Monitoring post-spawning movement, habitat use, and survival of adult anadromous rainbow smelt using acoustic telemetry in a New Hampshire estuary.

Anadromous rainbow smelt (Osmerus mordax, [Mitchill 1814]) are found along the northeast Atlantic coastline of North America, with their range now limited to north of Cape Cod, Massachusetts, USA. Although their anadromous life cycles are described broadly, gaps remain regarding how adult rainbow smelt use estuaries post-spawning, including movement behaviors, habitats used, and specific timing of emigration to coastal waters. In spring 2021, we used acoustic telemetry to characterize movements during and after the spawning season of rainbow smelt captured in tributaries to Great Bay, New Hampshire, USA, a large estuarine system near the southern edge of their range. Forty-four adult rainbow smelt (n = 35 male, n = 9 female) were tagged with Innovasea V5 180-kHz transmitters and an array of 22,180 kHz VR2W receivers were deployed throughout Great Bay to detect movements of tagged fish from March to October 2021. Rainbow smelt were detected 14,186 times on acoustic telemetry receivers, with 41 (93%) of the tagged individuals being detected at least once post-tagging. Individuals were detected moving between tributaries, revealing that rainbow smelt can use multiple rivers during the spawning season (March-April). Mark-recapture Cormack-Jolly-Seber models estimated 83% (95% confidence interval 66%-92%) of rainbow smelt survived to the mainstem Piscataqua River, and a minimum of 50% (22 of 44) reached the seaward-most receivers and were presumed to have survived emigration. Most individuals that survived remained in the estuary for multiple weeks (average = 19.47 ± 1.99 standard error days), displaying extended use of estuarine environments. Downstream movements occurred more frequently during ebb tides and upstream movements with flood tides, possibly a mechanism to reduce energy expenditures. Fish emigrated from the estuary by mid-May to the coastal Gulf of Maine. Our results underscore that rainbow smelt need access to a variety of habitats, including multiple tributaries and high-quality estuarine habitat, to complete their life cycle.

Racial and Ethnic Composition of Departments of Health Policy & Management and Health Education & Behavioral Sciences.

The diversity of racial/ethnic representation in the health services and policy research (HSPR) workforce plays a crucial role in addressing the health needs of underserved populations. We assessed changes (between 2012 and 2022) in the racial/ethnic composition of students and faculty from departments of Health Policy & Management (HPM) and Health Education & Behavioral Sciences (HEBS) among the Association of Schools and Programs of Public Health member institutions. We analyzed annual data from over 40 institutions that reported student and faculty data in 2012 and 2022 within each department. Racial/ethnic populations included American Indian/Alaska Native (AI/AN), Asian, Hispanic, Native Hawaiian/Pacific Islander (NH/PI), Black, White, Unknown, and Multiracial. We conducted analyses by department and examined racial/ethnic composition by student status, degree level, faculty rank, and tenure status. We found statistically significant increases in Black assistant professors (HPM and HEBS) and tenured faculty (HPM), Hispanic graduates and tenure-track faculty (HPM), Asian professors (HPM: full and tenured, HEBS: associate and tenured), and Multiracial students and graduates (HPM and HEBS). Statistically significant decreases were observed in White professors (HPM: assistant and full, HEBS: all ranks) and tenure-track faculty (HPM and HEBS), AI/AN associate professors and tenured faculty (HEBS), Hispanic associate professors (HPM), Asian assistant professors (HEBS), and NH/PI students (HPM and HEBS). Our findings highlight the importance of increasing racial/ethnic representation. Strategies to achieve this include facilitating workshops to raise awareness about the structural barriers encountered by Hispanic faculty, providing research support, evaluating promotion processes, establishing more pathway programs, and fostering interdisciplinary academic environments studying AI/AN or NH/PI populations.

Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Klotho deficiency may affect clinical outcomes in chronic kidney disease (CKD) through fibroblast growth factor-23 (FGF23)-dependent and -independent pathways. However, the association between circulating Klotho and clinical outcomes in CKD remains unresolved and was the focus of this study. STUDY DESIGN: Prospective observational study. SETTING & PARTICIPANTS: 1,088 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study with an estimated glomerular filtration rate (eGFR) of 20-70mL/min/1.73m2. EXPOSURE: Plasma Klotho level at the year-1 study visit. OUTCOMES: 5-year risks of all-cause mortality, heart failure hospitalization, atherosclerotic cardiovascular events, and a composite kidney end point that comprised a sustained 50% decrease in eGFR, dialysis, kidney transplant, or eGFR<15mL/min/1.73m2. ANALYTICAL APPROACH: We divided Klotho into 6 groups to account for its nonnormal distribution. We used Cox proportional hazards regression and subdistribution hazards models to compare survival and clinical outcomes, respectively, between Klotho groups. We sequentially adjusted for demographic characteristics, kidney function, cardiovascular risk factors, sample age, and FGF23. RESULTS: Mean eGFR was 42mL/min/1.73m2, and median Klotho concentration was 0.31ng/mL (IQR, 0.10-3.27ng/mL). When compared with the lowest Klotho group, survival (HR, 0.77; 95% CI, 0.32-1.89), heart failure hospitalization (HR, 1.10; 95% CI, 0.38-3.17), atherosclerotic cardiovascular events (HR, 1.19; 95% CI, 0.57-2.52), and CKD progression (HR, 1.05; 95% CI, 0.58-1.91) did not differ in the high Klotho group. In contrast, FGF23 was significantly associated with mortality and heart failure hospitalization independent of Klotho levels. LIMITATIONS: Despite adjustments, we cannot exclude the potential influence of residual confounding or sample storage on the results. A single measurement of plasma Klotho concentration may not capture Klotho patterns over time. CONCLUSIONS: In a large, diverse, well-characterized CKD cohort, Klotho was not associated with clinical outcomes, and Klotho deficiency did not confound the association of FGF23 with mortality or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY: Klotho is a protein that is vital to mineral metabolism and aging and may protect against cardiovascular disease. Klotho levels decrease in chronic kidney disease (CKD), but the association between Klotho and clinical outcomes in CKD remains uncertain. In a prospective cohort study of more than 1,000 people with CKD, circulating Klotho levels were not associated with kidney disease progression, cardiovascular outcomes, or mortality. These results suggest that the decrease in circulating Klotho levels in CKD does not play a prominent role in the development of poor clinical outcomes.

Reinforcing and adverse observable effects of nicotine and minor tobacco alkaloids in squirrel monkeys.

The most prevalent psychoactive chemical in tobacco smoke is nicotine, which has been shown to maintain tobacco consumption as well as cause acute adverse effects at high doses, like nausea and emesis. Recent studies in laboratory animals have suggested that many non-nicotine constituents of tobacco smoke (e.g., minor tobacco alkaloids) may also contribute to tobacco's overall reinforcing and adverse effects. Here, we used intravenous (IV) self-administration (n = 3) and observation (n = 4) procedures in squirrel monkeys to, respectively, compare the reinforcing and adverse observable effects of nicotine and three prominent minor tobacco alkaloids, nornicotine, anatabine, and myosmine. In self-administration studies, male squirrel monkeys were trained to respond under a second-order fixed-interval schedule of reinforcement and dose-effects functions for nicotine and each of the minor tobacco alkaloids nornicotine, anatabine, and mysomine were determined. Observation studies were conducted in a different group of male squirrel monkeys to quantify the ability of nicotine, nornicotine, anatabine, and mysomine to produce adverse overt effects, including hypersalivation, emesis, and tremors. Results show that nicotine and to a lesser extent nornicotine were readily self-administered, whereas anatabine and myosmine were not. In observation studies, all minor tobacco alkaloids produced adverse observable effects that were either comparable or more pronounced than nicotine. Collectively, the present results showing that nicotine and the minor tobacco alkaloids nornicotine, anatabine, and myosmine produce differential reinforcing and acute adverse observable effects in monkeys provides further evidence that these constituents may differently contribute to the psychopharmacological and adverse effects of tobacco consumption.

Federal Student Loan Debt in Public Health and the Opportunities for Loan Repayment Programs.

OBJECTIVES: A need persists for graduates with public health training in government public health roles; however, earnings for these positions tend to be lower when compared with earnings for people with undergraduate or graduate training who are working in other sectors, such as private health care or pharmaceuticals. This study assessed federal student loan debt associated with education for public health, with an aim to quantify the need that may be met through the federal Public Health Workforce Loan Repayment Program (PHWLRP), which is one tool that policy makers have proposed to incentivize people with public health training to pursue employment in government public health. METHODS: We analyzed federal student loan data provided by the National Center for Education Statistics College Scorecard for the 2018-2019 academic year. We merged these data with the Integrated Postsecondary Education Data System to estimate the number of degrees awarded. We used Spearman rank correlation to compare associations between debt and annual earnings by award level (bachelor's, master's, and doctoral degrees). RESULTS: Across all award levels, the median level of federal student loan debt associated with education for public health was $33 366. The median annual earnings 1 year after graduation were $80 687 for graduates with doctoral degrees and $33 279 for graduates with bachelor's degrees. CONCLUSIONS: As policy makers attempt to strengthen the public health workforce with a focus on funding and implementing the PHWLRP, the existing levels of student debt should be considered to ensure that programs such as the PHWLRP are funded and reflect the needs of graduates and government public health employers.

Investigation of monoclonal antibody CSX-1004 for fentanyl overdose.

The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.

Effects of cannabinoid agonists and antagonists in male rats discriminating the synthetic cannabinoid AM2201.

The synthetic forms of delta-9-tetrahydrocannabinol (Δ9-THC), dronabinol or nabilone, have been approved to treat several indications. However, due to safety concerns their clinical utility remains limited. Consequently, there is a need for developing cannabinoid (CB) ligands that display better behavioral pharmacological profiles than Δ9-THC. Here, we utilized drug discrimination methods to compare the interoceptive effects of CB ligands that vary in potency, efficacy, and selectivity at the CB receptors, including two ligands, AM411 and AM4089, that show CB1 partial agonist-like actions in vitro. Male rats were trained to discriminate 0.1 mg/kg AM2201 from saline under a fixed-ratio (FR) 10 response schedule of food reinforcement. After establishing AM2201's discriminative-stimulus effects, pretreatment tests with the CB1 antagonist/inverse agonist rimonabant blocked AM2201's effects, whereas the peripherally-restricted antagonist AM6545 had no effect. Next, the generalization profiles of AM411 and AM4089 with CB1 full agonists (JWH-018, CP-55,940, AM8936), partial agonist (Δ9-THC), and non-cannabinoids (fentanyl, atropine) were compared. The CBs either fully (AM2201, CP-55,940, JWH-018, AM8936, Δ9-THC) or partially (AM411, AM4089) substituted for AM2201, whereas fentanyl and atropine did not produce AM2201-like effects. All CB drugs were more potent than Δ9-THC and correlation analysis confirmed that the relative behavioral potencies of CBs corresponded strongly with their relative affinities at the CB1 but not CB2 receptors. Together, our results further demonstrate that AM411 and AM4089 exhibit better pharmacological profiles compared to Δ9-THC, in that they are more potent and display in vivo partial agonist-like actions that are centrally mediated via CB1 receptors.

Expectations of employers in the United States for entry-level public health job skills with a bachelor's degree: an analysis of the positions advertised in an online job portal.

Objectives: To analyze the current public health labor market for bachelor's-level graduates. Methods: Public health-related job postings (N = 365) from across the United States were collected from an online job portal, Indeed.com, from November 7-14, 2022. Job titles, organization type, degree requirements, work experience, job location, and preferred skills for bachelor's-level public health positions were analyzed. Results: Thirty-one job titles were identified. Approximately one-third (32.33%) of postings were from the Northeastern US; 23.56% were from the Southeastern region. Thirty-five job skill categories were identified. Most jobs (92.33%) required oral and written communication skills, and 85.21% specified educational skills for public health promotion. Cultural competency, project management, and case management abilities were also highly sought. Conclusion: This study revealed the needs of the public health workforce and bolstered the case that public health degree-seekers should be equipped with a set of strategic skills applicable to a range of multisectoral and multidisciplinary public health jobs. Policy implications: Given the rapid changes in the field of public health, ongoing analysis of the labor market benefits educators, employers, and policymakers alike.

The Quick FICS: 5 and 10 Item Versions of the Family Inpatient Communication Survey.

CONTEXT: Communication quality in the hospital impacts outcomes like satisfaction, depression, and anxiety for families, and assessment tools must be efficient and reliable. OBJECTIVES: We developed the Quick FICS-5 and -10, shorter versions of the 30-item Family Inpatient Communication Survey (FICS). METHODS: The Quick FICS were developed from the original FICS study of hospitalized patients 65+ and their surrogates. The development sample came from the original FICS-30 scale. The validation sample came from a randomized controlled trial of surrogates for adult ICU patients. Participants were family members of patients on medical ICU or inpatient medicine services at three hospitals in a Midwest metropolitan area. We evaluated validity and reliability using factor analysis, internal consistency, and associations with surrogate psychological and decision-making outcomes. RESULTS: In the development sample of 364 patient/surrogate dyads, most surrogates were adult children (66.8%), female (70.9%), and white (68.9%). We identified 5-item and 10-item surveys. Exploratory factor analysis supported an overall communication score for the FICS-5 and FICS-10, as well as information and emotional support subscales for the FICS-10. There was high internal reliability (Cronbach's alpha was 0.83 for the FICS-5 and 0.90 for the FICS-10; information and emotional support subscales were 0.89 and 0.75 respectively). There was good predictive validity when comparing FICS scores to outcomes six to eight weeks after discharge, including anxiety (P = -0.13; P = 0.0234), and satisfaction with the hospital stay (P = 0.48; P < 0.0001). Similarly, the validation sample (n = 188) revealed Cronbach's alpha ranging from 0.81 to 0.93 and significant correlations (P < 0.05) with concurrent distress, anxiety, depression, and decision regret. CONCLUSIONS: The Quick FICS offers efficient, valid, and reliable evaluation of communication quality in the hospital that can be useful for research and quality improvement.

Experiences of caregiving with Alzheimer's disease in the LGBT community.

BACKGROUND: The goal of this paper is to develop a more thorough understanding of the experiences of LGBT older adults living with dementia and their caregivers. METHODS: A phenomenological approach using in-depth interviews with current or former caregivers of LGBT persons living with Alzheimer's disease (AD) was conducted. RESULTS: Participants ranged in age from 44-77 years old; 74% were lesbian, 16% gay, 5% straight, and 5% unknown. Five themes were identified from the analysis: Caregiver tension and isolation; financial stress & security; lack of social support & connection; engineering grief support, and entrapment of past and present stigma and discrimination. CONCLUSIONS: Discrimination related to LGBT status was an important theme over the participants' lives and occurred for several during dementia care. While other themes were similar to prior AD studies, LGBT status affected these other aspects of the caregiving experience. Findings can inform future programs that better meet needs of LGBT people and those who care for them.

The Early Microbial Colonizers of a Short-Lived Volcanic Island in the Kingdom of Tonga.

The island of Hunga Tonga Hunga Ha'apai (HTHH) in the Kingdom of Tonga was formed by Surtseyan eruptions and persisted for 7 years before being obliterated by a massive volcanic eruption on 15 January 2022. Before it was destroyed, HTHH was an unparalleled natural laboratory to study primary succession on a newly formed landmass. We characterized the microbial communities found on the surface sediments of HTHH using a combination of quantitative PCR, marker gene sequencing, and shotgun metagenomic analyses. Contrary to expectations, photosynthetic cyanobacteria were not detected in these sediments, even though they are typically dominant in the earliest stages of primary succession in other terrestrial environments. Instead, our results suggest that the early sediment communities were composed of a diverse array of bacterial taxa, including trace gas oxidizers, anoxygenic photosynthesizers, and chemolithotrophs capable of metabolizing inorganic sulfur, with these bacteria likely sourced from nearby active geothermal environments. While the destruction of HTHH makes it impossible to revisit the site to conduct in situ metabolic measurements or observe how the microbial communities might have continued to change over time, our results do suggest that the early microbial colonizers have unique origins and metabolic capabilities. IMPORTANCE The volcanic island of Hunga Tonga Hunga Ha'apai in the Kingdom of Tonga represents a very rare example of new island formation and thus a unique opportunity to study how organisms colonize a new landmass. We found that the island was colonized by diverse microbial communities shortly after its formation in 2015, with these microbes likely originating from nearby geothermal environments. Primary succession in this system was distinct from that typically observed in other terrestrial environments, with the early microbial colonizers relying on unique metabolic strategies to survive on the surface of this newly formed island, including the capacity to generate energy via sulfur and trace gas metabolism.

A descriptive study of the multidisciplinary healthcare experiences of inpatient resuscitation events.

Background: In-hospital resuscitation events have complex and enduring effects on clinicians, with implications for job satisfaction, performance, and burnout. Ethically ambiguous cases are associated with increased moral distress. We aim to quantitatively describe the multidisciplinary resuscitation experience. Methods: Multidisciplinary in-hospital healthcare professionals at an adult academic health center in the Midwestern United States completed surveys one and six weeks after a resuscitation event. Surveys included demographic data, task load (NASA-TLX), overall and moral distress, anxiety, depression, and spiritual peace. Spearman's rank correlation was computed to assess task load and distress. Results: During the 5-month study period, the study included 12 resuscitation events across six inpatient units. Of 82 in-hospital healthcare professionals eligible for recruitment, 44 (53.7%) completed the one-week post-resuscitation event survey. Of those, 37 (84.1%) completed the six-week survey. Highest median task load burden at one week was seen for temporal demand, effort, and mental demand. Median moral distress scores were low, while "at peace" median scores tended to be high. There were no significant non-zero changes in task load or distress scores from weeks 1-6. Mental demand (r = 0.545, p < 0.001), physical demand (r = 0.464, p = 0.005), performance (r = -0.539, p < 0.001), and frustration (r = 0.545, p < 0.001) significantly correlated with overall distress. Performance (r = -0.371, p = 0.028) and frustration (r = 0.480, p = 0.004) also significantly correlated with moral distress. Conclusions: In-hospital healthcare professionals' experiences of resuscitation events are varied and complex. Aspects of task load burden including mental and physical demand, performance, and frustration contribute to overall and moral distress, deserving greater attention in clinical contexts.

Racial and Ethnic Composition of Students, Graduates, and Faculty in Environmental Health Sciences, 2011 to 2021.

The lack of diversity among the environmental health sciences (EHS) workforce has been an ongoing concern. However, limited research exists on the racial and ethnic composition of EHS students and faculty over time. We analyzed 2011 and 2021 data on EHS students, graduates, and faculty to compare changes in the racial and ethnic composition among Association of Schools and Programs of Public Health-member institutions. Among the institutions that reported data in both years, we observed significant proportion increases among Hispanic enrolled students (overall and master's: both P = .01), Multiracial enrolled students and graduates (overall: both P < .05, master's level: both P < .05), and Asian tenured professors (P = .01). Significant decreases were observed among Unknown enrolled students (overall: P = .01, master's level: P < .001), Unknown master's level graduates (P = .01), AI/AN enrolled students (overall and master's: both P < .05), and White full professors (P < .001) and tenured faculty (P < .001). Despite these findings, no substantial change existed among the other racial and ethnic groups. More efforts are needed to recruit, train, and promote racial and ethnic minorities who can leverage their lived experiences to provide novel solutions to environmental challenges.

Trends in Degree Conferrals, Degree-Associated Debt, and Employment Outcomes Among Undergraduate Public Health Degree Graduates, 2001‒2020.

Objectives. To characterize the trends in degree conferrals, degree-associated debt, and employment outcomes among undergraduate public health degree (UGPHD) graduates. Methods. We reported administrative data on degree conferrals from 2001 to 2020 from the National Center for Education Statistics (NCES). For alumni graduating from 2015 to 2019, we also reported degree-associated debt and earnings 1 year after graduation compiled by NCES. Finally, we utilized a data set on 1-year postgraduation employment outcomes for graduates from 2015 to 2020 from the Association of Schools and Programs of Public Health. Results. As of 2020, more than 18 000 UGPHDs were awarded each year, more than 140 000 in total over the past 20 years. UGPHD graduates are highly diverse, with more than 80% being women and 55% being individuals from communities of color. We find alumni worked mostly in for-profit organizations (34%), health care (28%), nonprofits (11%), academic organizations (10%), government (10%), and other (6%). Degree-associated debt was $24 000, and the median first-year earnings were $34 000. Conclusions. While growth in UGPHD conferrals has slowed, it remains among the fastest-growing degree in the nation. However, the limited pathways into government remains a significant challenge. (Am J Public Health. 2023;113(1):115-123. https://doi.org/10.2105/AJPH.2022.307113).

Effects of Spiritual Care on Well-Being of Intensive Care Family Surrogates: A Clinical Trial.

CONTEXT: Critical illness of a family member is associated with high emotional and spiritual distress and difficult medical decisions. OBJECTIVES: To determine if a semistructured spiritual care intervention improves the well-being of family surrogate decision makers in intensive care (ICU) settings. METHODS: This study is a randomized, allocation-concealed, parallel group, usual care-controlled, single-blind trial of patient/surrogate dyads in five ICUs in one Midwest, academic medical center. Patients were 18 and older admitted to the ICU and unable to make medical decisions. The intervention involved proactive contact from the chaplain, scheduled, semi-structured visits, weekly follow-up, and bereavement calls. The control group received usual care. The primary endpoint was the surrogate's anxiety (Generalized Anxiety Disorders-7 scale), six to eight weeks after discharge. RESULTS: Of 192 patient/surrogate dyads enrolled, 128 completed outcome assessments. At follow-up, anxiety in the intervention group was lower than control (median score 1 (interquartile range 0,6) vs. 4 (1,9), P = 0.0057). The proportion of patients with a minimal clinically important difference (MCID) in anxiety of 2+ was 65.2% in the intervention group vs. 49.2% in control. The odds of an MCID remained higher in adjusted analysis (Odds Ratio 3.11, 95% confidence interval 1.18, 8.21; P = 0.0218) The adjusted odds of an MCID were higher for spiritual well-being (OR 3.79, CI 1.41,10.17; P = 0.0081). Satisfaction with spiritual care was also higher (adjusted mean 3.5 ± 0.4 vs. 2.9 ± 0.1); P < .0001). CONCLUSIONS: Proactive, semistructured spiritual care delivered by chaplains improves well-being for ICU surrogates. Results provide evidence for inclusion of chaplains in palliative and intensive care teams.

Fibroblast Growth Factor (FGF) 23 and FGF Receptor 4 promote cardiac metabolic remodeling in chronic kidney disease.

Chronic kidney disease (CKD) is a global health epidemic that significantly increases mortality due to cardiovascular disease. Left ventricular hypertrophy (LVH) is an important mechanism of cardiac injury in CKD. High serum levels of fibroblast growth factor (FGF) 23 in patients with CKD may contribute mechanistically to the pathogenesis of LVH by activating FGF receptor (FGFR) 4 signaling in cardiac myocytes. Mitochondrial dysfunction and cardiac metabolic remodeling are early features of cardiac injury that predate development of hypertrophy, but these mechanisms of disease have been insufficiently studied in models of CKD. Wild-type mice with CKD induced by adenine diet developed LVH that was preceded by morphological changes in mitochondrial structure and evidence of cardiac mitochondrial and metabolic dysfunction. In bioengineered cardio-bundles and neonatal rat ventricular myocytes grown in vitro, FGF23-mediated activation of FGFR4 caused a mitochondrial pathology, characterized by increased bioenergetic stress and increased glycolysis, that preceded the development of cellular hypertrophy. The cardiac metabolic changes and associated mitochondrial alterations in mice with CKD were prevented by global or cardiac-specific deletion of FGFR4. These findings indicate that metabolic remodeling and eventually mitochondrial dysfunction are early cardiac complications of CKD that precede structural remodeling of the heart. Mechanistically, FGF23-mediated activation of FGFR4 causes mitochondrial dysfunction, suggesting that early pharmacologic inhibition of FGFR4 might serve as novel therapeutic intervention to prevent development of LVH and heart failure in patients with CKD.

Health Care System Distrust, Race, and Surrogate Decision-Making Regarding Code Status.

Purpose: Previous studies have shown that black patients are more likely to prefer life-sustaining treatments such as cardiopulmonary resuscitation at end-of-life (EOL) compared to non-Hispanic white patients. Given prior racial disparities in health care, distrust has been proposed to explain these preferences. As many hospitalized older adults require surrogates to make medical decisions, we explored surrogates' code status preferences and the role of trust in these decisions. Methods: We conducted secondary analyses of an observational study of patient/surrogate dyads admitted to three hospitals in a Midwest metropolitan area. Distrust was assessed using the Revised Health Care System Distrust Scale. A single item asked the surrogate which code status they thought was best for the patient, full code or do not resuscitate. Results: We enrolled 350 patient/surrogate dyads (101 black; 249 white). In bivariate analysis, higher proportion of black surrogates preferred full code (62.4% vs. 38.3%, p=0.0001). After adjusting for trust and sociodemographic and psychological covariates, race was still significantly associated with preference for full code (adjusted odds ratio=2.13; 95% confidence interval: 1.16-3.92; p=0.0153). Surrogate race was not associated with distrust in bivariate or multivariable analysis, adjusting for sociodemographic and psychological covariates (p=0.3049). Conclusion: Although black race was associated with preferences for full code status, we observed no association between race and distrust. Differences in code status preference may be due to other factors related to race and culture. To ensure that patients are receiving EOL care that is consistent with their values, more work is needed to understand the cultural complexities behind EOL care preferences.

Analysis of the caudate nucleus transcriptome in individuals with schizophrenia highlights effects of antipsychotics and new risk genes.

Most studies of gene expression in the brains of individuals with schizophrenia have focused on cortical regions, but subcortical nuclei such as the striatum are prominently implicated in the disease, and current antipsychotic drugs target the striatum's dense dopaminergic innervation. Here, we performed a comprehensive analysis of the genetic and transcriptional landscape of schizophrenia in the postmortem caudate nucleus of the striatum of 443 individuals (245 neurotypical individuals, 154 individuals with schizophrenia and 44 individuals with bipolar disorder), 210 from African and 233 from European ancestries. Integrating expression quantitative trait loci analysis, Mendelian randomization with the latest schizophrenia genome-wide association study, transcriptome-wide association study and differential expression analysis, we identified many genes associated with schizophrenia risk, including potentially the dopamine D2 receptor short isoform. We found that antipsychotic medication has an extensive influence on caudate gene expression. We constructed caudate nucleus gene expression networks that highlight interactions involving schizophrenia risk. These analyses provide a resource for the study of schizophrenia and insights into risk mechanisms and potential therapeutic targets.

Amygdala and anterior cingulate transcriptomes from individuals with bipolar disorder reveal downregulated neuroimmune and synaptic pathways.

Recent genetic studies have identified variants associated with bipolar disorder (BD), but it remains unclear how brain gene expression is altered in BD and how genetic risk for BD may contribute to these alterations. Here, we obtained transcriptomes from subgenual anterior cingulate cortex and amygdala samples from post-mortem brains of individuals with BD and neurotypical controls, including 511 total samples from 295 unique donors. We examined differential gene expression between cases and controls and the transcriptional effects of BD-associated genetic variants. We found two coexpressed modules that were associated with transcriptional changes in BD: one enriched for immune and inflammatory genes and the other with genes related to the postsynaptic membrane. Over 50% of BD genome-wide significant loci contained significant expression quantitative trait loci (QTL) (eQTL), and these data converged on several individual genes, including SCN2A and GRIN2A. Thus, these data implicate specific genes and pathways that may contribute to the pathology of BP.