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

The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that exist on a clinico-pathogenetic spectrum, designated ALS/FTD. The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC)n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. We observe significant aggregation of the hexanucleotide sequence (GGGGCC)n, which we associate to the formation of multimolecular G-quadruplexes (mG4s) by using a range of biophysical techniques. Exposing the condensates to G4-unfolding conditions leads to prompt disassembly, highlighting the key role of mG4-formation in the condensation process. We further validate the biological relevance of our findings by detecting an increased prevalence of G4-structures in C9orf72 mutant human motor neurons when compared to healthy motor neurons by staining with a G4-selective fluorescent probe, revealing signal in putative condensates. Our findings strongly suggest that RNA G-rich repetitive sequences can form protein-free condensates sustained by multimolecular G-quadruplexes, highlighting their potential relevance as therapeutic targets for C9orf72 mutation-related ALS/FTD

Prevalence of anxiety and post-traumatic stress (PTS) among the parents of babies admitted to neonatal units: a systematic review and meta-analysis

Background Parents of babies admitted to neonatal units (NNU) are exposed to a range of potentially distressing experiences, which can lead to mental health symptoms such as increased anxiety and post-traumatic stress (PTS). This review aimed to describe how anxiety and PTS are defined and assessed, and to estimate anxiety and PTS prevalence among parents of babies admitted to NNU. Method Medline, Embase, PsychoINFO, Cumulative Index to Nursing and Allied Health literature were searched to identify studies published prior to April 14, 2021. Included studies were assessed using Hoy risk of bias tool. A random-effects model was used to estimate pooled prevalence with 95% CIs. Potential sources of variation were investigated using subgroup analyses and meta-regression. The review is registered with PROSPERO (CRD42020162935). Findings Fifty six studies involving 6,036 parents met the review criteria; 21 studies assessed anxiety, 35 assessed PTS, and 8 assessed both. The pooled prevalence of anxiety was 41.9% (95%CI:30.9, 53.0) and the pooled prevalence of PTS was 39.9% (95%CI:30.8, 48.9) among parents up to one month after the birth. Anxiety prevalence decreased to 26.3% (95%CI:10.1, 42.5) and PTS prevalence to 24.5% (95%CI:17.4, 31.6) between one month and one year after birth. More than one year after birth PTS prevalence remained high 27.1% (95%CI:20.7, 33.6). Data on anxiety at this time point were limited. There was high heterogeneity between studies and some evidence from subgroup and meta-regression analyses that study characteristics contributed to the variation in prevalence estimates. Interpretation The prevalence of anxiety and PTS was high among parents of babies admitted to NNU. The rates declined over time, although they remained higher than population prevalence estimates for women in the perinatal period. Implementing routine screening would enable early diagnosis and effective intervention. Funding This research is funded by the National Institute for Health Research (NIHR) Policy Research Programme, conducted through the Policy Research Unit in Maternal and Neonatal Health and Care, PR-PRU-1217-21202. The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care

The maximum clique enumeration problem: algorithms, applications, and implementations

Background The maximum clique enumeration (MCE) problem asks that we identify all maximum cliques in a finite, simple graph. MCE is closely related to two other well-known and widely-studied problems: the maximum clique optimization problem, which asks us to determine the size of a largest clique, and the maximal clique enumeration problem, which asks that we compile a listing of all maximal cliques. Naturally, these three problems are View MathML /\u3e-hard, given that they subsume the classic version of the View MathML /\u3e-complete clique decision problem. MCE can be solved in principle with standard enumeration methods due to Bron, Kerbosch, Kose and others. Unfortunately, these techniques are ill-suited to graphs encountered in our applications. We must solve MCE on instances deeply seeded in data mining and computational biology, where high-throughput data capture often creates graphs of extreme size and density. MCE can also be solved in principle using more modern algorithms based in part on vertex cover and the theory of fixed-parameter tractability (FPT). While FPT is an improvement, these algorithms too can fail to scale sufficiently well as the sizes and densities of our datasets grow. Results An extensive testbed of benchmark graphs are created using publicly available transcriptomic datasets from the Gene Expression Omnibus (GEO). Empirical testing reveals crucial but latent features of such high-throughput biological data. In turn, it is shown that these features distinguish real data from random data intended to reproduce salient topological features. In particular, with real data there tends to be an unusually high degree of maximum clique overlap. Armed with this knowledge, novel decomposition strategies are tuned to the data and coupled with the best FPT MCE implementations. Conclusions Several algorithmic improvements to MCE are made which progressively decrease the run time on graphs in the testbed. Frequently the final runtime improvement is several orders of magnitude. As a result, instances which were once prohibitively time-consuming to solve are brought into the domain of realistic feasibility

Scientific review by the marine science advisory panel of Oregon University System scientists of the US Commission on ocean policy preliminary report for Governor Kulongoski's Oregon response

The U.S. Commission on Ocean Policy (USCOP) has articulated a set of overarching Guiding Principles to frame the creation of a new national ocean policy. When taken collectively, these principles provide a careful, circumspect, and ambitious context from which to develop policies that will promote vibrant coastal communities, healthy and resilient ecosystems, abundant wildlife, sustainable fisheries, clean and safe shorelines, and enjoyable and inspirational recreational opportunities—in short, the visions that Oregonians articulate for their coast and ocean. The Guiding Principles align closely with Oregon’s Statewide Planning Goals, policies, and values. In fact, they underscore the importance of weighing long-term interests more heavily than short-term ones in the balance of competing uses. They are holistic in geographic scope, rather than focused on a single component of a complex ecosystem. The USCOP Guiding Principles were conceived to foster an atmosphere of objective scientific inquiry to form the basis of policy and decision-making to reconcile the diverse needs of all Oregonians.Keywords: Estuary, Shellfish, Beach, Fish, Kelp, Estuarine, Habitat, Algae, Marine, Indicators, Freshwater, Mammal

Anterior anal sphincter repair can be of long term benefit: a 12-year case cohort from a single surgeon

BACKGROUND: Early surgical results of anterior sphincter repair for faecal incontinence can be good, but in the longer term are often disappointing. This study aimed to determine the short and long term outcomes from anterior sphincter repair and identify factors predictive of long term success. METHODS: Patients who underwent anterior sphincter repair between 1989 and 2001 in one institution were identified. Postal questionnaires were sent to patients, which included validated scoring systems for symptom severity and quality of life assessments for faecal incontinence. Patient demographics and risk factors were recorded as were the results of anorectal physiology studies and endoanal ultrasound. RESULTS: Eighty-five patients underwent repair by one consultant. The length of follow up ranged from 1 to 12 years. Most patients (96%) had early symptom improvement postoperatively. Of the 47 patients assessed long term (≥ 5 years), 28 (60%) maintained this success. Significant improvements in quality of life were observed (P < 0.001). Neither patient, surgical nor anorectal physiology study parameters were predictive of outcome. CONCLUSION: There were no predictive factors of outcome success and no changes in anal manometry identified, however anterior sphincter repair remains worthwhile. Changes in compliance of the anorectum may be responsible for symptom improvement

Association of Serum Ferritin Levels Before Start of Conditioning With Mortality After alloSCT - A Prospective, Non-interventional Study of the EBMT Transplant Complications Working Party

Elevated serum ferritin levels occur due to iron overload or during inflammation and macrophage activation. A correlation of high serum ferritin levels with increased mortality after alloSCT has been suggested by several retrospective analyses as well as by two smaller prospective studies. This prospective multicentric study aimed to study the association of ferritin serum levels before start of conditioning with alloSCT outcome. Patients with acute leukemia, lymphoma or MDS receiving a matched sibling alloSCT for the first time were considered for inclusion, regardless of conditioning. A comparison of outcomes between patients with high and low ferritin level was performed using univariate analysis and multivariate analysis using cause-specific Cox model. Twenty centers reported data on 298 alloSCT recipients. The ferritin cut off point was determined at 1500 mu g/l (median of measured ferritin levels). In alloSCT recipients with ferritin levels above cut off measured before the start of conditioning, overall survival (HR = 2.5, CI = 1.5-4.1, p = 0.0005) and progression-free survival (HR = 2.4, CI = 1.6-3.8, p <0.0001) were inferior. Excess mortality in the high ferritin group was due to both higher relapse incidence (HR = 2.2, CI = 1.2-3.8, p = 0.007) and increased non-relapse mortality (NRM) (HR = 3.1, CI = 1.5-6.4, p = 0.002). NRM was driven by significantly higher infection-related mortality in the high ferritin group (HR = 3.9, CI = 1.6-9.7, p = 0.003). Acute and chronic GVHD incidence or severity were not associated to serum ferritin levels. We conclude that ferritin levels can serve as routine laboratory biomarker for mortality risk assessment before alloSCT.Peer reviewe