Proteolytic regulation of calcium channels - avoiding controversy

The publication of papers containing data obtained with suboptimal rigor in the experimental design and choice of key reagents, such as antibodies, can result in a lack of reproducibility and generate controversy that can both needlessly divert resources and, in some cases, damage public perception of the scientific enterprise. This exemplary paper by Buonarati et al. (2018)1 shows how a previously published, potentially important paper on calcium channel regulation falls short of the necessary mark, and aims to resolve the resulting controversy

Leakage of an invagination pancreaticojejunostomy may have an influence on mortality

Purpose: No consensus exists regarding the most effective form of pancreaticojejunostomy (PJ) following pancreaticoduodenectomy (PD). Methods: Data were gathered through the American College of Surgeons-National Surgical Quality Improvement Program, Pancreatectomy Demonstration Project. A total of 1781 patients underwent a PD at 43 institutions. After appropriate exclusions, 890 patients were analyzed. Patients were divided into duct-to-mucosa (n = 734, 82%) and invagination (n = 156, 18%) groups and were compared by unadjusted analysis. Type of PJ was included in eight separate morbidity and mortality multivariable analyses. Results: Invagination patients had higher serum albumin (p < 0.01) and lower body mass index (p < 0.01), were less likely to have a preoperative biliary stent (p < 0.01), and were more likely to have a soft gland (p < 0.01). PJ anastomosis type was not associated with morbidity but was associated with mortality (duct-to-mucosa vs. invagination, odds ratio = 0.22, p < 0.01). Among patients who developed a clinically relevant pancreatic fistula, none of the 119 duct-to-mucosa, compared with 5 of 21 invagination, patients died (p < 0.01). Conclusion: Patients who undergo a PJ by duct-to-mucosa or invagination differ with respect to preoperative and intraoperative variables. When an invagination PJ leaks, there may be a greater influence on mortality than when a duct-to-mucosa PJ leaks

Zinc in innate and adaptive tumor immunity

Zinc is important. It is the second most abundant trace metal with 2-4 grams in humans. It is an essential trace element, critical for cell growth, development and differentiation, DNA synthesis, RNA transcription, cell division, and cell activation. Zinc deficiency has adverse consequences during embryogenesis and early childhood development, particularly on immune functioning. It is essential in members of all enzyme classes, including over 300 signaling molecules and transcription factors. Free zinc in immune and tumor cells is regulated by 14 distinct zinc importers (ZIP) and transporters (ZNT1-8). Zinc depletion induces cell death via apoptosis (or necrosis if apoptotic pathways are blocked) while sufficient zinc levels allows maintenance of autophagy. Cancer cells have upregulated zinc importers, and frequently increased zinc levels, which allow them to survive. Based on this novel synthesis, approaches which locally regulate zinc levels to promote survival of immune cells and/or induce tumor apoptosis are in order

Donor aid mentioning newborns and stillbirths, 2002-19: an analysis of levels, trends, and equity.

BACKGROUND: Global aid for reproductive, maternal, newborn, and child health has stagnated in recent years, and aid mentioning newborns or stillbirths has previously represented a very small proportion of aid for reproductive, maternal, newborn, and child health. Neonatal survival targets have been set by 78 countries, and stillbirth prevention targets have been set by 30 countries, to address the 4·4 million newborn deaths and stillbirths globally. We aimed to generate novel estimates of current levels of, and trends in, aid mentioning newborns and stillbirths over 2002-19, and to assess whether the amount of aid disbursed aligns with the associated mortality burden. METHODS: For this analysis, we did a manual review and coding of the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System database from 2002 to 2019 using key search terms for aid mentioning newborns and stillbirths. We compared these findings with estimates of aid for reproductive, maternal, newborn, and child health for 2002-19 based on the Muskoka2 method. Findings are presented in 2019 US$according to the OECD's Development Assistance Committee deflators, which account for variation in exchange rates and inflation in donor countries. FINDINGS: We identified 21 957 unique records in the 2002-19 period. Aid mentioning newborns and stillbirths comprised approximately 10$1·6 billion) of reproductive, maternal, newborn, and child health funding overall in 2019 ($15·9 billion), with a small decrease in value between 2015 and 2019. 1284 (6$535 million) of their total value mentioned aid focused only on newborn health. Ten donors contributed 87% ($13·7 billion) of the total value of aid mentioning newborns and stillbirths during 2002-19. Aid mentioning newborns and stillbirths was inequitably allocated in the least developed countries (as defined by the UN), ranging from$18 per death in Angola to $1389 per death in Timor-Leste. Stillbirths were not mentioned in any funding in 2002-09, and they were only mentioned in 46 of 21 957 records in 2010-19, comprising$44·4 million of aid disbursed during this period. INTERPRETATION: Aid mentioning newborns and stillbirths is poorly matched to their corresponding mortality burden (representing 10% of aid for reproductive, maternal, newborn, and child health overall, yet accounting for approximately 50% of mortality in children <5 years) and across recipient countries (with substantial variation in the amount of aid received per newborn death and stillbirth between countries with similar health and economic needs). Our findings indicate that aid needs to be better targeted to populations with the highest mortality burdens, creating greater potential for impact. FUNDING: John D and Catherine T MacArthur Foundation, Bill & Melinda Gates Foundation, ELMA Philanthropies, Children's Investment Fund Foundation UK, Lemelson Foundation, and Ting Tsung and Wei Fong Chao Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Landlabs: An Integrated Approach to Creating Agricultural Enterprises That Meet the Triple Botom Line

Global demand is increasing for food, feed, and fiber; for additional agricultural outputs, such as biofuels; and for ecosystem services, such as clean water and outdoor recreation. In response, new agricultural enterprises are needed that produce more outputs from existing lands while meeting the triple bottom line of high performance in economic, environmental, and social terms. Establishing such enterprises requires coordination and development within three critical domains: landscape configurations (i.e., types and arrangements of land uses), supply/value chains (i.e., processing and utilization), and policy and governance. In this essay, we describe our efforts, as land-grant university scientists, to support coordinated innovation and enterprise development in integrated place-based institutions, which we term landlabs. We describe our experiences in three prototyping efforts and outline key features of landlabs that are emerging from these efforts. Land-grant universities have a central and crucial role to play in organizing and operating landlabs

Predictors of contemporary coronary artery bypass grafting outcomes

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Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy