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

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

Walking the tightrope: communicating overdiagnosis in modern healthcare

Overdiagnosis and overtreatment have serious implications for individuals, healthcare systems, and society,1 2 and effective strategies are urgently needed to help the public, clinicians, and policy makers address this problem. Communication about overdiagnosis has been highlighted as essential for moving forward but presents several challenges, such as the potential to confuse the public, undermine trust, and adversely affect people who already have a diagnosis. Various communication based strategies offer real promise; we describe what is known and what we need to know to communicate effectively and safely about overdiagnosis and overtreatment. Key messages: Overdiagnosis provides no benefits to patients and is a challenge to the sustainability of modern healthcare systems Communication based strategies could help reduce overdiagnosis and its negative impact on individuals and health systems Mass media education, shared decision making, terminology changes for disease states, and deliberative methods (juries) all have potential as effective communication strategiesKJMcC is supported by a National Health and Medical Research Council (NHMRC) career development fellowship (1029241), JJ is supported by an NHMRC early career fellowship (1037028), and. JW is supported by a career development fellowship from Cancer Research UK (C7492/A17219)

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

Comment on Rojas-Bracho and Colleagues (2019): Unsubstantiated Claims Can Lead to Tragic Conservation Outcomes

The vaquita’s decline is a tragic story indeed. However, the lack of action to prevent the extinction of this species is not due to unsubstantiated claims and scientific uncertainty

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