Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

BACKGROUND: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner. PATIENTS AND METHODS: We used machine learning models of fragmentation patterns at the first coding exon in standard targeted cancer gene cfDNA sequencing panels to distinguish between cancer and non-cancer patients, as well as the specific tumor type and subtype. We assessed this approach in two independent cohorts: a published cohort from GRAIL (breast, lung, and prostate cancers, non-cancer, n = 198) and an institutional cohort from the University of Wisconsin (UW; breast, lung, prostate, bladder cancers, n = 320). Each cohort was split 70%/30% into training and validation sets. RESULTS: In the UW cohort, training cross-validated accuracy was 82.1%, and accuracy in the independent validation cohort was 86.6% despite a median ctDNA fraction of only 0.06. In the GRAIL cohort, to assess how this approach performs in very low ctDNA fractions, training and independent validation were split based on ctDNA fraction. Training cross-validated accuracy was 80.6%, and accuracy in the independent validation cohort was 76.3%. In the validation cohort where the ctDNA fractions were all <0.05 and as low as 0.0003, the cancer versus non-cancer area under the curve was 0.99. CONCLUSIONS: To our knowledge, this is the first study to demonstrate that sequencing from targeted cfDNA panels can be utilized to analyze fragmentation patterns to classify cancer types, dramatically expanding the potential capabilities of existing clinically used panels at minimal additional cost.

Successful complete oral rehabilitation of a patient with osteopetrosis with extensive pre-treatments, bone grafts, dental implants and fixed bridges: a multidisciplinary case report.

BACKGROUND: Osteopetrosis comprises a group of inherited disorders that are rare and result in abnormal bone structure. Bone remodeling is extremely inhibited because osteoclasts are nonfunctional or lacking. This condition causes overgrowth of bone with disappearance of the bone marrow, leading to aplastic anemia; obstruction of nerve passages in the skull leads to blindness and often hearing impairment. In most cases, osteopetrosis results in oral complications such as tooth deformation, hypomineralization, and delayed or absent tooth eruption. The only curative treatment is hematopoietic stem cell transplantation (HSCT). The main treatment of the oral complications during childhood and adolescence consists in protecting the erupted teeth against caries disease through prophylactic treatment aimed at optimal oral hygiene through frequent regular dental visits throughout life. Many patients with osteopetrosis require major oral rehabilitation to treat complications of the disease. Improved results of HSCT increase the likelihood that dental professionals will encounter patients with osteopetrosis. CASE PRESENTATION: In this case report, we show that individuals with osteopetrosis who have severe oral complications can be treated successfully if they are treated for osteopetrosis at an early age. The boy had his dental care in pedodontics, and regular multidisciplinary meetings were held for future treatment planning. At the age of 15, he was then referred for rehabilitation. The initial evaluations revealed no further growth in the alveolar bone. The rehabilitation was done stepwise, with extraction of malformed and malpositioned teeth. Initially, the patient received a removable partial denture followed by reconstruction of the width of the alveolar process, titanium implants, temporary fixed bridges, and finally screw-retained titanium-ceramic bridges with titanium frames for the upper and lower jaws. CONCLUSIONS: The three-year follow-up after loading indicated a stable marginal bone level and optimal oral hygiene as a result of frequent professional oral hygiene care. The patient showed no signs of symptoms from the temporomandibular joint and has adapted to the new jaw relation without any functional or phonetical issues.

A mobile app for the treatment of female mixed and urgency incontinence: a cost-effectiveness analysis in Sweden.

INTRODUCTION AND HYPOTHESIS: A previous randomized controlled trial (RCT) demonstrated that the app Tät II, for self-management of mixed urinary incontinence (MUI) and urgency urinary incontinence (UUI), yielded significant, clinically relevant improvements in symptom severity and quality of life (QoL) compared with a control group. We aimed to assess the cost-effectiveness of Tät II. METHODS: A cost-utility analysis with a 1-year societal perspective was carried out, comparing Tät II with an information app. Data were collected alongside an RCT: 122 community-dwelling women aged ≥18 years with MUI or UUI ≥2 times/week were randomized to 3 months of Tät II treatment focused on pelvic floor muscle training (PFMT) and bladder training (BT; n = 60), or to an information app (n = 62). Self-assessed data from validated questionnaires were collected at baseline and at 3-month and 1-year follow-ups. Costs for assessment, treatment delivery, incontinence aids, laundry, and time for PFMT and BT were included. We calculated quality-adjusted life-years (QALYs) using the International Consultation on Incontinence Modular Questionnaire Lower Urinary Tract Symptoms Quality of Life. The incremental cost-effectiveness ratio (ICER) between the groups was our primary outcome. Sensitivity analyses were performed. RESULTS: The mean age was 58.3 (SD = 9.6) years. Annual overall costs were €738.42 in the treatment group and €605.82 in the control group; annual QALY gains were 0.0152 and 0.0037 respectively. The base case ICER was €11,770.52; ICERs in the sensitivity analyses ranged from €-9,303.78 to €22,307.67. CONCLUSIONS: The app Tät II is a cost-effective treatment method for women with MUI and UUI.

Epstein-Barr virus is not detected in mucosal lichen planus.

BACKGROUND: Lichen planus (LP) is a chronic inflammatory, immunological, mucocutaneous disease can affect skin, genital and oral mucosa. Oral lichen planus (OLP) is the most common noninfectious, chronic inflammatory oral disease affecting 1-2% of the general adult population. World Health Organization (WHO) classifies OLP as a potentially malignant disorder. Epstein Barr virus or human herpesvirus-4, is a member of the herpes virus family and one of the most ubiquitous viruses known to human, infecting approximately 90% of the world's adult population. The virus often infects B lymphocytes resulting in a wide spectrum of mucocutaneous and systemic diseases, ranging from mild lesions to aggressive malignancies. The aim of this study was to investigate expression of the EBV encoded RNAs EBER1 and EBER2 in oral and genital lichen planus and compare results with normal tissues in situ hybridization which is considered the golden standard for detection of EBER. MATERIAL AND METHODS: A total of 68 biopsies, 25 oral LP, 26 genital LP, 10 oral controls and finally 7 genital controls were analysed using situ hybridization. RESULT: All samples had RNA as shown by the control slide, whereas no case contained neither EBER1 nor EBER2. CONCLUSIONS: Based on results from our study EBV is not involved in aetiology of lichen planus.

Folate and vitamin B12 concentrations are associated with plasma DHA and EPA fatty acids in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.

This study aimed to examine the association between vitamin B6, folate and vitamin B12 biomarkers and plasma fatty acids in European adolescents. A subsample from the Healthy Lifestyle in Europe by Nutrition in Adolescence study with valid data on B-vitamins and fatty acid blood parameters, and all the other covariates used in the analyses such as BMI, Diet Quality Index, education of the mother and physical activity assessed by a questionnaire, was selected resulting in 674 cases (43 % males). B-vitamin biomarkers were measured by chromatography and immunoassay and fatty acids by enzymatic analyses. Linear mixed models elucidated the association between B-vitamins and fatty acid blood parameters (changes in fatty acid profiles according to change in 10 units of vitamin B biomarkers). DHA, EPA) and n-3 fatty acids showed positive associations with B-vitamin biomarkers, mainly with those corresponding to folate and vitamin B12. Contrarily, negative associations were found with n-6:n-3 ratio, trans-fatty acids and oleic:stearic ratio. With total homocysteine (tHcy), all the associations found with these parameters were opposite (for instance, an increase of 10 nmol/l in red blood cell folate or holotranscobalamin in females produces an increase of 15·85 µmol/l of EPA (P value <0·01), whereas an increase of 10 nmol/l of tHcy in males produces a decrease of 2·06 µmol/l of DHA (P value <0·05). Positive associations between B-vitamins and specific fatty acids might suggest underlying mechanisms between B-vitamins and CVD and it is worth the attention of public health policies.

Association of heart rate and blood pressure among European adolescents with usual food consumption: The HELENA study.

BACKGROUND AND AIM: In adults, there is some evidence that improving diet reduces blood pressure (BP) and the subsequent risk of cardiovascular diseases (CVDs). However, studies that analyse this association in adolescents are still scarce. The objective of the present study was to examine the associations between heart rate, systolic (SBP), diastolic (DBP) and mean arterial blood pressure (MAP) among European adolescents and usual intake of vegetables, fruits, dairy products, meat, fish, high-sugar foods and savoury snacks. METHODS AND RESULTS: In total, 2283 adolescents from the HELENA-study (12.5-17.5 years old; 1253 girls) were included. Dietary intake was assessed using two computerized 24-hour dietary recalls. Age, sex, body mass index, maternal educational level, physical activity and Tanner stage were considered as confounders. Associations were examined by mixed model analysis stratified by sex. Tests for trend were assessed by tertiles of intake while controlling for the aforementioned confounders. Dairy products and fish intake were negatively associated with BP and heart rate. Significant decreasing trends were observed for heart rate and BP across tertiles of dairy products, fish intake and high-sugar foods intake (p < 0.05). Significant increasing trends were observed for SBP and MAP across tertiles of savoury snack intake (p < 0.05). CONCLUSION: Significant but small inverse associations between fish and dairy products consumption with blood pressure and heart rate have been found in European adolescents. Dietary intervention studies are needed to explore these associations in the context of the modification of several risk factors for the prevention of cardiovascular diseases.

ICIQ symptom and quality of life instruments measure clinically relevant improvements in women with stress urinary incontinence.

AIMS: To determine whether changes in questionnaire scores on symptoms and condition-specific quality of life reflect clinically relevant improvements in women with stress urinary incontinence (SUI). METHODS: We retrospectively analyzed questionnaires collected during a randomized controlled trial in women with SUI, that received pelvic floor muscle training (PFMT) in two different formats. We included 218 women that answered validated self-assessment questionnaires at baseline and at a 4-month follow-up. We registered changes on two questionnaires, the International Consultation on Incontinence Modular Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) and the Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol). We compared these score changes to responses from the Patient Global Impression of Improvement (PGI-I) questionnaire. Differences were analyzed with the Spearman rho and one-way-ANOVA. The minimum important difference (MID) was the mean change in score for women that experienced a small improvement. RESULTS: The PGI-I correlated significantly to both the ICIQ-UI SF (r = 0.547, P < 0.0001) and ICIQ-LUTSqol (r = 0.520, P < 0.0001). Thus, larger reductions in symptoms or quality of life scores were associated with greater impressions of improvement. The changes in ICIQ-UI SF and ICIQ-LUTSqol scores were significant across all PGI-I groups from "no change" to "very much improved" (P < 0.05). The MIDs were 2.52 (SD 2.56) for ICIQ-UI SF and 3.71 (SD 4.95) for ICIQ-LUTSqol. CONCLUSIONS: The change in ICIQ-UI SF and ICIQ-LUTSqol scores after PFMT reflected clinically relevant improvements in women with SUI. The MIDs established for this population may facilitate future research, treatment evaluations, and comparisons between studies.

Mechanisms of stress, energy homeostasis and insulin resistance in European adolescents--the HELENA study.

BACKGROUND AND AIMS: Stress is hypothesized to facilitate the development of obesity, whose the foundations are already set during childhood and adolescence. We investigated the relationship between the stress-system, selected mechanisms of energy homeostasis and insulin resistance (IR) in a sample of European adolescents. METHODS AND RESULTS: Within HELENA-CSS, 723 adolescents (12.5-17.5 years) from 10 European cities provided all the necessary data for this study. Fasting blood samples were collected for cortisol, leptin, insulin and glucose analysis. HOMA-IR was calculated from insulin and glucose concentrations. Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were assessed. For boys and girls separately, the relationship of cortisol with leptin, insulin, glucose and HOMA-IR was examined by computing Pearson correlation coefficients and Hierarchical Linear Models (HLMs), with 'city' as cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In boys, Pearson correlation coefficients illustrated positive correlations of cortisol with insulin (r = 0.144; p = 0.013), glucose (r = 0.315; p < 0.001) and HOMA-IR (r = 0.180; p = 0.002), whilst in girls, this positive relationship was observed for leptin (r = 0.147; p = 0.002), insulin (r = 0.095; p = 0.050) and HOMA-IR (r = 0.099; p = 0.041), but not for glucose (r = 0.054; p = 0.265). Observed associations were independent of adolescents' age, BF% and duration of exclusive breastfeeding after computing HLMs. CONCLUSION: This study suggests that the stress-system is positively related to mechanisms of energy homeostasis and IR in European adolescents, and reveals a potential small gender difference in this relationship. The hypothesis that stress might facilitate the development of obesity during adolescence is supported.

Combined influence of healthy diet and active lifestyle on cardiovascular disease risk factors in adolescents.

To investigate the combined influence of diet quality and physical activity on cardiovascular disease (CVD) risk factors in adolescents, adolescents (n = 1513; 12.5-17.5 years) participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence study were studied. Dietary intake was registered using a 24-h recall and a diet quality index was calculated. Physical activity was assessed by accelerometry. Lifestyle groups were computed as: healthy diet and active, unhealthy diet but active, healthy diet but inactive, and unhealthy diet and inactive. CVD risk factor measurements included cardiorespiratory fitness, adiposity indicators, blood lipid profile, blood pressure, and insulin resistance. A CVD risk score was computed. The healthy diet and active group had a healthier cardiorespiratory profile, fat mass index (FMI), triglycerides, and high-density lipoprotein cholesterol (HDL-C) levels and total cholesterol (TC)/HDL-C ratio (all P ≤ 0.05). Overall, active adolescents showed higher cardiorespiratory fitness, lower FMI, TC/HDL-C ratio, and homeostasis model assessment index and healthier blood pressure than their inactive peers with either healthy or unhealthy diet (all P ≤ 0.05). Healthy diet and active group had healthier CVD risk score compared with the inactive groups (all P ≤ 0.02). Thus, a combination of healthy diet and active lifestyle is associated with decreased CVD risk in adolescents. Moreover, an active lifestyle may reduce the adverse consequences of an unhealthy diet.

Evaluation of food and nutrient intake assessment using concentration biomarkers in European adolescents from the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

Accurate food and nutrient intake assessment is essential for investigating diet-disease relationships. In the present study, food and nutrient intake assessment among European adolescents using 24 h recalls (mean of two recalls) and a FFQ (separately and the combination of both) were evaluated using concentration biomarkers. Biomarkers included were vitamin C, ß-carotene, DHA+EPA, vitamin B12 (cobalamin and holo-transcobalamin) and folate (erythrocyte folate and plasma folate). For the evaluation of the food intake assessment 390 adolescents were included, while 697 were included for the nutrient intake assessment evaluation. Spearman rank and Pearson correlations, and validity coefficients, which are correlations between intake estimated and habitual true intake, were calculated. Correlations were higher between frequency of food consumption (from the FFQ) and concentration biomarkers than between mean food intake (from the recalls) and concentration biomarkers, especially for DHA+EPA (r 0·35 v. r 0·27). Most correlations were higher among girls than boys. For boys, the highest validity coefficients were found for frequency of fruit consumption (0·88) and for DHA+EPA biomarker (0·71). In girls, the highest validity coefficients were found for fruit consumption frequency (0·76), vegetable consumption frequency (0·74), mean fruit intake (0·90) and DHA+EPA biomarker (0·69). After exclusion of underreporters, correlations slightly improved. Correlations between usual food intakes, adjusted for food consumption frequency, and concentration biomarkers were higher than correlations between mean food intakes and concentration biomarkers. In conclusion, two non-consecutive 24 h recalls in combination with a FFQ seem to be appropriate to rank subjects according to their usual food intake.

Leg fat might be more protective than arm fat in relation to lipid profile.

PURPOSE: The objective of this study was to determine the independent relationships of trunk fat, leg fat and arm fat to cardiovascular (CVD) risk factors, after controlling for relevant confounders such as fat mass index, cardiorespiratory fitness and objectively measured physical activity. METHODS: This is a cross-sectional study involving 683 university students, aged 18-30 years. Total and regional body fat distribution was measured using dual-energy X-ray absorptiometry. The associations of trunk, leg and arm fat with CVD risk factors (triglycerides-TG-, high-density lipoprotein cholesterol-HDL-c-, TG/HDL-c ratio, HOMA(IR), mean arterial pressure, C-reactive protein) were examined using regression linear models, controlling for age, sex, fat mass index [total body fat(kg)/height(m(2))], maximal oxygen consumption and physical activity by accelerometer. RESULTS: After controlling for fat mass index, and other confounders, higher levels of trunk fat were found to be associated with a poorer lipid profile, while higher levels of leg fat were found to be associated with a better lipid profile. We did not find any association between arm fat and lipid profile after controlling for total fatness and other confounders. Neither trunk, leg or arm fat was found to be related to insulin resistance, blood pressure or inflammation markers. CONCLUSIONS: Our data suggest that the region where fat is accumulated might have a differential effect on lipid profile: trunk fat has an adverse effect, leg fat has a protective effect, and arm fat has no effect. The differences observed between upper- and lower-body peripheral fat depots should be further explored.

Role of socio-cultural factors on changes in fitness and adiposity in youth: a 6-year follow-up study.

BACKGROUND AND AIMS: Optimal cardio-respiratory fitness and adiposity levels are tightly related to health in youth. We analysed changes in fitness and adiposity in young individuals from two countries, and examined the role of maternal education in these changes. METHODS AND RESULTS: A 6-year follow-up study was conducted on 483 Estonian children (9 years) and 466 Swedish children (9-10 years) and adolescents (15 years). Fitness was assessed by a maximal bike test, and total and central adiposity were indirectly estimated by skinfolds (Slaughter's equation for fat mass) and waist circumference. At follow-up, fitness and adiposity had increased in the children cohort (P ≤ 0.001), while small or no change occurred in the adolescent cohort. In the children cohort, Estonian participants had a lower increase in fitness and a higher increase in adiposity (total and central) than Swedish participants. Higher maternal education increased the odds of remaining fit (top quartile) by half and reduced the risk of remaining fat (top quartile) by half; odds ratios = 1.56 (1.00-2.43), 0.50 (0.32-0.77) and 0.61 (0.39-0.94) for fitness, total and central adiposity, respectively. CONCLUSIONS: Our data suggest that the socioeconomic situation of a country might influence key cardiovascular risk factors (fitness and adiposity), being at higher risk for a low-middle income country (Estonia) than a higher income country (Sweden). The findings stress the role of socioeconomic status, particularly maternal education, in the maintenance of healthy fitness and adiposity levels from childhood into later life. Preventive efforts have to be taken from early age.

Physical activity attenuates the negative effect of low birth weight on leptin levels in European adolescents; the HELENA study.

We examined whether physical activity (PA) influences the association between birth weight and serum leptin in adolescents. The study comprised a total of 538 adolescents (315 girls), aged 12.5-17.49 years, born at term (≥ 37 weeks of gestation). We measured serum leptin levels and time engaged in moderate-vigorous PA (MVPA) by accelerometry. There was an interaction effect between birth weight and meeting the PA recommendations (60 min/day MVPA) on leptin levels in girls (P = 0.023) but not in boys (P = 0.809). Birth weight was negatively associated with leptin levels in girls not meeting the PA recommendations (i.e. more than 60 min/day of MVPA) (ß = -0.096, P = 0.009), whereas no significant association was observed in those meeting the PA recommendations (ß = -0.061, P = 0.433). In conclusion, meeting the PA recommendations may attenuate the negative effect of low birth weight on serum leptin levels in European female adolescents.

Self-reported and measured cardiorespiratory fitness similarly predict cardiovascular disease risk in young adults.

We aimed to (a) examine the validity and reliability of the International FItness Scale (IFIS) in Spanish young adults and (b) compare the capacity of self-reported vs measured fitness to predict cardiovascular disease (CVD) risk. The study comprised 276 participants (18-30 years). Fitness level (overall and specific components) was both self-reported (IFIS) and measured using standard fitness tests. Total and trunk fat was assessed by dual-energy X-ray absorptiometry. We computed a previously validated metabolic syndrome score. A separate sample of 181 of same age and characteristics fulfilled IFIS twice for reliability purposes. The results of the present study support the validity and reliability of self-reported fitness, as measured by IFIS, in Spanish young adults. Our data also suggest that not only measured cardiorespiratory fitness but also self-reported cardiorespiratory fitness predicts CVD risk, as assessed by adiposity and metabolic syndrome indicators. The associations for muscular fitness (both reported and measured) differed depending on how it was expressed (i.e., absolute vs relative terms). Self-reported fitness, as assessed by IFIS, can be a good alternative when physical fitness cannot be measured in large surveys.

Fibromyalgia's key symptoms in normal-weight, overweight, and obese female patients.

Factors affecting the symptomatology of fibromyalgia (FM) are not fully understood. The aim of the present study was to analyze the relationship of weight status with pain, fatigue, and stiffness in Spanish female FM patients, with special focus on the differences between overweight and obese patients. The sample comprised 177 Spanish women with FM (51.3 ± 7.3 years old). We assessed tenderness (using pressure algometry), pain and vitality using the General Health Short-Form Survey (SF36), and pain, fatigue, morning tiredness, and stiffness using the Fibromyalgia Impact Questionnaire (FIQ). The international criteria for body mass index was used to classify the patients as normal weight, overweight, or obese. Thirty-two percent were normal-weight, 35% overweight, and 32% obese. Both overweight and obese patients had higher levels of pain than normal-weight patients, as assessed by FIQ and SF36 questionnaires and tender point count (p < .01). The same pattern was observed for algometer score, yet the differences were not significant. Both overweight and obese patients had higher levels of fatigue, and morning tiredness, and stiffness (p < .05) and less vitality than normal-weight patients. No significant differences were observed in any of the variables studied between overweight and obese patients. In conclusion, FM symptomatology in obese patients did not differ from overweight patients, whereas normal-weight patients significantly differed from overweight and obese patients in the studied symptoms. These findings suggest that keeping a healthy (normal) weight is not only associated with decreased risk for developing FM but might also be a relevant and useful way of improving FM symptomatology in women.

Cardiorespiratory fitness and dietary intake in European adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence study.

The present study investigated the association between cardiorespiratory fitness (CRF) and dietary intake in European adolescents. The study comprised 1492 adolescents (770 females) from eight European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. CRF was assessed by the 20 m shuttle run test. Adolescents were grouped into low and high CRF levels according to the FITNESSGRAM Standards. Dietary intake was self-registered by the adolescents using a computer-based tool for 24 h dietary recalls (HELENA-Dietary Assessment Tool) on two non-consecutive days. Weight and height were measured, and BMI was calculated. Higher CRF was associated with higher total energy intake in boys (P = 0·003). No association was found between CRF and macronutrient intake (as percentage of energy), yet some positive associations were found with daily intake of bread/cereals in boys and dairy products in both boys and girls (all P < 0·003), regardless of centre, age and BMI. CRF was inversely related to sweetened beverage consumption in girls. These findings were overall consistent when CRF was analysed according to the FITNESSGRAM categories (high/low CRF). A high CRF was not related to compliance with dietary recommendations, except for sweetened beverages in girls (P = 0·002). In conclusion, a high CRF is associated with a higher intake of dairy products and bread/cereals, and a lower consumption of sweetened beverages, regardless of centre, age and BMI. The present findings contribute to the understanding of the relationships between dietary factors and physiological health indicators such as CRF.

Stress urinary incontinence and quality of life: a reliability study of a condition-specific instrument in paper and web-based versions.

AIMS: Quality of life is an important outcome measure in studies of urinary incontinence. Electronic collection of data has several advantages. We examined the reliability of the Swedish version of the highly recommended condition-specific quality of life questionnaire International Consultation on Incontinence Modular Questionnaire-Lower Urinary Tract Symptoms Quality of Life (ICIQ-LUTSqol), in paper and web-based formats in women with stress urinary incontinence. METHODS: Women aged 18-70 years, with stress urinary incontinence at least once weekly, were recruited via the project's website and answered the ICIQ-LUTSqol questionnaire. Respondents completed either the paper version twice (n = 78), or paper and web-based versions once each (n = 54). The ICIQ validation protocol was followed. RESULTS: The mean interval between answers was 18.1 (SD = 3.1) days in the paper versus paper setting and 15.0 (SD = 7.8) days in the paper versus web-based setting. Internal consistency was excellent, with Cronbach's alpha coefficients of 0.87 for the paper version and 0.86 for the web-based version. There was a high degree of agreement of overall scores with intraclass correlations in the paper versus paper and paper versus web-based settings: 0.95 (P < 0.001) and 0.92 (P < 0.001), respectively. The mean of each individual item's weighted kappa value was 0.61 in both settings. CONCLUSIONS: The questionnaire is reliable in women with stress urinary incontinence, and it can be used in either a paper or a web-based version.

Muscular strength and markers of insulin resistance in European adolescents: the HELENA Study.

The aim of the study was to examine the association of muscular strength with markers of insulin resistance in European adolescents. The study comprised a total of 1,053 adolescents (499 males; 12.5-17.5 years) from ten European cities participating in the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Cross-Sectional Study. Muscular strength was measured by the handgrip strength and standing long jump tests. Cardiorespiratory fitness was measured by the 20-m shuttle run test. Fasting insulin and glucose were measured and the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) indices were calculated. Weight, height, waist circumference and skinfold thickness were measured, and body mass index (BMI) was calculated. In males, the handgrip strength and standing long jump tests were negatively associated with fasting insulin and HOMA (all P < 0.05) after controlling for pubertal status, country and BMI or waist circumference. When skinfold thickness was included in the model, the association became non-significant. In females, the standing long jump test was negatively associated with fasting insulin and HOMA (all P < 0.001) after controlling for pubertal status, country and surrogate markers of total or central body fat (BMI, waist circumference or skinfold thickness). Findings were retained in males, but not in females after controlling for cardiorespiratory fitness. The findings of the present study suggest that preventive strategies should focus not only on decreasing fatness and increasing cardiorespiratory fitness but also on enhancing muscular strength.

Insulin sensitivity at childhood predicts changes in total and central adiposity over a 6-year period.

OBJECTIVE: To examine the associations of insulin resistance at childhood with adiposity changes over a 6-year period (from 9 to 15 years) in a sample of 659 Swedish and Estonian children (52.7% girls) participating in the European Youth Heart Study. RESEARCH, DESIGN AND METHODS: We measured weight, height, waist circumference, biceps, triceps, subscapular, suprailiac, and medial calf skinfolds, and we calculated body mass index (BMI), sum of five skinfolds, and body fat percentage. Fasting plasma glucose and insulin were measured and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Changes in puberty stage, sex, centre and the corresponding baseline adiposity values were used as confounders in all analysis. RESULTS: HOMA-IR at childhood was significantly and positively associated with changes in BMI (ß=0.265; P=0.024), sum of five skinfolds (ß=0.3445; P=0.003), body fat percentage (ß=1.042; P=0.016) and waist circumference (ß=0.806; P=0.002) from childhood to adolescence. These relationships persisted when overweight children were excluded from the analysis. BMI, sum of five skinfolds, body fat percentage and waist circumference at childhood were not significantly associated with changes in HOMA-IR (P for all >0.1). CONCLUSIONS: These results give further support to the concept that lower insulin sensitivity at childhood may predict subsequent total and central adiposity gain at adolescence. These findings enhance the role of insulin sensitivity as a target of obesity prevention already from the first decades of life.

Associations of muscular and cardiorespiratory fitness with total and central body fat in adolescents: the HELENA study.

OBJECTIVE: to examine the association of healthrelated physical fitness with total and central body fat in adolescents. PARTICIPANTS/METHODS: the present cross-sectional study comprises 363 Spanish adolescents (186 female participants) aged 12.5-17.5 years. We assessed fitness by the 20-m shuttle run test (cardiorespiratory fitness); the handgrip strength, the standing broad jump and the Abalakov tests (muscular strength); and the 4 × 10-m shuttle run test (speed-agility). Total body fat was measured by dual energy x-ray absorptiometry (DXA), BodPod and sum of six skinfolds, and central body fat was measured by DXA at three regions (R1, R2 and R3) and waist circumference. RESULTS: the Abalakov, the standing broad jump, the 4 × 10-m shuttle run and the 20-m shuttle run tests were negatively associated with all markers of total and central body fat in men and women after controlling for age, pubertal status and objectively assessed physical activity (p<0.01). Handgrip strength test was positively associated with waist circumference (p<0.01). CONCLUSIONS: lower body muscular strength and cardiorespiratory fitness are negatively and consistently associated with total and central body fat in adolescents, whereas levels of upper body muscular strength were superior in adolescents with higher levels of central body fat.