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Background: No previous research of university students in Finland assessed lifestyle behavioral risk factors (BRFs), grouped students into clusters, appraised the relationships of the clusters with their mental well-being, whilst controlling for confounders. The current study undertook this task., Methods: Students at the University of Turku (n = 1177, aged 22.96 ± 5.2 years) completed an online questionnaire that tapped information on sociodemographic variables (age, sex, income sufficiency, accommodation during the semester), four BRFs [problematic alcohol consumption, smoking, food consumption habits, moderate-to-vigorous physical activity (MVPA)], as well as depressive symptoms and stress. Two-step cluster analysis of the BRFs using log-likelihood distance measure categorized students into well-defined clusters. Two regression models appraised the associations between cluster membership and depressive symptoms and stress, controlling for sex, income sufficiency and accommodation during the semester., Results: Slightly more than half the study participants (56.8%) had always/mostly sufficient income and 33% lived with parents/partner. Cluster analysis of BRFs identified three distinct student clusters, namely Cluster 1 (Healthy Group), Cluster 2 (Smokers), and Cluster 3 (Nonsmokers but Problematic Drinkers). Age, sex and MVPA were not different across the clusters, but Clusters 1 and 3 comprised significantly more respondents with always/mostly sufficient income and lived with their parents/partner during the semester. All members in Clusters 1 and 3 were non-smokers, while all Cluster 2 members comprised occasional/daily smokers. Problematic drinking was significantly different between clusters (Cluster 1 = 0%, Cluster 2 = 54%, Cluster 3 = 100%). Cluster 3 exhibited significantly healthier nutrition habits than both other clusters. Regression analysis showed: (1) males and those with sufficient income were significantly less likely to report depressive symptoms or stress; (2) those living with parents/partner were significantly less likely to experience depressive symptoms; (3) compared to Cluster 1, students in the two other clusters were significantly more likely to report higher depressive symptoms; and (4) only students in Cluster 2 were more likely to report higher stress., Conclusions: BRFs cluster together, however, such clustering is not a clear-cut, all-or-none phenomenon. Students with BRFs consistently exhibited higher levels of depressive symptoms and stress. Educational and motivational interventions should target at-risk individuals including those with insufficient income or living with roommates or alone., (© 2024. The Author(s).)

Wastewater-based epidemiology (WBE) emerged during the coronavirus disease 2019 (COVID-19) pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden. The lack of high-resolution fecal shedding data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) limits our ability to link WBE measurements to disease burden. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as for the commonly used fecal indicators pepper mild mottle virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2-infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding. Of the individuals that provided at least three stool samples spanning more than 14 days, 77% had one or more samples that tested positive for SARS-CoV-2 RNA. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall. CrAssphage DNA was detected in at least one sample from 80% (38/48) of individuals and was detected in 48% (179/371) of all samples. The geometric mean concentrations of PMMoV and crAssphage in stool across all individuals were 8.7 × 10 4 and 1.4 × 10 4 gene copies/milligram-dry weight, respectively, and crAssphage shedding was more consistent for individuals than PMMoV shedding. These results provide us with a missing link needed to connect laboratory WBE results with mechanistic models, and this will aid in more accurate estimates of COVID-19 burden in sewersheds. Additionally, the PMMoV and crAssphage data are critical for evaluating their utility as fecal strength normalizing measures and for source-tracking applications. IMPORTANCE This research represents a critical step in the advancement of wastewater monitoring for public health. To date, mechanistic materials balance modeling of wastewater-based epidemiology has relied on SARS-CoV-2 fecal shedding estimates from small-scale clinical reports or meta-analyses of research using a wide range of analytical methodologies. Additionally, previous SARS-CoV-2 fecal shedding data have not contained sufficient methodological information for building accurate materials balance models. Like SARS-CoV-2, fecal shedding of PMMoV and crAssphage has been understudied to date. The data presented here provide externally valid and longitudinal fecal shedding data for SARS-CoV-2, PMMoV, and crAssphage which can be directly applied to WBE models and ultimately increase the utility of WBE., Competing Interests: The authors declare no conflict of interest.

Background: Brown adipose tissue (BAT) is an important tissue for thermogenesis, making it a potential target to decrease the risks of obesity, type 2 diabetes, and cardiovascular disease, and recent studies have also identified BAT as an endocrine organ. Although BAT has been implicated to be protective in cardiovascular disease, to this point there are no studies that identify a direct role for BAT to mediate cardiac function., Methods: To determine the role of BAT on cardiac function, we utilized a model of BAT transplantation. We then performed lipidomics and identified an increase in the lipokine 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME). We utilized a mouse model with sustained overexpression of 12,13-diHOME and investigated the role of 12,13-diHOME in a nitric oxide synthase type 1 deficient (NOS1 -/- ) mouse and in isolated cardiomyocytes to determine effects on function and respiration. We also investigated 12,13-diHOME in a cohort of human patients with heart disease., Results: Here, we determined that transplantation of BAT (+BAT) improves cardiac function via the release of the lipokine 12,13-diHOME. Sustained overexpression of 12,13-diHOME using tissue nanotransfection negated the deleterious effects of a high-fat diet on cardiac function and remodeling, and acute injection of 12,13-diHOME increased cardiac hemodynamics via direct effects on the cardiomyocyte. Furthermore, incubation of cardiomyocytes with 12,13-diHOME increased mitochondrial respiration. The effects of 12,13-diHOME were absent in NOS1 -/- mice and cardiomyocytes. We also provide the first evidence that 12,13-diHOME is decreased in human patients with heart disease., Conclusions: Our results identify an endocrine role for BAT to enhance cardiac function that is mediated by regulation of calcium cycling via 12,13-diHOME and NOS1.

Background: Due to unprecedented shortages in N95 filtering facepiece respirators, healthcare systems have explored N95 reprocessing. No single, full-scale reprocessing publication has reported an evaluation including multiple viruses, bacteria, and fungi along with respirator filtration and fit., Methods: We explored reprocessing methods using new 3M 1860 N95 respirators, including moist (50%-75% relative humidity [RH]) heat (80-82°C for 30 minutes), ethylene oxide (EtO), pulsed xenon UV-C (UV-PX), hydrogen peroxide gas plasma (HPGP), and hydrogen peroxide vapor (HPV). Respirator samples were analyzed using 4 viruses (MS2, phi6, influenza A virus [IAV], murine hepatitis virus [MHV)]), 3 bacteria ( Escherichia coli , Staphylococcus aureus , Geobacillus stearothermophilus spores, and vegetative bacteria), and Aspergillus niger . Different application media were tested. Decontaminated respirators were evaluated for filtration integrity and fit., Results: Heat with moderate RH most effectively inactivated virus, resulting in reductions of >6.6-log 10 MS2, >6.7-log 10 Phi6, >2.7-log 10 MHV, and >3.9-log 10 IAV and prokaryotes, except for G stearothermohphilus . Hydrogen peroxide vapor was moderately effective at inactivating tested viruses, resulting in 1.5- to >4-log 10 observable inactivation. Staphylococcus aureus inactivation by HPV was limited. Filtration efficiency and proper fit were maintained after 5 cycles of heat with moderate RH and HPV. Although it was effective at decontamination, HPGP resulted in decreased filtration efficiency, and EtO treatment raised toxicity concerns. Observed virus inactivation varied depending upon the application media used., Conclusions: Both moist heat and HPV are scalable N95 reprocessing options because they achieve high levels of biological indicator inactivation while maintaining respirator fit and integrity., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Supply shortages of N95 respirators during the coronavirus disease 2019 (COVID-19) pandemic have motivated institutions to develop feasible and effective N95 respirator reuse strategies. In particular, heat decontamination is a treatment method that scales well and can be implemented in settings with variable or limited resources. Prior studies using multiple inactivation methods, however, have often focused on a single virus under narrowly defined conditions, making it difficult to develop guiding principles for inactivating emerging or difficult-to-culture viruses. We systematically explored how temperature, humidity, and virus deposition solutions impact the inactivation of viruses deposited and dried on N95 respirator coupons. We exposed four virus surrogates across a range of structures and phylogenies, including two bacteriophages (MS2 and phi6), a mouse coronavirus (murine hepatitis virus [MHV]), and a recombinant human influenza A virus subtype H3N2 (IAV), to heat treatment for 30 min in multiple deposition solutions across several temperatures and relative humidities (RHs). We observed that elevated RH was essential for effective heat inactivation of all four viruses tested. For heat treatments between 72°C and 82°C, RHs greater than 50% resulted in a >6-log 10 inactivation of bacteriophages, and RHs greater than 25% resulted in a >3.5-log 10 inactivation of MHV and IAV. Furthermore, deposition of viruses in host cell culture media greatly enhanced virus inactivation by heat and humidity compared to other deposition solutions, such as phosphate-buffered saline, phosphate-buffered saline with bovine serum albumin, and human saliva. Past and future heat treatment methods must therefore explicitly account for deposition solutions as a factor that will strongly influence observed virus inactivation rates. Overall, our data set can inform the design and validation of effective heat-based decontamination strategies for N95 respirators and other porous surfaces, especially for emerging viruses that may be of immediate and future public health concern. IMPORTANCE Shortages of personal protective equipment, including N95 respirators, during the coronavirus (CoV) disease 2019 (COVID-19) pandemic have highlighted the need to develop effective decontamination strategies for their reuse. This is particularly important in health care settings for reducing exposure to respiratory viruses, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Although several treatment methods are available, a widely accessible strategy will be necessary to combat shortages on a global scale. We demonstrate that the combination of heat and humidity inactivates a range of RNA viruses, including both viral pathogens and common viral pathogen surrogates, after deposition on N95 respirators and achieves the necessary virus inactivation detailed by the U.S. Food and Drug Administration guidelines to validate N95 respirator decontamination technologies. We further demonstrate that depositing viruses onto surfaces when suspended in culture media can greatly enhance observed inactivation, adding caution to how heat and humidity treatment methods are validated., (Copyright © 2020 Rockey et al.)

Poor maternal environments, such as under- or overnutrition, can increase the risk for the development of obesity, type 2 diabetes and cardiovascular disease in offspring 1-9 . Recent studies in animal models have shown that maternal exercise before and during pregnancy abolishes the age-related development of impaired glucose metabolism 10-15 , decreased cardiovascular function 16 and increased adiposity 11,15 ; however, the underlying mechanisms for maternal exercise to improve offspring's health have not been identified. In the present study, we identify an exercise-induced increase in the oligosaccharide 3'-sialyllactose (3'-SL) in milk in humans and mice, and show that the beneficial effects of maternal exercise on mouse offspring's metabolic health and cardiac function are mediated by 3'-SL. In global 3'-SL knockout mice (3'-SL -/- ), maternal exercise training failed to improve offspring metabolic health or cardiac function in mice. There was no beneficial effect of maternal exercise on wild-type offspring who consumed milk from exercise-trained 3'-SL -/- dams, whereas supplementing 3'-SL during lactation to wild-type mice improved metabolic health and cardiac function in offspring during adulthood. Importantly, supplementation of 3'-SL negated the detrimental effects of a high-fat diet on body composition and metabolism. The present study reveals a critical role for the oligosaccharide 3'-SL in milk to mediate the effects of maternal exercise on offspring's health. 3'-SL supplementation is a potential therapeutic approach to combat the development of obesity, type 2 diabetes and cardiovascular disease.

Exercise affects whole-body metabolism through adaptations to various tissues, including adipose tissue (AT). Recent studies investigated exercise-induced adaptations to AT, focusing on inguinal white adipose tissue (WAT), perigonadal WAT, and interscapular brown adipose tissue (iBAT). Although these AT depots play important roles in metabolism, they account for only ∼50% of the AT mass in a mouse. Here, we investigated the effects of 3 weeks of exercise training on all 14 AT depots. Exercise induced depot-specific effects in genes involved in mitochondrial activity, glucose metabolism, and fatty acid uptake and oxidation in each adipose tissue (AT) depot. These data demonstrate that exercise training results in unique responses in each AT depot; identifying the depot-specific adaptations to AT in response to exercise is essential to determine how AT contributes to the overall beneficial effect of exercise., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Circulating factors released from tissues during exercise have been hypothesized to mediate some of the health benefits of regular physical activity. Lipokines are circulating lipid species that have recently been reported to affect metabolism in response to cold. Here, lipidomics analysis revealed that a bout of moderate-intensity exercise causes a pronounced increase in the circulating lipid 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) in male, female, young, old, sedentary, and active human subjects. In mice, both a single bout of exercise and exercise training increased circulating 12,13-diHOME and surgical removal of brown adipose tissue (BAT) negated the increase in 12,13-diHOME, suggesting that BAT is the tissue source for exercise-stimulated 12,13-diHOME. Acute 12,13-diHOME treatment of mice in vivo increased skeletal muscle fatty acid uptake and oxidation, but not glucose uptake. These data reveal that lipokines are novel exercise-stimulated circulating factors that may contribute to the metabolic changes that occur with physical exercise., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Alcohol drinking was linked to self-rated health in different populations, but the observed association was inconsistent. We studied the association among university students across three European countries with different patterns of drinking., Methods: We analyzed data from three universities, one from each country: Germany (beer dominant), Bulgaria (wine dominant), and Poland (unclassified among youths, spirits dominant in adults) ( N  = 2103). Frequency of drinking and problem drinking (≥2 positive responses on CAGE-scale), on the one side, and self-rated health, caring for one's own health, and worsening of health since the last year, on the other side, were assessed by means of self-administered questionnaire. The association between alcohol- (independent) and health-related (dependent) variables was evaluated by means of logistic regression, adjusting for country and sex., Results: Poor self-rated health and worsened health since previous year were associated with problem drinking {odds ratio 1.82 [95% confidence interval (CI) 1.21-2.73] and 1.61 (95% CI 1.17-2.21), respectively}, but not with a higher frequency of drinking. In contrast, not caring for one's own health was associated with frequent drinking [1.40 (95% CI 1.10-1.78)], but not with problem drinking [1.25 (95% CI 0.95-1.63)]. The results were consistent across the studied countries and for both sexes., Conclusion: The health status of university students was associated with problem drinking. A high frequency of drinking was associated with the lack of care of own health, but it was not associated with current health status. These associations were independent of the predominant pattern of drinking across the studied countries.

Aim: This study aims (i) to understand how descriptive normative beliefs (DNB) about typical students' alcohol use and self-regulation (SRG) are related to alcohol use (AU) by exploring the indirect effect of SRG on AU through DNB and (ii) to explore gender differences and the differences between universities in DNB, SRG and AU., Subject and Methods: The cross-sectional data were collected online from 817 Slovak university students from four universities (75.22% females; Mage = 19.61; SD = 1.42), who filled in the AUDIT-C items, items measuring the DNB about typical students' AU and SRG. T-tests, one-way Anova and structural equation modelling were used for data analysis., Results: Gender differences in AU and DNB were found with males having higher levels of both AU and DNB. The tested model of AU fits the data well. A significant association was found between DNB and (i) AU (positive) and (ii) SRG (negative). The analysis confirmed the existence of an indirect effect of SRG on AU through DNB., Conclusion: The study contributes to research concerning AU by the way in which DNB and SRG are linked to AU among Slovak university students. The research findings can also be used in developing prevention and intervention programs., (© The Author 2014. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The aim of this study was to investigate the association of perceived stress, depressive symptoms and religiosity with frequent alcohol consumption and problem drinking among freshmen university students from five European countries., Methods: 2529 university freshmen (mean age 20.37, 64.9% females) from Germany (n = 654), Poland (n = 561), Bulgaria (n = 688), the UK (n = 311) and Slovakia (n = 315) completed a questionnaire containing the modified Beck Depression Inventory for measuring depressive symptoms, the Cohen's perceived stress scale for measuring perceived stress, the CAGE-questionnaire for measuring problem drinking and questions concerning frequency of alcohol use and the personal importance of religious faith., Results: Neither perceived stress nor depressive symptoms were associated with a high frequency of drinking (several times per week), but were associated with problem drinking. Religiosity (personal importance of faith) was associated with a lower risk for both alcohol-related variables among females. There were also country differences in the relationship between perceived stress and problem drinking., Conclusion: The association between perceived stress and depressive symptoms on the one side and problem drinking on the other demonstrates the importance of intervention programs to improve the coping with stress.

Background: Alcohol use and misuse and their relation to sociodemograhic factors are well studied among university students in Western European countries and the USA, but less is known about students in Eastern Europe. The historical past as communistic countries might have affected the social life among these populations, which is again one of the main factors determining the alcohol consumption among university students. The aim of our study was to assess the association of selected sociodemographic factors with different patterns of alcohol use among university students in Slovakia., Methods: A sample of 813 young adults (mean age 21.1 years, 63.8% females; response rate of 71%) from four universities in Kosice answered questions about their sociodemographic background and about alcohol use. To obtain a detailed picture of different aspects, alcohol use was measured by four variables: frequency of alcohol use, heavy episodic drinking, frequency of drunkenness and problem drinking. Four separate logistic regression models were used to assess the association between sociodemographic and alcohol-related variables. To assess the potentially different effects in both genders, all two-way interactions with gender were tested., Results: While 41% of the students drank alcohol once a week or more often, 77% reported heavy episodic drinking and 49% had been drunk more than once in the last month. Problem drinking existed in 23.3% of the sample. Gender was consistently associated with all four alcohol-related variables, with males being at higher risk. A higher study year was associated only with lower levels of heavy episodic drinking, but displayed no association with the other studied variables. Living with parents during the semester was consistently associated with less frequent heavy episodic drinking, drunkenness episodes, and problem drinking while having an intimate relationship was associated with less problem drinking only., Conclusions: Our findings for the university students from Slovakia are in line with previous studies in Western Europe. Additionally, it appears that frequent alcohol use, excessive alcohol use (heavy episodic drinking and drunkenness) and problem drinking among university students represent a continuum and are influenced by the same sociodemographic factors.

Parental employment status is an important and often overlooked contextual factor that may influence parent-adolescent relationships. The aim of this study is to examine the effect of parental support on adolescents' health within the context of parental employment status. Data on perceived mother's and father's support, mother's and father's employment status and adolescents' perceived health were collected among 1992 adolescents (mean age 16.9) and analysed using chi-square and logistic regression. Father's support was significantly more often perceived as low when the father was unemployed, while the perception of mother's support did not differ in regards to the mother's employment. Among those with an unemployed father, mother's support appeared protective for adolescents' health, while when a mother was unemployed, father's support was more strongly associated with good health. Our results suggest that in the case of unemployment of one parent, support from the other parent may be more important for children., (Copyright © 2010 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Health-related quality of life (HRQoL) has become an important outcome in the evaluation of kidney transplantation (KT). Although the medical and sociodemographic predictors of HRQoL in patients after KT are well known, there is still a lack of knowledge about the psychological factors involved. This study focuses on the role of personality and actual psychological distress in predicting HRQoL after KT. Sociodemographic (gender, age, education, average income), medical (glomerular filtration, serum albumin, number of co-morbid diseases) and psychological data (neuroticism, extroversion, psychological distress) were collected from 177 (60.5% male subjects; 48 +/- 12.1 years) kidney transplant recipients, and physical and mental HRQoL were measured using the SF-36. A univariate general linear model analysis was performed. Higher physical HRQoL was associated with younger age, higher education and income, a low number of co-morbid diseases, lower neuroticism and distress. Higher mental HRQoL was associated with higher education and income, longer time from KT, higher extroversion, lower neuroticism and distress. In both physical and mental HRQoL, actual distress was the best predictor, even when controlled for neuroticism. These results confirm the importance of psychological distress in patients and its impact on their HRQoL after KT and can be applied in intervention programs focused on increasing HRQoL.

The aim was to explore the association of self-esteem and resilience with smoking and cannabis use among adolescents, separately for gender. A sample of 3694 adolescents (mean age 14.3 years) from elementary schools in Slovakia filled out the Rosenberg Self-esteem scale, the Resiliency scale and answered questions about cigarette and cannabis use. Logistic regression models showed associations between negative self-esteem and risky behavior, but only among boys. Regarding resilience, structured style and family cohesion were associated with a lower probability of smoking and cannabis use among both boys and girls. In contrast, social competence increased the probability of smoking and cannabis use among both groups. Negative self-esteem seems to play an important role regarding smoking and cannabis use among boys. Resilience seems to have mixed effects, some aspects being protective while other aspects increase the likelihood of smoking and use of cannabis. These results imply that the prevention of substance use should target not only specific individual characteristics, but also the possible risk or protective influences of the social environment, i.e. the family and social network.

Background: The aim of this cross-sectional study was to explore the association between parental divorce and adolescent drunkenness in the last 4 weeks and the contribution of socioeconomic position, family structure, social support from family and well-being to this association., Methods: We obtained data on 3,694 elementary school students from several cities in Slovakia (mean age 14.3, 49.0% males; response rate 93%). Respondents completed questionnaires on how often they had been drunk in the last 4 weeks, whether their parents were divorced, their socioeconomic position (education of parents, family affluence), the composition of the household (one or two parents/step-parents), social support from the family and their own well-being., Results: Parental divorce was found to have an effect on adolescent drunkenness in the last 4 weeks, as well as high socioeconomic position, low social support from the family and high depression/anxiety. The effect of divorce on drunkenness decreased only slightly after adding social support into the model., Conclusion: Our findings indicate that parental divorce has a persistent influence on risk behavior independent of the influence of socioeconomic position and well-being. Parental divorce may increase the likelihood of drunkenness more than other factors such as low parental support and poor socioeconomic position., (Copyright 2009 S. Karger AG, Basel.)

Objectives: The main purpose of this paper is to explore whether unemployment influences adolescents' subjective perception of health and whether perceived financial stress and social contacts can mediate the effect of employment status on health. We are also interested in the differences in financial situation and social contacts between unemployed secondary school leavers and their employed and studying counterparts., Methods: Data were obtained from 844 adolescents (mean age 19.6) from Slovakia. The effect of unemployment on several health indicators was measured and subsequently controlled for perceived financial strain of respondents and their social contacts., Results: The results showed highest financial strain among unemployed, whereas only small differences in social contacts were found between three groups. Negative influence of unemployment on perceived health of respondents was confirmed. Nevertheless, strong influence was found only on long-term well-being and mental health. Financial situation and social contacts contributed to the prediction of almost all health outcomes, and to some extent mediated the effect of unemployment., Conclusions: Although unemployment was found to have a negative impact on health of adolescents, sufficiency of social contacts and good financial situation seem to decrease this effect and protect the health of unemployed people.

For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening.

To date, more than 300 distinct small deletions, insertions and point mutations, mostly leading to premature termination of translation, have been reported in the breast/ovarian-cancer susceptibility gene BRCA1. The elevated frequencies of some mutations in certain ethnic subpopulations are caused by founder effects, rather than by mutation hotspots. Here we report that the currently available mutation spectrum of BRCA1 has been biased by PCR-based mutation-screening methods, such as SSCP, the protein truncation test (PTT) and direct sequencing, using genomic DNA as template. Three large genomic deletions that are not detected by these approaches comprise 36% of all BRCA1 mutations found in Dutch breast-cancer families to date. A 510-bp Alu-mediated deletion comprising exon 22 was found in 8 of 170 breast-cancer families recruited for research purposes and in 6 of 49 probands referred to the Amsterdam Family Cancer Clinic for genetic counselling. In addition, a 3,835-bp Alu-mediated deletion encompassing exon 13 was detected in 4 of 170 research families, while an deletion of approximately 14 kb was detected in a single family [corrected]. Haplotype analyses indicated that each recurrent deletion had a single common ancestor.

Progressive external ophthalmoplegia (PEO) and Kearns-Sayre syndrome (KSS) are caused by deletions in mitochondrial DNA. Identification of these deletions is important for diagnosis, prognosis and genetic counselling. As yet, the most frequently used test is Southern blot analysis of DNA isolated from a muscle biopsy. Here, we describe a sensitive PCR-based test for the identification of these deletions in DNA isolated from blood. The main advantage is that in the majority of cases a muscle biopsy is no longer necessary for the molecular diagnosis of PEO and KSS.

We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous.