Agrp neuron activity is required for alcohol-induced overeating

Alcohol intake associates with overeating in humans. This overeating is a clinical concern, but its causes are puzzling, because alcohol (ethanol) is a calorie-dense nutrient, and calorie intake usually suppresses brain appetite signals. The biological factors necessary for ethanol-induced overeating remain unclear, and societal causes have been proposed. Here we show that core elements of the brain’s feeding circuits—the hypothalamic Agrp neurons that are normally activated by starvation and evoke intense hunger—display electrical and biochemical hyperactivity on exposure to dietary doses of ethanol in brain slices. Furthermore, by circuit-specific chemogenetic interference in vivo, we find that the Agrp cell activity is essential for ethanol-induced overeating in the absence of societal factors, in single-housed mice. These data reveal how a widely consumed nutrient can paradoxically sustain brain starvation signals, and identify a biological factor required for appetite evoked by alcohol

Hydrothermally Emplaced, Lower Mississippian, Tripolitic Chert and Its Possible Relationship to the Tri-State Lead-Zinc Mining District

Across the southern Ozark Region, northern Arkansas, southwestern Missouri, and northeastern Oklahoma, exposures of the Lower Mississippian Boone Formation and its equivalents exhibit well-developed tripolitic chert that has been mined, more or less continuously, for at least 80 years. The tripolitic chert is a replacement of an interval within the basal portion of the upper Boone Formation in Arkansas and Oklahoma, and equivalent to the Elsey Formation in Missouri. The movement of silica-rich, hydrothermal fluids appears to have been much like that of a confined aquifer. It followed the basal upper Boone Formation (Arkansas) = Elsey Formation (Missouri) and was bound below by an impermeable interval at the top of the lower Boone Formation (Arkansas) = Reeds Spring Formation (Missouri), and above by the base of the upper Boone Formation (Arkansas) = Burlington-Keokuk (Missouri). The first hydrothermal event incompletely silicified the basal upper Boone = Elsey Formation. After leaching of the remnant carbonate, thus forming the tripolitic chert, a second hydrothermal event deposited terminated and doubly terminated quartz crystals, and druse in the tripolitic chert voids. This hydrothermal event may have pro-duced the Mississippi Valley-Type (MVT) lead-zinc deposits in northeast Oklahoma and southwestern Missouri. The famous deposits at Picher, Oklahoma, and Joplin, Missouri, appear to be positioned in the apparent path of the hydrothermal fluid migration. While timing of these hydrothermal events is unclear, they may reflect lateral secretion produced by the Ouachita Orogeny in the Late Pennsylvanian

Hodgkin's lymphoma presenting with heart failure: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cardiac involvement in malignant lymphoma is one of the least investigated subjects in oncology. This article reports a case of cardiac involvement in Hodgkin's lymphoma which presented as heart failure.</p> <p>Case presentation</p> <p>We report the case of an 8-year-old Afghan girl with Hodgkin's lymphoma. The disease presented with systemic signs and symptoms, including abdominal distension, weakness, pallor, chills, fever, generalized edema, hepatosplenomegaly and generalized lymphadenopathy, as well as signs of heart failure. Test results showed a rare form of heart metastasis.</p> <p>Conclusion</p> <p>We report a case of Hodgkin's lymphoma with metastasis to the heart, detected premortem. Although the involvement of the heart in a malignancy is relatively common, premortem detection is unusual and only few studies have reported it in the literature.</p

Political dynamics promoting the incremental regulation of secondhand smoke: a case study of New South Wales, Australia

BACKGROUND: The history of governmental responses to the accumulation of scientific evidence about the harms of secondhand smoke (SHS) presents an intriguing case study of incremental public health policy development. Australia has long been considered a world-leader in progressive tobacco control policies, but in the last decade has fallen behind other jurisdictions in introducing SHS legislation that protects all workers. Bars, clubs and pubs remain the only public indoor spaces where smoking is legally permitted, despite SHS exposure in the hospitality industry being higher and affecting more people than in any other setting after domestic exposure. This paper examines the political dynamics that have shaped this incremental approach to SHS. METHODS: In-depth interviews with 21 key stakeholders in the state of New South Wales (NSW), including politicians, their advisors, health officials and tobacco control advocates, were conducted and subjected to thematic content analysis. Interviewees' comments provided insights into the dynamics surrounding the debates and outcomes of SHS legislative attempts and the current political environment, and about how to progress SHS legislation. RESULTS: SHS restrictions have been delayed by several broad factors: the influence of industry groups successfully opposing regulation; issue wear-out; and political perceptions that there is not a salient constituency demanding that smoking be banned in bars and clubs. Interviewees also provided suggestions of strategies that advocates might utilise to best overcome the current political inertia of incremental compromises and achieve timely comprehensive smoking bans. CONCLUSION: Advocates concerned to shorten the duration of incremental endgames must continue to insist that governments address SHS fundamentally as a health issue rather than making political concessions to industry groups, and should broaden and amplify community voices calling on governments to finish the job. Publicity to the growing number of state and national governments that have successfully implemented total bans over the past decade is likely to make incrementalism an increasingly unattractive political option

Automated insulin delivery during the first 6 months postpartum (AiDAPT): a prespecified extension study

Background Clinical guidelines in the UK and elsewhere do not specifically address hybrid closed loop (HCL) use in the postpartum period when the demands of caring for a newborn are paramount. Our aim was to evaluate the safety and efficacy of HCL use during the first 6 months postpartum compared with standard care. Methods In this prespecified extension to a multicentre, randomised controlled trial, pregnant women with type 1 diabetes at nine UK sites were followed up for 6 months postpartum. Eligible participants (AiDAPT participants recruited after the implementation of the postpartum protocol amendment approval, those still pregnant or within six months of delivery at the time of amendment implementation and still using HCL or continuous glucose monitoring [CGM] therapy) continued their randomly assigned treatment, either standard insulin therapy with CGM or HCL therapy (CamAPS FX system version 0.3.1, CamDiab, Cambridge, UK). Participants were randomised in a 1:1 ratio with stratification by clinical site using randomly permuted block sizes of 2 or 4. The primary outcome was the between-group difference in percentage time in range ([TIR] 3·9–10·0 mmol/L [70–180mg/dL]), measured during the periods of month 0 up to 3, months 3 to 6, and over 6 months postpartum. The study is registered at ClinicalTrials.gov (ISRCTN56898625) and is complete. Findings Of the 124 AiDAPT trial participants, 66 (53%) were ineligible for inclusion in the postpartum extension, and 57 participants consented to continue their treatment per original random allocation. The mean age was 31 years (SD 4), and all participants had early pregnancy HbA1c 59·4 mmol/mol (SD 10·5 [7·6% SD 1·0%]). In the 6 months postpartum, mean time with glucose levels within the target range was higher in the HCL group compared with the standard care group (72% [SD 12%] vs 54% [17%]), with an adjusted treatment difference of 15% (95% CI 7 to 22). Results for hyperglycaemia (>10·0 mmol/L) and mean CGM glucose also favoured HCL (–14% [95% CI –23% to –6%] and –1·3 mmol/L [–2·3 to –0·3], respectively). Hypoglycaemia rates were low, with no between-group differences (2·4% vs 2·6%). There were no treatment effect changes depending on postpartum period (0 up to 3 months vs 3 to 6 months) and no unanticipated safety problems. Interpretation Participants in the HCL group maintained 70% TIR during the first 6 months postpartum, supporting continued use of HCL rather than standard insulin therapy for people with diabetes once they have given birth. Funding National Institute for Health Research, Juvenile Diabetes Research Foundation, and Diabetes Research & Wellness Foundation. CGM devices were provided by Dexcom at a discounted price

Defining sepsis on the wards: results of a multi-centre point-prevalence study comparing two sepsis definitions

Our aim was to prospectively determine the predictive capabilities of SEPSIS-1 and SEPSIS-3 definitions in the emergency departments and general wards. Patients with National Early Warning Score (NEWS) of 3 or above and suspected or proven infection were enrolled over a 24-h period in 13 Welsh hospitals. The primary outcome measure was mortality within 30 days. Out of the 5422 patients screened, 431 fulfilled inclusion criteria and 380 (88%) were recruited. Using the SEPSIS-1 definition, 212 patients had sepsis. When using the SEPSIS-3 definitions with Sequential Organ Failure Assessment (SOFA) score ≥ 2, there were 272 septic patients, whereas with quickSOFA score ≥ 2, 50 patients were identified. For the prediction of primary outcome, SEPSIS-1 criteria had a sensitivity (95%CI) of 65% (54–75%) and specificity of 47% (41–53%); SEPSIS-3 criteria had a sensitivity of 86% (76–92%) and specificity of 32% (27–38%). SEPSIS-3 and SEPSIS-1 definitions were associated with a hazard ratio (95%CI) 2.7 (1.5–5.6) and 1.6 (1.3–2.5), respectively. Scoring system discrimination evaluated by receiver operating characteristic curves was highest for Sequential Organ Failure Assessment score (0.69 (95%CI 0.63–0.76)), followed by NEWS (0.58 (0.51–0.66)) (p < 0.001). Systemic inflammatory response syndrome criteria (0.55 (0.49–0.61)) and quickSOFA score (0.56 (0.49–0.64)) could not predict outcome. The SEPSIS-3 definition identified patients with the highest risk. Sequential Organ Failure Assessment score and NEWS were better predictors of poor outcome. The Sequential Organ Failure Assessment score appeared to be the best tool for identifying patients with high risk of death and sepsis-induced organ dysfunction

Community as an equal partner for region-based climate change vulnerability, risk, and resilience assessments

Understanding and planning for climate change is a complex systems problem that is interdisciplinary and requires place-based and impact-specific management practices for communities to become resilient to a changing environment. The greater Charleston Harbor region is highly susceptible to the projected impacts of climate change due to low lying geography, a strongly bimodal socioeconomic spectrum, and invaluable coastal ecosystem services. Using Charleston as an example community, this paper discusses a selection of increasingly holistic approaches used in developing a system-level, community-focused assessment for vulnerability, risk, and resilience that aim to enable community involvement in the assessment of and planning for climate change-induced severe weather events, more extreme temperatures, and sea level rise