Bone marrow-derived mesenchymal stem cells mitigate chronic colitis and enteric neuropathy via anti-inflammatory and anti-oxidative mechanisms.

Current treatments for inflammatory bowel disease (IBD) are often inadequate due to limited efficacy and toxicity, leading to surgical resection in refractory cases. IBD's broad and complex pathogenesis involving the immune system, enteric nervous system, microbiome, and oxidative stress requires more effective therapeutic strategies. In this study, we investigated the therapeutic potential of bone marrow-derived mesenchymal stem cell (BM-MSC) treatments in spontaneous chronic colitis using the Winnie mouse model which closely replicates the presentation and inflammatory profile of ulcerative colitis. The 14-day BM-MSC treatment regimen reduced the severity of colitis, leading to the attenuation of diarrheal symptoms and recovery in body mass. Morphological and histological abnormalities in the colon were also alleviated. Transcriptomic analysis demonstrated that BM-MSC treatment led to alterations in gene expression profiles primarily downregulating genes related to inflammation, including pro-inflammatory cytokines, chemokines and other biomarkers of inflammation. Further evaluation of immune cell populations using immunohistochemistry revealed a reduction in leukocyte infiltration upon BM-MSC treatment. Notably, enteric neuronal gene signatures were the most impacted by BM-MSC treatment, which correlated with the restoration of neuronal density in the myenteric ganglia. Moreover, BM-MSCs exhibited neuroprotective effects against oxidative stress-induced neuronal loss through antioxidant mechanisms, including the reduction of mitochondrial-derived superoxide and attenuation of oxidative stress-induced HMGB1 translocation, potentially relying on MSC-derived SOD1. These findings suggest that BM-MSCs hold promise as a therapeutic intervention to mitigate chronic colitis by exerting anti-inflammatory effects and protecting the enteric nervous system from oxidative stress-induced damage.

Five ways to get a grip on teaching advocacy in medical education: the health humanities as a novel approach.

The advocate role is recognized as an intrinsic medical competency. Despite recent attention to pedagogical approaches, it is a role that remains poorly understood and difficult to teach. At the same time there is a growing body of evidence showing the necessity of incorporating humanities-based education into medical curricula. Here, we present five ways to use the humanities as a tool for teaching the advocate role including: decentre the physician as expert, develop engaged providers, engage learners in curricular decisions, value the humanities (and show it), and keep it practical.

Le rôle de défenseur des intérêts des patients est reconnu comme une compétence médicale à part entière. Malgré l'attention récente portée aux approches pédagogiques, ce rôle reste mal compris et difficile à enseigner. En parallèle, un nombre croissant de travaux démontrent la nécessité d'intégrer l'enseignement des sciences humaines dans les programmes d'études médicales. Nous présentons ici cinq façons d'utiliser les sciences humaines comme outil pour enseigner le rôle de défenseur des intérêts des patients, notamment : décentraliser le rôle d'expert du médecin, former des professionnels engagés, faire participer les apprenants aux décisions relatives au programme d'études, valoriser les sciences humaines (et le montrer), et rester pratique.

Sociocultural determinants of alcohol and cannabis use and misuse among Nunavimmiut.

OBJECTIVE: Stemming from historical traumas and changes in the Inuit way of life, substance use and its intertwined problems are a major cause of concern for Nunavimmiut. This study's objective is to investigate sociocultural determinants of substance use and misuse to inform culturally appropriate public health programs. METHODS: The 2017 Qanuilirpitaa? survey was conducted among a sample intended to be representative of Nunavimmiut aged 16 and over (total n = 1326). Sociocultural factors included cultural identity, land-based activities, involvement in community activities, social support, and family and community cohesion. The frequency of binge drinking (5 or more drinks on one occasion), cannabis use, and problematic substance use (CAGE and DAST-10) were documented. Data were analyzed using weighted multivariate logistic regressions. Inuit partners were involved from the planning of analyses to the co-interpretation of results. RESULTS: Nearly a third of Nunavimmiut aged 16 and over reported binge drinking at least once a week (29.3%), and 68.6% of drinkers were at risk of potential drinking problems. Forty-five percent (45%) reported using cannabis at least once a week, and 30% of drug users were at risk of potential drug abuse problems. Volunteering and participation in community activities were associated with lower odds of cannabis use, as was frequently going on the land with weekly binge drinking, potential drinking problems, and weekly cannabis use. Social support and community cohesion were associated with higher odds of weekly binge drinking, as was cultural identity (centrality scale) with potential drinking problems. CONCLUSION: Key determinants of substance use relevant to Inuit culture were identified. Results are in line with our Inuit partners' experience in their communities and are coherent with current land-based interventions implemented in Nunavik. A thorough understanding of substance use contexts and related stressors should guide the content and implementation of substance use programs in Nunavik.

RéSUMé: OBJECTIF: Suite aux traumas historiques et changements au mode de vie, l'usage de substance et les problèmes associés sont une source d'inquiétude majeure pour les Nunavimmiut. L'objectif de cette étude est d'investiguer les déterminants socioculturels de l'usage de substances pour adapter les programmes de santé publique à la culture Inuit. MéTHODES: L'enquête Qanuilirpitaa? 2017 repose sur un échantillon sélectionné pour être représentatif des Nunavimmiut (16 ans et plus; n = 1 326). Les déterminants socioculturels incluent : identité culturelle, activités sur le territoire, activités communautaires, support social, cohésion familiale et communautaire. La fréquence de consommation excessive d'alcool (5 consommations ou plus), l'usage du cannabis et l'usage problématique (CAGE et DAST-10) ont été documentés. Données analysées par régression multiple pondérée. Nos partenaires Inuit ont été impliqués de la planification des analyses à la co-interprétation des résultats. RéSULTATS: Près du tiers des Nunavimmiut de 16 ans et plus ont rapporté une consommation hebdomadaire excessive d'alcool (29,3 %) et 68,6 % de ceux consommant de l'alcool étaient potentiellement à risque de consommation problématique. Quarante-cinq pourcent (45 %) ont rapporté consommer du cannabis au moins une fois par semaine et 30 % des consommateurs de drogue étaient à risque de consommation potentiellement problématique. Le bénévolat et la participation aux activités communautaires étaient associés à une cote plus faible d'usage de cannabis, tout comme la pratique fréquente d'activités sur le territoire avec la consommation hebdomadaire excessive d'alcool, d'usage potentiellement problématique d'alcool et d'usage hebdomadaire de cannabis. Le support social et la cohésion communautaire étaient associés à une cote plus élevée de consommation excessive hebdomadaire d'alcool, tout comme l'identité culturelle (centralité) avec l'usage potentiellement problématique d'alcool. CONCLUSION: Des déterminants clés de l'usage de substance spécifiques aux Inuit ont été identifiés. Les résultats concordent avec le vécu de nos partenaires dans leurs communautés et le cadre théorique d'interventions déjà implémentées impliquant des activités sur le territoire et de guérison. Les contextes de consommation et les stresseurs associés devraient guider l'élaboration des programmes au Nunavik.

Profiles of childhood adversities in Inuit from Nunavik: description and associations with indicators of socioeconomic characteristics, support, and community involvement.

OBJECTIVES: Distress and associated health problems reported by Nunavik Inuit emanate from heterogeneous roots, including adverse childhood experiences. This study aims to (1) identify distinct childhood adversity profiles and (2) examine associations between these profiles and sex, socioeconomic characteristics, social support, and community involvement among Nunavimmiut. METHODS: In a sample of 1109 adult Nunavimmiut, sex, socioeconomic characteristics, support, community involvement, residential school attendance, and 10 forms of adverse childhood experiences (ACEs) were documented using questionnaires. Latent class analyses and weighted comparisons were performed for three subgroups: 18-49 years; 50 years and above with experience of residential school; and 50 years and above without experience of residential school. The analysis design, the manuscript drafts, and the key findings were discussed and co-interpreted with the collaboration of community representatives, taking into consideration Inuit culture and needs. RESULTS: A total of 77.6% of Nunavimmiut reported having experienced at least one form of childhood adversity. Three ACE profiles were identified among the 18-49-year-olds: low ACEs (43.0%), household stressors (30.7%), and multiple ACEs (26.3%). Two profiles characterized ACEs experienced among the 50-year-olds and over with and without history of residential schooling: low ACEs (80.1% and 77.2%, respectively) and multiple ACEs (19.9% and 22.8%, respectively). Among the group of 18-49-year-olds, as compared to the low ACE profile, the profile with household stressors included proportionally more women (odds ratio [OR] = 1.5) and was associated with lower involvement in volunteering and community activities (mean score reduced by 0.29 standard deviation [SD]) and lower family cohesion (SD = - 0.11), while the multiple ACE profile was related to a lower rate of employment (OR = 0.62), lower family cohesion (SD = - 0.28), and lower satisfaction with ability to practice traditional activities (SD = - 0.26). CONCLUSION: Childhood adversities among Nunavimmiut do not occur in isolation and experiencing multiple forms of childhood adversities predicts lower socioeconomic status, support, and community involvement in adulthood. Implications for the planning of health and community services in Nunavik are discussed.

RéSUMé: OBJECTIFS: La détresse et les problèmes de santé associés rapportés par les Inuits du Nunavik émanent de racines hétérogènes, notamment des expériences négatives durant l'enfance. Cette étude vise à : 1) identifier des profils distincts d'adversités vécues durant l'enfance; et 2) examiner les associations entre ces profils et le sexe, les caractéristiques socioéconomiques, le soutien social et l'engagement communautaire des Nunavimmiut. MéTHODES: Dans un échantillon de 1 109 adultes Nunavimmiut, le sexe, les caractéristiques socioéconomiques, le soutien, l'engagement communautaire, la fréquentation des pensionnats et 10 formes d'expériences négatives durant l'enfance (ENE) ont été documentés à l'aide de questionnaires. Des analyses de classes latentes et des comparaisons pondérées ont été réalisées pour trois sous-groupes : 18­49 ans; 50 ans et plus avec et sans expérience de pensionnat. Le plan d'analyses, les ébauches de manuscrit et les principaux résultats ont été discutés et co-interprétés avec la collaboration de représentants des communautés, en tenant compte de la culture et des besoins inuits. RéSULTATS: Un total de 77,6 % des Nunavimmiut ont déclaré avoir vécu au moins une forme d'adversité durant l'enfance. Trois profils d'ENE ont été identifiés chez les 18­49 ans : ENE faibles (43,0 %), facteurs de stress domestiques (30,7 %) et ENE multiples (26,3 %). Deux profils caractérisaient les ENE vécus chez les 50 ans et plus avec et sans antécédents de pensionnat : faibles ENE (80,1 % et 77,2 %, respectivement) et ENE multiples (19,9 % et 22,8 %, respectivement). Parmi le groupe des 18­49 ans, par rapport au profil des ENE faibles, le profil avec facteurs de stress domestiques incluait proportionnellement plus de femmes (rapport de cotes [RC] = 1,5) et était associé à une plus faible implication dans le bénévolat et les activités communautaires (score moyen réduit de 0,29 écart-type [ET]) et une cohésion familiale plus faible (ET = -0,11), tandis que le profil d'ENE multiples était lié à un taux d'emploi plus faible (RC = 0,62), à une cohésion familiale plus faible (ET = -0,28) et à une plus faible satisfaction à l'égard de la capacité à pratiquer des activités traditionnelles (ET = -0,26). CONCLUSION: Les adversités vécues en enfance par les Nunavimmiut ne surviennent pas de manière isolée et le fait de vivre de multiples formes d'ENE prédit un statut socio-économique, un soutien et une implication communautaire inférieurs à l'âge adulte. Les implications pour la planification des services de santé et communautaires au Nunavik sont discutées.

Using Twitter to Understand COVID-19 Vaccine-Related Ageism During the Pandemic.

BACKGROUND AND OBJECTIVES: During the rollout of coronavirus 2019 (COVID-19) vaccines, older adults in high-income countries were often prioritized for inoculation in efforts to reduce COVID-19-related mortality. However, this prioritization may have contributed to intergenerational tensions and ageism, particularly with the limited supply of COVID-19 vaccines. This study examines Twitter discourse to understand vaccine-related ageism during the COVID-19 pandemic to inform future vaccination policies and practices to reduce ageism. RESEARCH DESIGN AND METHODS: We collected 1,369 relevant tweets on Twitter using the Twint application in Python from December 8, 2020, to December 31, 2021. Tweets were analyzed using thematic analysis, and steps were taken to ensure rigor. RESULTS: Our research identified four main themes including (a) blame and hostility: "It's all their fault"; (b) incompetence and misinformation: "clueless boomer"; (c) ageist political slander; and (d) combatting ageism: advocacy and accessibility. DISCUSSION AND IMPLICATIONS: Our findings exposed issues of victim-blaming, hate speech, pejorative content, and ageist political slander that is deepening the divide of intergenerational conflict. Although a subset of tweets countered negative outcomes and demonstrated intergenerational solidarity, our findings suggest that ageism may have contributed to COVID-19 vaccine hesitancy among older adults. Consequently, urgent action is needed to counter vaccine misinformation, prohibit aggressive messaging, and promote intergenerational unity during the COVID-19 pandemic and beyond.

Perceptions of hospital care for persons with dementia during the COVID-19 pandemic: a social media sentiment analysis.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic led to many hospital service disruptions and strict visitor restrictions that impacted care of older adult populations. This study investigates perceptions of hospital care for persons with dementia during the COVID-19 pandemic as shared on Reddit's social media platform. RESEARCH DESIGN AND METHODS: This study combined an opinion mining framework with linguistic processing to conduct a sentiment analysis of word clusters and care-based content in a sample of 1205 posts shared between February 2020 and March 2023 in Reddit's English-language corpus. Data were classified based on reoccurring contiguous sequences of two words from our text sample. RESULTS: Hospital dementia care discourse on Reddit advanced four negative sentiment themes: (1) fear of poor medication management, hydration, and hygiene, (2) loss of patient advocacy, (3) precipitation of advance directive discussions, and (4) delayed discharge and loss of nursing home bed. One positive sentiment theme also emerged: gratitude towards hospital staff. DISCUSSION AND IMPLICATIONS: Negative sentiment Reddit posts constituted a larger share of the posts than positive posts regarding hospital care for persons with dementia. People who posted about their experiences shared their concerns about hospital care deficiencies and the importance of including informal caregivers in hospital settings, particularly in the context of a pandemic. Implications exist for dementia training, improved quality of care, advance care planning and transitions in care policies.

Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis.

The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.

Cholinergic signaling influences the expression of immune checkpoint inhibitors, PD-L1 and PD-L2, and tumor hallmarks in human colorectal cancer tissues and cell lines.

BACKGROUND: Cancer cells express immunosuppressive molecules, such as programmed death ligands (PD-L)1 and PD-L2, enabling evasion from the host's immune system. Cancer cells synthesize and secrete acetylcholine (ACh), acting as an autocrine or paracrine hormone to promote their proliferation, differentiation, and migration. METHODS: We correlated the expression of PD-L1, PD-L2, cholinergic muscarinic receptor 3 (M3R), alpha 7 nicotinic receptor (α7nAChR), and choline acetyltransferase (ChAT) in colorectal cancer (CRC) tissues with the stage of disease, gender, age, risk, and patient survival. The effects of a muscarinic receptor blocker, atropine, and a selective M3R blocker, 4-DAMP, on the expression of immunosuppressive and cholinergic markers were evaluated in human CRC (LIM-2405, HT-29) cells. RESULTS: Increased expression of PD-L1, M3R, and ChAT at stages III-IV was associated with a high risk of CRC and poor survival outcomes independent of patients' gender and age. α7nAChR and PD-L2 were not changed at any CRC stages. Atropine and 4-DAMP suppressed the proliferation and migration of human CRC cells, induced apoptosis, and decreased PD-L1, PD-L2, and M3R expression in CRC cells via inhibition of EGFR and phosphorylation of ERK. CONCLUSIONS: The expression of immunosuppressive and cholinergic markers may increase the risk of recurrence of CRC. These markers might be used in determining prognosis and treatment regimens for CRC patients. Blocking cholinergic signaling may be a potential therapeutic for CRC through anti-proliferation and anti-migration via inhibition of EGFR and phosphorylation of ERK. These effects allow the immune system to recognize and eliminate cancer cells.

High-Dose Vitamin B6 (Pyridoxine) Displays Strong Anti-Inflammatory Properties in Lipopolysaccharide-Stimulated Monocytes.

Vitamin B6 is shown to have anti-inflammatory properties, which makes it an interesting nutraceutical agent. Vitamin B6 deficiency is well established as a contributor to inflammatory-related conditions, whilst B6 supplementation can reverse these inflammatory effects. There is less information available regarding the effects of high-dose vitamin B6 supplementation as a therapeutic agent. This study set out to examine the effects of high-dose vitamin B6 on an LPS-stimulated monocyte/macrophage cell population via an analysis of protein and gene expression using an RT2 profiler PCR array for Human Innate and Adaptive Immune responses. It was identified that high-dose vitamin B6 has a global anti-inflammatory effect on lipopolysaccharide-induced inflammation in monocyte/macrophage cells by downregulating the key broad-spectrum inflammatory mediators CCL2, CCL5, CXCL2, CXCL8, CXCL10, CCR4, CCR5, CXCR3, IL-1ß, IL-5, IL-6, IL-10, IL-18, IL-23-a, TNF-α, CSF2, DDX58, NLRP3, NOD1, NOD2, TLR-1 -2 -4 -5 -7 -8 -9, MYD88, C3, FOXP3, STAT1, STAT3, STAT6, LYZ, CASP-1, CD4, HLA-E, MAPK1, MAPK8 MPO, MX-1, NF-κß, NF-κß1A, CD14, CD40, CD40LG, CD86, Ly96, ICAM1, IRF3, ITGAM, and IFCAM2. The outcomes of this study show promise regarding vitamin B6 within the context of a potent broad-spectrum anti-inflammatory mediator and could prove useful as an adjunct treatment for inflammatory-related diseases.

Using Cognitive-Motor Dual-Tasks and Functional Near-Infrared Spectroscopy to Characterize Older Adults with and without Subjective Cognitive Decline.

BACKGROUND: Subjective cognitive decline (SCD) refers to individuals who report persistent cognitive deficits but perform normally on neuropsychological tests. Performance may be facilitated by increased prefrontal cortex activation, known as neural compensation, and could be used to differentiate between older adults with and without SCD. OBJECTIVE: This cross-sectional pilot study measured changes in the hemodynamic response (ΔHbO2) using functional near-infrared spectroscopy (fNIRS) as well as cognitive and motor performance during fine and gross motor dual-tasks in older adults with and without SCD. METHODS: Twenty older adults over 60 years old with (n = 10) and without (n = 10) SCD were recruited. Two experiments were conducted using 1) gross motor walking and 2) fine motor finger tapping tasks that were paired with an n-back working memory task. Participants also completed neuropsychological assessments and questionnaires on everyday functioning. RESULTS: Repeated measures ANOVAs demonstrated slower response times during dual-task gait compared to the single task (p = 0.032) and in the non-SCD group, slower gait speed was also observed in the dual compared to single task (p = 0.044). Response times during dual-task finger tapping were slower than the single task (p = 0.049) and greater ΔHbO2 was observed overall in the SCD compared to non-SCD group (p = 0.002). CONCLUSIONS: Examining neural and performance outcomes revealed differences between SCD and non-SCD groups and single and dual-tasks. Greater brain activation during dual-task finger tapping may reflect neural compensation, which should be examined in a larger sample and longitudinally to better characterize SCD.

Effects of Physical Activity on Physical and Mental Health of Older Adults Living in Care Settings: A Systematic Review of Meta-Analyses.

Previous studies included in meta-analyses have highlighted the effects of physical activity on the physical and psychological health of older adults living in care settings. We conducted a systematic review of meta-analyses, of institutionalized older adults, to evaluate and conduct a narrative synthesis of the results of these meta-analyses. A literature search was conducted in three databases (PubMed, Web of Science, and Cochrane Library) until 22 March 2023. After screening the identified articles with the PRISMA criteria filters, we included 11 meta-analyses in this systematic review. Higgins' (2013) assessment tool of the meta-analyses demonstrates that the studies were of good quality although future meta-analyses need to provide more information on the treatment of missing data. A summary of the results of these meta-analyses shows that physical activity reduces the rate of falls, mobility issues, functional dependence, and depression, and improves health status. Future studies need to focus on new ways to promote and adapt physical activities to increase the participation of older adults in care settings.