Reversibility of frailty after lung transplantation

Background. Frailty contributes to increased morbidity and mortality in patients referred for and undergoing lung transplantation (LTX). &e study aim was to determine if frailty is reversible after LTX in those classified as frail at LTX evaluation. Methods. Consecutive LTX recipients were included. All patients underwent modified physical frailty assessment during LTX evaluation. For patients assessed as frail, frailty was reassessed on completion of the post-LTX rehabilitation program. Frailty was defined by the presence of ≥ 3 domains of the modified Fried Frailty Phenotype (mFFP). Results. We performed 166 lung transplants (frail patients, n = 27, 16%). Eighteen of the 27 frail patients have undergone frailty reassessment. Eight frail patients died, and one interstate recipient did not return for reassessment. In the 18 (66%) patients reassessed, there was an overall reduction in their frailty score post-LTX ((3.4 ± 0.6 to 1.0 ± 0.7), p < 0.001) with 17/18 (94%) no longer classified as frail. Improvements were seen in the following frailty domains: exhaustion, mobility, appetite, and activity. Handgrip strength did not improve posttransplant. Conclusions. Physical frailty was largely reversible following LTX, underscoring the importance of considering frailty a dynamic, not a fixed, entity. Further work is needed to identify those patients whose frailty is modifiable and establish specific interventions to improve frailty

A superadditivity and submultiplicativity property for cardinalities of sumsets

For finite sets of integers A1, . . . ,An we study the cardinality of the n-fold sumset A1 + · · · + An compared to those of (n − 1)-fold sumsets A1 + · · · + Ai−1 + Ai+1 + · · · + An. We prove a superadditivity and a submultiplicativity property for these quantities. We also examine the case when the addition of elements is restricted to an addition graph between the sets

Mll-AF4 Confers Enhanced Self-Renewal and Lymphoid Potential during a Restricted Window in Development.

MLL-AF4+ infant B cell acute lymphoblastic leukemia is characterized by an early onset and dismal survival. It initiates before birth, and very little is known about the early stages of the disease's development. Using a conditional Mll-AF4-expressing mouse model in which fusion expression is targeted to the earliest definitive hematopoietic cells generated in the mouse embryo, we demonstrate that Mll-AF4 imparts enhanced B lymphoid potential and increases repopulation and self-renewal capacity during a putative pre-leukemic state. This occurs between embryonic days 12 and 14 and manifests itself most strongly in the lymphoid-primed multipotent progenitor population, thus pointing to a window of opportunity and a potential cell of origin. However, this state alone is insufficient to generate disease, with the mice succumbing to B cell lymphomas only after a long latency. Future analysis of the molecular details of this pre-leukemic state will shed light on additional events required for progression to acute leukemia.Core facilities at the Cambridge Institute for Medical Research are supported by Strategic Award WT100140 and equipment grant 093026; core facilities at the Edinburgh MRC Centre for Regenerative Medicine are supported by centre grant MR/K017047/1. This work was funded by a Bloodwise Bennett Senior Fellowship (10015 to K.O.), a Wellcome Trust Clinical PhD Studentship (097454/z/11/z to N.A.B.) the Gabrielle’s Angel Foundation for Cancer Research (to K.O.), and the Kay Kendall Leukaemia Fund (to K.O.).This is the final version of the article. It first appeared from Cell Press/Elsevier at http://dx.doi.org/10.1016/j.celrep.2016.06.046

Risk Factor Models for Neurodevelopmental Outcomes in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review of Methodology and Reporting.

The prediction of long-term outcomes in surviving infants born very preterm (VPT) or with very low birth weight (VLBW) is necessary to guide clinical management, provide information to parents, and help target and evaluate interventions. There is a large body of literature describing risk factor models for neurodevelopmental outcomes in VPT/VLBW children, yet few, if any, have been developed for use in routine clinical practice or adopted for use in research studies or policy evaluation. We sought to systematically review the methods and reporting of studies that have developed a multivariable risk factor model for neurodevelopment in surviving VPT/VLBW children. We searched the MEDLINE, Embase, and PsycINFO databases from January 1, 1990, to June 1, 2014, and identified 78 studies reporting 222 risk factor models. Most studies presented risk factor analyses that were not intended to be used for prediction, confirming that there is a dearth of specifically designed prognostic modeling studies for long-term outcomes in surviving VPT/VLBW children. We highlight the strengths and weaknesses of the research methodology and reporting to date, and provide recommendations for the design and analysis of future studies seeking to analyze risk prediction or develop prognostic models for VPT/VLBW children

Sculpting DNA-based synthetic cells through phase separation and phase-targeted activity

Synthetic cells, like their biological counterparts, require internal compartments with distinct chemical and physical properties where different functionalities can be localized. Inspired by membrane-less compartmentalization in biological cells, here, we demonstrate how microphase separation can be used to engineer heterogeneous cell-like architectures with programmable morphology and compartment-targeted activity. The synthetic cells self-assemble from amphiphilic DNA nanostructures, producing core-shell condensates due to size-induced de-mixing. Lipid deposition and phase-selective etching are then used to generate a porous pseudo-membrane, a cytoplasm analog, and membrane-less organelles. The synthetic cells can sustain RNA synthesis via in vitro transcription, leading to cytoplasm and pseudo-membrane expansion caused by an accumulation of the transcript. Our approach exemplifies how architectural and functional complexity can emerge from a limited number of distinct building blocks, if molecular-scale programmability, emergent biophysical phenomena, and biochemical activity are coupled to mimic those observed in live cells

Association of atrial fibrillation and obstructive sleep apnea.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with recurrent atrial fibrillation (AF) after electrocardioversion. OSA is highly prevalent in patients who are male, obese, and/or hypertensive, but its prevalence in patients with AF is unknown. METHODS AND RESULTS: We prospectively studied consecutive patients undergoing electrocardioversion for AF (n=151) and consecutive patients without past or current AF referred to a general cardiology practice (n=312). OSA was diagnosed with the Berlin questionnaire, which is validated to identify patients with OSA. We also assessed its accuracy compared with polysomnography in a sample of the study population. Groups were compared with the 2-tailed t, Wilcoxon, and chi2 tests. Logistic regression modeled the association of AF and OSA after adjustment for relevant covariates. Patients in each group had similar age, gender, body mass index, and rates of diabetes, hypertension, and congestive heart failure. The questionnaire performed with 0.86 sensitivity, 0.89 specificity, and 0.97 positive predictive value in our sample. The proportion of patients with OSA was significantly higher in the AF group than in the general cardiology group (49% versus 32%, P=0.0004). The adjusted odds ratio for the association between AF and OSA was 2.19 (95% CI 1.40 to 3.42, P=0.0006). CONCLUSIONS: The novel finding of this study is that a strong association exists between OSA and AF, such that OSA is strikingly more prevalent in patients with AF than in high-risk patients with multiple other cardiovascular diseases. The coinciding epidemics of obesity and AF underscore the clinical importance of these results