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Accurately quantifying clinician time spent on electronic health record (EHR) activities outside the time scheduled with patients is critical for understanding occupational stress associated with ambulatory clinic environments. We make 3 recommendations regarding EHR workload measures that are intended to capture time working in the EHR outside time scheduled with patients, formally defined as work outside of work (WOW): (1) separate all time working in the EHR outside of time scheduled with patients from time working in the EHR during time scheduled with patients, (2) do not exclude any time before or after scheduled time with patients, and (3) encourage the EHR vendor and research communities to develop and standardize validated, vendor-agnostic methods for measuring active EHR use. Attributing all EHR work outside time scheduled with patients to WOW, regardless of when it occurs, will produce an objective and standardized measure better suited for use in efforts to reduce burnout, set policy, and facilitate research.

Despite the effectiveness of immuno-chemotherapy, 40% of patients with diffuse large B-cell lymphoma (DLBCL) experience relapse or refractory disease. Longitudinal studies have previously focused on the mutational landscape of relapse but fell short of providing a consistent relapse-specific genetic signature. In our study, we have focused attention on the changes in GEP accompanying DLBCL relapse using archival paired diagnostic/relapse specimens from 38 de novo patients with DLBCL. COO remained stable from diagnosis to relapse in 80% of patients, with only a single patient showing COO switching from activated B-cell–like (ABC) to germinal center B-cell–like (GCB). Analysis of the transcriptomic changes that occur following relapse suggest ABC and GCB relapses are mediated via different mechanisms. We developed a 30-gene discriminator for ABC–DLBCLs derived from relapse-associated genes that defined clinically distinct high- and low-risk subgroups in ABC–DLBCLs at diagnosis in datasets comprising both population-based and clinical trial cohorts. This signature also identified a population of

Objectives Treatments that target the biological causes of dementia remain limited, making prevention critically important. Well-being—defined broadly as living in accordance with one’s potential and experiencing one’s life as enjoyable and satisfying—is a promising avenue for prevention. It can be targeted by large-scale, noninvasive interventions and has been linked with better cognitive health and lower dementia risk. In the current review, we begin by summarizing empirical evidence linking well-being to cognitive functioning, cognitive decline, dementia diagnosis, and dementia-related neuropathology. Then, we highlight 3 key areas for future research. Methods We searched the literature on wellbeing, cognitive decline, and dementia, focusing on prospective and longitidinal evidence. Results The research reviewed here provides consistent evidence for associations of well-being with cognitive decline, dementia risk, and cognitive resilience to neuropathology. However, several open questions remain regarding (1) causality and mechanism(s), (2) specificity versus generalizability of associations, and (3) timing. Discussion To inform potential intervention efforts, the field must address complex open questions about whether, how, when, and for whom well-being influences dementia risk. The majority of existing research on well-being and cognitive health is correlational, and few studies have tested potential mechanisms that may explain those associations. Further, relatively little is known about the generalizability of associations across different aspects of well-being and for different sociocultural groups. Finally, we do not yet understand when in the life span and on what timescale well-being might influence cognitive health. We discuss challenges and opportunities for addressing each of these open questions, including concrete recommendations for research designs and use of open science practices.

Sexual functioning research has been slow to address sizeism within its volumes. Much of the sexual health science has adopted a weight normative model rather than a weight inclusive model. The purpose of this study was to, through systematic literature review, describe the sexual functioning research landscape with respect to weight inclusivity. The review included three databases (Google Scholar, Medline and Ebsco) between 2010 and 2020. Each article was double coded for weight inclusivity and sexual functioning. Sixty-seven articles met the criteria and were included in analysis. The articles, overall, only endorsed weight inclusive tenets 16 % of the time. Articles were most weight inclusive when discussing sexual satisfaction (22.5 %). Meanwhile, when discussing sexual arousal, the articles were the least weight inclusive (16.7 %). These findings suggest there is needs to be greater education and intention for sex educators, therapists, and clinicians, to explore and enhance body positivity and sexual health.

Historically, to minimize risks, living kidney donors have been highly selected and healthy. Operative risks are well-defined, yet concern remains about long-term risks. In the general population, even a mild reduction in glomerular filtration rate (GFR) is associated with cardiovascular disease, chronic kidney disease, and end-stage kidney disease (ESKD). However, reduction in GFR in the general population is due to kidney or systemic disease. Retrospective studies comparing donors with matched general population controls have found no increased donor risk. Prospective studies comparing donors with controls (maximum follow-up, 9 years) have reported that donor GFR is stable or increases slightly, whereas GFR decreases in controls. However, these same studies identified metabolic and vascular donor abnormalities. There are a few retrospective studies comparing donors with controls. Each has limitations in selection of the control group, statistical analyses, and/or length of follow-up. One such study reported increased donor mortality; 2 reported a small increase in absolute risk of ESKD. Risk factors for donor ESKD are similar to those in the general population. Postdonation pregnancies are also associated with increased risk of hypertension and preeclampsia. There is a critical need for long-term follow-up studies comparing donors with controls from the same era, geographic area, and socioeconomic status who are healthy, with normal renal function on the date matching the date of donation, and are matched on demographic characteristics with the donors. These data are needed to optimize donor candidate counseling and informed consent.

The urine metabolites and chemistries that contribute to kidney stone formation are not fully understood. This study examined differences between the urine metabolic and chemistries profiles of first-time stone formers and controls.High-resolutionsup1/supH-nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was performed in 24-hour urine samples from a prospective cohort of 418 first-time symptomatic kidney stone formers and 440 controls. In total, 48 NMR-quantified metabolites in addition to 12 standard urine chemistries were assayed. Analysis of covariance was used to determine the association of stone former status with urine metabolites or chemistries after adjusting for age and sex and correcting for the false discovery rate. Gradient-boosted machine methods with nested cross-validation were applied to predict stone former status.Among the standard urine chemistries, stone formers had lower urine oxalate and potassium and higher urine calcium, phosphate, and creatinine. Among NMR urine metabolites, stone formers had lower hippuric acid, trigonelline, 2-furoylglycine, imidazole, and citrate and higher creatine and alanine. A cross-validated model using urine chemistries, age, and sex yielded a mean AUC of 0.76 (95% CI, 0.73 to 0.79). A cross-validated model using urine chemistries, NMR-quantified metabolites, age, and sex did not meaningfully improve the discrimination (mean AUC, 0.78; 95% CI, 0.75 to 0.81). In this combined model, among the top ten discriminating features, four were urine chemistries and six NMR-quantified metabolites.Although NMR-quantified metabolites did not improve discrimination, several urine metabolic profiles were identified that may improve understanding of kidney stone pathogenesis.

Semiquantitative visual inspection for glomerulosclerosis, interstitial fibrosis, and arteriosclerosis is often used to assess chronic changes in native kidney biopsies. Morphometric evaluation of these and other chronic changes may improve the prognostic assessment.We studied a historical cohort of patients who underwent a native kidney biopsy between 1993 and 2015 and were followed through 2021 for ESKD and for progressive CKD (defined as experiencing 50% eGFR decline, temporary dialysis, or ESKD). Pathologist scores for the percentages of globally sclerosed glomeruli (GSG), interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis (luminal stenosis) were available. We scanned biopsy sections into high-resolution images to trace microstructures. Morphometry measures were percentage of GSG; percentage of glomerulosclerosis (percentage of GSG, ischemic-appearing glomeruli, or segmentally sclerosed glomeruli); percentage of IFTA; IFTA foci density; percentage of artery luminal stenosis; arteriolar hyalinosis counts; and measures of nephron size. Models assessed risk of ESKD or progressive CKD with biopsy measures adjusted for age, hypertension, diabetes, body mass index, eGFR, and proteinuria.Of 353 patients (followed for a median 7.5 years), 75 developed ESKD and 139 experienced progressive CKD events. Visually estimated scores by pathologists versus morphometry measures for percentages of GSG, IFTA, and luminal stenosis did not substantively differ in predicting outcomes. However, adding percentage of glomerulosclerosis, IFTA foci density, and arteriolar hyalinosis improved outcome prediction. A 10-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density, and any arteriolar hyalinosis outperformed a 10-point score based on percentages of GSG, IFTA, and luminal stenosis50% in discriminating risk of ESKD or progressive CKD.Morphometric characterization of glomerulosclerosis, IFTA, and arteriolar hyalinosis on kidney biopsy improves prediction of long-term kidney outcomes.

Objective The aim of this article is to compare the aims, measures, methods, limitations, and scope of studies that employ vendor-derived and investigator-derived measures of electronic health record (EHR) use, and to assess measure consistency across studies. Materials and Methods We searched PubMed for articles published between July 2019 and December 2021 that employed measures of EHR use derived from EHR event logs. We coded the aims, measures, methods, limitations, and scope of each article and compared articles employing vendor-derived and investigator-derived measures. Results One hundred and two articles met inclusion criteria; 40 employed vendor-derived measures, 61 employed investigator-derived measures, and 1 employed both. Studies employing vendor-derived measures were more likely than those employing investigator-derived measures to observe EHR use only in ambulatory settings (83% vs 48%, P = .002) and only by physicians or advanced practice providers (100% vs 54% of studies, P Discussion Vendor-derived measures are increasingly used to study EHR use, but only by certain clinical roles. Although poorly validated and variously defined, both vendor- and investigator-derived measures of EHR time are widely reported. Conclusion The number of studies using event logs to observe EHR use continues to grow, but with inconsistent measure definitions and significant differences between studies that employ vendor-derived and investigator-derived measures.

Purpose: Postswallow voice abnormality is often assumed to indicate the presence of material in the laryngeal airway (MIA), but prior research has not shown definitive evidence of a causal relationship. This study investigated if endoscopically confirmed MIA (prandial material or secretions) generates specific voice quality attributes that can be perceptually identified by experienced listeners. Method: Forty-four dysphagic adults underwent endoscopic evaluation of swallowing. Time-linked audiovisual recordings of pre- and postswallow phonation were analyzed to determine the presence, amount, and location of prandial material or secretions in the larynx during phonation. Expert listeners completed auditory-perceptual ratings of phonation samples. Results: Voice quality ratings did not differ significantly when there was MIA during postswallow phonation. However, judgments of voice quality abnormality for MIA samples were elevated when analyses controlled for effects of baseline dysphonia. Listeners were most likely to perceive voice quality abnormality when larger amounts of secretions were present, as compared to prandial material. Interrater reliability was variable and ranged from low to moderate across perceptual parameters. Conclusions: MIA during phonation occurred for many participants, but perception of voice quality abnormality was variable when MIA was present. Baseline dysphonia is common among individuals with dysphagia and may limit perception of voice quality abnormalities generated by MIA. Secretions in the laryngeal airway may have a greater impact on voice quality parameters.

The mere-exposure effect, in which repeated stimuli are liked more than novel stimuli, is a well-known effect. However, little research has studied adult age differences in mere-exposure effects, despite possible applications in helping older adults transition to new living environments. Here, we report four experiments assessing mere-exposure to neutral-face stimuli in groups of older and younger adult participants tested online. In each experiment, repeated face exposure did not increase liking within either age group; rather, Bayesian evidence favored the null hypothesis of no effect. Older adults reported higher overall liking ratings relative to younger adults, and both groups preferred younger faces, though this tendency was stronger in the younger group. Further exploratory analysis considering factors such as gender or race of the faces and participants did not reveal any consistent results for the mere-exposure effect. We discuss these findings in relation to other recent studies reporting mixed evidence for mere-exposure effects. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction In July 2018, the U.S. Department of Housing and Urban Development passed a rule requiring public housing authorities to implement smoke-free housing (SFH) policies. We measured secondhand smoke (SHS) exposure immediately before, and repeatedly up to 36 months post-SFH policy implementation in a purposeful sample of 21 New York City (NYC) high-rise buildings (>15 floors): 10 NYC Housing Authority (NYCHA) buildings subject to the policy and 11 privately managed buildings in which most residents received housing vouchers (herein “Section 8”). Aims and Methods We invited participants from nonsmoking households (NYCHA n = 157, Section-8 n = 118) to enroll in a longitudinal air monitoring study, measuring (1) nicotine concentration with passive, bisulfate-coated filters, and (2) particulate matter (PM2.5) with low-cost particle sensors. We also measured nicotine concentrations and counted cigarette butts in common areas (n = 91 stairwells and hallways). We repeated air monitoring sessions in households and common areas every 6 months, totaling six post-policy sessions. Results After 3 years, we observed larger declines in nicotine concentration in NYCHA hallways than in Section-8, [difference-in-difference (DID) = −1.92 µg/m3 (95% CI –2.98, −0.87), p = .001]. In stairwells, nicotine concentration declines were larger in NYCHA buildings, but the differences were not statistically significant [DID= −1.10 µg/m3 (95% CI −2.40, 0.18), p = .089]. In households, there was no differential change in nicotine concentration (p = .093) or in PM2.5 levels (p = .385). Conclusions Nicotine concentration reductions in NYCHA common areas over 3 years may be attributable to the SFH policy, reflecting its gradual implementation over this time. Implications Continued air monitoring over multiple years has demonstrated that SHS exposure may be declining more rapidly in NYCHA common areas as a result of SFH policy adherence. This may have positive implications for improved health outcomes among those living in public housing, but additional tracking of air quality and studies of health outcomes are needed. Ongoing efforts by NYCHA to integrate the SFH policy into wider healthier-homes initiatives may increase policy compliance.

A new species of Cyne (Loranthaceae) from Bucas Grande and Dinagat Islands, Philippines is described and named C. barcelonae in honor of the Filipina botanist Julie F. Barcelona. Phylogenetic analysis using the complete nuclear ribosomal DNA cistron confirms it is sister to C. banahaensis, the only species among the six in the genus with complete descriptions of floral morphology. The species is similar to the rare C. perfoliata of Papua New Guinea by having connate-perfoliate upper leaves but differs from others in the genus by possessing palmate leaf venation, inflorescences lacking an operculum, light green corollas, and stamens with filaments. No type material for Cyne quadriangula exists, thus this taxon is only known from the original protologue. It was rediscovered on Bucas Grande Island and that collection was described and used as the neotype for the species. A revised description of the genus and key to the seven species is provided.

American consumers fall short of dietary fiber intake recommended by dietary guidelines. Beans provide protein and fiber, however, less than 14% of adults include them in their daily diets. Nuña beans (

To compare dietary factors between incident symptomatic stone formers and controls, and among the incident stone formers, to determine whether dietary factors were predictive of symptomatic recurrence.We prospectively recruited 411 local incident symptomatic kidney stone formers (medical record validated) and 384 controls who were seen at Mayo Clinic in Minnesota or Florida between January 1, 2009, and August 31, 2018. Dietary factors were based on a Viocare, Inc, food frequency questionnaire administered during a baseline in-person study visit. Logistic regression compared dietary risk factors between incident symptomatic stone formers and controls. Incident stone formers were followed up for validated symptomatic recurrence in the medical record. Cox proportional hazards models estimated risk of symptomatic recurrence with dietary factors. Analyses adjusted for fluid intake, energy intake, and nondietary risk factors.In fully adjusted analyses, lower dietary calcium, potassium, caffeine, phytate, and fluid intake were all associated with a higher odds of an incident symptomatic kidney stone. Among incident stone formers, 73 experienced symptomatic recurrence during a median 4.1 years of follow-up. Adjusting for body mass index, fluid intake, and energy intake, lower dietary calcium and lower potassium intake were predictive of symptomatic kidney stone recurrence. With further adjustment for nondietary risk factors, lower dietary calcium intake remained a predictor of recurrence, but lower potassium intake only remained a predictor of recurrence among those not taking thiazide diuretics or calcium supplements.Enriching diets in stone formers with foods high in calcium and potassium may help prevent recurrent symptomatic kidney stones.

Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining. Eosinophil-deficient (ΔdblGata1) mice were used to investigate the role of eosinophils in 3 models of acute liver injury. In vivo experiments using Il33Hepatic accumulation of eosinophils was observed in patients with acetaminophen (APAP)-induced liver failure, whereas few eosinophils were detectable in healthy liver tissues. In mice treated with APAP, carbon tetrachloride or concanavalin A, eosinophils were recruited into the liver and played a profound protective role. Mice deficient of macrophages or IL-33 exhibited impaired hepatic eosinophil recruitment during acute liver injury. CCL24, but not CCL11, was increased after treatment of each hepatotoxin in an IL-33 and macrophage-dependent manner. In vitro experiments demonstrated that IL-33, by stimulating IL-4 release from eosinophils, promoted the production of CCL24 by macrophages.This is the first study to demonstrate that hepatic recruitment of and protection by eosinophils occur commonly in various models of acute liver injury. Our findings support further exploration of eosinophils as a therapeutic target to treat APAP-induced acute liver injury.The current study unveils that eosinophils are recruited into the liver and play a protective function during acute liver injury caused by acetaminophen overdose. The data demonstrate that IL-33-activated eosinophils trigger macrophages to release high amounts of CCL24, which promotes hepatic eosinophil recruitment. Our findings suggest that eosinophils could be an effective cell-based therapy for the treatment of acetaminophen-induced acute liver injury.

Although the population-level differences between estimated glomerular filtration rate (eGFR) and measured glomerular filtration rate (mGFR) are well recognized, the magnitude and potential clinical implications of individual-level differences are unknown.To quantify the magnitude and consequences of the individual-level differences between mGFRs and eGFRs.Cross-sectional study.Four U.S. community-based epidemiologic cohort studies with mGFR.3223 participants in 4 studies.The GFRs were measured using urinary iothalamate and plasma iohexol clearance; the eGFR was calculated from serum creatinine concentration alone (eGFRThe participants' mean age was 59 years; 32% were Black, 55% were women, and the mean mGFR was 68. The population-level differences between mGFR and eGFRSingle measurement of mGFR and serum markers without short-term replicates.A substantial individual-level discrepancy exists between the mGFR and the eGFR. Laboratories reporting eGFR should consider including the extent of this uncertainty to avoid misinterpretation of eGFR as an mGFR replacement.National Institutes of Health.

SummaryGrid cells and place cells constitute the basic building blocks of the medial entorhinal-hippocampal spatial cognitive map by representing the spatiotemporal continuum of an animal’s past, present and future locations. However, the spatiotemporal relationship between these different cell types is unclear. Here we co-recorded grid and place cells in freely foraging rats. We show that average time shifts in grid cells tend to be prospective and are proportional to their spatial scale, providing a nearly instantaneous readout of a spectrum of progressively increasing time horizons ranging hundreds of milliseconds. Average time shifts of place cells are generally larger compared to grid cells and also increase with place field sizes. Moreover, time shifts displayed nonlinear modulation by the animal’s trajectories in relation to the local boundaries and locomotion cues. Finally, long and short time shifts occurred at different parts of the theta cycle, which may facilitate their readout. Together, these findings suggest that progressively increasing time horizons of grid and place cells may provide a basis for calculating animal trajectories essential for goal-directed navigation and planning.

Background Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new “mind-body” intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD. Methods A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD. Results A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury may enhance central neuroplasticity, restoring lost sensorimotor function. These neuroplastic effects suggest that FES may be a promising innovative intervention for psychiatric disorders of disrupted brain connectivity, such as MDD. Recent pilot data on repetitive FES applied to the facial muscles in healthy participants and patients with MDD show early promise, suggesting that FES may attenuate the negative interoceptive bias associated with MDD by enhancing positive facial feedback. Neurobiologically, the amygdala and nodes of the emotion-to-motor transformation loop may serve as potential neural targets for facial FES in MDD, as they integrate proprioceptive and interoceptive inputs from muscles of facial expression and fine-tune their motor output in line with socio-emotional context. Conclusions Manipulating facial muscles may represent a mechanistically novel treatment strategy for MDD and other disorders of disrupted brain connectivity that is worthy of investigation in phase II/III trials.

Background The objective of this study was to evaluate the behavioral determinants associated with exclusive use of arsenic-safe water in the community-led Strong Heart Water Study (SHWS) arsenic mitigation program. Methods The SHWS is a randomized controlled trial of a community-led arsenic mitigation program designed to reduce arsenic exposure among private well users in American Indian Great Plains communities. All households received point-of-use (POU) arsenic filters installed at baseline and were followed for 2 years. Behavioral determinants selected were those targeted during the development of the SHWS program, and were assessed at baseline and follow-up. Results Among participants, exclusive use of arsenic-safe water for drinking and cooking at follow-up was associated with higher self-efficacy for accessing local resources to learn about arsenic (OR: 5.19, 95% CI: 1.48–18.21) and higher self-efficacy to resolve challenges related to arsenic in water using local resources (OR: 3.11, 95% CI: 1.11–8.71). Higher commitment to use the POU arsenic filter faucet at baseline was also a significant predictor of exclusive arsenic-safe water use for drinking (OR: 32.57, 95% CI: 1.42–746.70) and cooking (OR: 15.90, 95% CI: 1.33–189.52) at follow-up. From baseline to follow-up, the SHWS program significantly increased perceived vulnerability to arsenic exposure, self-efficacy, descriptive norms, and injunctive norms. Changing one’s arsenic filter cartridge after installation was associated with higher self-efficacy to obtain arsenic-safe water for drinking (OR: 6.22, 95% CI: 1.33–29.07) and cooking (OR: 10.65, 95% CI: 2.48–45.68) and higher perceived vulnerability of personal health effects (OR: 7.79, 95% CI: 1.17–51.98) from drinking arsenic-unsafe water. Conclusions The community-led SHWS program conducted a theory-driven approach for intervention development and evaluation that allowed for behavioral determinants to be identified that were associated with the use of arsenic safe water and changing one’s arsenic filter cartridge. These results demonstrate that theory-driven, context-specific formative research can influence behavior change interventions to reduce water arsenic exposure. The SHWS can serve as a model for the design of theory-driven intervention approaches that engage communities to reduce arsenic exposure. Trial registration The SHWS is registered with ClinicalTrials.gov (Identifier: NCT03725592).

Ischemic heart disease is the leading cause of death in the U.S. and worldwide. We recently demonstrated that infusion of leptin into the central nervous system (CNS) dramatically improves cardiac metabolism and function following ischemia/reperfusion (IR) injury. How the brain communicates with the heart during central leptin infusion to improve cardiac function after IR injury is still unknown. One potential mechanism may be via activation of brown adipose tissue (BAT), as central leptin administration has been shown to induce BAT-mediated thermogenesis. Furthermore, BAT has been proposed as an important source of extracellular vesicles (EVs) carrying bioactive molecules with cardioprotective effects. Thus, we investigated whether BAT contributes to the cardioprotective effect of central leptin infusion and the potential role of EVs in this protection. Male Sprague-Dawley rats (~8 weeks of age) were submitted to interscapular BAT ablation (iBATx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO), myocardial IR was induced by temporary (60 min) ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused chronically for 28 days starting 30 min after reperfusion using osmotic pumps implanted subcutaneously in the scapular region and connected to the ICV cannula. Cardiac function was assessed weekly by ECHO. Another set of animals with intact iBAT was treated with ICV leptin or vehicle for 2 weeks and had their iBAT collected for EVs isolation and quantification by differential ultracentrifugation and nanoparticle tracking analysis, respectively. Compared to vehicle-treated animals, ICV leptin infusion increases iBAT-derived EVs (5.6x109 vs 1.6 x109 particles/mg of tissue), and removal of iBAT prevent leptin’s CNS-mediated cardioprotective effects after IR injury as indicated by a lack of improvement in ejection fraction (26.9±2.5 vs 40.9±1.2%), stroke volume (154.6±15 vs 275.3±8μL) and global longitudinal strain (-7.4±1.1 vs -13.9±0.5%) at week 4 post-IR. These results suggest that the BAT plays an important role in mediating the cardioprotective effect of CNS leptin administration after I/R injury and that iBAT-derived EVs may be involved in delivering protective molecules to the heart during central leptin infusion. AHA 835218, NIGMS P20GM104357, NIDDK R00DK113280, R01DK121411 and P20GM104320 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Background There is uncertainty about the long-term risks of living kidney donation. Well-designed studies with controls well-matched on risk factors for kidney disease are needed to understand the attributable risks of kidney donation. Methods The goal of the Minnesota Attributable Risk of Kidney Donation (MARKD) study is to compare the long-term (> 50 years) outcomes of living donors (LDs) to contemporary and geographically similar controls that are well-matched on health status. University of Minnesota (n = 4022; 1st transplant: 1963) and Mayo Clinic LDs (n = 3035; 1st transplant: 1963) will be matched to Rochester Epidemiology Project (REP) controls (approximately 4 controls to 1 donor) on the basis of age, sex, and race/ethnicity. The REP controls are a well-defined population, with detailed medical record data linked between all providers in Olmsted and surrounding counties, that come from the same geographic region and era (early 1960s to present) as the donors. Controls will be carefully selected to have health status acceptable for donation on the index date (date their matched donor donated). Further refinement of the control group will include confirmed kidney health (e.g., normal serum creatinine and/or no proteinuria) and matching (on index date) of body mass index, smoking history, family history of chronic kidney disease, and blood pressure. Outcomes will be ascertained from national registries (National Death Index and United States Renal Data System) and a new survey administered to both donors and controls; the data will be supplemented by prior surveys and medical record review of donors and REP controls. The outcomes to be compared are all-cause mortality, end-stage kidney disease, cardiovascular disease and mortality, estimated glomerular filtration rate (eGFR) trajectory and chronic kidney disease, pregnancy risks, and development of diseases that frequently lead to chronic kidney disease (e.g. hypertension, diabetes, and obesity). We will additionally evaluate whether the risk of donation differs based on baseline characteristics. Discussion Our study will provide a comprehensive assessment of long-term living donor risk to inform candidate living donors, and to inform the follow-up and care of current living donors.

This paper examines how antiretroviral therapy (ART) use and fears towards the onward transmission of HIV have changed among people living with HIV (PLHIV) in Australia between 1997 and 2018. Participants were recruited as part of the HIV Futures study, a large cross-sectional survey of PLHIV in Australia, in 1997, 2003, 2012 and 2018 (total n = 3889). ART use, viral load detectability, and fear of onward HIV transmission were compared between years. Predictors of onward transmission fear were assessed among the 2018 subsample. While ART use within our sample decreased between 1997 and 2003, it subsequently increased to 97% in 2018. Self-reported viral load undetectability steadily increased over time, up to 88% in 2018. Notably, fewer PLHIV reported being fearful of transmitting HIV in 2018 compared to all other years. Being unfamiliar with the undetectable = untransmissible health movement, and having a detectable or uncertain viral load at last test, were significant predictors of being fearful of onward HIV transmission. Beyond the immediate medical considerations of HIV treatment, these results suggest that the undetectable = untransmissible movement may play a critical role in attenuating burdens experienced by PLHIV in Australia and that such messaging, in tandem with early and consistent ART use, should remain a salient feature of heath messaging among this population.

Background One of the challenges in living kidney donor screening is to estimate remaining kidney function after donation. Here we developed a new model to predict post-donation measured glomerular filtration rate (mGFR) from pre-donation serum creatinine, age and sex. Methods In the prospective development cohort (TransplantLines, n = 511), several prediction models were constructed and tested for accuracy, precision and predictive capacity for short- and long-term post-donation 125I-iothalamate mGFR. The model with optimal performance was further tested in specific high-risk subgroups (pre-donation eGFR 65 years) and validated in internal (n = 509) and external (Mayo Clinic, n = 1087) cohorts. Results In the development cohort, pre-donation estimated GFR (eGFR) was 86 ± 14 mL/min/1.73 m2 and post-donation mGFR was 64 ± 11 mL/min/1.73 m2. Donors with a pre-donation eGFR ≥90 mL/min/1.73 m2 (present in 43%) had a mean post-donation mGFR of 69 ± 10 mL/min/1.73 m2 and 5% of these donors reached an mGFR 65 years of age [bias 0.003 mL/min/1.73 m2 (IQR 9)]. Conclusions We developed a novel post-donation mGFR prediction model based on pre-donation serum creatinine, age and sex.

Changes to how gay, bisexual, and other men who have sex with men (GBM) connect with each other and with their communities have implications for HIV prevention. Social engagement with gay men (defined as having friends who are gay men and spending time with them) has been associated with HIV related outcomes over time among Australian GBM. Using data collected in national, repeated, cross-sectional surveys of GBM between 1998 and 2020 (N = 161,117), analyses of trends in the prevalence of gay social engagement (GSE) in Australia were conducted using linear regression. To assess changing associations with GSE at different time points in the HIV epidemic, three cross-sectional analyses were conducted on factors associated with high and low GSE in 1999/2000, 2009/2010, and 2019/2020 using bivariate and multivariable logistic regression. GSE (scored from 0 to 7) declined among all participants from 4.76 in 1998 to 4.04 in 2020 (p p

To determine if the addition of home environmental control strategies (ECSs) to controller medication titration reduces asthma controller medication requirements and in-home allergen concentrations among children with persistent asthma in Baltimore City. 155 children ages 5–17 with allergen-sensitized asthma were enrolled in a 6-month randomized clinical trial of multifaceted, individually-tailored ECS plus asthma controller medication titration compared to controller medication titration alone. Participants had to meet criteria for persistent asthma and have had an exacerbation in the previous 18 months. Allergen sensitization (mouse, cockroach, cat, dog, dust mite) was assessed at baseline and home dust allergen concentrations were measured at baseline, 3 and 6 months. ECS was delivered 3–4 times over the trial. Asthma controller medication was titrated using a guidelines-based algorithm at baseline, 2, 4, and 6 months. The primary outcome was controller medication treatment step at 6 months (0–6, as-needed albuterol to high-dose ICS + LABA). The population was predominately Black (90%), on public insurance (93%), and male (61%). The mean age was 10.1 years (SD 3.3). More than 70% were sensitized to a rodent, >50% to cockroach, and 70% were polysensitized. At 6 months, there were no differences in either treatment step (3.8 [SD 1.4] vs. 3.7 [SD 1.5]) or allergen concentrations between groups. Among this predominantly low-income, Black pediatric asthma population, the addition of ECS to controller medication titration reduced neither indoor allergen concentrations nor controller medication requirements compared to controller medication titration alone.

This practice parameter (PP) for Lutetium-177 (Lu-177) DOTATATE peptide receptor radionuclide therapy (PRRT) aims to guide authorized users in selection of appropriate adult candidates with gastroeneropancreatic neuroendocrine tumors (GEP-NETs) from foregut, midgut, and hindgut. The essential selection criteria include somatostatin receptor-positive GEP-NETs, which are usually inoperable and progressed despite standard therapy. Lu-177 DOTATATE is a radiopharmaceutical with high avidity for somatostatin receptors that are overexpressed by these tumors. This document ensures safe handling of Lu-177 DOTATATE by the authorized users and safe management of affected patients.The document was developed according to the systematic process developed by the American College of Radiology (ACR) and described on the ACR Web site (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards). The PP development was led by 2 ACR Committees on Practice Parameters (Nuclear Medicine and Molecular Imaging and Radiation Oncology) collaboratively with the American College of Nuclear Medicine, American Society of Radiation Oncology, and Society of Nuclear Medicine and Molecular Imaging.The Lu-177 DOTATATE PP reviewed pharmacology, indications, adverse effects, personnel qualifications, and required clinical evaluation before starting the treatment, as well as the recommended posttherapy monitoring, quality assurance, documentation, and appropriate radiation safety instructions provided in written form and explained to the patients.Lu-177 DOTATATE is available for therapy of inoperable and/or advanced GEP-NETs when conventional therapy had failed. It can reduce tumor size, improve symptoms, and increase the progression free survival. The PP document provides clinical guidance for authorized users to assure an appropriate, consistent, and safe practice of Lu-177 DOTATATE.