Expression of apolipoprotein E by cultured vascular smooth muscle cells is controlled by growth state.

Rat vascular smooth muscle cells (SMC) in culture synthesize and secrete a approximately 38,000-Mr protein doublet or triplet that, as previously described (Majack and Bornstein. 1984. J. Cell Biol. 99:1688-1695), rapidly and reversibly accumulates in the SMC culture medium upon addition of heparin. In the present study, we show that this approximately 38,000-Mr heparin-regulated protein is electrophoretically and immunologically identical to apolipoprotein E (apo-E), a major plasma apolipoprotein involved in cholesterol transport. In addition, we show that expression of apo-E by cultured SMC varies according to growth state: while proliferating SMC produced little apo-E and expressed low levels of apo-E mRNA, quiescent SMC produced significantly more apo-E (relative to other proteins) and expressed markedly increased levels of apo-E mRNA. Northern analysis of RNA extracted from aortic tissue revealed that fully differentiated, quiescent SMC contain significant quantities of apo-E mRNA. These data establish aortic SMC as a vascular source for apo-E and suggest new functional roles for this apolipoprotein, possibly unrelated to traditional concepts of lipid metabolism

The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials

Background: Kidney transplant recipients (KTRs) are characterised by adverse changes in physical fitness and body composition. Post-transplant management involves being physically active, although evidence for the effect of exercise is limited. Objective: To assess the effects of exercise training interventions in KTRs. Methods: NCBI PubMed (MEDLINE) and CENTRAL (EMBASE, WHO ICTRP) databases were searched up to March 2021 to identify eligible randomized controlled trials (RCTs) that studied exercise training in adult KTRs. Outcomes included exercise capacity, strength, blood pressure, body composition, heart rate, markers of dyslipidaemia and renal function, and health-related quality of life (QoL). Results: Sixteen RCTs, containing 827 KTRs, were included. The median intervention length was 14-weeks with participants exercising between 2–7x/week. Most studies used a mixture of aerobic and resistance exercise. Significant improvements were observed in cardiorespiratory function (VO2peak) (3.21 ml/kg/min, p = 0.003), 6MWT (76.3 meters, p = 0.009), physical function (STS-60, 4.8 repetitions, p = 0.04), and high-density lipoprotein (HDL) (0.13 mg/dL, p = 0.03). A moderate increase in maximum heart rate was seen (p = 0.06). A moderate reduction in creatinine was also observed (0.14 mg/dl, p = 0.05). Isolated studies reported improvements in strength, bone health, lean mass, and QoL. Overall, studies had high risk of bias suggestive of publication bias. Conclusions: Exercise training may confer several benefits in adult KTRs, particularly by increasing cardiorespiratory function and exercise capacity, strength, HDL levels, maximum heart rate, and improving QoL. Additional long-term large sampled RCTs, incorporating complex interventions requiring both exercise and dietary behaviour change, are needed to fully understand the effects of exercise in KTRs

The importance of lifestyle interventions in the prevention and treatment of Chronic Kidney Disease

EditorialRoman-Ulrich Müller received funding from the Ministry of Science North Rhine-Westphalia (Nachwuchsgruppen.NRW 2015–2021), the Marga and Walter Boll Foundation, the PKD Foundation and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—CECAD, EXC 2030–390661388 as well as DFG MU 3629/6-1 and DFG DI 1501/9

Usability and experience testing to refine an online intervention to prevent weight gain in new kidney transplant recipients

Data availability statement: The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Consent was not given for the full publication of transcripts.Supporting information is available online at: https://bpspsychub.onlinelibrary.wiley.com/doi/full/10.1111/bjhp.12471#support-information-section .Copyright © 2020 The Authors. Objectives Weight gain in the first year following kidney transplantation increases the risk of adverse health outcomes. Currently, there is no recognized intervention available to prevent weight gain after kidney transplantation. An online kidney transplant-specific resource, entitled Exercise in Renal Transplant Online (ExeRTiOn), has been co-created by a multi-professional team, including patients, to assist with weight prevention. This study aimed to evaluate patient and health care professional usability and experience of the ExeRTiOn online resource. Design Qualitative study utilizing ‘Think-Aloud’ and semi-structured interviews. Methods Participants (n = 17) were purposively sampled to include new kidney transplant recipients (n = 11) and transplant health care professionals (n = 6). Kidney transplant recipient participants were from a spread of physical activity levels based on scores from the General Practice Physical Activity Questionnaire (GPPAQ). ‘Think-Aloud’ interviews assessed the usability of ExeRTiOn. Semi-structured interviews explored participants’ experience of ExeRTiOn, weight gain, and physical activity. The data set were analysed thematically. Participant characteristics, including login data and self-reported body weight, were collected. Results Data analyses identified valued intervention content and usability aspects which were summarized by two themes. The first theme ‘You need to know how to manage yourself’ included subthemes: (1) the resource filled a guidance gap, (2) expert patient content resonated, and (3) the importance of goal setting and monitoring progress. The second theme ‘room for improvement’ included subthemes: (2) web support and (2) content and operational change suggestions. Conclusions Results have allowed for identification of potential areas for resource refinement. This has facilitated iterative enhancement of ExeRTiOn in preparation for a randomized controlled feasibility trial.Kidney Research UK Allied Health Professional PhD Fellowship; National Institute for Health Research/Health Education England (NIHR/HEE) Clinical Lectureship; KCH NIHR Clinical Research Facility; Kidney Research UK

Do Exercise, Physical Activity, Dietetic, or Combined Interventions Improve Body Weight in New Kidney Transplant Recipients? A Narrative Systematic Review and Meta-Analysis

Data Availability Statement: Data is contained within the article or Supplementary Material. The data presented in this study are available in this article and included Supplementary Material.Supplementary Materials: Available at: https://www.mdpi.com/2673-8236/1/2/14/s1?version=1633165351 (ZIP-Document, 999 KiB) The following are available online at www.mdpi.com/article/10.3390/kidneydial1020014/s1, Figure S1: Risk-of-bias plots for Non-RCTs (n = 6), Table S1: PRISMA checklist, Table S2: Search strategy, Table S3: Screening form, Table S4: Detailed sample characteristics, Table S5: Study characteristics of non-RCTs, Table S6: Details of intervention nonRCTs (n = 6), Table S7: Sensitivity analysis.Copyright: © 2021 by the authors. Weight gain within the first year of kidney transplantation is associated with adverse outcomes. This narrative systematic review and meta-analysis examines the effect of exercise, physical activity, dietary, and/or combined interventions on body weight and body mass index (BMI) within the first year of kidney transplantation. Seven databases were searched from January 1985 to April 2021 (Prospero ID: CRD42019140865), using a ‘Population, Intervention, Controls, Outcome’ (PICO) framework. The risk-of-bias was assessed by two reviewers. A random-effects meta-analysis was conducted on randomized controlled trials (RCTs) that included post-intervention body weight or BMI values. Of the 1197 articles screened, sixteen met the search criteria. Ten were RCTs, and six were quasi-experimental studies, including a total of 1821 new kidney transplant recipients. The sample sizes ranged from 8 to 452. Interventions (duration and type) were variable. Random-effects meta-analysis revealed no significant difference in post-intervention body weight (−2.5 kg, 95% CI −5.22 to 0.22) or BMI (−0.4 kg/m2, 95% CI −1.33 to 0.54). Despite methodological variance, statistical heterogeneity was not significant. Sensitivity analysis suggests combined interventions warrant further investigation. Five RCTs were classified as ‘high-risk’, one as ‘some-concerns’, and four as ‘low-risk’ for bias. We did not find evidence that dietary, exercise, or combined interventions led to significant changes in body weight or BMI post kidney transplantation. The number and quality of intervention studies are low. Higher quality RCTs are needed to evaluate the immediate and longer-term effects of combined interventions on body weight in new kidney transplant recipients.Kidney Research UK PhD Grant (AHPF_001_20171122); NIHR Advanced Research Fellowship (ICA-CL-2017-03-020); National Institute for Health Research (NIHR) (DRF-2017-10-105)

Cultural influences on physical activity and exercise beliefs in patients with chronic kidney disease: The Culture-CKD Study'-a qualitative study

Data availability statement: Data are available upon reasonable request. The datasets used and analysed during the current study are available from the corresponding author on reasonable request.Ethics approval: Ethical approval was granted from the North West Haydock Research Ethics Committee on 3 April 2018 (18/NW/02/37). This study has been registered on ClinicalTrials. gov with the identifier: NCT03709212.Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer- reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.Copyright © Author(s) (or their employer(s)) 2022. Objectives This study used a mixed-method approach to explore cultural and ethnic influences on the perception of, and decision to engage with or not to engage with, physical activity and exercise therapy in patients with chronic kidney disease (CKD). Design Qualitative research was conducted through the use of semistructured interviews and focus groups. Self-reported physical activity levels were measured using the General Practice Physical Activity Questionnaire (GPPAQ), and self-efficacy for exercise with Bandura's Self-Efficacy for Exercise Scale. Setting This study was conducted in a non-clinical setting of a single National Health Service Hospital Trust between April 2018 and July 2019. Participants Participants >18 years of age with a diagnosis of CKD, from black African, black Caribbean, South Asian or white ethnicity were eligible for the study. 84 patients with a diagnosis of CKD (stages 2-5), aged 25-79 (mean age 57) were recruited. Semistructured interviews (n=20) and six single-sex, ethnic-specific focus group discussions were undertaken (n=36). Outcomes Primary outcome was to explore the perceptions, attitudes and values about exercise and physical activity in different ethnic groups through qualitative interviews, analysed using an inductive thematic analysis approach. Questionnaires were analysed using Pearson correlation to determine if there was a significant relationship between the self-efficacy and GPPAQ levels. Results Qualitative analysis provided four primary themes: I am who I am, Change of identity, Influences to physical activity and exercise and Support and education. Quantitative analysis using Pearson correlation revealed a significant correlation between GPPAQ levels of activity and self-efficacy to regulate exercise behaviour (r=-0.40, p=0.001). Conclusion Understanding the cultural, attitudes and beliefs of individuals with CKD from a variety of ethnic backgrounds is complex. Understanding of patients' experiences, thoughts and beliefs may be of relevance to clinicians when designing CKD exercise services. Trial registration number NCT03709212; Pre-results.Kidney Care UK & BRS Joint Grants Programme 2017; Kidney Research UK through the KRUK AHP PhD fellowship (AHPF_001_20171122); NIHR HEE/NIHR ICA Pre- doctoral Clinical Academic Fellowship (NIHR301893)

Cultural influences on physical activity and exercise beliefs in patients with chronic kidney disease : ‘The Culture-CKD Study’—a qualitative study

Objectives: This study used a mixed-method approach to explore cultural and ethnic influences on the perception of, and decision to engage with or not to engage with, physical activity and exercise therapy in patients with chronic kidney disease (CKD). Design: Qualitative research was conducted through the use of semistructured interviews and focus groups. Self-reported physical activity levels were measured using the General Practice Physical Activity Questionnaire (GPPAQ), and self-efficacy for exercise with Bandura’s Self-Efficacy for Exercise Scale. Setting: This study was conducted in a non-clinical setting of a single National Health Service Hospital Trust between April 2018 and July 2019. Participants: Participants >18 years of age with a diagnosis of CKD, from black African, black Caribbean, South Asian or white ethnicity were eligible for the study. 84 patients with a diagnosis of CKD (stages 2–5), aged 25–79 (mean age 57) were recruited. Semistructured interviews (n=20) and six single-sex, ethnic-specific focus group discussions were undertaken (n=36). Outcomes: Primary outcome was to explore the perceptions, attitudes and values about exercise and physical activity in different ethnic groups through qualitative interviews, analysed using an inductive thematic analysis approach. Questionnaires were analysed using Pearson correlation to determine if there was a significant relationship between the self-efficacy and GPPAQ levels. Results: Qualitative analysis provided four primary themes: I am who I am, Change of identity, Influences to physical activity and exercise and Support and education. Quantitative analysis using Pearson correlation revealed a significant correlation between GPPAQ levels of activity and self-efficacy to regulate exercise behaviour (r=−0.40, p=0.001). Conclusion: Understanding the cultural, attitudes and beliefs of individuals with CKD from a variety of ethnic backgrounds is complex. Understanding of patients’ experiences, thoughts and beliefs may be of relevance to clinicians when designing CKD exercise services. Trial registration number: NCT03709212; Pre-results

Post-Partum Pituitary Insufficiency and Livedo Reticularis Presenting a Diagnostic Challenge in a Resource Limited Setting in Tanzania: A Case Report, Clinical Discussion and Brief Review of Existing Literature.

Pituitary disorders following pregnancy are an important yet under reported clinical entity in the developing world. Conversely, post partum panhypopituitarism has a more devastating impact on women in such settings due to high fertility rates, poor obstetric care and scarcity of diagnostic and therapeutic resources available. A 37 year old African female presented ten years post partum with features of multiple endocrine deficiencies including hypothyroidism, hypoadrenalism, lactation failure and secondary amenorrhea. In addition she had clinical features of an underlying autoimmune condition. These included a history of post-partum thyroiditis, alopecia areata, livedo reticularis and deranged coagulation indices. A remarkable clinical response followed appropriate hormone replacement therapy including steroids. This constellation has never been reported before; we therefore present an interesting clinical discussion including a brief review of existing literature. Post partum pituitary insufficiency is an under-reported condition of immense clinical importance especially in the developing world. A high clinical index of suspicion is vital to ensure an early and correct diagnosis which will have a direct bearing on management and patient outcome

The Feasibility and User-Experience of a Digital Health Intervention Designed to Prevent Weight Gain in New Kidney Transplant Recipients—The ExeRTiOn2 Trial

Data availability statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Supplementary material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2022. 887580/full#supplementary-materialCopyright © 2022 Castle, Dijk, Asgari, Shah, Phillips, Greenwood, Bramham, Chilcot and Greenwood. Half of kidney transplant recipients (KTRs) gain more than 5% of their body weight in the first year following transplantation. KTRs have requested support with physical activity (PA) and weight gain prevention, but there is no routine care offered. There are few high-quality studies investigating the clinical value of diet, PA or combined interventions to prevent weight gain. The development and evaluation of theoretically informed complex-interventions to mitigate weight gain are warranted. The aims of this mixed-methods randomized controlled trial (RCT) were to explore the feasibility, acceptability and user-experience of a digital healthcare intervention (DHI) designed to prevent post-transplant weight gain, in preparation for a large multi-center trial. New KTRs (<3 months) with access to an internet compatible device were recruited from a London transplant center. The usual care (UC) group received standard dietary and PA advice. The intervention group (IG) received access to a 12-week DHI designed to prevent post-transplant weight gain. Primary feasibility outcomes included screening, recruitment, retention, adherence, safety and hospitalizations and engagement and experience with the DHI. Secondary outcomes (anthropometrics, bioimpedance, arterial stiffness, 6-minute walk distance and questionnaires) were measured at baseline, 3- and 12-months. 38 KTRs were screened, of which 32 (84.2%) were eligible, and of those 20 (62.5%) consented, with 17 participants (85%) completing baseline assessment (Median 49 years, 58.8% male, Median 62 days post-transplant). Participants were randomized using a computer-generated list (n = 9 IG, n = 8 UC). Retention at 12-months was 13 (76.4%) (n = 6 IG, n = 7 UC). All a priori progression criteria were achieved. There were no associated adverse events. Reflexive thematic analysis revealed four themes regarding trial participation and experience whilst using the DHI. Halting recruitment due to COVID-19 resulted in the recruitment of 40% of the target sample size. Mixed-methods data provided important insights for future trial design. A definitive RCT is warranted and welcomed by KTRs. Clinical Trial Registration: www.clinicalTrials.gov, identifier: NCT03996551.Kidney Research UK Ph.D. Grant (AHPF_001_20171122); NIHR Advanced Research Fellowship (ICA-CL-2017-03-020); King’s College Hospital Foundation NHS Trust; King’s College London University; SPIKA Ltd. Fellowship grant (ExeRTiOn DHI).https://www.frontiersin.org/articles/10.3389/fnut.2022. 887580/full#supplementary-materia

Prevalence of type-specific HPV infection by age and grade of cervical cytology: data from the ARTISTIC trial

Human papillomavirus (HPV) infection causes cervical cancer and premalignant dysplasia. Type-specific HPV prevalence data provide a basis for assessing the impact of HPV vaccination programmes on cervical cytology. We report high-risk HPV (HR-HPV) type-specific prevalence data in relation to cervical cytology for 24 510 women (age range: 20–64; mean age 40.2 years) recruited into the ARTISTIC trial, which is being conducted within the routine NHS Cervical Screening Programme in Greater Manchester. The most common HR-HPV types were HPV16, 18, 31, 51 and 52, which accounted for 60% of all HR-HPV types detected. There was a marked decline in the prevalence of HR-HPV infection with age, but the proportion due to each HPV type did not vary greatly with age. Multiple infections were common below the age of 30 years but less so between age 30 and 64 years. Catch-up vaccination of this sexually active cohort would be expected to reduce the number of women with moderate or worse cytology by 45%, but the number with borderline or mild cytology would fall by only 7%, giving an overall reduction of 12% in the number of women with abnormal cytology and 27% in the number with any HR-HPV infection. In the absence of broader cross-protection, the large majority of low-grade and many high-grade abnormalities may still occur in sexually active vaccinated women