Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain.

Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and histological and ultrastructural analyses, we show that an ensemble of endothelial and mural cell subtypes tile the brain vasculature during the second trimester. These vascular cells follow distinct developmental trajectories and utilize diverse signaling mechanisms, including collagen, laminin, and midkine, to facilitate cell-cell communication and maturation. Interestingly, our results reveal that tip cells, a subtype of endothelial cells, are highly enriched near the ventricular zone, the site of active neurogenesis. Consistent with these observations, prenatal vascular cells transplanted into cortical organoids exhibit restricted lineage potential that favors tip cells, promotes neurogenesis, and reduces cellular stress. Together, our results uncover important mechanisms into vascular maturation during this critical period of human brain development.

Human microglia maturation is underpinned by specific gene regulatory networks.

Microglia phenotypes are highly regulated by the brain environment, but the transcriptional networks that specify the maturation of human microglia are poorly understood. Here, we characterized stage-specific transcriptomes and epigenetic landscapes of fetal and postnatal human microglia and acquired corresponding data in induced pluripotent stem cell (iPSC)-derived microglia, in cerebral organoids, and following engraftment into humanized mice. Parallel development of computational approaches that considered transcription factor (TF) co-occurrence and enhancer activity allowed prediction of shared and state-specific gene regulatory networks associated with fetal and postnatal microglia. Additionally, many features of the human fetal-to-postnatal transition were recapitulated in a time-dependent manner following the engraftment of iPSC cells into humanized mice. These data and accompanying computational approaches will facilitate further efforts to elucidate mechanisms by which human microglia acquire stage- and disease-specific phenotypes.

Monitoring of Adverse Events and Safety in Autoinflammatory Diseases: Real-Life Data from the Eurofever Registry.

OBJECTIVES: The study is aimed to evaluate the impact of safety events in the Eurofever registry for Autoinflammatory diseases. METHODS: This was a retrospective and longitudinal observational multicentre study. Data were retrieved from the international registry Eurofever, starting patients' enrolment since 2009. All moderate, severe, or very severe AEs reported by treating physician in Eurofever were analyzed regardless of a possible suspected causal relationship to any therapies and according to the latest release of the Medical Dictionary for Regulatory Activities. RESULTS: Complete information on safety were available in 2464 patients enrolled in the registry. In 1499 of them retrospective data encompassing the period from disease onset to enrolment were available, whereas 965 consecutive patients entered in the longitudinal part of the study. A total of 479 AEs have been reported in 275 patients. Eighty-two AEs were reported as serious and 99 were drug-related according to the physicians. Infections or infestations (94; 19.6%), gastrointestinal disorders (66; 13.8%), nervous system disorders (41; 8.6%) and systemic disorders or administration site reactions (35; 7.3%) were the most frequent reported events. The highest absolute number of drug-related AEs were related to biologic DMARDs (40/99 reports, 40,4%) and colchicine (31/99 reports, 31.3%). CONCLUSIONS: Present study shows the importance of a longitudinal and homogeneous registration of the AEs in rare conditions, with a particular focus on the safety profile of the treatments used in these conditions.

Perceived usefulness of the nurse-patient therapeutic relationship in the rehabilitation journey of people with urinary incontinence: A mixed-method study.

INTRODUCTION: Despite various studies on the impact of incontinence on patients' lives, the existing literature has not investigated the contribution of nursing care during rehabilitation in terms of quality of life. Fewer data, therefore, exist on the characteristics and perceived impact of the therapeutic relationship as part of the rehabilitation program. AIMS: To investigate the characteristics of the nurse-patient therapeutic relationship and its impact throughout the rehabilitation program; to describe the levels of patient burden on everyday activities. MATERIALS AND METHODS: A monocentric, retrospective, multimethod descriptive study was conducted in the nurse-led continence clinic of a major teaching hospital in Northern Italy. A phenomenological approach with semistructured interviews was adopted after 6 weeks of rehabilitation, following the method of phenomenological enquiry by Giorgi. The short form 12 questionnaire was administered upon admission of patients to the clinic, after 6 weeks, and during the last consultation to investigate the impact of urinary incontinence (UI) on daily activities and physical and psychological quality of life. RESULTS: Ninety-one adult patients of both genders presenting for nonneurogenic nonpostpartum UI were consecutively enrolled. Physical scores (PCS-12) and MCS-12 scores significantly increased over time. Psychological scores showed great variability upon admission, which was reduced halfway through the rehabilitation program. The thematic analysis highlighted four categories based on data saturation: the impact of UI on daily activities, strategies to face the problem, feelings, and the role of nurses. CONCLUSIONS: This mixed-method investigation suggests the importance of therapeutic nursing relationships, clinical expertise, and rehabilitative skills. Quality of life is arguably related to the positive results of the rehabilitation program but also to the environment, patients perceive in terms of support, honesty, and trust.

Adherence to the Mediterranean Diet and its association with sustainable dietary behaviors, sociodemographic factors, and lifestyle: a cross-sectional study in US University students.

BACKGROUND: Promoting healthy and sustainable diets is increasingly important and the Mediterranean Diet (MD) has been recognized as an appropriate example that can be adapted to different countries. Considering that the college years are the time when US young adults are most likely to adopt unhealthy eating habits, the present study assessed adherence to the MD and the sustainability of dietary behaviors in a nationally representative sample of US university students, aiming to identify crucial levers for improving their eating behaviors. METHODS: MD adherence and the adoption of healthy and sustainable dietary patterns were assessed through the KIDMED and the Sustainable-HEalthy-Diet (SHED Index questionnaires, respectively, administered through an online survey that also included sociodemographic and behavioral questions. Non-parametric and logistic regression analyses were performed. RESULTS: A sample of 1485 participants (median (IQR) age 21.0 (19.0-22.0); 59% women) correctly completed the survey. A medium adherence to the MD was the most prevalent (47%). According to multivariate logistic regression analysis, the likelihood of being more compliant with the MD increased when meeting physical activity recommendations, having a high SHED Index score, having the willingness to purchase and eat healthy and sustainable dishes, eating ultra-processed plant-based meat alternatives foods daily, and regularly attending the university canteen. CONCLUSIONS: Encouraging dietary patterns rich in plant-based foods and with a moderate intake of animal products is crucial to increasing the adoption of healthy and sustainable diets, and university dining services represent a suitable setting to build a supportive environment that educates students on human and planetary health.

Transcutaneous electrical nerve stimulation for pelvic pain: A scoping review of treatment protocols, practical indications, and caveats.

BACKGROUND: Neuromodulation (NM) is a family of therapies based on electrical stimulation to target specific nerves that control LUTS (Lower Urinary Tract Symptoms) and pain. The aim is to modulate what is happening within the nervous system to achieve therapeutic effects. A particular type of neuromodulation, called TENS (Transcutaneous Electrical Nerve Stimulation), has proven effective for treating pelvic pain. The available evidence provides indications regarding the many aspects of TENS that influence therapeutic effects, but a comprehensive review has yet to be conducted. METHODS: Scoping review on Pubmed, CINAHL, Embase, Scopus, and Web of Science, including clinical trials, reviews, case studies or series, and other descriptive studies, according to the Joanna Briggs and PRISMA methodology. RESULTS: The 31 papers retrieved allowed the formulation of precise indications about the DOs and DON'Ts of electrode placement, waveform, pulse duration, pulse frequency, amplitude, session duration, and frequency of sessions. This paper also discusses the biochemical and neuro urological mechanisms of TENS. CONCLUSION: TENS effectiveness is influenced by many factors, some self-evident, others subtle, which this paper elucidates. Pelvic pain requires a multimodal approach, of which TENS is just a part. TENS should therefore be viewed as one of the components of the rehabilitation program in the frame of thorough and continuous patient assessment.

Nurses' role in the management of persons with chronic urogenital pelvic pain syndromes: A scoping review.

BACKGROUND: Pelvic pain has cognitive, behavioral, sexual, and emotional consequences. Nurses involved in pelvic floor rehabilitation clinics have contacts with patients reporting chronic pain and should know the most appropriate service for patient referral, to submit the problem to professionals capable of correctly assessing and managing the condition. Furthermore, in some countries nurses can use conservative methods to treat the painful symptoms inside a multidisciplinary team such as breathing retraining, biofeedback, and noninvasive neuromodulation. This paper aims to provide an overview of the literature regarding the role of rehabilitation nurses in dealing with patients suffering from chronic urogenital pelvic pain or urogenital painful syndromes, inside a multidisciplinary team. METHODS: Scoping review on Pubmed, CINAHL, Embase, Scopus, Web of Science including trials, reviews, case studies or series, and other descriptive studies regarding the role of nurses inside the multidisciplinary team in the management of males and females presenting chronic pelvic pain (CPP) or chronic pelvic pain syndrome (CPPS). RESULTS: The 36 papers included in this review allowed answering research questions in four areas of nursing: collecting basic information, referring the person to appropriate services, evidence-based nursing interventions for CPP and CPPS, and proper documentation. Clinical history and assessment of breathing pattern, Muscular assessment and research of trigger points are the main points of data collection. Techniques for muscular relaxation and breathing retraining are important aspects of treatment, as well as biofeedback and noninvasive neuromodulation where the law allows nurses to practice such techniques. The McGill pain questionnaire and the pain inventory of the International Pain Society allow systematic data collection and handover. CONCLUSION: Rehabilitation nurses work inside multidisciplinary teams when dealing with persons suffering from pelvic pain; further research is needed as our comprehension of the underlying pathophysiological mechanisms of CPP and CPPS evolve.

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Transcriptomics and miRNomics data integration in lymphoblastoid cells highlights the key role of immune-related functions in lithium treatment response in Bipolar disorder.

BACKGROUND: Bipolar Disorder (BD) is a complex mental disease characterized by recurrent episodes of mania and depression. Lithium (Li) represents the mainstay of BD pharmacotherapy, despite the narrow therapeutic index and the high variability in treatment response. However, although several studies have been conducted, the molecular mechanisms underlying Li therapeutic effects remain unclear. METHODS: In order to identify molecular signatures and biological pathways associated with Li treatment response, we conducted transcriptome and miRNome microarray analyses on lymphoblastoid cell lines (LCLs) from 20 patients diagnosed with BD classified as Li responders (n = 11) or non-responders (n = 9). RESULTS: We found 335 mRNAs and 77 microRNAs (miRNAs) significantly modulated in BD responders versus non-responders. Interestingly, pathway and network analyses on these differentially expressed molecules suggested a modulatory effect of Li on several immune-related functions. Indeed, among the functional molecular nodes, we found NF-κB and TNF. Moreover, networks related to these molecules resulted overall inhibited in BD responder patients, suggesting anti-inflammatory properties of Li. From the integrative analysis between transcriptomics and miRNomics data carried out using miRComb R package on the same samples from patients diagnosed with BD, we found 97 significantly and negatively correlated mRNA-miRNA pairs, mainly involved in inflammatory/immune response. CONCLUSIONS: Our results highlight that Li exerts modulatory effects on immune-related functions and that epigenetic mechanisms, especially miRNAs, can influence the modulation of different genes and pathways involved in Li response. Moreover, our data suggest the potentiality to integrate data coming from different high-throughput approaches as a tool to prioritize genes and pathways.

A nurse-led educational intervention for relieving idiopathic constipation: a retrospective study.

BACKGROUND: Constipation is a common condition. Although numerous articles emphasise the importance of conservative interventions, none have set out a complete educational programme. AIMS: To describe the results of an evidence-based, nurse-led educational intervention for functional constipation in adults. METHODS: A retrospective study of patient records with an analysis of Wexner constipation scores and Bristol stool charts was carried out before and after a nurse-led educational programme on nutrition and bowel habits. FINDINGS: Twenty-nine patients were enrolled (19 women and 10 men), with a median age of 61 (53-71) years, a mean BMI of 24.4±3.88 kg/m2 and comparable baseline Wexner and Bristol scores. A statistically significant improvement in Wexner scores (P<0.001) and a clinically relevant but not statistically significant (P=0.682) improvement in Bristol scores were observed. CONCLUSION: The results suggest this investigation should be repeated on a larger scale. An educational intervention could be included in all consultations on any issue that could affect bowel activity.