Association between depressive symptoms and objectively measured daily step count in individuals at high risk of cardiovascular disease in South London, UK: a cross-sectional study.

OBJECTIVES: Depressive symptoms are common but rarely considered a risk factor for unhealthy lifestyles associated with cardiovascular disease (CVD). This study investigates whether depressive symptoms are associated with reduced physical activity (PA) in individuals at high risk of developing CVD. DESIGN: Secondary analysis of the cross-sectional baseline data from a randomised controlled trial of an intensive lifestyle intervention. SETTING: 135 primary care practices in South London, UK. PARTICIPANTS: 1742 adults, 49-74 years, 86% male at high (≥20%) risk of developing CVD in the next 10 years as defined via QRISK2 score. OUTCOME MEASURES: The main explanatory variable was depressive symptoms measured via the Patient Health Questionnaire-9 (PHQ-9). The main outcome was daily step count measured with an accelerometer (ActiGraph GT3X) stratified by weekdays and weekend days. RESULTS: The median daily step count of the total sample was 6151 (IQR 3510) with significant differences (P<0.001) in mean daily step count between participants with low (PHQ-9 score: 0-4), mild (PHQ-9 score: 5-9) and moderate to severe depressive symptoms (PHQ-9 score: ≥10). Controlling for age, gender, ethnicity, education level, body mass index (BMI), smoking, consumption of alcohol, day of the week and season, individuals with mild depressive symptoms and those with moderate to severe depressive symptoms walked 13.3% (95% CI 18.8% to 7.9%) and 15.6% (95% CI 23.7% to 6.5%) less than non-depressed individuals, respectively. Furthermore, male gender, white ethnicity, higher education level, lower BMI, non-smoking, moderate alcohol intake, weekdays and summer season were independently associated with higher step count. CONCLUSIONS: People at high risk of CVD with depressive symptoms have lower levels of PA. TRIAL REGISTRATION: ISRCTN84864870; Pre-results

Pulmonary metastasectomy versus continued active monitoring in colorectal cancer (PulMiCC): a multicentre randomised clinical trial

BACKGROUND: Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT). METHODS: Multidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%. RESULTS: Between December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56). CONCLUSIONS: Because of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23-62%) for metastasectomy patients and 29% (16-52%) in the well-matched controls. That is the new and important finding of this RCT. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT01106261. Registered on 19 April 2010

A community-based feasibility randomized controlled study to test food-specific inhibitory control training in people with disinhibited eating during COVID-19 in Italy

This is the final version. Available on open access from Springer via the DOI in this recordData availability: Data are available on request to the corresponding author.PURPOSE: The aim of this study was to expand the evidence on the feasibility and impact of food-specific inhibitory control training in a community sample of people with disinhibited eating. METHODS: Recruitment and data collection were conducted during the COVID-19 outbreak, in Italy. Ninety-four adult individuals with disinhibited eating were randomised to one of two conditions: App-based food-specific inhibitory control training or waiting list. Participants were assessed at baseline, end of intervention (2 weeks following baseline) and follow-up (one week later). The assessment measures included questionnaires about eating behaviour and mood. RESULTS: Seventy-three percent of the sample reported a diagnosis of binge eating disorder, and 20.4% a diagnosis of bulimia nervosa. Retention rates were 77% and 86% for the food-specific inhibitory control training and the waiting list conditions, respectively. Almost half of the participants allocated to the training condition completed the "recommended" dose of training (i.e., 10 or more sessions). Those in the training condition reported lower levels of wanting for high-energy dense foods (p < 0.05), a trend for lower levels of perceived hunger (p = 0.07), and lower levels of depression (p < 0.05). Binge eating symptoms, disinhibition, wanting for high-energy dense foods, stress and anxiety were significantly lower at end of intervention, compared to baseline (p < .05). CONCLUSION: Findings corroborated the feasibility of food-specific inhibitory control training, and its impact on high-energy dense foods liking. The study expands the evidence base for food-specific inhibitory control training by highlighting its impact on perceived hunger and depression. The mechanisms underlying these effects remain to be clarified. LEVEL OF EVIDENCE: Level I, Evidence obtained from at least one properly designed randomized controlled trials; systematic reviews and meta-analyses; experimental studies.National Institute for Health Research (NIHR)University of PadovaDipartimenti di Eccellenza, Ministero dell'Istruzione (MIUR

Augmentation index assessed by applanation tonometry is elevated in Marfan Syndrome

<p>Abstract</p> <p>Background</p> <p>To examine whether augmentation index (AIx) is increased in Marfan syndrome (MFS) and associated with increased aortic root size, and whether a peripheral-to-central generalised transfer function (GTF) can be applied usefully in MFS.</p> <p>Methods</p> <p>10 MFS patients and 10 healthy controls (matched for sex, age and height) were studied before and after 400 μg sub-lingual GTN. Arterial waveforms were recorded using applanation tonometry. AIx and pulse pressure (PP) were determined for the radial and carotid arteries. Pulse wave velocity (PWV) was measured between carotid and femoral arteries. GTFs were generated to examine the relationship between radial and carotid waveforms.</p> <p>Results</p> <p>AIx was greater in MFS compared to controls at radial (mean -31.4 (SD 14.3)% v -50.2(15.6)%, p = 0.003) and carotid (-7.6(11.2)% v -23.7(12.7)%, p = 0.004) sites. Baseline PP at all measurement sites, and PWV, did not differ between subject groups. Multivariate analysis demonstrated that PWV and carotid AIx were positively correlated with aortic root size (p < 0.001 and p = 0.012 respectively), independent of the presence of MFS. PP was not associated with aortic root size. GTN caused similar decreases in AIx in both controls and patients. Significant differences were found in GTFs between MFS and control subjects, which changed following GTN administration. However, when an independent GTF was used to derive carotid waves from radial waves, no differences were found in the degree of error between MFS and controls.</p> <p>Conclusion</p> <p>AIx is sensitive to the vascular abnormalities present in MFS, and may have a role as an adjunct to measurement of central PP and PWV. Differences between MFS and controls in the nature of the peripheral-to-central GTF are present, although have little effect on the pulse contour.</p

Myocardial perfusion reserve and contractile pattern after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy

In Idiopathic Dilated Cardiomyopathy (IDC) an imbalance between myocardial oxygen consumption and supply has been postulated. The ensuing subclinical myocardial ischemia may contribute to progressive deterioration of LV function. beta-blocker is the therapy of choice in these patients. However, not all patients respond to the same extent. The aim of this study was to elucidate whether differences between responders and non-responders can be identified with respect to regional myocardial perfusion reserve (MPR) and contractile performance. Patients with newly diagnosed IDC underwent Positron Emission Tomography (PET) scanning using both (13)N-ammonia as a perfusion tracer (baseline and dipyridamole stress), and (18)F-fluoro-deoxyglucose as a metabolism tracer, and a dobutamine stress MRI. MRI and PET were repeated 6 months after maximal beta-blocker therapy. MPR (assessed by PET) as well as wall motion score (WMS, assessed by MRI) were evaluated in a 17 segment-model. Functional response to beta-blocker therapy was assigned as a stable or improved LVEF or diminished LVEF. Sixteen patients were included (age 47.9 +/- A 11.5 years; 12 males, LVEF 28.6 +/- A 8.4%). Seven patients showed improved LVEF (9.7 +/- A 3.1%), and nine patients did not show improved LVEF (-3.4 +/- A 3.9%). MPR improved significantly in responders (1.56 +/- A .23 to 1.93 +/- A .49, P = .049), and MPR decreased in non-responders; however, not significantly (1.98 +/- A .70 to 1.61 +/- A .28, P = .064), but was significantly different between both groups (P = .017) after beta-blocker therapy. A significant correlation was found between change in perfusion reserve and change in LVEF: a decrease in perfusion reserve was associated with a decrease in LVEF and vice versa. Summed rest score of wall motion in responders improved from 26 to 21 (P = .022) whereas in non-responders no change was observed from 26 to 25) (P = ns). Summed stress score of wall motion in responders improved from 23 to 21 (P = .027) whereas in non-responders no change was observed from 27 to 26) (P = ns). In IDC patients, global as well as regional improvement after initiation of beta-blocker treatment is accompanied by an improvement in regional perfusion parameters. On the other hand in IDC patients with further left ventricular function deterioration after initiation of beta-blocker therapy this is accompanied by a decrease in perfusion reserve

Arginine Metabolism by Macrophages Promotes Cardiac and Muscle Fibrosis in mdx Muscular Dystrophy

Duchenne muscular dystrophy (DMD) is the most common, lethal disease of childhood. One of 3500 new-born males suffers from this universally-lethal disease. Other than the use of corticosteroids, little is available to affect the relentless progress of the disease, leading many families to use dietary supplements in hopes of reducing the progression or severity of muscle wasting. Arginine is commonly used as a dietary supplement and its use has been reported to have beneficial effects following short-term administration to mdx mice, a genetic model of DMD. However, the long-term effects of arginine supplementation are unknown. This lack of knowledge about the long-term effects of increased arginine metabolism is important because elevated arginine metabolism can increase tissue fibrosis, and increased fibrosis of skeletal muscles and the heart is an important and potentially life-threatening feature of DMD.We use both genetic and nutritional manipulations to test whether changes in arginase metabolism promote fibrosis and increase pathology in mdx mice. Our findings show that fibrotic lesions in mdx muscle are enriched with arginase-2-expressing macrophages and that muscle macrophages stimulated with cytokines that activate the M2 phenotype show elevated arginase activity and expression. We generated a line of arginase-2-null mutant mdx mice and found that the mutation reduced fibrosis in muscles of 18-month-old mdx mice, and reduced kyphosis that is attributable to muscle fibrosis. We also observed that dietary supplementation with arginine for 17-months increased mdx muscle fibrosis. In contrast, arginine-2 mutation did not reduce cardiac fibrosis or affect cardiac function assessed by echocardiography, although 17-months of dietary supplementation with arginine increased cardiac fibrosis. Long-term arginine treatments did not decrease matrix metalloproteinase-2 or -9 or increase the expression of utrophin, which have been reported as beneficial effects of short-term treatments.Our findings demonstrate that arginine metabolism by arginase promotes fibrosis of muscle in muscular dystrophy and contributes to kyphosis. Our findings also show that long-term, dietary supplementation with arginine exacerbates fibrosis of dystrophic heart and muscles. Thus, commonly-practiced dietary supplementation with arginine by DMD patients has potential risk for increasing pathology when performed for long periods, despite reports of benefits acquired with short-term supplementation

Eating disorders: the current status of molecular genetic research

Anorexia nervosa (AN) and bulimia nervosa (BN) are complex disorders characterized by disordered eating behavior where the patient’s attitude towards weight and shape, as well as their perception of body shape, are disturbed. Formal genetic studies on twins and families suggested a substantial genetic influence for AN and BN. Candidate gene studies have initially focused on the serotonergic and other central neurotransmitter systems and on genes involved in body weight regulation. Hardly any of the positive findings achieved in these studies were unequivocally confirmed or substantiated in meta-analyses. This might be due to too small sample sizes and thus low power and/or the genes underlying eating disorders have not yet been analyzed. However, some studies that also used subphenotypes (e.g., restricting type of AN) led to more specific results; however, confirmation is as yet mostly lacking. Systematic genome-wide linkage scans based on families with at least two individuals with an eating disorder (AN or BN) revealed initial linkage regions on chromosomes 1, 3 and 4 (AN) and 10p (BN). Analyses on candidate genes in the chromosome 1 linkage region led to the (as yet unconfirmed) identification of certain variants associated with AN. Genome-wide association studies are under way and will presumably help to identify genes and pathways involved in these eating disorders. The elucidation of the molecular mechanisms underlying eating disorders might improve therapeutic approaches