AimsTo investigate, for a given energy expenditure (EE) rise, the differential effects of glucagon infusion and cold exposure on brown adipose tissue (BAT) activation in humans.MethodsIndirect calorimetry and supraclavicular thermography was performed in 11 healthy male volunteers before and after: cold exposure; glucagon infusion (at 23 °C); and vehicle infusion (at 23 °C). All volunteers underwent 18F‐fluorodeoxyglucose (18F‐FDG) positron emission tomography (PET)/CT scanning with cold exposure. Subjects with cold‐induced BAT activation on 18F‐FDG PET/CT (n = 8) underwent a randomly allocated second 18F‐FDG PET/CT scan (at 23 °C), either with glucagon infusion (n = 4) or vehicle infusion (n = 4).ResultsWe observed that EE increased by 14% after cold exposure and by 15% after glucagon infusion (50 ng/kg/min; p < 0.05 vs control for both). Cold exposure produced an increase in neck temperature (+0.44 °C; p < 0.001 vs control), but glucagon infusion did not alter neck temperature. In subjects with a cold‐induced increase in the metabolic activity of supraclavicular BAT on 18F‐FDG PET/CT, a significant rise in the metabolic activity of BAT after glucagon infusion was not detected. Cold exposure increased sympathetic activation, as measured by circulating norepinephrine levels, but glucagon infusion did not.ConclusionsGlucagon increases EE by a similar magnitude compared with cold activation, but independently of BAT thermogenesis. This finding is of importance for the development of safe treatments for obesity through upregulation of EE.

Context:In vitro fertilization (IVF) treatment is an effective therapy for infertility, but can result in the potentially life-threatening complication, ovarian hyperstimulation syndrome (OHSS).Objective:This study aimed to investigate whether kisspeptin-54 can be used to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.Setting and Design:This was a phase 2, multi-dose, open-label, randomized clinical trial of 60 women at high risk of developing OHSS carried out during 2013–2014 at Hammersmith Hospital IVF unit, London, United Kingdom.Intervention:Following a standard recombinant FSH/GnRH antagonist protocol, patients were randomly assigned to receive a single injection of kisspeptin-54 to trigger oocyte maturation using an adaptive design for dose allocation (3.2 nmol/kg, n = 5; 6.4 nmol/kg, n = 20; 9.6 nmol/kg, n = 15; 12.8 nmol/kg, n = 20). Oocytes were retrieved 36 h after kisspeptin-54 administration, assessed for maturation, and fertilized by intracytoplasmic sperm injection with subsequent transfer of one or two embryos. Women were routinely screened for the development of OHSS.Main Outcome Measure:Oocyte maturation was measured by oocyte yield (percentage of mature oocytes retrieved from follicles ≥ 14 mm on ultrasound). Secondary outcomes include rates of OHSS and pregnancy.Results:Oocyte maturation occurred in 95% of women. Highest oocyte yield (121%) was observed following 12.8 nmol/kg kisspeptin-54, which was +69% (confidence interval, −16–153%) greater than following 3.2 nmol/kg. At all doses of kisspeptin-54, biochemical pregnancy, clinical pregnancy, and live birth rates per transfer (n = 51) were 63, 53, and 45%, respectively. Highest pregnancy rates were observed following 9.6 nmol/kg kisspeptin-54 (85, 77, and 62%, respectively). No woman developed moderate, severe, or critical OHSS.Conclusion:Kisspeptin-54 is a promising approach to effectively and safely trigger oocyte maturation in women undergoing IVF treatment at high risk of developing OHSS.

BackgroundThe language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined.ObjectiveWe aimed to quantify the extent of language deficits in this patient group.MethodsWe assessed a cohort of patients with bvFTD (n=24) in relation to patents with semantic variant primary progressive aphasia (svPPA; n=14), nonfluent variant primary progressive aphasia (nfvPPA; n=18) and healthy age-matched individuals (n=24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients’ brain magnetic resonance images.ResultsRelative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network.ConclusionsbvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker.