Explore the vast range of titles available.

Purpose This study aimed to identify optimal management decisions for surgeons preforming pancreatic head resection on patients with altered anatomy due to a previous Roux-en-Y gastric bypass (RYGB). Methods A multi-national (4), multi-center (28) collaborative of 55 pancreatic surgeons who have performed pancreatoduodenectomy or total pancreatectomy following RYGB for obesity (2005–2018) was created. Demographics, operative details, and perioperative outcomes from this cohort were analyzed and compared in a propensity-score matched analysis with a multi-center cohort of 5533 pancreatoduodenectomies without prior RYGB. Results Ninety-six patients with a previous RYGB undergoing pancreatic head resection were assembled. Pathologic indications between the RYGB and normal anatomy cohorts did not differ. Propensity score matching of RYGB vs. patients with unaltered anatomy demonstrated no differences in major postoperative outcomes. In total 20 distinct reconstructions were employed (of 37 potential options); the three most frequent reconstructions accounted for 52.1%, and none demonstrated superior outcomes. There were no differences in outcomes observed between original biliopancreatic limb use (66.7%) and those where a secondary Roux limb was created for biliopancreatic reconstruction. Remnant stomachs were removed in 54.7% of cases, with no outcome differences between resected and retained stomachs. Venting gastrostomy tubes were used in 36.2% of retained stomachs without obvious outcome benefits. Jejunostomy tubes were used infrequently (11.7%). Conclusions Pancreatic head resection after RYGB is an infrequently encountered, unique and challenging scenario for any given surgeon. These patients do not appear to suffer higher morbidity than those with unaltered anatomy. Various technical reconstructive options do not appear to confer distinct benefits.

Parkinson’s disease is a neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the substantia nigra compacta. Although the mechanisms that trigger the loss of dopaminergic neurons are unclear, mitochondrial dysfunction and inflammation are thought to have key roles 1 , 2 . An early-onset form of Parkinson’s disease is associated with mutations in the PINK1 kinase and PRKN ubiquitin ligase genes 3 . PINK1 and Parkin (encoded by PRKN ) are involved in the clearance of damaged mitochondria in cultured cells 4 , but recent evidence obtained using knockout and knockin mouse models have led to contradictory results regarding the contributions of PINK1 and Parkin to mitophagy in vivo 5 – 8 . It has previously been shown that PINK1 and Parkin have a key role in adaptive immunity by repressing presentation of mitochondrial antigens 9 , which suggests that autoimmune mechanisms participate in the aetiology of Parkinson’s disease. Here we show that intestinal infection with Gram-negative bacteria in Pink1 −/− mice engages mitochondrial antigen presentation and autoimmune mechanisms that elicit the establishment of cytotoxic mitochondria-specific CD8 + T cells in the periphery and in the brain. Notably, these mice show a sharp decrease in the density of dopaminergic axonal varicosities in the striatum and are affected by motor impairment that is reversed after treatment with l -DOPA. These data support the idea that PINK1 is a repressor of the immune system, and provide a pathophysiological model in which intestinal infection acts as a triggering event in Parkinson’s disease, which highlights the relevance of the gut–brain axis in the disease 10 . In mice lacking PINK1, bacterial infection in the intestine results in mitochondrial antigen presentation and generation of CD8 + T cells, and infected mice develop motor impairments, suggesting that PINK1 suppresses autoimmunity.

Solar water splitting is one of the key steps in artificial photosynthesis for future carbon-neutral, storable and sustainable source of energy. Here we show that one of the major obstacles for achieving efficient and stable overall water splitting over the emerging nanostructured photocatalyst is directly related to the uncontrolled surface charge properties. By tuning the Fermi level on the nonpolar surfaces of gallium nitride nanowire arrays, we demonstrate that the quantum efficiency can be enhanced by more than two orders of magnitude. The internal quantum efficiency and activity on p -type gallium nitride nanowires can reach ~51% and ~4.0 mol hydrogen h −1  g −1 , respectively. The nanowires remain virtually unchanged after over 50,000 μmol gas (hydrogen and oxygen) is produced, which is more than 10,000 times the amount of photocatalyst itself (~4.6 μmol). The essential role of Fermi-level tuning in balancing redox reactions and in enhancing the efficiency and stability is also elucidated. One of the obstacles in implementing solar water splitting is the requirement for materials with high internal quantum efficiency. Here, the authors investigate the effects of magnesium doping on the Fermi levels of gallium nitride nanowires, and tune this value to maximize redox efficiency.

Substance misuse and associated health-risking behaviors are prevalent in emerging adulthood. There is a knowledge gap concerning the post-high school effects of community-based delivery systems for universal preventive interventions implemented during young adolescence. This study reports effects of the PROSPER delivery system through age 19, 7.5 years past baseline. A cohort sequential design included 28 public school districts randomly assigned to the PROSPER partnership delivery system or usual-programming conditions. PROSPER community teams implemented a family-focused intervention in 6th grade and a school-based intervention in 7th grade. Outcomes for the age 19, post-high school report included lifetime, current, and frequency of substance misuse, as well as antisocial and health-risking sexual behaviors. Intent-to-treat, multi-level analyses of covariance of point-in-time outcomes were conducted, along with analyses of risk-related moderation of intervention effects. Results showed emerging adults from PROSPER communities reported significantly lower substance misuse across a range of types of substances, with relative reduction rates of up to 41.0%. No significant findings were observed for associated antisocial and health-risking sexual behavior indices; or for lifetime rates of sexually transmitted infections. Risk-related moderation effects were non-significant, suggesting generally comparable outcomes across higher- and lower-risk subgroups of emerging adults. The PROSPER delivery system for brief universal preventive interventions has potential for public health impact by reducing long-term substance misuse, with positive results extending beyond high school.

Solar water splitting for hydrogen generation can be a potential source of renewable energy for the future. Here we show that efficient and stable stoichiometric dissociation of water into hydrogen and oxygen can be achieved under visible light by eradicating the potential barrier on nonpolar surfaces of indium gallium nitride nanowires through controlled p -type dopant incorporation. An apparent quantum efficiency of ∼12.3% is achieved for overall neutral (pH∼7.0) water splitting under visible light illumination (400–475 nm). Moreover, using a double-band p- type gallium nitride/indium gallium nitride nanowire heterostructure, we show a solar-to-hydrogen conversion efficiency of ∼1.8% under concentrated sunlight. The dominant effect of near-surface band structure in transforming the photocatalytic performance is elucidated. The stability and efficiency of this recyclable, wafer-level nanoscale metal-nitride photocatalyst in neutral water demonstrates their potential use for large-scale solar-fuel conversion. Solar water splitting for hydrogen generation may be a future source of renewable energy. Here, the authors demonstrate that controlled p -type doping of metal-nitride nanowires can eradicate surface potential barriers and promotes stable stoichiometric dissociation of water under visible light.

Asthma is a common respiratory disease affecting ∼300 million people worldwide. Airway inflammation is thought to contribute to asthma pathogenesis, but the direct relationship between inflammation and airway hyperresponsiveness (AHR) remains unclear. This study investigates the role of inflammation in a steroid-insensitive, severe allergic airway disease model and in severe asthmatics stratified by inflammatory profile. First, we used the T-helper (TH)-17 cells adoptive transfer mouse model of asthma to induce pulmonary inflammation, which was lessened by tumor necrosis factor (TNF)-α neutralization or neutrophil depletion. Although decreased airspace inflammation following TNFα neutralization and neutrophil depletion rescued lung compliance, neither intervention improved AHR to methacholine, and tissue inflammation remained elevated when compared with control. Further, sputum samples were collected and analyzed from 41 severe asthmatics. In severe asthmatics with elevated levels of sputum neutrophils, but low levels of eosinophils, increased inflammatory markers did not correlate with worsened lung function. This subset of asthmatics also had significantly higher levels of TH17-related cytokines in their sputum compared with severe asthmatics with other inflammatory phenotypes. Overall, this work suggests that lung compliance may be linked with cellular inflammation in the airspace, whereas T-cell-driven AHR may be associated with tissue inflammation and other pulmonary factors.

Temporally harmonized elimination of damaged or unnecessary organelles and cells is a prerequisite of health. Under Type 2 inflammatory conditions, human airway epithelial cells (HAECs) generate proferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamines (HpETE-PEs) as proximate death signals. Production of 15-HpETE-PE depends on activation of 15-lipoxygenase-1 (15LO1) in complex with PE-binding protein-1 (PEBP1). We hypothesized that cellular membrane damage induced by these proferroptotic phospholipids triggers compensatory prosurvival pathways, and in particular autophagic pathways, to prevent cell elimination through programmed death. We discovered that PEBP1 is pivotal to driving dynamic interactions with both proferroptotic 15LO1 and the autophagic protein microtubule-associated light chain-3 (LC3). Further, the 15LO1–PEBP1-generated ferroptotic phospholipid, 15-HpETE-PE, promoted LC3-I lipidation to stimulate autophagy. This concurrent activation of autophagy protects cells from ferroptotic death and release of mitochondrial DNA. Similar findings are observed in Type 2 Hi asthma, where high levels of both 15LO1–PEBP1 and LC3-II are seen in HAECs, in association with low bronchoalveolar lavage fluid mitochondrial DNA and more severe disease. The concomitant activation of ferroptosis and autophagy by 15LO1–PEBP1 complexes and their hydroperoxy-phospholipids reveals a pathobiologic pathway relevant to asthma and amenable to therapeutic targeting.

Initiating drug use during adolescence increases the risk of developing addiction or other psychopathologies later in life, with long-term outcomes varying according to sex and exact timing of use. The cellular and molecular underpinnings explaining this differential sensitivity to detrimental drug effects remain unexplained. The Netrin-1/DCC guidance cue system segregates cortical and limbic dopamine pathways in adolescence. Here we show that amphetamine, by dysregulating Netrin-1/DCC signaling, triggers ectopic growth of mesolimbic dopamine axons to the prefrontal cortex, only in early-adolescent male mice, underlying a male-specific vulnerability to enduring cognitive deficits. In adolescent females, compensatory changes in Netrin-1 protect against the deleterious consequences of amphetamine on dopamine connectivity and cognitive outcomes. Netrin-1/DCC signaling functions as a molecular switch which can be differentially regulated by the same drug experience as function of an individual’s sex and adolescent age, and lead to divergent long-term outcomes associated with vulnerable or resilient phenotypes. Adolescent drug use augments psychiatric risk. Here the authors show that abused drugs dysregulate adolescent Netrin-1/DCC signaling, triggering ectopic long-distance dopamine axon growth in males while Netrin1 compensatory events protect females.

•The median American is willing to donate $42 towards global immunization programs for COVID-19.•Donor intentions vary by political affiliation in response to program manager and vaccine gaps.•Impure altruism (warm-glow, public good access, fiscal stability) primarily motivates donors.•Pure altruism (concerns for social justice, equitable access to resources) are secondary motives. To develop effective private donation campaigns that support vaccine distribution in low- and middle-income countries (LMICs), one must understand donors’ willingness to give, response to stimuli, and preferences for program management. We use a contingent valuation method to estimate United States citizens’ willingness to give to nongovernmental COVID-19 immunization programs in LMICs during the emergency phase of the pandemic. Using split-sample treatments, we evaluate the impact of the immunization program administrator (generic NGO or COVAX) and the role of priming communications on inequality in income and vaccination rates between the US and recipient countries. Results show that the median American would donate $42 towards global immunization programs. Preferences for program management and responses to priming communications are heterogeneous across political affiliations, after controlling for altruistic motives, experiences with COVID, giving behaviors, and sociodemographic characteristics. Specifically, Democrats and Independents are more likely to donate to the COVAX-administered fund, and more responsive to priming statements regarding vaccine-gaps. Policy implications are discussed.

During 2000-2016, the suicide rate among the U.S. working age population (persons aged 16-64 years) increased 34%, from 12.9 per 100,000 population to 17.3 (https://www.cdc.gov/injury/wisqars). To better understand suicide among different occupational groups and inform suicide prevention efforts, CDC analyzed suicide deaths by Standard Occupational Classification (SOC) major groups for decedents aged 16-64 years from the 17 states participating in both the 2012 and 2015 National Violent Death Reporting System (NVDRS) (https://www.cdc.gov/violenceprevention/nvdrs). The occupational group with the highest male suicide rate in 2012 and 2015 was Construction and Extraction (43.6 and 53.2 per 100,000 civilian noninstitutionalized working persons, respectively), whereas the group with the highest female suicide rate was Arts, Design, Entertainment, Sports, and Media (11.7 [2012] and 15.6 [2015]). The largest suicide rate increase among males from 2012 to 2015 (47%) occurred in the Arts, Design, Entertainment, Sports, and Media occupational group (26.9 to 39.7) and among females, in the Food Preparation and Serving Related group, from 6.1 to 9.4 (54%). CDC's technical package of strategies to prevent suicide is a resource for communities, including workplace settings (1).