• Hoffmann Vazquez posted an update 2 days, 11 hours ago

    © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.Wilson’s disease (WD) is an autosomal recessive disorder caused by ATP7B mutations. Subjects with only one mutation may show clinical signs and individuals with biallelic changes may remain asymptomatic. We aimed to achieve a conclusive genetic diagnosis for 34 patients clinically diagnosed of WD. Genetic analysis comprised from analysis of exons to WES (whole exome sequencing), including promoter, introns, UTRs (untranslated regions), besides of study of large deletions/duplications by MLPA (multiplex ligation-dependent probe amplification). Biallelic ATP7B mutations were identified in 30 patients, so that four patients were analyzed using WES. Two affected siblings resulted to be compound heterozygous for mutations in CCDC115, which is involved in a form of congenital disorder of glycosylation. In sum, the majority of patients with a WD phenotype carry ATP7B mutations. However, if genetic diagnosis is not achieved, additional genes should be considered because other disorders may mimic WD. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.OBJECTIVES Few studies examine the impact of frailty on long-term patient-oriented outcomes after emergency general surgery (EGS). We measured the prevalence of frailty among older EGS patients and examined the impact of frailty on 1-year outcomes. DESIGN Retrospective cohort study using 2008 to 2014 Medicare claims. SETTING Acute care hospitals. PARTICIPANTS Patients 65 years or older who received one of the five EGS procedures with the highest mortality burden (partial colectomy, small bowel resection, peptic ulcer disease repair, adhesiolysis, or laparotomy). MEASUREMENTS A validated claims-based frailty index (CFI) identified patients who were not frail (CFI  less then  .15), pre-frail (.15 ≤ CFI  less then  .25), mildly frail (.25 ≤ CFI  less then  .35), and moderately to severely frail (CFI ≥ .35). Multivariable Cox regression compared 1-year mortality. Multivariable Poisson regression compared rates of post-discharge hospital encounters (hospitalizations, intensive care unit stay, emergency department (256 and 203 vs 302 mean days; IRR = .97; CI = .96-.97 vs IRR = .95; CI = .94-.95, respectively). CONCLUSION Older EGS patients with frailty are at increased risk for poor 1-year outcomes and decreased home time. Targeted interventions for older EGS patients with frailty during the index EGS hospitalization are urgently needed to improve long-term outcomes. © 2020 The American Geriatrics Society.BACKGROUND/OBJECTIVES Improving glycemic control in older African Americans with diabetes and mild cognitive impairment (MCI) is important as the population ages and becomes more racially diverse. DESIGN Randomized controlled trial. SETTING Recruitment from primary care practices of an urban academic medical center. Community-based treatment delivery. PARTICIPANTS Older African Americans with MCI, low medication adherence, and poor glycemic control (N = 101). INTERVENTIONS Occupational therapy (OT) behavioral intervention and diabetes self-management education. MEASUREMENTS The primary outcome was a reduction in hemoglobin A1c level of at least 0.5% at 6 months, with maintenance effects assessed at 12 months. RESULTS At 6 months, 25 of 41 (61.0%) OT participants and 22 of 46 (48.2%) diabetes self-management education participants had a reduction in hemoglobin A1c level of at least 0.5%. The model-estimated rates were 58% (95% confidence interval [CI] = 45%-75%) and 48% (95% CI = 36%-64%), respectively (relative risk [RR] = 1.21; 95% CI = 0.84-1.75; P = .31). At 12 months, the respective rates were 21 of 39 (53.8%) OT participants and 24 of 49 (49.0%) diabetes self-management education participants. The model-estimated rates were 50% (95% CI = 37%-68%) and 48% (95% CI = 36%-64%), respectively (RR = 1.05; 95% CI = 0.70-1.57; P = .81). CONCLUSION Both interventions improved glycemic control in older African Americans with MCI and poor glycemic control. This result reinforces the American Diabetes Association’s recommendation to assess cognition in older persons with diabetes and demonstrates the potential to improve glycemic control in this high-risk population. Pirfenidone price © 2020 The American Geriatrics Society.Enzyme clustering into compact agglomerates could accelerate the processing of intermediates to enhance metabolic pathway flux. However, enzyme clustering is still a challenging task due to the lack of universal assembly strategy applicable to all enzymes. Therefore, we proposed an alternative enzyme assembly strategy based on functional inclusion bodies. First, functional inclusion bodies in cells were formed by the fusion expression of stomatin/prohibitin/flotillin/HflK/C (SPFH) domain and enhanced green fluorescent protein, as observed visually and by transmission electron microscopy. The formation of SPFH-induced functional inclusion bodies enhanced intermolecular polymerization as revealed by further analysis combined with Förster resonance energy transfer and bimolecular fluorescent complimentary. Finally, the functional inclusion bodies significantly improved the enzymatic catalysis in living cells, as proven by the examples with whole-cell biocatalysis of phenyllactic acid by Escherichia coli, and the production of N-acetylglucosamine by Bacillus subtilis. Our findings suggest that SPFH-induced functional inclusion bodies can enhance the cascade reaction of enzymes, to serve as a potential universal strategy for the construction of efficient microbial cell factories. © 2020 Wiley Periodicals, Inc.The increasing use of the question, “What matters most to you?” is a welcome development in the effort to provide patient-centered care. However, it is difficult for clinicians to translate answers to this question into treatment plans for chronic conditions, including recognizing when to consider options other than clinical practice guideline (CPG)-directed therapy. Goal elicitation is most helpful when a patient has different treatment options with clearly identifiable trade-offs. In the face of trade-offs, goal elicitation helps patients to prioritize among potentially competing outcomes. While decision aids (DAs) focus on trade-offs by delineating options and outcomes, the robust outcome data necessary to create DAs for older patients with multimorbidity are often lacking and even mild cognitive impairment makes the use of DAs difficult. The challenges for providing chronic disease care to older patients who are at risk for adverse events from CPG-directed therapy because of multimorbidity and/or frailty are to organize the complexity of individual combinations of diseases, conditions, and syndromes into common sets of trade-offs and to identify those goals or priorities that will directly inform a plan of care.