Cancer Patients' Symptom Burden and Health-related Quality of Life (HRQoL) at Tertiary Cancer Center from 2006 to 2013 : A Cross-sectional Study

Background/Aim: To observe changes in symptoms and health-related quality of life (HRQoL) over 7 years among cancer patients at different stages of the disease. Patients and Methods: This prospective cross-sectional study at the Helsinki University Hospital Cancer Center, was carried out in 2006 and repeated in 2013. All participants filled in the EORTC-QLQ-C30 questionnaire. Results: Altogether, 581 patients responded (49% in 2006 and 54% in 2013). The disease was local in 51% and advanced in 49% of patients. The HRQoL was significantly lower, except for emotional and cognitive functions, and the symptom burden more severe in advanced cancer. The most prevalent symptoms were fatigue (93% and 85%; moderate/severe 22% and 9%), pain (65% and 47%; moderate/severe 16% and 5%), and insomnia (64% and 60%; moderate/severe 20 and 21%), respectively. No changes in HRQoL or symptoms were found at 7 years. Conclusion: There is a need for early integrated palliative care to improve HRQoL during cancer treatments.Peer reviewe

Complete androgen insensitivity syndrome caused by a deep intronic pseudoexon-activating mutation in the androgen receptor gene

Mutations in the X-linked androgen receptor (AR) gene underlie complete androgen insensitivity syndrome (CAIS), the most common cause of 46, XY sex reversal. Molecular genetic diagnosis of CAIS, however, remains uncertain in patients who show normal coding region of AR. Here, we describe a novel mechanism of AR disruption leading to CAIS in two 46, XY sisters. We analyzed whole-genome sequencing data of the patients for pathogenic variants outside the AR coding region. Patient fibroblasts from the genital area were used for AR cDNA analysis and protein quantification. Analysis of the cDNA revealed aberrant splicing of the mRNA caused by a deep intronic mutation (c.2450-118A>G) in the intron 6 of AR. The mutation creates a de novo 5' splice site and a putative exonic splicing enhancer motif, which leads to the preferential formation of two aberrantly spliced mRNAs (predicted to include a premature stop codon). Patient fibroblasts contained no detectable AR protein. Our results show that patients with CAIS and normal AR coding region need to be examined for deep intronic mutations that can lead to pseudoexon activation.Peer reviewe

Prevalence and determinants of vitamin D deficiency and insufficiency among three immigrant groups in Finland : evidence from a population-based study using standardised 25-hydroxyvitamin D data

Objective: We investigated the determinants of serum 25-hydroxyvitamin D [S-25(OH)D] and dietary vitamin D sources among three immigrant groups in Finland and compared their S-25(OH)D to the general Finnish population. Design: Cross-sectional population-based Migrant Health and Wellbeing Study and the nationally representative Finnish Health 2011 Survey. S-25(OH)D was standardised according to the Vitamin D Standardisation Program. Vitamin D sources were assessed by interview. Setting: Six different municipalities in Finland (60 degrees-63 degrees N). Participants: Immigrants aged 18-64 years (446 Russians, 346 Somalis, 500 Kurds), 798 Finns aged 30-64 years. Results: The mean of S-25(OH)D was 64 (95 % CI 62, 66), 44 (95 % CI 41, 46), 35 (95 % CI 34, 37) and 64 (95 % CI 62, 66) nmol/l for Russians, Somalis, Kurds and Finns, respectively. S-25(OH)D among Somalis and Kurds was lower compared with Finns (P <0 center dot 001). The prevalence of vitamin D deficiency (S-25(OH)DPeer reviewe

The Metabolome in Finnish Carriers of the MYBPC3-Q1061X Mutation for Hypertrophic Cardiomyopathy

Aims Mutations in the cardiac myosin-binding protein C gene (MYBPC3) are the most common genetic cause of hypertrophic cardiomyopathy (HCM) worldwide. The molecular mechanisms leading to HCM are poorly understood. We investigated the metabolic profiles of mutation carriers with the HCM-causing MYBPC3-Q1061X mutation with and without left ventricular hypertrophy (LVH) and non-affected relatives, and the association of the meta-bolome to the echocardiographic parameters. Methods and Results 34 hypertrophic subjects carrying the MYBPC3-Q1061X mutation, 19 non-hypertrophic mutation carriers and 20 relatives with neither mutation nor hypertrophy were examined using comprehensive echocardiography. Plasma was analyzed for molecular lipids and polar metabolites using two metabolomics platforms. Concentrations of branched chain amino acids, triglycerides and ether phospholipids were increased in mutation carriers with hypertrophy as compared to controls and non-hypertrophic mutation carriers, and correlated with echocardiographic LVH and signs of diastolic and systolic dysfunction in subjects with the MYBPC3-Q1061X mutation. Conclusions Our study implicates the potential role of branched chain amino acids, triglycerides and ether phospholipids in HCM, as well as suggests an association of these metabolites with remodeling and dysfunction of the left ventricle.Peer reviewe

Airway obstruction, serum vitamin D and mortality in a 33-year follow-up study

Background and objective: Chronic obstructive pulmonary disease and low vitamin D status predict mortality, but their combined effect on mortality remains inconclusive. We aimed to investigate a joint effect of airway obstruction and vitamin D status on mortality in a nationally representative cohort. Methods: We analysed data of 6676 Finnish adults participating between 1978 and 1980 in a national health examination survey, undergoing spirometry and having all necessary data collected. We followed them up in national registers through record linkage until 31 December 2011. We categorised the subjects with obstruction using the lower limit of normal (LLN) and the measured serum 25-hydroxyvitamin-D (s-25(OH)D) into tertiles. Results: Both obstruction and low s-25(OH) D independently predicted mortality in a multivariate model adjusted also for age, sex, smoking, education, leisure physical activity, body mass index, asthma and serum C-reactive protein. However, a statistically significant (p = 0.007) interaction emerged: the adjusted mortality HRs (95% CI's) for s-25(OH)D in tertiles among the subjects without and with obstruction were 1.00 (lowest), 0.96 (0.87-1.05) and 0.89 (0.81-0.98); and 1.00, 0.96 (0.71-1.31) and 0.57 (0.40-0.80), respectively. Conclusions: In conclusion, obstruction and low s-25(OH)D predict mortality independently of each other. Our findings suggest that low vitamin D status might be particularly detrimental among subjects with obstruction.Peer reviewe

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.Peer reviewe