Microbes and mood: innovative biomarker approaches in depression.

Although the field of psychiatry has made gains in biomarker discovery, our ability to change long-term outcomes remains inadequate. Matching individuals to the best treatment for them is a persistent clinical challenge. Moreover, the development of novel treatments has been hampered in part due to a limited understanding of the biological mechanisms underlying individual differences that contribute to clinical heterogeneity. The gut microbiome has become an area of intensive research in conditions ranging from metabolic disorders to cancer. Innovation in these spaces has led to translational breakthroughs, offering novel microbiome-informed approaches that may improve patient outcomes. In this review we examine how translational microbiome research is poised to advance biomarker discovery in mental health, with a focus on depression.

Robust and persistent B-cell responses following SARS-CoV-2 vaccine determine protection from SARS-CoV-2 infection.

Introduction: A clear immune correlate of protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been defined. We explored antibody, B-cell, and T-cell responses to the third-dose vaccine and relationship to incident SARS-CoV-2 infection. Methods: Adults in a prospective cohort provided blood samples at day 0, day 14, and 10 months after the third-dose SARS-CoV-2 vaccine. Participants self-reported incident SARS-CoV-2 infection. Plasma anti-SARS-CoV-2 receptor-binding domain (RBD) and spike-subunit-1 and spike-subunit-2 antibodies were measured. A sub-study assessed SARS-CoV-2-specific plasma and memory B-cell and memory T-cell responses in peripheral blood mononuclear cells by enzyme-linked immunospot. Comparative analysis between participants who developed incident infection and uninfected participants utilised non-parametric t-tests, Kaplan-Meier survival analysis, and Cox proportional hazard ratios. Results: Of the 132 participants, 47 (36%) reported incident SARS-CoV-2 infection at a median 16.5 (16.25-21) weeks after the third-dose vaccination. RBD titres and B-cell responses, but not T-cell responses, increased after the third-dose vaccine. Whereas no significant difference in day 14 antibody titres or T-cell responses was observed between participants with and without incident SARS-CoV-2 infection, RBD memory B-cell frequencies were significantly higher in those who did not develop infection [10.0% (4.5%-16.0%) versus 4.9% (1.6%-9.3%), p = 0.01]. RBD titres and memory B-cell frequencies remained significantly higher at 10 months than day 0 levels (p < 0.01). Discussion: Robust antibody and B-cell responses persisted at 10 months following the third-dose vaccination. Higher memory B-cell frequencies, rather than antibody titres or T-cell responses, predicted protection from subsequent infection, identifying memory B cells as a correlate of protection.

Hierarchical neural processing in γ oscillations for syntactic and semantic operations accounts for first- and second-language epistemology.

Introduction: We discuss event-related power differences (ERPDs) in low- and broadband-γ oscillations as the embedded-clause edge is processed in wh-dependencies such as Which decision regarding/about him/her did Paul say that Lydie rejected without hesitation? in first (L1) and second language (L2) French speakers. Methods: The experimental conditions manipulated whether pronouns appeared in modifiers (Mods; regarding him/her) or in noun complements (Comps; about him/her) and whether they matched or mismatched a matrix-clause subject in gender. Results: Across L1 and L2 speakers, we found that anaphora-linked ERPDs for Mods vs. Comps in evoked power first arose in low γ and then in broadband γ. Referential elements first seem to be retrieved from working memory by narrowband processes in low γ and then referential identification seems to be computed in broadband-γ output. Interactions between discourse- and syntax-based referential processes for the Mods vs. Comps in these ERPDs furthermore suggest that multidomain γ-band processing enables a range of elementary operations for discourse and semantic interpretation. Discussion: We argue that a multidomain mechanism enabling operations conditioned by the syntactic and semantic nature of the elements processed interacts with local brain microcircuits representing features and feature sets that have been established in L1 or L2 acquisition, accounting for a single language epistemology across learning contexts.

Stroke survivors' telemedicine experiences during the COVID-19 pandemic: A phenomenological investigation.

Purpose: This study aimed to describe stroke survivors' experiences receiving telemedicine visits at the Lone Star Stroke Consortium during the COVID-19 pandemic. Materials and Methods: A qualitative descriptive phenomenological design was applied to gather patients' telemedicine experiences through in-depth interviews, using a study guide. Audio-recorded interviews were conducted via ZOOM and transcribed verbatim. Two independent reviewers used the Giorgi descriptive method to analyze the data and search for the essence of stroke survivors' follow-up telemedicine experiences during the COVID-19 pandemic. Results: Fifteen underserved patients were recruited: mean age, 51.8 (15.7), and 9 (60%) females. Three themes emerged: (1) vivid memory of the stroke acute phase, (2) poststroke care experiences, and (3) perceived telemedicine experiences. Conclusions: The phenomenon of follow-up telemedicine visits during COVID-19 pandemic, as experienced by the stroke survivors, was positive. It showed patients' improved care access for poststroke visits. Telemedicine was satisfactory, except where the full medical exam was needed. Study findings highlight the individual approach was important, as well as the need for reliable internet and training to improve patients' technological skills. A hybrid approach for post-pandemic follow-up visits (in-person and telemedicine) was recommended by stroke survivors. These findings suggest that telemedicine is feasible and effective for poststroke care. Additional strategies are needed to improve future telemedicine integration into the continuum of care.

Endocannabinoid concentrations in major depression: effects of childhood maltreatment and relation to hippocampal volume.

Evidence from preclinical animal models suggests that the stress-buffering function of the endocannabinoid (eCB) system may help protect against stress-related reductions in hippocampal volume, as is documented in major depressive disorder (MDD). However, stress exposure may also lead to dysregulation of this system. Thus, pathways from marked stress histories, such as childhood maltreatment (CM), to smaller hippocampal volumes and MDD in humans may depend on dysregulated versus intact eCB functioning. We examined whether the relation between MDD and peripheral eCB concentrations would vary as a function of CM history. Further, we examined whether eCBs moderate the relation of CM/MDD and hippocampal volume. Ninety-one adults with MDD and 62 healthy comparison participants (HCs) were recruited for a study from the Canadian Biomarker Integration Network in Depression program (CAN-BIND-04). The eCBs, anandamide (AEA) and 2-arachidonylglycerol (2-AG), were assessed from blood plasma. Severe CM history was assessed retrospectively via contextual interview. MDD was associated with eCBs, though not all associations were moderated by CM or in the direction expected. Specifically, MDD was associated with higher AEA compared to HCs regardless of CM history, a difference that could be attributed to psychotropic medications. MDD was also associated with higher 2-AG, but only for participants with CM. Consistent with hypotheses, we found lower left hippocampal volume in participants with versus without CM, but only for those with lower AEA, and not moderate or high AEA. Our study presents the first evidence in humans implicating eCBs in stress-related mechanisms involving reduced hippocampal volume in MDD.

Modulation of neural oscillations in escitalopram treatment: a Canadian biomarker integration network in depression study.

Current pharmacological agents for depression have limited efficacy in achieving remission. Developing and validating new medications is challenging due to limited biological targets. This study aimed to link electrophysiological data and symptom improvement to better understand mechanisms underlying treatment response. Longitudinal changes in neural oscillations were assessed using resting-state electroencephalography (EEG) data from two Canadian Biomarker Integration Network in Depression studies, involving pharmacological and cognitive behavioral therapy (CBT) trials. Patients in the pharmacological trial received eight weeks of escitalopram, with treatment response defined as ≥ 50% decrease in Montgomery-Åsberg Depression Rating Scale (MADRS). Early (baseline to week 2) and late (baseline to week 8) changes in neural oscillation were investigated using relative power spectral measures. An association was found between an initial increase in theta and symptom improvement after 2 weeks. Additionally, late increases in delta and theta, along with a decrease in alpha, were linked to a reduction in MADRS after 8 weeks. These late changes were specifically observed in responders. To assess specificity, we extended our analysis to the independent CBT cohort. Responders exhibited an increase in delta and a decrease in alpha after 2 weeks. Furthermore, a late (baseline to week 16) decrease in alpha was associated with symptom improvement following CBT. Results suggest a common late decrease in alpha across both treatments, while modulatory effects in theta may be specific to escitalopram treatment. This study offers insights into electrophysiological markers indicating a favorable response to antidepressants, enhancing our comprehension of treatment response mechanisms in depression.

New Challenges: Use and Interpretation of Radius Bone Mineral Density.

CONTEXT: It is unknown if isolated low bone mineral density (BMD) "osteoporosis" at the radius is associated with increased fracture risk, not only at the wrist but elsewhere and whether it reflects more generalized skeletal fragility. OBJECTIVE: To review the association of radius BMD and fracture risk, the epidemiology of wrist fractures, isolated osteoporosis at the radius and the concordance between radial BMD and femoral neck BMD. METHODS: We completed a narrative literature review on radius BMD and fracture risk and current recommendations for measurement of radial BMD. We updated results of radial BMD and fracture results from the Study of Osteoporotic Fractures over 20 years and examined the concordance of BMD at the distal and proximal radius with femoral neck BMD T -scores. RESULTS: Radius BMD is a robust predictor of all types of fractures including hip and wrist but there is insufficient evidence to suggest that radius BMD predicts wrist fractures better than fractures at other sites. Fractures of the wrist tend to occur in younger, healthier women compared with hip and spine fractures. Nevertheless, wrist fractures are associated with an increased risk of future fractures and represent a missed opportunity for intervention. On a population level, the discordance between radius BMD and femoral neck BMD is small. But women with isolated osteoporosis at the radius had biochemical and microarchitecture deterioration that were similar to women with hip osteoporosis. CONCLUSION: Future research should address the clinical implications of isolated osteoporosis at the radius and whether treatment is warranted.

Antiretroviral Therapy and Cardiovascular Risk in People With HIV in the United States-An Updated Analysis.

Background: Several antiretroviral therapy (ART) medications have been associated with increased cardiovascular risk, but less is known about the safety of modern ART. We sought to compare the risk of major adverse cardiac events (MACEs) among different ART regimens. Methods: Using insurance claims databases from 2008 to 2020, we identified adults aged <65 years who newly initiated ART. We compared non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to protease inhibitors (PI)- and integrase inhibitors (INSTI)-based regimens. We used propensity score-weighted Kaplan-Meier functions to estimate the 6, 12, 18, 24, 36, and 48 months' risk and risk differences (RD) of MACE. Results: Among 37 935 ART initiators (median age, 40 years; 23% female; 26% Medicaid-insured), 45% started INSTI-, 16% PI-, and 39% NNRTI-based regimens. MACE occurred in 418 individuals (1.1%) within 48 months after ART initiation. Compared to NNRTI initiators, the risk of MACE was higher at 12 months (RD, 0.50; 95% CI, 0.14-0.99), 18 months (RD, 0.53; 95% CI, 0.11-1.06), and 24 months (RD, 0.62; 95% CI, 0.04-1.29) for PI initiators, and at 12 (RD, 0.20; 95% CI, 0.03-0.37) and 18 months (RD, 0.31; 95% CI, 0.06-0.54) for INSTI initiators; the precision of estimates was limited for longer duration of follow-up. Conclusions: Among ART initiators, PI-based and INSTI-based regimens were associated with higher short-term risk of MACE compared to NNRTI-based regimens. The pattern of association between INSTIs and PIs with excess risk of MACE was similar.

Characterization of Lemongrass Extract (Cymbopagon citratus) Nanoemulsion and Its Application as an Antibiofilm Agent in Acrylic Resin.

Background: An antimicrobial agent is needed for denture cleaning, such as lemongrass (LG), which has a bioactive antimicrobial component. Methods: This research analyzed LG extract nanoparticles with a particle size analyzer, ZPA, and biofilm formation inhibition on resin acrylic surfaces. Results: We found that there is high stability in nanoparticle size, while other concentrations, including chlorhexidine as a positive control, did not show any statistical differences. Conclusion: Lemongrass oil nanoemulsion has proved to be an antibiofilm and effective as a denture cleaning agent because of its ability to inhibit Streptococcus mutans and Candida albicans growth.

24-Hour Activity Composition is Associated with Lower Fall and Fracture Risk in Older Men.

Physical activity (PA), sedentary behavior (SB), and sleep are each individually associated with falls and fractures, but often are not examined simultaneously. Compositional data analysis examined the combined prospective associations between the proportion of time in PA, SB, and sleep relative to the remaining behaviors with recurrent falls (2+ falls in any year), any fractures, and major osteoporotic fracture (MOF) from tri-annual questionnaires, with adjudication for fractures, in 2918 older men aged 78.9 ± 5.1 years in the Osteoporotic Fractures in Men (MrOS) Study. Accelerometers were worn on the right tricep for seven consecutive 24-hour periods and measured PA (>1.5 METs), SB (≤1.5 METs), and sleep. Generalized Estimating Equations evaluated associations with recurrent falls. Cox proportional hazards regression estimated any incident fracture and MOF risk separately. Over four years of follow-up 1025 (35.2%) experienced recurrent falls; over 10 ± 4 years of follow-up, 669 (22.9%) experienced incident fractures and 370 (12.7%) experienced a MOF. Higher proportions of PA relative to SB and sleep were associated with a lower odds of recurrent falls [Odds Ratio (OR): 0.87, 95% CI: 0.76-0.99]. Higher proportions of SB relative to PA and sleep were associated with a higher odds of recurrent falls (OR: 1.38, 95% CI: 1.06-1.81) and higher risk of any fracture [Hazard Ratio (HR): 1.42, 95% CI: 1.05-1.92]. Higher proportions of sleep relative to PA and SB were associated with a lower risk of fracture (HR: 0.74, 95% CI: 0.54-0.99). No associations of activity composition with MOF were observed. When accounting for the co-dependence of daily activities, higher proportions of SB relative to the proportion of PA and sleep were associated with higher odds of recurrent falls and fracture risk. Results suggest reducing SB (and increasing PA) may lower fall and fracture risk in older men, which could inform future interventions.

Physical activity, sedentary behavior, and sleep are each individually associated with falls and fractures. However, there is only a finite amount of time for each activity in a 24-hour day and the ideal structure of the day for these activities is unknown. We evaluated the association between the combination of physical activity, sedentary behavior, and sleep together with recurrent falls and fractures in older men. Spending a higher proportion of the day in physical activity was associated with a lower risk of falls, while a higher proportion of sedentary behavior was associated with a higher risk of falls and fractures. For sleep, higher proportions of the day spent sleeping were associated with a lower risk of fractures. These results can inform future physical activity interventions aimed at lowering falls and fracture risk in older men by focusing on increasing the amount of time in physical activity by specifically lowering the amount of time in sedentary behavior.

Limb Perfusion Delivery of a rAAV1 Alpha-1 Antitrypsin Vector in Non-Human Primates Is Safe but Insufficient for Therapy.

BACKGROUND/OBJECTIVES: α-1 antitrypsin (AAT) deficiency is an inherited, genetic condition characterized by reduced serum levels of AAT and increased risk of developing emphysema and liver disease. AAT is normally synthesized primarily in the liver, but muscle-targeting with a recombinant adeno-associated virus (rAAV) vector for α-1 antitrypsin (AAT) gene therapy has been used to minimize liver exposure to the virus and hepatotoxicity. Clinical trials of direct intramuscular (IM) administration of rAAV1-hAAT have demonstrated its overall safety and transgene expression for 5 years. However, the failure to reach the therapeutic target level after 100 large-volume (1.5 mL) IM injections of maximally concentrated vector led us to pursue a muscle-targeting approach using isolated limb perfusion. This targets the rAAV to a greater muscle mass and allows for a higher total volume (and thereby a higher dose) than is tolerable by multiple direct IM injections. Limb perfusion has been shown to be feasible in non-human primates using the rAAV1 serotype and a ubiquitous promoter expressing an epitope-tagged AAT matched to the host species. METHODS: In this study, we performed a biodistribution and preclinical safety study in non-human primates with a clinical candidate rAAV1-human AAT (hAAT) vector at doses ranging from 3.0 × 1012 to 1.3 × 1013 vg/kg, bracketing those used in our clinical trials. RESULTS: We found that limb perfusion delivery of rAAV1-hAAT was safe and showed a biodistribution pattern similar to previous studies. However, serum levels of AAT obtained with high-dose limb perfusion still reached only ~50% of the target serum levels. CONCLUSIONS: Our results suggest that clinically effective AAT gene therapy may ultimately require delivery at doses between 3.5 × 1013-1 × 1014 vg/kg, which is within the dose range used for approved rAAV gene therapies. Muscle-targeting strategies could be incorporated when delivering systemic administration of high-dose rAAV gene therapies to increase transduction of muscle tissues and reduce the burden on the liver, especially in diseases that can present with hepatotoxicity such as AAT deficiency.

A Comparative Analysis of Oral Health and Self-Rated Health: 'All of Us Research Program' vs. 'Health and Retirement Study'.

Poor oral health can impact overall health. This study assessed the association between dental factors (dentate status and dental utilization) and self-rated health (S-RH) among older adults in two cross-sectional datasets: (1) NIH "All of Us (AoU) Research Program" (May 2018-July 2022 release) and (2) U.S. nationally representative "Health and Retirement Study" (HRS) 2018 wave. Participants aged ≥ 51 years were included in these analyses if (1) from AoU, they had clinical dental and medical data from electronic health records (EHRs) and surveys (n = 5480), and (2) from HRS, they had dental and socio-demographic survey data (n = 14,358). S-RH was dichotomized (fair/poor vs. better) and analyzed with logistic regression. Sample survey weights for HRS and stratification and averaging AoU results used the weighted HRS race-ethnicity and age distribution standardized respective analyses to the U.S. population. Fair/poor S-RH was reported by 32.6% in AoU and 28.6% in HRS. Dentate status information was available from 7.7% of AoU EHRs. In population-standardized analyses, lack of dental service use increased odds of fair/poor S-RH in AoU, OR (95% CI) = 1.28 (1.11-1.48), and in HRS = 1.45 (1.09-1.94), as did having diabetes, less education, and ever being a smoker. Having no natural teeth was not statistically associated with fair/poor S-RH. Lack of dental service was positively associated with fair/poor S-RH in both datasets. More and better oral health information in AoU and HRS are needed.

Effects of older age on contraction-induced intramyocellular acidosis and inorganic phosphate accumulation in vivo: A systematic review and meta-analysis.

Although it is clear that the bioenergetic basis of skeletal muscle fatigue (transient decrease in peak torque or power in response to contraction) involves intramyocellular acidosis (decreased pH) and accumulation of inorganic phosphate (Pi) in response to the increased energy demand of contractions, the effects of old age on the build-up of these metabolites has not been evaluated systematically. The purpose of this study was to compare pH and [Pi] in young (18-45 yr) and older (55+ yr) human skeletal muscle in vivo at the end of standardized contraction protocols. Full study details were prospectively registered on PROSPERO (CRD42022348972). PubMed, Web of Science, and SPORTDiscus databases were systematically searched and returned 12 articles that fit the inclusion criteria for the meta-analysis. Participant characteristics, contraction mode (isometric, dynamic), and final pH and [Pi] were extracted. A random-effects model was used to calculate the mean difference (MD) and 95% confidence interval (CI) for pH and [Pi] across age groups. A subgroup analysis for contraction mode was also performed. Young muscle acidified more than older muscle (MD = -0.12 pH; 95%CI = -0.18,-0.06; p<0.01). There was no overall difference by age in final [Pi] (MD = 2.14 mM; 95%CI = -0.29,4.57; p = 0.08), although sensitivity analysis revealed that removing one study resulted in greater [Pi] in young than older muscle (MD = 3.24 mM; 95%CI = 1.72,4.76; p<0.01). Contraction mode moderated these effects (p = 0.02) such that young muscle acidified (MD = -0.19 pH; 95%CI = -0.27,-0.11; p<0.01) and accumulated Pi (MD = 4.69 mM; 95%CI = 2.79,6.59; p<0.01) more than older muscle during isometric, but not dynamic, contractions. The smaller energetic perturbation in older muscle indicated by these analyses is consistent with its relatively greater use of oxidative energy production. During dynamic contractions, elimination of this greater reliance on oxidative energy production and consequently lower metabolite accumulations in older muscle may be important for understanding task-specific, age-related differences in fatigue.

Factors associated with fall risk increasing drug use in older black and white men and women: the Health ABC Study.

BACKGROUND: Most older adults use medications that may increase falls, often defined as fall risk increasing drugs or "FRIDs". Two definitions for FRIDs, the Centers for Disease Control and Prevention's (CDC) Stopping Elderly Accidents, Deaths & Injuries (STEADI-Rx) and Swedish National Board of Health and Welfare (SNBHW) definitions, are widely accepted, though include different FRIDs in their definitions. Whether factors associated with FRID use in older adults differ by definition is unknown. METHODS: We hypothesized that factors for FRID use will vary by FRID definition in 1,352 community-dwelling older Black and White adults with medication information in the Health, Aging and Body Composition Study (Health ABC; 2007-08 clinic visit; 83.4 ± 2.8 years; 54.1% women; 65.1% White). Multivariable logistic regression and multivariable negative binomial regression, progressively entering groups of covariates (demographics, lifestyle/behavior factors, and multimorbidity), modeled FRID use (yes/no) and count. RESULTS: Of 87.0% participants using SNBHW FRIDs, 82.9% used cardiac medications, with lower use of all other FRIDs (range:1.1-12.4%). Of 86.6% participants using STEADI-Rx FRIDs, 80.5% used cardiac medications, with lower use of all other FRIDs (range:1.1-16.1%). Participants with FRID use by either definition were more likely to have chronic health conditions, a hospitalization in the prior year, higher non-FRIDs medication counts, higher Center for Epidemiologic Studies Depression Scale (CES-D) scores, and less physical activity (all p < 0.05). Participants with STEADI-Rx FRID use had poorer vision and higher Modified Mini-Mental State (3MS) scores. In multivariable logistic regression for SNBHW use, hypertension, body mass index (BMI), 3MS scores, and non-FRID count were positively associated with FRID use and poorer vision and Digit Symbol Substitution Test (DSST) scores were negatively associated. In addition to SNBHW factors, higher CES-D scores were associated with STEADI-Rx FRID use. In multivariable negative binomial regression, hypertension, higher BMI, CES-D scores, and non-FRID count were associated with higher FRID count and sleep problems with lower FRID count for both definitions. Higher 3MS and lower DSST scores were associated with higher STEADI-Rx FRID count. Women had lower SNBHW FRID count after adjustments. CONCLUSIONS: Risk factors for FRID use in older adults differ slightly by STEADI-Rx and SNBHW FRIDs definition, but are largely similar.

Absolute quantitative and base-resolution sequencing reveals comprehensive landscape of pseudouridine across the human transcriptome.

Pseudouridine (Ψ) is one of the most abundant modifications in cellular RNA. However, its function remains elusive, mainly due to the lack of highly sensitive and accurate detection methods. Here, we introduced 2-bromoacrylamide-assisted cyclization sequencing (BACS), which enables Ψ-to-C transitions, for quantitative profiling of Ψ at single-base resolution. BACS allowed the precise identification of Ψ positions, especially in densely modified Ψ regions and consecutive uridine sequences. BACS detected all known Ψ sites in human rRNA and spliceosomal small nuclear RNAs and generated the quantitative Ψ map of human small nucleolar RNA and tRNA. Furthermore, BACS simultaneously detected adenosine-to-inosine editing sites and N1-methyladenosine. Depletion of pseudouridine synthases TRUB1, PUS7 and PUS1 elucidated their targets and sequence motifs. We further identified a highly abundant Ψ114 site in Epstein-Barr virus-encoded small RNA EBER2. Surprisingly, applying BACS to a panel of RNA viruses demonstrated the absence of Ψ in their viral transcripts or genomes, shedding light on differences in pseudouridylation across virus families.

Correlates of fentanyl preference among people who use drugs in Rhode Island.

BACKGROUND: Fentanyl is increasingly pervasive in the unregulated drug supply and is a driver of drug overdose deaths in the United States. The aims of this study were to characterize and identify correlates of fentanyl preference among people who use drugs (PWUD) in Rhode Island (RI). METHODS: Using bivariate analysis, we examined associations between fentanyl preference and sociodemographic and psychosocial characteristics at baseline among participants enrolled in the RI Prescription Drug and Illicit Drug Study from August 2020-February 2023. Fentanyl preference was operationalized based on responses to a five-point Likert scale: "I prefer using fentanyl or drugs that have fentanyl in them." Participants who responded that they "strongly disagree," "disagree," or were "neutral" with respect to this statement were classified as not preferring fentanyl, whereas participants who responded that they "agree" or "strongly agree" were classified as preferring fentanyl. RESULTS: Among 506 PWUD eligible for inclusion in this analysis, 15% expressed a preference for fentanyl or drugs containing fentanyl as their drug of choice. In bivariate analyses, preference for fentanyl was positively associated with younger age, white race, lifetime history of overdose, history of injection drug use, past month enrollment in a substance use treatment program, past month treatment with medications for opioid use disorder, and preferences for heroin and crystal methamphetamine (all p < 0.05). Descriptive data yielded further insight into reasons for fentanyl preference, the predominant having to do with perceived effects of the drug and desire to avoid withdrawal symptoms. CONCLUSIONS: Only a relatively small subset of study participants preferred drugs containing fentanyl. Given the increased prevalence of fentanyl contamination across substances within the unregulated drug market, the result for PWUD is increasingly less agency with respect to choice of drug; for example, people may be forced to use fentanyl due to restricted supply and the need to mitigate withdrawal symptoms, or may be using fentanyl without intending to do so. Novel and more effective interventions for PWUD, including increased access to age-appropriate harm reduction programs such as fentanyl test strips and overdose prevention centers, are needed to mitigate fentanyl-related harms.

Psychosis Risk: Time to Look Empirically at a First-step Economical-pragmatic Way to Examine Anomalous Self-experience. Exploring the SQuEASE-11.

BACKGROUND: Since the late 1990s, there has been a worldwide surge of scientific interest in the pre-psychotic phase, resulting in the introduction of several clinical tools for early detection. The predictive accuracy of these tools has been limited, motivating the need for methodological and perspectival improvements. The EASE manual supports systematic assessment of anomalous self-experience, and proposes an overall model of understanding how most psychotic experiences may be initially generated on the basis of a unifying, fundamental, pre-reflective distortion of subjectivity. STUDY DESIGN: The EASE is time-consuming, so in order to spread the use of this essential perspective of psychosis risk we selected prototypical and frequent phenomena from the EASE, combining them into SQuEASE-11. To investigate this instrument for clinical relevance, basic psychometric properties, factor structure, and relationships with gold standard instruments and the full EASE, it was administered as an interview in the STEP intervention trial (Melbourne, Australia), with 328 clinical high-risk for psychosis (CHR-P) patients. STUDY RESULTS: The SQuEASE-11 had moderate internal consistency and revealed two correlated factors. Significant relationships were observed between the SQuEASE-11 and the widely used and validated instruments CAARMS, BPRS, SANS, MADRS, DACOBS, and SOFAS. The correlation with the full EASE was very strong. CONCLUSIONS: These 11 items do not necessarily relate specifically to ipseity disturbance, but the SQuEASE-11 seems to be a clinically relevant and brief supplementary first-line interview in CHR-P subjects. It may give a qualified indication of the need for a complete EASE interview, and it may also, importantly, inform treatment planning.

Weight change, variability, and trajectories and risk of hip fracture among older adults with Dysglycemia: the cardiovascular health study.

BACKGROUND: Type 2 diabetes mellitus and lower weight are both associated with osteoporotic fractures, but the roles of variability and trajectory are less clear.1 The associations of these factors among older adults with dysglycemia, who are at highest risk of fracture, with fracture risk and bone mineral density (BMD) remains uncertain. METHODS: We followed 775 men and 1080 women from the Cardiovascular Health Study (mean age 77.4 years) with abnormal oral glucose tolerance testing in 1989-1990. We measured their weights yearly through 1994-1995 and derived intra-individual mean weight, weight slope, and weight variability. We also used growth mixture modelling to derive four latent body-mass index trajectories over time. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for subsequent hip fracture through 2015 and linear regression models to estimate cross-sectional associations with bone mineral density (BMD) of the hip. RESULTS: Each 10 kg higher mean weight was associated with a lower risk of subsequent hip fracture overall (HR 0.81; CI 0.70-0.94) and among women (HR 0.76; CI 0.64-0.91) and with higher BMD (P-value <0.001). Higher weight variability was directly associated with incident hip fracture among women (HR 1.18; CI: 1.03-1.35). Compared with a stable trajectory, a "progressive overweight" trajectory was associated with lower risk of hip fracture (HR 0.66; CI: 0.44-0.99). An uncommon trajectory of "accelerating obesity" was associated with higher BMD. CONCLUSIONS: Among older adults with dysglycemia at high risk for fracture, lower mean weight is associated with higher fracture risk, but variability and trajectory may also contribute. These results highlight the complex effects of weight in older age.

Older adults with diabetes are susceptible to falls and fractures, but how their weight affects their bone strength and fractures remains uncertain. We followed 1855 men and women age 65 years and older with abnormal glucose in The Cardiovascular Health Study and used yearly measured weights to calculate average weight, change in weight over time, and variability in weight. Higher mean weight was associated with lower risk of hip fracture and higher bone density. Weight variability was associated with higher fracture risk among older women. Using trajectories, a group that slowly gained weight over time had a lower risk of hip fracture compared to a group with stable weight.

Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.

BACKGROUND: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear. OBJECTIVE: This study evaluates the effect of consuming kumara or kumara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome. METHODS: This study is a double-blind, randomized controlled trial of mothers and their 6-month-old infants (up to n=300) who have not yet started solids. Infants are randomized into one of 3 groups: control arm (C), standard kumara intervention (K), and a kumara intervention with added banana powder product (K+) to be consumed daily for 4 months until the infant is approximately 10 months old. Infants are matched for sex using stratified randomization. Data are collected at baseline (prior to commencing solid food) and at 2 and 4 months after commencing solid food (at around 8 and 10 months of age). Data and samples collected at each timepoint include weight and length, intervention adherence (months 2 and 4), illness and medication history, dietary intake (months 2 and 4), sleep (diary and actigraphy), maternal dietary intake, breast milk, feces (baseline and 4 months), and blood samples (baseline and 4 months). RESULTS: The trial was approved by the Health and Disability Ethics Committee of the Ministry of Health, New Zealand (reference 20/NTA/9). Recruitment and data collection did not commence until January 2022 due to the COVID-19 pandemic. Data collection and analyses are expected to conclude in January 2024 and early 2025, respectively. Results are to be published in 2024 and 2025. CONCLUSIONS: The results of this study will help us understand how the introduction of a specific prebiotic complementary food affects the microbiota and relative abundances of the microbial species, the modulation of immune development, and infant health. It will contribute to the expanding body of research that aims to deepen our understanding of the connections between nutrition, gut microbiota, and early-life postnatal health. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620000026921; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378654. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56772.

Biomedical optics: illuminating paths to enhance health equity in the Philippines.

Advancements in biomedical optics have significant potential to improve healthcare in low-to-middle-income countries, where preventable and treatable diseases remain prevalent. However, limited integration of relevant sciences hinders the development and application of optical techniques to medical research. Improving the biomedical optics research landscape requires comprehensive curriculum reforms, professional development initiatives, and the establishment of appropriate research infrastructure. Additionally, effective strategies for translating research into practical healthcare solutions include securing targeted funding grants, promoting interdisciplinary collaborations, and fostering international partnerships. These efforts can bridge the gap between advanced optics research and its real-world application, enhancing healthcare outcomes in resource-constrained settings.