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Nanotube porins form transmembrane nanomaterial-derived scaffolds that mimic the geometry and functionality of biological membrane channels. We report synthesis, transport properties, and osmotic energy harvesting performance of another member of the nanotube porin family: boron nitride nanotube porins (BNNTPs). Cryo-transmission electron microscopy imaging, liposome transport assays, and DNA translocation experiments show that BNNTPs reconstitute into lipid membranes to form functional channels of ~2-nm diameter. Ion transport studies reveal ion conductance characteristics of individual BNNTPs, which show an unusual C1/4 scaling with ion concentration and pronounced pH sensitivity. Reversal potential measurements indicate that BNNTPs have strong cation selectivity at neutral pH, attributable to the high negative charge on the channel. BNNTPs also deliver very large power density up to 12 kW/m2 in the osmotic gradient transport experiments at neutral pH, surpassing that of other BNNT-based devices by two orders of magnitude under similar conditions. Our results suggest that BNNTPs are a promising platform for mass transport and osmotic power generation.

Ensuring healthy and sustainable food systems in increasing social, economic, and ecological change is a key global priority to protect human and environmental health. Seafood is an essential component of these food systems and a critical source of nutrients, especially in coastal communities. However, despite rapid transformations in aquatic food systems, and our urgent need to understand them, there is a dearth of data connecting harvested food production to actualized food consumption. Many analyses suggest institutional, legal, or technological innovations to improve food systems, but few have analyzed the pathways through which people already gain access to nutritious food. Here, using a random forest model and cluster analysis of a nationally representative data set from Kiribati, we operationalize access theory to trace the flows of consumptive benefit in a fisheries-based food system. We demonstrate that the market access mechanism is the key mechanism mediating seafood access in Kiribati, but importantly, the highest seafood consumption households showed lower market access, pointing to the importance of non-market acquisition (e.g., home production and gifting). We reveal six distinct household strategies that employ different sets of access mechanisms to ensure high levels of local seafood consumption in different contexts. We demonstrate the impacts of these strategies on the composition of household seafoods consumed, stressing the need to support these existing successful strategies. Finally, we point to key policy and management insights (e.g., improved infrastructure, shifts in species management) that may be more effective in reinforcing these existing pathways than commonly proposed food system interventions.

Background: Youth may be reluctant to seek health care from school health providers due to feeling embarrassed or stigmatized in the health office environment or worried about their confidentiality. The purpose of this project was to create a set of youth-centered health posters that promote youth engagement with nursing staff and to standardize health messaging across high schools in Hawaii school-based clinics. Methods: Two community advisory boards, 1 composed of 10 youth stakeholders (mean age 17 years) and the other of 7 adult stakeholders, informed poster development utilizing web-based discussion groups. The discussions were transcribed, and additional data was collected using field notes and anonymous digital messages. Adult advisory board members also provided feedback on suggested poster text through an online survey. Results: Youth and adult advisory board participants identified 4 key health concerns facing youth: confidentiality, sexual health, relationships, and mental health. Based on input from the 2 advisory boards, 4 posters were developed, each centered on 1 key health issue. Implications for School Health Policy, Practice, and Equity: School-based posters can convey important messages to help youth understand their health care rights and responsibilities, as well as identify important issues open for discussion with nurses. Conclusion: Posters are an underutilized tool for school health providers to create welcoming, inclusive health care environments and facilitate health-related conversations with youth. This paper describes participant feedback about the characteristics of a memorable poster and briefly outlines current knowledge and recommendations for school health providers regarding each of the 4 health issues.

Over 65 million people suffer from recurrent, unprovoked seizures. The lack of validated biomarkers specific for myriad forms of epilepsy makes diagnosis challenging. Diagnosis and monitoring of childhood epilepsy add to the need for non-invasive biomarkers, especially when evaluating antiseizure medications. Although underlying mechanisms of epileptogenesis are not fully understood, evidence for mitochondrial involvement is substantial. Seizures affect 35%-60% of patients diagnosed with mitochondrial diseases. Mitochondrial dysfunction is pathophysiological in various epilepsies, including those of non-mitochondrial origin. Decreased ATP production caused by malfunctioning brain cell mitochondria leads to altered neuronal bioenergetics, metabolism and neurological complications, including seizures. Iron-dependent lipid peroxidation initiates ferroptosis, a cell death pathway that aligns with altered mitochondrial bioenergetics, metabolism and morphology found in neurodegenerative diseases (NDDs). Studies in mouse genetic models with seizure phenotypes where the function of an essential selenoprotein (GPX4) is targeted suggest roles for ferroptosis in epilepsy. GPX4 is pivotal in NDDs, where selenium protects interneurons from ferroptosis. Selenium is an essential central nervous system micronutrient and trace element. Low serum concentrations of selenium and other trace elements and minerals, including iron, are noted in diagnosing childhood epilepsy. Selenium supplements alleviate intractable seizures in children with reduced GPX activity. Copper and cuproptosis, like iron and ferroptosis, link to mitochondria and NDDs. Connecting these mechanistic pathways to selenoproteins provides new insights into treating seizures, pointing to using medicines including prodrugs of lipoic acid to treat epilepsy and to potential alternative therapeutic approaches including transcranial magnetic stimulation (transcranial), photobiomodulation and vagus nerve stimulation.

Collective impact (CI) is a structured approach that helps drive multi-sector collaborations to address social problems through systems changes. While the CI approach is gaining popularity, practitioners experience challenges in evaluating its implementation and intended outcomes. We conducted a systematic scoping review to understand evaluation methods specific to CI initiatives, identify challenges or limitations with these evaluations, and provide recommendations for the design of CI evaluations. Eighteen studies met the inclusion criteria. Process evaluations were the most frequently used evaluation design. Most studies collected cross-sectional data to evaluate their efforts. The complexity of CI was most frequently cited as the greatest evaluation challenge. Study recommendations primarily focused on improvements during the evaluation planning phase. Taking careful consideration in the planning of CI evaluations, developing context-specific data collection methods, and communicating results intentionally and effectively could prove useful to sufficiently capture and assess this systems-level approach to address social problems.

No prospective data have been described to inform guidelines on antibiotic prophylaxis for partial vulvectomies. Thus, we conducted a single-center, pilot, double-blind randomized controlled trial to assess the effectiveness of prophylactic antibiotics to prevent wound complications after partial vulvectomies. Patients were randomly assigned 1:1 to preoperative antibiotics or no preoperative antibiotics. The primary outcome of 30-day postoperative wound complications occurred in 31 (62 %) of all patients, with no differences between groups. The most common wound complications were superficial separation (54.2 % antibiotic prophylaxis vs. 65.3 % no prophylaxis, p = 0.37) and surgical site infection (0 % antibiotic prophylaxis vs 7.7 % no prophylaxis, p = 0.49). However, this study was limited by differences in patient characteristics between the groups. This study provides data to perform power calculations for a trial examining the effect of preoperative antibiotics on surgical site infection.

Abstract Objectives The aim of this study is to evaluate the impact of radiologist and urologist variability on detection of prostate cancer (PCa) and clinically significant prostate cancer (csPCa) with magnetic resonance imaging (MRI)‐transrectal ultrasound (TRUS) fusion prostate biopsies. Patients and methods The Prospective Loyola University MRI (PLUM) Prostate Biopsy Cohort (January 2015 to December 2020) was used to identify men receiving their first MRI and MRI/TRUS fusion biopsy for suspected PCa. Clinical, MRI and biopsy data were stratified by radiologist and urologist to evaluate variation in Prostate Imaging‐Reporting and Data System (PI‐RADS) grading, lesion number and cancer detection. Multivariable logistic regression (MVR) models and area under the curve (AUC) comparisons assessed the relative impact of individual radiologists and urologists. Results A total of 865 patients (469 biopsy‐naïve) were included across 5 urologists and 10 radiologists. Radiologists varied with grading 15.4% to 44.8% of patients with MRI lesions as PI‐RADS 3. PCa detection varied significantly by radiologist, from 34.5% to 66.7% (p = 0.003) for PCa and 17.2% to 50% (p = 0.001) for csPCa. Urologists' PCa diagnosis rates varied between 29.2% and 55.8% (p = 0.013) and between 24.6% and 39.8% (p = 0.36) for csPCa. After adjustment for case‐mix on MVR, a fourfold to fivefold difference in PCa detection was observed between the highest‐performing and lowest‐performing radiologist (OR 0.22, 95%CI 0.10–0.47, p

Abstract Background Hysterectomy is a common surgery among reproductive-aged U.S. patients, with rates highest among Black patients in the South. There is limited insight on causes of these racial differences. In the U.S., electronic medical records (EMR) data can offer richer detail on factors driving surgical decision-making among reproductive-aged populations than insurance claims-based data. Our objective in this cohort profile paper is to describe the Carolina Hysterectomy Cohort (CHC), a large EMR-based case-series of premenopausal hysterectomy patients in the U.S. South, supplemented with census and surgeon licensing data. To demonstrate one strength of the data, we evaluate whether patient and surgeon characteristics differ by insurance payor type. Methods We used structured and abstracted EMR data to identify and characterize patients aged 18–44 years who received hysterectomies for non-cancerous conditions between 10/02/2014–12/31/2017 in a large health care system comprised of 10 hospitals in North Carolina. We used Chi-squared and Kruskal Wallis tests to compare whether patients’ socio-demographic and relevant clinical characteristics, and surgeon characteristics differed by patient insurance payor (public, private, uninsured). Results Of 1857 patients (including 55% non-Hispanic White, 30% non-Hispanic Black, 9% Hispanic), 75% were privately-insured, 17% were publicly-insured, and 7% were uninsured. Menorrhagia was more prevalent among the publicly-insured (74% vs 68% overall). Fibroids were more prevalent among the privately-insured (62%) and the uninsured (68%). Most privately insured patients were treated at non-academic hospitals (65%) whereas most publicly insured and uninsured patients were treated at academic centers (66 and 86%, respectively). Publicly insured and uninsured patients had higher median bleeding (public: 7.0, uninsured: 9.0, private: 5.0) and pain (public: 6.0, uninsured: 6.0, private: 3.0) symptom scores than the privately insured. There were no statistical differences in surgeon characteristics by payor groups. Conclusion This novel study design, a large EMR-based case series of hysterectomies linked to physician licensing data and manually abstracted data from unstructured clinical notes, enabled identification and characterization of a diverse reproductive-aged patient population more comprehensively than claims data would allow. In subsequent phases of this research, the CHC will leverage these rich clinical data to investigate multilevel drivers of hysterectomy in an ethnoracially, economically, and clinically diverse series of hysterectomy patients.

Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.

In 2007 the Oregon Legislature passed a policy requiring students receive a minimum weekly amount of physical activity in school: 150 minutes for elementary and 225 minutes for middle school students. However, no implementation guidance for teachers or school districts were included in the policy. This pilot study examines the differences between teachers using a single paid curriculum versus various free or readily available resources to implement physical activity. Fifteen elementary-level classroom teachers (8 intervention, 7 control) engaged in the study. Intervention teachers received access to Focused Fitness Curriculum; control teachers used already available resources, representing treatment as usual. Researchers administered teacher surveys, classroom activity logs, classroom observations, and teacher interviews to look at activities conducted, time in physical activity, and teacher perceptions. The average duration of physical activity was almost double in the control group compared to the intervention group. Additionally, the control group maintained small increases in activity level throughout the semester, while activity levels of the intervention group fell. However, the treatment group had higher average activity levels and student participation. The treatment group, using the paid curriculum, was not better than the control group. Both groups saw positive outcomes of students engaging in physical activity. Rather than one set curriculum, the more important factors are providing support and flexibility for implementation.

DZNep (3-deazaneplanocin A) is commonly used to reduce lysine methylation. DZNep inhibits S-adenosyl-l-homocysteine hydrolase (AHCY), preventing the conversion of S-adenosyl-l-homocysteine (SAH) into L-homocysteine. As a result, the SAM-to-SAH ratio decreases, an indicator of the methylation potential within a cell. Many studies have characterized the impact of DZNep on histone lysine methylation or in specific cell or disease contexts, but there has yet to be a study looking at the potential downstream impact of DZNep treatment on proteins other than histones. Recently, protein thermal stability has provided a new dimension for studying the mechanism of action of small-molecule inhibitors. In addition to ligand binding, post-translational modifications and protein–protein interactions impact thermal stability. Here, we sought to characterize the protein thermal stability changes induced by DZNep treatment in HEK293T cells using the Protein Integral Solubility Alteration (PISA) assay. DZNep treatment altered the thermal stability of 135 proteins, with over half previously reported to be methylated at lysine residues. In addition to thermal stability, we identify changes in transcript and protein abundance after DZNep treatment to distinguish between direct and indirect impacts on thermal stability. Nearly one-third of the proteins with altered thermal stability had no changes at the transcript or protein level. Of these thermally altered proteins, CDK6 had a stabilized methylated peptide, while its unmethylated counterpart was unaltered. Multiple methyltransferases were among the proteins with thermal stability alteration, including DNMT1, potentially due to changes in the SAM/SAH levels. This study systematically evaluates DZNep’s impact on the transcriptome, the proteome, and the thermal stability of proteins.

The new experimental measurements of beam spin asymmetry were performed for the deeply virtual exclusive π0 production in a wide kinematic region with the photon virtualities Q2 up to 6.6 GeV2 and the Bjorken scaling variable xB in the valence regime. The data were collected by the CEBAF Large Acceptance Spectrometer (CLAS12) at Jefferson Lab with longitudinally polarized 10.6 GeV electrons scattered on an unpolarized liquid-hydrogen target. Sizable asymmetry values indicate a substantial contribution from transverse virtual photon amplitudes to the polarized structure functions. The interpretation of these measurements in terms of the Generalized Parton Distributions (GPDs) demonstrates their sensitivity to the chiral-odd GPD E¯T, which contains information on quark transverse spin densities in unpolarized and polarized nucleons and provides access to the nucleon's transverse anomalous magnetic moment. Additionally, the data were compared to a theoretical model based on a Regge formalism that was extended to the high photon virtualities.

Introduction: Adolescent access to quality healthcare is key to prevention and early intervention for health risk behaviors. This paper provides a healthcare provider perspective on barriers and facilitators to youth accessing care. Methods: Five focus groups were conducted from November to December 2020 with providers from a variety of healthcare settings. Participants were asked to describe their respective adolescent patient populations, adolescent-specific health concerns, and organizational accommodations specific for youth services. Transcripts were analyzed using Inductive Thematic Analysis and themes were grouped using a social-ecological framework. Results: At an individual level, providers noted that an adolescent’s knowledge and ability to navigate services varied greatly across settings. Providers identified provider trust and parent/guardian support as key interpersonal factors that support adolescents’ access to services. Organizational factors included bureaucratic barriers and the clinic’s reputation among youth. Community factors centered on mistrust within healthcare systems and stigmatization of seeking certain types of services. Participants also described how state-level policies influence parent/guardian consent requirements, which can limit adolescents’ access to care. Conclusion: Adolescent access to and utilization of healthcare in the United States is a complex problem requiring systems-level change. Healthcare organizations and providers have the opportunity and capacity to positively influence adolescents’ healthcare access and experiences, however a lack of standardized, clinic-level priorities and guidelines can limit adolescent-centered care.

US Latinos, a growing, aging population, are disproportionately burdened by cognitive decline and dementia. Identification of modifiable risk factors is needed for interventions aimed at reducing risk. Broad sociocultural context may illuminate complex etiology among culturally diverse Latinos. Among 1,418 older (≥60 years), low-socioeconomic position (SEP) Latinos (predominantly of Mexican descent) in Sacramento, California, we examined whether US acculturation was associated with cognitive performance, cognitive decline, and dementia/ cognitive impairment without dementia over a 10-year period and whether education modified the associations (Sacramento Area Latino Study on Aging, 1998-2008). Analyses used linear mixed models, competing-risk regression, and inverse probability of censoring weights for attrition. Participants with high US acculturation had better cognitive performance (0.21 fewer cognitive errors at grand-mean-centered age 70 years) than those with low acculturation after adjustment for sociodemographic factors, practice effects, and survey language. Results may have been driven by cultural language use rather than identity factors (e.g., ethnic identity, interactions). Rate of cognitive decline and risk of dementia/cognitive impairment without dementia did not differ by acculturation, regardless of education (β = 0.00 (standard error, 0.00) and hazard ratio = 0.81 (95% confidence interval: 0.49, 1.35), respectively). High US acculturation was associated with better cognitive performance among these older, low-SEP Latinos. Acculturation may benefit cognition when SEP is low. Future studies should incorporate extended longitudinal assessments among more diverse groups.

The Sexual Health And Peer Education (SHAPE) program implemented in middle schools in Oklahoma County utilizes a hybrid adult and peer educator model to deliver sexual health programming. While peer educators have been incorporated into school-based sexual health programs in the past, this program is unique in its approach to preparing and engaging peer educators. Researchers synthesized data from interviews with program implementers and focus group discussions with teenage peer educators and middle school students who recently participated in the program to understand the process elements that contribute to the benefit of the SHAPE program model. Interviews with program implementers described the thorough peer educator recruitment and training process. Teenage peer educators felt well-prepared to deliver lessons, and through this program, they developed leadership skills, confidence, and grew personally. Middle school students revealed that peer educators were relatable and provided a positive experience where they could engage and ask questions. The application of a hybrid adult and teenage peer educator model proved useful for delivering sexual health topics and benefited students and teenage peer educators. This study's findings highlight elements that can be utilized in future sexual health programming to prepare and engage teenage peer educators in more meaningful ways.

Game-based learning offers an interactive and effective way to teach health content and skills. This article discusses feasibility testing of "Using the Connect" ("UTC"), an innovative, game-based sexuality education program to evaluate its acceptability among youth. Utilizing mixed methods in a single case study design, qualitative and quantitative data was collected from youth (surveys, facilitated discussions, and observations). Qualitative data triangulated quantitative findings that youth liked the program design, felt the games and content were relatable, and learned knowledge and skills around adolescent development, accessing information, communication, and making healthy decisions through playing the games. Overall, "UTC" was highly acceptable to the youth; they had fun and learned information and skills. Not only would most participants recommend the program to friends, all reported they would participate in the program again and use the information they learned in the future.

?I think that some culturally sensitive mental health information could have been provided?: What Black mothers with preterm infants want for their mental health care: A qualitative study

Although US teenage birth rates substantially decreased over the past two decades, it still remains the highest in the developed world. More innovative, community-wide initiatives are needed to combat the issue. In Oklahoma County, Oklahoma, the Central Oklahoma Teen Pregnancy Prevention Collaboration is utilizing the collective impact model to convene multiple organizations with the goal of making systems-level changes related to teenage pregnancy within the community. This study used an interorganizational network analysis to evaluate the current strength of relationships between organizations in the Collaboration. An interorganizational network survey assessed collaborative relationships (e.g. information sharing and joint planning) within the network. Using R software, network diagrams were developed to depict partner relationships, and network measures, including node-, group- and network-level measures, were calculated. The network depiction (n = 23) revealed that the network core was composed of organizations from multiple sectors, and the backbone organization served as the most central organization for most centrality measures. This study provides insight into how organizational relationships can be assessed in order to increase community capacity to address teenage pregnancy. Continuous monitoring of the strength of relationships is important to ensure success in achieving goals as well as collective impact.

A traditional phase 3 clinical efficacy study for a Zika vaccine may be unfeasible because of the current low transmission of Zika virus (ZIKV). An alternative clinical development approach to evaluate Zika vaccine efficacy (VE) is therefore required, delineated in the US FDA’s Accelerated Approval Program for licensure, which utilizes an anti-Zika neutralizing antibody (Zika NAb) titer correlated with non-human primate (NHP) protection as a surrogate endpoint. In this accelerated approval approach, the estimation of VE would be inferred from the percentage of phase 3 trial participants achieving the established surrogate endpoint. We provide a statistical framework to predict the probability of protection for human participants vaccinated with a purified inactivated ZIKV vaccine (TAK-426), in the absence of VE measurements, using NHP data under a single-correlate model. Based on a logistic regression (LR) with bias-reduction model, a probability of 90% protection in humans is expected with a ZIKV NAb geometric mean titer (GMT) ≥ 3.38 log10 half-maximal effective concentration (EC50). The predicted probability of protection of TAK-426 against ZIKV infection was determined using the two-parameter LR model that fit the calculated VE in rhesus macaques and the flavivirus-naïve phase 1 trial participants’ ZIKV NAb GMTs log10 EC50, measured by a ZIKV reporter virus particle assay, at 1 month post dose 2. The TAK-426 10 µg dose predicted a probability of protection from infection of 98% among flavivirus-naïve phase 1 trial participants.

In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.

ObjectiveDespite growing evidence that discrimination may contribute to poor mental health, few studies have assessed this association among US Latinos. Furthermore, the interaction between discrimination and educational attainment in shaping Latino mental health is virtually unexplored. This study aims to examine the association between perceived discrimination and depressive symptoms and the modifying role of education among a population of Mexican-origin adults.DesignWe utilized population-based data from 629 Mexican-origin adults (mean age = 52.8 years) participating the Niños Lifestyle and Diabetes Study (2013-2014). Perceived discrimination was defined as responding 'sometimes' or 'often' to at least one item on the 9-item Everyday Discrimination Scale. High depressive symptoms were defined as scoring ≥10 on the CESD-10. We used log-binomial and linear-binomial models to estimate prevalence ratios (PR) and prevalence differences (PD), respectively, of high depressive symptoms for levels of perceived discrimination. Final models were adjusted for age, sex, education, cultural orientation, and nativity. General estimating equations were employed to account for within-family clustering.ResultsPrevalence of perceived discrimination and high depressive symptoms were 49.5% and 29.2%, respectively. Participants experiencing discrimination had higher depressive symptom prevalence than those never or rarely experiencing discrimination [PR = 1.94, 95% confidence interval (CI): 1.46-2.58; PD = 0.19, 95% CI: 0.12-0.27]. The strength of this association varied by education level. The association between discrimination and depressive symptoms was stronger among those with >12 years of education (PR = 2.69; PD = 0.24) compared to those with ≤12 years of education (PR = 1.36; PD = 0.09).ConclusionUS Latinos suffer a high burden of depressive symptoms, and discrimination may be an important driver of this burden. Our results suggest that effortful coping strategies, such as achieving high education despite high perceived discrimination, may magnify discrimination's adverse effect on Latino mental health.

Psychological functioning is shaped by how people navigate their environment. Accordingly, psychopathology is often caused and maintained by patterns of responding to the environment that do not meet situational demands. In particular, psychopathology is often expressed in an inflexible or intense manner of coping with stressful situations. Prior research on psychopathology and daily life stress is limited by an overreliance on negative affect reactivity, which neglects the myriad responses that can create problems in a person's life. In this study, we assessed a broad range of daily manifestations of psychopathology to examine daily psychopathology–stress associations. We conceptualized individual differences in functioning as psychopathology traits and daily fluctuations in the interrelated thoughts, behaviors, and emotions as psychopathology states, with traits and states corresponding to the same domains of functioning (i.e., antagonism, detachment, disinhibition, negative affectivity, anankastia, psychoticism). Data have been taken from two samples enriched for psychopathology (N = 112, N = 294 participants) who completed daily assessments of stressors and psychopathological states (n = 9,201, n = 4,292 days). We used multilevel structural equation models to examine average, within-person associations between stressors and psychopathological states and correlations between psychopathological traits and stress responses. Results showed that (a) most people experience increases in psychopathological states when stressed and (b) psychopathological traits relate to more consistent and stronger increases in psychopathological states. Our study suggests that psychopathology reflects how people cope with stressful situations, and what distinguishes people with high-trait psychopathology from those who experience typical upticks in psychopathology when stressed is the consistency and extremity of their responses. General Scientific Summary: Our results suggest that a general feature of psychopathology is the tendency to have extreme and consistent behavioral and emotional responses to daily stress and that different forms of psychopathology are each distinguished by a unique patterning of stress responses. [ABSTRACT FROM AUTHOR]

Acculturation may shape the disproportionate burden of poor sleep among Latinos in the United States. Existing studies are limited by unidimensional acculturation proxies that are incapable of capturing cultural complexities across generations. Understanding how acculturation relates to sleep may lead to the identification of modifiable intervention targets. We used multivariable regression and latent class methods to examine cross-sectional associations between a validated multidimensional scale of US acculturation and self-reported poor sleep measures. We analyzed an intergenerational cohort: first-generation (GEN1) older Latinos (Sacramento Area Latino Study on Aging; N = 1,716; median age: 69.5) and second-generation (GEN2) middle-aged offspring and relatives of GEN1 (Niños Lifestyle and Diabetes Study; N = 670; median age: 54.0) in Sacramento, California. GEN1 with high US acculturation, compared with high acculturation towards another origin/ancestral country, had less restless sleep (prevalence ratio [PR] [95% confidence interval (CI)]: 0.67 [0.54, 0.84]) and a higher likelihood of being in the best sleep class than the worst (OR [95% CI]: 1.62 [1.09, 2.40]), but among nonmanual occupations, high intergenerational US acculturation was associated with more general fatigue (PR [95% CI: 1.86 [1.11, 3.10]). GEN2 with high intergenerational US acculturation reported shorter sleep (PR [95% CI]: 2.86 [1.02, 7.99]). High US acculturation shaped sleep differentially by generation, socioeconomic context, and intergenerational acculturative status. High US acculturation was associated with better sleep among older, lower socioeconomic Latinos, but with shorter sleep duration among middle-aged, higher socioeconomic Latinos; results also differed by parental acculturation status. Upon replication, future studies should incorporate prospective and intergenerational designs to uncover sociobehavioral pathways by which acculturation may shape sleep to ultimately inform intervention efforts.

PurposeNeighborhood segregation related to cultural factors, such as language use, may influence elderly Latino depression. We examined the association between neighborhood-level Spanish language segregation and individual depressive symptoms among elderly Latinos.MethodsWe linked U.S. Census language use data with geocoded population-based data from 1789 elderly Latinos (mean age = 70.6 years) participating in the Sacramento Area Latino Study on Aging (1998-2008). Neighborhood language segregation was measured with the Index of Concentration at the Extremes, which demonstrates the extent to which residents are concentrated at extremes of deprivation and privilege. We fit two-level generalized linear-mixed models with random intercepts for census tracts to quantify the association between neighborhood-level language segregation and depressive symptoms, adjusting for identified confounders.ResultsAfter adjusting for age, sex, and nativity, residents of highly segregated Spanish-speaking neighborhoods had more depressive symptoms than those in highly segregated English-only-speaking neighborhoods (β = -4.410; 95% confidence interval [CI] = -6.851 to -1.970). This association was largely attenuated upon adjustment for individual-level education (β = -2.119; 95% CI = -4.650 to 0.413).ConclusionsLinguistically segregated communities may benefit from targeted outreach given the high depression prevalence in these neighborhoods. Furthermore, our findings suggest that limited access to fundamental social protections, such as education, may drive the segregation-depression association among U.S. Latinos.

Few studies have collected intergenerational data to assess the association between educational mobility across multiple generations and offspring depression. Using data from the Sacramento Area Latino Study on Aging (1998-2008), we assessed the influence of intergenerational education on depressive symptoms over 10 years among 1,786 Latino individuals (mean age = 70.6 years). Educational mobility was classified as stable-low (low parental/low offspring education), upwardly mobile (low parental/high offspring education), stable-high (high parental/high offspring education), or downwardly mobile (high parental/low offspring education). Depressive symptoms were measured with the Center for Epidemiological Studies-Depression Scale (CES-D); higher scores indicated more depressive symptoms. To quantify the association between educational mobility and CES-D scores over follow-up, we used generalized estimating equations to account for repeated CES-D measurements and adjusted for identified confounders. Within individuals, depressive symptoms remained relatively stable over follow-up. Compared with stable-low education, stable-high education and upward mobility were associated with significantly lower CES-D scores (β = -2.75 and -2.18, respectively). Downwardly mobile participants had slightly lower CES-D scores than stable-low participants (β = -0.77). Our results suggest that sustained, low educational attainment across generations may have adverse mental health consequences, and improved educational opportunities in underresourced communities may counteract the adverse influence of low parental education on Latino depression.

Hearing loss, the most common neurological disorder and the fourth leading cause of years lived with disability, can have profound effects on quality of life. The impact of this "invisible disability," with significant consequences, economic and personal, is most substantial in low- and middle-income countries, where >80% of affected people live. Given the importance of hearing for communication, enjoyment, and safety, with up to 500 million affected globally at a cost of nearly $800 billion/year, research on new approaches toward prevention and treatment is attracting increased attention. The consequences of noise pollution are largely preventable, but irreversible hearing loss can result from aging, disease, or drug side effects. Once damage occurs, treatment relies on hearing aids and cochlear implants. Preventing, delaying, or reducing some degree of hearing loss may be possible by avoiding excessive noise and addressing major contributory factors such as cardiovascular risk. However, given the magnitude of the problem, these interventions alone are unlikely to be sufficient. Recent advances in understanding principal mechanisms that govern hearing function, together with new drug discovery paradigms designed to identify efficacious therapies, bode well for pharmaceutical intervention. This review surveys various causes of loss of auditory function and discusses potential neurological underpinnings, including mitochondrial dysfunction. Mitochondria mitigate cell protection, survival, and function and may succumb to cumulative degradation of energy production and performance; the end result is cell death. Energy-demanding neurons and vestibulocochlear hair cells are vulnerable to mitochondrial dysfunction, and hearing impairment and deafness are characteristic of neurodegenerative mitochondrial disease phenotypes. Beyond acting as cellular powerhouses, mitochondria regulate immune responses to infections, and studies of this phenomenon have aided in identifying nuclear factor kappa B and nuclear factor erythroid 2-related factor 2/antioxidant response element signaling as targets for discovery of otologic drugs, respectively, suppressing or upregulating these pathways. Treatment with free radical scavenging antioxidants is one therapeutic approach, with lipoic acid and corresponding carnitine esters exhibiting improved biodistribution and other features showing promise. These compounds are also histone deacetylase (HDAC) inhibitors, adding epigenetic modulation to the mechanistic milieu through which they act. These data suggest that new drugs targeting mitochondrial dysfunction and modulating epigenetic pathways via HDAC inhibition or other mechanisms hold great promise.