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1.
Evol Appl ; 17(7): e13741, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957311

ABSTRACT

Chinook salmon (Oncorhynchus tshawytscha) display remarkable life history diversity, underpinning their ability to adapt to environmental change. Maintaining life history diversity is vital to the resilience and stability of Chinook salmon metapopulations, particularly under changing climates. However, the conditions that promote life history diversity are rapidly disappearing, as anthropogenic forces promote homogenization of habitats and genetic lineages. In this study, we use the highly modified Yuba River in California to understand if distinct genetic lineages and life histories still exist, despite reductions in spawning habitat and hatchery practices that have promoted introgression. There is currently a concerted effort to protect federally listed Central Valley spring-run Chinook salmon populations, given that few wild populations still exist. Despite this, we lack a comprehensive understanding of the genetic and life history diversity of Chinook salmon present in the Yuba River. To understand this diversity, we collected migration timing data and GREB1L genotypes from hook-and-line, acoustic tagging, and carcass surveys of Chinook salmon in the Yuba River between 2009 and 2011. Variation in the GREB1L region of the genome is tightly linked with run timing in Chinook salmon throughout their range, but the relationship between this variation and entry on spawning grounds is little explored in California's Central Valley. We found that the date Chinook salmon crossed the lowest barrier to Yuba River spawning habitat (Daguerre Point Dam) was tightly correlated with their GREB1L genotype. Importantly, our study confirms that ESA-listed spring-run Chinook salmon are spawning in the Yuba River, promoting a portfolio of life history and genetic diversity, despite the highly compressed habitat. This work highlights the need to identify and protect this life history diversity, especially in heavily impacted systems, to maintain healthy Chinook salmon metapopulations. Without protection, we run the risk of losing the last vestiges of important genetic variation.

2.
J Fish Biol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982714

ABSTRACT

Intraspecific biodiversity is vital for species persistence in an increasingly volatile world. By embracing methods that integrate information at different spatiotemporal scales, we can directly monitor and reconstruct changes in intraspecific biodiversity. Here we combined genetics and otolith biochronologies to describe the genotypic and phenotypic diversity of Chinook salmon (Oncorhynchus tshawytscha) in the Yuba River, California, comparing cohorts that experienced a range of hydroclimatic conditions. Yuba River salmon have been heavily impacted by habitat loss and degradation, and large influxes of unmarked hatchery fish each year have led to concern about introgression and uncertainty around the viability of its wild populations, particularly the rarer spring-run salmon. Otolith strontium isotopes showed that Yuba River origin fish represented, on average, 42% (range 7%-73%) of spawners across six return years (2009-2011, 2018-2020), with large interannual variability. The remainder of adult Chinook salmon in the river were primarily strays from the nearby Feather River hatchery, and since 2018 from the Mokelumne River hatchery. Among the Yuba-origin spawners, on average, 30% (range 14%-50%) exhibited the spring-run genotype. The Yuba-origin fish also displayed a variety of outmigration phenotypes that differed in the timing and size at which they left the Yuba river. Early-migrating fry dominated the returns (mean 59%, range 33%-89%), and their contribution rates were negatively correlated with freshwater flows. It is unlikely that fry survival rates are elevated during droughts, suggesting that this trend reflects disproportionately low survival of larger later migrating parr, smolts, and yearlings along the migratory corridor in drier years. Otolith daily increments indicated generally faster growth rates in non-natal habitats, emphasizing the importance of continuing upstream restoration efforts to improve in-river growing conditions. Together, these findings show that, despite a long history of habitat degradation and hatchery introgression, the Yuba River maintains intraspecific biodiversity that should be taken into account in future management, restoration, and reintroduction plans. The finding that genotypic spring-run are reproducing, surviving, and returning to the Yuba River every year suggests that re-establishment of an independent population is possible, although hatchery-wild interactions would need to be carefully considered. Integrating methods is critical to monitor changes in key genetic, physiological, and behavioral traits to assess population viability and resilience.

3.
Vaccines (Basel) ; 12(6)2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38932342

ABSTRACT

We report on a highly significant, positive association between anthrax vaccination and occurrence of Gulf War Illness (GWI) in 111 Gulf War veterans (42 with GWI and 69 controls). GWI was diagnosed in 47.1% of vaccinated veterans but only in 17.2% of non-vaccinated veterans (Pearson χ2 = 7.08, p = 0.008; odds ratio = 3.947; relative risk = 2.617), with 1.6x higher GWI symptom severity in vaccinated veterans (p = 0.007, F-test in analysis of covariance). Next, we tested the hypothesis that the susceptibility to GWI following anthrax vaccination could be due to inability to make antibodies against the anthrax protective antigen (PA), the key protein contained in the vaccine. Since the first step in initiating antibody production would be the binding of PA peptide fragments (typically 15-amino acid long [15-mer]) to peptide-binding motifs of human leukocyte antigen (HLA) Class II molecules, we assessed the binding-motif affinities of such HLA specific molecules to all linear 15-mer peptide fragments of the anthrax PA. We identified a total of 58 HLA Class II alleles carried by the veterans in our sample and found that, of those, 18 (31%) were present in the vaccinated group that did not develop GWI but were absent from the vaccinated group who developed GWI. Remarkably, in silico analyses revealed very high binding affinities of peptide-binding motifs of those 18 HLA alleles with fragments of anthrax vaccine PA, leading to the successful production of anti-PA antibodies. Conversely, the absence of these protective HLA alleles points to a reduced ability to develop antibodies against PA, thus resulting in harmful PA persistence and development of GWI.

6.
J Int AIDS Soc ; 27(5): e26254, 2024 May.
Article in English | MEDLINE | ID: mdl-38695101

ABSTRACT

INTRODUCTION: Adolescent girls and young women (AGYW), a priority population for HIV prevention in Africa, show high interest but difficulty in sustained effective use of pre-exposure prophylaxis (PrEP). With ongoing PrEP scale-up focused on increasing access, it is important to understand what influences AGYW's choice of PrEP delivery platforms. METHODS: The POWER implementation study in Cape Town provided PrEP between 2017 and 2020 to AGYW (16-25 years) from four differentiated delivery platforms: mobile clinic, government facility, courier delivery or community-based youth club. Healthcare providers at government and mobile clinics provided PrEP (initiation and refills) as part of comprehensive, integrated sexual and reproductive health services. Courier and youth club platforms provided light-touch PrEP refill services incorporating rapid HIV self-testing. We conducted in-depth interviews with a purposive sample of AGYW who had ≥3 months of PrEP-use and accessed ≥2 PrEP delivery platforms. The thematic analysis explored AGYW's preferences, decision-making and habits related to PrEP access to inform market segmentation. RESULTS: We interviewed 26 AGYW (median age 20) PrEP-users between November 2020 and March 2021. AGYW PrEP-users reported accessing different services with, 24 accessing mobile clinics, 17 courier delivery, 9 government health facilities and 6 youth clubs for their PrEP refills. Qualitative findings highlighted four potential behavioural profiles. The "Social PrEP-user" preferred PrEP delivery in peer spaces, such as youth clubs or adolescent-friendly mobile clinics, seeking affirmation and social support for continued PrEP use. The "Convenient PrEP-user" favoured PrEP delivery at easily accessible locations, providing quick (courier) or integrated contraception-PrEP refill visits (mobile and government clinic). The "Independent PrEP-user" preferred PrEP delivery that offered control over delivery times that fit into their schedule, such as the courier service. The "Discreet PrEP-user" highly valued privacy regarding their PrEP use (courier delivery) and avoided delivery options where unintentional disclosure was evident (youth club). Comfort with HIV self-testing had minimal influence on PrEP delivery choice. CONCLUSIONS: Market segmentation of AGYW characterizes different types of PrEP-users and has the potential to enhance tailored messaging and campaigns to reach specific segments, with the aim of improving sustained PrEP use and HIV prevention benefits.


Subject(s)
Anti-HIV Agents , HIV Infections , Pre-Exposure Prophylaxis , Humans , Adolescent , Female , South Africa , HIV Infections/prevention & control , Pre-Exposure Prophylaxis/methods , Young Adult , Adult , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosage , Interviews as Topic , Patient Acceptance of Health Care
7.
Focus (Am Psychiatr Publ) ; 22(1): 97-108, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38694151

ABSTRACT

Objective: The menopause transition is associated with difficulties in executive function. However, it is unclear whether these difficulties persist past perimenopause. This study investigated whether potential confounders, including natural vs. surgical postmenopause and menopause-related psychological symptoms, influence whether executive dysfunction persists into postmenopause. Study Design: A cross-sectional sample of women aged 35-65 years (N = 1971) in one of four groups, premenopause, perimenopause, natural postmenopause, and surgical postmenopause, were surveyed. Participants self-reported executive functioning with the Brown Attention Deficit Disorder Scale (BADDS), anxiety symptom severity with the Generalized Anxiety Disorder Questionnaire (GAD-7), and depression symptom severity with the Center for Epidemiologic Studies Depression Scale (CES-D). Main Outcome Measures: We analyzed the association between group and BADDS scores using linear regression models - first, by controlling for age, education, and self-reported attention deficit hyperactivity disorder (ADHD) diagnosis (Model #1) and, second, by further controlling for current difficulty sleeping, anxiety, and depression (Model #2). Results: In both models, BADDS scores were significantly elevated (indicating more difficulties in executive function) among women in the perimenopausal and surgical postmenopausal groups compared with those in the premenopausal group. Likewise, the perimenopausal and surgical postmenopausal groups had the highest proportions of participants who reported difficulty sleeping and clinical levels of anxiety and depression. BADDS scores were significantly higher in natural postmenopausal vs. premenopausal women without controlling for difficulty sleeping, anxiety, and depression (Model #1), but not when adjusting for these variables (Model #2). Conclusions: The type of menopause and psychological symptoms are important confounders of the relationship between the menopause transition and executive dysfunction, and help explain whether executive dysfunction persists or recovers in postmenopause.Reprinted from Maturitas 2023; 170:64-73, with permission from Elsevier. Copyright © 2023.

8.
Transpl Int ; 37: 12605, 2024.
Article in English | MEDLINE | ID: mdl-38711816

ABSTRACT

Patients of Asian and black ethnicity face disadvantage on the renal transplant waiting list in the UK, because of lack of human leucocyte antigen and blood group matched donors from an overwhelmingly white deceased donor pool. This study evaluates outcomes of renal allografts from Asian and black donors. The UK Transplant Registry was analysed for adult deceased donor kidney only transplants performed between 2001 and 2015. Asian and black ethnicity patients constituted 12.4% and 6.7% of all deceased donor recipients but only 1.6% and 1.2% of all deceased donors, respectively. Unadjusted survival analysis demonstrated significantly inferior long-term allograft outcomes associated with Asian and black donors, compared to white donors. On Cox-regression analysis, Asian donor and black recipient ethnicities were associated with poorer outcomes than white counterparts, and on ethnicity matching, compared with the white donor-white recipient baseline group and adjusting for other donor and recipient factors, 5-year graft outcomes were significantly poorer for black donor-black recipient, Asian donor-white recipient, and white donor-black recipient combinations in decreasing order of worse unadjusted 5-year graft survival. Increased deceased donation among ethnic minorities could benefit the recipient pool by increasing available organs. However, it may require a refined approach to enhance outcomes.


Subject(s)
Asian People , Black People , Graft Survival , Kidney Transplantation , Tissue Donors , Humans , United Kingdom , Male , Female , Adult , Middle Aged , Tissue Donors/supply & distribution , Black People/statistics & numerical data , Registries , White People/statistics & numerical data , Treatment Outcome , Aged , Proportional Hazards Models , Waiting Lists , Transplant Recipients/statistics & numerical data
9.
Biol Psychiatry ; 2024 May 29.
Article in English | MEDLINE | ID: mdl-38821195

ABSTRACT

BACKGROUND: Adverse childhood experiences (ACEs) increase risk for mental illness in women and their children, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may play a role. The impact of ACEs on the HPA axis may be strongest when ACEs occur prepubertally and in those exposed to abuse ACEs. METHODS: To test this, we measured salivary cortisol in 96 mother-infant dyads while mothers were separated from their infant experiencing a laboratory stressor. Mothers completed the ACE questionnaire, ACEs occurring prepubertally (pACEs) were measured, and mother-infant dyads were grouped based on maternal pACE history: no pACEs, 1+ pACEs with abuse, or 1+ pACEs but no abuse. RESULTS: Mothers with 1+ pACEs exhibited decreases in cortisol (relative to pre-infant stressor), which differed significantly from the cortisol increase mothers with no pACEs experienced, regardless of abuse presence (p=.001) or absence (p=.002). These 1+ pACE groups did not differ from one another (p=.929). Significant sex differences in infant cortisol were observed in infants of mothers with 1+ pACEs (regardless of abuse) but not in infants of mothers with no pACEs. When mothers had 1+ pACEs, males showed decreases in cortisol in response to a stressor whereas females demonstrated increases, and males and females differed significantly when their mothers had 1+ pACEs with (p=0.025) and without (p=0.032) abuse. CONCLUSIONS: Regardless of maternal exposure to childhood abuse, in response to a stressor, prepubertal ACEs were associated with lower cortisol response in mothers and sex differences in six-month-old infants, with males showing a lower cortisol response than females.

10.
Clin Infect Dis ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38666412

ABSTRACT

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

11.
BMJ Open ; 14(4): e082047, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38670614

ABSTRACT

INTRODUCTION: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk. METHODS AND ANALYSIS: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England. Patients on the palliative care register or residents in a nursing home are excluded. Eligible people are identified using electronic patient records from general practices and sent an invitation and consent form to participate by post. Consenting participants are randomised at a ratio of 2:1 (control:intervention) with clustering by household. Those randomised to the intervention arm are sent an information leaflet inviting them to participate in screening, which involves use of a handheld single-lead ECG four times a day for 3 weeks. ECG traces identified by an algorithm as possible AF are reviewed by cardiologists. Participants with AF are seen by a general practitioner for consideration of anticoagulation. The primary outcome is stroke. Major secondary outcomes are: death, major bleeding and cardiovascular events. Follow-up will be via electronic health records for an average of 4 years. The primary analysis will be by intention-to-treat using time-to-event modelling. Results from this trial will be combined with follow-up data from the cluster-randomised pilot trial by fixed-effects meta-analysis. ETHICS AND DISSEMINATION: The London-Central National Health Service Research Ethics Committee (19/LO/1597) provided ethical approval. Dissemination will include public-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.


Subject(s)
Atrial Fibrillation , Mass Screening , Stroke , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/complications , Aged , Stroke/prevention & control , Mass Screening/methods , Electrocardiography , England/epidemiology , Female , Male , Randomized Controlled Trials as Topic , Aged, 80 and over , Anticoagulants/therapeutic use
12.
Sci Prog ; 107(2): 368504241242276, 2024.
Article in English | MEDLINE | ID: mdl-38614463

ABSTRACT

Objective: This pilot study assessed the effects of electronic noise-masking earbuds on subjective sleep perception and objective sleep parameters among healthcare workers (HCWs) reporting sleep difficulties during the COVID-19 pandemic. Methods: Using a pre-post design, 77 HCWs underwent 3 nights of baseline assessment followed by a 7-night intervention period. Participants wore an at-home sleep monitoring headband to assess objective sleep measures and completed subjective self-report assessments. The difference in mean sleep measures from baseline to intervention was estimated in linear mixed models. Results: Compared to baseline assessments, HCWs reported significant improvements in sleep quality as measured by the Insomnia Severity Index (ISI) (Cohen's d = 1.74, p < 0.001) and a significant reduction in perceived sleep onset latency (SOL) during the intervention (M = 17.2 minutes, SD = 7.7) compared to baseline (M = 24.7 minutes, SD = 16.1), (Cohen's d = -0.42, p = 0.001). There were no significant changes in objective SOL (p = 0.703). However, there was a significant interaction between baseline objective SOL (<20 minutes vs >20 minutes) and condition (baseline vs intervention) (p = 0.002), such that individuals with objective SOL >20 minutes experienced a significant decrease in objective SOL during the intervention period compared to baseline (p = 0.015). Conclusions: HCWs experienced a significant improvement in perceived SOL and ISI scores after using the electronic noise-masking earbuds. Our data provide preliminary evidence for a nonpharmacological intervention to improve the sleep quality of HCWs which should be confirmed by future controlled studies.


Subject(s)
Pandemics , Sleep , Humans , Pilot Projects , Technology , Electronics , Health Personnel
13.
Am J Speech Lang Pathol ; : 1-13, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38306506

ABSTRACT

PURPOSE: Transcranial direct current stimulation (tDCS) is a neuromodulation tool to amplify neural excitability and enhance outcomes associated with speech-language therapy (SLT). Stimulation currents to the left and right hemispheres vary in applying anodal (excitatory), cathodal (inhibitory), or bihemispheric signals. Several systematic reviews (SRs) and meta-analyses (MAs) have summarized the large literature examining tDCS for aphasia rehabilitation. The purpose of this project was to appraise the quality of SRs and MAs of tDCS for aphasia and examine the weight of the evidence for language outcomes in individuals with aphasia beyond SLT alone. METHOD: We searched four databases for SRs/MAs examining effects of tDCS for poststroke aphasia. We identified 16 reviews, with nine that incorporated MA to quantify results. Two reviewers reliably coded articles for methodological rigor using the AMSTAR 2 (A MeaSurement Tool to Assess Systematic Reviews, Version 2). We then summarized findings of the 16 reviews. RESULTS: The AMSTAR 2 appraisal criteria suggest that critical weaknesses were noted among all reviews except those by Elsner et al. (2015, 2019). Reviews summarized three to 48 studies, as some included only randomized crossover trials and others included all trial designs. All SRs and one MA reported improvements following tDCS stimulation for general aphasia abilities and measures of repetition and speech fluency. Five recent MAs reported significant naming improvements following tDCS using all stimulation arrays. No tDCS effects were noted for comprehension measures. CONCLUSIONS: As the tDCS literature matured, the conclusions of MAs merged with earlier SRs reporting statistically positive benefits over SLT alone. Most consistent results are reported for naming measures, leaving some to question the clinical significance of tDCS effects for functional measures of aphasia recovery. Although the tDCS literature is expansive, important questions remain before the technique can be confidently recommended for clinical practice.

14.
Suicide Life Threat Behav ; 54(3): 489-500, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38380441

ABSTRACT

INTRODUCTION: The US Department of Defense recommends lethal means safety counseling (LMSC) to promote firearm injury prevention via secure storage of personal firearms. We describe the rollout of a universal, peer-delivered adaptation of Project Safe Guard (PSG)-a brief, single-session LMSC discussion-at a US Space Force installation. METHOD: Program evaluation data were collected via anonymous, voluntary, and online surveys. Of approximately 862 eligible active-duty service members and embedded civilians, 324 completed the preprogram survey and 68 and 37 completed the 1- and 2-month follow-ups, respectively. RESULTS: At preprogram, 69.1% agreed that peer-delivered LMSC is appropriate. After rollout, 100% of the 222 firearm locking devices available to service members were requested from the on-base Violence Prevention Integrator. The effectiveness of PSG was indeterminable due to the low survey response rates. CONCLUSIONS: Despite strong preprogram support for peer-delivered LMSC and behavioral indicators of secure firearm storage (e.g., firearm locking device requests), several challenges limited the uptake and evaluability of the PSG program in this naturalistic environment, including military survey fatigue and competing mission priorities. Additional work is needed to determine the effectiveness of peer-delivered LMSC in a military context. Sustained base support and military-civilian collaborations will be critical.


Subject(s)
Counseling , Firearms , Military Personnel , Peer Group , Wounds, Gunshot , Humans , Military Personnel/psychology , United States , Counseling/methods , Male , Adult , Female , Wounds, Gunshot/prevention & control , Program Evaluation , Safety
15.
ACS Infect Dis ; 10(2): 582-593, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38226592

ABSTRACT

An impermeable outer membrane and multidrug efflux pumps work in concert to provide Gram-negative bacteria with intrinsic resistance against many antibiotics. These resistance mechanisms reduce the intracellular concentrations of antibiotics and render them ineffective. The natural product thiomarinol A combines holothin, a dithiolopyrrolone antibiotic, with marinolic acid A, a close analogue of mupirocin. The hybridity of thiomarinol A converts the mupirocin scaffold from inhibiting Gram-positive bacteria to inhibiting both Gram-positive and -negative bacteria. We found that thiomarinol A accumulates significantly more than mupirocin within the Gram-negative bacterium Escherichia coli, likely contributing to its broad-spectrum activity. Antibiotic susceptibility testing of E. coli mutants reveals that thiomarinol A overcomes the intrinsic resistance mechanisms that render mupirocin inactive. Structure-activity relationship studies suggest that the dithiolopyrrolone is a privileged moiety for improving the accumulation and antibiotic activity of the mupirocin scaffold without compromising binding to isoleucyl-tRNA synthetase. These studies also highlight that accumulation is required but not sufficient for antibiotic activity. Our work reveals a role of the dithiolopyrrolone moiety in overcoming intrinsic mupirocin resistance in E. coli and provides a starting point for designing dual-acting and high-accumulating hybrid antibiotics.


Subject(s)
Anti-Bacterial Agents , Mupirocin , Mupirocin/analogs & derivatives , Anti-Bacterial Agents/chemistry , Mupirocin/pharmacology , Mupirocin/chemistry , Escherichia coli , Gram-Negative Bacteria
16.
Int J Circumpolar Health ; 83(1): 2300858, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38184792

ABSTRACT

Indigenous Elder advisors in Pelican Narrows, a Cree community in Northern Saskatchewan, have indicated that Western pain scales may not be responsive tools for pain assessments within their community. This study employed a mixed methods research design that involved two phases. Phase one was the development of a pain scale in collaboration with an Elder and a Knowledge Keeper. Phase two was a pilot of the CDPS utilised during virtual physiotherapy sessions for chronic back pain. Twenty-seven participants completed the pre-physiotherapy treatment questionnaires, and 10 participants engaged in semi-structured interviews (9 community members; 1 healthcare provider). A weighted kappa analysis yielded k = 0.696, indicating a good agreement between the CDPS and Faces Pain Scale-Revised in terms of documenting participants' pain. Qualitative data from interviews with community members revealed three major themes: 1) Learnings Regarding Pain Scales, 2) Patient Centered Care; and 3) Strength-Based Solutions for Improving Pain Communication. Two themes were uncovered through conversations with the HCP: 1) Perspectives on CDPS and 2) Healthcare Provider Experiences Communicating about Pain. Moreover, a patient-centredcentred approach is important to ensure comprehensive pain assessments.


Subject(s)
Pain Measurement , Pain , Humans , Communication , Saskatchewan
17.
Nat Chem Biol ; 20(2): 162-169, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37537379

ABSTRACT

Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMY3R, and San45 bound to AMY3R or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMY3R. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects.


Subject(s)
Islet Amyloid Polypeptide , Receptors, Calcitonin , Humans , Receptors, Calcitonin/agonists , Receptors, Calcitonin/metabolism , Islet Amyloid Polypeptide/metabolism , Obesity , Lipids
18.
Stress Health ; 40(2): e3313, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37679965

ABSTRACT

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.


Subject(s)
C-Reactive Protein , Depression , Stress, Psychological , Female , Humans , C-Reactive Protein/analysis , Inflammation , Interleukin-6 , Stress, Psychological/metabolism , Tumor Necrosis Factor-alpha
19.
J Appl Gerontol ; 43(4): 454-464, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38087851

ABSTRACT

This study examines the relationship of decisional conflict about driving habits between older adult drivers (≥70 years old) and their family members and close friends. This secondary analysis utilizes data originating from a multi-site randomized controlled trial assessing the effect of a driving decision aid (DDA) intervention. Decisional conflict about stopping or changing driving habits for drivers was measured with the Decisional Conflict Scale (DCS). Dyadic associations between drivers' and study partners' (SPs') DCS scores were analyzed using an actor-partner interdependence model. Among 228 driver-SP dyads, Dyadic DCS was correlated at baseline (r = .18, p < .01), and pre-intervention DCS was associated with post-intervention DCS (p < .001 for SPs [ß = .73] and drivers [ß = .73]). Drivers' baseline DCS and SPs' post-intervention DCS were slighly correlated (ß = .10; p = .036). Higher decisional conflict about driving among older drivers is frequently shared by their SPs. Shared decisional conflict may persist beyond intervening to support decision-making about driving cessation.


Subject(s)
Conflict, Psychological , Friends , Humans , Aged , Family , Decision Making
20.
J Midwifery Womens Health ; 69(1): 9-16, 2024.
Article in English | MEDLINE | ID: mdl-37641584

ABSTRACT

INTRODUCTION: Prior to the coronavirus disease 2019 (COVID-19) pandemic, studies of innovative telehealth perinatal care models showed similar clinical outcomes and perceived quality of care between groups receiving a combination of virtual video and in-person visits. However, these studies included primarily White, English-speaking participants, excluding those who were economically disenfranchised or did not speak English. The purpose of this qualitative study was to describe perinatal patients' and providers' experiences with telehealth during and after the acute phase of the COVID-19 pandemic to inform future utilization of telehealth to drive the delivery of high-quality, accessible, and equitable perinatal care to diverse communities. METHODS: This descriptive qualitative study included a purposive sample of 14 patients and 17 providers who received or provided perinatal care via telehealth in either a certified nurse-midwifery practice or the nurse-family partnership care model between March 2020 and April 2022. Maximum variation sampling offered a diverse population based on race, ethnicity, and rurality. Researchers conducted 2 rounds of semistructured interviews with a focus on understanding social and geographic context. RESULTS: Six themes were identified through inductive analysis: (1) unexpected advantages of telehealth, (2) patient empowerment, (3) providers' fear of adverse outcomes, (4) concern for equitable care, (5) strategies to enhance the telehealth experience, and (6) strategies to address access to perinatal telehealth. Patients appreciated the increased ease and reduced cost of accessing visits, which led to fewer missed appointments. Health care providers saw great opportunity in telehealth but expressed concerns about accessibility for patients with language barriers or limited resources. DISCUSSION: This study provides insight into priorities for continued telehealth utilization focused on providing equitable access to perinatal care. Rather than returning to practices from before the COVID-19 pandemic formed from longstanding routines and perceived limitations, providers are encouraged to capitalize on the rapid innovations in telehealth to build a more effective, equitable, and patient-centered approach to perinatal care.


Subject(s)
COVID-19 , Midwifery , Telemedicine , Female , Pregnancy , Humans , Pandemics , COVID-19/epidemiology , Certification
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