Impact of GLP-1 receptor agonist versus omega-3 fatty acids supplement on obesity-induced alterations of mitochondrial respiration

ObjectiveTo compare administration of the glucagon-like peptide-1 (GLP-1) analogue, exenatide, versus dietary supplementation with the omega-3 fatty acid-rich Calanus oil on obesity-induced alterations in mitochondrial respiration. MethodsSix-week-old female C57BL/6JOlaHSD mice were given high fat diet (HFD, 45% energy from fat) for 12 weeks to induce obesity. Thereafter, they were divided in three groups where one received exenatide (10 mu g/kg/day) via subcutaneously implanted mini-osmotic pumps, a second group received 2% Calanus oil as dietary supplement, while the third group received HFD without any treatment. Animals were sacrificed after 8 weeks of treatment and tissues (skeletal muscle, liver, and white adipose tissue) were collected for measurement of mitochondrial respiratory activity by high-resolution respirometry, using an Oroboros Oxygraph-2k (Oroboros instruments, Innsbruck, Austria). ResultsIt was found that high-fat feeding led to a marked reduction of mitochondrial respiration in adipose tissue during all three states investigated - LEAK, OXPHOS and ETS. This response was to some extent attenuated by exenatide treatment, but not with Calanus oil treatment. High-fat feeding had no major effect on hepatic mitochondrial respiration, but exenatide treatment resulted in a significant increase in the various respiratory states in liver. Mitochondrial respiration in skeletal muscle was not significantly influenced by high-fat diet or any of the treatments. The precise evaluation of mitochondrial respiration considering absolute oxygen flux and ratios to assess flux control efficiency avoided misinterpretation of the results. ConclusionsExenatide increased hepatic mitochondrial respiration in high-fat fed mice, but no clear beneficial effect was observed in skeletal muscle or fat tissue. Calanus oil did not negatively affect respiratory activity in these tissues, which maintains its potential as a dietary supplement, due to its previously reported benefits on cardiac functio

The challenges with managing polycystic ovary syndrome : A qualitative study of women’s and clinicians’ experiences

Funding The study was funded by the University of Sydney Lifespan Research Network and the National Health and Medical Research Council (NHMRC) Program Grant (APP1113532), Australia. Acknowledgements We gratefully acknowledge the women and clinicians who participated in the study, and the project’s PCOS consumers: Nicola Smith, Wendy Liang and Belinda Snape. We recognise that non-binary people and people of various gender identities can be affected by PCOS. All participants with PCOS identified as women in the current study, so for the purposes of this paper, the term ‘women’ will be used throughout.Peer reviewedPostprin

Ectopic pregnancy: when is expectant management safe?

This study was conducted to evaluate expectant management in asymptomatic patients with an initial serum beta-hCG titer of <2,500 IU/l and to determine the independent ability of initial serum beta-hCG titers and trend of serum beta-hCG to predict successful expectant management. A cohort of patients (N = 418) with suspected ectopic pregnancy (EP) between January 1991 and July 2008 is described. Three groups were defined: group I (n = 182), immediate surgical intervention (<24 h); group IIa (n = 130), unsuccessful expectant management (surgical intervention during follow-up), and group IIb (n = 99), successful expectant management (spontaneous regression of trophoblast). Hospital protocol was not complied in 35 cases (Table 1). Beta-hCG levels >3,000 IU/l occur in our expectant management group; however, none of these cases were successful. Unnecessary surgery was prevented in 14% (n = 7) of asymptomatic patients with initial beta-hCG of >2,000 IU/l. The success rate of expectant management was 49%, without a rise in complication rate or number of acute cases. In conclusion, the initial serum beta-hCG cutoff level of 2,000 IU/l is not a rigid upper limit for accepting expectant management in suspected EP and best practice is case specific. In asymptomatic patients, the serum beta-hCG cutoff level of at least 2,500 IU/l can be used for expectant management. This cutoff could be higher, but interpretation is limited due to censure in follow-up inherent to the predefined clinical protocol. There is no gain in including patients for expectant management with initial serum beta-hCG level >3,000 IU/l

Too Much Medicine in older people? Deprescribing through Shared Decision Making

Too much medicine is an increasingly recognised problem,1 2 and one manifestation is inappropriate polypharmacy in older people. Polypharmacy is usually defined as taking more than five regular prescribed medicines.3 It can be appropriate (when potential benefits outweigh potential harms)4 but increases the risk of older people experiencing adverse drug reactions, impaired physical and cognitive function, and hospital admission.5 6 7 There is limited evidence to inform polypharmacy in older people, especially those with multimorbidity, cognitive impairment, or frailty.8 Systematic reviews of medication withdrawal trials (deprescribing) show that reducing specific classes of medicines may decrease adverse events and improve quality of life.9 10 11 Two recent reviews of the literature on deprescribing stressed the importance of patient involvement and shared decision making.12 13 Patients and clinicians typically overestimate the benefits of treatments and underestimate their harms.14 When they engage in shared decision making they become better informed about potential outcomes and as a result patients tend to choose more conservative options (eg, fewer medicines), facilitating deprescribing.15 However, shared decision making in this context is not easy, and there is little guidance on how to do it.16 We draw together evidence from the psychology, communication, and decision making literature (see appendix on thebmj.com). For each step of the shared decision making process we describe the unique tasks required for deprescribing decisions; identify challenges for older adults, their companions, and clinicians (figure); give practical advice on how challenges may be overcome; highlight where more work is needed; and identify priorities for future research (table). Key messages Deprescribing is a process of planned and supervised tapering or ceasing of inappropriate medicines Shared decision making should be an integral part of the deprescribing process Many factors affect this process, including trust in clinicians’ advice, contradictory patient attitudes about medication, cognitive biases that lead to a preference for the status quo and positive information, and information processing difficulties There is uncertainty about the effect of risk communication and preference elicitation tools in older people Older people’s preferences for discussing life expectancy and quality of life vary widely, but even those who wish to delegate their decisions still appreciate discussion of optionsJJ is supported by a National Health and Medical Research Council (NHMRC) early career fellowship (1037028) and KM is supported by an NHMRC career development fellowship (1029241

Sea ice variability in the southern Norwegian Sea during glacial Dansgaard-Oeschger climate cycles.

The last glacial period was marked by pronounced millennial-scale variability in ocean circulation and global climate. Shifts in sea ice cover within the Nordic Seas are believed to have amplified the glacial climate variability in northern high latitudes and contributed to abrupt, high-amplitude temperature changes over Greenland. We present unprecedented empirical evidence that resolves the nature, timing, and role of sea ice fluctuations for abrupt ocean and climate change 32 to 40 thousand years ago, using biomarker sea ice reconstructions from the southern Norwegian Sea. Our results document that initial sea ice reductions at the core site preceded the major reinvigoration of convective deep-water formation in the Nordic Seas and abrupt Greenland warming; sea ice expansions preceded the buildup of a deep oceanic heat reservoir. Our findings suggest that the sea ice variability shaped regime shifts between surface stratification and deep convection in the Nordic Seas during abrupt climate changes

Sea ice variability in the southern Norwegian Sea during glacial Dansgaard-Oeschger climate cycles.

Ground was broken two weeks ago for the new women\u27s dormitory which will be known as Compton. Professor Robert Bonthius of the department of religion has resigned from the College of Wooster. He will be going to New York to be a chaplain and professor of religion at Vassar College. Five senior art majors will have their art on display beginning May 9th. Head of the department of chemistry, Dr. Roy I. Grady, will act in the place of Dean William Taeusch for the 1954-1955 school year.https://openworks.wooster.edu/voice1951-1960/1071/thumbnail.jp

Vaquita Face Extinction from Bycatch. Comment on Manjarrez-Bringas, N. et al., Lessons for Sustainable Development: Marine Mammal Conservation Policies and Its Social and Economic Effects.

We are among the scientists who have documented the environmental and ecological changes to the Upper Gulf of California following the reduction in the Colorado River’s flow. We object to any suggestion that our research supports Manjarrez-Bringas et al.’s conclusion that the decline in the Colorado River’s flow is the reason for the decline in the population of the endangered vaquita porpoise (Phocoena sinus). Manjarrez-Bringas et al.’s conclusions are incongruent with their own data, their logic is untenable, their analyses fail to consider current illegal fishing practices, and their recommendations are unjustified and misdirected. Vaquita face extinction because of bycatch, not because of the lack of river flow

Global Health Education: a cross-sectional study among German medical students to identify needs, deficits and potential benefits (Part 1 of 2: Mobility patterns & educational needs and demands)

<p>Abstract</p> <p>Background</p> <p>In recent years, education and training in global health has been the subject of recurring debate in many countries. However, in Germany, there has been no analysis of the educational needs or demands of medical students, or the educational deficits or potential benefits involved in global health education. Our purpose is to analyse international health elective patterns of medical students enrolled at German universities and assess whether or how they prepare for their electives abroad. We examine the exposure of medical students enrolled at German universities to training courses in tropical medicine or global health and assess students' perceived needs and demands for education in global health.</p> <p>Methods</p> <p>Cross-sectional study among medical students in Germany including all 36 medical schools during the second half of the year 2007. All registered medical students were eligible to participate in the study. Recruitment occurred via electronic mailing-lists of students' unions. We developed a web-based, semi-structured questionnaire to capture students' international mobility patterns, preparation before electives, destination countries, exposure to and demand for global health learning opportunities.</p> <p>Results</p> <p>1126 online-replies were received and analysed from all registered medical students in Germany (N = 78.067). 33.0% of all respondents (370/1126) declared at least one international health elective and of these, 36.0% (133/370) completed their electives in developing countries. 36.0% (131/363) did not prepare specifically at all, 59.0% (214/363) prepared either by self-study or declared a participation in specific preparation programmes. 87.8% of 5^thand 6^thyear students had never participated in a global health course and 72.6% (209/288) had not completed a course in tropical medicine. 94.0% (861/916) endorsed the idea of introducing global health into medical education.</p> <p>Conclusion</p> <p>Students in our sample are highly mobile during their studies. International health electives are common, also in developing countries. Formal preparation beyond self-study is virtually non-existent amongst our sample and the participation rate in courses of tropical medicine or global health is appallingly low. We have identified unmet perceived needs and the demand for more learning opportunities in global health in our sample, urging for reforms to adjust curricula to a globalising world.</p

Decreased expression of ABAT and STC2 hallmarks ER-positive inflammatory breast cancer and endocrine therapy resistance in advanced disease

Background: Patients with Estrogen Receptor α-positive (ER+) Inflammatory Breast Cancer (IBC) are less responsive to endocrine therapy compared with ER+ non-IBC (nIBC) patients. The study of ER+ IBC samples might reveal biomarkers for endocrine resistant breast cancer. Materials & methods: Gene expression profiles of ER+ samples from 201 patients were explored for genes that discriminated between IBC and nIBC. Classifier genes were applied onto clinically annotated expression data from 947 patients with ER+ breast cancer and validated with RT-qPCR for 231 patients treated with first-line tamoxifen. Relationships with metastasis-free survival (MFS) and progression-free survival (PFS) following adjuvant and first-line endocrine treatment, respectively, were investigated using Cox regression analysis. Results: A metagene of six genes including the genes encoding for 4-aminobutyrate aminotransferase (ABAT) and Stanniocalcin-2 (STC2) were identified to distinguish 22 ER+ IBC from 43 ER+ nIBC patients and remained discriminatory in an independent series of 136 patients. The metagene and two genes were not prognostic in 517 (neo)adjuvant untreated lymph node-negative ER+ nIBC breast cancer patients. Only ABAT was related to outcome in 250 patients treated with adjuvant tamoxifen. Three independent series of in total 411 patients with advanced disease showed increased metagene scores and decreased expression of ABAT and STC2 to be correlated with poor first-line endocrine therapy outcome. The biomarkers remained predictive for first-line tamoxifen treatment outcome in multivariate analysis including traditional factors or published signatures. In an exploratory analysis, ABAT and STC2 protein expression levels had no relation with PFS after first-line tamoxifen. Conclusions: This study utilized ER+ IBC to identify a metagene including ABAT and STC2 as predictive biomarkers for endocrine therapy resistance