172 research outputs found
ROS homeostasis and metabolism: a dangerous liason in cancer cells
Tumor cells harbor genetic alterations that promote a continuous and elevated production of reactive oxygen species. Whereas such oxidative stress conditions would be harmful to normal cells, they facilitate tumor growth in multiple ways by causing DNA damage and genomic instability, and ultimately, by reprogramming cancer cell metabolism. This review outlines the metabolic-dependent mechanisms that tumors engage in when faced with oxidative stress conditions that are critical for cancer progression by producing redox cofactors. In particular, we describe how the mitochondria has a key role in regulating the interplay between redox homeostasis and metabolism within tumor cells. Last, we will discuss the potential therapeutic use of agents that directly or indirectly block metabolism
Role of splenectomy for immune thrombocytopenic purpura (ITP) in the era of new second-line therapies and in the setting of a high prevalence of HIV-associated ITP
Background. New agents are being used as second-line treatment for immune thrombocytopenia (ITP) and have brought into question the relevance of splenectomy for steroid-resistant ITP.Methods. We retrospectively analysed 73 patients who underwent splenectomy for ITP at our institution over an 11-year period. The median follow-up period was 25 months; patients with follow-up of <1 month were excluded. The outcomes of splenectomy were compared in HIV-positive v. HIV-negative patients.Results. The rate of complete response was 83%, and response was sustained for at least 1 year or until latest follow-up in 80% of patients. Twelve patients were HIV-positive. Splenectomy was laparoscopic in 43 patients (62%) with an overall 16% complication rate. The 90-day mortality rate was 1.38%. There was no statistically significant difference in response or complication rate in the HIV-positive patients. There was a statistically significant (p=0.017) poorer response to splenectomy in the patients with steroid-resistant ITP.Conclusion. Splenectomy is effective and safe irrespective of HIV status and remains an appropriate second-line treatment for ITP. Further research is needed to corroborate our finding of lower response in patients who are steroid-resistant, as this might be a subgroup of patients who may benefit from thrombopoietin agonists as second-line therapy
A multicentre evaluation of emergency abdominal surgery in South Africa: Results from the GlobalSurg-1 South Africa study
Background. GlobalSurg-1 was a multicentre, international, prospective cohort study conducted to address the global lack of surgical outcomes data. Six South African (SA) hospitals participated in the landmark surgical outcomes study. In this subsequent study, we collated the data from these six local participants and hypothesised that the location of surgery was an independent risk factor for an adverse outcome following emergency intraperitoneal surgery.Methods. Participating hospitals contributed 30-day outcomes data of consecutive emergency intraperitoneal surgical operations performed during a 2 week period between July and November 2014. The six heterogeneous hospital cohorts were compared by categorical confounders. The primary outcome measure was in-hospital mortality; secondary outcome measures were in hospital morbidity and length of stay of >14 days. The unadjusted association between hospital and adverse outcome and the univariate association between categorical confounders and adverse outcome were tested. Significant associations were further tested by a multivariate stepwise forward logistic regression model built for each outcome of interest.Results. Six hospitals (designated 1 - 6) contributed outcomes data for 169 operations. The mean age of the patients was 34.9 years (range 9 - 82), 116 (68.6%) were male, and the majority (37.2%) presented as a result of trauma. Hospital 5 was associated with 76-fold increased odds of in-hospital death and 58-fold increased odds of a major in-hospital complication, and hospital 3 was associated with 3-fold increased odds of any in-hospital complication. The final model predicting in-hospital death had a receiver operating characteristic curve statistic of 0.8892.Conclusion. The hospital is an independent risk factor for risk-adjusted adverse outcomes following emergency intraperitoneal surgery in SA
General Surgery in crisis - the critical shortage
Introduction: General surgery is facing a serious crisis. There has been a significant decline in the number of applicants for registrar posts and an inability to attract and retain general surgical specialists in the state sector. The Association of Surgeons of South Africa (ASA) undertook this study to determine the extent and cause of the problem. Methods: The study involved a combination of desk research and structured interviews. In addition, the Health Professions Council of South Africa (HPCSA) database was reviewed and compared with the South African Medical Association (SAMA) and ASA databases. The medical schools provided information about student numbers and demographics, and the National Department of Health provided information about the status of medical practitioner and specialist posts in the state sector. Results: Overall, 26.1% of the specialist posts were vacant. The situation was particularly critical in Mpumalanga and the Eastern Cape, where 84% and 58% of the specialist posts were vacant. Using a predictive model, a conservative estimate of the need for general surgeons was found to be at least 50 per year. Currently the eight medical schools graduate about 25 general surgeons per year. The changing demographics of medical students may be partly responsible for the decline in registrar applicants. Conclusion. The findings from this study have revealed that the shortage of general surgeons in the state sector has reached critical levels
Risk of blood splashes to the eye during surgery
Background. With the advent of a new infectious era involving the HIV and hepatitis B and C viruses, concern has arisen about transmission of these viruses through ocular blood splashes during surgery. The purpose of the study was to determine the risk of ocular blood splashes to surgeons and their assistants during surgery.
Method. Surgeons and assistants in several surgical disciplines were requested to wear facemasks with a transparent plastic visor. The visors were collected postoperatively and inspected for macroscopic and microscopic blood splashes.
Results. Fifty-nine per cent of the surgeons and assistants refused to wear facemasks with a visor. The incidence of blood splashes in those who participated was 45%. There was a trend for blood splashes to be more common during major surgery and during elective surgery. Surgeons and assistants were subject to similar risk.
Conclusion. This study confirms the significant risk of ocular blood splashes during surgery, while also suggesting that both surgeons and assistants lack appreciation of the risk
Surgical training and capacity development in the South African internship programme
Medical practitioners in South Africa manage a quadruple burden of disease. Junior doctors, who contribute significantly to the health workforce, must complete 2 years of internship training and 1 year of community service work in state health facilities after graduation to register as an independent medical practitioner. The aim of this article is to give a critical appraisal of the current national internship programme and why it was implemented, and outline suggestions for future changes. There is a compelling need to train competent, confident doctors while ensuring that the requirements and demands of our health system remain a central concern
Origin and transformation of light hydrocarbons ascending at an active pockmark on Vestnesa Ridge, Arctic Ocean
We report on the geochemistry of hydrocarbons and pore waters down to 62.5 mbsf, collected by drilling with the MARUMâMeBo70 and by gravity coring at the Lunde pockmark in the Vestnesa Ridge. Our data document the origin and transformations of volatiles feeding gas emissions previously documented in this region. Gas hydrates are present where a fracture network beneath the pockmark focusses migration of thermogenic hydrocarbons characterized by their C1/C2+ and stable isotopic compositions (δ2HâCH4, δ13CâCH4). Measured geothermal gradients (~80°C kmâ1) and known formation temperatures (>70°C) suggest that those hydrocarbons are formed at depths >800 mbsf.
A combined analytical/modeling approach, including concentration and isotopic mass balances, reveals that pockmark sediments experience diffuse migration of thermogenic hydrocarbons. However, at sites without channeled flow this appears to be limited to depths > ~50 mbsf. At all sites we document a contribution of microbial methanogenesis to the overall carbon cycle that includes a component of secondary carbonate reduction (CR) â i.e. reduction of dissolved inorganic carbon (DIC) generated by anaerobic oxidation of methane (AOM) in the uppermost methanogenic zone. AOM and CR rates are spatially variable within the pockmark and are highest at highâflux sites. These reactions are revealed by δ13CâDIC depletions at the sulfateâmethane interface at all sites. However, δ13CâCH4 depletions are only observed at the low methane flux sites because changes in the isotopic composition of the overall methane pool are masked at highâflux sites. 13Câdepletions of TOC suggest that at seeps sites, methaneâderived carbon is incorporated into de novo synthesized biomass
Aspartate metabolism in endothelial cells activates the mTORC1 pathway to initiate translation during angiogenesis
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