Cortical surface area profile mediates effects of childhood disadvantage on later-life general cognitive ability.

OBJECTIVES: Childhood disadvantage is associated with lower general cognitive ability (GCA) and brain structural differences in midlife and older adulthood. However, the neuroanatomical mechanisms underlying childhood disadvantage effects on later-life GCA remain poorly understood. Although total surface area (SA) has been linked to lifespan GCA differences, total SA does not capture the non-uniform nature of childhood disadvantage effects on neuroanatomy, which varies across unimodal and transmodal cortices. Here, we examined whether cortical SA profile-the extent to which the spatial patterning of SA deviates from the normative unimodal-transmodal cortical organization-is a mediator of childhood disadvantage effects on later-life GCA. METHOD: In 477 community-dwelling men aged 56-72 years old, childhood disadvantage index (CDI) was derived from four indicators of disadvantages and GCA was assessed using a standardized test. Cortical SA was obtained from structural magnetic resonance imaging. For cortical SA profile, we calculated the spatial similarity between maps of individual cortical SA and MRI-derived principal gradient (i.e., unimodal-transmodal organization). Mediation analyses were conducted to examine the indirect effects of CDI through cortical SA profile on GCA. RESULTS: Around 1.31% of CDI effects on later-life GCA were mediated by cortical SA profile, whereas total SA did not. Higher CDI was associated with more deviation of the cortical SA spatial patterning from the principal gradient, which in turn related to lower later-life GCA. DISCUSSION: Childhood disadvantage may contribute to later-life GCA differences partly by influencing the spatial patterning of cortical SA in a way that deviates from the normative cortical organizational principle.

Differences in COVID-19 Outpatient Antiviral Treatment Among Adults Aged ≥65 Years by Age Group - National Patient-Centered Clinical Research Network, United States, April 2022-September 2023.

Adults aged ≥65 years experience the highest risk for COVID-19-related hospitalization and death, with risk increasing with increasing age; outpatient antiviral treatment reduces the risk for these severe outcomes. Despite the proven benefit of COVID-19 antiviral treatment, information on differences in use among older adults with COVID-19 by age group is limited. Nonhospitalized patients aged ≥65 years with COVID-19 during April 2022-September 2023 were identified from the National Patient-Centered Clinical Research Network. Differences in use of antiviral treatment among patients aged 65-74, 75-89, and ≥90 years were assessed. Multivariable logistic regression was used to estimate the association between age and nonreceipt of antiviral treatment. Among 393,390 persons aged ≥65 years, 45.9% received outpatient COVID-19 antivirals, including 48.4%, 43.5%, and 35.2% among those aged 65-75, 76-89, and ≥90 years, respectively. Patients aged 75-89 and ≥90 years had 1.17 (95% CI = 1.15-1.19) and 1.54 (95% CI = 1.49-1.61) times the adjusted odds of being untreated, respectively, compared with those aged 65-74 years. Among 12,543 patients with severe outcomes, 2,648 (21.1%) had received an outpatient COVID-19 antiviral medication, compared with 177,874 (46.7%) of 380,847 patients without severe outcomes. Antiviral use is underutilized among adults ≥65 years; the oldest adults are least likely to receive treatment. To prevent COVID-19-associated morbidity and mortality, increased use of COVID-19 antiviral medications among older adults is needed.

Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.

Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aß-40, Aß-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.

Provider Perspectives on Rapid Treatment Initiation Among People Newly Diagnosed With HIV: A New Message of "Urgency"?

BACKGROUND: Early initiation of antiretroviral therapy improves human immunodeficiency virus (HIV) outcomes. However, achieving earlier treatment initiation is challenging for many reasons including provider awareness and clinic barriers; this study sought to understand perceptions of an early initiation program. METHODS: We interviewed 10 providers from 3 HIV clinics in North Carolina (October-November 2020). We asked providers about overall perceptions of early initiation and the pilot program. We developed narrative summaries to understand individual contexts and conducted thematic analysis using NVivo. RESULTS: Providers believed earlier initiation would signal an "extra sense of urgency" about the importance of antiretroviral therapy-a message not currently reflected in standard of care. Safety was a consistent concern. Cited implementation barriers included transportation assistance, medication sustainability, and guidance to address increased staff time and appointment availability. CONCLUSION: Our qualitative findings highlight the need for training on the safety of early initiation and addressing staffing needs to accommodate quicker appointments.

Doctor and clinic staff perspectives on a program to immediately start HIV treatment among patients newly diagnosed with HIVTreating human immunodeficiency virus (HIV) is easier than ever. Starting newly diagnosed persons on HIV medication as soon as possible is a now recommended goal. However, starting patients right away can be challenging. This study interviewed doctors and clinic staff to better understand their perspectives prior to implementing a program that would provide newly diagnosed patients with HIV treatment immediately. Results showed that some doctors are worried patients will not return after receiving their medications. Providers want support for linking patients to the clinic and ensuring they will be able to receive their next dose of medication when they come in. Other providers saw the benefits of reducing HIV stigma if the program can more quickly start patients on treatment. Some providers explained that when you go to the doctor and are sick you receive medications immediately, yet for newly diagnosed patients living with HIV, patients can be told to come back a month later to start treatment. Some providers believe shifting this messaging may also help patients take their medications better. Most providers saw the need for clinics to have more same-day appointment availability to meet the needs of the new program. Overall, providers were excited about the opportunity to improve the HIV care by offering HIV medications to newly diagnosed patients immediately.

Optimizing recovery of Haemophilus influenzae from vaginal-rectal specimens and determining carriage rates in pregnant women.

PURPOSE: Haemophilus influenzae (HINF), primarily non-typeable H. influenzae: (NTHi), is an important cause of neonatal sepsis and meningitis. The goal of this study was to investigate the point prevalence of HINF vaginal-rectal carriage in pregnant women, which could impact neonatal health. METHODS: Simulated vaginal-rectal swabs were cultured and tested to establish optimal recovery methods for HINF. These methods were then applied to vaginal-rectal swabs from a prospective cohort of pregnant women (n = 300) undergoing routine Group B Streptococcus: (GBS) screening. Both culture and PCR were used for detection of HINF. Subject demographics, reproductive history, and genitourinary test results were documented. A retrospective surveillance study was conducted to determine incidence of invasive neonatal HINF infections from 7/1/2017-6/30/2023. RESULTS: HINF was recovered from 42/42 (100%) simulated vaginal-rectal swabs at 2-45 CFU/plate via direct plating onto chocolate and chocolate + bacitracin agar. HINF was rarely recovered following LIM broth enrichment at 0-75 CFU/plate in 1/42 (2.4%) simulated swabs, but was recovered from BHI/Fildes broth enrichment in 22/42 (52%) specimens at high abundance (> 100 CFU/plate). Among pregnant women prospectively screened for HINF, the median age was 29 (IQR, 24-33) years and gestational age was 36 (IQR, 34-36) weeks. HINF was recovered in 1 of 300 prospective specimens by culture but 0/100 by PCR. A six-year retrospective analysis showed there were seven total cases of neonatal sepsis and majority of HINF was isolated from respiratory specimens followed by blood/CSF overall. CONCLUSION: This study established a sensitive culture method for recovering HINF from vaginal-rectal swab specimens and demonstrated low prevalence of HINF carriage rate in pregnant women. These findings highlight the need for further research to pinpoint the source for transmission of HINF to neonates.

Detection of mecA-mediated methicillin resistance and evaluation of disk-diffusion antimicrobial susceptibility characteristics of Staphylococcus saprophyticus isolates from geographically diverse locations: Staphylococcus saprophyticus antibiotic susceptibility testing.

Staphylococcus saprophyticus, a common uropathogen, is usually susceptible to urine-concentrating antimicrobials, so routine AST is not recommended by CLSI. Our study evaluated the antimicrobial resistance profiles of 277 S. saprophyticus isolates from North America and a globally diverse cohort. Notably, 24% (67/277) of our isolates come from non-urinary sources. AST was performed against 12 antimicrobials using standard disk diffusion, PCR for mecA and mecC, PBP2a production assays, and cefinase. 5% (13/277) of isolates were mecA positive and cefinase positive, 63% (176/277) were mecA negative but cefinase positive, 4% (11/277) were mecA positive but cefinase negative, and 28% (77/277) were mecA and cefinase negative. All (277/277) isolates were susceptible to delafloxacin, ciprofloxacin, rifampin, linezolid, and nitrofurantoin and 95% (262/277) were susceptible to trimethoprim-sulfamethoxazole. Our results showed that regardless of using CLSI or EUCAST breakpoints oxacillin had low categorical agreement for mecA presence, making it unsuitable for surrogate testing, while cefoxitin disk diffusion had high very major error rate. If possible, PBP2a or mecA testing is recommended for guiding therapy for non-urinary infections. Our work supports CLSI guidelines on routine susceptibility to urinary tract antibiotics.

Reticulated pigmentary changes and Terry's nails in a patient with a TERT variant-associated telomere biology disorder.

Telomere biology disorders (TBD) are a complex set of inherited illnesses characterized by short telomeres. Dyskeratosis congenita (DC), which is now considered a severe TBD phenotype, is characterized by reticulated pigmentary changes, nail dystrophy, premalignant oral leukoplakia, and systemic involvement. This case describes a 2-year-old female with reticulated pigmentary changes and Terry's nails who was found to have a TERT variant and short telomeres; she lacked other mucocutaneous and systemic features of TBD. This report describes a unique clinical presentation of TBD and highlights the importance of upholding suspicion for TBD in individuals with limited or subtle features of classic DC.

Educational Gaps in Dermatologic Diagnoses Among Otolaryngology Residents.

Otolaryngologists frequently serve as the first touchpoint for patients presenting with dermatologic conditions of the head and neck. This study aims to identify and quantify gaps in dermatologic training among otolaryngology residents, and to assess their diagnostic accuracy in comparison to dermatology residents. It comprised 14 multiple-choice questions focused on common dermatologic diagnoses related to the head and neck. Sixty-one dermatology and 36 otolaryngology residents participated in the study. Dermatology residents significantly outperformed otolaryngology residents, with average scores of 90% (SD = 8) compared to 71% (SD = 10) (P < .001). The observed effect size (Cohen's d = 2.010) significantly exceeded the expected effect size (0.603). Otolaryngology residents performed significantly lower on 7 out of the 14 questions. Analysis based on postgraduate year level showed no significant differences in scores within dermatology (P = .119) or otolaryngology (P = .402) residency programs.

Palliative care for patients with heart failure and family caregivers in rural Appalachia: a randomized controlled trial.

BACKGROUND: Heart failure (HF) is a debilitating disease with worsening symptoms and family caregiving burden. HF affects more than 8 million Americans. West Virginia has the highest HF death rate in the U.S. and limited healthcare services. This study tested whether the family HF palliative and end-of-life care intervention (FamPALcare) improved patient and caregiver outcomes at 3- and 6-month study endpoints. METHODS: This study used a randomized controlled trial design. Patients with HF and their caregivers were randomly assigned together to the intervention (n = 21) or control (n = 18) group. The intervention included five telephone coaching sessions on the HF home, palliative, and end-of-life care. The outcome data collected at baseline and at 3 and 6 months were from the patients' (a) HF-related health status and depression/anxiety scale scores; and from caregivers' (b) caregiving burden and depression/anxiety scale scores; and (c) anonymous ratings on the 11-item FamPALcare helpfulness scale, completed by the intervention participants. RESULTS: The mean age of the patients was 65.66 (SD = 13.72) years, and 67% were White males. The mean age of the caregivers was 62.05 (SD = 13.14) years, and 77% were White females. Compared to the controls, patients in the intervention group had significantly greater scores for HF-related health status (p < .05) and lower depression/anxiety scores at 6 months, the study endpoint. The family caregivers in the intervention group had significantly lower scores on caregiving burden (p < .05) and depression/anxiety (p < .01) at 3 months. The mean helpfulness rating was M = 4.46 out of 5 (SD = 0.49). CONCLUSIONS: The FamPALcare intervention was found to be effective at improving patient HF-related health status and reducing caregiver burden and improving both patient and caregiver depression and anxiety scores. The FamPALcare HF intervention was found feasible and consistently delivered (fidelity). The FamPALcare intervention's cost-effectiveness and helpfulness ratings information will be used to plan for subsequent clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153890, Registered on 4 November 2019, https://clinicaltrials.gov/ct2/show/NCT04153890 .

Elevated C-Reactive Protein in Older Men With Chronic Pain: Association With Plasma Amyloid Levels and Hippocampal Volume.

BACKGROUND: Chronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with Alzheimer's disease (AD)-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation. METHODS: Participants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aß42, n = 871), Aß40 (n = 887), total tau (t-tau, n = 841), and neurofilament light chain (NfL, n = 915), and serum high-sensitivity C-reactive protein (hs-CRP, n = 968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n = 385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use. RESULTS: Chronic pain was related to higher Aß40 (ß = 0.25, p = .009), but hs-CRP was unrelated to AD-related biomarkers (ps > .05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aß42 (ß = 0.36, p = .001) and Aß40 (ß = 0.29, p = .003). Chronic pain and hs-CRP did not interact to predict levels of Aß42/Aß40, t-tau, or NfL. Furthermore, there were significant interactions such that Aß42 and Aß40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP × Aß42: ß = -0.19, p = .002; hs-CRP × Aß40: ß = -0.21, p = .001), regardless of chronic pain status. CONCLUSIONS: Chronic pain was associated with higher plasma Aß, especially when hs-CRP was also elevated. Higher hs-CRP and Aß levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate the risk of neurodegeneration in AD-vulnerable regions.

Engaging oncology and occupational medicine to inform design of a Total Worker Health® intervention to address employment, financial, and well-being outcomes in cancer survivors.

OBJECTIVES: Few Total Worker Health® studies, and fewer interventions, examine well-being in the work context of cancer survivorship. We investigated the possibility of occupation and oncology professionals working together to address employed survivors' work-associated needs. METHODS: We employed a community-based participatory research (CBPR) approach to examine the educational, contextual, and workflow needs of oncology care team members to inform intervention design. Focus groups were conducted with oncology care team members and occupational medicine physicians. Key themes from each group were then examined. RESULTS: Themes included oncology care team's role in helping patients navigate resources, providing psychosocial support, and educating patients. Major themes for ways to better provide employment-related support during treatment included referring patients to employment experts and providing education on employment support. CONCLUSIONS: Occupational health professionals in collaboration with oncology clinics could play an important role in assisting cancer survivors' ability to navigate employment challenges.

The genetic and environmental etiology of novel frequency-driven regional parcellations of abnormal white matter.

The prevalence of white matter disease increases with age and is associated with cerebrovascular disease, cognitive decline, and risk for dementia. MRI measures of abnormal signal in the white matter (AWM) provide estimates of damage, however, regional patterns of AWM may be differentially influenced by genetic or environmental factors. With our data-driven regional parcellation approach, we created a probability distribution atlas using Vietnam Era Twin Study of Aging (VETSA) data (n = 475, mean age 67.6 years) and applied a watershed algorithm to define separate regional parcellations. We report biometrical twin modeling for five anatomically distinct regions: (1) Posterior, (2) Superior frontal and parietal, (3) Anterior and inferior frontal with deep areas, (4) Occipital, and (5) Anterior periventricular. We tested competing multivariate hypotheses to identify unique influences and to explain sources of covariance among the parcellations. Family aggregation could be entirely explained by additive genetic influences, with additive genetic variance (heritability) ranging from 0.69 to 0.79. Most genetic correlations between parcellations ranged from moderate to high (rg = 0.57-0.85), although two were small (rg = 0.35-0.39), consistent with varying degrees of unique genetic influences. This proof-of-principle investigation demonstrated the value of our novel, data-driven parcellations, with identifiable genetic and environmental differences, for future exploration.

Comparison of potential contact allergens in best-selling adult and baby cleansers.

are that the contents of this article are their own original unpublished findings. Title: Comparison of potential contact allergens in best-selling adult and baby cleansers Authors: Jayden Galamgam1 MD, Sasan D Noveir2 BA, Carol E Cheng1 MD Affiliations: 1Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA, 2 David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA Corresponding Author: Jayden Galamgam MD, Division of Dermatology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, Email: jgalamgam@mednet.ucla.edu.

A twin analysis to estimate genetic and environmental factors contributing to variation in weighted gene co-expression network module eigengenes.

Multivariate network-based analytic methods such as weighted gene co-expression network analysis are frequently applied to human and animal gene-expression data to estimate the first principal component of a module, or module eigengene (ME). MEs are interpreted as multivariate summaries of correlated gene-expression patterns and network connectivity across genes within a module. As such, they have the potential to elucidate the mechanisms by which molecular genomic variation contributes to individual differences in complex traits. Although increasingly used to test for associations between modules and complex traits, the genetic and environmental etiology of MEs has not been empirically established. It is unclear if, and to what degree, individual differences in blood-derived MEs reflect random variation versus familial aggregation arising from heritable or shared environmental influences. We used biometrical genetic analyses to estimate the contribution of genetic and environmental influences on MEs derived from blood lymphocytes collected on a sample of N = 661 older male twins from the Vietnam Era Twin Study of Aging (VETSA) whose mean age at assessment was 67.7 years (SD = 2.6 years, range = 62-74 years). Of the 26 detected MEs, 14 (56%) had statistically significant additive genetic variation with an average heritability of 44% (SD = 0.08, range = 35%-64%). Despite the relatively small sample size, this demonstration of significant family aggregation including estimates of heritability in 14 of the 26 MEs suggests that blood-based MEs are reliable and merit further exploration in terms of their associations with complex traits and diseases.

Verbal Learning and Memory Deficits across Neurological and Neuropsychiatric Disorders: Insights from an ENIGMA Mega Analysis.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

Resolvins D5 and D1 undergo phase II metabolism by uridine 5'-diphospho-glucuronosyltransferases.

Specialized pro-resolving mediators (SPMs) are oxidized lipid mediators that have been shown to resolve inflammation in cellular and animal models as well as humans. SPMs and their biological precursors are even commercially available as dietary supplements. It has been understood for more than forty years that pro-inflammatory oxidized lipid mediators, including prostaglandins and leukotrienes, are rapidly inactivated via metabolism. Studies on the metabolism of SPMs are, however, limited. Herein, we report that resolvin D5 (RvD5) and resolvin D1 (RvD1), well-studied SPMs, are readily metabolized by human liver microsomes (HLM) to glucuronide conjugated metabolites. We further show that this transformation is catalyzed by specific uridine 5'-diphospho-glucuronosyltransferase (UGT) isoforms. Additionally, we demonstrate that RvD5 and RvD1 metabolism by HLM is influenced by non-steroidal anti-inflammatory drugs (NSAIDs), which can act as UGT inhibitors through cyclooxygenase-independent mechanisms. The results from these studies highlight the importance of considering metabolism, as well as factors that influence metabolic enzymes, when seeking to quantify SPMs in vivo.

Using Concept Mapping to Identify Community Partners' and Researchers' Perceptions of Social Justice: A Path Toward Eliminating Chronic Disease Disparities.

Background: A social justice framework can be used to inform healthy equity-focused research, and operationalizing social justice can inform strategic planning for research and practice models. This study aimed to develop a working definition of social justice based on input from a diverse group of collaborators to better inform the work conducted within the Center for Research, Health, and Social Justice. Methods: A concept mapping study was conducted from March to May 2022. A prompt designed to elicit social justice themes was developed (phase 1). At a study website, participants brainstormed statements that represented their definition of social justice (phase 2). Participants then sorted statements based on similarity and rated statements on importance (phase 3). Multidimensional scaling and hierarchical cluster analysis were used to identify nonoverlapping thematic clusters of statements (phase 4). Models were reviewed for best fit, and clusters were assigned names based on theme (phase 5). Results: Participants (n = 49) generated 52 unique statements that were sorted into 5 clusters describing social justice themes. Clusters included (1) Empathy, Awareness, and Understanding (n = 11); (2) Education and Systems Change (n = 10); (3) Policy Design and Implementation (n = 9); (4) Equity and Leveling the Playing Field (n = 11); and (5) Access to Services and Fair Living Standard (n = 11). High mean cluster ratings ranging from 5.22 to 6.02 out of 7 indicated all clusters were rated as being very important aspects of social justice. Conclusions: These data can guide the restructuring of research ecosystems that help eliminate race- and place-based health disparities.

Obtaining informed consent in veterinary clinical trials mini review.

In September 2023 the United States Food and Drug Administration (FDA) released draft guidance for comment about how informed client consent for companion animal clinical trials should be obtained. This guidance has the potential to substantially change how informed consent documents are written and presented to clients in the veterinary community. It provides specifics not only about how to obtain informed consent from owners but also the timeframe within which consent should be obtained, the formatting and language in the consent forms, and details on elements that are required to be in these consent forms. These changes will involve additional efforts by investigators to ensure compliance yet might lead to increased owner compliance and higher enrollment in clinical studies with subsequent benefits for all.