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Repairing the damaged blood-CNS-barrier in amyotrophic lateral sclerosis (ALS) is necessary to prevent entry of detrimental blood-borne factors contributing to motor neuron dysfunction. Recently, we showed benefits of human bone marrow endothelial progenitor cell (hBM-EPC) transplantation into symptomatic ALS mice on barrier restoration by replacing damaged endothelial cells (ECs). Additionally, transplanted cells may endogenously repair ECs by secreting angiogenic factors as our subsequent in vitro study demonstrated. Based on these study results, hBM-EPCs may secrete extracellular vesicles, which may contain and transfer diverse vesicular biomolecules towards maintenance of EC functionality. VX-809 price The study aimed to characterize extracellular vesicles (EVs) derived from hBM-EPCs as potential cell-free therapeutics for endothelium repair in ALS. EVs were isolated from hBM-EPC media at different culture times and vesicle properties were evaluated. The protective effects of EVs on mouse brain endothelial cells (mBECs) exposed to ALS mouse plasma were investigated. Uptake and blockage of EVs from GFP-transfected hBM-EPCs in ECs were determined in vitro. Results showed that EVs isolated from hBM-EPCs as nanosized vesicles significantly reduced mBEC damage from the pathological environment and these EVs were taken up by cells. Blockage of β1 integrin on EVs prevented internalization of vesicles in mBECs. Together, these results provide evidence for potential of hBM-EPC-derived EVs as novel cell-free therapeutics for repair of endothelium in ALS. Although determining translational potential of hBM-EPC-derived EVs will require evaluation in vivo, this in vitro study represents a step towards an extracellular vesicle-based approach for repair of the damaged microvascular endothelium in ALS.
Polypharmacy and use of inappropriate medications have been linked to increased risk of falls, hospitalizations, cognitive impairment, and death. The primary objective of this review was to evaluate the effectiveness, comparative effectiveness, and harms of deprescribing interventions among community-dwelling older adults.
We searched OVID MEDLINE Embase, CINAHL, and the Cochrane Library from 1990 through February 2019 for controlled clinical trials comparing any deprescribing intervention to usual care or another intervention. Primary outcomes were all-cause mortality, hospitalizations, health-related quality of life, and falls. The secondary outcome was use of potentially inappropriate medications (PIMs). Interventions were categorized as comprehensive medication review, educational initiatives, and computerized decision support. Data abstracted by one investigator were verified by another. We used the Cochrane criteria to rate risk of bias for each study and the GRADE system to determine certainty of eally inappropriate medications.
PROSPERO - CRD42019132420.
PROSPERO - CRD42019132420.
Healthcare providers use a life expectancy of at least 5 to 10 years in shared clinical decision-making with older adults about cancer screening, major surgeries, and disease prevention interventions. At present, few prognostic indexes predict long-term mortality beyond 10 years or are suited for use in primary care settings.
We developed and validated an 8-item multidimensional index predicting 11-year mortality for use in primary care.
Using data from the Singapore Longitudinal Ageing Studies (SLAS), we developed a Primary Care Prognostic (PCP) Index for predicting 11-year mortality risk in a development cohort (n = 1550) and validated it in a geographically different cohort (n = 928).
The PCP Index was derived from eight indicators (body mass loss, weakness, slow gait, comorbidity, polypharmacy, IADL/BADL dependency, low albumin, low total cholesterol, out of 25 candidate indicators) using stepwise Cox proportional hazard models.
In the developmental cohort, the mortality hazard ratio increased by 53% per PCP point score increase, independent of age and sex. Across risk categories, absolute risks of mortality increased from 5% (score 0) to 67.9% (scores 7-9), with area under curve (AUC = 0.77 (95% CI 0.73-0.80)). The PCP Index also predicted mortality in the validation cohort, with AUC = 0.70 (95% CI 0.64-0.75).
The PCP Index using simple clinical assessments and point scoring is a potentially useful prognostic tool for predicting long-term mortality and is well suited for risk stratification and shared clinical decision-making with older adults in primary care.
The PCP Index using simple clinical assessments and point scoring is a potentially useful prognostic tool for predicting long-term mortality and is well suited for risk stratification and shared clinical decision-making with older adults in primary care.Previous research has shown an association between cognitive control deficits and problematic behavior such as antisocial behavior and substance use, but little is known about the predictive value of cognitive control for treatment outcome. The current study tests whether selected markers of baseline cognitive control predict (1) treatment completion of a day treatment program involving a combination of approaches for multiproblem young adults and (2) daytime activities a year after the start of treatment, over and above psychological, social, and criminal characteristics. We assessed individual, neurobiological, and neurobehavioral measures, including functional brain activity during an inhibition task and two electroencephalographic measures of error processing in 127 male multiproblem young adults (age 18-27 years). We performed two hierarchical regression models to test the predictive power of cognitive control for treatment completion and daytime activities at follow-up. link2 The overall models did not significantly predict treatment completion or daytime activities at follow-up. However, activity in the anterior cingulate cortex (ACC) during response inhibition, years of regular alcohol use, internalizing problems, and ethnicity were all significant individual predictors of daytime activity at follow-up. In conclusion, cognitive control could not predict treatment completion or daytime activities a year after the start of treatment over and above individual characteristics. However, results indicate a direct association between brain activity during response inhibition and participation in daytime activities, such as work or school, after treatment. As adequate baseline inhibitory control is associated with a positive outcome at follow-up, this suggests interventions targeting cognitive control might result in better outcomes at follow-up.
This study aimed to characterize a commercially available primary human nasal epithelial cell culture and its gene expression of a wide range of drug transporters under different culture conditions.
Human nasal cells were cultured in three different types of culture media at the air-liquid (A-L) or liquid-liquid (L-L) interfaces for 1 or 3 wks. The effects of the different cell culture conditions were evaluated using light and electron microscopy, transepithelial electrical resistance (TEER) measurements, permeation studies with dextran, and gene expression profiling of 84 drug transporters.
The type of culture medium affected cell ultrastructure, TEER, and dextran permeation across epithelia. The expression of 20 drug transporter genes depended on the culture interface and/or time in culture; the A-L interface and longer time in culture favored higher expression levels of five ABC and seven SLC transporters.
Culture conditions influence the morphology, barrier formation, permeation properties, and drug transporter expression of human nasal epithelial cells, and this must be taken into consideration during the establishment and validation of in vitro models. A thorough characterization of a nasal epithelial model and its permeability properties is necessary to obtain an appropriate standardized model for the design of aerosol therapeutics and drug transport studies.
Culture conditions influence the morphology, barrier formation, permeation properties, and drug transporter expression of human nasal epithelial cells, and this must be taken into consideration during the establishment and validation of in vitro models. A thorough characterization of a nasal epithelial model and its permeability properties is necessary to obtain an appropriate standardized model for the design of aerosol therapeutics and drug transport studies.
Mentoring has become aprevalent educational strategy in medical education, with various aims. link3 Published reviews of mentoring report very little on group-based mentorship programs. The aim of this systematic review was to identify group-based mentorship programs for undergraduate medical students and describe their aims, structures, contents and program evaluations. Based on the findings of this review, the authors provide recommendations for the organization and assessment of such programs.
Asystematic review was conducted, according to PRISMA guidelines, and using the databases Ovid MEDLINE, EMBASE, PsycINFO and ERIC up to July 2019. Eight hundred abstracts were retrieved and 20studies included. Quality assessment of the quantitative studies was done using the Medical Education Research Study Quality Instrument (MERSQI).
The 20included studies describe 17different group mentorship programs for undergraduate medical students in seven countries. The programs were differently structured and used avariety medical education for regular meetings where discussions and personal reflection occur in a supportive environment.
Work meaning has gained attention as an important contributor to physician job engagement and well-being but little is known about how faculty participation in medical school learning communities might influence this phenomena. Our study goals were to determine how physician faculty members may derive meaning from serving as mentors for longitudinal learning communities of medical students, to understand how that meaning may impact other areas of their work, and relate our findings to existing literature and theoretical frameworks.
The research team conducted, recorded, transcribed, and coded 25semi-structured telephone interviews of faculty mentors from four US medical schools with curricular learning communities. The team used an iterative interview coding process to generate final themes and relate these themes to existing literature.
The authors identified five themes of meaning faculty derive from participation as learning community mentors "Iam abetter professional," "Iam more connected," "Iam rejon faculty. As learning communities become increasingly common within medical schools, this understanding may be important for leaders in academic medicine considering potential indirect benefits of this educational model.
There still remains agap between those who conduct science and those who engage in educating others about health sciences through various forms of social media. Few empirical studies have sought to define useful practices for engaging in social media for academic use in the health professions. Given the increasing importance of these platforms, we sought to define good practices and potential pitfalls with help of those respected for their work in this new field.
We conducted aqualitative study, guided by constructivist grounded theory principles, of 17 emerging experts in the field of academic social media. We engaged in asnowball sampling technique and conducted aseries of semi-structured interviews. The analytic team consisted of adiverse group of researchers with arange of experience in social media.
Understanding the strengths of various platforms was deemed to be of critical importance across all the participants. Key to building online engagement were the following 1)Culture-building strategies; 2)Tailoring the message; 3)Responsiveness; and 4)Heeding rules of online engagement.
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