus is yet to be fully elucidated. We aimed to identify the most frequently reported and differential expressed genes (DEGs) in diabetes by using bioinformatics approaches. Text mining was used to screen 40,225 article abstracts from diabetes literature. These studies highlighted 5939 diabetes-related genes spread across 22 human chromosomes, with 112 genes mentioned in more than 50 studies. Among these genes, HNF4A, PPARA, VEGFA, TCF7L2, HLA-DRB1, PPARG, NOS3, KCNJ11, PRKAA2, and HNF1A were mentioned in more than 200 articles. These genes are correlated with the regulation of glycogen and polysaccharide, adipogenesis, AGE/RAGE, and macrophage differentiation. Three datasets (44 patients and 57 controls) were subjected to gene expression analysis. The analysis revealed 135 significant DEGs, of which CEACAM6, ENPP4, HDAC5, HPCAL1, PARVG, STYXL1, VPS28, ZBTB33, ZFP37 and CCDC58 were the top 10 DEGs. These genes were enriched in aerobic respiration, T-cell antigen receptor pathway, tricarboxylic acid metabolic process, vitamin D receptor pathway, toll-like receptor signaling, and endoplasmic reticulum (ER) unfolded protein response. The results of text mining and gene expression analyses used as attribute values for machine learning (ML) analysis. The decision tree, extra-tree regressor and random forest algorithms were used in ML analysis to identify unique markers that could be used as diabetes diagnosis tools. These algorithms produced prediction models with accuracy ranges from 0.6364 to 0.88 and overall confidence interval (CI) of 95%. There were 39 biomarkers that could distinguish diabetic and non-diabetic patients, 12 of which were repeated multiple times. The majority of these genes are associated with stress response, signalling regulation, locomotion, cell motility, growth, and muscle adaptation. Machine learning algorithms highlighted the use of the HLA-DQB1 gene as a biomarker for diabetes early detection. Our data mining and gene expression analysis have provided useful information about potential biomarkers in diabetes

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat’s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms

Nanogold Particles Suppresses 5-Flurouracil-Induced Renal Injury: An Insight into the Modulation of Nrf-2 and Its Downstream Targets, HO-1 and γ-GCS

The development of the field of nanotechnology has revolutionized various aspects in the fields of modern sciences. Nano-medicine is one of the primary fields for the application of nanotechnology techniques. The current study sheds light on the reno-protective impacts of gold nano-particles; nanogold (AuNPs) against 5-flurouracil (5-FU)-induced renal toxicity. Indeed, the use of 5-FU has been associated with kidney injury which greatly curbs its therapeutic application. In the current study, 5-FU injection was associated with a significant escalation in the indices of renal injury, i.e., creatinine and urea. Alongside this, histopathological and ultra-histopathological changes confirmed the onset of renal injury. Both gene and/or protein expression of nuclear factor erythroid 2–related factor 2 (Nrf-2) and downstream antioxidant enzymes revealed consistent paralleled anomalies. AuNPs administration induced a significant renal protection on functional, biochemical, and structural levels. Renal expression of the major sensor of the cellular oxidative status Nrf-2 escalated with a paralleled reduction in the renal expression of the other contributor to this axis, known as Kelch-like ECH-associated protein 1 (Keap-1). On the level of the effector downstream targets, heme oxygenase 1 (HO-1) and gamma-glutamylcysteine synthetase (γ-GCS) AuNPs significantly restored their gene and protein expression. Additionally, combination of AuNPs with 5-FU showed better cytotoxic effect on MCF-7 cells compared to monotreatments. Thus, it can be inferred that AuNPs conferred reno-protective impact against 5-FU with an evident modulatory impact on Nrf-2/Keap-1 and its downstream effectors, HO-1 and γ-GCS, suggesting its potential use in 5-FU regimens to improve its therapeutic outcomes and minimize its underlying nephrotoxicity

Potential role of A\u3csub\u3e2A\u3c/sub\u3e adenosine receptor in traumatic optic neuropathy

In traumatic optic neuropathy (TON), apoptosis of retinal ganglion cells is closely related to the local production of reactive oxygen species and inflammatory mediators from activated microglial cells. Adenosine receptor A2A (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in TON. In the present study, we examined the role of A2AAR in retinal complications associated with TON. Initial studies in wild-type mice revealed that treatment with the A2AAR agonist resulted in marked decreases in the TON-induced microglial activation, retinal cell death and releases of reactive oxygen species and pro-inflammatory cytokines TNF-α and IL-6. To further assess the role of A2AAR in TON, we studied the effects of A2AAR ablation on the TON-induced retinal abnormalities. A2AAR-/- mice with TON showed a significantly higher mRNA level of TNF-α, Iba1-1 in retinal tissue, and ICAM-1 expression in retinal sections compared with wild-type mice with TON. To explore a potential mechanism by which A2AAR-signaling regulates inflammation in TON, we performed additional studies using hypoxia- or LPS-treated microglial cells as an in vitro model for TON. Activation of A2AAR attenuates hypoxia or LPS-induced TNF-α release and significantly repressed the inflammatory signaling, ERK in the activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in TON and suggests that the retinal protective effect of A2AAR is mediated by attenuating the inflammatory response that occurs in microglia via interaction with MAPKinase pathway. © 2013 Elsevier B.V

α-Lipoic Acid Protects against Cyclosporine A-Induced Hepatic Toxicity in Rats: Effect on Oxidative Stress, Inflammation, and Apoptosis

The clinical application of cyclosporine A (CsA) as an immunosuppressive agent is limited by its organ toxicity. We aimed to evaluate the effectiveness of α-lipoic acid against CsA-induced hepatotoxicity and to delineate the underlying molecular mechanisms. Male Wistar rats (n = 24, 8 per each group) received the vehicle, CsA (25 mg/kg) and/or ALA (100 mg/kg, p.o.) for 3 weeks. Biochemical markers of liver function (serum ALT, AST, ALP < GGT), oxidative stress (MDA, TAC, SOD, GSH, Nrf2/HO-1), inflammation (NF-κB, CD68, iNOS, NO, COX-2), and apoptosis (caspase-3) were assessed in serum and tissue. Liver histological analysis using H&E and Sirius red was performed. The development of liver injury in CsA-treated animals was indicated by elevated levels of liver enzymes, oxidants/antioxidants imbalance, inflammatory cells infiltration, up-regulated expression of inflammatory mediators, and apoptosis. These changes were associated with altered architecture of hepatic cells and fibrous connective tissue. ALA co-administration protected against CsA-induced liver damage and ameliorated biochemical changes and cellular injury. In conclusion, ALA demonstrated hepatoprotective potential against CsA-induced liver injury through combating oxidative stress, inflammation, and apoptosis, highlighting ALA as a valuable adjunct to CsA therapy

Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines

In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury&mdash;Insight into Oxidative Injury/Inflammation/Apoptosis Modulation

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium&ndash;glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-&kappa;B and TNF-&alpha; expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune&ndash;histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury