Mesenchymal stem cells (MSCs) are the nonhematopoietic multipotent progenitor cells found in various adult tissues. They are characterized by their ease of isolation and their rapid growth in vitro ...while maintaining their differentiation potential, allowing for extensive expansion in culture that yields large quantities suitable for therapeutic use. This article reviews the immunomodulatory activities associated with MSCs. Numerous studies have demonstrated that MSCs are potently immunosuppressive in vitro and in vivo. However, this article presents a new paradigm in MSC biology, in which MSCs, at least in vitro, can undergo polarization into either a pro-inflammatory or an immunosuppressive phenotype.
IntroductionThere is widespread use of all-terrain vehicles (ATVs) in the USA for both work-related and recreational activities. In this study, we aimed to determine the difference in injury ...severity, Glasgow Coma scales and length of stay between ATV-related injuries and injuries sustained from motorcycles (MOTOs) and automobiles (AUTOs).MethodsWe retrospectively analysed ATV, MOTO and AUTO injuries from a Level 2 Trauma Center between 01 January 2015 and 31 August 2020. Proportional odds regression analyses, as well as multivariable regression models, were used to analyse the data.ResultsThere were significantly more male and paediatric patients that suffered ATV-related injuries compared with MOTO or AUTO injuries. Victims of ATV-related injuries were also more likely to have open fractures. Paediatric patients were less likely to sustain an injury from either AUTO or MOTO accidents compared with ATV accidents. Patients with no drug use during injury and those who used protective equipment such as seat belts and child seats were significantly associated with lower Injury Severity Scores and higher Glasgow Coma Scale scores, indicating less severe injuries.DiscussionPaediatric patients are very likely to suffer sequela and long-term disability due to the severity of ATV-related injuries. Public awareness campaigns to educate our population, especially our youth, about the danger of ATV use are highly needed.
Chronic ethanol consumption increases sensitivity of the mitochondrial permeability transition (MPT) pore induction in liver. Ca(2+) promotes MPT pore opening, and genetic ablation of cyclophilin D ...(CypD) increases the Ca(2+) threshold for the MPT. We used wild-type (WT) and CypD-null (CypD(-/-)) mice fed a control or an ethanol-containing diet to investigate the role of the MPT in ethanol-mediated liver injury. Ca(2+)-mediated induction of the MPT and mitochondrial respiration were measured in isolated liver mitochondria. Steatosis was present in WT and CypD(-/-) mice fed ethanol and accompanied by increased terminal deoxynucleotidyl transferase dUTP-mediated nick-end label-positive nuclei. Autophagy was increased in ethanol-fed WT mice compared with ethanol-fed CypD(-/-) mice, as reflected by an increase in the ratio of microtubule protein 1 light chain 3B II to microtubule protein 1 light chain 3B I. Higher levels of p62 were measured in CypD(-/-) than WT mice. Ethanol decreased mitochondrial respiratory control ratios and select complex activities in WT and CypD(-/-) mice. Ethanol also increased CypD protein in liver of WT mice. Mitochondria from control- and ethanol-fed WT mice were more sensitive to Ca(2+)-mediated MPT pore induction than mitochondria from their CypD(-/-) counterparts. Mitochondria from ethanol-fed CypD(-/-) mice were also more sensitive to Ca(2+)-induced swelling than mitochondria from control-fed CypD(-/-) mice but were less sensitive than mitochondria from ethanol-fed WT mice. In summary, CypD deficiency was associated with impaired autophagy and did not prevent ethanol-mediated steatosis. Furthermore, increased MPT sensitivity was observed in mitochondria from ethanol-fed WT and CypD(-/-) mice. We conclude that chronic ethanol consumption likely lowers the threshold for CypD-regulated and -independent characteristics of the ethanol-mediated MPT pore in liver mitochondria.
Historically, light curve studies of supernovae (SNe) and other transient classes have focused on individual objects with copious and high signal-to-noise observations. In the nascent era of wide ...field transient searches, objects with detailed observations are decreasing as a fraction of the overall known SN population, and this strategy sacrifices the majority of the information contained in the data about the underlying population of transients. A population level modeling approach, simultaneously fitting all available observations of objects in a transient sub-class of interest, fully mines the data to infer the properties of the population and avoids certain systematic biases. We present a novel hierarchical Bayesian statistical model for population level modeling of transient light curves, and discuss its implementation using an efficient Hamiltonian Monte Carlo technique. As a test case, we apply this model to the Type IIP SN sample from the Pan-STARRS1 Medium Deep Survey, consisting of 18,837 photometric observations of 76 SNe, corresponding to a joint posterior distribution with 9176 parameters under our model. Our hierarchical model fits provide improved constraints on light curve parameters relevant to the physical properties of their progenitor stars relative to modeling individual light curves alone. Moreover, we directly evaluate the probability for occurrence rates of unseen light curve characteristics from the model hyperparameters, addressing observational biases in survey methodology. We view this modeling framework as an unsupervised machine learning technique with the ability to maximize scientific returns from data to be collected by future wide field transient searches like LSST.
Human cathelicidin LL‐37, a host defense peptide derived from leukocytes and epithelial cells, plays a crucial role in innate and adaptive immunity. Not only does LL‐37 eliminate pathogenic microbes ...directly but also modulates host immune responses. Emerging evidence from tumor biology studies indicates that LL‐37 plays a prominent and complex role in carcinogenesis. Although overexpression of LL‐37 has been implicated in the development or progression of many human malignancies, including breast, ovarian and lung cancers, LL‐37 suppresses tumorigenesis in gastric cancer. These data are beginning to unveil the intricate and contradictory functions of LL‐37. The reasons for the tissue‐specific function of LL‐37 in carcinogenesis remain to be elucidated. Here, we review the relationship between LL‐37, its fragments and cancer progression as well as discuss the potential therapeutic implications of targeting this peptide.
Behavioral health integration (BHI) in primary care settings is critical to mental health care in the United States. Family medicine resident experience in BHI in family medicine residency (FMR) ...continuity clinics is essential preparation for practice. We surveyed FMR program directors to characterize the status of BHI in FMR training.
Using the Council of Academic Family Medicine Educational Research Alliance (CERA) 2017 survey, FMR program directors (n=478, 261 respondents, 54.6% response rate) were queried regarding the stage of BHI within the residency family medicine center (FMC), integration activities at the FMC, and the professions of the BH faculty. BHI was characterized by Substance Abuse and Mental Health Services Agency (SAMHSA) designations within FMRs, and chi-square or ANOVA with Tukey honest significant difference (HSD) post hoc testing was used to assess differences in reported BHI attributes.
Program directors reported a high level of BHI in their FMCs (44.1% full integration, 33.7% colocated). Higher levels of BHI were associated with increased use of warm handoffs, same day consultation, shared health records, and the use of behavioral health (BH) professionals for both mental health and medical issues. Family physicians, psychiatrists, and psychologists were most likely to be training residents in BHI.
Almost half of FMR programs have colocated BH care or fully integrated BH as defined by SAMHSA. Highly integrated FMRs use a diversity of behavioral professionals and activities. Residencies currently at the collaboration stage could increase BH provider types and BHI practices to better prepare residents for practice. Residencies with full BHI may consider focusing on supporting BHI-trained residents transitioning into practice, or disseminating the model in the general primary care community.
Spatiotemporal Controls on the Urban Aerobiome Mhuireach, Gwynne Á.; Betancourt-Román, Clarisse M.; Green, Jessica L. ...
Frontiers in ecology and evolution,
03/2019, Letnik:
7
Journal Article
Recenzirano
Odprti dostop
Greater exposure to environmental microorganisms has been hypothesized to reduce the likelihood of developing autoimmune disorders, and vegetation is known to be a source of diverse microbiota to the ...air. However, the spatiotemporal dynamics of airborne microbial communities in urban environments with varying amounts and types of vegetation are poorly understood. In this study we used high-throughput sequencing of the bacterial 16S rRNA gene to assess whether fine-scale variation in urban vegetation influences the diversity, composition, or structure of airborne bacterial communities over time. We used passive settling dishes to collect airborne bacteria from 36 sites representing three urban land cover types (forest, grassland, paved) over a 3-month period in Eugene-Springfield, Oregon, USA. We used remote sensing data (aerial 4-band orthoimagery and LiDAR) and geographic information systems (GIS) to assess detailed site characteristics (e.g., total vegetation cover and structural diversity) for each site. Our initial analysis indicated that site was the most important factor explaining variation in bacterial community structure (R2 = 0.32, p < 0.001), followed by sampling date (R2 = 0.24, p < 0.001), while land cover type was a significant but weak predictor (R2 = 0.06, p < 0.001) and other vegetation metrics were even less predictive. However, when samples were analyzed separately by date, the explanatory power of land cover type increased substantially; six of nine dates showed significant effects (p < 0.05) with R2 ranging from 0.16–0.31, indicating that land cover type had a marked influence on bacterial community structure that was obscured by the effects of site and sampling date. Despite the importance of site as a predictor of bacterial community structure, Mantel tests for spatial correlation were insignificant for most sampling dates, suggesting that localized site characteristics were driving this relationship. We use our results to propose a space-time conceptual model of the interactions between site-scale environmental features (e.g., vegetation characteristics) and regional-scale temporal processes and events (e.g., agricultural harvesting) to understand and perhaps manage intraurban airborne bacterial communities.
Through our diet, we are exposed to numerous natural and man-made chemicals, including polyphenols with hormone-like properties. The most abundant hormonally active polyphenols are characterized as ...weak estrogens. These chemicals are hypothesized to interfere with signaling pathways involved in important diseases such as breast cancer, which in most cases is initially estrogen dependent. Two such chemicals are bisphenol A (BPA), a plasticizer, and genistein, a component of soy. In spite of both possessing estrogenic properties, BPA and genistein yield different health outcomes. The exposure of rats during the prepubertal period to BPA increases the susceptibility of adult animals for mammary cancer development, whereas genistein decreases this susceptibility in a chemically induced model. Because both BPA and genistein possess estrogenic properties, it is certainly plausible that additional mechanisms are affected by these chemicals. Hence, it was our goal to investigate at the protein level how exposure to these 2 chemicals can contribute to mammary cancer causation as opposed to cancer chemoprevention. Using 2-dimensional gel electrophoresis followed by MS analysis, we identified differentially regulated proteins from the mammary glands of rats prepubertally exposed to BPA and genistein. Following protein identification, we used immunoblotting techniques to validate the identity and regulation of these proteins and to identify downstream signaling proteins. Our studies highlight the importance of proteomics technology in elucidating signaling pathways altered by exposure to hormonally active chemicals and its potential value in identifying biomarkers for mammary cancer.
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