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Aim: In rodent models of nephrotic syndrome (NS), edema formation was prevented by blockade of the epithelial sodium channel ENaC with amiloride. However, apart from case reports, there is no evidence favoring ENaC blockade in patients with NS. Methods: The monocentric randomized controlled AMILOR study investigated the antiedematous effect of amiloride (starting dose 5 mg/day, max. 15 mg/day) in comparison to standard therapy with the loop diuretic furosemide (40 mg/day, max. 120 mg/day) over 16 days. Overhydration (OH) was measured by bioimpedance spectroscopy (BCM, Fresenius). Depending on the OH response, diuretic dose was adjusted on days 2, 5, 8 and 12, and if necessary, hydrochlorothiazide (HCT) was added from d8 (12.5 mg/day, max. 25 mg/day). The primary endpoint was the decrease in OH on d8. The study was terminated prematurely due to insufficient recruitment and a low statistical power due to a low actual effect size. Results: Median baseline OH was +26.4 (interquartile range 15.5–35.1)% extracellular water (ECW) in the amiloride arm and + 27.9 (24.1–29.4)% ECW in the furosemide arm and decreased by 1.95 (0.80–6.40) and 5.15 (0.90–8.30)% ECW after 8 days, respectively, and by 10.10 (1.30–14.40) and 7.40 (2.80–10.10)% ECW after 16 days, respectively. OH decrease on d8 and d16 was not significantly different between both arms. Conclusion: The AMILOR study is the first randomized controlled pilot study suggesting a similar antiedematous effect as furosemide. Further studies are required to better define the role of amiloride in NS (EudraCT 2019‐002607‐18). [ABSTRACT FROM AUTHOR]

This article, titled "Lipid droplets in health and disease," provides an overview of the functions and roles of lipid droplets in both physiological and pathological states. Lipid droplets are organelles found in eukaryotic cells that store neutral lipids and play important roles in lipid biology. The article discusses the architecture of lipid droplets, their formation at the endoplasmic reticulum, and the proteins involved in their biogenesis. It also explores the processes of lipid droplet growth, degradation, and communication with other organelles. The authors highlight recent advancements in understanding lipid droplet functions and their implications in various diseases. [Extracted from the article]

Hydrogels with adjustable mechanical properties have been engineered as matrices for mammalian cells and allow the dynamic, mechano‐responsive manipulation of cell fate and function. Recent research yields hydrogels, where biological photoreceptors translated optical signals into a reversible and adjustable change in hydrogel mechanics. While their initial application provides important insights into mechanobiology, broader implementation is limited by a small dynamic range of addressable stiffness. Herein, this limitation is overcome by developing a photoreceptor‐based hydrogel with reversibly adjustable stiffness from ≈800 Pa to the sol state. The hydrogel is based on star‐shaped polyethylene glycol, functionalized with the red/far‐red light photoreceptor phytochrome B (PhyB), or phytochrome‐interacting factor 6 (PIF6). Upon illumination with red light, PhyB heterodimerizes with PIF6, thus crosslinking the polymers and resulting in gelation. However, upon illumination with far‐red light, the proteins dissociate and trigger a complete gel‐to‐sol transition. The hydrogel's light‐responsive mechanical properties are comprehensively characterized and it is applied as a reversible extracellular matrix for the spatiotemporally controlled deposition of mammalian cells within a microfluidic chip. It is anticipated that this technology will open new avenues for the site‐ and time‐specific positioning of cells and will contribute to overcome spatial restrictions. [ABSTRACT FROM AUTHOR]

Introduction: Despite a growing body of research on associations between adolescent digital use and well‐being, few studies have investigated these associations a) longitudinally and b) across socioeconomic status. The present study uses high‐quality longitudinal data to examine how digital engagement shapes socioemotional and educational outcomes from early to late adolescence across socioeconomic status (SES). Methods: Participants are 7685 individuals (49.0% female) from the 1998 birth cohort of the longitudinal Growing Up In Ireland (GUI) survey. The survey was administered to Irish parents and children between 2007 and 2016 (at ages 9, 13, and 17/18). Fixed‐effects regression modeling was used to establish associations between digital engagement and socioemotional and educational outcomes. Further Fixed‐Effects models were analyzed separately by SES, to assess how associations between digital use and adolescent outcomes differ by socioeconomic groups. Results: Results show that digital screen time increases markedly from early to late adolescence, but to a higher extent among low‐SES versus high‐SES groups. Heavy levels of digital screen time (i.e., 3+ hours daily) are associated with declines in well‐being, particularly for external and prosocial functioning, while engagement in learning‐oriented digital activities and gaming is associated with better adolescent outcomes. Yet, low‐SES adolescents are globally more harmed than high‐SES adolescents by their digital engagement, and high‐SES adolescents benefit more from moderate levels of digital use and from engaging in learning‐oriented digital activities. Conclusions: This study suggests that digital engagement is associated with socioeconomic inequalities in adolescents' socioemotional well‐being and, to a lesser extent, educational outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To identify temporal patterns of emergency dispatches as initiated by Veteran Crisis Line (VCL) responders and among moderate‐ and high‐risk contacts. Methods: Incidence rate ratios (IRRs) were used to examine the incidence of emergency dispatches among all 1,437,543 VCL contacts across 2019–2020. Results: Emergency dispatches were initiated in 57,077 (4.0%) contacts. IRRs were elevated during Labor Day, IRR (95% CI) = 1.33 (1.15–1.54), and Independence Day, IRR (95% CI) = 1.22 (1.05–1.43), weekends, Saturdays, IRR (95% CI) = 1.04 (1.01–1.08), Sunday (reference), and 6 pm to 11:59 pm, IRR (95% CI) = 1.06 (1.04–1.09). IRRs for moderate‐ and high‐risk contacts were higher on Memorial Day, IRR (95% CI) = 1.16 (1.00–1.33), Sunday (reference), and 6 pm to 11:59 pm (reference). Conclusions: The initiation of emergency dispatches fluctuates over time and were highest during Labor Day and Independence Day, weekends, and evenings. Moderate‐ and high‐risk contact also fluctuate over time and were highest on Memorial Day, Sundays, and midnight to 5:59 am. VCL policy makers can use knowledge of temporal fluctuations to allocate public health resources for increased efficiency and greatest impact; however, additional research on temporal stability and generalizability is needed. [ABSTRACT FROM AUTHOR]

Background: Abiraterone and enzalutamide are castration‐resistant prostate cancer (CRPC) therapies with potentially distinct associations with mental health symptoms given their differing antiandrogen targets. Methods: We used national Veterans Health Administration data to identify patients with CRPC who received first‐line abiraterone or enzalutamide from 2010 to 2017. Using Poisson regression, we compared outpatient mental health encounters per 100 patient‐months on drug between the abiraterone and enzalutamide cohorts adjusting for patient factors (e.g., age). We compared mental health encounters in the year before versus after starting therapy using the McNemar test. Results: We identified 2902 CRPC patients who received abiraterone (n = 1992) or enzalutamide (n = 910). We found no difference in outpatient mental health encounters between the two groups (adjusted incident rate ratio [aIRR] 1.04, 95% confidence interval [CI] 0.95–1.15). However, men with preexisting mental health diagnoses received 81.3% of the outpatient mental health encounters and had higher rates of these encounters with enzalutamide (aIRR 1.21, 95% CI 1.09–1.34). Among patients with ≥1 year of enrollment before and after starting abiraterone (n = 1139) or enzalutamide (n = 446), there was no difference in mental health care utilization before versus after starting treatment (17.0% of patients vs. 17.6%, p = 0.60, abiraterone; 16.4% vs. 18.4%, p = 0.26, enzalutamide). Conclusion: We found no overall differences in mental health care utilization between CRPC patients who received first‐line abiraterone versus enzalutamide. However, men with preexisting mental health diagnoses received the majority of mental health care and had more mental health visits with enzalutamide. [ABSTRACT FROM AUTHOR]

Background and Objectives: Public health surveillance for overdose sometimes depends on nonfatal drug overdoses recorded in health records. However, the proportion of total overdoses identified through health record systems is unclear. Comparison of overdoses from health records to those that are self‐reported may provide insight on the proportion of nonfatal overdoses that are not identified. Methods: We conducted a cohort study linking survey data on overdose from a national survey of Veterans to United States Department of Veterans Affairs (VA) health records, including community care paid for by VA. Self‐reported overdose in the prior 3 years was compared to diagnostic codes for overdoses and substance use disorders in the same time period. Results: The sensitivity of diagnostic codes for overdose, compared to self‐report as a reference standard for this analysis, varied by substance: 28.1% for alcohol, 23.1% for sedatives, 12.0% for opioids, and 5.5% for cocaine. There was a notable concordance between substance use disorder diagnoses and self‐reported overdose (sensitivity range 17.9%–90.6%). Discussion and Conclusions: Diagnostic codes in health records may not identify a substantial proportion of drug overdoses. A health record diagnosis of substance use disorder may offer a stronger inference regarding the size of the population at risk. Alternatively, screening for self‐reported overdose in routine clinical care could enhance overdose surveillance and targeted intervention. Scientific Significance: This study suggests that diagnostic codes for overdose are insensitive. These findings support consideration of alternative approaches to overdose surveillance in public health. [ABSTRACT FROM AUTHOR]

Sodium retention and edema are hallmarks of nephrotic syndrome (NS). Different experimental rodent models have been established for simulating NS, however, not all of them feature sodium retention which requires proteinuria to exceed a certain threshold. In rats, puromycin aminonucleoside nephrosis (PAN) is a classic NS model introduced in 1955 that was adopted as doxorubicin‐induced nephropathy (DIN) in 129S1/SvImJ mice. In recent years, mice with inducible podocin deletion (Nphs2Δipod) or podocyte apoptosis (POD‐ATTAC) have been developed. In these models, sodium retention is thought to be caused by activation of the epithelial sodium channel (ENaC) in the distal nephron through aberrantly filtered serine proteases or proteasuria. Strikingly, rodent NS models follow an identical chronological time course after the development of proteinuria featuring sodium retention within days and spontaneous reversal thereafter. In DIN and Nphs2Δipod mice, inhibition of ENaC by amiloride or urinary serine protease activity by aprotinin prevents sodium retention, opening up new and promising therapeutic approaches that could be translated into the treatment of nephrotic patients. However, the essential serine protease(s) responsible for ENaC activation is (are) still unknown. With the use of nephrotic rodent models, there is the possibility that this (these) will be identified in the future. This review summarizes the various rodent models used to study experimental nephrotic syndrome and the insights gained from these models with regard to the pathophysiology of sodium retention. [ABSTRACT FROM AUTHOR]

Green schoolyards may buffer against the effects of urbanization through increasing access to nature and its benefits. The present study was a community‐academic partnership that examined the effects of green schoolyard renovations on utilization, physical activity (PA), and social interactions as well as perceptions of safety, neighborhood climate, and social cohesion among those living in low‐income, urban neighborhoods. Utilizing behavioral mapping techniques and multi‐informant surveys (i.e., caregivers, teachers, and community members), changes from pre‐ to postrenovation were assessed at two low‐income, urban schools. Behavioral mapping results demonstrated increases in utilization and prosocial interactions among youth from pre‐ to postrenovation. Levels of moderate‐to‐vigorous PA also increased from pre‐ to postrenovation at one school. Survey data from community stakeholders revealed improvements in the perception of schoolyard safety and school–community relationships as well as reductions in bullying postrenovation. Green schoolyards may offer a safe space for children and adults to engage in social, outdoor activities, particularly in low‐income, urban neighborhoods. Highlights: This multimethod study examined the impact of two green schoolyard renovations on utilization, physical activity (PA), social interactions, and perceptions of the surrounding neighborhood/community in low‐income, urban areas of Chicago.Green schoolyards were better utilized by youth following the schoolyard renovations.Youth physical activity and prosocial interactions increased following the schoolyard renovations, with some variation between schools.Community stakeholders and teachers reported using the schoolyard for exercise, leisure activities, and as an extension of the classroom.Community stakeholders reported perceptions of increased safety within the community and better relationships between the school and community following the renovation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate whether pain management clinic laws and prescription drug monitoring program (PDMP) prescriber check mandates, two state opioid policies with relatively rapid adoption across states, reduced opioid dispensing more or less in Black versus White patients. Data Sources: Pharmacy claims data, US sample of commercially insured adults, 2007–2018. Study Design: Stratifying by race, we used generalized estimating equations with an event‐study specification to estimate time‐varying effects of each policy on opioid dispensing, comparing to the four pre‐policy quarters and states without the policy. Outcomes included high‐dosage opioids, overlapping opioid prescriptions, concurrent opioid/benzodiazepines, opioids from >3 prescribers, opioids from >3 pharmacies. Data Extraction Methods: We identified all prescription opioid dispensing to Black and White adults aged 18–64 without a palliative care or cancer diagnosis code. Principal Findings: Exactly 7,096,592 White and 1,167,310 Black individuals met inclusion criteria. Pain management clinic laws were associated with reductions in two outcomes; their association with high‐dosage receipt was larger among White patients. In contrast, reductions due to PDMP mandates appeared limited to, or larger in, Black patients compared with White patients in four of five outcomes. For example, PDMP mandates reduced high‐dosage receipt in Black patients by 0.7 percentage points (95% CI: 0.36–1.08 ppt.) over 4 years: an 8.4% decrease from baseline; there was no apparent effect in White patients. Similarly, while there was limited evidence that mandates reduced overlapping opioid receipt in White patients, they appeared to reduce overlapping opioid receipt in Black patients by 1.3 ppt. (95% CI: −1.66–−1.01 ppt.) across post‐policy years—a 14.4% decrease from baseline. Conclusions: PDMP prescriber check mandates but not pain management clinic laws appeared to reduce opioid dispensing more in Black patients than White patients. Future research should discern the mechanisms underlying these disparities and their consequences for pain management. [ABSTRACT FROM AUTHOR]

Background and Aims: This study aimed to (1) describe trends in stimulant‐alone and stimulant and other substance use overdose deaths from 2012 to 2018 and (2) measure patient and service use characteristics across stimulant‐related overdose death profiles. Design Retrospective cohort study of patients who died from stimulant‐involved overdose between annual years 2012 and 2018. Setting: United States Veterans Health Administration (VHA). A total of 3631 patients died from stimulant‐involved overdose, as identified through the National Death Index. Measurements Stimulant‐involved overdose deaths were categorized by stimulant type (cocaine or methamphetamine/other) and other substance co‐involvement. Cause of death data were linked to patient characteristics, including demographic and treatment use preceding overdose from VHA administrative data. We examined trends over time and compared treatment use factors between the following mutually exclusive overdose profiles: cocaine alone, methamphetamine alone, cocaine + opioid, methamphetamine + opioid, any stimulant + other substance and cocaine + methamphetamine. Findings The rate of overdose death was 3.06 times higher in 2018 than 2012, with increases across all toxicology profiles. Compared with cocaine‐involved overdoses, methamphetamine‐involved overdoses were less likely in people who were older [adjusted odds ratio (aOR) = 0.22, 95% confidence interval (CI) = 0.06–0.87 aged 65+ versus 18–29] and more likely among those who lived in rural areas (aOR = 2.73, 95% CI = 1.43–5.23). People who died from stimulant + opioid overdoses had lower odds of a stimulant use disorder diagnosis compared with stimulant alone deaths (cocaine: aOR = 0.55, 95% CI = 0.41–0.75, methamphetamine: aOR = 0.44, 95% CI = 0.29–0.68). Conclusions: The rate of deaths among US Veterans from stimulant‐related overdose was three times higher in 2018 than 2012. Key differences in characteristics of patients across overdose toxicology profiles, such as geographic location and health‐care use, point to distinct treatment needs based on stimulant use type. [ABSTRACT FROM AUTHOR]

Wheat blast caused by Magnaporthe oryzae pathotype Triticum (MoT), initially restricted to South America, is a global threat for wheat after spreading to Asia in 2016 by the introduction of contaminated seeds, raising the question about transmission of the pathogen from seeds to seedlings, a process so far not well understood. We therefore studied the relationship between seed infection and disease symptoms on seedlings and adult plants. To accomplish this objective, we inoculated spikes of wheat cv. Apogee with a transgenic isolate (MoT‐DsRed, with the addition of being resistant to hygromycin). We identified MoT‐DsRed in experiments using hygromycin resistance for selection or by observation of DsRed fluorescence. The seeds from infected plants looked either apparently healthy or shrivelled. To evaluate the transmission, two experimental designs were chosen (blotter test and greenhouse) and MoT‐DsRed was recovered from both. This revealed that MoT is able to colonize wheat seedlings from infected seeds under the ground. The favourable conditions of temperature and humidity allowed a high recovery rate of MoT from wheat shoots when grown in artificial media. Around 42 days after germination of infected seeds, MoT‐DsRed could not be reisolated, indicating that fungal progression, at this time point, did not proceed systemically/endophytically. We hypothesize that spike infection might occur via spore dispersal from infected leaves rather than within the plant. Because MoT‐DsRed was not only successfully reisolated from seed coats and germinating seeds with symptoms, but also from apparently healthy seeds, urgent attention is needed to minimize the risks of inadvertent dispersal of inoculum. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a debilitating complication of many chronic disease states and disuse conditions including denervation. However, molecular and signaling mechanisms of muscle wasting remain less understood. Here, we demonstrate that the levels of several toll‐like receptors (TLRs) and their downstream signaling adaptor, myeloid differentiation primary response 88 (MyD88), are induced in skeletal muscle of mice in response to sciatic nerve denervation. Muscle‐specific ablation of MyD88 mitigates denervation‐induced skeletal muscle atrophy in mice. Targeted ablation of MyD88 suppresses the components of ubiquitin‐proteasome system, autophagy, and FOXO transcription factors in skeletal muscle during denervation. We also found that specific inhibition of MyD88 reduces the activation of canonical nuclear factor‐kappa (NF‐κB) pathway and expression of receptors for inflammatory cytokines in denervated muscle. In contrast, inhibition of MyD88 stimulates the activation of non‐canonical NF‐κB signaling in denervated skeletal muscle. Ablation of MyD88 also inhibits the denervation‐induced increase in phosphorylation of AMPK without having any effect on the phosphorylation of mTOR. Moreover, targeted ablation of MyD88 inhibits the activation of a few components of the unfolded protein response (UPR) pathways, especially X‐box protein 1 (XBP1). Importantly, myofiber‐specific ablation of XBP1 mitigates denervation‐induced skeletal muscle atrophy in mice. Collectively, our experiments suggest that TLR‐MyD88 signaling mediates skeletal muscle wasting during denervation potentially through the activation of canonical NF‐κB signaling, AMPK and UPR pathways. [ABSTRACT FROM AUTHOR]

Background and aims: Research from cohorts of individuals with recreational cannabis use indicates that cannabis withdrawal symptoms are reported by more than 40% of those using regularly. Withdrawal symptoms are not well understood in those who use cannabis for medical purposes. Therefore, we prospectively examined the stability of withdrawal symptoms in individuals using cannabis to manage chronic pain. Design, Setting, Participants: Using latent class analysis (LCA) we examined baseline cannabis withdrawal to derive symptom profiles. Then, using latent transition analysis (LTA) we examined the longitudinal course of withdrawal symptoms across the time points. Exploratory analyses examined demographic and clinical characteristics predictive of withdrawal class and transitioning to more or fewer withdrawal symptoms over time. A cohort of 527 adults with chronic pain seeking medical cannabis certification or re‐certification was recruited between February 2014 and June 2015. Participants were recruited from medical cannabis clinic waiting rooms in Michigan, USA. Participants were predominantly white (82%) and 49% identified as male, with an average age of 45.6 years (standard deviation = 12.8). Measurements Baseline, 12‐month and 24‐month assessments of withdrawal symptoms using the Marijuana Withdrawal Checklist–revised. Findings A three‐class LCA model including a mild (41%), moderate (34%) and severe (25%) symptom class parsimoniously represented withdrawal symptoms experienced by people using medical cannabis. Stability of withdrawal symptoms using a three‐class LTA at 12 and 24 months ranged from 0.58 to 0.87, with the most stability in the mild withdrawal class. Younger age predicted greater severity and worsening of withdrawal over time. Conclusions: Adults with chronic pain seeking medical cannabis certification or re‐certification appear to experience mild to severe withdrawal symptoms. Withdrawal symptoms tend to be stable over a 2‐year period, but younger age is predictive of worse symptoms and of an escalating withdrawal trajectory. [ABSTRACT FROM AUTHOR]

Aim: The serine protease prostasin (Prss8) is expressed in the distal tubule and stimulates proteolytic activation of the epithelial sodium channel (ENaC) in co‐expression experiments in vitro. The aim of this study was to explore the role of prostasin in proteolytic ENaC activation in the kidney in vivo. Methods: We used genetically modified knockin mice carrying a Prss8 mutation abolishing proteolytic activity (Prss8‐S238A) or a mutation leading to a zymogen‐locked state (Prss8‐R44Q). Mice were challenged with low sodium diet and diuretics. Regulation of ENaC activity by Prss8‐S238A and Prss8‐R44Q was studied in vitro using the Xenopus laevis oocyte expression system. Results: Co‐expression of murine ENaC with Prss8‐wt or Prss8‐S238A in oocytes caused maximal proteolytic ENaC activation, whereas ENaC was activated only partially in oocytes co‐expressing Prss8‐R44Q. This was paralleled by a reduced proteolytic activity at the cell surface of Prss8‐R44Q expressing oocytes. Sodium conservation under low sodium diet was preserved in Prss8‐S238A and Prss8‐R44Q mice but with higher plasma aldosterone concentrations in Prss8‐R44Q mice. Treatment with the ENaC inhibitor triamterene over four days was tolerated in Prss8‐wt and Prss8‐S238A mice, whereas Prss8‐R44Q mice developed salt wasting and severe weight loss associated with hyperkalemia and acidosis consistent with impaired ENaC function and renal failure. Conclusion: Unlike proteolytically inactive Prss8‐S238A, zymogen‐locked Prss8‐R44Q produces incomplete proteolytic ENaC activation in vitro and causes a severe renal phenotype in mice treated with the ENaC inhibitor triamterene. This indicates that Prss8 plays a role in proteolytic ENaC activation and renal function independent of its proteolytic activity. [ABSTRACT FROM AUTHOR]

Aims: To understand the role of comorbid substance use disorders (SUDs), or polysubstance use, in the treatment of opioid use disorder (OUD), this study compared patients with OUD only to those with additional SUDs and examined association with OUD treatment receipt. Design, setting and participants: Retrospective national cohort study of Veterans diagnosed with OUD (n = 65 741) receiving care from the US Veterans Health Administration (VHA) in fiscal year (FY) 2017. Measurements: Patient characteristics were compared among those diagnosed with OUD only versus those with one other SUD (OUD + 1 SUD) and with multiple SUDs (OUD + ≥ 2 SUDs). The study examined the relationship between comorbid SUDs and receipt of buprenorphine, methadone and SUD outpatient treatment during 1‐year follow‐up, adjusting for patient demographic characteristics and clinical conditions. Findings Among the 65 741 Veterans with OUD in FY 2017, 41.2% had OUD only, 22.9% had OUD + 1 SUD and 35.9% had OUD + ≥ 2 SUDs. Common comorbid SUDs included alcohol use disorder (41.3%), cocaine/stimulant use disorder (30.0%) and cannabis use disorder (22.4%). Adjusting for patient characteristics, patients with OUD + 1 SUD [adjusted odds ratio (aOR) = 0.87, 95% confidence interval (CI) = 0.82–0.93] and patients with OUD +≥ 2 SUDs (aOR = 0.65, 95% CI = 0.61–0.69) had lower odds of receiving buprenorphine compared with OUD only patients. There were also lower odds of receiving methadone for patients with OUD + 1 SUD (aOR = 0.91, 95% CI = 0.86–0.97)and for those with OUD + ≥2 SUDs (aOR = 0.79, 95% CI = 0.74–0.84). Patients with OUD + 1 SUD (aOR = 1.85, 95% CI = 1.77–1.93) and patients with OUD + ≥2 SUDs (aOR = 3.25, 95% CI = 3.103.41) were much more likely to have a SUD clinic visit. Conclusions: The majority of Veterans in the US Veterans Health Administration diagnosed with opioid use disorder appeared to have at least one comorbid substance use disorder and many have multiple substance use disorders. Despite the higher likelihood of a substance use disorder clinic visit, having a non‐opioid substance use disorder is associated with lower likelihood of buprenorphine treatment, suggesting the importance of addressing polysubstance use within efforts to expand treatment for opioid use disorder. [ABSTRACT FROM AUTHOR]

Aim: Sodium retention is the hallmark of nephrotic syndrome (NS) and mediated by the proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases. Plasmin is highly abundant in nephrotic urine and has been proposed to be the principal serine protease responsible for ENaC activation in NS. However, a proof of the essential role of plasmin in experimental NS is lacking. Methods: We used a genetic mouse model of NS based on an inducible podocin knockout (Bl6‐Nphs2tm3.1Antc*Tg(Nphs1‐rtTA*3G)8Jhm*Tg(tetO‐cre)1Jaw or nphs2Δipod). These mice were crossed with plasminogen deficient mice (Bl6‐Plgtm1Jld or plg−/−) to generate double knockout mice (nphs2Δipod*plg−/−). NS was induced after oral doxycycline treatment for 14 days and mice were followed for subsequent 14 days. Results: Uninduced nphs2Δipod*plg−/− mice had normal kidney function and sodium handling. After induction, proteinuria increased similarly in both nphs2Δipod*plg+/+ and nphs2Δipod*plg−/− mice. Western blot revealed the urinary excretion of plasminogen and plasmin in nphs2Δipod*plg+/+ mice which were absent in nphs2Δipod*plg−/− mice. After the onset of proteinuria, amiloride‐sensitive natriuresis was increased compared to the uninduced state in both genotypes. Subsequently, urinary sodium excretion dropped in both genotypes leading to an increase in body weight and development of ascites. Treatment with the serine protease inhibitor aprotinin prevented sodium retention in both genotypes. Conclusions: This study shows that mice lacking urinary plasminogen are not protected from ENaC‐mediated sodium retention in experimental NS. This points to an essential role of other urinary serine proteases in the absence of plasminogen. [ABSTRACT FROM AUTHOR]

BACKGROUND/OBJECTIVES: Benzodiazepines (BZDs) are widely prescribed to older adults. Although prescribing has declined in the U.S. Department of Veterans Affairs (VA), Medicare introduced BZD coverage in 2013. It is unknown whether declines in the VA have been widespread among older adults in the United States. DESIGN: Observational study in traditional fee‐for‐service Medicare, commercial insurance, and the VA. SETTING: United States, 2013–2017. PARTICIPANTS: Adults aged 55 and older in traditional Medicare (234,290,693 person‐months), commercial insurance (337,827,125 person‐months), and the VA (256,590,369 person‐months). MEASUREMENTS: (1) Change in BZD and BZD‐opioid co‐prescribing modeled by Poisson regression over time; and (2) standardized ratios of BZD and BZD‐opioid co‐prescribing, using Medicare as the reference. RESULTS: From April 2013 to December 2017, the monthly percentage of adults aged 55 and older who received BZDs fell from 10.4% to 9.3% in Medicare, 6.6% to 6.5% in commercial insurance, and 5.7% to 3.0% in the VA. Monthly BZD‐opioid co‐prescribing over the same time fell from 4.0% to 3.0% in Medicare, 2.3% to 2.0% in commercial, and 2.2% to.6% for the VA. Age‐ and sex‐adjusted rates of decline for BZD and BZD‐opioid co‐prescribing were statistically significant for all systems. Annual BZD rate reductions were.98 (Medicare),.99 (commercial), and.87 (VA; P <.001 for all); co‐prescribing rate reductions were.95,.99, and.75 (P <.001 for all). Using standardized ratios accounting for demographic and clinical characteristics, both prescribing and co‐prescribing were lowest for the VA relative to Medicare (standardized BZD ratio =.40; 95% confidence interval [CI] =.39–.40; standardized BZD‐opioid co‐prescribing ratio =.35; 95% CI =.35–.35). Prescribing in commercial insurance was also lower (BZD =.65; 95% CI =.65–.65; BZD‐opioid co‐prescribing =.65; 95% CI =.65–.65). CONCLUSION: BZD prescribing has declined much more to older adults receiving care through the VA than Medicare or commercial insurance. Other systems may learn from strategies implemented in the VA. [ABSTRACT FROM AUTHOR]

BACKGROUND: The structure provided by school settings even with no specific obesity‐intervention may prevent weight gain. This meta‐analytic study considered this premise by examining weight outcomes from control groups in published randomized controlled trials of school‐year obesity‐related interventions conducted in‐school and out‐of‐school. METHODS: A systematic review and random‐effects meta‐analysis were conducted in accordance with Preferred Reporting Items of Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Databases were systematically searched and resulted in 1976 unique citations, with 14 retained for analysis. Analyses examined the change in weight outcomes among control group participants. RESULTS: For studies (N = 6) reporting body mass index (BMI) (kg/m2) the overall standardized mean difference (SMD) from pre‐ to post‐intervention was 0.085 (raw units 0.278 kg/m2); for studies (N = 9) reporting zBMI, the SMD was 0.022 (0.020 z‐scores), for studies (N = 2) reporting waist circumference (cm), the SMD was 0.149 (1.609 cm); for studies (N = 2) reporting BMI percentile, the SMD was 0.064 (0.985 percentiles); and for studies (N = 1) reporting percent body fat, the SMD was 0.031 (0.30 percentage). CONCLUSIONS: Children assigned to control conditions (as part of school‐based obesity‐related interventions) experience, on average, minimal changes in weight outcomes during the school year. Therefore, routine practices of schools may protect against unhealthy weight gains. [ABSTRACT FROM AUTHOR]

A Raman‐based, strain‐independent, semi‐automated method is presented that allows the rapid (<3 hours) determination of antibiotic susceptibility of bacterial pathogens isolated from clinical samples. Applying a priori knowledge about the mode of action of the respective antibiotic, we identified characteristic Raman marker bands in the spectrum and calculated batch‐wise weighted sum scores from standardized Raman intensity differences between spectra of antibiotic exposed and nonexposed samples of the same strains. The lead substances for three relevant antibiotic classes (fluoroquinolone ciprofloxacin, third‐generation cephalosporin cefotaxime, ureidopenicillin piperacillin) against multidrug‐resistant Gram‐negative bacteria (MRGN) revealed a high sensitivity and specificity for the susceptibility testing of two Escherichia coli laboratory strains and 12 clinical isolates. The method benefits from the parallel incubation of control and treated samples, which reduces the variance due to alterations in cultivation conditions and the standardization of differences between batches leading to long‐term comparability of Raman measurements. [ABSTRACT FROM AUTHOR]

Background: Alcohol can lead to fatal and nonfatal overdose (OD) through its neurobiological inhibitory effects when used alone or with other drugs. Little research has examined alcohol OD characteristics in the context of concomitant drug use. Methods: This study utilized alcohol OD data (defined as alcohol poisoning, passing out, or blacking out) collected in a large residential addiction treatment facility (N = 660). Latent class analysis identified classes of alcohol OD events based on concomitant drug use at the time of OD. We evaluated correlates of alcohol OD classes, including depression, emergency medical services, and hospitalization, using latent class regression. Results: Only 20% of alcohol ODs involved alcohol alone. Marijuana was the most commonly used drug during the most recent alcohol OD (43.2%), followed by sedatives (27.9%), cocaine or crack (25.9%), prescription opioids (26.1%), and heroin (20%). The final latent class model included 3 classes: no/low drug involvement (61%), moderate drug involvement (33%), and high drug involvement (6%). Relative to the no/low drug involvement class, participants admitted to the hospital were 6.4‐fold more likely to be in the high drug involvement class (95% CI: 2.4 to 16.6) and 2.9‐fold more likely to be in the moderate drug involvement class (95% CI: 1.2 to 7.2). Participants receiving emergency medical services were more likely to be in the high drug involvement class (aOR: 2.2, 95% CI: 2.2, 1.1 to 4.5) and less likely to be in the moderate drug involvement class (aOR 0.39, 95% CI: 0.2 to 0.96). Conclusions: Combining drug classes with alcohol prior to OD was common and associated with a higher likelihood of hospitalization. Overdose prevention efforts should address acute risks of alcohol ingestion with other drugs. [ABSTRACT FROM AUTHOR]

Barth syndrome (BTHS) is a rare X‐linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6′6′H2 glucose and U‐13C palmitate and indirect calorimetry during rest, 30‐minutes of moderate exercise (50% V˙O2peak), and recovery. Cardiac function, cardioskeletal mitochondrial energetics, and exercise capacity were examined via echocardiography, 31P magnetic resonance spectroscopy, and peak exercise testing, respectively. The glucose turnover rate was significantly higher in individuals with BTHS during rest (33.2 ± 9.8 vs 27.2 ± 8.1 μmol/kgFFM/min, P < .01) and exercise (34.7 ± 11.2 vs 29.5 ± 8.8 μmol/kgFFM/min, P < .05) and tended to be higher postexercise (33.7 ± 10.2 vs 28.8 ± 8.0 μmol/kgFFM/min, P < .06) compared to controls. Increases in total fat (−3.9 ± 7.5 vs 10.5 ± 8.4 μmol/kgFFM/min, P < .0001) and plasma fatty acid oxidation rates (0.0 ± 1.8 vs 5.1 ± 3.9 μmol/kgFFM/min, P < .0001) from rest to exercise were severely blunted in BTHS compared to controls. Conclusion: An inability to upregulate fat metabolism during moderate intensity exercise appears to be partially compensated by elevations in glucose metabolism. Derangements in fat and glucose metabolism are characteristic of the pathophysiology of BTHS. A severely blunted ability to upregulate fat metabolism during a modest level of physical activity is a defining pathophysiologic characteristic in children, adolescents, and young adults with BTHS. [ABSTRACT FROM AUTHOR]

Summary: The fungicide fludioxonil causes hyperactivation of the Hog1p MAPK within the high‐osmolarity glycerol signaling pathway essential for osmoregulation in pathogenic fungi. The molecular regulation of MoHog1p phosphorylation is not completely understood in pathogenic fungi. Thus, we identified and characterized the putative MoHog1p‐interacting phosphatase gene MoPTP2 in the filamentous rice pathogen Magnaporthe oryzae. We found overexpression of MoPTP2 conferred fludioxonil resistance in M. oryzae, whereas the 'loss of function' mutant ΔMoptp2 was more susceptible toward the fungicide. Additionally, quantitative phosphoproteome profiling of MoHog1p phosphorylation revealed lower phosphorylation levels of MoHog1p in the MoPtp2p overexpression mutant compared to the wild‐type strain, whereas MoHog1p phosphorylation increased in the ΔMoptp2 mutant. Furthermore, we identified a set of MoHog1p‐dependent genes regulated by the MoPtp2p expression level. Our results indicate that the phosphatase MoPtp2p is involved in the regulation of MoHog1p phosphorylation and that overexpression of the gene MoPTP2 is a novel molecular mechanism of fungicide resistance. Elucidation of the molecular principles of fungicide resistance is of great importance in order to identify new antifungal drugs and understanding fungal physiology. In this study, we demonstrated for the first time that overexpression of the phosphatase MoPtp2p represents a novel molecular mechanism of fludioxonil resistance in a filamentous pathogen – the rice blast fungus Magnaporthe oryzae. [ABSTRACT FROM AUTHOR]

BACKGROUND: The mitogen‐activated protein kinase MoHog1p was fused with a green fluorescent protein (GFP) in the filamentous fungus Magnaporthe oryzae. The MoHOG1::GFP mutant was found to be an excellent tool visualizing in vivo fungicide‐dependent translocation of MoHog1p into the nucleus. Validation of pathway specificity was achieved by generating fluorescence‐labelled MoHog1p in the ΔMohik1 'loss of function' mutant strain. RESULTS: GFP‐labelled MoHog1p expressed in the wildtype and in ΔMohik1 demonstrates that fludioxonil is acting on the HOG pathway and even more precisely that fungicide action is dependent on the group III histidine kinase MoHik1p. GFP‐tagged MoHog1p translocated into the nucleus upon fungicide treatment in the MoHOG1::GFP mutant within seconds, but did not do so in the ΔMohik1/HOG1::GFP mutant. CONCLUSION: Here, we developed a rapid in vivo tool for fluorescent‐based validation of fungicides targeting the HOG‐signaling pathway. Furthermore, using the fluorescent mutants generated in this study, we are able to visualize that fungicide action is dependent on the histidine kinase MoHik1p but operates in a different mechanism of pathway activation compared to osmotic stress. © 2018 Society of Chemical Industry This article presents a rapid in vivo tool for fluorescent‐based validation of fungicides with direct reference to the target location. [ABSTRACT FROM AUTHOR]

Skeletal muscle mass is regulated by the coordinated activation of several anabolic and catabolic pathways. The endoplasmic reticulum (ER) is a major site of protein folding and a reservoir for calcium ions. Accretion of misfolded proteins or depletion in calcium concentration causes stress in the ER, which leads to the activation of a signaling network known as the unfolded protein response (UPR). In the present study, we investigated the role of the protein kinase R-like endoplasmic reticulum kinase (PERK) arm of the UPR in the regulation of skeletal muscle mass and function in naive conditions and in a mouse model of cancer cachexia. Our results demonstrate that the targeted inducible deletion of PERK reduces skeletal muscle mass, strength, and force production during isometric contractions. Deletion of PERK also causes a slow-to-fast fiber type transition in skeletal muscle. Furthermore, short hairpin RNA-mediated knockdown or pharmacologic inhibition of PERK leads to atrophy in cultured myotubes. While increasing the rate of protein synthesis, the targeted deletion of PERK leads to the increased expression of components of the ubiquitin-proteasome system and autophagy in skeletal muscle. Ablation of PERK also increases the activation of calpains and deregulates the gene expression of the members of the FGF19 subfamily. Furthermore, the targeted deletion of PERK increases muscle wasting in Lewis lung carcinoma tumor-bearing mice. Our findings suggest that the PERK arm of the UPR is essential for the maintenance of skeletal muscle mass and function in adult mice. [ABSTRACT FROM AUTHOR]

Copyright of Tropical Medicine & International Health is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Moreover, it demonstrates that uPA knockout mice do not compensate the chronic lack of uPA by upregulating other serine proteases with the ability to convert plasminogen into plasmin in nephrotic urine. We also agree that very low concentrations of plasmin are sufficient to cause proteolytic ENaC activation as we have previously shown in vitro.[5] Therefore, we cannot rule out the possibility that in nephrotic uPA knockout mice very low concentrations of urinary plasmin may contribute to proteolytic ENaC activation. In our view, both studies question the current concept of uPA-mediated plasmin generation as a key mechanism of proteolytic ENaC activation and sodium retention in nephrotic syndrome. Urokinase-type plasminogen activator (uPA) is not essential for epithelial sodium channel (ENaC)-mediated sodium retention in experimental nephrotic syndrome. [Extracted from the article]

Abstract: Aim: Recent work has demonstrated that activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases causes sodium retention in nephrotic syndrome. The aim of this study was to elucidate a potential role of plasma kallikrein (PKLK) as a candidate serine protease in this context. Methods: We analysed PKLK in the urine of patients with chronic kidney disease (CKD, n = 171) and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in PKLK‐deficient mice (klkb1−/−) with experimental nephrotic syndrome induced by doxorubicin injection. Results: In patients with CKD, we found that PKLK is excreted in the urine up to a concentration of 2 μg mL−1 which was correlated with albuminuria (r = .71) and overhydration as assessed by bioimpedance spectroscopy (r = .44). PKLK increased ENaC‐mediated whole‐cell currents, which was associated with the appearance of a 67 kDa γ‐ENaC cleavage product at the cell surface consistent with proteolytic activation. Mutating a putative prostasin cleavage site in γ‐ENaC prevented channel stimulation by PKLK. In a mouse model for nephrotic syndrome, active PKLK was present in nephrotic urine of klkb1+/+ but not of klkb1−/− mice. However, klkb1−/− mice were not protected from ENaC activation and sodium retention compared to nephrotic klkb1+/+ mice. Conclusion: Plasma kallikrein is detected in the urine of proteinuric patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site. However, PKLK is not essential for volume retention in nephrotic mice. [ABSTRACT FROM AUTHOR]

Abstract: Optical fibers possessing a crystalline oxide core have significant potential for novel and useful electro‐ or nonlinear‐optic waveguides. Presently, however, their utility suffers from the slow speed and limited cladding materials afforded by conventional crystal‐fiber‐growth techniques. Described herein is the development of single phase bismuth germanium oxide crystalline core fibers using conventional glass fiber drawing. More specifically, fibers were fabricated and evaluated based on 2 embodiments of the molten core method. In a first approach, a Bi4Ge3O12 single crystal was employed as the precursor and sleeved inside a borosilicate glass cladding. In the second approach, additional Bi2O3 was included along with the Bi4Ge3O12 precursor single crystal. Glass clad fibers drawn from the precursor Bi4Ge3O12 single crystal resulted in a polycrystalline core with various crystal morphologies (line‐like, dendrite‐like, and uniform grains) as will be discussed, while fibers drawn from the Bi4Ge3O12 single crystal surrounded by Bi2O3 resulted in a more homogeneous microstructure. The eulytine crystal structure was crystallized using both approaches, with the formation of a secondary crystal phase using the second approach. More particularly, this work aims at showing that single phase and phase pure crystalline oxide core optical fibers can be achieved using conventional glass fiber draw processes, although further optimization is necessary for obtaining single crystalline core fibers. [ABSTRACT FROM AUTHOR]

Summary: Due to increasingly high rates of child overweight and obesity, it is important to identify risk and protective factors that may inform more effective prevention and intervention. The degree of organization in the family home environment is a studied, but not well‐specified, factor that may impact child weight. Prior research on household organization has examined an array of constructs, including family routines, limit setting, household chaos, crowding and the broad home environment. This study systematically reviews literature on organization within the family home environment and weight among children ages 2–12. Six hundred thirty‐seven studies were reviewed by four coders for eligibility, and 32 studies were included in the final synthesis. Overall, 84% of studies provided evidence for relations between at least one indicator of organization within the family home environment and child weight. Studies provided compelling evidence across several constructs, suggesting that the relevance of household organization to child weight extends beyond a single indicator. Directions for future work include (i) examining the mediating role of health behaviours, (ii) examining the moderating role of socioeconomic factors, (iii) broadening this evidence base across cultures and nationalities and (iv) integrating constructs to develop a comprehensive model of organization within the home environment. [ABSTRACT FROM AUTHOR]

Summary: Background: The latest generation of radiofrequency, nanofractional radiofrequency, allows the heat energy to be delivered through the use of pins or needles as electrodes, facilitating increased efficacy and reduced pain, downtime, and side effects. Objective: The objective of this prospective pilot clinical study was to evaluate the efficacy of nanofractional radiofrequency in skin resurfacing. Methods and materials: Seventeen subjects were enrolled in the study, and each received three nanofractional radiofrequency (160‐pin tip) treatments in the facial area at 3‐week intervals. Follow‐up visits were scheduled at 1 and 2 months after the final treatment. Clinical photography, patient, and investigator assessments were conducted during the treatment visits and follow‐up. Results: All subjects completed the study. At the 1‐ and 2‐month follow‐up, there was a moderate to significant improvement (2.6 and 3.5, respectively, P = .01) according to the investigator global esthetic improvement scale rating. Most subjects reported that they were satisfied or very satisfied with the outcome and level of comfort. Conclusion: Nanofractional radiofrequency is a safe and effective strategy for improving texture, tone, and skin laxity with high patient satisfaction and tolerable safety profile. [ABSTRACT FROM AUTHOR]

Skeletal muscle is the most abundant tissue in the human body and can adapt its mass as a consequence of physical activity, metabolism, growth factors, and disease conditions. Skeletal muscle contains an extensive network of endoplasmic reticulum (ER), called sarcoplasmic reticulum, which plays an important role in the regulation of proteostasis and calcium homeostasis. In many cell types, environmental and genetic factors that disrupt ER function cause an accumulation of misfolded and unfolded proteins in the ER lumen that ultimately leads to ER stress. To alleviate the stress and restore homeostasis, the ER activates a signaling network called the unfolded protein response (UPR). The UPR has three arms, which regulate protein synthesis and expression of many ER chaperone and regulatory proteins. However, the role of individual UPR pathways in skeletal muscle has just begun to be investigated. Recent studies suggest that UPR pathways play pivotal roles in muscle stem cell homeostasis, myogenic differentiation, and regeneration of injured skeletal muscle. Moreover, markers of ER stress and the UPR are activated in skeletal muscle in diverse conditions such as exercise, denervation, starvation, high fat diet, cancer cachexia, and aging. Accumulating evidence also suggests that ER stress may have important roles in the pathogenesis of inflammatory myopathies and genetic muscle disorders. The purpose of this review article is to discuss the role and potential mechanisms by which ER stress and the individual arms of the UPR regulate skeletal muscle formation, plasticity, and function in various physiological and pathophysiological conditions. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma ( PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes next-generation sequencing ( NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into treatmentmap. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed (e.g. KRAS, TP53). Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all patients. At least one biomarker associated with increased toxicity could be detected in all patients. Patients had been receiving one of the currently approved chemotherapy agents. In two patients, toxicity could have been correctly predicted by the software analysis. The results suggest that NGS, in combination with an evidence-based software, could be conducted within a 2-week period, thus being feasible for clinical routine. Therapy recommendations were principally off-label use. Based on the predominant KRAS mutations, other drugs were predicted to be ineffective. The pharmacogenomic biomarkers indicative of increased toxicity could be retrospectively linked to reported negative side effects in the respective patients. Finally, the occurrence of somatic and germline mutations in cancer syndrome-associated genes is noteworthy, despite a high frequency of these particular variants in the background population. These results suggest software-analysis of NGS data provides evidence-based information on effective, ineffective and toxic drugs, potentially forming the basis for precision cancer medicine in PDAC. [ABSTRACT FROM AUTHOR]

Background and Objectives: We examined use of non-pharmacological treatments for pain in addiction treatment patients.Methods: Patients in addiction treatment with chronic pain (N = 501) were classified based on use of non-pharmacological pain treatments. Demographic and clinical correlates were compared.Results: A total of 49% (N = 243) of patients used a non-pharmacological treatment in the past year versus 72% (N = 361) who used opioids. Non-pharmacological treatment users were more likely to use opioids and other pain medications.Conclusions: Non-pharmacological treatments are less commonly used than opioids by addiction treatment patients.Scientific Significance: Findings highlight the need to better understand pain treatment decision-making among addiction treatment patients. (Am J Addict 2017;26:564-567). [ABSTRACT FROM AUTHOR]

Aims To examine efficacy of drug brief interventions (BIs) among adults presenting to a low-income urban emergency department (ED). Design Randomized controlled trial on drug use outcomes at 3, 6 and 12 months. Participants were assigned to (1) computer-delivered BI (Computer BI), (2) therapist-delivered, computer-guided BI (Therapist BI) or (3) enhanced usual care (EUC-ED) for drug-using adults. Participants were re-randomized after the 3-month assessment to either adapted motivational enhancement therapy (AMET) booster or enhanced usual care booster (EUC-B). Setting Patients recruited from low-income urban emergency departments (ED) in Flint, Michigan, USA. Participants A total of 780 ED patients reporting recent drug use, 44% males, mean age = 31 years. Interventions Computer BI consisted of an interactive program guided by a virtual health counselor. Therapist BI included computer guidance. The EUC-ED conditions included review of community health and HIV prevention resources. The BIs and boosters were based on motivational interviewing, focusing on reduction of drug use and HIV risk behaviors. Measurements Primary outcome was past 90 days using drugs at 6 and 12 months and secondary outcomes were weighted drug-days and days of marijuana use. Findings Percentage changes in mean days used any drug from baseline to 12 months were: Computer BI + EUC-B: -10.9%, P = 0.0844; Therapist BI + EUC-B: -26.7%, P = 0.0041, for EUC-ED + EUC-B: -20.9, P = 0.0011. In adjusted analyses, there was no significant interaction between ED intervention and booster AMET for primary and secondary outcomes. Compared with EUC-ED, Therapist BI reduced number of days using any drug [95% confidence interval (CI) = −0.41, −0.07, P = 0.0422] and weighted drug-days (95% CI = -0.41, −0.08, P = 0.0283). Both Therapist and Computer BI had significantly fewer number of days using marijuana compared to EUC-ED (Therapist BI: 95% CI = -0.42, −0.06, P = 0.0104, Computer BI: 95% CI = -0.34, −0.01, P = 0.0406). Booster effects were not significant. Conclusions An emergency department-based motivational brief intervention, delivered by a therapist and guided by computer, appears to reduce drug use among adults seeking emergency department care compared with enhanced usual care. [ABSTRACT FROM AUTHOR]

Background and Aims Limited information is available regarding links between specific substance use disorders (SUDs) and suicide mortality; however, the preliminary evidence that is available suggests that suicide risk associated with SUDs may differ for men and women. This study aimed to estimate associations between SUDs and suicide for men and women receiving Veterans Health Administration (VHA) care. Design A cohort study using national administrative health records. Setting National VHA system, USA. Participants All VHA users in fiscal year (FY) 2005 who were alive at the beginning of FY 2006 ( n = 4 863 086). Measurements The primary outcome of suicide mortality was assessed via FY 2006-2011 National Death Index (NDI) records. Current SUD diagnoses were the primary predictors of interest, and were assessed via FY 2004-2005 VHA National Patient Care Database (NPCD) records. Findings In unadjusted analyses, a diagnosis of any current SUD and the specific current diagnoses of alcohol, cocaine, cannabis, opioid, amphetamine and sedative use disorders were all associated significantly with increased risk of suicide for both males and females [hazard ratios (HRs)] ranging from 1.35 for cocaine use disorder to 4.74 for sedative use disorder for men, and 3.89 for cannabis use disorder to 11.36 for sedative use disorder for women]. Further, the HR estimates for the relations between any SUD, alcohol, cocaine and opioid use disorders and suicide were significantly stronger for women than men ( P < 0.05). After adjustment for other factors, most notably comorbid psychiatric diagnoses, associations linking SUDs with suicide were attenuated markedly and the greater suicide risk among females was observed for only any SUD and opioid use disorder ( P < 0.05). Conclusions Current substance use disorders (SUDs) signal increased suicide risk, especially among women, and may be important markers to consider including in suicide risk assessment strategies. None the less, other co-occurring psychiatric disorders may partially explain associations between SUDs and suicide, as well as the observed excess suicide risk associated with SUDs among women. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Traumatic Stress is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Latino youth have the highest rate of overweight and obesity across ethnic and racial groups, placing these individuals at increased risk for a variety of negative immediate and long-term health outcomes. Many studies have shown that acculturative factors play a role in this process for adults, while less is known about the impact of these factors for children and adolescents. This study systematically reviews the current literature on acculturative factors and obesity among Latino children. Three hundred and seventy-nine studies were independently reviewed by two coders for eligibility. Twenty-nine studies met eligibility criteria and were included in the final review. Results indicated that relations between acculturation and obesity among Latino children are equivocal. Across studies reviewed, the significance and directionality of this relation differed. Heterogeneity across studies reviewed, including age, specific population and measures used for assessing acculturation, likely contributed to the mixed results. To provide greater clarity on the role of acculturative factors on obesity, future studies should (i) utilize a longitudinal design; (ii) control for potential confounding factors such as socioeconomic status; and (iii) examine potential moderating and mediating influences. [ABSTRACT FROM AUTHOR]

Objective: To determine associations between need, enabling, and predisposing factors with mental health service use among National Guard soldiers in the first year following a combat deployment to Iraq or Afghanistan.Data Sources/study Setting: Primary data were collected between 2011 and 2013 from 1,426 Guard soldiers representing 36 units.Study Design: Associations between Guard soldier factors and any mental health service use were assessed using multivariable logistic regression models in a cross-sectional study. Further analysis among service users (N = 405) assessed VA treatment versus treatment in other settings.Principal Findings: Fifty-six percent of Guard soldiers meeting cutoffs on symptom scales received mental health services with 81 percent of those reporting care from the VA. Mental health service use was associated with need (mental health screens and physical health) and residing in micropolitan communities. Among service users, predisposing factors (middle age range and female gender) and enabling factors (employment, income above $50,000, and private insurance) were associated with greater non-VA services use.Conclusion: Overall service use was strongly associated with need, whereas sector of use (non-VA vs. VA) was insignificantly associated with need but strongly associated with enabling factors. These findings have implications for the recent extension of veteran health coverage to non-VA providers. [ABSTRACT FROM AUTHOR]

Cachexia is a devastating syndrome that causes morbidity and mortality in a large number of patients with cancer. However, the mechanisms of cancer cachexia remain poorly understood. Accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes stress. The ER responds to this stress through activating certain pathways commonly known as the unfolding protein response (UPR). The main function of UPR is to restore homeostasis, but excessive or prolonged activation of UPR can lead to pathologic conditions. In this study, we examined the role of ER stress and UPR in regulation of skeletal muscle mass in naïve conditions and during cancer cachexia. Our results demonstrate that multiple markers of ER stress are highly activated in skeletal muscle of Lewis lung carcinoma (LLC) and ApcMin/+ mouse models of cancer cachexia. Treatment of mice with 4-phenylbutyrate (4-PBA), a chemical chaperon and a potent inhibitor of ER stress, significantly reduced skeletal muscle strength and mass in both control and LLC-bearing mice. Blocking the UPR also increased the proportion of fast-type fibers in soleus muscle of both control and LLC-bearing mice. Inhibition of UPR reduced the activity of Akt/mTOR pathway and increased the expression of the components of the ubiquitin-proteasome system and autophagy in LLC-bearing mice. Moreover, we found that the inhibition of UPR causes severe atrophy in cultured myotubes. Our study provides initial evidence that ER stress and UPR pathways are essential for maintaining skeletal muscle mass and strength and for protection against cancer cachexia. [ABSTRACT FROM AUTHOR]

Background and Aims Chronic pain is difficult to treat in individuals with substance use disorders and, when not resolved, can have a negative impact on substance use disorder treatment outcomes. This study tested the efficacy of a psychosocial pain management intervention, ImPAT (improving pain during addiction treatment), that combines pain management with content related to managing pain without substance use. Design Single-site, parallel-groups randomized controlled trial comparing ImPAT to a supportive psychoeducational control (SPC) condition; follow-up assessments occurred at 3, 6 and 12 months. Setting The Ann Arbor VA Substance Use Disorder treatment program, USA. Participants Veterans Health Administration patients { n = 129; mean [standard deviation (SD)], age = 51.7 (9.5); 115 of 129 (89%) male; ImPAT ( n = 65); SPC ( n = 64)}. Intervention ImPAT combines principles of cognitive-behavioral therapy and acceptance-based approaches to pain management with content related to avoiding the use of substances as a coping mechanism for pain. The SPC used a psychoeducational attention control treatment for alcoholism modified to cover other substances in addition to alcohol. Measurements Primary: Pain intensity over 12 months; secondary: pain-related functioning, frequency of alcohol and drug use over 12 months. Findings Primary: randomization to the ImPAT intervention versus SPC predicted significantly lower pain intensity {β [standard error (SE)] = −0.71 (0.29); 95% confidence interval (CI) = −1.29, −0.12}; secondary: relative to the SPC condition, those who received ImPAT also reported improved pain-related functioning [β (SE) = 0.27 (0.11); 95% CI = 0.05, 0.49] and lower frequency of alcohol consumption [β (SE) = −0.77; 95% CI = −1.34, −0.20]. No differences were found between conditions on frequency of drug use over follow-up. Conclusions For adults with pain who are enrolled in addictions treatment, receipt of a psychological pain management intervention (improving pain during addiction treatment) reduced pain and alcohol use and improves pain-related functioning over 12 months relative to a matched-attention control condition. [ABSTRACT FROM AUTHOR]

Mesembryanthemum crystallinum (ice plant) exhibits extreme tolerance to salt. Epidermal bladder cells ( EBCs), developing on the surface of aerial tissues and specialized in sodium sequestration and other protective functions, are critical for the plant's stress adaptation. We present the first transcriptome analysis of EBCs isolated from intact plants, to investigate cell type-specific responses during plant salt adaptation., We developed a de novo assembled, nonredundant EBC reference transcriptome. Using RNAseq, we compared the expression patterns of the EBC-specific transcriptome between control and salt-treated plants., The EBC reference transcriptome consists of 37 341 transcript-contigs, of which 7% showed significantly different expression between salt-treated and control samples. We identified significant changes in ion transport, metabolism related to energy generation and osmolyte accumulation, stress signalling, and organelle functions, as well as a number of lineage-specific genes of unknown function, in response to salt treatment., The salinity-induced EBC transcriptome includes active transcript clusters, refuting the view of EBCs as passive storage compartments in the whole-plant stress response. EBC transcriptomes, differing from those of whole plants or leaf tissue, exemplify the importance of cell type-specific resolution in understanding stress adaptive mechanisms. [ABSTRACT FROM AUTHOR]

This cross-sectional study examined relations between affluent adolescent adjustment and culturally salient factors within parent–child relationship and extracurricular domain. Bootstrapping techniques evaluated mediated effects among parental perfectionism, perceived parental pressure, intensity of organized activity (OA) involvement, and adolescent adjustment (i.e., depressive and anxiety symptoms, life satisfaction) within a sample of 10th graders and their parents ( n = 88 parent–child pairs) from four high schools in affluent communities. Findings indicated that adolescents with more perfectionistic parents perceived more parental pressure and experienced poorer adjustment. Results also demonstrated that affluent adolescents who perceived more parental pressure were more intensely involved in OAs, but that higher OA intensity was linked to better adjustment. Findings highlight the importance of considering parental perfectionism when understanding adolescent behaviors and psychological outcomes, confirm the negative direct effects of parental pressure on adjustment, and corroborate prior research dispelling that highly intense OA involvement is linked to adolescent maladjustment. [ABSTRACT FROM AUTHOR]

Youth engagement is the least researched, but potentially most important, aspect of participation in afterschool programs. The level of youth engagement can vary across programs, across youth within a program, and within individual youth over time. Engagement is important for both recruiting and retaining participants, and has been associated with more positive academic outcomes over time. This chapter integrates perspectives from practitioners, researchers, and the school engagement literature. Reasons why engagement is an important dimension of afterschool programming, different methods for assessing engagement, key features of engaging afterschool programs, and implications for practice are also outlined. [ABSTRACT FROM AUTHOR]

Individuals with substance use disorders (SUDs) are at high risk of suicidal behaviors, highlighting the need for an improved understanding of potentially influential factors. One such domain is self-efficacy to manage suicidal thoughts and impulses. Psychometric data about the Self-Efficacy to Avoid Suicidal Action (SEASA) Scale within a sample of adults seeking SUD treatment (N = 464) is provided. Exploratory factor analysis supported a single self-efficacy construct. Lower SEASA scores, or lower self-efficacy, were reported in those with more severe suicidal ideation and those with more suicide attempts, providing evidence for convergent validity. Implications of measuring self-efficacy in the context of suicide risk assessment are discussed. [ABSTRACT FROM AUTHOR]

Germination of seeds from individual seed capsules of Mesembryanthemum crystallinum (common ice plant) is spread out over time with some seeds germinating within 1 d (early, E) and others germinating up to more than 4 weeks after imbibition (late, L). L-seeds are characterized by a lack of expression of Cdc2-related transcripts and an increase of Vp1-transcripts after water uptake, while Cdc2-related transcripts increase early and Vp1 decline early in E-seeds. Maintenance of Vp1 transcription, which can be disrupted by abolishing translation activity, seems to be at the basis of prolonged dormancy in L-seeds. We have in addition characterized the expression of several MIP (water channel) proteins during germination and in organs of adult plants. Using probes specific for individual ice plant Mip, we observed differences during germination that are not exclusively due to water uptake. Mip transcripts increase before L-seeds begin to germinate. Gene-specific probes indicate that the expression of all Mip is high in germinating seedlings, but differences in expression exist in the root, hypocotyl and cotyledon. In adult plants, all Mip-transcripts are expressed at a significantly lower rate than in seedlings, and organ-specific expression of individual Mip transcripts is observed. Their expression, measured by MIP-specific antibodies, indicates developmental specificity of MIP in different organs and highest amounts in actively growing tissues. [ABSTRACT FROM AUTHOR]