Constitutive Activation of AKT2 in Humans Leads to Hypoglycemia Without Fatty Liver or Metabolic Dyslipidemia

$\textbf{Context:}$ The activating p.Glu17Lys mutation in AKT2, a kinase mediating many of insulin’s metabolic actions, causes hypoinsulinemic hypoglycemia and left-sided hemihypertrophy. The wider metabolic profile and longer-term natural history of the condition has not yet been reported. $\textbf{Objective:}$ To characterize the metabolic and cellular consequences of the AKT2 p.Glu17Lys mutation in two previously reported males at the age of 17 years. $\textbf{Design and Intervention:}$ Body composition analysis using dual-energy X-ray absorptiometry, overnight profiling of plasma glucose, insulin, and fatty acids, oral glucose tolerance testing, and magnetic resonance spectroscopy to determine hepatic triglyceride content was undertaken. Hepatic $\textit{de novo}$ lipogenesis was quantified using deuterium incorporationinto palmitate. Signalingin dermal fibroblasts was studied $\textit{ex vivo}$. $\textbf{Results:}$ Both patients had 37% adiposity. One developed hypoglycemia after 2 hours of overnight fasting with concomitant suppression of plasma fatty acids and ketones, whereas the other maintained euglycemia with an increase in free fatty acids. Blood glucose excursions after oral glucose were normal in both patients, albeit with low plasma insulin concentrations. In both patients, plasma triglyceride concentration, hepatic triglyceride content, and fasting hepatic $\textit{de novo}$ lipogenesis were normal. Dermal fibroblasts of one proband showed low-level constitutive phosphorylation of AKT and some downstream substrates, but no increased cell proliferation rate. $\textbf{Conclusions:}$ The p.Glu17Lys mutation of AKT2 confers low-level constitutive activity upon the kinase and produces hypoglycemia with suppressed fatty acid release from adipose tissue, but not fatty liver, hypertriglyceridemia, or elevated hepatic $\textit{de novo}$ lipogenesis. Hypoglycemia may spontaneously remit.This work was supported by Wellcome Trust Grant WT098498, the Medical Research Council (MRC_MC_UU_12012/5), the United Kingdom National Institute for Health Research Cambridge Biomedical Research Centre, the European Union/ European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking (European Medical Information Framework Grant 115372), and the Cambridge Gates Foundation

Assessment of burnout in veterinary medical students using the Maslach Burnout Inventory-Educational Survey: a survey during two semesters

BACKGROUND: Burnout among veterinary students can result from known stressors in the absence of a support system. The objectives of this study were to evaluate use of the Maslach Burnout Inventory-Educator Survey (MBI-ES) to assess burnout in veterinary students and evaluate the factors that predict the MBI-ES scores. METHODS: The MBI-ES was administered to first (Class of 2016) and second year (Class of 2015) veterinary medical students during the 2012-2013 academic year in the fall and spring semesters. Factor analysis and test reliability for the survey were determined. Mean scores for the subscales determining burnout namely emotional exhaustion (EE), depersonalization (DP) and lack of personal accomplishment (PA) were calculated for both classes in the 2 semesters. Multiple regression analysis was performed to evaluate other factors that predict the MBI-ES scores. RESULTS: A non-probability sampling method was implemented consisting of a voluntary sample of 170 and 123 students in the fall and spring semesters, respectively. Scores for EE, DP and PA were not different between the 2 classes within the same semester. Mean ± SD scores for EE, DP and PA for the fall semester were 22.9 ± 9.6, 5.0 ± 4.8 and 32.3 ± 6.7, respectively. Mean ± SD scores for EE, DP and PA the spring semester were 27.8 ± 10.7, 6.5 ± 6.1and 31.7 ± 6.8, respectively. The EE score was higher in spring compared to fall while DP and PA scores were not different between the 2 semesters. Living arrangements specifically as to whether or not a student lived with another veterinary medical students was the only variable significantly associated with the MBI-ES scores. Students in this study had moderate levels of burnout based on the MBI-ES scores. CONCLUSIONS: The MBI-ES was an acceptable instrument for assessing burnout in veterinary medical students. The EE scores were higher in the spring semester as compared to the fall semester. Thus students in the first and second years of veterinary school under the current curriculum experience the greatest levels of emotional exhaustion during the spring semester. This has administrative implications for the school, when considering the allocation and use of resources for student support systems during each semester

High rates of burnout among maternal health staff at a referral hospital in Malawi: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Burnout among maternal healthcare workers in sub-Saharan Africa may have a negative effect on services provided and efforts to mitigate high maternal mortality rates. In Malawi, research on burnout is limited and no empirical research has been conducted specifically among maternal health staff. Therefore, the aims of the study were to examine the prevalence and degree of burnout reported by healthcare workers who provide antenatal, intrapartum, and postnatal services in a district referral hospital in Malawi; and, to explore factors that may influence the level of burnout healthcare workers experience.</p> <p>Methods</p> <p>In the current cross-sectional study, levels of burnout among staff working in obstetrics and gynaecology at a referral hospital in Malawi were examined, in addition to individual and job characteristics that may be associated with burnout.</p> <p>Results</p> <p>In terms of the three dimensions of burnout, of the 101 participants, nearly three quarters (72%) reported emotional exhaustion, over one third (43%) reported depersonalization while almost three quarters (74%) experienced reduced personal accomplishment.</p> <p>Conclusions</p> <p>Based on these findings, burnout appears to be common among participating maternal health staff and they experienced more burnout than their colleagues working in other medical settings and countries. Further research is needed to identify factors specific to Malawi that contribute to burnout in order to inform the development of prevention and treatment within the maternal health setting.</p

Impact of a physical activity program on the anxiety, depression, occupational stress and burnout syndrome of nursing professionals

OBJECTIVE: to assess the effects of a workplace physical activity (WPA) program on levels of anxiety, depression, burnout, occupational stress and self-perception of health and work-related quality of life of a nursing team in a palliative care unit.METHODS: the WPA was conducted five days per week, lasting ten minutes, during three consecutive months. Twenty-one nursing professionals were evaluated before and after the intervention, with the Hospital Anxiety and Depression Scale, the Maslch Burnout Inventory, and the Job Stress Scale. The changes in self-perceived health and work-related quality of life were measured using a semi-structured questionnaire.RESULTS: the WPA did not yield significant results on the levels of anxiety, depression, burnout or occupational stress. However, after the intervention, participants reported improved perceptions of bodily pain and feeling of fatigue at work.CONCLUSION: the WPA did not lead to beneficial effects on occupational stress and psychological variables, but it was well accepted by the nursing professionals, who reported improvement in perceptions of health and work-related quality of life

Reproductive health and burn-out among female physicians: nationwide, representative study from Hungary

BACKGROUND: There is a worldwide rising tendency of women deciding to become physicians; hence, one of the most remarkable fields of investigation is the wellbeing of female doctors. The aim of this study was to describe female physicians' reproductive health in Hungary and to explore the potential correlation between their reproductive disorders and burnout symptoms. Up to our present knowledge, there have not been any studies investigating the correlation between reproductive disorders and burnout of female physicians; therefore, our study represents a unique approach. METHODS: Data in this representative cross-sectional epidemiological study were obtained from online questionnaires completed by 3039 female physicians. Participants in a representative nationwide survey (Hungarostudy, 2013) served as controls (n = 1069). Differences between physicians and the control group were disclosed by chi-square test. Correlations between certain factors of reproductive health and the three dimensions of burnout were detected by Pearson correlations and X2 test. Binary logistic regression analysis was used to determine the association between burnout and reproductive health. RESULTS: Female physicians were more often characterised by time-to-pregnancy interval longer than one year (18.4% vs. 9.8%), were bearing more high-risk pregnancies (26.3% vs.16.3%), and were more likely to be undergoing infertility therapy (8.5% vs. 3.4%) and experiencing miscarriage (20.8% vs. 14.6%) during their reproductive years, compared with the general female population. With the exception of miscarriages, the difference remained significant in all comparisons with the professional control group. Both high-risk pregnancies and miscarriages of doctors were associated with depersonalisation (p = 0.028 and p = 0.012 respectively) and personal accomplishment (p = 0.016 and p = 0.008 respectively) dimensions of burnout. Results of the multivariate analysis showed that, beside traditional risk factors, depersonalisation acted as an important explanatory factor in case of high-risk pregnancies (OR = 1.086). CONCLUSIONS: There is a circulatory causality between burnout and the development of reproductive disorders. Burnout is an important risk factor for high-risk pregnancies and miscarriages, and it has a negative effect on the outcome of pregnancies. At the same time, women suffering from reproductive disorders are more likely to develop burnout syndrome. Improvement of working conditions and prevention of burnout in female doctors are equally important tasks

The role of rewards and demands in burnout among surgical nurses

Job rewards have both, an intrinsic and an extrinsic motivational potential, and lead to employees’ development as well as help them to achieve work goals. Rewards can balance job demands and protect from burnout. Due to changes on the labour market, new studies are needed. The aim of our study was to examine the role of demands and individual rewards (and their absence) in burnout among surgical nurses. Materials and Methods: The study was conducted in 2009 and 2010 with 263 nurses who worked in surgical wards and clinics in hospitals in Southern Poland. The hypotheses were tested by the use of measures of demands and rewards (Effort-Reward Imbalance Questionnaire by Siegrist) and burnout syndrome (Maslach Burnout Inventory). A cross-sectional, correlational study design was applied. Results: Nurses experienced the largest deficiencies in salary and prestige. Exhaustion was explained by stronger demands and lack of respect (large effect). Depersonalization was explained by stronger demands, lack of respect and greater job security (medium effect). Reduced personal achievement was explained by more demands and greater job security (small effect). Conclusions: Excessive demands and lack of esteem are key reasons for burnout among surgical nurses. Job security can increase burnout when too many resources are invested and career opportunities do not appear. These results may help to improve human resource management in the healthcare sector

Toward validating the Italian version of the "Spanish Burnout Inventory": a preliminary study

AbstractOBJECTIVEThe aim of this study was to develop the Italian version of the Spanish Burnout Inventory (SBI) and to examine its psychometric properties within a sample of nursing staff.METHODThe study was cross-sectional and not randomized. The data were gathered using an anonymous, self-report questionnaire. The sample consisted of 391 staff nurses employed in three hospitals in the Northern Region of Italy To evaluate burnout, the SBI and the Maslach Burnout Inventory were administered.RESULTSAn Exploratory Factor Analysis showed a four-factor structure close to the expected one. All Cronbach's alpha values were satisfactory. Furthermore, correlations support the concurrent validity.CONCLUSIONOverall, the results of this study provided evidence that the SBI is an adequate instrument to study burnout in the Italian nursing sample and indicated the feeling of guilt as an important dimension to gauge the structure of this phenomenon

Geography of non-melanoma skin cancer and ecological associations with environmental risk factors in England.

This is the author's peer reviewed version of the article. Please cite the published, final version which is available via the DOI link in this record.This study investigates the geography of non-melanoma skin cancer (NMSC) in England, and ecological associations with three widespread environmental hazards: radon, arsenic and ultraviolet radiation from the sun.European Regional Development FundEuropean Social Fund Convergence Programme for Cornwall and the Isles of Scill