Variation of subclinical psychosis as a function of population density across different European settings: Findings from the multi-national EU-GEI study.

BACKGROUND: Urbanicity is a well-established risk factor for psychosis. Our recent multi-national study found an association between urbanicity and clinical psychosis in Northern Europe but not in Southern Europe. In this study, we hypothesized that the effect of current urbanicity on variation of schizotypy would be greater in North-western Europe countries than in Southern Europe ones. METHODS: We recruited 1080 individuals representative of the populations aged 18-64 of 14 different sites within 5 countries, classified as either North-western Europe (England, France, and The Netherlands) with Southern Europe (Spain and Italy). Our main outcome was schizotypy, assessed through the Structured Interview for Schizotypy-Revised. Our main exposure was current urbanicity, operationalized as local population density. A priori confounders were age, sex, ethnic minority status, childhood maltreatment, and social capital. Schizotypy variation was assessed using multi-level regression analysis. To test the differential effect of urbanicity between North-western and Southern European, we added an interaction term between population density and region of recruitment. RESULTS: Population density was associated with schizotypy (ß = 0.248,95%CI = 0.122-0.375;p < 0.001). The addition of the interaction term improved the model fit (likelihood test ratio:χ2 = 6.85; p = 0.009). The effect of urbanicity on schizotypy was substantially stronger in North-western Europe (ß = 0.620,95%CI = 0.362-0.877;p < 0.001) compared with Southern Europe (ß = 0.190,95%CI = 0.083-0.297;p = 0.001). CONCLUSIONS: The association between urbanicity and both subclinical schizotypy and clinical psychosis, rather than being universal, is context-specific. Considering that urbanization is a rapid and global process, further research is needed to disentangle the specific factors underlying this relationship.

irCLIP-RNP and Re-CLIP reveal patterns of dynamic protein associations on RNA.

RNA binding proteins ( RBPs ) control varied processes, including RNA splicing, stability, transport, and translation 1-3 . Dysfunctional RNA-RBP interactions contribute to the pathogenesis of human disease 1,4,5 , however, characterizing the nature and dynamics of multiprotein assemblies on RNA has been challenging. To address this, non-isotopic ligation-based ultraviolet crosslinking immunoprecipitation 6 was combined with mass spectrometry ( irCLIP-RNP ) to identify RNA-dependent associated proteins ( RDAPs ) co-bound to RNA with any RBP of interest. irCLIP-RNP defined landscapes of multimeric protein assemblies on RNA, uncovering previously unknown patterns of RBP-RNA associations, including cell-type-selective combinatorial relationships between RDAPs and primary RBPs. irCLIP-RNP also defined dynamic RDAP remodeling in response to epidermal growth factor ( EGF ), uncovering EGF-induced recruitment of UPF1 adjacent to HNRNPC to effect splicing surveillance of cell proliferation mRNAs. To identify the RNAs simultaneously co-bound by multiple studied RBPs, a sequential immunoprecipitation irCLIP ( Re-CLIP ) method was also developed. Re-CLIP confirmed binding relationships seen in irCLIP-RNP and detected simultaneous HNRNPC and UPF1 co-binding on RND3 and DDX3X mRNAs. irCLIP-RNP and Re-CLIP provide a framework to identify and characterize dynamic RNA-protein assemblies in living cells.

Sarcopenia in general practice: Towards improving muscle health screening, assessment and management in Australia.

BACKGROUND: An estimated one in five Australians aged 60 years and older have sarcopenia, marked by progressive and accelerated loss in muscle mass, strength and function. Sarcopenia is associated with considerable healthcare costs and a myriad of adverse health outcomes, including increased risk of death. Despite its clinical importance, muscle health is often overlooked in routine clinical practice, hindering diagnosis and treatment. OBJECTIVE: In July 2023, eight representatives from Australia's primary care and research communities convened to discuss barriers to sarcopenia screening, assessment and management within routine clinical practice. Solutions were proposed to improve the implementation of muscle health assessment and management in general practice. This article summarises the key discussions and outcomes from this meeting. DISCUSSION: Strategies to improve the implementation of muscle health assessment and management in general practice include (1) improving public awareness; (2) professional education; (3) provision of tools and resources; (4) advocacy and policy; and (5) increasing collaborative efforts between healthcare professionals, professional societies, universities, electronic medical record software vendors and the government.

Gait stability improves following unilateral total ankle arthroplasty.

End-stage ankle arthritis is often treated surgically by total ankle arthroplasty (TAA) due to its potential to improve gait through increased joint range of motion and reduce pain. However, TAA's effect on gait stability is not well understood. This study explores the impact of TAA on gait stability, measured by Margin of Stability (MoS), in 148 patients with end-stage ankle arthritis. Kinematic data were collected pre-operatively, at 1-year post-op, and at 2-years post-op and the MoS was determined at heel strike and midstance for the anteroposterior (MoSAP) and mediolateral (MoSML) directions. A linear mixed effects model including gait speed as a factor was used to assess the effects of limb, session, and their interaction on outcome measures. A significant interaction (p < 0.002) between limb (surgical, nonsurgical) and session (pre-op, 1-year post-op, 2-years post-op) was identified for each MoS variable of interest. Cumulatively, our results suggest that the nonsurgical limb, MoSAP at heel strike and MoSML at midstance improved (increased) as time from surgery increased. These results suggest patients developed a compensatory movement pattern to navigate surgical limb single support. TAA reduces this compensation improving side-to-side symmetry, while not fully restoring symmetry by 2-years post-op. These results indicate that TAA could improve gait stability in patients with end-stage ankle arthritis, but further work is needed to understand the impact of TAA on altering fall risk.

Training clinical professionals to deliver a patient centered intervention in healthcare settings.

Within the healthcare settings of the United States Department of Veterans Affairs (VA), one patient-centered intervention, Advance Care Planning via Group Visits (ACP-GV), engages veterans and those they trust in advance care planning (ACP) by facilitating a discussion that encourages participants to plan for future healthcare needs. ACP-GV is a one-hour, single session group intervention facilitated by a trained clinical professional (e.g., physician, nurse, social worker, psychologist, chaplain) and delivered in a healthcare or community-based setting. Using reporting guidelines for group-based and educational interventions, this paper aims to describe the ACP-GV Facilitator Training used to prepare clinical professionals to offer the ACP-GV intervention to participants. We provide health professional students and early career health professionals with an overview of the training and key tips for using group modalities in the clinical setting. Although the training is initially directed towards health professionals who are learning to offer ACP-GV for the first time, our tips for teaching also focus on and extend to facilitating ACP-GV directly with veterans, caregivers, and those they trust. The ACP-GV Facilitator Training is sequential in that it expects clinicians to first learn the required educational content and how to plan a group, then it engages clinicians in practicing group facilitation skills. At the conclusion of the training, clinicians are then instructed to use the training materials to transfer the information and skills they learned about ACP-GV to patients they encounter in their respective work settings. The culmination of the ACP-GV Facilitator Training is, therefore, when the clinician is able to facilitate their own group, guide discussions and activities, actively use training materials, and encourage veterans and those they trust to participate in a discussion regarding ACP in a group setting. Finally, we share key resources for publicly available and accessible online trainings to promote spread outside of VA. ACP-GV's Facilitator Training can assist healthcare professionals in implementing ACP-GV in a variety of care settings.

Severity and Number of Substances Used are Independently Associated with Antiretroviral Therapy Adherence Over Time among People with HIV in the Current Treatment Era.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.

Biomarkers of microbial translocation and generalized inflammation are associated with frailty among people with HIV.

BACKGROUND: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH. METHODS: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score. RESULTS: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up. CONCLUSIONS: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.

Association between social determinants of health and select neurosurgical procedures in the National Spina Bifida Patient Registry.

OBJECTIVE: Myelomeningocele (MMC) is a lifelong condition requiring complex multidisciplinary management. Using the National Spina Bifida Patient Registry (NSBPR), the authors tested the association between sociodemographic variables and odds of undergoing neurosurgical procedures. METHODS: The authors extracted sociodemographic, clinical, and neurosurgical procedure data on participants with MMC aged ≥ 1 year who visited an NSBPR clinic between 2009 and 2020. The zip code of the participant's residence at the time of the last spina bifida clinic visit was linked to the Distressed Communities Index (DCI) tier. Multivariate models were built to identify factors associated with undergoing CSF diversion, shunt revision, tethered cord release (TCR), and Chiari decompression. RESULTS: There were 7924 participants with a median visit age of 13 years (IQR 7-20 years); 49.1% were male, 30.2% were non-Hispanic Black or Hispanic, 54.5% had public/supplemental insurance, and 16.9% were from distressed communities. CSF diversion, shunt revision, TCR, and Chiari decompression were performed in 81.8%, 47.7%, 22.9%, and 8.7% of participants, respectively. In multivariate analyses controlling for age, sex, insurance, DCI tier, lesion level, and surgical closure timing, Hispanic individuals were less likely than their non-Hispanic White counterparts to undergo shunt revision (p = 0.013). Non-Hispanic Black and Hispanic individuals were less likely to undergo TCR (p < 0.001 each) or Chiari decompression (p < 0.001 each). Compared with privately insured individuals, publicly insured individuals were more likely to undergo CSF diversion (p = 0.031). Those in distressed communities had increased odds of undergoing CSF diversion (p = 0.004) than those in prosperous communities. CONCLUSIONS: Among individuals with MMC participating in the NSBPR, there were differences in receiving neurosurgical procedures by race/ethnicity, insurance type, and DCI tier. Additional prospective studies are necessary to elucidate the reasons for these variations and their impact on long-term outcomes for this patient population in order to created targeted interventions.

Multimorbidity and the risk of malnutrition, frailty and sarcopenia in adults with cancer in the UK Biobank.

BACKGROUND: Malnutrition, sarcopenia and frailty are distinct, albeit interrelated, conditions associated with adverse outcomes in adults with cancer, but whether they relate to multimorbidity, which affects up to 90% of people with cancer, is unknown. This study investigated the relationship between multimorbidity with malnutrition, sarcopenia and frailty in adults with cancer from the UK Biobank. METHODS: This was a cross-sectional study including 4122 adults with cancer (mean [SD] age 59.8 [7.1] years, 50.7% female). Malnutrition was determined using the Global Leadership Initiative on Malnutrition criteria. Probable sarcopenia and sarcopenia were defined using the European Working Group on Sarcopenia in Older People 2 criteria. (Pre-)frailty was determined using the Fried frailty criteria. Multimorbidity was defined as ≥2 long-term conditions with and without the cancer diagnosis included. Logistic regression models were fitted to estimate the odds ratios (ORs) of malnutrition, sarcopenia and frailty according to the presence of multimorbidity. RESULTS: Genitourinary (28.9%) and breast (26.1%) cancers were the most common cancer diagnoses. The prevalence of malnutrition, (probable-)sarcopenia and (pre-)frailty was 11.1%, 6.9% and 51.2%, respectively. Of the 11.1% of participants with malnutrition, the majority (9%) also had (pre-)frailty, and 1.1% also had (probable-)sarcopenia. Of the 51.2% of participants with (pre-)frailty, 6.8% also had (probable-)sarcopenia. No participants had (probable-)sarcopenia alone, and 1.1% had malnutrition, (probable-)sarcopenia plus (pre-)frailty. In total, 33% and 65% of participants had multimorbidity, including and excluding the cancer diagnosis, respectively. The most common long-term conditions, excluding the cancer diagnosis, were hypertension (32.5%), painful conditions such as osteoarthritis or sciatica (17.6%) and asthma (10.4%). Overall, 80% of malnourished, 74% of (probable-)sarcopenia and 71.5% of (pre-)frail participants had multimorbidity. Participants with multimorbidity, including the cancer diagnosis, had higher odds of malnutrition (OR 1.72 [95% confidence interval, CI, 1.31-2.30; P < 0.0005]) and (pre-)frailty (OR 1.43 [95% CI 1.24-1.68; P < 0.0005]). The odds increased further in people with ≥2 long-term conditions in addition to their cancer diagnosis (malnutrition, OR 2.41 [95% CI 1.85-3.14; P < 0.0005]; (pre-)frailty, OR 2.03 [95% CI 1.73-2.38; P < 0.0005]). There was little evidence of an association of multimorbidity with sarcopenia. CONCLUSIONS: In adults with cancer, multimorbidity was associated with increased odds of having malnutrition and (pre-)frailty but not (probable-)sarcopenia. This highlights that multimorbidity should be considered a risk factor for these conditions and evaluated during nutrition and functional screening and assessment to support risk stratification within clinical practice.

Analysis of Limb Loading and Lower Extremity Strength Recovery Across Time After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Evidence as to how patient thigh muscle strength and limb loading (LL) during a squatting task recovers throughout rehabilitation after anterior cruciate ligament reconstruction (ACLR) is lacking. HYPOTHESIS: Patients will improve LL and strength throughout rehabilitation. Changes in LL and strength over time will be positively correlated. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 60 participants (28 male/32 female; age, 22.5 ± 9.35 years) participated in 2 visits post-ACLR, assessing LL and strength. Using an instrumented pressure mat, patients completed 3 sets of 3 repetitions of bodyweight squats. Peak force (N), unilateral cumulative load (%), and quadriceps and hamstring isokinetic peak torque (N·m) were calculated and recorded bilaterally. LL and peak torque were compared over time and between limbs. RESULTS: A significant limb-by-time interaction was observed for LL peak force (N), where patients underloaded the ACLR limb at visit 1 compared with the contralateral limb (P < 0.01). Patients increased their ACLR LL across visits (P = 0.04). A limb-by-time interaction for quadriceps peak torque (N·m) was observed where the ACLR limb increased peak torque across visits (P < 0.01); however, strength deficits persisted at visit 2 (P < 0.01) when compared with the nonoperative limb. Weak correlations were observed between all change scores metrics (r, 0.20-0.25). CONCLUSION: Patients recovering from ACLR exhibited more symmetric loading during a squatting task and improved their lower extremity strength over time. Changes in strength were not related to changes in LL during a squatting task over time. CLINICAL RELEVANCE: Squatting tasks are safe and easily implemented throughout ACLR recovery. As changes in functional LL and strength recovery are not related, both should be considered in serial postoperative testing for more comprehensive function and strength assessments.

The Bidirectional Effects of Periodontal Disease and Oral Dysbiosis on Gut Inflammation in Inflammatory Bowel Disease.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) flares can lead to excessive morbidity and mortality. This study aimed to determine whether oral dysbiosis/periodontal disease (PD) is common in IBD and is associated with disease activity in IBD. METHODS: This single-center, prospective, cross-sectional, proof-of-concept, observational study assessed the frequency of periodontal inflammatory disease and interrogated oral and stool microbiota using 16S rRNA gene amplicon sequencing of active-IBD (aIBD), inactive-IBD (iIBD), and healthy controls (HC). Questionnaires assessed diet, alcohol usage, oral hygiene behavior, and disease activity. A subset of participants underwent comprehensive dental examinations to evaluate PD. RESULTS: PD was severer in aIBD subjects than in HC, as aIBD had poorer quality diets (lower Mediterranean diet scores) than iIBD and HC. Significant differences in microbial community structure were observed in unstimulated saliva, stimulated saliva, gingiva, and stool samples, primarily between aIBD and HC. Saliva from aIBD had higher relative abundances of putative oral pathobionts from the genera Streptococcus, Granulicatella, Rothia, and Actinomyces relative to HC, despite similar oral hygiene behaviors between groups. CONCLUSION: Our study suggests that patients with aIBD have severer periodontal disorders and higher relative abundances of putative "pro-inflammatory" microbiota in their oral cavity, despite normal oral hygiene behaviors. Our data are consistent with the potential presence of an oral-gut inflammatory-axis that could trigger IBD flare-ups in at-risk patients. Routine dental health assessments in all IBD patients should be encouraged as part of the health maintenance of IBD and as a potential strategy to decrease the risk of IBD flares.

Research Priorities of the Oncology Nursing Society: 2024-2027.

PROBLEM STATEMENT: To define the Oncology Nursing Society Research Agenda for 2024-2027. DESIGN: An iterative, multiple data sources consolidation through the Research Agenda Project Team. DATA SOURCES: Previous research priorities, literature review, stakeholder survey, and research priorities from other cancer care organizations and funding agencies. FINDINGS: 10 evergreen statements articulated foundational values for oncology nurse scientists, and 5 topics emerged as research priorities for the upcoming three years: Advance patient-centric, precision symptom science; provide evidence for safe and effective cancer care delivery models and support of the oncology nursing workforce; describe the impact of the environment on cancer care outcomes; integrate patient navigation into cancer care across the trajectory; and advance the use of innovative methodologies in oncology nursing research. IMPLICATIONS FOR NURSING: The Oncology Nursing Society Research Agenda is an effective resource for directing the organization's research vision. This foundational document directs funding awards and requests, mentorship, and policy initiatives.

The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis.

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (ß = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (ß = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (ß = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (ß = -0.34, 95% CI = [-0.660, -0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.

Associations of psychotic symptom dimensions with clinical and developmental variables in twin and general clinical samples.

BACKGROUND: Positive, negative and disorganised psychotic symptom dimensions are associated with clinical and developmental variables, but differing definitions complicate interpretation. Additionally, some variables have had little investigation. AIMS: To investigate associations of psychotic symptom dimensions with clinical and developmental variables, and familial aggregation of symptom dimensions, in multiple samples employing the same definitions. METHOD: We investigated associations between lifetime symptom dimensions and clinical and developmental variables in two twin and two general psychosis samples. Dimension symptom scores and most other variables were from the Operational Criteria Checklist. We used logistic regression in generalised linear mixed models for combined sample analysis (n = 875 probands). We also investigated correlations of dimensions within monozygotic (MZ) twin pairs concordant for psychosis (n = 96 pairs). RESULTS: Higher symptom scores on all three dimensions were associated with poor premorbid social adjustment, never marrying/cohabiting and earlier age at onset, and with a chronic course, most strongly for the negative dimension. The positive dimension was also associated with Black and minority ethnicity and lifetime cannabis use; the negative dimension with male gender; and the disorganised dimension with gradual onset, lower premorbid IQ and substantial within twin-pair correlation. In secondary analysis, disorganised symptoms in MZ twin probands were associated with lower premorbid IQ in their co-twins. CONCLUSIONS: These results confirm associations that dimensions share in common and strengthen the evidence for distinct associations of co-occurring positive symptoms with ethnic minority status, negative symptoms with male gender and disorganised symptoms with substantial familial influences, which may overlap with influences on premorbid IQ.

Understanding the impact of pandemics on long-term medication adherence: directly observed therapy in a tuberculosis treatment cohort pre- and post-COVID-19 lockdowns.

BACKGROUND: The COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa. METHODS: We analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered 'pre-COVID-19' and those enrolled after September 2020 were considered 'post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown. RESULTS: DOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04-1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17-2.67; p = 0.006). CONCLUSION: The COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

Impact of provision of abdominal aortic calcification results on fruit and vegetable intake: 12-week randomized phase 2 controlled trial.

Provision of non-invasive vascular imaging results to individuals has been shown to improve cardiovascular disease risk factor control: its impact on diet remains uncertain. In this two-arm, single-blind, parallel, 12-week randomized controlled trial, 240 participants, 57.5% females aged 60-80 y had abdominal aortic calcification and clinical assessments performed at a hospital clinic. Participants were randomized 1:1 to receive (intervention n = 121) or not (control n = 119) their calcification results. Both groups received educational resources on cardiovascular disease risk control and were unblinded to the intervention. Outcome measures were performed at baseline and 12 weeks. The primary outcomes of the study were changes in fruit and vegetable intake measures over 12 weeks assessed using plasma carotenoid concentrations (biomarkers of FV intake) and a food frequency questionnaire. Secondary outcomes included 12-week changes in other aspects of the diet, physical activity, body weight, blood pressure, heart rate, lipid profile, glucose concentrations, estimated cardiovascular disease risk score, and medication use. Between-group differences were tested using linear mixed-effects regression. There were no between-group differences in the primary outcomes at 12 weeks: plasma carotenoids (mean difference +0.03 µg/mL [95%CI -0.06, 0.13]) and fruit and vegetable intakes (+18 g/d [-37, 72]). However, the provision of calcification results led to between-group differences in serum total (-0.22 mmol/L [-0.41, -0.04]) and non-HDL (-0.19 mmol/L [-0.35, -0.03]) cholesterol, and estimated cardiovascular disease risk score (-0.24% [-0.47, -0.02]). No between-group differences were seen for other secondary outcomes. In this work, providing vascular imaging results did not improve diet but did improve some cardiovascular disease risk factors (Australian and New Zealand Clinical Trials Registry ACTRN12618001087246).

Subtracting the background by reducing cell-free DNA's confounding effects on Mycobacterium tuberculosis quantitation and the sputum microbiome.

DNA characterisation in people with tuberculosis (TB) is critical for diagnostic and microbiome evaluations. However, extracellular DNA, more frequent in people on chemotherapy, confounds results. We evaluated whether nucleic acid dyes [propidium monoazide (PMA), PEMAX] and DNaseI could reduce this. PCR [16S Mycobacterium tuberculosis complex (Mtb) qPCR, Xpert MTB/RIF] was done on dilution series of untreated and treated (PMA, PEMAX, DNaseI) Mtb. Separately, 16S rRNA gene qPCR and sequencing were done on untreated and treated sputa before (Cohort A: 11 TB-negatives, 9 TB-positives; Cohort B: 19 TB-positives, PEMAX only) and 24-weeks after chemotherapy (Cohort B). PMA and PEMAX reduced PCR-detected Mtb DNA for dilution series and Cohort A sputum versus untreated controls, suggesting non-intact Mtb is present before treatment-start. PEMAX enabled sequencing-based Mycobacterium-detection in 7/12 (58%) TB-positive sputa where no such reads otherwise occurred. In Cohort A, PMA- and PEMAX-treated versus untreated sputa had decreased α- and increased ß-diversities. In Cohort B, ß-diversity differences between timepoints were only detected with PEMAX. DNaseI had negligible effects. PMA and PEMAX (but not DNaseI) reduced extracellular DNA in PCR and improved pathogen detection by sequencing. PEMAX additionally detected chemotherapy-associated taxonomic changes that would otherwise be missed. Dyes enhance microbiome evaluations especially during chemotherapy.

Functionally redundant roles of ID family proteins in spermatogonial stem cells.

Spermatogonial stem cells (SSCs) are essential for sustained sperm production, but SSC regulatory mechanisms and markers remain poorly defined. Studies have suggested that the Id family transcriptional regulator Id4 is expressed in SSCs and involved in SSC maintenance. Here, we used reporter and knockout models to define the expression and function of Id4 in the adult male germline. Within the spermatogonial pool, Id4 reporter expression and inhibitor of DNA-binding 4 (ID4) protein are found throughout the GFRα1+ fraction, comprising the self-renewing population. However, Id4 deletion is tolerated by adult SSCs while revealing roles in meiotic spermatocytes. Cultures of undifferentiated spermatogonia could be established following Id4 deletion. Importantly, ID4 loss in undifferentiated spermatogonia triggers ID3 upregulation, and both ID proteins associate with transcription factor partner TCF3 in wild-type cells. Combined inhibition of IDs in cultured spermatogonia disrupts the stem cell state and blocks proliferation. Our data therefore demonstrate critical but functionally redundant roles of IDs in SSC function.