Psychosocial burden in patients with chronic laryngopharyngeal symptoms with and without pathologic acid reflux.

BACKGROUND: Patients with chronic laryngopharyngeal symptoms, with or without pathologic reflux, frequently have poor response to standard therapies, which may be a result of overlapping cognitive-affective processes. Therefore, the aims of this study included measuring psychosocial distress and laryngeal-specific cognitive distress in patients with chronic laryngopharyngeal symptoms (LPS) as well as comparing these among laryngeal symptomatic patients with and without conclusive gastroesophageal reflux disease (GERD). METHODS: This prospective, single-center study enrolled adults with chronic LPS from 9/22 to 6/23. Patients completed eight questionnaires on quality of life, symptom burden, and psychosocial distress. The laryngeal cognitive affective tool (LCAT) assessed laryngeal-specific hypervigilance and anxiety; LCAT scores ≥33 were elevated. All patients underwent objective testing with endoscopy and/or ambulatory reflux monitoring and were categorized as proven GERD (GER+) or no proven GERD (GER-). KEY RESULTS: One hundred twenty-nine patients were included: 66% female, mean age 54.1 (17.5) years, mean BMI 27.6 (6.8) kg/m2, 66% Caucasian, 57% with an elevated LCAT, and 53% GER+. Moderate-to-severe anxiety was found in 39% and moderate-to-severe depression in 19%. An elevated LCAT alone or with an elevated anxiety/depression score was found in 58%. Patient-reported outcomes scores, including LCAT scores (32.9 (13.8) GER- vs. 33.1 (12.6) GER+, p = 0.91), were similar between patients with and without GER+. CONCLUSIONS AND INFERENCES: Patients with chronic LPS experience heightened levels of hypervigilance, symptom-specific anxiety, and psychosocial distress, regardless of the presence of pathologic GER.

The effects of psychotherapy for anhedonia on subcortical brain volumes measured with ultra-high field MRI.

BACKGROUND: Anhedonia is a transdiagnostic symptom often resistant to treatment. The identification of biomarkers sensitive to anhedonia treatment will aid in the evaluation of novel anhedonia interventions. METHODS: This is an exploratory analysis of changes in subcortical brain volumes accompanying psychotherapy in a transdiagnostic anhedonic sample using ultra-high field (7-Tesla) MRI. Outpatients with clinically impairing anhedonia (n = 116) received Behavioral Activation Treatment for Anhedonia, a novel psychotherapy, or Mindfulness-Based Cognitive Therapy (ClinicalTrials.gov Identifiers NCT02874534 and NCT04036136). Subcortical brain volumes were estimated via the MultisegPipeline, and regions of interest were the amygdala, caudate nucleus, hippocampus, pallidum, putamen, and thalamus. Bivariate mixed effects models estimated pre-treatment relations between anhedonia severity and subcortical brain volumes, change over time in subcortical brain volumes, and associations between changes in subcortical brain volumes and changes in anhedonia symptoms. RESULTS: As reported previously (Cernasov et al., 2023), both forms of psychotherapy resulted in equivalent and significant reductions in anhedonia symptoms. Pre-treatment anhedonia severity and subcortical brain volumes were not related. No changes in subcortical brain volumes were observed over the course of treatment. Additionally, no relations were observed between changes in subcortical brain volumes and changes in anhedonia severity over the course of treatment. LIMITATIONS: This trial included a modest sample size and did not have a waitlist-control condition or a non-anhedonic comparison group. CONCLUSIONS: In this exploratory analysis, psychotherapy for anhedonia was not accompanied by changes in subcortical brain volumes, suggesting that subcortical brain volumes may not be a candidate biomarker sensitive to response to psychotherapy.

How researchers can translate health evidence into books for children.

The health promotion literature that considers how scientific evidence can be effectively communicated tends to focus on evaluating the effectiveness of communication materials. This has resulted in a knowledge gap regarding effective knowledge translation processes. This study explores the process, reasoning and practices for developing books for children that incorporate evidence-based information to aid understanding of scientific evidence about health and environmental or natural disasters. This study is informed by a systematic review of the literature combined with responses to an email interview with authors of books for children. Nine published studies were included in the systematic review. Twenty-two authors responded to the email survey (25% response rate, following 86 invitations). We report seven key findings to guide the development of health-promoting books for children: (i) understand the needs and expectations of the audience, (ii) articulate the topic and research evidence, (iii) assemble a team with a mix of content knowledge and creative expertise, (iv) format should be chosen to suit the user group and guided by the creative team, (v) early testing with children and their support system is crucial, (vi) develop a dissemination strategy to reach the user group and (vii) engage in reflexivity through evaluation of effectiveness of messaging. The current investigation can guide the process, reasoning and practice of developing books for children that incorporate evidence about health and environmental disasters.

Application of Statistical Analysis and Machine Learning to Identify Infants' Abnormal Suckling Behavior.

OBJECTIVE: Identify infants with abnormal suckling behavior from simple non-nutritive suckling devices. BACKGROUND: While it is well known breastfeeding is beneficial to the health of both mothers and infants, breastfeeding ceases in 75 percent of mother-child dyads by 6 months. The current standard of care lacks objective measurements to screen infant suckling abnormalities within the first few days of life, a critical time to establish milk supply and successful breastfeeding practices. MATERIALS AND METHODS: A non-nutritive suckling vacuum measurement system, previously developed by the authors, is used to gather data from 91 healthy full-term infants under thirty days old. Non-nutritive suckling was recorded for a duration of sixty seconds. We establish normative data for the mean suck vacuum, maximum suck vacuum, suckling frequency, burst duration, sucks per burst, and vacuum signal shape. We then apply computational methods (Mahalanobis distance, KNN) to detect anomalies in the data to identify infants with abnormal suckling. We finally provide case studies of healthy newborn infants and infants diagnosed with ankyloglossia. RESULTS: In a series of case evaluations, we demonstrate the ability to detect abnormal suckling behavior using statistical analysis and machine learning. We evaluate cases of ankyloglossia to determine how oral dysfunction and surgical interventions affect non-nutritive suckling measurements. CONCLUSIONS: Statistical analysis (Mahalanobis Distance) and machine learning [K nearest neighbor (KNN)] can be viable approaches to rapidly interpret infant suckling measurements. Particularly in practices using the digital suck assessment with a gloved finger, it can provide a more objective, early stage screening method to identify abnormal infant suckling vacuum. This approach for identifying those at risk for breastfeeding complications is crucial to complement complex emerging clinical evaluation technology. CLINICAL IMPACT: By analyzing non-nutritive suckling using computational methods, we demonstrate the ability to detect abnormal and normal behavior in infant suckling that can inform breastfeeding intervention pathways in clinic.Clinical and Translational Impact Statement: The work serves to shed light on the lack of consensus for determining appropriate intervention pathways for infant oral dysfunction. We demonstrate using statistical analysis and machine learning that normal and abnormal infant suckling can be identified and used in determining if surgical intervention is a necessary solution to resolve infant feeding difficulties.

Association between dietary magnesium intake, inflammation, and neurodegeneration.

BACKGROUND: Consistent evidence shows that magnesium (Mg) intake is associated with lower blood pressure (BP), and that lower BP is associated with improved cerebral health. However, recent findings indicate that the positive effect of dietary Mg intake on cerebral health is not mediated by a decrease in BP. As Mg's anti-inflammatory action is a plausible alternative mechanism, the objective of this study was to investigate the associations between Mg intake and inflammation to determine whether it mediates any neuroprotective effect. METHODS: Participants from the UK Biobank (n = 5775, aged 40-73 years, 54.7% female) were assessed for dietary magnesium using an online food questionnaire, brain and white matter lesion (WML) volumes were segmented with FreeSurfer software, and inflammation markers including high-sensitivity C-reactive protein (hs-CRP), leukocyte, erythrocyte count, and Glycoprotein acetylation (GlycA) were measured using specific laboratory techniques such as immunoturbidimetry, automated cell counting, and nuclear magnetic resonance. Hierarchical linear regression models were performed to investigate the association between dietary Mg, and inflammatory markers and between dietary Mg, brain and WMLs volumes. Mediation analysis was performed to test a possible mediation role of inflammation on the association between dietary Mg and brain and WMLs volumes. RESULTS: Higher dietary Mg intake was associated with lower inflammation: hs-CRP level (- 0.0497%; 95% confidence interval [CI] - 0.0497%,  - 0.0199%) leukocytes count (- 0.0015%; 95%CI - 0.00151%,  - 0.0011%), and GlycA (- 0.0519%; 95%CI - 0.1298%,  - 0.0129%). Moreover, higher dietary Mg intake was associated with larger grey matter volume (0.010%; 95%CI 0.004%, 0.017%), white matter volume (0.012%; 95%CI 0.003,  0.022) and right hippocampal volume (0.002%; 95%CI 0.0007, -0.0025%). Lower hs-CRP levels mediated the positive association between higher dietary Mg intake and larger grey matter volume. CONCLUSIONS: The anti-inflammatory effects of dietary Mg intake in the general population, appears to mediate its neuroprotective effect.

Laryngeal Recalibration Therapy Improves Laryngopharyngeal Symptoms in Patients With Suspected Laryngopharyngeal Reflux Disease.

INTRODUCTION: Laryngopharyngeal symptoms such as cough, throat clearing, voice change, paradoxic vocal fold movement, or laryngospasm are hyper-responsive behaviors resulting from local irritation (e.g., refluxate) and heightened sympathetic tone. Laryngeal recalibration therapy (LRT) guided by a speech-language pathologist (SLP) provides mechanical desensitization and cognitive recalibration to suppress hyper-responsive laryngeal patterns. The aim of this study was to assess symptom response to LRT among patients with chronic laryngopharyngeal symptoms undergoing evaluation of gastroesophageal reflux disease (GERD). METHODS: Adults with chronic laryngopharyngeal symptoms referred for evaluation of GERD to a single center were prospectively followed. Inclusion criteria included ≥2 SLP-directed LRT sessions. Data from endoscopy, ambulatory reflux monitoring, and patient-reported outcomes were collected when available. The primary outcome was symptom response. RESULTS: Sixty-five participants completed LRT: mean age 55.4 years (SD 17.2), 46 (71%) female, mean body mass index 25.6 kg/m 2 (6.8), and mean of 3.7 (1.9) LRT sessions. Overall, 55 participants (85%) met criteria for symptom response. Specifically, symptom response was similar between those with isolated laryngopharyngeal symptoms (13/15, 87%) and concomitant laryngopharyngeal/esophageal symptoms (42/50, 84%). Among participants who underwent reflux monitoring, symptom response was similar between those with proven, inconclusive for, and no GERD (18/21 [86%], 8/9 [89%], 10/13 [77%]). DISCUSSION: Eighty-five percent of patients with chronic laryngopharyngeal symptoms referred for GERD evaluation who underwent LRT-experienced laryngeal symptom response. Rates of symptom response were maintained across patients with or without proven GERD and patients with or without concomitant esophageal reflux symptoms. SLP-directed LRT is an effective approach to incorporate into multidisciplinary management of chronic laryngopharyngeal symptoms/laryngopharyngeal reflux disease.

Evaluating online patient education materials for liver cirrhosis.

BACKGROUND & AIMS: Liver cirrhosis affects 4.5 million adults in the United States (US). As more patients educate themselves online, we evaluated the accessibility, quality, understandability, accuracy, readability, and comprehensiveness (AQUA-RC) of online patient education materials for cirrhosis. METHODS: Cross-sectional analysis using Google® and YouTube® on a cleared internet browser from 12 cities across the US. The authors independently reviewed the top 25 search results from each platform using search terms "liver cirrhosis" and "cirrhosis". Accessibility was evaluated from twelve cities in six regions across the US. We evaluated resource quality using the DISCERN score, understandability using the PEMAT score, readability using the Flesch-Kinkaid score, and accuracy/comprehensiveness using a list of author-generated criteria. AQUA-RC was compared between 1) academic websites (AW) vs. non-academic websites (NAW), and 2) websites vs. YouTube® videos. RESULTS: 28 websites and 25 videos were included. Accessibility was equal across all regions. Websites had higher average quality scores than videos, although this was not statistically significant (p = 0.84). Websites were more understandable than videos (p < 0.00001). Both websites and videos were 100% accurate. Readability for websites was higher than recommended standards. Websites were more comprehensive than videos (p = 0.02). CONCLUSION: Online patient education materials for cirrhosis in the US are equally accessible, but readability and understandability are too complex. Websites are of greater quality, accuracy, and comprehensiveness than YouTube videos, which are often narrowly focused and targeted at the medical community rather than patients. Further efforts should be made to improve online patient education and expand content across platforms.

Validation of the Laryngeal Cognitive-Affective Tool.

BACKGROUND & AIMS: Cognitive-affective processes, including hypervigilance and symptom-specific anxiety, may contribute to chronic laryngeal symptoms and are potentially modifiable; however, a validated instrument to assess these constructs is lacking. The aims of this study were to develop and validate the Laryngeal Cognitive-Affective Tool (LCAT) instrument. METHODS: This 2-phase single-center prospective study enrolled participants from November 2021 to June 2023. In the initial phase 1:1 patient cognitive interviews and multidisciplinary team consensus were conducted to develop the LCAT. In the second phase asymptomatic and symptomatic participants completed a series of questionnaires to examine psychometric properties of the LCAT. RESULTS: A total of 268 participants were included: 8 in the initial phase and 260 in the validation phase (56 asymptomatic; 204 symptomatic). A 15-item LCAT was developed. In the validation phase, mean total LCAT and hypervigilance/anxiety subscores were significantly higher in symptomatic versus asymptomatic participants (P < .01). The LCAT had excellent internal consistency (α = 0.942) and split-half reliability (Guttman = 0.853). Using a median split, a score of 33 or greater was defined as elevated. CONCLUSIONS: The 15-item LCAT evaluates laryngeal hypervigilance and symptom-specific anxiety among patients with laryngeal symptoms. It has excellent reliability and construct validity. The LCAT highlights burdensome cognitive-affective processes that can accordingly help tailor treatments.

Cognitive Function Is Associated with the Genetically Determined Efficiency of DNA Repair Mechanisms.

Several modifiable risk factors for neurodegeneration and dementia have been identified, although individuals vary in their vulnerability despite a similar risk of exposure. This difference in vulnerability could be explained at least in part by the variability in DNA repair mechanisms' efficiency between individuals. Therefore, the aim of this study was to test associations between documented, prevalent genetic variation (single nucleotide polymorphism, SNP) in DNA repair genes, cognitive function, and brain structure. Community-living participants (n = 488,159; 56.54 years (8.09); 54.2% female) taking part in the UK Biobank study and for whom cognitive and genetic measures were available were included. SNPs in base excision repair (BER) genes of the bifunctional DNA glycosylases OGG1 (rs1052133, rs104893751), NEIL1 (rs7402844, rs5745906), NEIL2 (rs6601606), NEIL3 (rs10013040, rs13112390, rs13112358, rs1395479), MUTYH (rs34612342, rs200165598), NTHL1 (rs150766139, rs2516739) were considered. Cognitive measures included fluid intelligence, the symbol-digit matching task, visual matching, and trail-making. Hierarchical regression and latent class analyses were used to test the associations between SNPs and cognitive measures. Associations between SNPs and brain measures were also tested in a subset of 39,060 participants. Statistically significant associations with cognition were detected for 12 out of the 13 SNPs analyzed. The strongest effects amounted to a 1-6% difference in cognitive function detected for NEIL1 (rs7402844), NEIL2 (rs6601606), and NTHL1 (rs2516739). Associations varied by age and sex, with stronger effects detected in middle-aged women. Weaker associations with brain measures were also detected. Variability in some BER genes is associated with cognitive function and brain structure and may explain variability in the risk for neurodegeneration and dementia.

Effects of cortisol administration on heart rate variability and functional connectivity across women with different depression histories.

Abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system have been implicated in depression. Studies have reported glucocorticoid insensitivity and reduced heart rate variability (HRV) in depressive disorders. However, little is known about the effects of cortisol on HRV and resting-state functional connectivity (rsFC) of the central autonomic network (CAN) in depression. We collected resting-state fMRI and cardiac data for women with different depression histories (n = 61) after administration of cortisol and placebo using a double-blind crossover design. We computed rsFC for R-amygdala and L-amygdala seeds and assessed the change in HRV after cortisol (cortisol-placebo). Analyses examined the effects of acute cortisol administration on HRV and rsFC of the R-amygdala and L-amygdala. There was a significant interaction between HRV and treatment for rsFC between the amygdala and CAN regions. We found lower rsFC between the L-amygdala and putamen for those with a greater decrease in HRV after cortisol. There was also reduced rsFC between the R-amygdala and dorsomedial prefrontal cortex, putamen, middle cingulate cortex, insula, and cerebellum in those with lower HRV after cortisol. These results remained significant after adjusting for depression symptoms, age, and race. Our findings suggest that the effect of cortisol on CAN connectivity is related to its effects on HRV. Overall, these results could inform transdiagnostic interventions targeting HRV and the stress response systems across clinical and non-clinical populations.

Sex-specific increases in myostatin and SMAD3 contribute to obesity-related insulin resistance in human skeletal muscle and primary human myotubes.

The purpose of the present study was to determine the effects of obesity and biological sex on myostatin expression in humans and to examine the direct effects of myostatin, SMAD2, and SMAD3 on insulin signaling in primary human skeletal muscle cells (HSkMCs). For cohort 1, 15 lean [body mass index (BMI): 22.1 ± 0.5 kg/m2; n = 8 males; n = 7 females] and 14 obese (BMI: 40.6 ± 1.4 kg/m2; n = 7 males; n = 7 females) individuals underwent skeletal muscle biopsies and an oral glucose tolerance test. For cohort 2, 14 young lean (BMI: 22.4 ± 1.9 kg/m2; n = 6 males; n = 8 females) and 14 obese (BMI: 39.3 ± 7.9 kg/m2; n = 6 males; n = 8 females) individuals underwent muscle biopsies for primary HSkMC experiments. Plasma mature myostatin (P = 0.041), skeletal muscle precursor myostatin (P = 0.048), and skeletal muscle SMAD3 (P = 0.029) were elevated in obese females compared to lean females, and plasma mature myostatin (r = 0.58, P = 0.029) and skeletal muscle SMAD3 (r = 0.56, P = 0.037) were associated with insulin resistance in females but not males. Twenty-four hours of myostatin treatment impaired insulin signaling in primary HSkMCs derived from females (P < 0.024) but not males. Overexpression of SMAD3, but not SMAD2, impaired insulin-stimulated AS160 phosphorylation in HSkMCs derived from lean females (-27%, P = 0.040), whereas silencing SMAD3 improved insulin-stimulated AS160 phosphorylation and insulin-stimulated glucose uptake (25%, P < 0.014) in HSkMCs derived from obese females. These results suggest for the first time that myostatin-induced impairments in skeletal muscle insulin signaling are sex specific and that increased body fat in females is associated with detrimental elevations in myostatin and SMAD3, which contribute to obesity-related insulin resistance.NEW & NOTEWORTHY Obesity is considered a main risk factor for the development of insulin resistance and type 2 diabetes. The present study utilizes in vivo and in vitro experiments in human skeletal muscle to demonstrate for the first time that females are inherently more susceptible to myostatin-induced insulin resistance, which is further enhanced with obesity due to increased myostatin and SMAD3 expression.

Effects of Cortisol Administration on Resting-State Functional Connectivity in Women with Depression.

Previous resting-state functional connectivity (rsFC) research has identified several brain networks impacted by depression and cortisol, including default mode (DMN), frontoparietal (FPN), and salience networks (SN). In the present study, we examined the effects of cortisol administration on rsFC of these networks in individuals varying in depression history and severity. We collected resting-state fMRI scans and self-reported depression symptom severity for 74 women with and without a history of depression after cortisol and placebo administration using a double-blind, crossover design. We conducted seed-based rsFC analyses for DMN, FPN, and SN seeds to examine rsFC changes after cortisol vs. placebo administration in relation to depression history group and severity. Results revealed a main effect of depression group, with lower left amygdala (SN)-middle temporal gyrus connectivity in women with a history of depression. Cortisol administration increased insula (SN)-inferior frontal gyrus and superior temporal gyrus connectivity. We also found that greater depression severity was associated with increased PCC (DMN)-cerebellum connectivity after cortisol. These results did not survive Bonferroni correction for seed ROIs and should be interpreted with caution. Our findings indicate that acute cortisol elevation may normalize aberrant connectivity of DMN and SN regions, which could help inform clinical treatments for depression.

Measuring civilian moral injury: Adaptation and validation of the Moral Injury Events Scale (Civilian) and Expressions of Moral Injury Scale (Civilian).

OBJECTIVE: Moral injury (MI) research has been expanded to populations beyond the military in recent years. A key barrier to further research into MI in civilian populations is the lack of valid, reliable measures of the construct appropriate for general civilian use. This article addresses this barrier by adapting two existing military measures and exploring their psychometrics in a general civilian sample: the Moral Injury Events Scale-Civilian (MIES-C) and Expressions of Moral Injury Scale-Military (EMIS-C). METHOD: A sample of civilian women (n = 192) and men (n = 88) completed the above measures, and additional scales designed to capture theoretically supported primary and secondary markers of MI (guilt, shame, anger; depression, posttraumatic stress symptoms, anxiety). RESULTS: Confirmatory factor analyses found that the factor structure of the MIES-C and EMIS-C replicated well within our civilian sample. Discriminant validity was indicated through a significant negative correlation with well-being. Both measures correlated as predicted with each other and measures of MI markers at the total score level. Correlations of individual subscales with each of these measures were more varied. CONCLUSIONS: Results shed light on differential relationships between the type of MI event and clinical outcomes, suggesting some conceptual differences in how MI is experienced in general civilian populations. Results suggest that civilian populations are also susceptible to MI, but that existing measures may have problems capturing this effectively. While the MIES-C and EMIS-C are supported for civilian use, further scale construction efforts for this population are warranted. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Mapping the citation network on vitamin D research in Australia: a data-driven approach.

Vitamin D research can vary geographically, as vitamin D status is influenced by latitude, season, dietary intake, body mass index, ethnicity, and public health initiatives. Over the last two decades, research on vitamin D has increased in Australia, where the potential for sun exposure (a major source of vitamin D) is high. We aimed to identify key topics and gaps in vitamin D research in Australia using a data-driven approach. A literature search limited to Australian studies was conducted in the Web of Science Core Collection database. Citation network analysis was conducted to identify clusters and sub-clusters, depicted using word clouds. Topic analysis of each cluster and sub-cluster was conducted to identify topics and sub-topics, respectively. From 934 publications (over the period 1984-2022), nine topics and 60 sub-topics were identified. The nine topics were: vitamin D in vulnerable populations and its impact on child development; impact of sun exposure and ultraviolet-B radiation on various health conditions; vitamin D and falls and fractures in older adults; vitamin D and its association with health outcomes; vitamin D from sun exposure; testing of vitamin D status in Australia; vitamin D, calcium, and musculoskeletal health; vitamin D status and knee osteoarthritis; and vitamin D status and exercise performance in athletes. There were limited publications on vitamin D in Aboriginal and Torres Strait Islander peoples and dietary vitamin D. We have provided an overview of vitamin D research in Australia. The research trends and knowledge gaps identified can guide future research to better inform public health initiatives in Australia.

Antiviral epithelial-macrophage crosstalk permits secondary bacterial infections.

IMPORTANCE: Miscommunication of antiviral and antibacterial immune signals drives worsened morbidity and mortality during respiratory viral-bacterial coinfections. Extracellular vesicles (EVs) are a form of intercellular communication with broad implications during infection, and here we show that epithelium-derived EVs released during the antiviral response impair the antibacterial activity of macrophages, an innate immune cell crucial for bacterial control in the airway. Macrophages exposed to antiviral EVs display reduced clearance of Staphylococcus aureus as well as altered inflammatory signaling and anti-inflammatory metabolic reprogramming, thus revealing EVs as a source of dysregulated epithelium-macrophage crosstalk during coinfection. As effective epithelium-macrophage communication is critical in mounting an appropriate immune response, this novel observation of epithelium-macrophage crosstalk shaping macrophage metabolism and antimicrobial function provides exciting new insight and improves our understanding of immune dysfunction during respiratory coinfections.

Effects of estrogen and progesterone on neuroactive steroids and cytokines in patients with suicidality.

BACKGROUND: In ovulating psychiatric patients experiencing suicidality, suicidal ideation (SI) often peaks perimenstrually. Our recent double-blind, placebo-controlled, crossover randomized clinical trial (RCT; NCT03720847) showed that perimenstrual administration of estradiol and progesterone (EP) can prevent this peak in SI and depressed mood. In this pre-registered follow-up analysis, we studied how the menstrual cycle and experimental manipulation affected two neurobiological systems associated with the menstrual cycle and suicide risk: GABAergic neuroactive steroids (NAS) and peripheral cytokines. METHODS: In 26 psychiatric outpatients with natural menstrual cycles and past-month SI, we analyzed serum samples from three blood draws (midluteal, perimenstrual, midfollicular) per experimental condition (EP vs placebo) timed to a luteinizing hormone-surge ovulation test. Using gas chromatography/mass spectrometry (GC/MS), we measured the progesterone (P4)-derived pregnane NAS (3α,5α)- 3-hydroxypregnan20-one (3α,5α-THP), (3α,5ß)- 3-hydroxypregnan-20-one (3α,5ß-THP), (3α,5α)- 3,21-dihydroxypregnan-20-one (3α,5α-THDOC), (3α,5α)- 3-hydroxyandrostan-17-one (3α,5α-A), the androstane NAS (3α,5ß)- 3-hydroxyandrostan-17-one (3α,5ß-A), (3α,5α,17ß)-androstane-3,17-diol (3α,5α-A-diol), (3α,5ß,17ß)-androstane-3,17-diol (3α,5ß-A-diol), and their precursor pregnenolone. High sensitivity multiplex assay kits quantified peripheral cytokines IL-1ß, IL-6, and TNF-α. RESULTS: P4-derived NAS fluctuated in parallel with P4 and increased with exogenous perimenstrual administration of EP. Conversely, androstane NAS either did not fluctuate or fluctuated inversely from P4, and these NAS decreased with exogenous EP. Peripheral cytokines did not show cyclical patterns, but each significantly predicted SI, depressed mood, or anxiousness. Concomitant SSRI medication use predicted lower androstane NAS. CONCLUSIONS: While preliminary and exploratory, our findings provide critical descriptive context for future studies. Further, our work presents menstrual cycle-related patterns for ten frequently-studied biomarkers, allowing for improved quality of comparisons involving naturally-cycling populations in research.

Creating ophthalmology experiences in undergraduate medical education: pilot of a cased-based learning ophthalmology tool.

PURPOSE: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum. METHODS: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments. RESULTS: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop. CONCLUSION: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge.

Provision of health services for elderly populations in rural and remote areas in Australia: A systematic scoping review.

INTRODUCTION: Although various studies have examined availability, access barriers and patient experiences of rural health services for the ageing population, no synthesis of this literature exists in Australia. OBJECTIVE: The objective of this study was to examine the current literature surrounding rural service provision and to evaluate the barriers to access for older individuals and to recognise gaps in the literature. DESIGN: A systematic scoping review of peer-reviewed literature from three online databases (PUBMED, SCOPUS and Web of Science). FINDINGS: Thirty-two papers were included in analysis. The most prominent types of health service discussed were residential aged care (n = 12) and community health care (n = 10). More studies explored the perspectives of health personnel than the service end users. Qualitative synthesis revealed three themes associated with health service and rural ageing: access to services, health workforce experiences and end user experiences. DISCUSSION: Access to health services for the elderly population is a complex issue. Promoting positive experiences for both health providers and patients is critical to assisting in healthy ageing for people living in rural and remote areas. This requires intervention on a social and institutional level. Key research gaps in the literature include the effectiveness of an integrated approach to institutional interventions, utilisation of preventative measures such as screening programs for cancer and greater identification of the health needs and perceptions among culturally diverse elderly residents. These studies are critical to promote appropriate and patient-centred care for elderly populations in rural and remote areas. CONCLUSION: The review highlights the need to address availability, retention and service innovations across health services to improve access to care and health outcomes of rural elderly residents.

Mapping young people's journeys through mental health services: A prospective longitudinal qualitative study protocol.

Mental ill health is a major health risk for young people. There is unmet need for mental health assessment and treatment across Australia despite significant investment in government-funded plans to cover mental health and youth-oriented services. Understandings of mental health care for young people are impeded by a lack of longitudinal research. Without this research, it is difficult to understand how services do or do not support the recovery of young people over time. This project will analyse the healthcare journeys of young people aged 16-25 years experiencing their first episode of mental ill health for which they have sought GP support, over 12 months in the Australian Capital Territory. The study team will recruit up to 25 diverse young people and their general practitioners (GPs), and conduct four qualitative semi-structured interviews over 12 months with each participant. GP interviews will explore their role in the mental health care and care coordination for the young person. Interviews with young people will explore experiences and perceptions of navigating the health system, and the supports and resources they engaged with during the 12-month period. In between interviews, young people will be asked to keep a record of their mental health care experiences, through their choice of media. Participant-produced materials will also form the basis for interviews, providing stimuli to discuss the lived experience of care. Through analysing the narratives of both young people and their GPs, the study will establish how young people understand value in mental health care delivery. The study will use longitudinal qualitative mapping of healthcare journeys to identify key barriers and enablers to establishing effective, person-centred health care for young people with mental ill health.

Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation.

BACKGROUND: Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample. METHODS: Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors. RESULTS: Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC. CONCLUSIONS: Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.