PI3 kinase inhibition also abolished α-klotho’s ability to suppress food intake and improve glucose clearance. These results indicate a prominent role of hypothalamic α-klotho/FGFR1/PI3K signaling in the modulation of NPY/AgRP neuron activity and maintenance of energy homeostasis, thus providing new insight into the pathophysiology of metabolic disease. © 2020 by the American Diabetes Association.Chronic low-grade inflammation plays a central role in the pathophysiology of gestational diabetes mellitus (GDM). In order to investigate the ability of different inflammatory blood cell parameters in predicting the development of GDM and pregnancy outcomes, 258 women with GDM and 1154 women without were included in this retrospective study. First-trimester neutrophil count outperformed white blood cell (WBC) count, and neutrophil-to-lymphocyte ratio (NLR) in the predictability for GDM. Subjects were grouped based on tertiles of neutrophil count during their first-trimester pregnancy. The results showed that as the neutrophil count increased, there was a step-wise increase in GDM incidence, as well as glucose and glycosylated hemoglobin (HbA1c) level, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), macrosomia incidence and newborn weight. Neutrophil count was positively associated with pre-pregnancy Body Mass Index (BMI), HOMA-IR and newborn weight. Additionally, neutrophil count was an independent risk factor for the development of GDM, regardless of the history of GDM. Spline regression showed that there was a significant linear association between GDM incidence and continuous neutrophil count when it exceeded 5.0 × 109/L. This work suggested that first-trimester neutrophil count is closely associated with the development of GDM and adverse pregnancy outcomes. © 2020 by the American Diabetes Association.Diabetes occurs due to a loss of functional β-cells, resulting from β-cell death and dysfunction. Lactogens protect rodent and human β-cells in vitro and in vivo against triggers of β-cell cytotoxicity relevant to diabetes, many of which converge onto a common pathway, endoplasmic reticulum (ER) stress. However, whether lactogens modulate the ER stress pathway is unknown. This study examines if lactogens can protect β-cells against ER stress and mitigate diabetes incidence in Akita mice, a rodent model of ER stress-induced diabetes, akin to neonatal diabetes in humans. We show that lactogens protect INS1 cells, primary rodent and human β-cells in vitro against two distinct ER stressors, tunicamycin and thapsigargin, through activation of the JAK2/STAT5 pathway. Lactogens mitigate expression of pro-apoptotic molecules in the ER stress pathway that are induced by chronic ER stress in INS1 cells and rodent islets. Transgenic expression of placental lactogen in β-cells of Akita mice drastically reduces the severe hyperglycemia, diabetes incidence, hypoinsulinemia, β-cell death, and loss of β-cell mass observed in Akita littermates. These are the first studies in any cell type demonstrating lactogens modulate the ER stress pathway, causing enhanced β-cell survival and reduced diabetes incidence in the face of chronic ER stress. © 2020 by the American Diabetes Association.Healthcare systems around the world are struggling to maintain a sufficient workforce to provide adequate care during the COVID-19 pandemic. Staffing problems have been exacerbated by healthcare workers (HCWs) refusing to work out of concern for their families. I sketch a deontological framework for assessing when it is morally permissible for HCWs to abstain from work to protect their families from infection and when it is a dereliction of duty to patients. I argue that it is morally permissible for HCWs to abstain from work when their duty to treat is outweighed by the combined risks and burdens of that work. For HCWs who live with their families, the obligation to protect one’s family from infection contributes significantly to those burdens. There are, however, a range of complicating factors including the strength of duty to treat which varies according to the HCW’s role, the vulnerability of family members to the disease, the willingness of family members to risk infection and the resources available to the HCW to protect their family. In many cases, HCWs in ‚frontline‘ roles with a weak duty to treat and families at home will be morally permitted to abstain from work given the risks posed by COVID-19; therefore, society should provide additional incentives to maintain sufficient staff in these roles. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.Testimonial injustice occurs when bias against the credibility of certain social identities results in discounting of their contributions to deliberations. In this analysis, we describe testimonial injustice against women and how it figures in macroallocation procedure. We show how it harms women as deliberators, undermines the objective of inclusivity in macroallocation and affects the justice of resource distributions. CL-82198 nmr We suggest that remedial action is warranted in order to limit the effects of testimonial injustice in this context, especially on marginalised and disadvantaged groups, and propose three areas for action, whose implementation might feasibly be achieved by those immediately involved in macroallocation. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Medical trainees should learn from the actions of Nazi physicians to inform a more just contemporary practice by examining the subtle assumptions, or moral orientations, that led to such heinous actions. One important moral orientation that still informs contemporary medical practice is the moral orientation of elimination in response to suffering patients. We propose that the moral orientation of presence, described by theologian Stanley Hauerwas, provides a more fitting response to suffering patients, in spite of the significant barriers to enacting such a moral orientation for contemporary trainees. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.The decision-making environment in intensive care units (ICUs) is influenced by the transformation of intensive care medicine, the staffing situation and the increasing importance of patient autonomy. Normative implications of time in intensive care, which affect all three areas, have so far barely been considered. The study explores patterns of decision making concerning the continuation, withdrawal and withholding of therapies in intensive care. A triangulation of qualitative data collection methods was chosen. Data were collected through non-participant observation on a surgical ICU at an academic medical centre followed by semi-structured interviews with nurses and physicians. The transcribed interviews and observation notes were coded and analysed using qualitative content analysis according to Mayring. Three themes related to time emerged regarding the escalation or de-escalation of therapies influence of time on prognosis, time as a scarce resource and timing in regards to decision making. The study also reveals the ambivalence of time as a norm for decision making. The challenge of dealing with time-related efforts in ICU care results from the tension between the need to wait to optimise patient care, which must be balanced against the significant time pressure which is characteristic of the ICU setting. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.’Futility‘ is a contentious term that has eluded clear definition, with proposed descriptions either too strict or too vague to encompass the many facets of medical care. Requests for futile care are often surrogates for requests of a more existential character, covering the whole range of personal, emotional, cultural and spiritual needs. Physicians and other practitioners can use requests for futile care as a valuable opportunity to connect with their patients at a deeper level than the mere biomedical diagnosis. Current debate around Canada’s changing regulatory and legal framework highlights challenges in appropriately balancing the benefits and burdens created by requests for futile care. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Medical assistance in dying (MAID) legislation in Canada followed much deliberation after the Supreme Court of Canada’s ruling in Carter v. Canada Included in this deliberation was the Special Joint Committee on Physician Assisted Dying’s recommendation to extend MAID legislation beyond the inclusion of adults to mature minors. Children’s agency is a construct advanced within childhood studies literature which entails eliciting children’s voices in order to recognise children as active participants in constructing their own childhoods. Using this framework, we consider the possible extension of MAID legislation to most minors. We highlight important questions regarding how insights from children’s voices could be mobilised in the life or death context of MAID. We conclude that children’s voices have the potential to help determine their eligibility for MAID; however, incorporating children’s voices in the context of MAID requires careful consideration due to the complexity of voice. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.BACKGROUND The practice of giving animal research subjects proper names is frowned on by the academic scientific community. While researchers provide a number of reasons for desisting from giving their animal subjects proper names, the most common are that (1) naming leads to anthropomorphising which, in turn, leads to data and results that are unobjective and invalid; and (2) while naming does not necessarily entail some mistake on the researcher’s part, some feature of the research enterprise renders the practice impossible or ill-advised. OBJECTIVES My aim is to assess whether the scientific community’s attitude towards naming animal research subjects is justified. That is, I wish to consider whether the practice of naming animal research subjects is good or bad for the purposes of scientific research. METHOD After reviewing the extant literature, I constructed a list of the main arguments researchers provide for desisting from naming their animal research subjects. I then analysed these arguments, with a view to determining whether they in fact provide good reasons to avoid naming animal research subjects. CONCLUSION I argue that none of the aforementioned reasons usually provide good grounds for not naming animal research subjects. Moreover, there are usually powerful reasons in favour of researchers giving their research animals proper names. This is because the practice usually leads to greater empathy and so to improved animal well-being. This, in turn, leads to better animal science. Thus, the scientific community’s attitude towards naming animal research subjects is not justified. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.