Perceptions of Therapeutic Climbing for Patients with Multiple Sclerosis in Neurorehabilitation: A Qualitative Study.

BACKGROUND: Therapeutic climbing (TC) has emerged as a prospective rehabilitation approach for individuals with multiple sclerosis (MS). The existing literature primarily focuses on the physical and psychological benefits of TC across diverse populations but is limited concerning its application and efficacy for patients with MS. OBJECTIVES: This study aimed to delineate the experiences, subjective effects, and perceptions of both individuals with MS and therapists regarding TC, highlighting the potential benefits and challenges of this therapeutic approach. METHODS: Using a qualitative design, semi-structured interviews were conducted with patients living with MS (N = 5) and therapists (N = 7) involved in TC sessions at a rehabilitation facility. The interviews were recorded, transcribed verbatim, and subjected to thematic qualitative text analysis. RESULTS: Our analysis resulted in the identification of five main categories: (1) motivational factors, (2) training conditions, (3) training content, (4) observed effects, and (5) safety protocol. Our findings primarily centred around the motivational aspects of TC. Participants consistently reported experiencing feelings of accomplishment, success, enjoyment, and increased self-confidence. Furthermore, TC was often perceived as a comprehensive intervention, addressing endurance, strength, flexibility, neuromotor functions, cognition, and mental health while having a low-risk profile. However, due to the demanding nature of TC, careful fatigue management is crucial. This entails personalised intensity adjustments during sessions and coordinating TC with other physically demanding therapies when implementing TC within a rehabilitation environment. CONCLUSIONS: TC shows promise within MS rehabilitation and can be considered safe under certain framework conditions. This research sheds light on its potential benefits, facilitators, and barriers and provides insights for practical integration into rehabilitation programs.

Cancer risk factors and access to cancer prevention services for people experiencing homelessness.

Cancer is one of the most pressing global health issues, and populations with complex needs, such as people experiencing homelessness, have higher cancer incidence and mortality rates compared with the housed population. We mapped the evidence on cancer risk factors as well as barriers and facilitators to cancer prevention services among people experiencing homelessness, which is key to localising research gaps and identifying strategies for tailored interventions adapted to people experiencing homelessness. The results of 40 studies contribute to an understanding of the dynamic, interactive factors at different levels that determine access to cancer prevention services: socioeconomic, psychological, and physical factors (individual level); practical support and relational loops between health-care providers and people experiencing homelessness (interpersonal level); housing and regular medical care (system level); and interventions to facilitate access to cancer prevention (policy level). Furthermore, studies reported higher prevalence of various cancer-associated risk factors among people experiencing homelessness with the most common being tobacco use, ranging from 26% to 73%. The results show the importance of interventions to facilitate cancer prevention services through social support and low-threshold interventions (eg, navigation programmes), and training health-care staff in creating supportive and trusting environments that increase the likelihood of the continuity of care among people experiencing homelessness.

Experiences of Vegans with General Practitioners in the Austrian Health Care System: A Qualitative Study.

This article explores the factors influencing the choice of general practitioners (GPs) and their role in the health care of vegans in Austria. The number of people identifying as vegan is on the rise, and GPs are increasingly confronted with vegan patients. A qualitative method was chosen for this study, and 14 semi-structured interviews with vegans were conducted between April 2022 and July 2022. Participants were recruited primarily through vegan social media groups. In their experiences with health care, vegans felt treated unequally or sometimes incorrectly. The experiences described highlight that participants felt that most GPs were biased against their veganism. Information exchange among vegans primarily takes place online and through publications of vegan associations, while GPs play a minor role in information provision. As the number of vegans grows, an appreciative way of communicating between GPs and vegan patients ought to be promoted. Voluntary interdisciplinary nutritional training, collaboration of the medical field with support organizations, provision of evidence-based information, and collaboration with dietitians and nutritionists could enrich the care of patients with a vegan diet.

Trophoblast Organoids as a Novel Tool to Study Human Placental Development and Function.

The human placenta provides the site of exchange between the maternal and fetal bloodstreams, acts as an endocrine organ, and has immunological functions. The majority of pregnancy disorders including preeclampsia and fetal growth restriction have their roots in pathological placentation. Yet, the underlying molecular causes of these complications remain largely unknown, not least due to the lack of reliable in vitro models. Recent establishment of 2D human trophoblast stem cells and 3D trophoblast organoids has been a major advancement that opened new avenues for trophoblast research. Here we provide a protocol detailing isolation of cytotrophoblast from the first trimester human placenta, establishment of trophoblast organoids, their culture and differentiation conditions. Overall, we describe an in vitro system that offers an excellent model to study the molecular basis of placental development and disease.

Gene-network based analysis of human placental trophoblast subtypes identifies critical genes as potential targets of therapeutic drugs.

During early pregnancy, extravillous trophoblasts (EVTs) play a crucial role in modifying the maternal uterine environment. Failures in EVT lineage formation and differentiation can lead to pregnancy complications such as preeclampsia, fetal growth restriction, and pregnancy loss. Despite recent advances, our knowledge on molecular and external factors that control and affect EVT development remains incomplete. Using trophoblast organoid in vitro models, we recently discovered that coordinated manipulation of the transforming growth factor beta (TGFß) signaling is essential for EVT development. To further investigate gene networks involved in EVT function and development, we performed weighted gene co-expression network analysis (WGCNA) on our RNA-Seq data. We identified 10 modules with a median module membership of over 0.8 and sizes ranging from 1005 (M1) to 72 (M27) network genes associated with TGFß activation status or in vitro culturing, the latter being indicative for yet undiscovered factors that shape the EVT phenotypes. Lastly, we hypothesized that certain therapeutic drugs might unintentionally interfere with placentation by affecting EVT-specific gene expression. We used the STRING database to map correlations and the Drug-Gene Interaction database to identify drug targets. Our comprehensive dataset of drug-gene interactions provides insights into potential risks associated with certain drugs in early gestation.

Associations of Apolipoprotein ε4 Genotypes with Motor and Nonmotor Symptoms in Parkinson's Disease: A Cross-Sectional Study.

Background: The apolipoprotein E (APOE) ε4 allele has been associated with cognitive decline in Parkinson's disease (PD), but little is known about its relationship with motor and other nonmotor symptoms and whether APOE ε4 retains an influence on cognition when other factors are considered. Objective: To investigate the impact of APOE ε4 on motor/nonmotor symptoms and its relationship with other factors affecting cognition in individuals with PD. Methods: We analyzed data from 7616 individuals, comparing motor/nonmotor symptoms in different APOE genotypes using binary logistic regression. Multivariate logistic regression examined factors associated with cognitive impairments, including APOE ε4, Geriatric Depression Scale (GDS) score, Non-motor Symptom Questionnaire (NMS) score, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II score, and physical activity level. Results: APOE ε4 heterozygosity was modestly associated with lower cognitive scores (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.87-0.99), whereas no significant association was found for any other nonmotor and motor symptoms. However, in multivariate analysis, cognitive impairment was associated with higher GDS (OR, 1.28; 95% CI, 1.23-1.34), NMS (OR, 1.22; 95% CI, 1.19-1.25), and MDS-UPDRS Part II (OR, 1.07; 95% CI, 1.06-1.09) scores, whereas physical activity was negatively associated (OR, 0.99; 95% CI, 0.98-0.99). APOE ε4 was no longer significant after adjusting for these factors. Conclusions: There is a link between cognition and APOE ε4 in patients with PD; however, when considering multiple factors, APOE ε4 plays a subordinate role. Other factors, such as depression, physical activity, and other nonmotor symptoms, demonstrate a stronger influence on cognitive impairment.

NOTCH3 signalling controls human trophoblast stem cell expansion and differentiation.

Failures in growth and differentiation of the early human placenta are associated with severe pregnancy disorders such as pre-eclampsia and fetal growth restriction. However, regulatory mechanisms controlling development of placental epithelial cells, the trophoblasts, remain poorly elucidated. Using trophoblast stem cells (TSCs), trophoblast organoids (TB-ORGs) and primary cytotrophoblasts (CTBs) of early pregnancy, we herein show that autocrine NOTCH3 signalling controls human placental expansion and differentiation. The NOTCH3 receptor was specifically expressed in proliferative CTB progenitors and its active form, the nuclear NOTCH3 intracellular domain (NOTCH3-ICD), interacted with the transcriptional co-activator mastermind-like 1 (MAML1). Doxycycline-inducible expression of dominant-negative MAML1 in TSC lines provoked cell fusion and upregulation of genes specific for multinucleated syncytiotrophoblasts, which are the differentiated hormone-producing cells of the placenta. However, progenitor expansion and markers of trophoblast stemness and proliferation were suppressed. Accordingly, inhibition of NOTCH3 signalling diminished growth of TB-ORGs, whereas overexpression of NOTCH3-ICD in primary CTBs and TSCs showed opposite effects. In conclusion, the data suggest that canonical NOTCH3 signalling plays a key role in human placental development by promoting self-renewal of CTB progenitors.

Health aspects of vegan diets among children and adolescents: a systematic review and meta-analyses.

Health effects of vegan diets among children and adolescents are a controversial public health topic. Thus, the aim of the present systematic review is to evaluate a broad range of health outcomes among vegan children and adolescents aged 0 to 18 years. 18 studies met the inclusion criteria (17 cross-sectional, 1 RCT). Meta-analyses showed lower protein, calcium, vitamin B2, saturated fatty acid, and cholesterol intakes, and lower ferritin, HDL and LDL levels as well as height in vegan compared to omnivorous children/adolescents. Higher intakes of carbohydrates, polyunsaturated fatty acids, fiber, folate, vitamins C and E, magnesium, iron, and potassium were observed in vegans. Blood levels of vitamin B12 were higher among vegan children due to supplement use. Single study results suggested further differences between vegan and non-vegan children, such as lower bone mineral content or urinary iodine among vegan children. Risk of Bias was rated as high or very high in 7 out of 18 studies. The certainty of evidence for the meta-analyses was low (n = 2) or very low (n = 46). Overall, the available evidence points to both risks and benefits associated with a vegan diet among children, although more and better designed studies are needed.

Cancer risk factors and access to cancer prevention services for people experiencing homelessness: a scoping review protocol.

INTRODUCTION: Homelessness is a complex social issue that significantly impairs the health of those affected. People experiencing homelessness (PEH) have a higher prevalence of adverse health outcomes, including premature mortality, compared with the general population, with cancer being the second-leading cause of death. The objective of this scoping review is to map the evidence to assess the exposure of PEH to known cancer risk factors and identify barriers and facilitators PEH experience in accessing cancer prevention services. METHODS AND ANALYSIS: This scoping review will be conducted in line with the Joanna Briggs Institute guidelines for scoping reviews. For a time window from the date of database establishment until 20 February 2023, the research team will create a detailed search strategy and apply it to the following databases: CINAHL, Embase, Global Index Medicus, PubMed, Scopus and Web of Science. In addition, we will search OpenGrey and Google for grey literature and contact non-governmental organisations to request relevant reports. In the first stage, eligibility criteria will be assessed through a blinded title/abstract assessment, and following this assessment, a full-text screening will be performed. Subsequently, the research team will perform the data extraction and synthesise all relevant information in relation to the scoping review question. ETHICS AND DISSEMINATION: As this protocol does not involve gathering primary data, ethical approval is not necessary. The results of this review will be published in a peer-reviewed journal and on institutional websites.

Generation of extracellular fluids from first-trimester decidual tissues and their validation by detecting tissue-specific secreted proteins.

The human placenta comes in direct contact with maternal cells and blood at two interfaces. The syncytiotrophoblast layer is surrounded by maternal blood at the intervillous space, and extravillous trophoblasts breach the vascular endothelial cells layer upon spiral artery remodeling and invasion of decidual veins. However, little knowledge exists about EVT-derived secreted factors, which may serve as predictive markers for obstetrical syndromes or shape the local environment at the maternal-fetal interface. Here, we define secreted EVT-associated genes and describe a method that yields interstitial fluids from patient-matched first-trimester decidua basalis and parietalis tissues.

Human organoid systems in modeling reproductive tissue development, function, and disease.

Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to human embryonic material has necessitated the use of animals, primarily rats and mice, and short-term primary cell cultures derived from human patient material. While reproductive developmental processes are generally conserved across mammals, specific features unique to human reproduction have resulted in the development of human-based in vitro systems designed to retain or recapitulate key molecular and cellular processes important in humans. Of note, major advances in 3D epithelial stem cell-based systems modeling human reproductive organ development have been made. These cultures, broadly referred to as organoids, enable research aimed at understanding cellular hierarchies and processes controlling cellular differentiation and function. Moreover, organoids allow the pre-clinical testing of pharmacological substances, both from safety and efficacy standpoints, and hold large potential in driving aspects of personalized medicine that were previously not possible with traditional models. In this mini-review, we focus on summarizing the current state of regenerative organoid culture systems of the female and male reproductive tracts that model organ development, maintenance, and function. Specifically, we will introduce stem cell-based organoid models of the ovary/fallopian tube, endometrium, cervix, prostate gland, and testes. We will also describe organoid systems of the pre-implanting blastocyst and trophoblast, as the blastocyst and its extraembryonic trophectoderm are central to fetal, maternal, and overall pregnancy health. We describe the foundational studies leading to their development and outline the utility as well as specific limitations that are unique and common to many of these in vitro platforms.

The Association between Vegan Dietary Patterns and Physical Activity-A Cross-Sectional Online Survey.

A balanced diet and sufficient physical activity (PA) are known to have positive health effects. The relationship between a vegan diet and PA levels is understudied. This cross-sectional online survey aimed to analyze whether different vegan dietary patterns differ in PA. In total, 516 vegan participants were included (June to August 2022). Different dietary patterns were compiled through principal component analysis, while group differences were calculated using independent tests, or chi-squared tests as well as logistic regression analyses. The population had an average age of 28.0 (SD: 7.7) years and had been living vegan for 2.6 (95% CI: 2.5-3.0) years. Two dietary patterns, the "convenience" and the "health-conscious" group, were identified. People with a convenience dietary pattern had significantly higher odds of sitting more (OR 1.10, 95% CI 1.04-1.18) and not achieving aerobic PA (OR 1.81, 95% CI 1.18-2.79) or strength training recommendations (OR 1.81, 95% CI 1.26-2.61) than people with a health-conscious dietary pattern. This study suggests the heterogeneity of vegan diets and that dietary patterns must be differentiated, as they also differ in the level of PA. Additional studies involving complete dietary assessment with a focus on ultraprocessed foods, blood metabolite analysis, and objective PA assessment are required.

3D organoid formation and EVT differentiation of various trophoblastic cell lines.

3-dimensional trophoblast organoids (TB-ORG) represent a reliable model for studying extravillous trophoblast (EVT) lineage formation and differentiation. However, restricted access to first trimester placentae requires alternative cell sources for establishing placental organoids. Recently, we demonstrated EVT differentiation in JEG-3-derived organoids. Consequently, we herein tested whether other commonly used trophoblastic cell lines, ACH-3P, HTR-8/SVneo, and SWAN-71 were capable of self-organizing into organoids and subsequent EVT differentiation. Notably, only ACH-3P formed organoids under stemness conditions mimicking TB-ORG architectures, and induction of EVT differentiation provoked formation of HLA-Gpos areas. Hence ACH-3P-ORGs provide another organoid model for studying controlled EVT lineage formation and differentiation.

The human placenta shapes the phenotype of decidual macrophages.

During human pregnancy, placenta-derived extravillous trophoblasts (EVTs) invade the decidua and communicate with maternal immune cells. The decidua distinguishes into basalis (decB) and parietalis (decP). The latter remains unaffected by EVT invasion. By defining a specific gating strategy, we report the accumulation of macrophages in decB. We describe a decidua basalis-associated macrophage (decBAM) population with a differential transcriptome and secretome compared with decidua parietalis-associated macrophages (decPAMs). decBAMs are CD11chi and efficient inducers of Tregs, proliferate in situ, and secrete high levels of CXCL1, CXCL5, M-CSF, and IL-10. In contrast, decPAMs exert a dendritic cell-like, motile phenotype characterized by induced expression of HLA class II molecules, enhanced phagocytosis, and the ability to activate T cells. Strikingly, EVT-conditioned media convert decPAMs into a decBAM phenotype. These findings assign distinct macrophage phenotypes to decidual areas depending on placentation and further highlight a critical role for EVTs in the induction of decB-associated macrophage polarization.

Steady increase of obesity prevalence in Austria: Analysis of three representative cross-sectional national health interview surveys from 2006 to 2019.

BACKGROUND: Obesity is associated with adverse health consequences throughout life. Monitoring obesity trends is important to plan and implement public heath interventions adapted to specific target groups. We aimed to analyze the development of obesity prevalence in the Austrian population using data from the most recent representative Austrian Health Interview Surveys. METHODS: The three cross-sectional Austrian health interview surveys from 2006/2007, 2014 and 2019 were used (n = 45,707). Data correction for self-reported body mass index (BMI) was applied. Sex, age, education level, employment status, country of birth, urbanization, and family status were used as sociodemographic factors. Logistic regression models were applied. RESULTS: Prevalence of obesity increased in both sexes in the study period (men 13.7% to 20.0%, women 15.2% to 17.8%, p < 0.001). Adjusted odds ratios (95% confidence interval [CI]) for the increase in obesity prevalence was 1.47 (95% CI: 1.38-1.56). In men, obesity prevalence almost doubled from 2006/2007 to 2019 in subgroups of 15-29-year-olds (4.8% to 9.0%), unemployed (13.5% to 27.6%), men born in non-EU/non-EFTA countries (13.9% to 26.2%), and not being in a relationship (8.1% to 15.4%). In women, the largest increase was found in subgroups of 30-64-year-olds (15.8% to 18.7%), women born in non-EU/non-EFTA countries (19.9% to 22.8%) and in women living in the federal capital Vienna (16.5% to 19.9%). CONCLUSION: Obesity prevalence in the Austrian population continues to rise significantly. We identified distinct subgroups with a fast-growing obesity prevalence in recent years, emphasizing the importance of regular long-term data collection as a basis for sustainable and target group-specific action planning.

Obesity, Fruit and Vegetable Intake, and Physical Activity Patterns in Austrian Farmers Compared to the General Population.

Low fruit and vegetable (F&V) intake, sedentary behavior, excessive alcohol consumption, and smoking are risk factors for the development of non-communicable diseases. This study describes the patterns and factors of nutrition (F&V and alcohol intake), physical activity (PA), obesity, and other chronic diseases of 10,053 adult farmers (52.7% female) in Austria, based on the cross-sectional survey from the Austrian Social Insurance Institution for the Self-Employed and compared with the results of the general Austrian population from 2019 (n = 14,606; 53.7% female). Compared to the general Austrian population, farmers showed a higher prevalence of overweight and obesity (42.8% vs. 36.5%; 18.8% vs. 17.1%), as well as hypertension, hypercholesterolemia, and diabetes mellitus. Additionally, farmers ate less F&V (0 servings/day 39.7% vs. 14.0%; 1−4 servings/day 55.5% vs. 80.8%) and only 4.8% vs. 5.1% (p < 0.001) fulfilled the F&V recommendations. Lower participation in endurance training (38.3% vs. 52.1%) was found, whereas farmers did more strength training (64.1% vs. 27.6%). Those who failed to fulfill the PA recommendations reported worse health status (OR: 3.14; 95%-CI: 2.08−4.76) and a higher chance for obesity (OR: 1.68; 95%-CI: 1.38−2.05). Since obesity rates among farmers are high and recommendations have rarely been met, every opportunity should be taken to promote healthy eating and adequate PA.

Transforming growth factor-ß signaling governs the differentiation program of extravillous trophoblasts in the developing human placenta.

Abnormal placentation has been noticed in a variety of pregnancy complications such as miscarriage, early-onset preeclampsia, and fetal growth restriction. Defects in the developmental program of extravillous trophoblasts (EVTs), migrating from placental anchoring villi into the maternal decidua and its vessels, is thought to be an underlying cause. Yet, key regulatory mechanisms controlling commitment and differentiation of the invasive trophoblast lineage remain largely elusive. Herein, comparative gene expression analyses of HLA-G-purified EVTs, isolated from donor-matched placenta, decidua, and trophoblast organoids (TB-ORGs), revealed biological processes and signaling pathways governing EVT development. In particular, bioinformatics analyses and manipulations in different versatile trophoblast cell models unraveled transforming growth factor-ß (TGF-ß) signaling as a crucial pathway driving differentiation of placental EVTs into decidual EVTs, the latter showing enrichment of a secretory gene signature. Removal of Wingless signaling and subsequent activation of the TGF-ß pathway were required for the formation of human leukocyte antigen-G+ (HLA-G+) EVTs in TB-ORGs that resemble in situ EVTs at the level of global gene expression. Accordingly, TGF-ß-treated EVTs secreted enzymes, such as DAO and PAPPA2, which were predominantly expressed by decidual EVTs. Their genes were controlled by EVT-specific induction and genomic binding of the TGF-ß downstream effector SMAD3. In summary, TGF-ß signaling plays a key role in human placental development governing the differentiation program of EVTs.

WNT and NOTCH signaling in human trophoblast development and differentiation.

Correct development of the human placenta and its differentiated epithelial cells, syncytial trophoblasts (STBs) and extravillous trophoblasts (EVTs), is crucial for a successful pregnancy outcome. STBs develop by cell fusion of mononuclear cytotrophoblasts (CTBs) in placental floating villi, whereas migratory EVTs originate from specialized villi anchoring to the maternal decidua. Defects in trophoblast differentiation have been associated with severe pregnancy disorders such as early-onset preeclampsia and fetal growth restriction. However, the evolutionary pathways underlying normal and adverse placentation are poorly understood. Herein, we discuss Wingless (WNT) and NOTCH signaling, two pathways that play pivotal roles in human placenta and trophoblast development. Whereas WNT is necessary for expansion of trophoblast progenitors and stem cells, NOTCH1 is required for proliferation and survival of EVT precursors. Differentiation of the latter is orchestrated by a switch in NOTCH receptor expression as well as by changes in WNT ligands and their downstream effectors.

Implementation of a Mobile DBT App and Its Impact on Suicidality in Transitional Age Youth with Borderline Personality Disorder: A Qualitative Study.

Contemporary performance and accessibility are features that enable mobile devices to be increasingly beneficial in the context of optimizing the treatment of psychiatric disorders. Smartphones have the potential to effectively support psychotherapeutic interventions among adolescents and young adults who require them. In the present study, the use and subjective influence of a smartphone app with content from dialectical behavior therapy (DBT) was investigated among transitional age youth (TAY) with borderline personality disorder, focusing on suicidality and non-suicidal self-injury (NSSI), in a natural setting. A longitudinal qualitative approach was used by means of individual semi-structured interviews, where participants were asked about their experiences and associated emotions before and after a testing period of 30 days. A total of 13 TAY with a diagnosed borderline personality disorder between the ages of 18 and 23 were included. Six overarching themes were identified through qualitative text analysis: (1) experiences with DBT skills, (2) phenomenon of self-harm, (3) feelings connected with self-harm, (4) dealing with disorder-specific symptoms, (5) prevention of self-harm, and (6) attitude toward skills apps. In general, the provision of an app with DBT content achieved a positive response among participants. Despite a small change in the perception of suicidality and NSSI, participants could imagine its benefits by integrating their use of the app as a supportive measure for personal psychotherapy sessions.