Long-term pulse wave velocity outcomes with aerobic and resistance training in kidney transplant recipients – A pilot randomised controlled trial

Supporting information: S1 Fig. study protocol.(available at https://doi.org/10.1371/journal.pone.0171063.s001 (DOCM)); S1 Table. supplementary raw data (available at: https://doi.org/10.1371/journal.pone.0171063.s002 (XLSX)); S2 Fig. Consort checklist (available at: https://doi.org/10.1371/journal.pone.0171063.s003 (DOC)).Copyright: © 2017 O’Connor et al. Background This pilot study examined long-term pulse wave velocity (PWV) and peak oxygen uptake (VO2peak) outcomes following a 12-week moderate-intensity aerobic or resistance training programme in kidney transplant recipients. Method Single-blind, bi-centre randomised controlled parallel trial. 42 out of 60 participants completed a 9-month follow-up assessment (Aerobic training = 12, Resistance training = 10 and usual care = 20). Participants completed 12 weeks of twice-weekly supervised aerobic or resistance training. Following the 12-week exercise intervention, participants were transitioned to self-managed community exercise activity using motivational interviewing techniques. Usual care participants received usual encouragement for physical activity during routine clinical appointments in the transplant clinic. PWV, VO2peak, blood pressure and body weight were assessed at 12 weeks and 12 months, and compared to baseline. Results ANCOVA analysis, covarying for baseline values, age, and length of time on dialysis pre-transplantation, revealed a significant mean between-group difference in PWV of -1.30 m/sec (95%CI -2.44 to -0.17, p = 0.03) between resistance training and usual care groups. When comparing the aerobic training and usual care groups at 9-month follow-up, there was a mean difference of -1.05 m/sec (95%CI -2.11 to 0.017, p = 0.05). A significant mean between-group difference in relative VO2peak values of 2.2 ml/kg/min (95% CI 0.37 to 4.03, p = 0.02) when comparing aerobic training with usual care was revealed. There was no significant between group differences in body weight or blood pressure. There were no significant adverse effects associated with the interventions. Conclusions Significant between-group differences in 9-month follow-up PWV existed when comparing resistance exercise intervention with usual care. A long-term between-group difference in VO2peak was only evident when comparing aerobic intervention with usual care. This pilot study, with a small sample size, did not aim to elucidate mechanistic mediators related to the exercise interventions. It is however suggested that a motivational interviewing approach, combined with appropriate transition to community training programmes, could maintain the improvements gained from the 12-week exercise interventions and further research in this area is therefore warranted. Trial registration study number: ISRCTN43892586.National Institute for Health Research (NIHR). The study was hosted in the KCH NIHR Clinical Research Facility. This paper presents independent research funded by the NIHR

Theories of behaviour change synthesised into a set of theoretical groupings: Introducing a thematic series on the Theoretical Domains Framework

Behaviour change is key to increasing the uptake of evidence into healthcare practice. Designing behaviour-change interventions first requires problem analysis, ideally informed by theory. Yet the large number of partly overlapping theories of behaviour makes it difficult to select the most appropriate theory. The need for an overarching theoretical framework of behaviour change was addressed in research in which 128 explanatory constructs from 33 theories of behaviour were identified and grouped. The resulting Theoretical Domains Framework (TDF) appears to be a helpful basis for investigating implementation problems. Research groups in several countries have conducted TDF-based studies. It seems timely to bring together the experience of these teams in a thematic series to demonstrate further applications and to report key developments. This overview article describes the TDF, provides a brief critique of the framework, and introduces this thematic series. In a brief review to assess the extent of TDF-based research, we identified 133 papers that cite the framework. Of these, 17 used the TDF as the basis for empirical studies to explore health professionals’ behaviour. The identified papers provide evidence of the impact of the TDF on implementation research. Two major strengths of the framework are its theoretical coverage and its capacity to elicit beliefs that could signify key mediators of behaviour change. The TDF provides a useful conceptual basis for assessing implementation problems, designing interventions to enhance healthcare practice, and understanding behaviour-change processes. We discuss limitations and research challenges and introduce papers in this series

oHSV Genome Editing by Means of galK Recombineering

open8noThis work was supported by European Research Council (ERC) Advanced Grant number 340060, VII framework program to G. C.-F., by RFO (University of Bologna) to L.M. and T.G, and by Fondi Pallotti to T.G.Since the cloning of the herpes simplex virus (HSV) genome as BAC (bacterial artificial chromosome), the genetic engineering of the viral genome has become readily feasible. The advantage is that the modification of the animal virus genome is carried out in bacteria, with no replication or production of viral progeny, and is separated from the reconstitution or regeneration of the recombinant virus in mammalian cells. This allows an easy engineering of essential genes, as well. Many technologies have been developed for herpesvirus BAC engineering. In our hands the most powerful is galK recombineering that exploits a single marker (galK) for positive and negative selection and PCR amplicons for seamless modification in the desired genome locus. Here we describe the engineering of the HSV recombinant BAC 115 by the insertion of a heterologous cassette for the expression of murine interleukin 12 (mIL12) in the intergenic sequence between US1 and US2 ORFs.embargoed_20201017Laura Menotti, Valerio Leoni, Valentina Gatta, Biljana Petrovic, Andrea Vannini, Simona Pepe, Tatiana Gianni, Gabriella Campadelli-FiumeLaura Menotti, Valerio Leoni, Valentina Gatta, Biljana Petrovic, Andrea Vannini, Simona Pepe, Tatiana Gianni, Gabriella Campadelli-Fium

An Intact Kidney Slice Model to Investigate Vasa Recta Properties and Function in situ

Background: Medullary blood flow is via vasa recta capillaries, which possess contractile pericytes. In vitro studies using isolated descending vasa recta show that pericytes can constrict/dilate descending vasa recta when vasoactive substances are present. We describe a live kidney slice model in which pericyte-mediated vasa recta constriction/dilation can be visualized in situ. Methods: Confocal microscopy was used to image calcein, propidium iodide and Hoechst labelling in ‘live’ kidney slices, to determine tubular and vascular cell viability and morphology. DIC video-imaging of live kidney slices was employed to investigate pericyte-mediated real-time changes in vasa recta diameter. Results: Pericytes were identified on vasa recta and their morphology and density were characterized in the medulla. Pericyte-mediated changes in vasa recta diameter (10–30%) were evoked in response to bath application of vasoactive agents (norepinephrine, endothelin-1, angiotensin-II and prostaglandin E2) or by manipulating endogenous vasoactive signalling pathways (using tyramine, L-NAME, a cyclo-oxygenase (COX-1) inhibitor indomethacin, and ATP release). Conclusions: The live kidney slice model is a valid complementary technique for investigating vasa recta function in situ and the role of pericytes as regulators of vasa recta diameter. This technique may also be useful in exploring the role of tubulovascular crosstalk in regulation of medullary blood flow

Variation in Estimated Medicare Prescription Drug Plan Costs and Affordability for Beneficiaries Living in Different States

BACKGROUND: Medicare Part D prescription drug plans (PDPs) implemented in January 2006 are designed to improve beneficiaries’ access to pharmaceuticals and use market competition to yield affordable drug costs. Variations in estimated PDP costs for beneficiaries living in different states have not previously been characterized. OBJECTIVE: To describe variations in the estimated costs of PDPs (plan premium, copays, and coinsurance) within and across states. DESIGN: To estimate PDP costs based on 4 actual patient cases that exemplify common conditions and prescription drug combinations for Medicare beneficiaries, we used the online tool provided by the Centers for Medicare and Medicaid Services. MEASUREMENTS: Principal study outcomes included (a) variation across states in the estimated annual cost of the lowest-cost PDP for each case and (b) variation in the estimated affordability of the lowest-cost PDPs across states, based on cost-of-living-adjusted median income for zero-earner households. RESULTS: For all 4 patient cases, we found substantive within-state and between-state differences in the estimated costs of Medicare PDPs incurred by beneficiaries. The estimated annual costs to beneficiaries of the lowest-cost PDPs varied across states by as much as $320 for medications in the least expensive scenario, and by as much as$13,000 for the most expensive scenario. On average across states, a beneficiary with cost-of-living-adjusted median income would expect to spend 3%–28% of annual income to pay for medications in the lowest-cost PDPs in the 4 patient cases. The affordability of the lowest-cost plans varied across states, and for 2 of the 4 cases the lowest-cost PDP estimates were negatively correlated with cost-of-living-adjusted median income. CONCLUSIONS: Substantive differences in estimated PDP costs are evident across states for patients with common Medicare conditions. Importantly, the lowest-cost plans were not proportionally affordable with respect to state-specific cost-of-living-adjusted median income. Refinement of the Medicare drug program may be needed to improve national balance in PDP affordability for beneficiaries living in different states. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at http://dx.doi.org/10.1007/s11606-006-0018-y and is accessible for authorized users

Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury

Predictors of patients’ choices for breast-conserving therapy or mastectomy: a prospective study

A study was undertaken to describe the treatment preferences and choices of patients with breast cancer, and to identify predictors of undergoing breast-conserving therapy (BCT) or mastectomy (MT). Consecutive patients with stage I/II breast cancer were eligible. Information about predictor variables, including socio-demographics, quality of life, patients' concerns, decision style, decisional conflict and perceived preference of the surgeon was collected at baseline, before decision making and surgery. Patients received standard information (n = 88) or a decision aid (n = 92) as a supplement to support decision making. A total of 180 patients participated in the study. In all, 72% decided to have BCT (n = 123); 28% chose MT (n = 49). Multivariate analysis showed that what patients perceived to be their surgeons' preference and the patients' concerns regarding breast loss and local tumour recurrence were the strongest predictors of treatment preference. Treatment preferences in itself were highly predictive of the treatment decision. The decision aid did riot influence treatment choice. The results of this study demonstrate that patients' concerns and their perceptions of the treatment preferences of the physicians are important factors in patients' decision making. Adequate information and communication are essential to base treatment decisions on realistic concerns, and the treatment preferences of patients, (C) 2004 Cancer Research U

Impulsivity and self-harm in adolescence: a systematic review

Research supports an association between impulsivity and self-harm, yet inconsistencies in methodology across studies have complicated understanding of this relationship. This systematic review examines the association between impulsivity and self-harm in community-based adolescents aged 11-25 years and aims to integrate findings according to differing concepts and methods. Electronic searches of EMBASE, MEDLINE, PsychINFO, CINAHL, PubMed and The Cochrane Library, and manual searches of reference lists of relevant reviews, identified 4,496 articles published up to July 2015, of which 28 met inclusion criteria. Twenty-four of the studies reported an association between broadly specified impulsivity and self-harm. However, findings varied according to the conception and measurement of impulsivity and the precision with which self-harm behaviours were specified. Specifically, lifetime non-suicidal self-injury was most consistently associated with mood-based impulsivity related traits. However, cognitive facets of impulsivity (relating to difficulties maintaining focus or acting without forethought) differentiated current self-harm from past self-harm. These facets also distinguished those with thoughts of self-harm (ideation) from those who acted on thoughts (enaction). The findings suggested that mood-based impulsivity is related to the initiation of self-harm, while cognitive facets of impulsivity are associated with the maintenance of self-harm. In addition, behavioural impulsivity is most relevant to self-harm under conditions of negative affect. Collectively, the findings indicate that distinct impulsivity facets confer unique risks across the life-course of self-harm. From a clinical perspective, the review suggests that interventions focusing on reducing rash reactivity to emotions or improving self-regulation and decision-making may offer most benefit in supporting those who self-harm

The Legionella effector WipB is a translocated Ser/Thr phosphatase that targets the host lysosomal nutrient sensing machinery

Legionella pneumophila infects human alveolar macrophages and is responsible for Legionnaire’s disease, a severe form of pneumonia. L. pneumophila encodes more than 300 putative effectors, which are translocated into the host cell via the Dot/Icm type IV secretion system. These effectors highjack the host’s cellular processes to allow bacterial intracellular growth and replication. Here we adopted a multidisciplinary approach to investigate WipB, a Dot/Icm effector of unknown function. The crystal structure of the N-terminal domain at 1.7 Å resolution comprising residues 25 to 344 revealed that WipB harbours a Ser/Thr phosphatase domain related to the eukaryotic phospho-protein phosphatase (PPP) family. The C-terminal domain (residues 365–524) is sufficient to pilot the effector to acidified LAMP1-positive lysosomal compartments, where WipB interacts with the v-ATPase and the associated LAMTOR1 phosphoprotein, key components of the lysosomal nutrient sensing (LYNUS) apparatus that controls the mammalian target of rapamycin (mTORC1) kinase complex at the lysosomal surface. We propose that WipB is a lysosome-targeted phosphatase that modulates cellular nutrient sensing and the control of energy metabolism during Legionella infection

Pre-divorce problems in 3-year-olds: a prospective study in boys and girls

Objective: We examined to what extent internalizing and externalizing problems at age 3 preceded and predicted parental divorce, and if divorce and the time lapse since divorce were related to internalizing and externalizing problems at age 12. Methods: Parental ratings of internalizing and externalizing problems were collected with the Child Behavior Checklist (CBCL) in a large sample (N = 6,426) of 3-yearold children. All these children were followed through the age of 12 years, at which parents completed the CBCL again, while teachers completed the Teacher's Report Form. Children whose parents divorced between age 3 and age 12 were compared with children whose families remained intact. Results: Girls whose parents divorced between ages 3 and 12 already showed more externalizing problems at age 3 than girls whose parents stayed married. Higher levels of externalizing problems in girls at age 3 predicted later parental divorce. Parental reports indicated that 12-year-olds with divorced parents showed more internalizing and externalizing problems than children with married parents. Levels of teacher-reported problems were not different between children with married versus divorced parents. However, children whose parents divorced between ages 3 and 12 showed more teacher-rated internalizing problems at age 12 when the divorce was more recent than when the divorce was less recent. Parental ratings of both internalizing and externalizing problems at age 12 were not associated with the time lapse since divorce. Conclusion: Externalizing problems in girls precede and predict later parental divorce. Post-divorce problems in children vary by raters, and may depend on the time lapse since divorce