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3-Dimensional (3D)-shaped rings are largely adopted for tricuspid annuloplasty, but evidence about their long-term results is scanty. The goal of this study was to analyse the long-term results of tricuspid annuloplasty with 3D-shaped rings.

A retrospective review of our prospectively maintained database was carried out to identify all patients who underwent tricuspid valve repair with 3D-shaped rings between January 2011 and December 2014. Kaplan-Meier methods were used to analyse long-term survival. Cumulative incidence function using death as the competitive outcome was used to estimate cardiac death.

A total of 168 patients were identified. The median age was 66 years. Eighty-two patients (49%) were in advanced New York Heart Association functional class III-IV. Atrial fibrillation (AF) was present in 101 (60%); the median ejection fraction was 60%. In 82 (49%) patients, a Medtronic 3D Contour annuloplasty ring was employed; in the remaining 86 (51%) patients, an Edwards MC3 ring was used. Cumulative incidence function of cardiac death, with non-cardiac death as a competing risk, was 1.9 ± 1.1%, 95% confidence interval (CI) (0.51-4.95) at 7 years. The cumulative incidence function of recurrence of tricuspid regurgitation (TR) ≥2+ at 7 years was 14 ± 3.17%, 95% CI (8.49-20.82). Recurrence of TR ≥2+ at 7 years was not significantly different between the Medtronic 3D Contour and the Edwards MC3 rings (P = 0.3). AF was identified as the only independent predictor of recurrence of TR ≥2+.

3D-shaped rings are effective and durable. TR recurrence was relatively low at 7 years and usually moderate (2+/4+) without a significant difference between the 2 types of rings. The role of AF as a predictor of TR recurrence was confirmed.

3D-shaped rings are effective and durable. TR recurrence was relatively low at 7 years and usually moderate (2+/4+) without a significant difference between the 2 types of rings. The role of AF as a predictor of TR recurrence was confirmed.Down syndrome (DS) is the most common genetic form of intellectual disability caused by the presence of an additional copy of human chromosome 21 (Hsa21). To provide novel insights into genotype-phenotype correlations, we used standardized behavioural tests, magnetic resonance imaging and hippocampal gene expression to screen several DS mouse models for the mouse chromosome 16 region homologous to Hsa21. First, we unravelled several genetic interactions between different regions of chromosome 16 and how they contribute significantly to altering the outcome of the phenotypes in brain cognition, function and structure. Then, in-depth analysis of misregulated expressed genes involved in synaptic dysfunction highlighted six biological cascades centred around DYRK1A, GSK3β, NPY, SNARE, RHOA and NPAS4. Finally, we provide a novel vision of the existing altered gene-gene crosstalk and molecular mechanisms targeting specific hubs in DS models that should become central to better understanding of DS and improving the development of therapies.We recently described aberrantly increased cytoplasmic SFPQ intron-retaining transcripts (IRTs) and concurrent SFPQ protein mislocalization as new hallmarks of amyotrophic lateral sclerosis (ALS). However the generalizability and potential roles of cytoplasmic IRTs in health and disease remain unclear. Here, using time-resolved deep-sequencing of nuclear and cytoplasmic fractions of hiPSCs undergoing motor neurogenesis, we reveal that ALS-causing VCP gene mutations lead to compartment-specific aberrant accumulation of IRTs. P110δ-IN-1 price Specifically, we identify >100 IRTs with increased cytoplasmic abundance in ALS samples. Furthermore, these aberrant cytoplasmic IRTs possess sequence-specific attributes and differential predicted binding affinity to RNA binding proteins (RBPs). Remarkably, TDP-43, SFPQ and FUS-RBPs known for nuclear-to-cytoplasmic mislocalization in ALS-abundantly and specifically bind to this aberrant cytoplasmic pool of IRTs, as opposed to any individual IRT. Our data are therefore consistent with a novel role for cytoplasmic IRTs in regulating compartment-specific protein abundance. This study provides new molecular insight into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.

Reorientation programmes have been an important component of neurotrauma rehabilitation for adults who suffer from post-traumatic amnesia (PTA) after traumatic brain injury (TBI); however, research testing the efficacy of acute programmes is limited.

This study aimed to determine if it is feasible to provide a standardized environmental reorientation programme to adults suffering from PTA after TBI in an acute care hospital setting, and whether it is likely to be beneficial.

We conducted a randomized controlled trial with concealed allocation and intention-to-treat analysis. A total of 40 participants suffering from PTA after TBI were included. The control group received usual care; the experimental group received usual care plus a standardized orientation programme inclusive of environmental cues. The primary outcome measure was time to emergence from PTA measured by the Westmead PTA Scale, assessed daily from hospital admission or on regaining consciousness.

Adherence to the orientation programme wa power of 80%.

The Veterans Affairs Frailty Index (VA-FI) is an electronic frailty index developed to measure frailty using administrative claims and electronic health records data in Veterans. An update to ICD-10 coding is needed to enable contemporary measurement of frailty.

International Classification of Diseases, ninth revision (ICD-9) codes from the original VA-FI were mapped to ICD-10 first using the Centers for Medicaid and Medicare Services (CMS) General Equivalence Mappings. The resulting ICD-10 codes were reviewed by 2 geriatricians. Using a national cohort of Veterans aged 65 years and older, the prevalence of deficits contributing to the VA-FI and associations between the VA-FI and mortality over years 2012-2018 were examined.

The updated VA-FI-10 includes 6422 codes representing 31 health deficits. Annual cohorts defined on October 1 of each year included 2 266 191 to 2 428 115 Veterans, for which the mean age was 76 years, 97%-98% were male, 78%-79% were White, and the mean VA-FI was 0.20-0.22. The VA-FI-10 deficits showed stability before and after the transition to ICD-10 in 2015, and maintained strong associations with mortality.

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