Search

Abstract Background Pain, related to Raynaud’s phenomenon or digital ulceration, has been identified as very prevalent and debilitating symptoms of systemic sclerosis (SSc), both significantly affecting patients’ quality of life (QoL). Pharmacological therapeutic strategies were found not to be sufficiently effective in the management of SSc-induced pain and fatigue, and evidence for exercise is scarce. As yet, the effects of a long-term, tailored exercise programme on pain and fatigue in patients with SSc have not been explored. In addition to pain and fatigue, this study aims to evaluate the effects of exercise on QoL, physical fitness, functional capacity, and vascular structure in people with SSc (PwSSc). Methods This will be a multicentre (n = 6) randomised controlled clinical trial to assess the effect of a previously established, supervised 12-week combined exercise programme on pain and fatigue as compared to no exercise in PwSSc. The study will recruit 180 patients with SSc that will be allocated randomly to two groups. Group A will perform the exercise programme parallel to standard usual care and group B will receive usual care alone. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30-min high-intensity interval training (HIIT) (30-s 100% peak power output/30-s passive recovery) on an arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be pain and fatigue assessed via questionnaires. Secondary outcomes include quality of life, structure of digital microvasculature, body composition, physical fitness, and functional capacity. Discussion Data from this multi-centre research clinical trial will primarily be used to establish the effectiveness of a combined exercise protocol to improve pain and fatigue in SSc. In parallel, this study will be the first to explore the effects of long-term exercise on potential microvascular alterations assessed via NVC. Overall, this study will provide sufficient data to inform current clinical practice guidelines and may lead to an improvement of QoL for patients with SSc. Trial registration ClinicalTrials.gov NCT05234671. Registered on 14 January 2022

Here the authors analyze the 3D genome structure of murine thymocytes and show that SATB1, a predominantly T-cell specific protein, helps to establish a regulatory, finer-scale organizational layer built upon a pre-existing chromatin scaffold mediated by other architectural proteins, such as CTCF.

Introduction: Cardiovascular disease (CVD) remains the main cause of death in the Western world. Our recent findings demonstrate potential CVD risk reduction in older adults who undertake regular swimming exercise. Nevertheless, it remains unknown whether an exercise intervention based on swimming is feasible and effective prior to a wider implementation of a CVD risk prevention strategy.Methods: This was a pragmatic, two-group, randomised controlled trial. A total of 40 older adults were randomly split into two groups (n = 20 per group). The swimming exercise group consisted of participants who engaged in swimming exercise (2–3 days/week, for 8 weeks). The control group did not perform any exercise. Flow-mediated dilation (%FMD) was the primary outcome. Secondary outcomes included raw cutaneous vascular conductance. Feasibility outcomes (e.g., recruitment, adherence, and attrition rates) were also assessed.Results: Statistically significant macrovascular (%FMD; swimming group: 9.8% ± 4.2%, p

Summary: Cell identity is orchestrated through an interplay between transcription factor (TF) action and genome architecture. The mechanisms used by TFs to shape three-dimensional (3D) genome organization remain incompletely understood. Here we present evidence that the lineage-instructive TF CEBPA drives extensive chromatin compartment switching and promotes the formation of long-range chromatin hubs during induced B cell-to-macrophage transdifferentiation. Mechanistically, we find that the intrinsically disordered region (IDR) of CEBPA undergoes in vitro phase separation (PS) dependent on aromatic residues. Both overexpressing B cells and native CEBPA-expressing cell types such as primary granulocyte-macrophage progenitors, liver cells, and trophectoderm cells reveal nuclear CEBPA foci and long-range 3D chromatin hubs at CEBPA-bound regions. In short, we show that CEBPA can undergo PS through its IDR, which may underlie in vivo foci formation and suggest a potential role of PS in regulating CEBPA function.

Abstract Background Smoking is a major risk factor for cardiovascular disease and smoking cessation reduces excess risk. E-cigarettes are popular for smoking cessation but there is little evidence on their cardiovascular health effect. Our objective was to compare the medium- and longer-term cardiovascular effects in smokers attempting to quit smoking using e-cigarettes with or without nicotine or prescription nicotine replacement therapy (NRT). Methods This was a single-center, pragmatic three-arm randomized (1:1:1) controlled trial, which recruited adult smokers (≥ 10 cigarettes/day), who were willing to attempt to stop smoking with support (n = 248). Participants were randomized to receive behavioral support with either (a) e-cigarettes with 18 mg/ml nicotine, (b) e-cigarettes without nicotine, and (c) NRT. Flow-mediated dilation (%FMD) and peak cutaneous vascular conductance (CVCmax) responses to acetylcholine (ACh) and sodium nitroprusside (SNP), mean arterial pressure (MAP), and other outcomes were recorded at baseline, 3, and 6 months after stopping smoking. Data were analyzed using generalized estimating equations (GEE). Results At 3- and 6-month follow-up, %FMD showed an improvement over baseline in all three groups (e.g., p

Here, we describe how the speed of C/EBPα-induced B cell to macrophage transdifferentiation (BMT) can be regulated, using both mouse and human models. The identification of a mutant of C/EBPα (C/EBPαR35A) that greatly accelerates BMT helped to illuminate the mechanism. Thus, incoming C/EBPα binds to PU.1, an obligate partner expressed in B cells, leading to the release of PU.1 from B cell enhancers, chromatin closing and silencing of the B cell program. Released PU.1 redistributes to macrophage enhancers newly occupied by C/EBPα, causing chromatin opening and activation of macrophage genes. All these steps are accelerated by C/EBPαR35A, initiated by its increased affinity for PU.1. Wild-type C/EBPα is methylated by Carm1 at arginine 35 and the enzyme’s perturbations modulate BMT velocity as predicted from the observations with the mutant. Increasing the proportion of unmethylated C/EBPα in granulocyte/macrophage progenitors by inhibiting Carm1 biases the cell’s differentiation toward macrophages, suggesting that cell fate decision velocity and lineage directionality are closely linked processes.

Sedentary lifestyles have adverse effects on health and wellbeing and are especially prevalent amongst office-based employees. This project goes above and beyond currently existing physical activity initiatives in the workplace, by examining the feasibility of using a "Bait-and-Tease" stealth marketing intervention promoting increased physical activity and reduction of sedentary behaviour in the workplace amongst office-based employees. The intervention focused on promoting employee pro-environmental behaviour in the workplace (i.e., energy saving and recycling). This was the "Bait" part of the technique, which made no reference to physical activity. The spillovers of employee pro-environmental behaviour change on employee physical activity and sedentary behaviour were then evaluated. This was followed by a reveal stage, the "Tease" part of the technique, where the link between health and the environment was made explicit (e.g., taking the stairs instead of the elevator saves energy while also increasing walking time) and participants were informed of the true purpose of the intervention. Initial employee focus groups, grounded on the Behaviour Change Wheel framework, fed into an intervention co-development workshop. The developed intervention, which included an informational campaign and a green champion, was piloted within a Higher Education Institution and targeted academics, professional service members, and postgraduate research students as university employees with office-based jobs. The pilot involved an intervention and a control-group, with a "before" and "after" research design. Both self-reported (i.e., employee surveys measuring pro-environmental behaviour) and observational (i.e., tracking walking and standing time via a mobile application, recording sedentary time and counting stairs via trained observers) data were collected. Results indicate that the intervention was found feasible and the pilot study shows potential for large-scale implementation, even though the pilot sample size was small. The goals of the study were achieved and problems in relation to recruitment, adherence and measurements were identified with multiple future research directions.

Abstract Background Polycystic ovary syndrome (PCOS) affects up to 20% of women and is characterised by higher amounts of visceral fat, obesity, insulin resistance, dyslipidemia and reproductive and cardiometabolic complications. Increased oxidised low-density lipoprotein (LDL) concentrations have been associated with an increased risk of cardiovascular disease (CVD)-related events. Oxidised LDL is rarely used as a marker for CVD risk in PCOS-related studies despite its widely accepted role in atherogenesis and the increased risk factors associated with PCOS. Additionally, prolonged periods of sedentary behaviour can negatively affect metabolic health. No studies have specifically examined the effects of reducing sedentary behaviour on CVD risk in PCOS with a lifestyle physical activity intervention. The aim of the current study is to measure the feasibility of a randomised controlled trial (RCT) examining the effects of supervised exercise and reducing sedentary behaviour in women with PCOS on CVD risk. Methods/design A feasibility, exploratory RCT will be conducted. Fifty-one pre-menopausal females will be randomly allocated between an exercise group (EG), a lifestyle physical activity group (LPAG) and a control group. Participants in the EG will undertake a 12-week supervised aerobic exercise programme. The LPAG will aim to increase daily physical activity and reduce sedentary behaviour for 12 weeks. The control group will not take part in any intervention. Primary outcomes are feasibility and acceptability of the intervention and procedures. Secondary outcomes are oxidised LDL, aerobic fitness, blood lipid profile, fasting glucose and insulin, testosterone and inflammatory markers. Discussion PCOS is associated with various increased risk factors for CVD, including hypertension, dyslipidemia, abdominal obesity, insulin resistance, and inflammation. Whether oxidised LDL has a role in this increased risk is not yet known. The present study aims to measure the feasibility of implementing structured exercise training and/or increased lifestyle physical activity in women with PCOS, so that a subsequent adequately powered RCT can be designed. The results from the study will be used to refine the interventions and determine the acceptability of the study design. A limitation is that some self-monitoring in the lifestyle physical activity group may not be reliable or replicable, for example inputting information about time spent cleaning/gardening. Trial registration ClinicalTrials.gov, NCT03678714. Registered 20 September 2018.

Background: Vascular dysfunction and its concomitant multi-organ involvement, including cardiac involvement, affects prognosis in systemic sclerosis (SSc) patients. Regular exercise has demonstrated to be able to improve vascular function in SSc. However, the effects of an exercise program on the heart and specifically in right ventricular (RV) morphology and function in SSc have yet to be explored. The study aimed to examine whether a 3-month combined exercise program can affect RV morphology and function in SSc patients. Methods: Twenty-eight SSc patients were randomly allocated to either the exercise training (ET) or the control (CON) group. Baseline and follow-up assessments consisted of a cardiopulmonary exercise test along with both a conventional and a two-dimensional speckle tracking echocardiography (2DSTE) focused on RV morphology and function. Following the baseline assessments, Group ET participated in a supervised combined exercise program for 12 weeks, while group CON received their usual care. Results: The ET group demonstrated increases in peak oxygen consumption by 25.1% (p < 0.001), global RV free wall longitudinal systolic strain by 6.69% (p < 0.03), RV free wall longitudinal systolic strain of the basal segment by 13.5% (p < 0.001), and global RV four-chamber longitudinal systolic strain by 6.76% (p < 0.03) following the exercise program. No differences were observed in group CON. Conclusions: Combined exercise improved cardiorespiratory efficiency and indices of RV systolic function, as assessed by the 2DSTE, in SSc patients.

The multitasking promyelocytic leukemia (PML) protein was originally recognized as a tumor‐suppressive factor, but more recent evidence has implicated PML in tumor cell prosurvival actions and poor patient prognosis in specific cancer settings. Here, we report that inducible PMLIV expression inhibits cell proliferation as well as self‐renewal and impairs cell cycle progression of breast cancer cell lines in a reversible manner. Transcriptomic profiling identified a large number of PML‐deregulated genes associated with various cell processes. Among them, cell cycle‐ and division‐related genes and their cognitive regulators are highly ranked. In this study, we focused on previously unknown PML targets, namely the Forkhead transcription factors. PML suppresses the Forkhead box subclass M1 (FOXM1) transcription factor at both the RNA and protein levels, along with many of its gene targets. We show that FOXM1 interacts with PMLIV primarily via its DNA‐binding domain and dynamically colocalizes in PML nuclear bodies. In parallel, PML modulates the activity of Forkhead box O3 (FOXO3), a factor opposing certain FOXM1 activities, to promote cell survival and stress resistance. Thus, PMLIV affects the balance of FOXO3 and FOXM1 transcriptional programs by acting on discrete gene subsets to favor both growth inhibition and survival. Interestingly, PMLIV‐specific knockdown mimicked ectopic expression vis‐à‐vis loss of proliferative ability and self‐renewal, but also led to loss of survival ability as shown by increased apoptosis. We propose that divergent or similar effects on cell physiology may be elicited by high or low PMLIV levels dictated by other concurrent genetic or epigenetic cancer cell states that may additionally account for its disparate effects in various cancer types.

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrinopathy, affecting 4–12% of reproductive-aged women. Women with PCOS often exhibit many metabolic abnormalities that are associated with an increased cardiovascular disease (CVD) risk, independent of obesity. Exercise interventions from 12 to 24 weeks have been shown to have positive effects on blood lipid profile, ovulation and insulin resistance in women with PCOS. However, no consensus on which exercise interventions are effective (i.e. duration, type of exercise, frequency), including for different phenotypes, currently exists. The aim of this systematic review and meta-analysis is to define effective types of exercise interventions to improve cardiometabolic profile, across the range of phenotypes of PCOS. Methods We will conduct electronic database searches, including randomised-controlled trials (RCT), quasi-RCT and clinical trials. Primary outcomes sought will be lipid profile, carotid-intima media thickness, fasting blood glucose, %HbA1c, blood pressure, waist circumference, waist-to-hip ratio, abdominal adiposity and inflammation markers. Secondary outcomes sought will be free and total testosterone, sex hormone binding globulin and insulin resistance. The Cochrane Risk Assessment Tool will be used to assess study quality. Data will be analysed in RevMan. Analysis of heterogeneity will be undertaken using the I 2 statistic. Significant heterogeneity will be explored, and sensitivity analyses carried out as appropriate. A subgroup analysis based on androgen profile will be undertaken if data are sufficient. Discussion A large proportion of women are affected by PCOS. It is prudent to examine how CVD risk can be mitigated in this high-risk population, and this review aims to provide evidence-driven recommendations on the types of exercise interventions that are effective for this. The review will seek to provide recommendations regarding type, frequency and duration of exercise interventions to improve cardiometabolic profile in PCOS. The subgroup analysis may be able to highlight difference in intervention effects between normo-androgenic and hyper-androgenic profile. Limitations include heterogeneity across studies and a scarcity of clinical trials involving a PCOS control group not undertaking any intervention. Systematic review registration PROSPERO CRD42018086117

Introduction Compression is the mainstay of treatment for venous leg ulcers (VLUs) and there are few effective adjuvant treatments. There is only observational evidence supporting the use of hypochlorous acid (HOCl) as a topical wound solution on VLU and some limited randomised evidence for the effect of a prescribed regimen of exercise.Methods and analysis The Factorial4VLU trial is a pragmatic, blinded, factorial randomised controlled trial, with 380 participants receiving either a prescribed exercise regimen compared with usual care and either active HOCl wound solution or placebo wound solution at each dressing change for up to 24 weeks. All participants will receive compression therapy. The primary outcome is the proportion of participants with healed VLU at 12 weeks after randomisation as adjudicated by blinded review of ulcer photographs. Secondary outcomes are proportion healed at 24 weeks, time to healing, estimated change in ulcer area, change in 2-Minute Walk Test, change in health-related quality of life, incidence of infection and incidence of all-cause adverse events. If either of the interventions shows a statistically significant positive difference on healing outcomes, cost-effectiveness will be modelled using a health service perspective.Ethics and dissemination The Factorial4VLU trial received ethical approval from the Northern B Health and Disability Ethics Committee. We plan to publish the results within 1 year of trial completion and will include the results on the trial registration page.Trial registration numbers Australia and New Zealand Clinical Trials Register (http://www.anzctr.org.au) (ACTRN12620000116921); Universal Trial Number (WHO) (U1111-1236-2997).

IntroductionCardiovascular aging is implicated in the development of cardiovascular disease (CVD). Aquatic exercise is being considered as a co-adjuvant form of rehabilitation, but there is limited evidence for its cardiovascular risk-reduction properties for older people. Our study aimed to address this by exploring the cardiovascular effects of long-term aquatic exercise in older adults in comparison to those who are either inactive or engaged in land-based/mixed training by measurement of micro- and macro-circulation. Flow Mediated Dilatation (FMD) was the primary outcome.MethodsThis was a pragmatic, 4-group, cross-sectional study. Eighty normotensive adults constituted four (n = 20) groups. The Aqua group (aged 63.7 ± 7 years) and Land group (aged 65 ± 6 years) consisted of participants engaged in aquatic and land-based training, respectively. The mixed group (Mix) (aged 66 ± 6 years) consisted of participants engaged in both land-based and aquatic training. Self-reported training consisted of ≥2/week for ≥6 months (mean sessions/week = 4 ± 1, 4 ± 1, and 5 ± 2 for each group, respectively). The sedentary group (Sed) (aged 63 ± 6 years) consisted of people who were sedentary for ≥6 months (mean sessions/week 0 ± 0). The primary outcome was %FMD. Secondary outcomes included raw cutaneous vascular conductance (CVC) and CVC max.ResultsStatistically significant differences (%FMD, raw CVC variables other than baseline) were found between each of the exercise groups (Aqua, Land, Mix) and the sedentary group (Sed) (i.e., 11.2 (4.2) vs. 5.0 (2.3); p < 0.0005, between the Aqua group and Sed group, for %FMD). No specific advantage could be attributed to any one of the exercise groups.ConclusionWe reported improvements in NO-mediated endothelial function at micro- and macro-circulatory levels, observing no differences between exercise modes. Our findings provide evidence for the role of aquatic exercise as a “shield” against CVD in older populations.

Abstract Background Raynaud’s phenomenon is one of the first clinical manifestations observed in systemic sclerosis (SSc). This microvasculature disorder affects mostly the digits in over 95% of SSc patients, significantly affecting their health-related quality of life (HRQoL) and incurring higher hospital admissions and other healthcare costs. Exercise is known to improve both micro- and macrovascular function – aerobic exercise and resistance training, separately or combined, have been demonstrated to lead to significant vasculo-physiological improvements in conditions that present vasculopathy. However, the effects of a combined exercise programme on microcirculation in SSc patients has yet to be investigated. Therefore, the purpose of this study is to assess the effects of high-intensity interval training (HIIT) combined with circuit resistance training on the microvascular function in the digital area of SSc patients. Methods This will be a randomised controlled, feasibility trial with two arms, wherein 30 patients with SSc in receipt of medical treatment will be randomly assigned to usual care (medical treatment) or to a 12-week supervised exercise programme. Patients in the exercise group will undertake two, 45-min sessions each week consisting of 30 min HIIT (30 s 100% peak power output/30 s passive recovery) on the arm crank ergometer and 15 min of upper body circuit resistance training. Patients will be assessed before as well as at 3 and 6 months following randomisation. Primary outcomes of the study will be recruitment and retention rate, intervention acceptability and adherence to the exercise programme. Secondary outcomes include the digital area cutaneous microvascular function (laser Doppler fluximetry combined with iontophoresis), physical fitness, functional ability, upper back transcutaneous oxygen tension, body composition and quality of life (EQ-5D-5L). Selected interviews with a subsample of patients will be undertaken to explore their experiences of having Raynaud’s phenomenon and the acceptability of the exercise intervention and study procedures. Discussion Data from this study will be used to identify the feasibility of a combined exercise programme to be implemented in SSc patients, the acceptability of the intervention and the study design, and to determine the effects of exercise on the microvasculature. Overall, this study will provide sufficient data to inform and support a full multicentre clinical trial. Trial registration ClinicalTrials.gov (NCT number): NCT03058887, February 23, 2017.

Abstract Background Aerobic exercise in general and high-intensity interval training (HIIT) specifically is known to improve vascular function in a range of clinical conditions. HIIT in particular has demonstrated improvements in clinical outcomes, in conditions that have a strong macroangiopathic component. Nevertheless, the effect of HIIT on microcirculation in systemic sclerosis (SSc) patients is yet to be investigated. Therefore, the purpose of the study was to compare the effects of two HIIT protocols (cycle and arm cranking) on the microcirculation of the digital area in SSc patients. Methods Thirty-four limited cutaneous SSc patients (65.3 ± 11.6 years old) were randomly allocated in three groups (cycling, arm cranking and control group). The exercise groups underwent a 12- week exercise program twice per week. All patients performed the baseline and post-exercise intervention measurements where physical fitness, functional ability, transcutaneous oxygen tension (ΔTcpO2), body composition and quality of life were assessed. Endothelial-dependent as well as -independent vasodilation were assessed in the middle and index fingers using LDF and incremental doses of acetylcholine (ACh) and sodium nitroprusside (SNP). Cutaneous flux data were expressed as cutaneous vascular conductance (CVC). Results Peak oxygen uptake increased in both exercise groups (p

Smoking increases cardiovascular disease (CVD) risk by leading to endothelial injury. E-cigarettes remain a popular way to stop smoking. Evidence on their effect on cardiovascular health is growing but remains limited, particularly in the short-term. The main objective of this study was to compare short-term cardiovascular effects in smokers who quit smoking using e-cigarettes with or without nicotine or prescription nicotine replacement therapy (NRT). This was a single-centre (Sheffield, UK) pragmatic three-arm randomised controlled trial which recruited adult smokers (≥10 cigarettes per day), who were willing to attempt to stop smoking with support (n = 248). Participants were randomised to receive either: (a) behavioral support and e-cigarettes with 18 mg/mL nicotine (n = 84); (b) behavioral support and e-cigarettes without nicotine (n = 82); (c) behavioral support and NRT (n = 82). Flow Mediated Dilation (%FMD), peak cutaneous vascular conductance responses to acetylcholine (ACh) and sodium nitroprusside (SNP) and mean arterial pressure (MAP) were recorded at baseline and three days after stopping smoking. General Linear Models were used to compare changes between groups and changes from follow-up. Adjusting for baseline, at follow-up, all outcomes (for the 208 participants that completed the 3-day assessments) with the exception of SNP had improved significantly over baseline and there were no differences between groups (%FMD F = 1.03, p = 0.360, df = 2,207; ACh F = 0.172, p = 0.84, df = 2,207; SNP F = 0.382, p = 0.68, df = 2,207; MAP F = 0.176, p = 0.84, df = 2,207). For smokers ≥20 cigarettes per day, benefits were also pronounced. Smoking cessation showed positive cardiovascular impact even after a 3-day period and the effects did not differ between nicotine-containing e-cigarettes, nicotine-free e-cigarettes and NRT.

Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. During differentiation of embryoid bodies, PML influences cell-fate decisions between mesoderm and endoderm by controlling the expression of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced pluripotent stem cells by inhibiting the transforming growth factor β pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC naive pluripotency and somatic cell reprogramming.

Abstract Background The estimated number of cigarette smokers in the world is 1.3 billion, expected to rise to 1.7 billion by 2025, with 10 million smokers living in the U.K. Smoking is the leading, preventable death-cause worldwide, being responsible for almost 650,000 deaths in the E.U. annually. A combination of pharmacological interventions, including nicotine replacement therapy, bupropion and varenicline, and behavioural support is the most effective approach to smoking cessation. However, even the best methods have high relapse rates of approximately 75% within 6 months. Electronic (or “e-“) cigarettes use battery power to disperse a solution that usually contains propylene glycol or glycerine, water, flavouring and nicotine. E-cigarettes have become the most popular smoking cessation aid in England, however, information on their effects on cardiovascular function is limited and contradictory. As e-cigarettes are not solely nicotine-based products, existing research exploring the effects of nicotine on the cardio-vasculature provides only limited information, while their extensive uptake urges the need of evidence to inform the general public, smokers and policy-makers. Methods This is a pragmatic, 3-group, randomised, assessor-blinded, single-centre trial exploring the cardiovascular physiological effects of the use of e-cigarettes (nicotine-free and nicotine-inclusive, assessed separately) combined with behavioural support as a smoking cessation method in comparison to the combination of NRT and behavioural support. The primary outcome will be macro-vascular function, determined by a Flow Mediated Dilatation ultrasound assessment, 6 months following participants’ “quit date”. Discussion Participants will be assessed at baseline, 3 days following their self-determined “quit date”, at intervention end (3 months) and 6 months following their “quite date”. Findings are expected to give an indication of the cardiovascular effects of e-cigarettes both in the short- and in the medium-term period, informing the general public, policy holders and researchers, helping to define the future role of e-cigarettes as a smoking cessation aid. Trial registration Clinicaltrials.gov NCT03061253 . Registered 17th February 2017.

Sleep is a vital element of adolescents’ overall health; it influences their body and mind and thus affects their quality of life. Adequate sleep quality and duration are essential for maintaining optimal metabolic health and lowering the risk of developing several medical conditions, such as cardiovascular disease. The current study aimed to assess the perceived sleep quality and duration of 1717 European adolescents from three different European countries (Spain, Iceland and Estonia) aged 13- to 16-years (900 boys, 817 girls) using the Pittsburgh Sleep Quality Index (PSQI). A multivariate analysis of variance (MANOVA) was performed to examine differences between groups and two-factor analysis of variance (ANOVA) was used to analyze city and age differences. The probability of having poor sleep quality and duration was calculated by Odd-Ratio (OR). Our study found poor sleep quality in 44% of the boys and 53% of the girls, whereas 68% and 69%, respectively did not get the recommended hours of sleep (i.e., 8–10 h). No difference was found between adolescents from Estonia, Iceland and Spain regarding sleep duration. In contrast, Spanish and Estonian adolescents reported higher probabilities of having poor sleep quality. Finally, girls had a significantly higher probability of poor sleep quality than boys.

Pure red cell aplasia (PRCA) is a rare bone marrow failure syndrome defined by a progressive normocytic anaemia and reticulocytopenia without leukocytopenia and thrombocytopenia. Secondary PRCA can be associated with various haematological disorders, such as chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma (NHL). The aim of the present review is to investigate the infrequent association between PRCA and lymphoproliferative disorders. PRCA might precede the appearance of lymphoma, may present simultaneously with the lymphoid neoplastic disease, or might appear following the lymphomatic disorder. Possible pathophysiological molecular mechanisms to explain the rare association between PRCA and lymphoproliferative disorders are reported. Most cases of PRCA are presumed to be autoimmune mediated by antibodies against either erythroblasts or erythropoietin, by T-cells secreting factors selectively inhibiting erythroid colonies in the bone marrow or by NK cells directly lysing erythroblasts. Finally, focus is given to the therapeutical approach, as several treatment regimens have failed for PRCA. Immunosuppressive therapy and/or chemotherapy are effective for improving anaemia in the majority of patients with lymphoma-associated PRCA. Further investigation is required to define the pathophysiology of PRCA at a molecular level and to provide convincing evidence why it might appear as a rare complication of lymphoproliferative disorders.

We report a case of a bone marrow aspiration and trephine biopsy (BMATB) associated haematoma in an 85 years old male without any predisposing risk factors. Six days after BMATB, he suffered from a massive thigh and buttock haematoma and a fall in haematocrit. It is important to know that BMATB can have complications aiding early recognition and therapy.