Caldwellbroberg5257
Understanding these aspects of cellular crosstalk within an atherosclerotic plaque may shed light on how to modify cell behavior and identify novel approaches to transform rupture-prone atheromas into stable lesions.
The intestine occupies the critical interface between cholesterol absorption and excretion. Surprisingly little is known about the role of de novo cholesterol synthesis in this organ, and its relationship to whole body cholesterol homeostasis. Here, we investigate the physiological importance of this pathway through genetic deletion of the rate-limiting enzyme.
Mice lacking 3-hydroxy-3-methylglutaryl-coenzyme A reductase (
) in intestinal villus and crypt epithelial cells were generated using a
-Cre transgene. Plasma lipids, intestinal morphology, mevalonate pathway metabolites, and gene expression were analyzed.
Mice with intestine-specific loss of
were markedly smaller at birth, but gain weight at a rate similar to wild-type littermates, and are viable and fertile into adulthood. Intestine lengths and weights were greater relative to body weight in both male and female
intestinal knockout mice. Male intestinal knockout had decreased plasma cholesterol levels, whereas fasting triglycerides were lower in both sexes. Lipidomics revealed substantial reductions in numerous nonsterol isoprenoids and sterol intermediates within the epithelial layer, but cholesterol levels were preserved.
intestinal knockout mice also showed robust activation of SREBP-2 (sterol-regulatory element binding protein-2) target genes in the epithelium, including the LDLR (low-density lipoprotein receptor). At the cellular level, loss of
is compensated for quickly after birth through a dramatic expansion of the stem cell compartment, which persists into adulthood.
Loss of
in the intestine is compatible with life through compensatory increases in intestinal absorptive surface area, LDLR expression, and expansion of the resident stem cell compartment.
Loss of Hmgcr in the intestine is compatible with life through compensatory increases in intestinal absorptive surface area, LDLR expression, and expansion of the resident stem cell compartment.Tweetable abstract Treating Clostridioides difficile infection with miRNAs alone or combined with live biotherapeutic products may augment therapeutic efficacy and help counteract drug resistance in the future.Background Lactic acid bacteria (LAB) confer beneficial health effects in humans. However, the safety of these bacteria and their potential to spread resistance in the environment must be evaluated. Materials & methods Fifty-three LAB were isolated from different food samples and assessed for the prevalence of virulence determinants and antibiotic resistance profile. Results Multiple resistance was reported for Lactobacillus brevis MIM04, having revealed phenotypic resistance to vancomycin (MIC >128 μg/ml), ampicillin, cefotaxime, oxacillin and gentamicin. Virulence traits (cylA, gelE, esp and agg) were detected using specific primers. Enterococcus faecium CHE32, Lactobacillus plantarum CHE37 and E. faecium MLK68 lack virulence genes, possess antimicrobial activity and survive in low pH and bile salt conditions. Conclusion Isolated LAB revealed probiotic properties.Aim The objective of this study was to determine the effect of standard and candidate prebiotics on the adhesion and biofilm formation of Bacteroides sp. in monoculture and co-culture with Clostridioides difficile. Materials & methods The effect of seven prebiotics on the adhesion and biofilm formation of Bacteroides sp. to three human cell lines was determined. The effect of Bacteroides sp. and fructooligosaccharides (FOS) on the adhesion and biofilm formation of C. difficile was tested by the co-incubation assay. Results Inulin, mannose and raffinose presented the best anti-adhesion properties against Bacteroides sp. Combination of Bacteroides sp. Wnt inhibitor with FOS decreased the adhesion of C. difficile. Conclusion The study shows the potential role of prebiotics and synbiotics in decreasing the burden of C. difficile infections.All patients surviving an acute aortic dissection require continued lifelong surveillance of their diseased aorta. Late complications, driven predominantly by chronic false lumen degeneration and aneurysm formation, often require surgical, endovascular, or hybrid interventions to treat or prevent aortic rupture. Imaging plays a central role in the medical decision-making of patients with chronic aortic dissection. Accurate aortic diameter measurements and rigorous, systematic documentation of diameter changes over time with different imaging equipment and modalities pose a range of practical challenges in these complex patients. Currently, no guidelines or recommendations for imaging surveillance in patients with chronic aortic dissection exist. In this document, we present state-of-the-art imaging and measurement techniques for patients with chronic aortic dissection and clarify the need for standardized measurements and reporting for lifelong surveillance. We also examine the emerging role of imaging and computer simulations to predict aortic false lumen degeneration, remodeling, and biomechanical failure from morphological and hemodynamic features. These insights may improve risk stratification, individualize contemporary treatment options, and potentially aid in the conception of novel treatment strategies in the future.Aim The current study was performed to define the role of KDM3A in thoracic aortic dissection (TAD). Methods The binding of HIF1α and KDM3A in HES1 was detected by ChIP and dual-luciferase reporter gene assay. Loss and gain-of function assays of HIF1α, KDM3A and HES1 were further performed in Ang-II-induced mouse aortic smooth muscle cell line (MOVAS) cells. Lastly, in vivo TAD models were established. Results HIF1α was highly expressed in TAD. KDM3A promoted the transcription activation of HES1. HIF1α enhanced the proliferation and migration of Ang-II-induced MOVAS cells, in addition to increasing thoracic aorta dilation to induce TAD formation in vivo. Silencing of HES1 reversed the effects of HIF1α in vivo and in vitro. Conclusion The findings indicated that interaction between HIF1α and KDM3A enhances the proliferation and migration of MOVAS cells to induce TAD.Research has shown that the months after hospital discharge following treatment for suicidal thoughts or behaviors is a high-risk period for suicide. Moreover, the needs of a subset of youths at increased risk for suicide are not being met by community mental health providers, resulting in frequent emergency department (ED) visits. While undertaking a quality improvement effort, the authors' health care system piloted caring text messages to support youths discharged from the hospital after screening positive for suicide risk in the ED. The text-messaging intervention was feasible and acceptable, and youths reported that the messages helped reduce their suicidal thoughts and behaviors postdischarge. The results of this text-messaging intervention prompted the Maryland Department of Health to offer a similar intervention to all Marylanders.The authors of this column describe and reflect on challenges and successes encountered during implementation of a participatory research collaborative focused on the pathways to mental health care for youths and young adults. The collaborative centered development of stakeholder partner-led, small-scale research projects, supported by the academic research team. The column calls for greater investment in research projects that are selected and designed by community stakeholders.The collaborative care model (CoCM) is a strategy of integrating behavioral health into primary care to expand access to high-quality mental health services in areas with few psychiatrists. CoCM is multifaceted, and its implementation is accelerating in high-resource settings. However, in low-resource settings, it may not be feasible to implement all CoCM components. Guidance is lacking on CoCM implementation when only some of its components are feasible. In this column, the authors used a cost-benefit approach to refine strategies for addressing common implementation challenges, incorporating the authors' experiences in what was gained and what was lost at each implementation step in three CoCM programs in diverse clinical settings in rural Nepal.
Online resources represent an important avenue to identify and support individuals who may be experiencing symptoms of psychosis but have yet to engage in care. Understanding the experiences and needs of this group is critical to inform outreach for early psychosis and improve outcomes by addressing barriers to early treatment.
The authors conducted a retrospective, explorative, cross-sectional analysis by using data collected by Mental Health America as part of their online psychosis screening and support program. Data included scores from the Prodromal Questionnaire-Brief, basic demographic information, and respondents' plans for next steps.
Of 120,937 respondents, most (82.1%) reported distressing psychosis-like experiences at levels sufficient to merit a referral to specialty care for additional evaluation. However, only 17.1% planned to seek treatment as a next step, with most (53.6%) wanting instead more information. Higher distress was only weakly associated with the plan to seek treatment. In ths want, how services should be presented, and what barriers may limit help seeking. These steps are critical to improve access to early intervention for individuals with psychosis spectrum disorders.
Although implementation science has taken hold in many areas of psychiatric services research, a need remains for developing effective, low-cost interventions for specific subpopulations with mental health conditions. The experimental therapeutics approach has gained momentum as a framework for developing effective interventions. However, few studies have taken steps to rigorously apply experimental therapeutics. This article provides a blueprint for applying this approach.
A focused literature review was conducted to document the frequency of the application of experimental therapeutics among articles published between 2011 and 2021 in some of the American Psychiatric Association's journals. Independently of the review, the authors delineated a four-component approach for applying experimental therapeutics in research and present practical, innovative strategies to advance psychiatric services research.
The four-component approach includes outlining prerequisites, identifying target mechanisms, proposing intervention strategies to address target mechanisms, and using advanced analytic methods. The strategies described for each component are not exhaustive; rather, they suggest promising avenues for research that can lead to more effective interventions and deeper understanding of how, and for whom, an intervention works.
The application of experimental therapeutics in psychiatric services research can lead to increased development, refinement, and implementation of effective interventions for specific populations or conditions.
The application of experimental therapeutics in psychiatric services research can lead to increased development, refinement, and implementation of effective interventions for specific populations or conditions.
