Prevalence of Pathogenic Germline Variants in Women with Non-Familial Unilateral Triple-Negative Breast Cancer.

Introduction: International guidelines recommend genetic testing for women with familial breast cancer at an expected prevalence of pathogenic germline variants (PVs) of at least 10%. In a study sample of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), we have previously shown that women with TNBC diagnosed before the age of 50 years but without a family history of breast or ovarian cancer (sTNBC) meet this criterion. The present study investigates the PV prevalence in BRCA1, BRCA2, and nine additional cancer predisposition genes in an extended sTNBC study sample including a cohort of women with a later age at sTNBC diagnosis. Patients and Methods: In 1,600 women with sTNBC (median age at diagnosis: 41 years, range 19-78 years), we investigated the association between age at diagnosis and PV occurrence in cancer predisposition genes using logistic regression. Results: 260 sTNBC patients (16.2%) were found to have a PV in cancer predisposition genes (BRCA1: n = 170 [10.6%]; BRCA2: n = 46 [2.9%], other: n = 44 [2.8%]). The PV prevalence in women diagnosed between 50 and 59 years (n = 194) was 11.3% (22/194). Logistic regression showed a significant increase in PV prevalence with decreasing age at diagnosis (OR 1.41 per 10 years younger age at diagnosis; 95% confidence interval: 1.21-1.65; p < 0.001). The PV prevalence predicted by the model was above 10% for diagnoses before the age of 56.8 years. Conclusion: Based on the data presented, we recommend genetic testing by gene panel analysis for sTNBC patients diagnosed before the age of 60 years. Due to the still uncertain estimate for women with sTNBC diagnosed above the age of 60 years, further studies are needed.

Physical activity and mental health: the connection between step count and depression, anxiety and quality of sleep.

While there are studies connecting everyday physical activity (PA) to mental health, they mostly use self-report measures for PA which are biased in multiple ways. Nevertheless, a realistic assessment of everyday PA is important for the development and implementation of low-threshold public health interventions. Therefore, we want to analyze the relationship between objectively measured daily steps and mental health. We included 1451 subjects from a subsample of the population-based LIFE-Adult-Study (2011-2014) with an average age of 55.0 years, 52.1% were female. We analyzed the effects of PA (step count measured via SenseWear Pro 3) on depression (CES-D), anxiety (GAD-7), and quality of sleep (PSQI). The regression analysis showed a significant negative association between low to moderate PA [Incidence rate ratio: 0.87 (0.77; 0.98)] as well as high to very high PA [0.84 (0.74; 0.95)] and depression and no significant associations between PA and anxiety [l-m: 0.98 (0.81; 1.18)/h-vh: 1.00 (0.82; 1.21)] or quality of sleep [l-m: 0.94 (0.84, 1.06)/h-vh: 0.92 (0.82, 1.03)], controlling for sociodemographic variables and personality. Low-threshold interventions that increase daily step count could be a useful approach for the prevention of depression. The use of objective PA measurement for research is highly encouraged.

Connecting chronic stress and anxiety: a multi-dimensional perspective.

Studies show a connection between anxiety and stress, but with little differentiation between different domains of stress. In this article, we utilize a multi-dimensional approach to better understand the relationship between different chronic stress domains and anxiety. This will allow researchers to identify and address those areas of stress that are most relevant with regard to anxiety. We used data from a sub sample of the LIFE-Adult-Study (n = 1085) to analyze the association between nine different areas of chronic stress (Trier Inventory for Chronic Stress, TICS) and anxiety (General Anxiety Disorder 7, GAD-7), controlling for sociodemographic variables, personality, and social support. There was a significant and positive association between Work Overload, Pressure to Perform, Social Tensions, Social Isolation, Chronic Worrying, and anxiety. After including the control variables, only Work Overload and Chronic Worrying remained significant. By focusing on Work Overload and Chronic Worrying researchers, practitioners, and policy makers can help to mitigate anxiety and related health problems in the population in an efficient way.

The Leipzig Health Atlas-An Open Platform to Present, Archive, and Share Biomedical Data, Analyses, and Models Online.

BACKGROUND: Clinical trials, epidemiological studies, clinical registries, and other prospective research projects, together with patient care services, are main sources of data in the medical research domain. They serve often as a basis for secondary research in evidence-based medicine, prediction models for disease, and its progression. This data are often neither sufficiently described nor accessible. Related models are often not accessible as a functional program tool for interested users from the health care and biomedical domains. OBJECTIVE: The interdisciplinary project Leipzig Health Atlas (LHA) was developed to close this gap. LHA is an online platform that serves as a sustainable archive providing medical data, metadata, models, and novel phenotypes from clinical trials, epidemiological studies, and other medical research projects. METHODS: Data, models, and phenotypes are described by semantically rich metadata. The platform prefers to share data and models presented in original publications but is also open for nonpublished data. LHA provides and associates unique permanent identifiers for each dataset and model. Hence, the platform can be used to share prepared, quality-assured datasets and models while they are referenced in publications. All managed data, models, and phenotypes in LHA follow the FAIR principles, with public availability or restricted access for specific user groups. RESULTS: The LHA platform is in productive mode (https://www.health-atlas.de/). It is already used by a variety of clinical trial and research groups and is becoming increasingly popular also in the biomedical community. LHA is an integral part of the forthcoming initiative building a national research data infrastructure for health in Germany.

Different Areas of Chronic Stress and Their Associations with Depression.

BACKGROUND: Research shows a connection between stress and depression, but there is little differentiation between areas of stress, making it difficult to identify and address specific areas in the context of public health measures. We utilized a multi-dimensional approach to chronic stress to better understand the relationship between different areas of stress and depression. METHODS: We conducted linear regression analyses and used data from a sub-sample of the LIFE-Adult-Study (N = 1008) to analyze the connection between nine different areas of chronic stress (TICS) and depression (CES-D). In the second analysis, we controlled for sociodemographic variables, personality, physical activity, and social support. RESULTS: There was a significant positive association between the stress domains Excessive Demands from Work, Lack of Social Recognition, Social Isolation, and Chronic Worrying and depression and a significant negative association between Pressure to Perform and depression. After adding control variables, only Pressure to Perform, Social Isolation, and Chronic Worrying remained significant predictors. CONCLUSIONS: By focusing on the connections between chronic stress and depression, researchers can help identify the areas that matter most and contribute to the creation of meaningful and efficient interventions. On the basis of our results, measures for the prevention of depression that focus on the reduction of worrying and social isolation are recommended.

Adenoma and colorectal cancer risks in Lynch syndrome, Lynch-like syndrome and familial colorectal cancer type X.

Lynch syndrome (LS), Lynch-like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk-adapted surveillance policies in LS, LLS and FCCX.

[HerediCaRe: Documentation and IT Solution of a Specialized Registry for Hereditary Breast and Ovarian Cancer]. / HerediCaRe: Dokumentations- und IT-Lösung eines spezialisierten Registers für erblichen Brust- und Eierstockkrebs.

The national registry "HerediCaRe" for the evaluation and improvement of risk-adjusted prevention in hereditary breast and ovarian cancer is one of six "model registries in health services research" funded by the BMBF. In this paper, we describe and discuss the documentation and IT solution chosen for standardized data collection based on the specific functional requirements previously defined. The documentation is divided into different modules to be used individually for each patient, which are based on a previously defined catalog of documentation items. Due to special functional requirements, a specific data entry application based on ORACLE and ORACLE Forms was developed and implemented. The specific requirements included the integration of graphical pedigree representations, the structured upload of pedigree data and molecular genetic information, the automated transfer of old data from the previous system, as well as the free programmability of complex database queries for central data quality control. A database for patient-independent management of genetic risk variants was seamlessly integrated into the application and linked to the patient-related data. The advantages and disadvantages of the chosen IT solution are critically discussed. Overall, we come to the conclusion that, in view of the complex documentation and the special functional requirements, there are no alternative ready-made software products to the in-house development we have chosen.

Analyzing the link between anxiety and eating behavior as a potential pathway to eating-related health outcomes.

Anxiety is a widespread phenomenon that affects various behaviors. We want to analyze in how far anxiety is connected to eating behaviors since this is one potential pathway to understanding eating-related health outcomes like obesity or eating disorders. We used data from the population-based LIFE-Adult-Study (n = 5019) to analyze the connection between anxiety (GAD-7) and the three dimensions of eating behaviors (FEV)-Cognitive Restraint, Disinhibition, and Hunger-while controlling for sociodemographic variables, smoking, physical activity, personality, and social support. Multivariate regression analyses showed significant positive associations between anxiety and Disinhibition as well as Hunger, but not between anxiety and Cognitive Restraint. Interventions that help individuals to better regulate and cope with anxiety, could be one potential pathway to reducing eating disorders and obesity in the population.

Depressive Symptomatology in Early Retirees Associated With Reason for Retirement-Results From the Population-Based LIFE-Adult-Study.

BACKGROUND: Transition from employment to retirement is regarded a crucial event. However, there is mixed evidence on associations between retirement and mental health, especially regarding early retirement. In Germany, cases of early retirement due to ill health-particularly, mental ill health-are increasing. Therefore, we investigated the association between early retirement and depressive symptoms, including information on different types of early retirement. METHODS: We analyzed data from 4,808 participants of the population-based LIFE-Adult-Study (age: 40-65 years, 654 retired, 4,154 employed), controlling for sociodemographic information, social network, pre-existing health conditions, and duration of retirement. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale. Regression analysis using entropy balancing was applied to achieve covariate balance between retired and employed subjects. RESULTS: We found no overall-differences in depressive symptoms between employed and retired persons (men: b = -.52; p = 0.431; women: b = .05; p = .950). When looking at different types of early retirement, ill-health retirement was linked to increased depressive symptoms in women (b = 4.68, 95% CI = 1.71; 7.65), while voluntary retirement was associated with reduced depressive symptoms in men (b= -1.83, 95% CI = -3.22; -.43) even after controlling for covariates. For women, statutory retirement was linked to lower depressive symptomatology (b = -2.00, 95% CI = -3.99; -.02). CONCLUSION: Depressive symptomatology among early retirees depends on reason for retirement: For women, ill-health retirement is linked to higher levels of depressive symptoms. Women who retire early due to ill-health constitute a risk group for depressive symptoms that needs specific attention in the health care and social security system.

Cancer risks in Lynch syndrome, Lynch-like syndrome, and familial colorectal cancer type X: a prospective cohort study.

BACKGROUND: Individuals with pathogenic germline variants in DNA mismatch repair (MMR) genes are at increased risk of developing colorectal, endometrial and other cancers (Lynch syndrome, LS). While previous studies have extensively described cancer risks in LS, cancer risks in individuals from families without detectable MMR gene defects despite MMR deficiency (Lynch-like syndrome, LLS), and in individuals from families fulfilling the Amsterdam-II criteria without any signs of MMR deficiency (familial colorectal cancer type X, FCCX) are less well studied. The aim of this prospective study was to characterise the risk for different cancer types in LS, LLS, and FCCX, and to compare these with the cancer risks in the general population. METHODS: Data was taken from the registry of the German Consortium for Familial Intestinal Cancer, where individuals were followed up prospectively within the framework of an intensified surveillance programme at recommended annual examination intervals. A total of 1120 LS, 594 LLS, and 116 FCCX individuals were analysed. From this total sample, eight different cohorts were defined, in which age-dependent cumulative risks and standardised incidence ratios were calculated regarding the first incident occurrence of any, colorectal, stomach, small bowel, urothelial, female breast, ovarian, and endometrial cancer, separately for LS, LLS, and FCCX. RESULTS: The number of individuals at risk for first incident cancer ranged from 322 to 1102 in LS, 120 to 586 in LLS, and 40 to 116 in FCCX, depending on the cancer type of interest. For most cancer types, higher risks were observed in LS compared to LLS, FCCX, and the general population. Risks for any, colorectal, stomach, urothelial, and endometrial cancer were significantly higher in LLS compared to the general population. No significantly increased risks could be detected in FCCX compared to LLS patients, and the general population. Colorectal and endometrial cancer risks tended to be higher in LLS than in FCCX. CONCLUSIONS: The characterisation of cancer risks in patients with LLS and FCCX is important to develop appropriate surveillance programmes for these specific intermediate risk groups. Larger prospective studies are needed to obtain more precise risk estimates.

Associations of Pathogenic Variants in MLH1, MSH2, and MSH6 With Risk of Colorectal Adenomas and Tumors and With Somatic Mutations in Patients With Lynch Syndrome.

BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.

Breast cancer risk in BRCA1/2 mutation carriers and noncarriers under prospective intensified surveillance.

Comparably little is known about breast cancer (BC) risks in women from families tested negative for BRCA1/2 mutations despite an indicative family history, as opposed to BRCA1/2 mutation carriers. We determined the age-dependent risks of first and contralateral breast cancer (FBC, CBC) both in noncarriers and carriers of BRCA1/2 mutations, who participated in an intensified breast imaging surveillance program. The study was conducted between January 1, 2005, and September 30, 2017, at 12 university centers of the German Consortium for Hereditary Breast and Ovarian Cancer. Two cohorts were prospectively followed up for incident FBC (n = 4,380; 16,398 person-years [PY], median baseline age: 39 years) and CBC (n = 2,993; 10,090 PY, median baseline age: 42 years). Cumulative FBC risk at age 60 was 61.8% (95% CI 52.8-70.9%) for BRCA1 mutation carriers, 43.2% (95% CI 32.1-56.3%) for BRCA2 mutation carriers and 15.7% (95% CI 11.9-20.4%) for noncarriers. FBC risks were significantly higher than in the general population, with incidence rate ratios of 23.9 (95% CI 18.9-29.8) for BRCA1 mutation carriers, 13.5 (95% CI 9.2-19.1) for BRCA2 mutation carriers and 4.9 (95% CI 3.8-6.3) for BRCA1/2 noncarriers. Cumulative CBC risk 10 years after FBC was 25.1% (95% CI 19.6-31.9%) for BRCA1 mutation carriers, 6.6% (95% CI 3.4-12.5%) for BRCA2 mutation carriers and 3.6% (95% CI 2.2-5.7%) for noncarriers. CBC risk in noncarriers was similar to women with unilateral BC from the general population. Further studies are needed to confirm whether less intensified surveillance is justified in women from BRCA1/2 negative families with elevated risk.

No Difference in Colorectal Cancer Incidence or Stage at Detection by Colonoscopy Among 3 Countries With Different Lynch Syndrome Surveillance Policies.

BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.

The association between unemployment and depression-Results from the population-based LIFE-adult-study.

BACKGROUND: Unemployment is a risk factor for impaired mental health. Based on a large population-based sample, in this study we therefore sought to provide detailed information on the association between unemployment and depression including information on (i) differences between men and women, (ii) differences between different types of unemployment, and (iii) on the impact of material and social resources on the association. METHODS: We studied 4,842 participants (18-65 years) of the population-based LIFE-Adult-Study. Depression was assessed using the Center for Epidemiological Studies Depression Scale. Employment status was divided into three groups: being employed, being unemployed receiving entitlement-based benefits, being unemployed receiving means-tested benefits. Multivariate logistic regression models were applied to assess the association between employment status and depression. RESULTS: Statistically significantly increased depression risk was solely found for unemployed persons receiving means-tested benefits. Adjusting for differences in sociodemographic factors, net personal income and risk of social isolation, comparable associations of being unemployed and receiving means-tested benefits with elevated depression risk were found for men (Odds Ratio/OR = 2.17, 95%-CI = 1.03-4.55) and women (OR = 1.98, 95%-CI:1.22-3.20). LIMITATIONS: No conclusions regarding causality can be drawn due to the cross-sectional study design. It was not possible to assess length of unemployment spells. CONCLUSION: Unemployed persons receiving means-tested benefits in Germany constitute a risk group for depression that needs specific attention in the health care and social security system. The negative impact of unemployment on depression risk cannot be explained solely by differences in material and social resources. Contrasting earlier results, women are equally affected as men.

Prevalence of pathogenic BRCA1/2 germline mutations among 802 women with unilateral triple-negative breast cancer without family cancer history.

BACKGROUND: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group. METHODS: The study comprised 802 women (median age 40 years, range 19-76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation. RESULTS: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20-29 years compared to 6.9% in the age group 60-69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50-2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years. CONCLUSIONS: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.

Prevalence of BRCA1/2 germline mutations in 21†401 families with breast and ovarian cancer.

PURPOSE: To characterise the prevalence of pathogenic germline mutations in BRCA1 and BRCA2 in families with breast cancer (BC) and ovarian cancer (OC) history. PATIENTS AND METHODS: Data from 21 401 families were gathered between 1996 and 2014 in a clinical setting in the German Consortium for Hereditary Breast and Ovarian Cancer, comprising full pedigrees with cancer status of all individual members at the time of first counselling, and BRCA1/2 mutation status of the index patient. RESULTS: The overall BRCA1/2 mutation prevalence was 24.0% (95% CI 23.4% to 24.6%). Highest mutation frequencies were observed in families with at least two OCs (41.9%, 95% CI 36.1% to 48.0%) and families with at least one breast and one OC (41.6%, 95% CI 40.3% to 43.0%), followed by male BC with at least one female BC or OC (35.8%; 95% CI 32.2% to 39.6%). In families with a single case of early BC (<36 years), mutations were found in 13.7% (95% CI 11.9% to 15.7%). Postmenopausal unilateral or bilateral BC did not increase the probability of mutation detection. Occurrence of premenopausal BC and OC in the same woman led to higher mutation frequencies compared with the occurrence of these two cancers in different individuals (49.0%; 95% CI 41.0% to 57.0% vs 31.5%; 95% CI 28.0% to 35.2%). CONCLUSIONS: Our data provide guidance for healthcare professionals and decision-makers to identify individuals who should undergo genetic testing for hereditary breast and ovarian cancer. Moreover, it supports informed decision-making of counselees on the uptake of genetic testing.

Incremental value of Veterans Specific Activity Questionnaire and the YMCA-step test for the assessment of cardiorespiratory fitness in population-based studies.

BACKGROUND: Cardiorespiratory fitness is a well-established independent predictor of cardiovascular health. However, the relevance of alternative exercise and non-exercise tests for cardiorespiratory fitness assessment in large cohorts has not been studied in detail. We aimed to evaluate the YMCA-step test and the Veterans Specific Activity Questionnaire (VSAQ) for the estimation of cardiorespiratory fitness in the general population. METHODS: One hundred and five subjects answered the VSAQ, performed the YMCA-step test and a maximal cardiopulmonary exercise test (CPX) and gave BORG ratings for both exercise tests (BORGSTEP, BORGCPX). Correlations of peak oxygen uptake on a treadmill (VO2_PEAK) with VSAQ, BORGSTEP, one-minute, post-exercise heartbeat count, and peak oxygen uptake during the step test (VO2_STEP) were determined. Moreover, the incremental values of the questionnaire and the step test in addition to other fitness-related parameters were evaluated using block-wise hierarchical regression analysis. RESULTS: Eighty-six subjects completed the step test according to the protocol. For completers, correlations of VO2_PEAK with the age- and gender-adjusted VSAQ, heartbeat count and VO2_STEP were 0.67, 0.63 and 0.49, respectively. However, using hierarchical regression analysis, age, gender and body mass index already explained 68.8% of the variance of VO2_PEAK, while the additional benefit of VSAQ was rather low (3.4%). The inclusion of BORGSTEP, heartbeat count and VO2_STEP increased R(2) by a further 2.2%, 3.3% and 5.6%, respectively, yielding a total R(2) of 83.3%. CONCLUSIONS: Neither VSAQ nor the YMCA-step test contributes sufficiently to the assessment of cardiorespiratory fitness in population-based studies.

Association between IgE-mediated allergies and diabetes mellitus type 1 in children and adolescents.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by an immunological reaction that is dominated by type-1 T helper (Th1) cells, whereas immunoglobulin E (IgE)-mediated allergies are associated with Th2 cell. According to the Th1/Th2-hypothesis, the immune system is said to either develop into the direction of Th1 or Th2 cells. This would mean that a child developing T1DM is unlikely to develop an IgE-mediated allergy and vice versa. OBJECTIVE: The aim of the study was to investigate the association between the prevalence of T1DM and IgE-mediated allergies. METHODS: We designed a prospective case control study with 94 children and adolescents with T1DM and 188 age- and sex-matched control children. The basis of our investigations was a questionnaire concerning the family and children's history as to the presence of IgE-mediated allergies. Moreover, the following blood investigations were done: total serum IgE, specific IgE antibodies to major inhalant allergens, and a multiplex cytokine analysis measuring levels of specific cytokines representing either Th1- or Th2- cytokines. RESULTS: Children with T1DM reported the presence of IgE-mediated allergies significantly more often than children of the control group. Children with T1DM had significantly higher tumor necrosis factor alpha (TNFα) levels than healthy controls. Levels of interleukin-2 (IL-2) and IL-6 were higher in the groups of children with the presence of a personal history of allergies, regardless of the presence of T1DM. CONCLUSIONS: Our results suggest that T1DM is associated with a higher risk of a self-reported presence of IgE-mediated allergies and that the Th1/Th2-hypothesis may be an oversimplification.

Reference intervals for leukocyte subsets in adults: Results from a population-based study using 10-color flow cytometry.

BACKGROUND: Reference intervals for leukocyte subsets from peripheral blood are helpful for the understanding of disease states and therapy effects. METHODS: We performed in-depth immunophenotyping for 608 healthy German adults from the Leipzig region from 40 to 79 years by 10-color flow cytometry (FCM) to gain reference information for various leukocyte subsets including subsets of granulocytes, monocytes and lymphocytes. RESULTS: First, we derived gender- and age-specific reference intervals for males and females from 40 to 59 and from 60 to 79 years, respectively. Second, we further investigated the influence of gender and age on leukocyte counts. We found significantly higher cell counts for monocytes (P < 0.001) and NK cells (P < 0.001) in men, whereas women had higher counts for B cells (P < 0.001), Th cells (P < 0.001) and regulatory T cells (P = 0.008). Furthermore, with increasing age, a decrease in Tc cells (about 8% within 5 years) and an increase in NK cells (<4% within 5 years) were observed. CONCLUSION: In future research, it should be investigated whether these are real ageing effects that can be confirmed in longitudinal studies. Furthermore, it is important to understand if the Tc cell count drop is functionally compensated by the increase of NK cells.

Validation of a brief step-test protocol for estimation of peak oxygen uptake.

BACKGROUND: Physical exercise capacity has been shown to predict cardiovascular disease incidence and is increasingly measured in epidemiological studies. However, direct measurement of peak oxygen uptake is too time consuming in large-scale studies. We therefore investigated whether a brief 3-minute step-test protocol can be used to estimate peak oxygen uptake in these settings. DESIGN AND METHODS: A group of 97 subjects performed the YMCA step test and a maximal treadmill test with continuous measurement of oxygen uptake. Correlation and linear regression analyses were used to identify VO2peak predictors obtained from the step test and to develop models for VO2peak estimation. RESULTS: The YMCA model, including the 1-minute heart beat count, predicted VO2peak with R = 0.83. A novel simplified model based on the heart rate at 45 s of recovery performed comparable (R = 0.83). However, models based on heart rate measures were only valid in subjects who completed the test according to protocol, but not in subjects who terminated prematurely. For the applicability in subjects with low exercise capacity, a new model including gas exchange analysis enabled prediction of VO2peak (R = 0.89). All models were validated in an independent sample (r = 0.86-0.91). Exercise time of the step test was less than one-hird of standard ergospirometry (treadmill test: 654 ± 151 s, step test: 180 s, p < 0.001). CONCLUSION: In large-scale epidemiological studies with limited time slots for exercise testing and significant proportions of subjects with low exercise capacity a modified version of the YMCA step test may be used to predict VO2peak.