DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion.

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.

Metabolic control of arginine and ornithine levels paces the progression of leaf senescence.

Leaf senescence can be induced by stress or aging, sometimes in a synergistic manner. It is generally acknowledged that the ability to withstand senescence-inducing conditions can provide plants with stress resilience. Although the signaling and transcriptional networks responsible for a delayed senescence phenotype, often referred to as a functional stay-green trait, have been actively investigated, very little is known about the subsequent metabolic adjustments conferring this aptitude to survival. First, using the individually darkened leaf (IDL) experimental setup, we compared IDLs of wild-type (WT) Arabidopsis (Arabidopsis thaliana) to several stay-green contexts, that is IDLs of two functional stay-green mutant lines, oresara1-2 (ore1-2) and an allele of phytochrome-interacting factor 5 (pif5), as well as to leaves from a WT plant entirely darkened (DP). We provide compelling evidence that arginine and ornithine, which accumulate in all stay-green contexts-likely due to the lack of induction of amino acids (AAs) transport-can delay the progression of senescence by fueling the Krebs cycle or the production of polyamines (PAs). Secondly, we show that the conversion of putrescine to spermidine (SPD) is controlled in an age-dependent manner. Thirdly, we demonstrate that SPD represses senescence via interference with ethylene signaling by stabilizing the ETHYLENE BINDING FACTOR1 and 2 (EBF1/2) complex. Taken together, our results identify arginine and ornithine as central metabolites influencing the stress- and age-dependent progression of leaf senescence. We propose that the regulatory loop between the pace of the AA export and the progression of leaf senescence provides the plant with a mechanism to fine-tune the induction of cell death in leaves, which, if triggered unnecessarily, can impede nutrient remobilization and thus plant growth and survival.

Flawed conclusions on the Västerbotten Intervention Program by San Sebastian et .al.

An evaluation of Västerbotten Intervention Programme (VIP) was recently conducted by San Sebastian et al. (BMC Public Health 19:202, 2019). Evaluation of health care interventions of this kind require 1) an understanding of both the design and the nature of the intervention, 2) correct definition of the target population, and 3) careful choice of the appropriate evaluation method. In this correspondence, we review the approach used by San Sebastian et al. as relates to these three criteria. Within this framework, we suggest important explanations for why the conclusions drawn by these authors contradict a large body of research on the effectiveness of the VIP.

Treatment of stress urinary incontinence with a mobile app: factors associated with success.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence is common among women. First-line treatment includes pelvic floor muscle training (PFMT) and lifestyle advice, which can be provided via a mobile app. The efficacy of app-based treatment has been demonstrated in a randomized controlled trial (RCT). In this study, we aimed to analyze factors associated with successful treatment. METHODS: Secondary analysis of data from the RCT. At baseline and 3-month follow-up, participants (n = 61) answered questions about symptoms, quality of life, background, and PFMT. Success was defined as rating the condition as much or very much better according to the validated Patient Global Impression of Improvement questionnaire. Factors possibly associated with success were analyzed with univariate logistic regression; if p < 0.20, the factor was entered into a multivariate model that was adjusted for age. Variables were then removed stepwise. RESULTS: At follow-up, 34 out of 61 (56%) of participants stated that their condition was much or very much better. Three factors were significantly associated with success: higher expectations for treatment (odds ratio [OR] 11.38, 95% confidence interval [CI] 2.02-64.19), weight control (OR 0.44 per kg gained, 95% CI 0.25-0.79), and self-rated improvement of pelvic floor muscle strength (OR 35.54, 95% CI 4.96-254.61). Together, these factors accounted for 61.4% (Nagelkerke R2) of the variability in success. CONCLUSION: These results indicate that app-based treatment effects are better in women who are interested in and have high expectations of such treatment. Also, the findings underline the importance of strengthening the pelvic floor muscles and offering lifestyle advice.

A cost-effectiveness analysis of a community based CVD program in Sweden based on a retrospective register cohort.

BACKGROUND: Several large scale community-based cardiovascular disease prevention programs were initiated in the 80s, and one was the Västerbotten Intervention Programme, Sweden. As an initial step in 1985, a pilot study was introduced in the Norsjö municipality that combined individual disease prevention efforts among the middle-aged population with community-oriented health promotion activities. All citizens at 30, 40, 50, and 60 years of age were invited to a physical examination combined with a healthy dialogue at the local primary health care centre. Västerbotten Intervention Program is still running following the same lines and is now a part of the ordinary public health in the county. The purpose of this study is to estimate the costs of running Västerbotten Intervention Programme from 1990 to 2006, versus the health gains and savings reasonably attributable to the program during the same time period. METHODS: A previous study estimated the number of prevented deaths during the period 1990-2006 which can be attributed to the programme. We used this estimate and calculated the number of QALYs gained, as well as savings in resources due to prevented non-fatal cases during the time period 1990 to 2006. Costs for the programmes were based on previously published scientific articles as well as current cost data from the county council, who is responsible for the programme. RESULT: The cost per QALY gained from a societal perspective is SEK 650 (Euro 68). From a health care sector perspective, the savings attributable to the VIP exceeded its costs. CONCLUSION: Our analysis shows that Västerbotten Intervention Programme is extremely cost-effective in relation to the Swedish threshold value (SEK 500000 per QALY gained or Euro 53,000 per QALY gained). Other research has also shown a favorable effect of Västerbotten Intervention Programme on population health and the health gap. We therefore argue that all health care organizations, acting in settings reasonably similar to Sweden, have good incentive to implement programs like Västerbotten Intervention Programme.

Mobile app for treatment of stress urinary incontinence: A randomized controlled trial.

AIMS: To evaluate the effect of a mobile app treatment for stress urinary incontinence (SUI) in women. METHODS: Randomized controlled trial, conducted 2013-2014 in Sweden. Community-dwelling adult women with ≥1 SUI episode/week recruited through our website and randomized to app treatment (n = 62) or control group (postponed treatment, n = 61). One participant from each group was lost to follow-up. Intervention was the mobile app Tät® with a treatment program focused on pelvic floor muscle training (PFMT), and information about SUI and lifestyle factors. Primary outcomes, 3 months after randomization: symptom severity (International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form [ICIQ-UI SF]); and condition-specific quality of life (ICIQ Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). RESULTS: One hundred and twenty-three women were included (mean age 44.7), with moderate/severe SUI (97.5%, 120/123), mean ICIQ-UI SF score 11.1 (SD 2.8) and mean ICIQ-LUTSqol score 34.4 (SD 6.1) at baseline. At follow-up, the app group reported improvements in symptom severity (mean ICIQ-UI SF score reduction: 3.9, 95% confidence interval 3.0-4.7) and condition-specific quality of life (mean ICIQ-LUTSqol score reduction: 4.8, 3.4-6.2) and the groups were significantly different (mean ICIQ-UI SF score difference: -3.2, -4.3to -2.1; mean ICIQ-LUTSqol score difference: -4.6, -7.8 to -1.4). In the app group, 98.4% (60/61) performed PFMT at follow-up, and 41.0% (25/61) performed it daily. CONCLUSIONS: The mobile app treatment was effective for women with SUI and yielded clinically relevant improvements. This app may increase access to first-line treatment and adherence to PFMT.

Scoring of Hand Eczema: Good Reliability of Hand Eczema Extent Score (HEES).

There is good agreement between dermatological staff and patients using the Hand Eczema Extent Score (HEES). The aim of this study was to assess inter- and intra-observer reliability of the HEES in dermatologists and intra-observer reliability of the HEES in patients with hand eczema. Six dermatologists assessed 18 patients twice. Only the hands of the patients were visible to the assessors. Patients performed a self-assessment twice. Inter- and intra-observer reliability was tested with intraclass correlation coefficient (ICC). The mean HEES score for all dermatologists' assessments was 21.0 (range 3.6-46.3). The corresponding mean scores for all patients' own assessments were 24.9 (range 4.0-54.0). Inter-observer reliability in the dermatologists' observations ICC classification was very good, median value 0.82 (range 0.56-0.92). The overall intra-observer reliability for the 6 dermatologists' ICC classification was very good (range 0.88-0.94). Intra-observer reliability in the patients' 2 self-assessments ICC classification was very good (ICC 0.95). In conclusion, HEES is a reliable tool for both dermatologists and patients to grade the extent of hand eczema.

Impact of climate change on global malaria distribution.

Malaria is an important disease that has a global distribution and significant health burden. The spatial limits of its distribution and seasonal activity are sensitive to climate factors, as well as the local capacity to control the disease. Malaria is also one of the few health outcomes that has been modeled by more than one research group and can therefore facilitate the first model intercomparison for health impacts under a future with climate change. We used bias-corrected temperature and rainfall simulations from the Coupled Model Intercomparison Project Phase 5 climate models to compare the metrics of five statistical and dynamical malaria impact models for three future time periods (2030s, 2050s, and 2080s). We evaluated three malaria outcome metrics at global and regional levels: climate suitability, additional population at risk and additional person-months at risk across the model outputs. The malaria projections were based on five different global climate models, each run under four emission scenarios (Representative Concentration Pathways, RCPs) and a single population projection. We also investigated the modeling uncertainty associated with future projections of populations at risk for malaria owing to climate change. Our findings show an overall global net increase in climate suitability and a net increase in the population at risk, but with large uncertainties. The model outputs indicate a net increase in the annual person-months at risk when comparing from RCP2.6 to RCP8.5 from the 2050s to the 2080s. The malaria outcome metrics were highly sensitive to the choice of malaria impact model, especially over the epidemic fringes of the malaria distribution.

Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling.

Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a (13)CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1 The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and (13)C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions.

Non-face-to-face treatment of stress urinary incontinence: predictors of success after 1 year.

INTRODUCTION AND HYPOTHESIS: The objective was to determine predictors of long-term success in women with stress urinary incontinence (SUI) treated with a 3-month pelvic floor muscle training (PFMT) program delivered via the Internet or a brochure. METHODS: We included 169 women with SUI ≥1 time/week who completed the 1-year follow-up (n = 169, mean age 50.3, SD 10.1 years). Three outcome variables defined success after 1 year: Patient Global Impression of Improvement (PGI-I), International Consultation on Incontinence Modular Questionnaire Urinary Incontinence Short Form (ICIQ-UI SF), and sufficient treatment. Using logistic regression, we analyzed data from the baseline, and from the 4-month and 1-year follow-ups, for potential predictors of success. RESULTS: Of the participants, 77 % (129 out of 169) were successful in ≥1 of the outcomes, 23 % (37 out of 160) were successful in all 3. Participants with successful short-term results were more likely to succeed in the corresponding outcome at 1 year than those without successful short-term results (adjusted odds ratios [ORs]: PGI 5.15, 95 % confidence interval [CI] 2.40-11.03), ICIQ-UI SF 6.85 (95 % CI 2.83-16.58), and sufficient treatment 3.78 (95 % CI 1.58-9.08). Increasing age predicted success in PGI-I and sufficient treatment (adjusted OR 1.06, 95 % CI 1.02-1.10, and 1.08, 95 % CI, 1.03-1.13 respectively). Compared with not training regularly, regular PFMT at 1 year predicted success for PGI and sufficient treatment (adjusted OR 2.32, 95 % CI 1.04-5.20, and 2.99, 95 % CI 1.23-7.27 respectively). CONCLUSION: The long-term success of a non-face-to-face treatment program for SUI with a focus on PFMT can be predicted by successful short-term results, increasing age, and the performance of regular PFMT after 1 year.

Internet-based treatment of stress urinary incontinence: 1- and 2-year results of a randomized controlled trial with a focus on pelvic floor muscle training.

OBJECTIVES: To evaluate the long-term effects of two non-face-to-face treatment programmes for stress urinary incontinence (SUI) based on pelvic floor muscle training (PFMT). SUBJECTS AND METHODS: The present study was a randomized controlled trial with online recruitment of 250 community-dwelling women aged 18-70 years with SUI ≥ one time/week. Diagnosis was based on validated self-assessed questionnaires, 2-day bladder diary and telephone interview with a urotherapist. Consecutive computer-generated block randomization was carried out with allocation by an independent administrator to 3 months of treatment with either an internet-based treatment programme (n = 124) or a programme sent by post (n = 126). Both interventions focused mainly on PFMT. The internet group received continuous e-mail support from a urotherapist, whereas the postal group trained on their own. Follow-up was performed after 1 and 2 years via self-assessed postal questionnaires. The primary outcomes were symptom severity (International Consultation on Incontinence Questionnaire Short Form [ICIQ-UI SF]) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptoms Quality of Life [ICIQ-LUTSqol]). Secondary outcomes were the Patient Global Impression of Improvement, health-specific quality of life (EQ-visual analogue scale [EQ-VAS]), use of incontinence aids, and satisfaction with treatment. There was no face-to-face contact with the participants at any time. Analysis was based on intention-to-treat. RESULTS: We lost 32.4% (81/250) of participants to follow-up after 1 year and 38.0% (95/250) after 2 years. With both interventions, we observed highly significant (P < 0.001) improvements with large effect sizes (>0.8) for symptoms and condition-specific quality of life (QoL) after 1 and 2 years, respectively. No significant differences were found between the groups. The mean (sd) changes in symptom score were 3.7 (3.3) for the internet group and 3.2 (3.4) for the postal group (P = 0.47) after 1 year, and 3.6 (3.5) for the internet group and 3.4 (3.3) for the postal group (P = 0.79) after 2 years. The mean changes (sd) in condition-specific QoL were 5.5 (6.5) for the internet group and 4.7 the for postal group (6.5) (P = 0.55) after 1 year, and 6.4 (6.0) for the internet group and 4.8 (7.6) for the postal group (P = 0.28) after 2 years. The proportions of participants perceiving they were much or very much improved were similar in both intervention groups after 1 year (internet, 31.9% [28/88]; postal, 33.8% [27/80], P = 0.82), but after 2 years significantly more participants in the internet group reported this degree of improvement (39.2% [29/74] vs 23.8% [19/80], P = 0.03). Health-specific QoL improved significantly in the internet group after 2 years (mean change in EQ-VAS, 3.8 [11.4], P = 0.005). We found no other significant improvements in this measure. At 1 year after treatment, 69.8% (60/86) of participants in the internet group and 60.5% (46/76) of participants in the postal group reported that they were still satisfied with the treatment result. After 2 years, the proportions were 64.9% (48/74) and 58.2% (46/79), respectively. CONCLUSION: Non-face-to-face treatment of SUI with PFMT provides significant and clinically relevant improvements in symptoms and condition-specific QoL at 1 and 2 years after treatment.

Probiotics during weaning: a follow-up study on effects on body composition and metabolic markers at school age.

PURPOSE: An aberrant gut microbiome has been suggested to contribute to the worldwide epidemic of obesity. In animal models, the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) induced upregulation of genes involved in energy homoeostasis, reduced body fat and altered the serum (S) lipoprotein profile. In our previous report, feeding LF19 to infants during weaning impacted the global plasma metabolome. LF19 lowered palmitoleic acid, a monounsaturated fatty acid associated with hypertriglyceridemia and increased visceral adiposity. Therefore, we assessed if feeding LF19 from 4 to 13 months of age would have long-term effects on body composition, growth and metabolic markers. METHODS: Of 179 children included in our baseline study, 120 entered the follow-up at 8-9 years of age, n = 58 in the probiotic and n = 62 in the placebo group. Body composition was measured using dual energy X-ray absorptiometry. Anthropometrics of the child and accompanying parent(s) were assessed. S-lipids, insulin, glucose and transaminases were determined after overnight fasting. RESULTS: LF19 did not affect body mass index z-score, sagittal abdominal diameter, fat-free mass, fat mass index, truncal fat %, android or gynoid fat % and had no long-term impact on any of the assessed metabolic markers (p > 0.05). CONCLUSION: Feeding LF19 during infancy did not modulate body composition, growth or any of the assessed metabolic markers at school age. The steady increase in probiotic products targeting infants and children calls for long-term follow-up of initiated probiotic intervention studies.

Exposure to formaldehyde, nitrogen dioxide, ozone, and terpenes among office workers and associations with reported symptoms.

PURPOSE: To compare exposure to formaldehyde, nitrogen dioxide, ozone and terpenes among office workers with and without sick building syndrome and the odds ratio for exposure. Are there significant differences? METHODS: In this cross-sectional study of office workers, we investigated the associations between exposure to formaldehyde, nitrogen dioxide, ozone, α-pinene, and D-limonene using a case-control analysis. Data on perceived general, mucosal, and skin symptoms were obtained by questionnaires. Personal exposure measurements of the compounds were performed among cases and controls, and the odds ratios for exposures to the substances, both singly and in combination, were investigated. RESULTS: Exposures varied for formaldehyde between 0.23 and 45 µg/m(3), nitrogen dioxide between 0.26 and 110 µg/m(3), ozone between <16 and 165 µg/m(3), α-pinene between 0.2 and 170 µg/m(3), and D-limonene between 0.8 and 1,400 µg/m(3). No consistent differences in exposure odds ratios were found between cases and controls or for individual symptoms.

Impact of probiotics during weaning on the metabolic and inflammatory profile: follow-up at school age.

We hypothesised that feeding the probiotic Lactobacillus paracasei ssp. paracasei F19 (LF19) (dep. nr LMG P-17806) during weaning would program the metabolic and inflammatory profile and studied its association with previously assessed body composition. In a double-blind, placebo-controlled trial, 179 infants were randomised to daily feeding of cereals with or without LF19 10(8) CFU from 4 to 13 months of age. At age 8-9 years, 120 children were re-assessed. Using high-sensitivity multiplex immunoassay technology and ELISA, we found that overweight/obese children had increased plasma C-peptide, plasminogen activator inhibitor-1, leptin and serum high-sensitivity C-reactive protein (hsCRP) after overnight fasting compared with normal weight children, independently of LF19. After excluding the obese, leptin and hsCRP were still increased, revealing an aberrant metabolic and inflammatory state already in overweight, pre-pubertal children. Higher body mass index z-score, sagittal abdominal diameter, truncal and total body fat % were associated with an aberrant metabolic and inflammatory profile, emphasising the need for early prevention strategies although no programming effect of LF19 was observed.

The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk factors may depend on age.

The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus (EBV) infection have been suggested to interact statistically, but the results are conflicting. In a prospective study on 192 MS cases and 384 matched controls, we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive and multiplicative scales, and estimated the effects of the risk factors across strata of each other. The results suggest that a negative interaction may be present in samples drawn at a young age, and a positive interaction among older subjects.

Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis.

OBJECTIVE: The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the onset of symptoms of rheumatoid arthritis (RA) by several years. The aim of this study was to analyze antibodies against 10 citrullinated autoantigen-derived peptides for reactivity before the onset of RA symptoms. METHODS: A case-control study was conducted within the Medical Biobank of Northern Sweden. The study was performed in 409 individuals, 386 of whom donated 717 blood samples before the onset of symptoms of RA (pre-patients). The median period of time predating the onset of RA was 7.4 years. A total of 1,305 population-based control subjects were also studied. Antibodies to 10 citrullinated peptides, fibrinogen α573 (Fibα573), Fibα591, Fibß36-52, Fibß72, Fibß74, α-enolase (citrullinated α-enolase peptide 1 [CEP-1]), triple-helical type II collagen peptide C1 (citC1III), filaggrin, vimentin 2-17 (Vim2-17), and Vim60-75, were analyzed using a microarray system. RESULTS: The fluorescence intensity of antibodies against Fibß36-52, Fibß74, CEP-1, citC1III, and filaggrin was significantly increased in pre-patients compared with controls (P<0.001). The levels of the earliest-detectable antibodies (Fibα591 and Vim60-75) fluctuated over time, with only a slight increase after the onset of disease. The frequency of antibodies against Fibß36-52, CEP-1, and filaggrin increased gradually, reaching the highest levels before symptom onset. The frequency of a cluster of antibodies, citC1III, Fibα573, and Fibß74, increased only slightly before the onset of symptoms but increased prominently after disease onset. The odds ratio for the development of RA in individuals expressing both CEP-1 and Fibß36-52 antibodies (using data from samples obtained <3.35 years predating symptom onset) was 40.4 (95% confidence interval 19.8-82.3) compared with having either antibody alone. CONCLUSION: Development of an immune response toward citrullinated peptides is initially restricted but expands with time to induce a more specific response, with levels, particularly those of antibodies against CEP-1, Fibß36-52, and filaggrin, increasing during the predating time period closer to the onset of symptoms.

Predictors of smoking among Swedish adolescents.

BACKGROUND: Smoking most often starts in adolescence, implying that understanding of predicting factors for smoking initiation during this time period is essential for successful smoking prevention. The aim of this study was to examine predicting factors in early adolescence for smoking in late adolescence. METHODS: Longitudinal cohort study, involving 649 Swedish adolescents from lower secondary school (12-13 years old) to upper secondary school (17-18 years old). Tobacco habits, behavioural, intra- and interpersonal factors and socio-demographic variables were assessed through questionnaires. Descriptive statistics, univariable and multivariable logistic regression were used to identify predicting factors. RESULTS: Smoking prevalence increased from 3.3% among 12-13 year olds to 25.1% among 17-18 year olds. Possible predictors of smoking were: female sex, lower parental education, poorer family mood, poorer self-rated health, poorer self-esteem, less negative attitude towards smoking, binge drinking, snus use and smoking. In a multivariable logistic regression analysis, female sex (OR 1.64, CI 1.08-2.49), medium and low self-esteem (medium: OR 1.57, CI 1.03-2.38, low: 2.79, CI 1.46-5.33), less negative attitude towards smoking (OR 2.81, CI 1.70-4.66) and ever using snus (OR 3.43, CI 1.78-6.62) remained significant independent predicting factors. CONCLUSIONS: The study stresses the importance of strengthening adolescents' self-esteem, promoting anti-smoking attitudes in early adolescence, as well as avoidance of early initiation of snus. Such measures should be joint efforts involving parents, schools, youth associations, and legislating authorities.

Diagnostic characteristics and prognoses of primary-care patients referred for clinical exercise testing: a prospective observational study.

BACKGROUND: Evaluation of angina symptoms in primary care often includes clinical exercise testing. We sought to identify clinical characteristics that predicted the outcome of exercise testing and to describe the occurrence of cardiovascular events during follow-up. METHODS: This study followed patients referred to exercise testing for suspected coronary disease by general practitioners in the County of Jämtland, Sweden (enrolment, 25 months from February 2010). Patient characteristics were registered by pre-test questionnaire. Exercise tests were performed with a bicycle ergometer, a 12-lead electrocardiogram, and validated scales for scoring angina symptoms. Exercise tests were classified as positive (ST-segment depression >1 mm and chest pain indicative of angina), non-conclusive (ST depression or chest pain), or negative. Odds ratios (ORs) for exercise-test outcome were calculated with a bivariate logistic model adjusted for age, sex, systolic blood pressure, and previous cardiovascular events. Cardiovascular events (unstable angina, myocardial infarctions, decisions on revascularization, cardiovascular death, and recurrent angina in primary care) were recorded within six months. A probability cut-off of 10% was used to detect cardiovascular events in relation to the predicted test outcome. RESULTS: We enrolled 865 patients (mean age 63.5 years, 50.6% men); 6.4% of patients had a positive test, 75.5% were negative, 16.4% were non-conclusive, and 1.7% were not assessable. Positive or non-conclusive test results were predicted by exertional chest pain (OR 2.46, 95% confidence interval (CI) 1.69-3.59), a pathologic ST-T segment on resting electrocardiogram (OR 2.29, 95% CI 1.44-3.63), angina according to the patient (OR 1.70, 95% CI 1.13-2.55), and medication for dyslipidaemia (OR 1.51, 95% CI 1.02-2.23). During follow-up, cardiovascular events occurred in 8% of all patients and 4% were referred to revascularization. Cardiovascular events occurred in 52.7%, 18.3%, and 2% of patients with positive, non-conclusive, or negative tests, respectively. The model predicted 67/69 patients with a cardiovascular event. CONCLUSIONS: Clinical characteristics can be used to predict exercise test outcome. Primary care patients with a negative exercise test have a very low risk of cardiovascular events, within six months. A predictive model based on clinical characteristics can be used to refine the identification of low-risk patients.

The Metabolomic Profile of Microscopic Colitis Is Affected by Smoking but Not Histopathological Diagnosis, Clinical Course, Symptoms, or Treatment.

Microscopic colitis (MC) is classified as collagenous colitis (CC) and lymphocytic colitis (LC). Genetic associations between CC and human leucocyte antigens (HLAs) have been found, with smoking being a predisposing external factor. Smoking has a great impact on metabolomics. The aim of this explorative study was to analyze global metabolomics in MC and to examine whether the metabolomic profile differed regarding the type and course of MC, the presence of IBS-like symptoms, treatment, and smoking habits. Of the 240 identified women with MC aged ≤73 years, 131 completed the study questionnaire; the Rome III questionnaire; and the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS). Blood samples were analyzed by ultra-high-performance liquid chromatograph mass spectrometry (UHLC-MS/UHPLC-MSMS). The women, 63.1 (58.7-67.2) years old, were categorized based on CC (n = 76) and LC (n = 55); one episode or refractory MC; IBS-like symptoms or not; use of corticosteroids or not; and smoking habits. The only metabolomic differences found in the univariate model after adjustment for false discovery rate (FDR) were between smokers and non-smokers. Serotonin was markedly increased in smokers (p < 0.001). No clear patterns appeared when conducting a principal component analysis (PCA). No differences in the metabolomic profile were found depending on the type or clinical course of the disease, neither in the whole MC group nor in the subgroup analysis of CC.

Sleep apnoea is a common occurrence in females.

Obstructive sleep apnoea (OSA) is primarily regarded as a male disorder, presenting with snoring, daytime sleepiness and cardiovascular disease. We aimed to determine the frequency of sleep apnoea among females in the general population. We investigated 400 females from a population-based random sample of 10,000 females aged 20-70 yrs. They answered a questionnaire and performed overnight polysomnography. OSA (apnoea/hypopnoea index (AHI) ≥5) was found in 50% (95% CI 45-55%) of females aged 20-70 yrs. Sleep apnoea was related to age, obesity and hypertension, but not to daytime sleepiness. Severe sleep apnoea (AHI ≥30) was present in 14% (95% CI 8.1-21%) of females aged 55-70 yrs and in 31% (95% CI 12-50%) of obese females with a body mass index of ≥30 kg·m(-2) aged 55-70 yrs. Sleep apnoea with daytime sleepiness and sleep apnoea with hypertension were observed as two different phenotypes of OSA. OSA occurs in 50% of females aged 20-70 yrs. 20% of females have moderate and 6% severe sleep apnoea. Sleep apnoea in females is related to age, obesity and hypertension, but not to daytime sleepiness. When searching for sleep apnoea in females, females with hypertension or obesity should be investigated.