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In addition, chronic Triagonist treatment also up-regulated the expression levels of synaptophysin and PSD-95 in the hippocampus of 3xTg-AD mice. These results indicate that the Triagonist could improve memory formation, as well as synaptic transmission, Ca2+ balance, and neuronal excitability in 3xTg-AD mice. These neuroprotective effects of Triagonist may be involved in the up-regulation of synaptophysin and PSD-95. Therefore, the study suggests that multi-receptor agonists might be a novel therapeutic strategy for the treatment of AD. BACKGROUND Olive oil intake has been associated with lower risk of cardiovascular disease (CVD) in Mediterranean populations, but little is known about these associations in the U.S population. OBJECTIVES To examine whether olive oil intake is associated with total CVD, coronary heart disease (CHD) and stroke risk. METHODS We included 61,181 women from the Nurses' Health Study (1990-2014) and 31,797 men from the Health Professionals Follow-up Study (1990-2014) who were free of cancer, heart disease, and stroke at baseline. Diet was assessed using food frequency questionnaires at baseline and then every 4 years. Cox proportional hazards regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS During 24 years of follow-up, we documented 9,797 incident cases of CVD, including 6,034 CHD cases and 3,802 stroke cases. After adjusting for major diet and lifestyle factors, compared with non-consumers, those with higher olive oil intake (>1/2 tablespoon/d or >7g/d) had 14% lower risk of CVD [pooled HR (95% CI) 0.86 (0.79, 0.94)] and 18% lower risk of CHD [pooled HR (95% CI) 0.82 (0.73, 0.91)]. No significant associations were observed for total or ischemic stroke. Replacing 5g/d of margarine, butter, mayonnaise, or dairy fat with the equivalent amount of olive oil was associated with 5-7% lower risk of total CVD and CHD. No significant associations were observed when olive oil was compared with other plant oils combined. In a subset of participants, higher olive oil intake was associated with lower levels of circulating inflammatory biomarkers and a better lipid profile. CONCLUSIONS Higher olive oil intake was associated with lower risk of CHD and total CVD in two large prospective cohorts of U.S. men and women. The substitution of margarine, butter, mayonnaise, and dairy fat with olive oil could lead to lower risk of CHD and CVD. BACKGROUND The contribution of lung transplantation to the treatment of patients with end-stage cystic fibrosis (CF) has been debated. We aimed to describe achievable outcomes from high-volume CF and lung transplant programs. This study reports on the largest single-center experience of lung transplantation for adult and pediatric patients with CF. It also highlights the evolution of practice and outcomes over time. METHODS A retrospective analysis of the prospectively collected Toronto Lung Transplant database was carried out. Post-transplant survival in CF was calculated using the Kaplan-Meier method and analyzed with log-rank tests. RESULTS From 1983 to 2016, a total of 1,885 transplants were performed at our institution, where 364 (19.3%) were CF recipients and another 39 (2.1%) were CF retransplants. The mean age at first transplant was 29.5 ± 9.7 years where 56.6% were males and 91.5% were adults. Pre-transplantation, 88 patients (24.2%) were Burkholderia cepacia complex (BCC)-positive, 143 (39.3%) had diabetes mellitus, and the mean forced expiratory volume in one second was 26.0 ± 7.2%, as predicted at listing. The 1-, 5-, and 10-year probabilities of survival in adults who were BCC-negative were 94%, 70%, and 53%, respectively. Pediatric, BCC-positive, and retransplant recipients had worse survival than adult patients who were BCC-negative. Strategies to improve the donor pool did not affect survival but possibly reduced waitlist mortality. For the entire cohort, the most common causes of death after lung transplant were infection and chronic lung allograft dysfunction. CONCLUSIONS Lung transplantation for CF provides excellent short- and long-term outcomes. These results strongly support lung transplantation as the standard of care for patients with CF having advanced lung disease. The clustered regularly interspaced short palindromic repeat (CRISPR) has great potential to revolutionize biomedical research and disease therapy. The specific and efficient genome editing strongly depends on high efficiency of delivery of the CRISPR payloads. However, optimization of CRISPR delivery vehicles still remains a major obstacle. Recently, various non-viral vectors have been utilized to deliver CRISPR tools. Many of these vectors have multi-layer structures assembled. In this review, we will introduce the development of CRISPR-Cas9 systems and their general therapeutic applications by summarizing current CRISPR-Cas9 based clinical trials. We will highlight the multi-layer nanoparticles (NPs) that have been developed to deliver CRISPR cargos in vitro and in vivo for various purposes, as well the potential building blocks of multi-layer NPs. We will also discuss the challenges in making the CRISPR tools into viable pharmaceutical products and provide potential solutions on efficiency and biosafety issues. V.BACKGROUND There is conflicting evidence regarding the association between atrial fibrillation and the risk of subsequent fractures. METHODS We included participants aged 45 years or older from the Framingham Heart Study Offspring, Third Generation, New Offspring Spouse, Omni 1, and Omni 2 cohorts. We prespecified analyzing index age 65 years as our primary analysis; we repeated analyses for index ages 45, 55, and 75 years. The primary outcome was any incident bone fracture, except finger, toe, foot, skull, and facial fractures. We assessed the association between time-varying atrial fibrillation and subsequent fractures by an illness-death model that accounted for the competing risk of death. We estimated hazard ratios (HR) adjusted for age, sex, body mass index, smoking, diabetes, alcohol intake, and prior fracture. RESULTS We included 3,403 participants (mean age of 68 years, 53.3% female) in the analysis at index age 65 years and above. In all, 525 (15%) participants suffered incident fractures during follow-up (median 12.5 years). The HR between atrial fibrillation and subsequent fracture was 1.37 95%CI (1.06-1.79). There was no evidence of effect modification by sex (HR 1.55, 95%CI 1.06-2.26 in men; HR 1.22, 95%CI 0.84-1.77 in women; interaction p value 0.27). Results were consistent at other index ages. CONCLUSION Atrial Fibrillation was associated with increased risk of incident fracture in the community-based Framingham Heart Study. BACKGROUND Systemic corticosteroids are not indicated for acute respiratory tract infections yet are nonetheless prescribed in outpatient care. Acute respiratory tract infections are the most common diagnosis in direct to consumer (DTC) telemedicine. The objective of this study was to characterize use of corticosteroids for acute respiratory tract infections in this setting and assess the association between corticosteroid receipt and patient satisfaction. METHODS Encounters with acute respiratory tract infection patients 18 years and older on a nationwide DTC telemedicine platform were conducted by physicians between July 2016 and July 2018. Mixed effects logistic regression was used to assess differences in the odds of corticosteroid prescription. A second mixed effects model assessed differences in patient satisfaction by corticosteroid or antibiotic receipt. Adjusted prescribing rates for individual physicians were estimated. Models included diagnoses, patient age and geographic region, physician specialty and geographic region and antibiotic prescription. RESULTS Of the 85,972 encounters with 465 physicians, 11% resulted in a corticosteroid. The median physician prescribing rate was 4.0% (range less then 1% to 81%). Corticosteroid receipt was associated with higher satisfaction versus receiving nothing (OR2.54; 95%CI2.25-2.87). Patients who received both an antibiotic and a corticosteroid reported the highest satisfaction (OR 3.91; 95%CI3.27-4.68). There was no correlation between individual physicians' corticosteroid and antibiotic prescribing rates. CONCLUSIONS Corticosteroid receipt was associated with patient satisfaction. Most physicians rarely prescribed corticosteroids, yet a small number prescribed them frequently. Identification of high prescribing physicians for educational interventions could reduce use of corticosteroids for acute respiratory tract infections. The authors had access to all data and were involved in all aspects of this Clinical Communication to the Editor's preparation. They have no conflicts of interest to disclose and received no financial support in the preparation of this manuscript. CONTEXT Patients who have suffered from persistent symptoms often undergo lumbar spinal surgery (LSS). Motor imagery should be added to postoperative home exercises to reduce patient complaints. OBJECTIVE The aim of this study was to compare the effects of home exercise plus motor imagery and only home exercise in patients undergoing LSS. see more DESIGN A randomized controlled study. SETTINGS This study was designed by researchers at Dokuz Eylul University. PARTICIPANTS Thirty-seven patients undergoing LSS were randomized to motor imagery group (n = 19) and control group (n = 18). MAIN OUTCOME MEASURES Pain was measured by Visual Analogue Scale, disability related to low back pain by Oswestry Disability Index, pain-related fear by Tampa Scale of Kinesiophobia, depression by Beck Depression Inventory, quality of life by World Health Organization Quality of Life Scale-Short Form (WHOQOL-BREF). All assessments were repeated in the preoperative period, three weeks after and six weeks after the surgery. INTERVENTIONS Motor imagery group underwent home exercise plus motor imagery program applied by voice recording. Control group underwent only home exercise program. Exercise program compliance was monitored by exercise diary and telephone calls once every week. RESULTS There was a significant improvement in pain at rest and during activity, disability, kinesiophobia, depression, physical health and psychological sub-parameters of WHOQOL-BREF between preoperative period, and the third week and sixth week in both groups (p less then 0.05). When comparing groups for gain scores, there was a more significant improvement in pain during activity in motor imagery group (p less then 0.05). Motor imagery should be addressed as an effective treatment after LSS. INTRODUCTION Disease-related malnutrition (DRM) is underdiagnosed and underreported despite its well-known association with a worse prognosis. The emergence of Big Data and the application of artificial intelligence in Medicine have revolutionized the way knowledge is generated. The aim of this study is to assess whether a Big Data tool could help us detect the amount of DRM in our hospital. METHODOLOGY This was a descriptive, retrospective study using the Savana Manager® tool, which allows for automatically analyzing and extracting the relevant clinical information contained in the free text of the electronic medical record. A search was performed using the term "malnutrition", comparing the characteristics of patients with DRM to the population of hospitalized patients between January 2012 and December 2017. RESULTS Among the 180,279 hospitalization records with a discharge report in that period, only 4,446 episodes (2.47%) included the diagnosis of malnutrition. The mean age of patients with DRM was 75 years (SD 16), as compared to 59 years (SD 25) for the overall population.
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