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1.
Bela Anand-Apte Jennifer R. Chao Ruchira Singh Heidi Stöhr 《Journal of neuroscience research》2019,97(1):88-97
Sorsby fundus dystrophy (SFD), an autosomal dominant, fully penetrant, degenerative disease of the macula, is manifested by symptoms of night blindness or sudden loss of visual acuity, usually in the third to fourth decades of life due to choroidal neovascularization (CNV). SFD is caused by specific mutations in the Tissue Inhibitor of Metalloproteinase-3, (TIMP3) gene. The predominant histo-pathological feature in the eyes of patients with SFD are confluent 20–30 m thick, amorphous deposits found between the basement membrane of the retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch's membrane. SFD is a rare disease but it has generated significant interest because it closely resembles the exudative or “wet” form of the more common age-related macular degeneration (AMD). In addition, in both SFD and AMD donor eyes, sub-retinal deposits have been shown to accumulate TIMP3 protein. Understanding the molecular functions of wild-type and mutant TIMP3 will provide significant insights into the patho-physiology of SFD and perhaps AMD. This review summarizes the current knowledge on TIMP3 and how mutations in TIMP3 cause SFD to provide insights into how we can study this disease going forward. Findings from these studies could have potential therapeutic implications for both SFD and AMD. 相似文献
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Emma J. Kilford Iroise Dumontheil Nicholas W. Wood Sarah-Jayne Blakemore 《Social cognitive and affective neuroscience》2015,10(6):777-782
The catechol-O-methyltransferase (COMT) enzyme is a major determinant of prefrontal dopamine levels. The Val158Met polymorphism affects COMT enzymatic activity and has been associated with variation in executive function and affective processing. This study investigated the effect of COMT genotype on the flexible modulation of the balance between processing self-generated and processing stimulus-oriented information, in the presence or absence of affective distractors. Analyses included 124 healthy adult participants, who were also assessed on standard working memory (WM) tasks. Relative to Val carriers, Met homozygotes made fewer errors when selecting and manipulating self-generated thoughts. This effect was partly accounted for by an association between COMT genotype and visuospatial WM performance. We also observed a complex interaction between the influence of affective distractors, COMT genotype and sex on task accuracy: male, but not female, participants showed a sensitivity to the affective distractors that was dependent on COMT genotype. This was not accounted for by WM performance. This study provides novel evidence of the role of dopaminergic genetic variation on the ability to select and manipulate self-generated thoughts. The results also suggest sexually dimorphic effects of COMT genotype on the influence of affective distractors on executive function. 相似文献
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Julia H. Vermylen Gordon J. Wood Elaine R. Cohen Jeffrey H. Barsuk William C. McGaghie Diane B. Wayne 《Journal of pain and symptom management》2019,57(3):682-687
Introduction
Physician communication impacts patient outcomes. However, communication skills, especially around difficult conversations, remain suboptimal, and there is no clear way to determine the validity of entrustment decisions. The aims of this study were to 1) describe the development of a simulation-based mastery learning (SBML) curriculum for breaking bad news (BBN) conversation skills and 2) set a defensible minimum passing standard (MPS) to ensure uniform skill acquisition among learners.Innovation
An SBML BBN curriculum was developed for fourth-year medical students. An assessment tool was created to evaluate the acquisition of skills involved in a BBN conversation. Pilot testing was completed to confirm improvement in skill acquisition and set the MPS.Outcomes
A BBN assessment tool containing a 15-item checklist and six scaled items was developed. Students' checklist performance improved significantly at post-test compared to baseline (mean 65.33%, SD = 12.09% vs mean 88.67%, SD = 9.45%, P < 0.001). Students were also significantly more likely to have at least a score of 4 (on a five-point scale) for the six scaled questions at post-test. The MPS was set at 80%, requiring a score of 12 items on the checklist and at least 4 of 5 for each scaled item. Using the MPS, 30% of students would require additional training after post-testing.Comments
We developed a SBML curriculum with a comprehensive assessment of BBN skills and a defensible competency standard. Future efforts will expand the mastery model to larger cohorts and assess the impact of rigorous education on patient care outcomes. 相似文献6.
Alexander C. Egbe Rosalyn Adigun Vidhu Anand Collin P. West Victor M. Montori Hassan M. Murad Emmanuel Akintoye Karim Osman Heidi M. Connolly 《The Canadian journal of cardiology》2019,35(12):1784-1790
BackgroundAlthough there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia.MethodsWe used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOf the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001).ConclusionsLV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem. 相似文献
7.
Rachel P. Winograd Ned Presnall Erin Stringfellow Claire Wood Phil Horn Alex Duello 《The American journal of drug and alcohol abuse》2019,45(4):333-340
Background: The opioid addiction and overdose crisis continues to ravage communities across the U.S. Maintenance pharmacotherapy using buprenorphine or methadone is the most effective intervention for Opioid Use Disorder (OUD), yet few have immediate and sustained access to these medications. Objectives: To address lack of medication access for people with OUD, the Missouri Department of Mental Health began implementing a Medication First (Med First) treatment approach in its publicly-funded system of comprehensive substance use disorder treatment programs. Methods: This Perspective describes the four principles of Med First, which are based on evidence-based guidelines. It draws conceptual comparisons between the Housing First approach to chronic homelessness and the Med First approach to pharmacotherapy for OUD, and compares state certification standards for substance use disorder (SUD) treatment (the traditional approach) to Med First guidelines for OUD treatment. Finally, the Perspective details how Med First principles have been practically implemented. Results: Med First principles emphasize timely access to maintenance pharmacotherapy without requiring psychosocial services or discontinuation for any reason other than harm to the client. Early results regarding medication utilization and treatment retention are promising. Feedback from providers has been largely favorable, though clinical- and system-level obstacles to effective OUD treatment remain. Conclusion: Like the Housing First model, Medication First is designed to decrease human suffering and activate the strengths and capacities of people in need. It draws on decades of research and facilitates partnerships between psychosocial and medical treatment providers to offer effective and life-saving care to persons with OUD. 相似文献
8.
Heidi J Kalkwarf John A Shepherd Didier Hans Elena Gonzalez Rodriguez Joseph M Kindler Joan M Lappe Sharon Oberfield Karen K Winer Babette S Zemel 《Journal of bone and mineral research》2022,37(4):776-785
Trabecular bone score (TBS) is used for fracture prediction in adults, but its utility in children is limited by absence of appropriate reference values. We aimed to develop reference ranges for TBS by age, sex, and population ancestry for youth ages 5 to 20 years. We also investigated the association between height, body mass index (BMI), and TBS, agreement between TBS and lumbar spine areal bone mineral density (aBMD) and bone mineral apparent density (BMAD) Z-scores, tracking of TBS Z-scores over time, and precision of TBS measurements. We performed secondary analysis of spine dual-energy X-ray absorptiometry (DXA) scans from the Bone Mineral Density in Childhood Study (BMDCS), a mixed longitudinal cohort of healthy children (n = 2014) evaluated at five US centers. TBS was derived using a dedicated TBS algorithm accounting for tissue thickness rather than BMI. TBS increased only during ages corresponding to pubertal development with an earlier increase in females than males. There were no differences in TBS between African Americans and non-African Americans. We provide sex-specific TBS reference ranges and LMS values for calculation of TBS Z-scores by age and means and SD for calculation of Z-scores by pubertal stage. TBS Z-scores were positively associated with height Z-scores at some ages. TBS Z-scores explained only 27% and 17% of the variance of spine aBMD and BMAD Z-scores. Tracking of TBS Z-scores over 6 years was lower (r = 0.47) than for aBMD or BMAD Z-scores (r = 0.74 to 0.79), and precision error of TBS (2.87%) was greater than for aBMD (0.85%) and BMAD (1.22%). In sum, TBS Z-scores provide information distinct from spine aBMD and BMAD Z-scores. Our robust reference ranges for TBS in a well-characterized pediatric cohort and precision error estimates provide essential tools for clinical assessment using TBS and determination of its value in predicting bone fragility in childhood and adolescence. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
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Philippe A. Eigenmann Motohiro Ebisawa Matthew Greenhawt Jonathan O’B Hourihane Tamara T. Perry Benjamin C. Remington Robert A. Wood 《Pediatric allergy and immunology》2021,32(4):658-666
Risk is a concept inherent in every medical procedure. It can be defined as the probability of an adverse event in a defined population over a specified period of time. In the frame of food allergy management, it might be related to a diagnostic procedure, a treatment, or the consumption of foods. The risk of an adverse event can also be augmented by individual factors. This rostrum article discusses various aspects faced by children with food allergies in the light of risk, and their practical implications. Identifying personal risks for severe reaction, such as unstable asthma, and correcting them whenever possible also contribute to a reduction of the risk inherent to food allergy. Among the facets discussed, oral food challenges (OFC) are the most common diagnostic procedures implying an inherent risk. The risk of OFCs can be minimized by correct indication and timing of the test, a safe setting, as well as by ensuring that the patient is otherwise well without potential stressor potentially increasing the risk of a more severe reaction. Oral immunotherapy (OIT) has been studied as a potential treatment for increasing the threshold dose for reaction, and thus reducing the risk of accidental reaction. Nevertheless, the procedure is not devoid of risk as the patients may and do often react during the course of the procedure. Ingestion of trace amounts in processed foods, mainly in community settings such as restaurants, schools, or day care, represents a potential risk of reactions, although for a minority of patients. Precautionary allergen labeling (PAL) is a widespread strategy to reduce the potential risk of reactions due to traces. However, PAL is currently inefficient due to inconsistent labeling, also not indicating a clear maximum amount possibly present in the manufactured food. Finally, cost-effectiveness needs to be considered in risk management, as many risk reduction procedures are clearly not cost-effective. 相似文献