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α7-Nicotinic acetylcholine receptor (α7nAChR) agonists confer protection against a wide variety of cytotoxic insults and suppress oxidative stress and apoptosis in various cell systems, including hepatocytes. We recently demonstrated that nicotine, when combined with a high-fat diet (HFD), triggers oxidative stress, activates hepatocyte apoptosis, and exacerbates HFD-induced hepatic steatosis in male mice. This study evaluates whether PNU-282987 (PNU), a specific α7nAChR agonist, is effective in preventing nicotine plus HFD-induced hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice-daily intraperitoneal injections of 0.75 mg/kg body weight (BW) of nicotine, PNU (0.26 mg/kg BW), PNU plus nicotine, or saline for 10 weeks. PNU treatment was effective in attenuating nicotine plus HFD-induced increase in hepatic triglyceride levels, hepatocyte apoptosis, and hepatic steatosis. The preventive effects of PNU on nicotine plus HFD-induced hepatic steatosis were mediated by suppression of oxidative stress and activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) together with inhibition of its downstream target sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-coenzyme A-carboxylase (ACC). We conclude that the α7nAChR agonist PNU protects against nicotine plus HFD-induced hepatic steatosis in obese mice. PNU appears to work at various steps of signaling pathways involving suppression of oxidative stress, activation of AMPK, and inhibition of SREBP1c, FAS, and ACC. α7nAChR agonists may be an effective therapeutic strategy for ameliorating fatty liver disease, especially in obese smokers.

OBJECTIVE: Articles previously published by Sullivan et al. and Cristofalo et al. were reanalyzed using the proportion of cow milk-based nutrition received to determine whether that affected clinical outcomes during hospitalization for infants birth weight 500-1250 g. Abrams et al. showed in the same cohort incidences of necrotizing enterocolitis (NEC), NEC requiring surgery and sepsis increased proportionally to the amount of dietary cow milk. METHODS: The data from the two studies conducted under essentially the same protocol were combined yielding a cohort of 260 infants receiving a diet ranging from 0% to 100% cow milk. Data analysis utilized negative binomial regression which mitigates differences between subjects in terms of their time on study by incorporating that number into the statistical model. The percent of cow milk-based nutrition was the only predictor investigated. RESULTS: For all outcomes the larger the amount of cows milk in the diet the greater the number of days of that intervention required. A trend toward statistical significance was seen for ventilator days; however, only parenteral nutrition (PN) days and days to full feeds achieved statistical significance. CONCLUSIONS: Incorporation of any cow milk-based nutrition into the diet of extremely premature infants correlates with more days on PN and a longer time to achieve full feeds. There was a nonstatistically significant trend toward increased ventilator days. These represent additional clinical consequences of the use of any cow milk-based protein in feeding EP infants.

BackgroundInadequate protein intake and hypoalbuminemia, indicators of protein-energy wasting, are among the strongest mortality predictors in hemodialysis patients. Hemodialysis patients are frequently counseled on dietary phosphorus restriction, which may inadvertently lead to decreased protein intake. We hypothesized that, in hypoalbuminemic hemodialysis patients, provision of high-protein meals during hemodialysis combined with a potent phosphorus binder increases serum albumin without raising phosphorus levels.MethodsWe conducted a randomized controlled trial in 110 adults undergoing thrice-weekly hemodialysis with serum albumin

Many of the CM carbonaceous chondrites are regolith breccias and so should have abundant evidence for collisional processing. The constituent clasts of these fragmental rocks frequently display compactional petrofabrics; yet, olivine microstructures show that most CMs are unshocked. To better understand the reasons for this contradiction, we have sought other evidence for hypervelocity impact processing of CM chondrites using the Cold Bokkeveld meteorite. We find that this regolith breccia contains rare particles of vesicular shock melt that are close in chemical composition to bulk CM chondrite. Transmission electron microscopy of a melt bead shows that it is composed of silicate glass with inclusions of pentlandite, pyrrhotite, and wüstite. Characterization of shards of another bead by atom probe tomography reveals nanoscale clusters of sulfur that represent sulfide inclusions arrested at an early stage of growth. These glass particles are mineralogically comparable to micrometeoroid impact melt described from the Cb‐type asteroid Ryugu and melt that has been experimentally produced by pulsed laser irradiation of CM targets. The glass could have formed by in situ shock‐melting, but petrographic evidence is more consistent with an origin as ballistic ejecta from a distal impact. The scarcity of melt in this meteorite, and CM chondrites more broadly, is consistent with the explosive fragmentation of hydrous asteroids following energetic collisions. Cold Bokkeveld's parent body is likely to be a second‐generation asteroid that was constructed from the debris of one or more earlier bodies, and only a small proportion of the reaccreted material had been highly shocked and melted. [ABSTRACT FROM AUTHOR]

The given text provides summaries of various research studies presented at the Middle East Immunology Summit. The first study discusses a case of Evan syndrome secondary to systemic lupus erythematosus (SLE) in a pediatric patient. The second study examines the impact of COVID-19 vaccination on circulating cytokine profiles in individuals in Saudi Arabia. The third study explores the prevalence of food and inhalation allergen-specific IgE antibody positivity in residents of the Northern Emirates of the UAE, highlighting differences between Arab and non-Arab individuals. These studies contribute to our understanding of autoimmune diseases, vaccine responses, and allergies in the Middle East region. [Extracted from the article]

Background: Iodinated contrast is commonly used for radiological procedures, with one dose delivering several hundred-fold the daily requirements needed for normal thyroid hormone production. Risks of excess iodine include incident thyroid dysfunction, which is associated with adverse cardiac outcomes, yet there are no prospective studies investigating the changes in cardiac physiology following iodine contrast administration. This study was conducted to investigate the longitudinal relationships between the amount of iodinated contrast administration and changes in cardiac electrophysiology and structure. Methods: A longitudinal cohort study was conducted with prospectively enrolled participants who received iodine contrast for elective computed tomography or coronary angiography. Serum thyroid function tests, electrocardiograms (EKG), and transthoracic echocardiograms were obtained serially until 36 months. Trends of electrical and structural cardiac changes following iodine contrast administration were assessed using mixed effect models. Results: The cohort was composed of 129 patients (median age, 70 [interquartile range: 63, 75] years; 98% male). Larger amounts of iodine exposure were associated with increases in QRS and QTc durations and decreased ejection fraction (EF), and these associations were still observed for follow-up EF after additionally adjusting for baseline values (the high-iodine contrast group vs. the low-iodine contrast group, −4.23% [confidence interval, −7.66% to −0.79%]). Dose–response analyses also showed lower EF with larger amounts of iodine received; these trends were not significant for the EKG parameters studied. Conclusions: Over a period of up to 36 months, a larger amount of administered iodine contrast was associated with lower EF among participants. Further investigation is needed to elucidate the long-term trends of electrical and structural cardiac function after iodine contrast administration. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine whether electronic health record (EHR) tools improve documentation of pre- and postanalytic care processes for genetic tests ordered by nongeneticists. METHODS: We conducted a nonrandomized, controlled, pre-/postintervention study of EHR point-of-care tools (informational messages and template report) for three genetic tests. Chart review assessed documentation of genetic testing processes of care, with points assigned for each documented item. Multiple linear and logistic regressions assessed factors associated with documentation. RESULTS: Preimplementation, there were no significant site differences (P > 0.05). Postimplementation, mean documentation scores increased (5.9 (2.1) vs. 5.0 (2.2); P = 0.0001) and records with clinically meaningful documentation increased (score >5: 59 vs. 47%; P = 0.02) at the intervention versus the control site. Pre- and postimplementation, a score >5 was positively associated with abnormal test results (OR = 4.0; 95% CI: 1.8-9.2) and trainee provider (OR = 2.3; 95% CI: 1.2-4.6). Postimplementation, a score >5 was also positively associated with intervention site (OR = 2.3; 95% CI: 1.1-5.1) and specialty clinic (OR = 2.0; 95% CI: 1.1-3.6). There were also significantly fewer tests ordered after implementation (264/100,000 vs. 204/100,000; P = 0.03), with no significant change at the control site (280/100,000 vs. 257/100,000; P = 0.50). CONCLUSIONS: EHR point-of-care tools improved documentation of genetic testing processes and decreased utilization of genetic tests commonly ordered by nongeneticists.Genet Med 19 1, 112-120.

BackgroundStepped wedge designs have gained recognition as a method for rigorously assessing implementation of evidence-based quality improvement interventions (QIIs) across multiple healthcare sites. In theory, this design uses random assignment of sites to successive QII implementation start dates based on a timeline determined by evaluators. However, in practice, QII timing is often controlled more by site readiness. We propose an alternate version of the stepped wedge design that does not assume the randomized timing of implementation while retaining the method's analytic advantages and applying to a broader set of evaluations. To test the feasibility of a nonrandomized stepped wedge design, we developed simulated data on patient care experiences and on QII implementation that had the structures and features of the expected data from a planned QII. We then applied the design in anticipation of performing an actual QII evaluation.MethodsWe used simulated data on 108,000 patients to model nonrandomized stepped wedge results from QII implementation across nine primary care sites over 12 quarters. The outcome we simulated was change in a single self-administered question on access to care used by Veterans Health Administration (VA), based in the United States, as part of its quarterly patient ratings of quality of care. Our main predictors were QII exposure and time. Based on study hypotheses, we assigned values of 4 to 11 % for improvement in access when sites were first exposed to implementation and 1 to 3 % improvement in each ensuing time period thereafter when sites continued with implementation. We included site-level (practice size) and respondent-level (gender, race/ethnicity) characteristics that might account for nonrandomized timing in site implementation of the QII. We analyzed the resulting data as a repeated cross-sectional model using HLM 7 with a three-level hierarchical data structure and an ordinal outcome. Levels in the data structure included patient ratings, timing of adoption of the QII, and primary care site.ResultsWe were able to demonstrate a statistically significant improvement in adoption of the QII, as postulated in our simulation. The linear time trend while sites were in the control state was not significant, also as expected in the real life scenario of the example QII.ConclusionsWe concluded that the nonrandomized stepped wedge design was feasible within the parameters of our planned QII with its data structure and content. Our statistical approach may be applicable to similar evaluations.

ContextAlthough recent randomized controlled trials support early palliative care for patients with advanced cancer, the specific processes of care associated with these findings and whether these improvements can be replicated in the broader health care system are uncertain.ObjectivesThe aim of this study was to evaluate the occurrence of palliative care consultation and its association with specific processes of supportive care in a national cohort of Veterans using the Cancer Quality ASSIST (Assessing Symptoms Side Effects and Indicators of Supportive Treatment) measures.MethodsWe abstracted data from 719 patients' medical records diagnosed with advanced lung, colorectal, or pancreatic cancer in 2008 over a period of three years or until death who received care in the Veterans Affairs Health System to evaluate the association of palliative care specialty consultation with the quality of supportive care overall and by domain using a multivariate regression model.ResultsAll but 54 of 719 patients died within three years and 293 received at least one palliative care consult. Patients evaluated by a palliative care specialist at diagnosis scored seven percentage points higher overall (P

ImportanceGene transfer has rarely been tested in randomized clinical trials.ObjectiveTo evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure.Design, setting, and participantsA randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt) and decline (-dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization.InterventionsIntracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo.Main outcomes and measuresPrimary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and -dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5).ResultsFifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants had increased EF at 4 weeks (+6.0 [1.7] EF units; n = 21; P

BACKGROUND: The Veterans Health Administration (VA) has invested substantially in evidence-based mental health care. Yet no electronic performance measures for assessing the level at which the population of Veterans with depression receive appropriate care have proven robust enough to support rigorous evaluation of the VAs depression initiatives. OBJECTIVE: Our objectives were to develop prototype longitudinal electronic population-based measures of depression care quality, validate the measures using expert panel judgment by VA and non-VA experts, and examine detection, follow-up and treatment rates over a decade (2000-2010). We describe our development methodology and the challenges to creating measures that capture the longitudinal course of clinical care from detection to treatment. DESIGN AND PARTICIPANTS: Data come from the National Patient Care Database and Pharmacy Benefits Management Database for primary care patients from 1999 to 2011, from nine Veteran Integrated Service Networks. MEASURES: We developed four population-based quality metrics for depression care that incorporate a 6-month look back and 1-year follow-up: detection of a new episode of depression, 84 and 180 day follow-up, and minimum appropriate treatment 1-year post detection. Expert panel techniques were used to evaluate the measure development methodology and results. Key challenges to creating valid longitudinal measures are discussed. KEY RESULTS: Over the decade, the rates for detection of new episodes of depression remained stable at 7-8 %. Follow-up at 84 and 180 days were 37 % and 45 % in 2000 and increased to 56 % and 63 % by 2010. Minimum appropriate treatment remained relatively stable over the decade (82-84 %). CONCLUSIONS: The development of valid longitudinal, population-based quality measures for depression care is a complex process with numerous challenges. If the full spectrum of care from detection to follow-up and treatment is not captured, performance measures could actually mask the clinical areas in need of quality improvement efforts.

BackgroundParkinson's disease, the second most common neurodegenerative disease, is diagnostically defined by motor impairments, but also includes often under-recognized impairments in cognition, mood, sleep, and the autonomic nervous system. These problems can severely affect individuals' quality of life. In our prior research, we have developed indicators to measure the quality of care delivered to patients with Parkinson's disease, and we identified gaps in delivering evidence-based treatments for this population. Effective strategies to close these gaps are needed to improve patient quality of life.Methods/designBuilding on prior research we developed a multi-faceted proactive implementation program called Care Coordination for Health Promotion and Activities in Parkinson's Disease (CHAPS). To be eligible, patients had to have at least two visits with a primary diagnosis of idiopathic Parkinson's disease (ICD-9 code: 332.0) at one of five Veterans Affairs Medical Centers in the southwestern United States from 2010 to 2014. The program consists of telephone assessments, evidence-based protocols, and tools to enhance patient self-management, care planning, and coordination of care across providers, including an electronic database to support and track coordination of care. Our mixed-methods study employs a randomized, controlled trial design to test whether the CHAPS intervention improves performance in 38 quality measures among an analytic sample of 346 patients. The 38 quality measures are categorized into overarching areas of communication, education, and continuity; regulatory reporting; diagnosis; periodic assessment; medication use; management of motor and non-motor symptoms; use of non-pharmacological approaches and therapies; palliative care; and health maintenance. Secondary outcomes are patient health-related quality of life, self-efficacy, and perceptions of care quality. We are also evaluating the extent of the CHAPS Program implementation and measuring program costs and impacts on health services utilization, in order to perform a analysis of the CHAPS program from the perspective of the Veterans Health Administration (VA). Outcomes are assessed by interviewer-administered surveys collected at baseline and at 6, 12, and 18 months, and by medical record chart abstractions. Analyses will be intention-to-treat.DiscussionThe CHAPS Program is poised for dissemination within the VA National Parkinson's Disease Research, Education, and Clinical Center Consortium if demonstrated efficacious.Trial registrationClinicalTrials.gov NCT01532986; registered on January 13, 2012.

ObjectiveWe studied the impact of continuing versus discontinuing pioglitazone on hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and weight when starting bedtime insulin in patients with poor glycemic control.MethodsWe retrospectively analyzed data from a 13-month randomized control trial on 77 patients with type 2 diabetes mellitus (DM), who despite maximum doses of three oral diabetes medications (metformin, sulfonylurea and pioglitazone) had HbA1C levels above 7.5%. Patients were randomized to either continuing or discontinuing pioglitazone in addition to starting and up-titrating bedtime insulin. HbA1C, FPG, and weight were assessed at baseline, 3months, 7months and 13months with the differences from baseline for the two groups compared at each of the three time points using the Wilcoxon rank sum test.ResultsWe found that HbA1c was significantly lower at the 7-month (p=0.01) and 13-month time points (p=0.036), and FPG was significantly lower at all three time points in the group continuing pioglitazone compared with those discontinuing pioglitazone. Continuing pioglitazone resulted in a greater increase in weight at the 3-month (p=0.002), 7-month (p=0.0001) and 13-month (p=0.00003) time points. Patients with the lowest HbA1c (

Transmission electron microscopy analyses of Hayabusa2 samples show that Ryugu organic matter exhibits a range of morphologies, elemental compositions, and carbon functional chemistries consistent with those of carbonaceous chondrites that have experienced low‐temperature aqueous alteration. Both nanoglobules and diffuse organic matter are abundant. Non‐globular organic particles are also present, and including some that contain nanodiamond clusters. Diffuse organic matter is finely distributed in and around phyllosilicates, forms coatings on other minerals, and is also preserved in vesicles in secondary minerals such as carbonate and pyrrhotite. The average elemental compositions determined by energy‐dispersive spectroscopy of extracted, demineralized insoluble organic matter samples A0107 and C0106 are C100N3O9S1 and C100N3O7S1, respectively, with the difference in O/C slightly outside the difference in the standard error of the mean. The functional chemistry of the nanoglobules varies from mostly aromatic C=C to mixtures of aromatic C=C, ketone C=O, aliphatic (CHn), and carboxyl (COOH) groups. Diffuse organic matter associated with phyllosilicates has variable aromatic C, ketone and carboxyl groups, and some localized aliphatics, but is dominated by molecular carbonate (CO3) absorption, comparable to prior observations of clay‐bound organic matter in CI meteorites. [ABSTRACT FROM AUTHOR]