'What is my risk really?': a qualitative exploration of preventive interventions among individuals at risk of rheumatoid arthritis.

Objectives: Intervention in the pre-arthritis phase of RA could prevent or delay the onset of disease. The primary aim of this study was to explore perspectives of being at risk and potential preventive interventions among individuals at risk of developing RA and to identify factors influencing their engagement with prevention. A secondary aim, established during the analytical process, was to understand and compare different approaches to health-related behaviours related to prevention of RA. Methods: Anti-CCP-positive (CCP+) at-risk individuals with musculoskeletal symptoms but no synovitis participated in semi-structured interviews. Data were analysed using reflexive thematic analysis, followed by a secondary ideal-type analysis. Results: Nineteen CCP+ at-risk individuals (10 women; age range 35-70 years) participated. Three overarching themes were identified: being CCP+ at risk; aiming to prevent RA; and influencers of engagement. Participants described distress related to symptoms and uncertainty about disease progression. Many participants had concerns about medication side effects. In contrast, most participants expressed willingness to make lifestyle changes with the aim of preventing RA. Engagement with preventive measures was influenced by symptom severity, personal risk level, co-morbidities, experiences of taking other medications/supplements, knowledge of RA, risk factors and medications, and perceived effort. Three types of participants were identified from the data: proactive preventers, change considerers and fearful avoiders. Overall orientation to health behaviours also impacted the attitude towards preventing RA. Conclusion: Findings could inform recruitment and retention in RA prevention research and promote uptake of preventive interventions in clinical practice.

Non-Gaussian Displacements in Active Transport on a Carpet of Motile Cells.

We study the dynamics of micron-sized particles on a layer of motile cells. This cell carpet acts as an active bath that propels passive tracer particles via direct mechanical contact. The resulting nonequilibrium transport shows a crossover from superdiffusive to normal-diffusive dynamics. The particle displacement distribution is distinctly non-Gaussian even at macroscopic timescales exceeding the measurement time. We obtain the distribution of diffusion coefficients from the experimental data and introduce a model for the displacement distribution that matches the experimentally observed non-Gaussian statistics. We argue why similar transport properties are expected for many composite active matter systems.

Isochrony in barks of Cape fur seal (Arctocephalus pusillus pusillus) pups and adults.

Animal vocal communication often relies on call sequences. The temporal patterns of such sequences can be adjusted to other callers, follow complex rhythmic structures or exhibit a metronome-like pattern (i.e., isochronous). How regular are the temporal patterns in animal signals, and what influences their precision? If present, are rhythms already there early in ontogeny? Here, we describe an exploratory study of Cape fur seal (Arctocephalus pusillus pusillus) barks-a vocalisation type produced across many pinniped species in rhythmic, percussive bouts. This study is the first quantitative description of barking in Cape fur seal pups. We analysed the rhythmic structures of spontaneous barking bouts of pups and adult females from the breeding colony in Cape Cross, Namibia. Barks of adult females exhibited isochrony, that is they were produced at fairly regular points in time. Instead, intervals between pup barks were more variable, that is skipping a bark in the isochronous series occasionally. In both age classes, beat precision, that is how well the barks followed a perfect template, was worse when barking at higher rates. Differences could be explained by physiological factors, such as respiration or arousal. Whether, and how, isochrony develops in this species remains an open question. This study provides evidence towards a rhythmic production of barks in Cape fur seal pups and lays the groundwork for future studies to investigate the development of rhythm using multidimensional metrics.

Bacterial Diversity in Old Hydrocarbon Polluted Sediments of Ecuadorian Amazon River Basins.

The Ecuadorian Amazon rainforest stands out as one of the world's most biodiverse regions, yet faces significant threats due to oil extraction activities dating back to the 1970s in the northeastern provinces. This research investigates the environmental and societal consequences of prolonged petroleum exploitation and oil spills in Ecuador's Amazon. Conducted in June 2015, the study involved a comprehensive analysis of freshwater sediment samples from 24 locations in the Rio Aguarico and Napo basins. Parameters such as water and air temperature, conductivity, soil pH, and hydrocarbon concentrations were examined. Total petroleum hydrocarbon (TPH) concentrations ranged from 9.4 to 847.4 mg kg-1, with polycyclic aromatic hydrocarbon (PAH) levels varying from 10.15 to 711.1 mg kg-1. The pristane/phytane ratio indicated historic hydrocarbon pollution in 8 of the 15 chemically analyzed sediments. Using non-culturable techniques (Illumina), bacterial analyses identified over 350 ASV, with prominent families including Comamonadaceae, Chitinophagaceae, Anaeromyxobacteraceae, Sphingomonadaceae, and Xanthobacteraceae. Bacterial diversity, assessed in eight samples, exhibited a positive correlation with PAH concentrations. The study provides insights into how microbial communities respond to varying levels of hydrocarbon pollution, shedding light on the enduring impact of oil exploitation in the Amazonian region. Its objective is to deepen our understanding of the environmental and human well-being in the affected area, underscoring the pressing need for remedial actions in the face of ongoing ecological challenges.

The Natural History and Risk Factors for the Development of Food Allergies in Children and Adults.

PURPOSE OF REVIEW: This narrative review explores food allergy prevalence and natural history stratified by life stages, especially in context of evolving knowledge over the last few decades. RECENT FINDINGS: The prevalence of food allergy remains highest in early childhood with common food triggers being cow's milk, soy, hen's egg, wheat, peanut, tree nuts, sesame, fish, and shellfish. This correlates with certain risk factors especially pertinent in the postnatal period which appear to predispose an individual to developing a food allergy. Some allergies (such as milk and egg) were previously thought to be easily outgrown in early life; however, recent studies suggest increasing rates of persistence of these allergies into young adulthood; the reason behind this is unknown. Despite this, there is also evidence demonstrating that food allergies can be outgrown in adolescents and adults. An understanding of the paradigm shifts in the natural history of food allergy allows clinicians to provide updated, age-appropriate, and tailored advice for patients on the management and prognosis of food allergy.

Patients' perspectives on systemic sclerosis-related Raynaud's phenomenon in the feet: A qualitative study from the OMERACT Foot and Ankle Working Group.

OBJECTIVE: To explore, from patients' perspectives, the symptoms and impact of Raynaud's phenomenon (RP) on the feet of patients with systemic sclerosis (SSc-RP), and to identify which foot-related domains are important to patients. METHODS: Forty participants (34 women) with SSc-RP took part in one of six focus groups held in the United Kingdom or United States. Participants were purposively sampled to ensure diversity in disease type, duration, and ethnicity. The topic guide included questions on RP impact, self-management, and treatment expectations. Qualitative content analysis was employed to identify key concepts in the data relating to foot-specific symptoms and their impact. Themes were organized by corresponding domains of potential importance. RESULTS: Twenty-eight participants (70 %) reported experiencing RP in their feet. Five themes were identified corresponding to domains of potential importance: temperature changes, pain, cramping and stiffness, numbness, and color changes. These issues negatively affected participants' lives, impairing walking, driving, and socializing, and causing issues with footwear and hosiery. CONCLUSIONS: This large qualitative study exploring the experiences of patients with SSc-RP in the feet identified several key domains of high importance to patients. SSc-RP is common in the feet, presents in several patterns, and impacts multiple aspects of patients' lives. These findings indicate where future foot-specific interventions for RP could be targeted. Findings from this study improve understanding of what domains are important to patients with SSc-RP affecting the feet and will contribute to the development of a core outcome set for foot and ankle disorders in rheumatic and musculoskeletal diseases.

Evolving and evaluating the OMERACT fellows program: insights and implications from OMERACT 2023 fellows.

OBJECTIVE: To describe the evolution of the OMERACT Fellows Program (OM FP) and to evaluate the innovative changes implemented in the 2023 program. METHODS: The OM FP, the first of its kind in global rheumatology, was developed in 2000 to mentor early career researchers in methods and processes for reaching evidence-driven consensus for outcome measures in clinical studies. The OM FP has evolved through continuing iterations of face to face and online feedback. Key new features delivered in 2023 included e-learning modules, virtual introductory pre-meetings, increased networking with Patient Research Partners (PRPs), learning opportunities to give and receive personal feedback, ongoing performance feedback during the meeting from Fellow peers, PRPs, senior OMERACTers (members of the OMERACT community) and Emerging Leader mentors, involvement in pitching promotions, two-minute Lightning Talks in a plenary session and an embedded poster tour. An online survey was distributed after the meeting to evaluate the program. RESULTS: OM FP has included 208 fellows from 16 countries across 4 continents covering 47 different aspects of rheumatology outcomes since its inception. Over 50 % have remained engaged with OMERACT work. In 2023, 18 Fellows attended and 15 (83 %) completed the post-meeting survey. A dedicated OM FP was deemed important by all respondents, and 93 % would attend the meeting in future. The PRP/Fellow Connection Carousel and Lightning Talks were rated exceptional by 93 %. Key components to improve included clarification of expectations, overall workload, the Emerging Leaders Mentoring Program, and the content and duration of daily summary sessions. CONCLUSION: The innovations in the 2023 OM FP were well received by the majority of participants and supports early career rheumatology researchers to develop collaborations, skills and expertise in outcome measurement. Implementation of feedback from Fellows will enhance the program for future meetings, continuing to facilitate learning and succession planning within OMERACT.

ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97.

The t(X,17) chromosomal translocation, generating the ASPSCR1::TFE3 fusion oncoprotein, is the singular genetic driver of alveolar soft part sarcoma (ASPS) and some Xp11-rearranged renal cell carcinomas (RCCs), frustrating efforts to identify therapeutic targets for these rare cancers. Here, proteomic analysis identifies VCP/p97, an AAA+ ATPase with known segregase function, as strongly enriched in co-immunoprecipitated nuclear complexes with ASPSCR1::TFE3. We demonstrate that VCP is a likely obligate co-factor of ASPSCR1::TFE3, one of the only such fusion oncoprotein co-factors identified in cancer biology. Specifically, VCP co-distributes with ASPSCR1::TFE3 across chromatin in association with enhancers genome-wide. VCP presence, its hexameric assembly, and its enzymatic function orchestrate the oncogenic transcriptional signature of ASPSCR1::TFE3, by facilitating assembly of higher-order chromatin conformation structures demonstrated by HiChIP. Finally, ASPSCR1::TFE3 and VCP demonstrate co-dependence for cancer cell proliferation and tumorigenesis in vitro and in ASPS and RCC mouse models, underscoring VCP's potential as a novel therapeutic target.

The multispecies microbial cluster of Fusobacterium, Parvimonas, Bacteroides and Faecalibacterium as a precision biomarker for colorectal cancer diagnosis.

The incidence of colorectal cancer (CRC) has increased worldwide, and early diagnosis is crucial to reduce mortality rates. Therefore, new noninvasive biomarkers for CRC are required. Recent studies have revealed an imbalance in the oral and gut microbiomes of patients with CRC, as well as impaired gut vascular barrier function. In the present study, the microbiomes of saliva, crevicular fluid, feces, and non-neoplastic and tumor intestinal tissue samples of 93 CRC patients and 30 healthy individuals without digestive disorders (non-CRC) were analyzed by 16S rRNA metabarcoding procedures. The data revealed that Parvimonas, Fusobacterium, and Bacteroides fragilis were significantly over-represented in stool samples of CRC patients, whereas Faecalibacterium and Blautia were significantly over-abundant in the non-CRC group. Moreover, the tumor samples were enriched in well-known periodontal anaerobes, including Fusobacterium, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella. Co-occurrence patterns of these oral microorganisms were observed in the subgingival pocket and in the tumor tissues of CRC patients, where they also correlated with other gut microbes, such as Hungatella. This study provides new evidence that oral pathobionts, normally located in subgingival pockets, can migrate to the colon and probably aggregate with aerobic bacteria, forming synergistic consortia. Furthermore, we suggest that the group composed of Fusobacterium, Parvimonas, Bacteroides, and Faecalibacterium could be used to design an excellent noninvasive fecal test for the early diagnosis of CRC. The combination of these four genera would significantly improve the reliability of a discriminatory test with respect to others that use a single species as a unique CRC biomarker.

Overlay databank unlocks data-driven analyses of biomolecules for all.

Tools based on artificial intelligence (AI) are currently revolutionising many fields, yet their applications are often limited by the lack of suitable training data in programmatically accessible format. Here we propose an effective solution to make data scattered in various locations and formats accessible for data-driven and machine learning applications using the overlay databank format. To demonstrate the practical relevance of such approach, we present the NMRlipids Databank-a community-driven, open-for-all database featuring programmatic access to quality-evaluated atom-resolution molecular dynamics simulations of cellular membranes. Cellular membrane lipid composition is implicated in diseases and controls major biological functions, but membranes are difficult to study experimentally due to their intrinsic disorder and complex phase behaviour. While MD simulations have been useful in understanding membrane systems, they require significant computational resources and often suffer from inaccuracies in model parameters. Here, we demonstrate how programmable interface for flexible implementation of data-driven and machine learning applications, and rapid access to simulation data through a graphical user interface, unlock possibilities beyond current MD simulation and experimental studies to understand cellular membranes. The proposed overlay databank concept can be further applied to other biomolecules, as well as in other fields where similar barriers hinder the AI revolution.

Rhythmic properties of Sciaena umbra calls across space and time in the Mediterranean Sea.

In animals, the rhythmical properties of calls are known to be shaped by physical constraints and the necessity of conveying information. As a consequence, investigating rhythmical properties in relation to different environmental conditions can help to shed light on the relationship between environment and species behavior from an evolutionary perspective. Sciaena umbra (fam. Sciaenidae) male fish emit reproductive calls characterized by a simple isochronous, i.e., metronome-like rhythm (the so-called R-pattern). Here, S. umbra R-pattern rhythm properties were assessed and compared between four different sites located along the Mediterranean basin (Mallorca, Venice, Trieste, Crete); furthermore, for one location, two datasets collected 10 years apart were available. Recording sites differed in habitat types, vessel density and acoustic richness; despite this, S. umbra R-calls were isochronous across all locations. A degree of variability was found only when considering the beat frequency, which was temporally stable, but spatially variable, with the beat frequency being faster in one of the sites (Venice). Statistically, the beat frequency was found to be dependent on the season (i.e. month of recording) and potentially influenced by the presence of soniferous competitors and human-generated underwater noise. Overall, the general consistency in the measured rhythmical properties (isochrony and beat frequency) suggests their nature as a fitness-related trait in the context of the S. umbra reproductive behavior and calls for further evaluation as a communicative cue.

A Multivariate Probit Regression of the Uptake of Adolescent Vaccines Among Racial/Ethnic Minority Adolescents Before and During the COVID-19 Pandemic.

PURPOSE: The uptake of adolescent vaccines has improved over the years. However, research of the effects of the COVID-19 pandemic on this uptake among racial/ethnic minority adolescents has been limited. This study was conducted to compare the probability of uptake of the human papillomavirus (HPV); tetanus, diphtheria, and acellular pertussis (Tdap); and quadrivalent meningococcal conjugate (MenACWY) vaccines among racial/ethnic minority adolescents ages 13-17 years in 2019, 2020, and 2021. METHODS: Using a cross-sectional design to examine data from the National Immunization Survey-Teen (2019-2021), multivariate probit regression was used to model variation in uptake of these three adolescent vaccines (n = 38,128). The outcome measures were HPV, Tdap, and MenACWY vaccine uptake. RESULTS: The probability of uptake of HPV vaccine was higher in 2020 (Coef = 0.09 [95% confidence interval (CI), 0.03-0.16]) and 2021 (Coef = 0.07 [95% CI, 0.00-0.15]) than in 2019. The probability of uptake of MenACWY vaccine was higher in 2020 (Coef = 0.08 [95% CI, 0.02-0.15]) than in 2019. The probability of uptake of recommended vaccines varied among racial/ethnic minorities with non-Hispanic Black adolescents exhibiting higher probability of uptake of HPV vaccine (Coef = 0.10 [95% CI, 0.01-0.19]) than Tdap vaccine. U.S. Census region and insurance status were associated with the uptake of all recommended vaccines. DISCUSSION: Progress in the uptake of these recommended vaccines may not have been interrupted by the COVID-19 pandemic. Also, disparities in uptake of the recommended vaccines still exist despite increased uptake during the pandemic. Future research should examine the disparities as well as examine regional differences in the uptake of these three adolescent vaccines.

Normative tDCS over V5 and FEF reveals practice-induced modulation of extraretinal smooth pursuit mechanisms, but no specific stimulation effect.

The neural networks subserving smooth pursuit eye movements (SPEM) provide an ideal model for investigating the interaction of sensory processing and motor control during ongoing movements. To better understand core plasticity aspects of sensorimotor processing for SPEM, normative sham, anodal or cathodal transcranial direct current stimulation (tDCS) was applied over visual area V5 and frontal eye fields (FEF) in sixty healthy participants. The identical within-subject paradigm was used to assess SPEM modulations by practice. While no specific tDCS effects were revealed, within- and between-session practice effects indicate plasticity of top-down extraretinal mechanisms that mainly affect SPEM in the absence of visual input and during SPEM initiation. To explore the potential of tDCS effects, individual electric field simulations were computed based on calibrated finite element head models and individual functional localization of V5 and FEF location (using functional MRI) and orientation (using combined EEG/MEG) was conducted. Simulations revealed only limited electric field target intensities induced by the applied normative tDCS montages but indicate the potential efficacy of personalized tDCS for the modulation of SPEM. In sum, results indicate the potential susceptibility of extraretinal SPEM control to targeted external neuromodulation (e.g., personalized tDCS) and intrinsic learning protocols.

Desire for Body Contouring Surgery after Bariatric Surgery: A Nationwide Cross-sectional Study in Saudi Arabia.

Background: The obesity pandemic in Saudi Arabia has led to a high demand for bariatric surgery (BS). Post-BS patients experience rapid and massive weight loss, with most patients experiencing redundant skin, leading to a desire for body contouring surgery (BCS). Methods: A cross-sectional study was conducted from September 2022 to May 2023 among patients who underwent BS in Saudi Arabia, using an online self-administered questionnaire. The questionnaire comprised sociodemographic data, weight, and BS-related questions, and the post-BS appearance questionnaire assessed the desire for BCS, excess skin satisfaction, and overall appearance. Results: A total of 410 of the patients electively enrolled. The mean perceived satisfaction of post-BS patients with the body's excess skin was rated as 4.28 ±â€…1.69 out of 7 points. The overall desire for BCS among the post-BS population was equal to a collective mean desire of 2.10 ±â€…0.92 out of 4 points. The desired body sites for BCS were focused on the abdomen/waist, followed by the lower back, then upper arms, buttocks, and thighs. Only 25.1% of the patients fulfilled their desires and recently underwent BCS. Conclusions: The study highlights the importance of incorporating plastic and reconstructive surgery as an integral part of the multidisciplinary approach to morbidly obese patients after BS and the need for national guidelines on the referral pathway for post-BS BCS.

Internet-based interdisciplinary therapeutic group (Grupo Interdisciplinar Online, GIO) for perinatal anxiety and depression-a randomized pilot study during COVID-19.

Early interventions may promote reductions in mothers' anxiety-depression (AD) symptoms and improvements in their offspring. This longitudinal randomized research was conducted to assess the effects of interdisciplinary online therapeutic groups (GIO) in at-risk mothers and babies during the COVID-19 pandemic in a disadvantaged neighborhood in Barcelona (Spain). A total of 135 babies were born from March 2020 to June 2021 in a primary healthcare center of Barcelona (Spain). Pregnant woman and new mothers were screened for AD symptomatology through EPDS and STAI questionnaires. Seventy-two of them met high-risk criteria for AD and were included in the study. They were randomly assigned into the two groups of the study: 40 participants were assigned to GIO, the therapeutic group (TG), while 32 of them were assigned to the control group (CG) and received treatment as usual. The course of the mothers' symptomatology was assessed, as well as the baby's development at 6 months old in a blind pediatric follow-up. No differences were found in AD between both groups before the intervention. However, we obtained a significant decrease in AD symptomatology (EPDS p < .001; STAI state p = .015 and STAI trait p < .001at 6 months of life) after the intervention in the TG compared to the CG. Pediatric follow-up at 6 months demonstrated significant differences between groups in babies' development assessment (manipulation p = .003; language p < .001; sociability p < .001). The GIO helped to ensure healthy development of the baby and reduction of the mothers' depressive-anxiety symptomatology.

Potential roles of FGF5 as a candidate therapeutic target in prostate cancer.

Fibroblast growth factor (FGF) is a secreted ligand that is widely expressed in embryonic tissues but its expression decreases with age. In the developing prostate, FGF5 has been proposed to interact with the Hedgehog (Hh) signaling pathway to guide mitogenic processes. In the adult prostate, the FGF/FGFR signaling axis has been implicated in prostate carcinogenesis, but focused studies on FGF5 functions in the prostate are limited. Functional studies completed in other cancer models point towards FGF5 overexpression as an oncogenic driver associated with stemness, metastatic potential, proliferative capacity, and increased tumor grade. In this review, we explore the significance of FGF5 as a therapeutic target in prostate cancer (PCa) and other malignancies; and we introduce a potential route of investigation to link FGF5 to benign prostatic hyperplasia (BPH). PCa and BPH are two primary contributors to the disease burden of the aging male population and have severe implications on quality of life, psychological wellbeing, and survival. The development of new FGF5 inhibitors could potentially alleviate the health burden of PCa and BPH in the aging male population.

Critical Velocity, Maximal Lactate Steady State, and Muscle MCT1 and MCT4 after Exhaustive Running in Mice.

Although the critical velocity (CV) protocol has been used to determine the aerobic capacity in rodents, there is a lack of studies that compare CV with maximal lactate steady state intensity (iMLSS) in mice. As a consequence, their physiological and molecular responses after exercise until exhaustion at CV intensity remain unclear. Thus, we aimed to compare and correlate CV with iMLSS in running mice, following different mathematical models for CV estimation. We also evaluated their physiological responses and muscle MCT1 and MCT4 after running until exhaustion at CV. Thirty C57BL/6J mice were divided into two groups (exercised-E and control-C). Group E was submitted to a CV protocol (4 days), using linear (lin1 and lin2) and hyperbolic (hyp) mathematical models to determine the distance, velocity, and time to exhaustion (tlim) of each predictive CV trial, followed by an MLSS protocol. After a running effort until exhaustion at CV intensity, the mice were immediately euthanized, while group C was euthanized at rest. No differences were observed between iMLSS (21.1 ± 1.1 m.min-1) and CV estimated by lin1 (21.0 ± 0.9 m.min-1, p = 0.415), lin2 (21.3 ± 0.9 m.min-1, p = 0.209), and hyp (20.6 ± 0.9 m.min-1, p = 0.914). According to the results, CV was significantly correlated with iMLSS. After running until exhaustion at CV (tlim = 28.4 ± 8,29 min), group E showed lower concentrations of hepatic and gluteal glycogen than group C, but no difference in the content of MCT1 (p = 0.933) and MCT4 (p = 0.123) in soleus muscle. Significant correlations were not found between MCT1 and MCT4 and tlim at CV intensity. Our results reinforce that CV is a valid and non-invasive protocol to estimate the maximal aerobic capacity in mice and that the content of MCT1 and MCT4 was not decisive in determining the tlim at CV, at least when measured immediately after the running effort.