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Sample records for suspected genetic predisposition

  1. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition

    DEFF Research Database (Denmark)

    Wadt, Karin A W; Aoude, Lauren G; Krogh, Lotte

    2015-01-01

    Both environmental and host factors influence risk of cutaneousmelanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E3...... cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma....

  2. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

    Science.gov (United States)

    Wadt, Karin A W; Aoude, Lauren G; Krogh, Lotte; Sunde, Lone; Bojesen, Anders; Grønskov, Karen; Wartacz, Nine; Ek, Jakob; Tolstrup-Andersen, Morten; Klarskov-Andersen, Mette; Borg, Åke; Heegaard, Steffen; Kiilgaard, Jens F; Hansen, Thomas V O; Klein, Kerenaftali; Jönsson, Göran; Drzewiecki, Krzysztof T; Dunø, Morten; Hayward, Nicholas K; Gerdes, Anne-Marie

    2015-01-01

    Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.

  3. Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

    Directory of Open Access Journals (Sweden)

    Karin A W Wadt

    Full Text Available Both environmental and host factors influence risk of cutaneous melanoma (CM, and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.

  4. Dietary management and genetic predisposition

    DEFF Research Database (Denmark)

    Jensen, Hanne Holbæk; Larsen, Lesli Hingstrup

    2013-01-01

    epidemically worldwide, the investigation of genetic predisposition might help to prevent and treat obesity. Predisposition to obesity includes syndromes, such as Prader-Willi Syndrome (PWS), severe early-onset obesity, such as mutations in the melanocortin 4 receptor (MC4R), and common forms of obesity......, such as genetic variation in the fat mass and obesity associated gene (FTO). Several studies have explored gene-diet interactions in obesity, weight loss, and regain, but there is a lack of consistency in the identified interactions. This inconsistency is most probably due to a low-moderate effect size...... variation, and epigenetics might identify additional genetic contributions to obesity, and the use of omics data with integration of nutrigenetics and nutrigenomics will identify genetic subgroups who will benefit from specific dietary advice to optimize health and prevent disease. Keywords: Diet . Mutation...

  5. Genetic predisposition to bronchopulmonary dysplasia.

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    Lal, Charitharth Vivek; Ambalavanan, Namasivayam

    2015-12-01

    The objective of this study is to review the candidate gene and genome-wide association studies relevant to bronchopulmonary dysplasia, and to discuss the emerging understanding of the complexities involved in genetic predisposition to bronchopulmonary dysplasia and its outcomes. Genetic factors contribute much of the variance in risk for BPD. Studies to date evaluating single or a few candidate genes have not been successful in yielding results that are replicated in GWAS, perhaps due to more stringent p-value thresholds. GWAS studies have identified only a single gene (SPOCK2) at genome-wide significance in a European White and African cohort, which was not replicated in two North American studies. Pathway gene-set analysis in a North American cohort confirmed involvement of known pathways of lung development and repair (e.g., CD44 and phosphorus oxygen lyase activity) and indicated novel molecules and pathways (e.g., adenosine deaminase and targets of miR-219) involved in genetic predisposition to BPD. The genetic basis of severe BPD is different from that of mild/moderate BPD, and the variants/pathways associated with BPD vary by race/ethnicity. A pilot study of whole exome sequencing identified hundreds of genes of interest, and indicated the overall feasibility as well as complexity of this approach. Better phenotyping of BPD by severity and pathophysiology, and careful analysis of race/ethnicity is required to gain a better understanding of the genetic basis of BPD. Future translational studies are required for the identification of potential genetic predispositions (rare variants and dysregulated pathways) by next-generation sequencing methods in individual infants (personalized genomics). Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Genetic predisposition to kidney cancer.

    Science.gov (United States)

    Schmidt, Laura S; Linehan, W Marston

    2016-10-01

    Kidney cancer is not a single disease but is made up of a number of different types of cancer classified by histology that are disparate in presentation, clinical course, and genetic basis. Studies of families with inherited renal cell carcinoma (RCC) have provided the basis for our understanding of the causative genes and altered metabolic pathways in renal cancer with different histologies. Von Hippel-Lindau disease was the first renal cancer disorder with a defined genetic basis. Over the next two decades, the genes responsible for a number of other inherited renal cancer syndromes including hereditary papillary renal carcinoma, Birt-Hogg-Dube´syndrome, hereditary leiomyomatosis and renal cell carcinoma, and succinate dehydrogenase-associated renal cancer were identified. Recently, renal cell carcinoma has been confirmed as part of the clinical phenotype in individuals from families with BAP1-associated tumor predisposition syndrome and MiTF-associated cancer syndrome. Here we summarize the clinical characteristics of and causative genes for these and other inherited RCC syndromes, the pathways that are dysregulated when the inherited genes are mutated, and recommended clinical management of patients with these inherited renal cancer syndromes. Published by Elsevier Inc.

  7. Genetic predisposition to Parkinson's disease

    DEFF Research Database (Denmark)

    Halling, Jónrit; Petersen, Maria Skaalum; Grandjean, Philippe

    2008-01-01

    OBJECTIVE: To investigate whether the genetic variants of CYP2D6 and HFE are more frequent in Parkinson's disease (PD) patients compared with controls in a population where the prevalence of these variants and PD are increased. METHODS: Blood samples were collected from 79 PD patients and 154...

  8. Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

    Science.gov (United States)

    Yurgelun, Matthew B; Allen, Brian; Kaldate, Rajesh R; Bowles, Karla R; Judkins, Thaddeus; Kaushik, Praveen; Roa, Benjamin B; Wenstrup, Richard J; Hartman, Anne-Renee; Syngal, Sapna

    2015-09-01

    Multigene panels are commercially available tools for hereditary cancer risk assessment that allow for next-generation sequencing of numerous genes in parallel. However, it is not clear if these panels offer advantages over traditional genetic testing. We investigated the number of cancer predisposition gene mutations identified by parallel sequencing in individuals with suspected Lynch syndrome. We performed germline analysis with a 25-gene, next-generation sequencing panel using DNA from 1260 individuals who underwent clinical genetic testing for Lynch syndrome from 2012 through 2013. All patients had a history of Lynch syndrome-associated cancer and/or polyps. We classified all identified germline alterations for pathogenicity and calculated the frequencies of pathogenic mutations and variants of uncertain clinical significance (VUS). We also analyzed data on patients' personal and family history of cancer, including fulfillment of clinical guidelines for genetic testing. Of the 1260 patients, 1112 met National Comprehensive Cancer Network (NCCN) criteria for Lynch syndrome testing (88%; 95% confidence interval [CI], 86%-90%). Multigene panel testing identified 114 probands with Lynch syndrome mutations (9.0%; 95% CI, 7.6%-10.8%) and 71 with mutations in other cancer predisposition genes (5.6%; 95% CI, 4.4%-7.1%). Fifteen individuals had mutations in BRCA1 or BRCA2; 93% of these met the NCCN criteria for Lynch syndrome testing and 33% met NCCN criteria for BRCA1 and BRCA2 analysis (P = .0017). An additional 9 individuals carried mutations in other genes linked to high lifetime risks of cancer (5 had mutations in APC, 3 had bi-allelic mutations in MUTYH, and 1 had a mutation in STK11); all of these patients met NCCN criteria for Lynch syndrome testing. A total of 479 individuals had 1 or more VUS (38%; 95% CI, 35%-41%). In individuals with suspected Lynch syndrome, multigene panel testing identified high-penetrance mutations in cancer predisposition genes, many

  9. Genetic predisposition and implications for radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, Christian [University Clinics, Essen, Essen (Germany)

    2000-05-01

    Treatments of cancer patients with ionizing radiation have shown in some cases severe acute radiation effects after radiation doses which are very well tolerated by most patients. Skin fibroblasts of these patients studied after in vitro irradiation also showed a high radiosensitivity frequently. It was found that these effects are based on genetic predisposition which was usually inherited from their parents. During recent years quite a number of these syndromes have been described in humans and often the responsible genes have been characterized: Ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, Li Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Neurofibromatosis, Nijmegen breakage syndrome, Retinoblastoma. In most cases it was found that the regulation processes of DNA repair processes and of the cell cycle for cell proliferation are disturbed. Frequently these processes cannot be separated from each other. Quite a number of these syndromes also show genomic instability which can also be induced by radiation exposures. These Phenomena have mainly been studied by determining the rate of chromosomal aberrations many cell generations after the exposure took place. Genomic instability apparently plays an important role for the development of stochastic late effects for which multistep events are necessary. This is especially for carcinogenesis the case. In mice it has been shown that radiation-induced genomic instability can be transmitted to the next mouse generation. In mouse models and also with radiotherapy patients it has been shown that genetic predisposition not only increases radiosensitivity with respect to cell survival and chromosomal damage but also to carcinogenesis. This has been observed cf. with p53-knock out mice and with children after radiotherapy cf. treatment of retinoblastoma. In the children with a genetic predisposition for retinoblastoma secondary tumours occurred to a much higher rate than in those children with

  10. Genetic predisposition to breast cancer: past, present, and future.

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    Turnbull, Clare; Rahman, Nazneen

    2008-01-01

    In recent years, our understanding of genetic predisposition to breast cancer has advanced significantly. Three classes of predisposition factors, categorized by their associated risks of breast cancer, are currently known. BRCA1 and BRCA2 are high-penetrance breast cancer predisposition genes identified by genome-wide linkage analysis and positional cloning. Mutational screening of genes functionally related to BRCA1 and/or BRCA2 has revealed four genes, CHEK2, ATM, BRIP1, and PALB2; mutations in these genes are rare and confer an intermediate risk of breast cancer. Association studies have further identified eight common variants associated with low-penetrance breast cancer predisposition. Despite these discoveries, most of the familial risk of breast cancer remains unexplained. In this review, we describe the known genetic predisposition factors, expound on the methods by which they were identified, and consider how further technological and intellectual advances may assist in identifying the remaining genetic factors underlying breast cancer susceptibility.

  11. Genetic predisposition in nonalcoholic fatty liver disease.

    Science.gov (United States)

    Sookoian, Silvia; Pirola, Carlos J

    2017-03-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.

  12. The genetic predisposition to bronchopulmonary dysplasia

    Science.gov (United States)

    Yu, Kun-Hsing; Li, Jingjing; Snyder, Michael; Shaw, Gary M.; O’Brodovich, Hugh M.

    2016-01-01

    Purpose of review Bronchopulmonary dysplasia (BPD) is a prevalent chronic lung disease in premature infants. Twin studies have shown strong heritability underlying this disease; however, the genetic architecture of BPD remains unclear. Recent findings A number of studies employed different approaches to characterize the genetic aberrations associated with BPD, including candidate gene studies, genome-wide association studies, exome sequencing, integrative omics analysis, and pathway analysis. Candidate gene studies identified a number of genes potentially involved with the development of BPD, but the etiological contribution from each gene is not substantial. Copy number variation studies and three independent genome-wide association studies did not identify genetic variations significantly and consistently associated with BPD. A recent exome-sequencing study pointed to rare variants implicated in the disease. In this review, we summarize these studies’ methodology and findings, and suggest future research directions to better understand the genetic underpinnings of this potentially life-long lung disease. Summary Genetic factors play a significant role in the development of BPD. Recent studies suggested that rare variants in genes participating in lung development pathways could contribute to BPD susceptibility. PMID:26963946

  13. Ataxic cerebral palsy and genetic predisposition.

    OpenAIRE

    Miller, G.

    1988-01-01

    It was calculated that in the 962 family members of 36 patients with ataxic cerebral palsy there were 75 (8%) with a history of neurodevelopmental disorder and 31 (3%) with a major congenital malformation. This was not significantly greater than expected, and does not support the hypothesis of a genetic non-Mendelian role in the aetiology of ataxic cerebral palsy.

  14. Retinal vein occlusion: genetic predisposition and systemic risk factors.

    Science.gov (United States)

    Giannaki, Kassiani; Politou, Marianna; Rouvas, Alexandros; Merkouri, Efrossyni; Travlou, Anthi; Theodosiadis, Panayiotis; Gialeraki, Argyri

    2013-04-01

    The role of systemic risk factors (age, smoking, diabetes, arterial hypertension) in the development of retinal vein occlusion (RVO) is well established. However, the association of RVO with genetic predisposition to thrombosis remains poorly understood. The aim of the study was to assess any possible additional effect of genetic predisposition to the already well known 'classical' risk factors of RVO in a cohort of elderly Greek patients. Fifty-one elderly patients with RVO and 51 healthy individuals matched for age and sex were evaluated for systemic risk factors (smoking, diabetes, dyslipidemia, arterial hypertension) and coagulation defects (lupus anticoagulant, natural inhibitors of coagulation). Additionally, genotyping was performed for mutations/polymorphisms involved in haemostasis such as: FV G1691A, FV G4070A, FIIG 20210A, MTHFR C677T and A1298C, PAI-1-675 4G/5G, F XIII exon 2G/T, EPCR A4600G and G4678C. We identified systemic risk factors in the majority of the patients Hypertension (P=0.001), dyslipidemia (P=0.029) and diabetes (P=0.01) are associated with RVO in the majority of the patients. The prevalence of prothrombotic risk factors was not significantly different in the patients with RVO compared to controls. Apart from systemic risk factors, genetic predisposition to thrombosis does not seem to have an important association with RVO in this group of elderly patients.

  15. Genetic Predisposition to Dyslipidemia and Risk of Preeclampsia.

    Science.gov (United States)

    Spracklen, Cassandra N; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2015-07-01

    Large epidemiologic studies support the role of dyslipidemia in preeclampsia; however, the etiology of preeclampsia or whether dyslipidemia plays a causal role remains unclear. We examined the association between the genetic predisposition to dyslipidemia and risk of preeclampsia using validated genetic markers of dyslipidemia. Preeclampsia cases (n = 164) and normotensive controls (n = 110) were selected from live birth certificates to nulliparous Iowa women during the period August 2002 to May 2005. Disease status was verified by medical chart review. Genetic predisposition to dyslipidemia was estimated by 4 genetic risk scores (GRS) (total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), and triglycerides) on the basis of established loci for blood lipids. Logistic regression analyses were used to evaluate the relationships between each of the 4 genotype scores and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The GRS related to higher levels of TC, LDL-C, and triglycerides demonstrated no association with the risk of preeclampsia in either the Iowa or replication population. The GRS related to lower HDL-C was marginally associated with an increased risk for preeclampsia (odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.99-1.07; P = 0.10). In the independent replication population, the association with the HDL-C GRS was also marginally significant (OR = 1.03, 95% CI: 1.00-1.06; P = 0.04). Our data suggest a potential effect between the genetic predisposition to dyslipidemic levels of HDL-C and an increased risk of preeclampsia, and, as such, suggest that dyslipidemia may be a component along the causal pathway to preeclampsia. © American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. Ethical aspects of genetic predisposition to environmentally-related disease.

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    Grandjean, P; Sorsa, M

    1996-05-17

    Some individuals are highly susceptible to disease caused by chemical exposures and this hypersusceptibility can be genetically determined. Because biomarker technology for the determination of genetic predisposition is at the disposal of researchers, the capability therefore exists to include genetic screening in epidemiologic studies. The application of this technological advance in population-based research is, however, fraught with ethical tensions heretofore unknown. Moral duties alone are of limited use in resolving these problems. Scientific documentation is almost always insufficient to clarify the exact nature of the ethical implications, and ways to deal with uncertainties arising as a result of information generated from genetic screening studies must be considered. The most important tensions relate to autonomy and the right to privacy, fairness and equality, while balancing potential public interest in paternalistic measures. Because no moral framework has been accepted for dealing with this technological advance, an ethical discourse in an open forum is required with all affected parties. Scientists alone, or any other group in isolation, should not expect to resolve these questions, but they should participate in and facilitate the process.

  17. Genetic predisposition to obesity and risk of subclinical atherosclerosis.

    Science.gov (United States)

    Shi, Juan; Hong, Jie; Qi, Lu; Cui, Bin; Gu, Weiqiong; Zhang, Yifei; Li, Lijuan; Miao, Lin; Wang, Rui; Wang, Weiqing; Ning, Guang

    2014-10-10

    Obesity has been associated with increased common carotid artery (CCA) intima-media thickness (IMT), a measure of subclinical atherosclerosis. We assessed the association between genetic predisposition to obesity and CCA IMT. The study included 428 young Chinese adults with CCA IMT measured using a high-resolution B-mode tomographic ultrasound system. We created a genetic risk score (GRS) by summing the risk alleles of 6 obesity-associated genetic variants confirmed in our previous analyses. The GRS was significantly associated with greater CCA IMT (pobesity status, but remained significant (p=0.009). In addition, we found that blood pressure significantly modified the association between the GRS and CCA IMT (p for interaction=0.001). The associations between the GRS and CCA IMT were stronger in participants with systolic blood pressure (SBP) ≥120 mmHg and/or diastolic blood pressure (DBP) ≥80 mmHg (per 2 allele increment of the GRS relating to 0.028 mm greater CCA IMT, p for trendobesity and development of subclinical atherosclerosis. Elevated blood pressure might amplify the adverse effect of obesity on cardiovascular risk. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Unclassified sequence variants (UVS and genetic predisposition to cancer

    Directory of Open Access Journals (Sweden)

    Yves-Jean Bignon

    2011-06-01

    Full Text Available Hereditary breast and ovarian cancers are mainly attributable to predisposition genes whose germinal mutations are responsible for the disease. The most common genes associated with breast/ovarian cancer are BRCA1 and BRCA2 but at least 20 other genes of medium of high penetrance have been associated with these types of cancer. Lifetime risk of breast cancer for BRCA mutations carriers approaches 90%. Appropriate medical follow-up is therefore essential for women carrying mutations in these genes. BRCA mutational spectrum has not been entirely characterized but not all sequence variants are pathogenic. These are classified as benign polymorphisms or unclassified variants (UV with unknown pathological potential. To date, 43,5% of over 3500 genetic variants BRCA1 and BRCA2 are reported as having uncertain clinical significance. Whether one sequence variant has or not a pathogenicity implication is often a hard decision to take, involving important consequences for diagnosis and medical follow-up. Here we present several cases of unclassified sequence variants detection and interpretation by in-silico analysis.

  19. Genetic predisposition to ductal carcinoma in situ of the breast.

    Science.gov (United States)

    Petridis, Christos; Brook, Mark N; Shah, Vandna; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Levi, Dina; Papouli, Efterpi; Orr, Nick; Cox, Angela; Cross, Simon S; Dos-Santos-Silva, Isabel; Peto, Julian; Swerdlow, Anthony; Schoemaker, Minouk J; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Benitez, Javier; González-Neira, Anna; Tessier, Daniel C; Vincent, Daniel; Li, Jingmei; Figueroa, Jonine; Kristensen, Vessela; Borresen-Dale, Anne-Lise; Soucy, Penny; Simard, Jacques; Milne, Roger L; Giles, Graham G; Margolin, Sara; Lindblom, Annika; Brüning, Thomas; Brauch, Hiltrud; Southey, Melissa C; Hopper, John L; Dörk, Thilo; Bogdanova, Natalia V; Kabisch, Maria; Hamann, Ute; Schmutzler, Rita K; Meindl, Alfons; Brenner, Hermann; Arndt, Volker; Winqvist, Robert; Pylkäs, Katri; Fasching, Peter A; Beckmann, Matthias W; Lubinski, Jan; Jakubowska, Anna; Mulligan, Anna Marie; Andrulis, Irene L; Tollenaar, Rob A E M; Devilee, Peter; Le Marchand, Loic; Haiman, Christopher A; Mannermaa, Arto; Kosma, Veli-Matti; Radice, Paolo; Peterlongo, Paolo; Marme, Frederik; Burwinkel, Barbara; van Deurzen, Carolien H M; Hollestelle, Antoinette; Miller, Nicola; Kerin, Michael J; Lambrechts, Diether; Floris, Giuseppe; Wesseling, Jelle; Flyger, Henrik; Bojesen, Stig E; Yao, Song; Ambrosone, Christine B; Chenevix-Trench, Georgia; Truong, Thérèse; Guénel, Pascal; Rudolph, Anja; Chang-Claude, Jenny; Nevanlinna, Heli; Blomqvist, Carl; Czene, Kamila; Brand, Judith S; Olson, Janet E; Couch, Fergus J; Dunning, Alison M; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Pinder, Sarah E; Schmidt, Marjanka K; Tomlinson, Ian; Roylance, Rebecca; García-Closas, Montserrat; Sawyer, Elinor J

    2016-02-17

    Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci. To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip. Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8). In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

  20. Measuring and Validating a General Cancer Predisposition Perception Scale: An Adaptation of the Revised-IPQ-Genetic Predisposition Scale.

    Directory of Open Access Journals (Sweden)

    Wendy Wing Tak Lam

    Full Text Available Illness perceptions are linked to individual help-seeking and preventive behaviors. Previous illness perception studies have identified five dimensions of illness-related experience and behaviour. The Revised Illness Perception Questionnaire (IPQ-R for genetic predisposition (IPQ-R-GP was developed to measure illness perceptions in those genetically-predisposed to blood disease. We adapted the IPQ-R-GP to measure perceptions of generalized cancer predisposition. This paper describes the development and validation of the Cancer Predisposition Perception Scale (CPPS.The draft CPPS scale was first administered to 167 well Hepatitis B carriers and 123 other healthy individuals and the factor structure was examined using Exploratory Factor Analysis. Then the factor structure was confirmed in a second sample comprising 148 healthy controls, 150 smokers and 152 passive smokers using Confirmatory Factor Analysis (CFA.Six-factors comprising 26 items provided optimal fit by eigen and scree-plot methods, accounting for 58.9% of the total variance. CFA indicated good fit of the six-factor model after further excluding three items. The six factors, Emotional representation (5 items, Illness coherence (4 items, Treatment control (3 items, Consequences (5 items, Internal locus of control (2 items and External locus of control (4 items demonstrated adequate-to-good subscale internal consistency (Cronbach's α = 0.63-0.90. Divergent validity was suggested by low correlations with optimism, self-efficacy, and scales for measuring physical and psychological health symptoms.The CPPS appears to be a valid measure of perceived predisposition to generic cancer risks and can be used to examine cancer-risk-related cognitions in individuals at higher and lower cancer risk.

  1. Genetics Home Reference: BAP1 tumor predisposition syndrome

    Science.gov (United States)

    ... have dozens. Atypical Spitz tumors are generally considered benign, although it is unclear if they can become cancerous. Skin cancers are also associated with BAP1 tumor predisposition syndrome , including cutaneous melanoma and basal cell carcinoma . A type of eye ...

  2. Spontaneous preterm birth: advances toward the discovery of genetic predisposition.

    Science.gov (United States)

    Strauss, Jerome F; Romero, Roberto; Gomez-Lopez, Nardhy; Haymond-Thornburg, Hannah; Modi, Bhavi P; Teves, Maria E; Pearson, Laurel N; York, Timothy P; Schenkein, Harvey A

    2018-03-01

    Evidence from family and twin-based studies provide strong support for a significant contribution of maternal and fetal genetics to the timing of parturition and spontaneous preterm birth. However, there has been only modest success in the discovery of genes predisposing to preterm birth, despite increasing sophistication of genetic and genomic technology. In contrast, DNA variants associated with other traits/diseases have been identified. For example, there is overwhelming evidence that suggests that the nature and intensity of an inflammatory response in adults and children are under genetic control. Because inflammation is often invoked as an etiologic factor in spontaneous preterm birth, the question of whether spontaneous preterm birth has a genetic predisposition in the case of pathologic inflammation has been of long-standing interest to investigators. Here, we review various genetic approaches used for the discovery of preterm birth genetic variants in the context of inflammation-associated spontaneous preterm birth. Candidate gene studies have sought genetic variants that regulate inflammation in the mother and fetus; however, the promising findings have often not been replicated. Genome-wide association studies, an approach to the identification of chromosomal loci responsible for complex traits, have also not yielded compelling evidence for DNA variants predisposing to preterm birth. A recent genome-wide association study that included a large number of White women (>40,000) revealed that maternal loci contribute to preterm birth. Although none of these loci harbored genes directly related to innate immunity, the results were replicated. Another approach to identify DNA variants predisposing to preterm birth is whole exome sequencing, which examines the DNA sequence of protein-coding regions of the genome. A recent whole exome sequencing study identified rare mutations in genes encoding for proteins involved in the negative regulation (dampening) of the

  3. Genetic predisposition increases the tic severity, rate of comorbidities, and psychosocial and educational difficulties in children with Tourette syndrome.

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    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-03-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition. © The Author(s) 2014.

  4. Narcolepsy: genetic predisposition and neuropharmacological mechanisms. REVIEW ARTICLE.

    Science.gov (United States)

    Nishino, Seiji; Okura, Mutsumi; Mignot, Emmanuel

    2000-02-01

    Narcolepsy is a disabling sleep disorder characterized by excessive daytime somnolence (EDS), cataplexy and REM sleep-related abnormalities. It is a frequently-occurring but under-diagnosed condition that affects 0.02 to 0.18% of the general population in various countries. Although most cases occur sporadically, familial clustering may be observed; the risk of a first-degree relative of a narcoleptic developing narcolepsy is 10-40 times higher than in the general population. The disorder is tightly associated with the specific human leukocyte antigen (HLA) allele, DQB1*0602 [most often in combination with HLA-DR2 (DRB1*15)]. Genetic transmission is, however, likely to be polygenic in most cases, and genetic factors other than HLA-DQ are also likely to be implicated. In addition, environmental factors are involved in disease predisposition; most monozygotic twins pairs reported in the literature are discordant for narcolepsy. Narcolepsy was reported to exist in canines in the early 1970s. Both sporadic and familial cases are also observed in this animal species. A highly-penetrant single autosomal recessive gene, canarc-1, is involved in the transmission of narcolepsy in Doberman pinschers and Labrador retrievers. Positional cloning of this gene is in progress, and a human homologue of this gene, or a gene with a functional relationship to canarc-1, might be involved in some human cases. Human narcolepsy is currently treated with central nervous system (CNS) stimulants for EDS and antidepressants for cataplexy and abnormal REM sleep. These treatments are purely symptomatic and induce numerous side effects. These compounds disturb nocturnal sleep in many patients, and tolerance may develop as a result of continuous treatment. The canine model is an invaluable resource for studying the pharmacological and physiological control of EDS and cataplexy. Experiments using canine narcolepsy have demonstrated that increased cholinergic and decreased monoaminergic

  5. Genetic predisposition syndromes: when should they be considered in the work-up of MDS?

    Science.gov (United States)

    Babushok, Daria V; Bessler, Monica

    2015-03-01

    Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes. Here, we will discuss the importance of recognizing an underlying genetic predisposition syndrome a patient with MDS, will review clinical scenarios when genetic predisposition should be considered, and will provide a practical overview of the common BMFS and familial MDS/AML syndromes which may be encountered in adult patients with MDS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

    NARCIS (Netherlands)

    I.P. Vogelaar (Ingrid P.); R.S. Van Der Post (Rachel S.); J.H. Van Krieken (J. Han); L. Spruijt (Liesbeth); W.A. van Zelst-Stams; C.M. Kets; J. Lubinski (Jan); A. Jakubowska (Anna); U. Teodorczyk (Urszula); C.M. Aalfs (Cora); L.P. Hest (Liselotte); H. Pinheiro (Hugo); Oliveira, C. (Carla); S.N. Jhangiani (Shalini N.); D. Muzny (Donna); Gibbs, R.A. (Richard A.); J.R. Lupski (James R.); J. de Ligt (Joep); L.E.L.M. Vissers; A. Hoischen (Alex); C. Gilissen (Christian); Van De Vorst, M. (Maartje); J.J. Goeman (Jelle); H.K. Schackert (Hans); G.N. Ranzani (Guglielmina N.); V. Molinaro (Valeria); E.B.G. Garcia; F.J. Hes (Frederik); E. Holinski-Feder (Elke); M. Genuardi (Maurizio); M.G.E.M. Ausems (Margreet); R.H. Sijmons (Rolf); A. Wagner (Anja); L. van der Kolk (Lizet); I. Bjørnevoll (Inga); H. Høberg Vetti (Hildegunn); A.G. van Kessel (Ad Geurts); R. Kuiper (Ruud); M.J. Ligtenberg (Marjolijn); N. Hoogerbrugqe (N.)

    2017-01-01

    textabstractRecognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients

  7. Unraveling genetic predisposition to familial or early onset gastric cancer using germline whole-exome sequencing

    NARCIS (Netherlands)

    Vogelaar, Ingrid P.; van der Post, Rachel S.; Van Krieken, J. Han J M; Spruijt, Liesbeth; van Zelst-Stams, Wendy A. G.; Kets, C. Marleen; Lubinski, Jan; Jakubowska, Anna; Teodorczyk, Urszula; Aalfs, Cora M.; Van Hest, Liselotte P.; Pinheiro, Hugo; Oliveira, Carla; Jhangiani, Shalini N.; Muzny, Donna M.; Gibbs, Richard A.; Lupski, James R; De Ligt, Joep; Vissers, Lisenka E L M; Hoischen, Alexander; Gilissen, Christian; Van De Vorst, Maartje; Goeman, Jelle J.; Schackert, Hans K; Ranzani, Guglielmina N.; Molinaro, Valeria; García, Encarna B.Gómez; Hes, Frederik J.; Holinski-Feder, Elke; Genuardi, Maurizio; Ausems, Margreet G.E.M.|info:eu-repo/dai/nl/18756969X; Sijmons, Rolf H.; Wagner, Anja; Van Der Kolk, Lizet E.; Bjørnevoll, Inga; Høberg Vetti, Hildegunn; van Kessel, Ad Geurts; Kuiper, Roland P.; Ligtenberg, Marjolijn J. L.; Hoogerbrugge, Nicoline

    2017-01-01

    Recognition of individuals with a genetic predisposition to gastric cancer (GC) enables preventive measures. However, the underlying cause of genetic susceptibility to gastric cancer remains largely unexplained. We performed germline whole-exome sequencing on leukocyte DNA of 54 patients from 53

  8. Genetic predisposition toward suicidal ideation in patients with acute coronary syndrome.

    Science.gov (United States)

    Kang, Hee-Ju; Bae, Kyung-Yeol; Kim, Sung-Wan; Shin, Il-Seon; Hong, Young Joon; Ahn, Youngkeun; Jeong, Myung Ho; Yoon, Jin-Sang; Kim, Jae-Min

    2017-11-07

    The genetic predisposition toward suicidal ideation has been explored to identify subgroups at high risk and to prevent suicide. Acute coronary syndrome (ACS) is associated with an increased risk of suicide, but few studies have explored the genetic predisposition toward suicide in ACS populations. Therefore, this longitudinal study explored the genetic predisposition toward suicidal ideation in ACS patients. In total, of 969 patients within 2 weeks after ACS, 711 were followed at 1 year after ACS. Suicidal ideation was evaluated with the relevant items on the Montgomery-Åsberg Depression Rating Scale. Ten genetic polymorphisms associated with serotonergic systems, neurotrophic factors, carbon metabolism, and inflammatory cytokines were examined. Associations between genetic polymorphisms and suicidal ideation within 2 weeks and 1 year of ACS were investigated using logistic regression models. The 5-HTTLPR s allele was significantly associated with suicidal ideation within 2 weeks of ACS after adjusting for covariates and after the Bonferroni correction. TNF-α -308 G/A , IL-1β -511 C/T , and IL-1β + 3953C/T were significantly associated with suicidal ideation within 2 weeks after ACS, but these associations did not reach significance after the Bonferroni correction in unadjusted analyses and after adjusting for covariance. However, no significant association between genetic polymorphisms and suicidal ideation was found at 1 year. Genetic predisposition, 5-HTTLPR s allele in particular, may confer susceptibility to suicidal ideation in ACS patients during the acute phase of ACS.

  9. Genetic testing for clinically suspected spinocerebellar ataxias ...

    Indian Academy of Sciences (India)

    Mahesh

    Yichuanxue Zazhi = Chinese Journal of Medical Genetics 27(5): 501–505. Wu, Y. R., H. Y. Lin, C. M. Chen, et al. 2004 Genetic Testing in Spinocerebellar Ataxia in Taiwan: Expansions of Trinucleotide Repeats in SCA8 and SCA17 Are Associated with Typical Parkinson's Disease. Clinical Genetics 65(3): 209–214.

  10. Being at risk for cardiovascular disease: Perceptions and preventive behavior in people with and without a known genetic predisposition

    NARCIS (Netherlands)

    Claassen, E.A.M.; Henneman, L.; van der Weijden, T.; Marteau, T.M.; Timmermans, D.R.M.

    2012-01-01

    This study compares and explains differences in perceptions of cardiovascular disease (CVD) risk and preventive behaviors in people with and without a known genetic predisposition to CVD. A cross-sectional study using two samples was performed. The first sample (genetic predisposition; n=51)

  11. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    NARCIS (Netherlands)

    Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, R.; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V.; Vonk, M.C.; Hoogen, F.H.J. van den; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Coenen, M.J.H.; Airo, P.; Beretta, L.; Scorza, R.; Laar, J. van; Gonzalez-Escribano, M.F.; Nelson, J.L.; Radstake, T.R.D.J.; Martin, J.

    2009-01-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy

  12. Developing national guidance on genetic testing for breast cancer predisposition: the role of economic evidence?

    NARCIS (Netherlands)

    Sullivan, W.; Evans, D.G.; Newman, W.G.; Ramsden, S.C.; Scheffer, H.; Payne, K.

    2012-01-01

    Advancements in genetic testing to identify predisposition for hereditary breast cancer (HBC) mean that it is important to understand the incremental costs and benefits of the new technologies compared with current testing strategies. This study aimed to (1) identify and critically appraise existing

  13. Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool

    NARCIS (Netherlands)

    Jongmans, M.C.; Loeffen, J.L.C.M.; Waanders, E.; Hoogerbrugge, P.M.; Ligtenberg, M.J.; Kuiper, R.P.; Hoogerbrugge, N.

    2016-01-01

    Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy.

  14. Recognition of genetic predisposition in pediatric cancer patients : An easy-to-use selection tool

    NARCIS (Netherlands)

    Jongmans, Marjolijn C J; Loeffen, Jan L C M; Waanders, Esmé; Hoogerbrugge, Peter M; Ligtenberg, Marjolijn J L; Kuiper, Roland P; Hoogerbrugge, Nicoline

    Genetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent malignancy.

  15. Recognition of genetic predisposition in pediatric cancer patients: An easy-to-use selection tool

    NARCIS (Netherlands)

    M.C. Jongmans (Marjolijn C.); J. Loeffen; E. Waanders (Esmé); P.M. Hoogerbrugge (Peter); M.J. Ligtenberg (Marjolijn); R.P. Kuiper (Roland); N. Hoogerbrugqe (N.)

    2016-01-01

    textabstractGenetic predisposition for childhood cancer is under diagnosed. Identifying these patients may lead to therapy adjustments in case of syndrome-related increased toxicity or resistant disease and syndrome-specific screening programs may lead to early detection of a further independent

  16. Childhood neuroendocrine tumours : a descriptive study revealing clues for genetic predisposition

    NARCIS (Netherlands)

    Diets, I J; Nagtegaal, I D; Loeffen, J; de Blaauw, I; Waanders, E; Hoogerbrugge, N; Jongmans, M C J

    2017-01-01

    BACKGROUND: Neuroendocrine tumours (NETs) are rare in children and limited data are available. We aimed to specify tumour and patient characteristics and to investigate the role of genetic predisposition in the aetiology of paediatric NETs. METHODS: Using the Dutch Pathology Registry PALGA, we

  17. Genetic screens to identify pathogenic gene variants in the common cancer predisposition Lynch syndrome

    DEFF Research Database (Denmark)

    Drost, Mark; Lützen, Anne; van Hees, Sandrine

    2013-01-01

    In many individuals suspected of the common cancer predisposition Lynch syndrome, variants of unclear significance (VUS), rather than an obviously pathogenic mutations, are identified in one of the DNA mismatch repair (MMR) genes. The uncertainty of whether such VUS inactivate MMR, and therefore...... function. When a residue identified as mutated in an individual suspected of Lynch syndrome is listed as critical in such a reverse diagnosis catalog, there is a high probability that the corresponding human VUS is pathogenic. To investigate the applicability of this approach, we have generated....... Nearly half of these critical residues match with VUS previously identified in individuals suspected of Lynch syndrome. This aids in the assignment of pathogenicity to these human VUS and validates the approach described here as a diagnostic tool. In a wider perspective, this work provides a model...

  18. Genetic causes of cancer predisposition in children and adolescents

    National Research Council Canada - National Science Library

    Saletta, Federica; Dalla Pozza, Luciano; Byrne, Jennifer A

    2015-01-01

    ... at high risk of cancer diagnosis. This review will discuss examples of cancer syndromes in children, adolescents and young adults, the main underlying gene mutations, and the use of genetic testing to identify gene mutation carriers...

  19. Genetic predisposition to salt-sensitivity : a systematic review

    NARCIS (Netherlands)

    Beeks, Esther; Kessels, Alfons G H; Kroon, Abraham A; van der Klauw, Melanie M; de Leeuw, Peter W

    PURPOSE: To assess the role of genetic polymorphisms in salt sensitivity of blood pressure. DATA IDENTIFICATION: We conducted a systematic review by searching the Medline literature from March 1993 to June 2003. Each paper was scrutinized and data concerning study population, method of salt

  20. Genetic predisposition for femoral neck stress fractures in military conscripts

    Directory of Open Access Journals (Sweden)

    Barral Sandra

    2010-10-01

    Full Text Available Abstract Background Stress fractures are a significant problem among athletes and soldiers and may result in devastating complications or even permanent handicap. Genetic factors may increase the risk, but no major susceptibility genes have been identified. The purpose of this study was to search for possible genetic factors predisposing military conscripts to femoral neck stress fractures. Results Eight genes involved in bone metabolism or pathology (COL1A1, COL1A2, OPG, ESR1, VDR, CTR, LRP5, IL-6 were examined in 72 military conscripts with a femoral neck stress fracture and 120 controls. The risk of femoral neck stress fracture was significantly higher in subjects with low weight and body mass index (BMI. An interaction between the CTR (rs1801197 minor allele C and the VDR C-A haplotype was observed, and subjects lacking the C allele in CTR and/or the C-A haplotype in VDR had a 3-fold higher risk of stress fracture than subjects carrying both (OR = 3.22, 95% CI 1.38-7.49, p = 0.007. In addition, the LRP5 haplotype A-G-G-C alone and in combination with the VDR haplotype C-A was associated with stress fractures through reduced body weight and BMI. Conclusions Our findings suggest that genetic factors play a role in the development of stress fractures in individuals subjected to heavy exercise and mechanical loading. The present results can be applied to the design of future studies that will further elucidate the genetics of stress fractures.

  1. Genetic predisposition to schizophrenia associated with increased use of cannabis.

    Science.gov (United States)

    Power, R A; Verweij, K J H; Zuhair, M; Montgomery, G W; Henders, A K; Heath, A C; Madden, P A F; Medland, S E; Wray, N R; Martin, N G

    2014-11-01

    Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric disorder affecting ~1% of the population over their lifetime. Although considerable evidence implicates cannabis use as a component cause of schizophrenia, it remains unclear whether this is entirely due to cannabis directly raising risk of psychosis, or whether the same genes that increases psychosis risk may also increase risk of cannabis use. In a sample of 2082 healthy individuals, we show an association between an individual's burden of schizophrenia risk alleles and use of cannabis. This was significant both for comparing those who have ever versus never used cannabis (P=2.6 × 10(-4)), and for quantity of use within users (P=3.0 × 10(-3)). Although directly predicting only a small amount of the variance in cannabis use, these findings suggest that part of the association between schizophrenia and cannabis is due to a shared genetic aetiology. This form of gene-environment correlation is an important consideration when calculating the impact of environmental risk factors, including cannabis use.

  2. Genetic predisposition to chikungunya – a blood group study in chikungunya affected families

    OpenAIRE

    Ramakrishna Vadde; Sarojamma Vemula; Sudarsanareddy Lokireddy

    2009-01-01

    Abstract Chikungunya fever is a viral disease transmitted to humans by the bite of CHIKV virus infected Aedes mosquitoes. During monsoon outbreak of chikungunya fever, we carried out the genetic predisposition to chikungunya in disease affected 100 families by doing blood group (ABO) tests by focusing on individuals who were likely to have a risk of chikungunya and identified the blood group involved in susceptibility/resistance to chikungunya. In the present study, based on blood group antig...

  3. Genetic and familial predisposition to rotator cuff disease: a systematic review.

    Science.gov (United States)

    Dabija, Dominique I; Gao, Chan; Edwards, Todd L; Kuhn, John E; Jain, Nitin B

    2017-06-01

    Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria. Four studies assessed familial predisposition to rotator cuff disease. One of these demonstrated that siblings of an individual with a rotator cuff tear were more likely to develop a full-thickness tear and more likely to be symptomatic. A 5-year follow-up showed that the relative risks were increased for the siblings to have a full-thickness tear, for a tear to progress in size, and for being symptomatic. Another study demonstrated that a significantly higher number of individuals with tears had family members with a history of tears or surgery than those without tears did. The other 3 studies investigated whether a genetic predisposition to rotator cuff disease exists and found significant association of haplotypes in DEFB1, FGFR1, FGF3, ESRRB, and FGF10 and 2 single-nucleotide polymorphisms within SAP30BP and SASH1. Prior studies provide preliminary evidence for genetic and familial predisposition to rotator cuff disease. However, there is a lack of large genome-wide studies that can provide more definitive information and guide early detection of individuals at risk, prophylactic rehabilitation, and potential gene therapies and regenerative medicine interventions. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  4. Interaction between genetic predisposition to adiposity and dietary protein in relation to subsequent change in body weight and waist circumference

    DEFF Research Database (Denmark)

    Ankarfeldt, Mikkel Zøllner; Larsen, Sofus C; Ängquist, Lars

    2014-01-01

    BACKGROUND: Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry. OBJECTIVE: To investigate the interaction between genetic predisposition to higher body mass index (BMI), waist circumference (WC) or waist-hip ratio adjusted for BMI (WHRBMI......, as well as potential confounders. Mean follow-up time was ∼5 years. Four genetic predisposition-scores were based on the SNPs; a complete-score including all selected adiposity- associated SNPs, and three scores including BMI, WC or WHRBMI associated polymorphisms, respectively. The association between...... energy% protein/risk allele, [-0.1; 0.1]). Similar results were seen when protein replaced fat. CONCLUSION: This study indicates that the genetic predisposition to general and abdominal adiposity, assessed by gene-scores, does not seem to modulate the influence of dietary protein on ΔBW or ΔWC....

  5. Interaction between genetic predisposition to obesity and dietary calcium in relation to subsequent change in body weight and waist circumference

    DEFF Research Database (Denmark)

    Larsen, Sofus C; Angquist, Lars; Ahluwalia, Tarun Veer Singh

    2014-01-01

    Studies indicate an effect of dietary calcium on change in body weight (BW) and waist circumference (WC), but the results are inconsistent. Furthermore, a relation could depend on genetic predisposition to obesity.......Studies indicate an effect of dietary calcium on change in body weight (BW) and waist circumference (WC), but the results are inconsistent. Furthermore, a relation could depend on genetic predisposition to obesity....

  6. Genetic predisposition to colorectal cancer: where we stand and future perspectives.

    Science.gov (United States)

    Valle, Laura

    2014-08-07

    The development of colorectal cancer (CRC) can be influenced by genetic factors in both familial cases and sporadic cases. Familial CRC has been associated with genetic changes in high-, moderate- and low-penetrance susceptibility genes. However, despite the availability of current gene-identification techniques, the genetic causes of a considerable proportion of hereditary cases remain unknown. Genome-wide association studies of CRC have identified a number of common low-penetrance alleles associated with a slightly increased or decreased risk of CRC. The accumulation of low-risk variants may partly explain the familial risk of CRC, and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance genes. Understanding the predisposition to develop CRC will require investigators to address the following challenges: the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis; the classification of variants of unknown significance in known CRC-predisposing genes; and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation carriers. We performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of low- and moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene approaches. Current challenges and future perspectives in the field of CRC predisposition are also discussed.

  7. Genetic predisposition to colorectal cancer: Where we stand and future perspectives

    Science.gov (United States)

    Valle, Laura

    2014-01-01

    The development of colorectal cancer (CRC) can be influenced by genetic factors in both familial cases and sporadic cases. Familial CRC has been associated with genetic changes in high-, moderate- and low-penetrance susceptibility genes. However, despite the availability of current gene-identification techniques, the genetic causes of a considerable proportion of hereditary cases remain unknown. Genome-wide association studies of CRC have identified a number of common low-penetrance alleles associated with a slightly increased or decreased risk of CRC. The accumulation of low-risk variants may partly explain the familial risk of CRC, and some of these variants may modify the risk of cancer in patients with mutations in high-penetrance genes. Understanding the predisposition to develop CRC will require investigators to address the following challenges: the identification of genes that cause uncharacterized hereditary cases of CRC such as familial CRC type X and serrated polyposis; the classification of variants of unknown significance in known CRC-predisposing genes; and the identification of additional cancer risk modifiers that can be used to perform risk assessments for individual mutation carriers. We performed a comprehensive review of the genetically characterized and uncharacterized hereditary CRC syndromes and of low- and moderate-penetrance loci and variants identified through genome-wide association studies and candidate-gene approaches. Current challenges and future perspectives in the field of CRC predisposition are also discussed. PMID:25110415

  8. Whole Exome Sequencing Reveals Genetic Predisposition in a Large Family with Retinitis Pigmentosa

    Directory of Open Access Journals (Sweden)

    Juan Wu

    2014-01-01

    Full Text Available Next-generation sequencing has become more widely used to reveal genetic defect in monogenic disorders. Retinitis pigmentosa (RP, the leading cause of hereditary blindness worldwide, has been attributed to more than 67 disease-causing genes. Due to the extreme genetic heterogeneity, using general molecular screening alone is inadequate for identifying genetic predispositions in susceptible individuals. In order to identify underlying mutation rapidly, we utilized next-generation sequencing in a four-generation Chinese family with RP. Two affected patients and an unaffected sibling were subjected to whole exome sequencing. Through bioinformatics analysis and direct sequencing confirmation, we identified p.R135W transition in the rhodopsin gene. The mutation was subsequently confirmed to cosegregate with the disease in the family. In this study, our results suggest that whole exome sequencing is a robust method in diagnosing familial hereditary disease.

  9. Genetic Predisposition Increases the Tic Severity, Rate of Comorbidities, and Psychosocial and Educational Difficulties in Children With Tourette Syndrome

    DEFF Research Database (Denmark)

    Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

    2015-01-01

    This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition...... to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related...... to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic...

  10. Testing positive for a genetic predisposition to depression magnifies retrospective memory for depressive symptoms.

    Science.gov (United States)

    Lebowitz, Matthew S; Ahn, Woo-Kyoung

    2017-11-01

    Depression, like other mental disorders and health conditions generally, is increasingly construed as genetically based. This research sought to determine whether merely telling people that they have a genetic predisposition to depression can cause them to retroactively remember having experienced it. U.S. adults (men and women) were recruited online to participate (Experiment 1: N = 288; Experiment 2: N = 599). After conducting a test disguised as genetic screening, we randomly assigned some participants to be told that they carried elevated genetic susceptibility to depression, whereas others were told that they did not carry this genetic liability or were told that they carried elevated susceptibility to a different disorder. Participants then rated their experience of depressive symptoms over the prior 2 weeks on a modified version of the Beck Depression Inventory-II. Participants who were told that their genes predisposed them to depression generally reported higher levels of depressive symptomatology over the previous 2 weeks, compared to those who did not receive this feedback. Given the central role of self-report in psychiatric diagnosis, these findings highlight potentially harmful consequences of personalized genetic testing in mental health. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. Childhood cancer predisposition syndromes-A concise review and recommendations by the Cancer Predisposition Working Group of the Society for Pediatric Oncology and Hematology.

    Science.gov (United States)

    Ripperger, Tim; Bielack, Stefan S; Borkhardt, Arndt; Brecht, Ines B; Burkhardt, Birgit; Calaminus, Gabriele; Debatin, Klaus-Michael; Deubzer, Hedwig; Dirksen, Uta; Eckert, Cornelia; Eggert, Angelika; Erlacher, Miriam; Fleischhack, Gudrun; Frühwald, Michael C; Gnekow, Astrid; Goehring, Gudrun; Graf, Norbert; Hanenberg, Helmut; Hauer, Julia; Hero, Barbara; Hettmer, Simone; von Hoff, Katja; Horstmann, Martin; Hoyer, Juliane; Illig, Thomas; Kaatsch, Peter; Kappler, Roland; Kerl, Kornelius; Klingebiel, Thomas; Kontny, Udo; Kordes, Uwe; Körholz, Dieter; Koscielniak, Ewa; Kramm, Christof M; Kuhlen, Michaela; Kulozik, Andreas E; Lamottke, Britta; Leuschner, Ivo; Lohmann, Dietmar R; Meinhardt, Andrea; Metzler, Markus; Meyer, Lüder H; Moser, Olga; Nathrath, Michaela; Niemeyer, Charlotte M; Nustede, Rainer; Pajtler, Kristian W; Paret, Claudia; Rasche, Mareike; Reinhardt, Dirk; Rieß, Olaf; Russo, Alexandra; Rutkowski, Stefan; Schlegelberger, Brigitte; Schneider, Dominik; Schneppenheim, Reinhard; Schrappe, Martin; Schroeder, Christopher; von Schweinitz, Dietrich; Simon, Thorsten; Sparber-Sauer, Monika; Spix, Claudia; Stanulla, Martin; Steinemann, Doris; Strahm, Brigitte; Temming, Petra; Thomay, Kathrin; von Bueren, Andre O; Vorwerk, Peter; Witt, Olaf; Wlodarski, Marcin; Wössmann, Willy; Zenker, Martin; Zimmermann, Stefanie; Pfister, Stefan M; Kratz, Christian P

    2017-04-01

    Heritable predisposition is an important cause of cancer in children and adolescents. Although a large number of cancer predisposition genes and their associated syndromes and malignancies have already been described, it appears likely that there are more pediatric cancer patients in whom heritable cancer predisposition syndromes have yet to be recognized. In a consensus meeting in the beginning of 2016, we convened experts in Human Genetics and Pediatric Hematology/Oncology to review the available data, to categorize the large amount of information, and to develop recommendations regarding when a cancer predisposition syndrome should be suspected in a young oncology patient. This review summarizes the current knowledge of cancer predisposition syndromes in pediatric oncology and provides essential information on clinical situations in which a childhood cancer predisposition syndrome should be suspected. © 2017 Wiley Periodicals, Inc.

  12. Genetic predisposition of IL-10 promoter polymorphisms with risk of multiple sclerosis: A meta-analysis.

    Science.gov (United States)

    Ramakrishnan, V; Akram Husain, R S; Ahmed, Shiek Ssj

    2017-05-15

    Interleukin-10 (IL-10) is a anti-inflammatory cytokine, which controls inflammation by inhibiting the synthesis of several cytokines produced by Th1 cells and macrophages. The association between Interleukin-10 promoter polymorphisms with the risk of multiple sclerosis (MS) remains inconclusive. In this study, a meta-analysis has been performed to assess the relationship between IL-10 gene polymorphisms rs1800896, rs1800871 and rs1800872 with the risk of MS. Nine case-control studies were selected involving 2755 participants. The association between the polymorphisms and MS was examined by the pooled odds ratios (ORs) with 95% confidence intervals (CIs) in allelic, homozygote, heterozygote, dominant and recessive genetic models. Of analyzed genetic models, the pooled ORs and CIs of each SNPs calculated based on random (I 2 >50) or fixed effects (I 2 0.05) of genetic predisposition with MS susceptibility across Asian and Caucasian populations. In addition, assessment based on funnel plot and Egger's linear regression test suggests no publication bias in all analyzed genetic models. Overall, our results demonstrated that rs1800896, rs1800871 and rs1800872 polymorphisms may not be the risk factor for the development of MS in both the populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Chromosomal radiosensitivity in breast cancer patients with a known or putative genetic predisposition.

    LENUS (Irish Health Repository)

    Baeyens, A

    2002-12-02

    The chromosomal radiosensitivity of breast cancer patients with a known or putative genetic predisposition was investigated and compared to a group of healthy women. The chromosomal radiosensitivity was assessed with the G2 and the G0-micronucleus assay. For the G2 assay lymphocytes were irradiated in vitro with a dose of 0.4 Gy (60)Co gamma-rays after 71 h incubation, and chromatid breaks were scored in 50 metaphases. For the micronucleus assay lymphocytes were exposed in vitro to 3.5 Gy (60)Co gamma-rays at a high dose rate or low dose rate. 70 h post-irradiation cultures were arrested and micronuclei were scored in 1000 binucleate cells. The results demonstrated that the group of breast cancer patients with a known or putative genetic predisposition was on the average more radiosensitive than a population of healthy women, and this with the G2 as well as with the high dose rate and low dose rate micronucleus assay. With the G2 assay 43% of the patients were found to be radiosensitive. A higher proportion of the patients were radiosensitive with the micronucleus assay (45% with high dose rate and 61% with low dose rate). No correlation was found between the G2 and the G0-micronucleus chromosomal radiosensitivity. Out of the different subgroups considered, the group of the young breast cancer patients without family history showed the highest percentage of radiosensitive cases in the G2 (50%) as well as in the micronucleus assay (75-78%).

  14. Genetic predisposition to higher blood pressure increases risk of incident hypertension and cardiovascular diseases in Chinese.

    Science.gov (United States)

    Lu, Xiangfeng; Huang, Jianfeng; Wang, Laiyuan; Chen, Shufeng; Yang, Xueli; Li, Jianxin; Cao, Jie; Chen, Jichun; Li, Ying; Zhao, Liancheng; Li, Hongfan; Liu, Fangcao; Huang, Chen; Shen, Chong; Shen, Jinjin; Yu, Ling; Xu, Lihua; Mu, Jianjun; Wu, Xianping; Ji, Xu; Guo, Dongshuang; Zhou, Zhengyuan; Yang, Zili; Wang, Renping; Yang, Jun; Yan, Weili; Gu, Dongfeng

    2015-10-01

    Although multiple genetic markers associated with blood pressure have been identified by genome-wide association studies, their aggregate effect on risk of incident hypertension and cardiovascular disease is uncertain, particularly among East Asian who may have different genetic and environmental exposures from Europeans. We aimed to examine the association between genetic predisposition to higher blood pressure and risk of incident hypertension and cardiovascular disease in 26 262 individuals in 2 Chinese population-based prospective cohorts. A genetic risk score was calculated based on 22 established variants for blood pressure in East Asian. We found the genetic risk score was significantly and independently associated with linear increases in blood pressure and risk of incident hypertension and cardiovascular disease (P range from 4.57×10(-3) to 3.10×10(-6)). In analyses adjusted for traditional risk factors including blood pressure, individuals carrying most blood pressure-related risk alleles (top quintile of genetic score distribution) had 40% (95% confidence interval, 18-66) and 26% (6-45) increased risk for incident hypertension and cardiovascular disease, respectively, when compared with individuals in the bottom quintile. The genetic risk score also significantly improved discrimination for incident hypertension and cardiovascular disease and led to modest improvements in risk reclassification for cardiovascular disease (all the Pblood pressure is an independent risk factor for blood pressure increase and incident hypertension and cardiovascular disease and provides modest incremental information to cardiovascular disease risk prediction. The potential clinical use of this panel of blood pressure-associated polymorphisms remains to be determined. © 2015 American Heart Association, Inc.

  15. Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition

    DEFF Research Database (Denmark)

    Mikropoulos, Christos; Selkirk, Christina G Hutten; Saya, Sibel

    2018-01-01

    BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PS...

  16. Assessment of false-negative cases of breast MR imaging in women with a familial or genetic predisposition

    NARCIS (Netherlands)

    Obdeijn, Inge-Marie A.; Loo, Claudette E.; Rijnsburger, Adriana J.; Wasser, Martin N. J. M.; Bergers, Elisabeth; Kok, Theo; Klijn, Jan G. M.; Boetes, Carla

    In order to assess the characteristics of malignant breast lesions those were not detected during screening by MR imaging. In the Dutch MRI screening study (MRISC), a non-randomized prospective multicenter study, women with high familial risk or a genetic predisposition for breast cancer were

  17. The effect of bacillus Calmette-Guerin immunization depends on the genetic predisposition to Th2-type responsiveness

    NARCIS (Netherlands)

    Hylkema, MN; Timens, W; Luinge, M; van der Werf, N; Hoekstra, MO

    The aim of this study was to investigate whether the effect of bacillus Calmette-Guerin (BCG) immunization on ovalbumin-induced allergic inflammation in a rat model depends on the genetic predisposition to react with a T helper cell (Th) 2-type cytokine response. This study was performed in an

  18. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Aalfs, Cora M.; Berger, Lieke P. V.; Bleeker, Fonnet E.; Dommering, Charlotte J.; Jongmans, Marjolijn C. J.; Letteboer, Tom G. W.; Olderode-Berends, Maran J. W.; Wagner, Anja; Hennekam, Raoul C.; Merks, Johannes H. M.

    2017-01-01

    Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a child for genetic

  19. Is There a Genetic Predisposition to Anterior Cruciate Ligament Tear? A Systematic Review.

    Science.gov (United States)

    John, Rakesh; Dhillon, Mandeep Singh; Sharma, Siddhartha; Prabhakar, Sharad; Bhandari, Mohit

    2016-12-01

    Injuries to the anterior cruciate ligament (ACL) are among the most common knee ligament injuries and frequently warrant reconstruction. The etiopathogenesis of these injuries has focused mainly on mechanism of trauma, patient sex, and anatomic factors as predisposing causes. Several genetic factors that could predispose to an ACL tear have recently been reported. This systematic review summarizes the current evidence for a genetic predisposition to ACL tears. The principal research question was to identify genetic factors, based on the available literature, that could predispose an individual to an ACL tear. Systematic review. The PubMed, EMBASE, Cochrane, and HuGE databases were searched; the search was run from the period of inception until June 21, 2015. A secondary search was performed by screening the references of full-text articles obtained and by manually searching selected journals. Articles were screened with prespecified inclusion criteria. The quality of studies included in the review was assessed for risk of bias by 2 reviewers using the Newcastle-Ottawa Scale. A total of 994 records were identified by the search, out of which 17 studies (16 case-control studies and 1 cross-sectional study) were included in the final review. Two studies observed a familial predisposition to an ACL tear. Fourteen studies looked at specific gene polymorphisms in 20 genes, from which different polymorphisms in 10 genes were positively associated with an ACL tear. In addition to these polymorphisms, 8 haplotypes were associated with ACL tear. One study looked at gene expression analysis. Although specific gene polymorphisms and haplotypes have been identified, it is difficult to come to a conclusion on the basis of the existing literature. Several sources of bias have been identified in these studies, and the results cannot be extrapolated to the general population. More studies are needed in larger populations of different ethnicities. Gene-gene interactions and gene

  20. Effects of early life trauma are dependent on genetic predisposition: a rat study

    Directory of Open Access Journals (Sweden)

    Russell Vivienne A

    2011-05-01

    Full Text Available Abstract Background Trauma experienced early in life increases the risk of developing a number of psychological and/or behavioural disorders. It is unclear, however, how genetic predisposition to a behavioural disorder, such as attention-deficit/hyperactivity disorder (ADHD, modifies the long-term effects of early life trauma. There is substantial evidence from family and twin studies for susceptibility to ADHD being inherited, implying a strong genetic component to the disorder. In the present study we used an inbred animal model of ADHD, the spontaneously hypertensive rat (SHR, to investigate the long-term consequences of early life trauma on emotional behaviour in individuals predisposed to developing ADHD-like behaviour. Methods We applied a rodent model of early life trauma, maternal separation, to SHR and Wistar-Kyoto rats (WKY, the normotensive control strain from which SHR were originally derived. The effects of maternal separation (removal of pups from dam for 3 h/day during the first 2 weeks of life on anxiety-like behaviour (elevated-plus maze and depressive-like behaviour (forced swim test were assessed in prepubescent rats (postnatal day 28 and 31. Basal levels of plasma corticosterone were measured using radioimmunoassay. Results The effect of maternal separation on SHR and WKY differed in a number of behavioural measures. Similar to its reported effect in other rat strains, maternal separation increased the anxiety-like behaviour of WKY (decreased open arm entries but not SHR. Maternal separation increased the activity of SHR in the novel environment of the elevated plus-maze, while it decreased that of WKY. Overall, SHR showed a more active response in the elevated plus-maze and forced swim test than WKY, regardless of treatment, and were also found to have higher basal plasma corticosterone compared to WKY. Maternal separation increased basal levels of plasma corticosterone in SHR females only, possibly through adaptive

  1. A Parallel Genetic Algorithm to Discover Patterns in Genetic Markers that Indicate Predisposition to Multifactorial Disease

    Science.gov (United States)

    Rausch, Tobias; Thomas, Alun; Camp, Nicola J.; Cannon-Albright, Lisa A.; Facelli, Julio C.

    2008-01-01

    This paper describes a novel algorithm to analyze genetic linkage data using pattern recognition techniques and genetic algorithms (GA). The method allows a search for regions of the chromosome that may contain genetic variations that jointly predispose individuals for a particular disease. The method uses correlation analysis, filtering theory and genetic algorithms (GA) to achieve this goal. Because current genome scans use from hundreds to hundreds of thousands of markers, two versions of the method have been implemented. The first is an exhaustive analysis version that can be used to visualize, explore, and analyze small genetic data sets for two marker correlations; the second is a GA version, which uses a parallel implementation allowing searches of higher-order correlations in large data sets. Results on simulated data sets indicate that the method can be informative in the identification of major disease loci and gene-gene interactions in genome-wide linkage data and that further exploration of these techniques is justified. The results presented for both variants of the method show that it can help genetic epidemiologists to identify promising combinations of genetic factors that might predispose to complex disorders. In particular, the correlation analysis of IBD expression patterns might hint to possible gene-gene interactions and the filtering might be a fruitful approach to distinguish true correlation signals from noise. PMID:18547558

  2. The genetic predisposition and the interplay of host genetics and gut microbiome in Crohn disease.

    Science.gov (United States)

    Jianzhong, Hu

    2014-12-01

    Extensive genetic studies have identified more than 140 loci predisposing to Crohn disease (CD). Several major CD susceptibility genes have been shown to impair biological function with regard to immune response to recognizing and clearance of bacterial infection. Recent human microbiome studies suggest that the gut microbiome composition is differentiated in carriers of many risk variants of major CD susceptibility genes. This interplay between host genetics and its associated gut microbiome may play an essential role in the pathogenesis of CD. The ongoing microbiome research is aimed to investigate the detailed host genetics-microbiome interacting mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk

    Science.gov (United States)

    Holzapfel, Christina; Ambrosini, Gina L.; Fuller, Nicholas R.; Loos, Ruth J. F.; Hauner, Hans; Caterson, Ian D.; Jebb, Susan A.

    2015-01-01

    The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention. PMID:26154605

  4. Genetic predisposition to albuminuria is associated with increased arterial stiffness: role of elastin.

    Science.gov (United States)

    Gil-Ortega, M; García-Prieto, C F; Ruiz-Hurtado, G; Steireif, C; González, M C; Schulz, A; Kreutz, R; Fernández-Alfonso, M S; Arribas, S; Somoza, B

    2015-09-01

    The Munich Wistar Frömter (MWF) rat strain represents an experimental model to study cardiovascular alterations under conditions of progressive albuminuria. The aim of this study was to evaluate the association between genetic predisposition to albuminuria and the development of arterial stiffness and/or vascular remodelling. Experiments were performed in mesenteric arteries from 12-week-old MWF, Wistar Kyoto (WKY) and consomic MWF-6(SHR) and MWF-8(SHR) rats in which chromosomes 6 or 8 associated with albuminuria from MWF were replaced by the respective chromosome from spontaneously hypertensive rats (SHR). Incremental distensibility, wall stress and strain were reduced, and arterial stiffness was significantly increased in albuminuric MWF compared with WKY. Albuminuria suppression in both consomic strains was associated with lower β-values in MWF-8(SHR) and MWF-6(SHR) compared with MWF. Moreover, elastin content was significantly lower in MWF external elastic lamina compared with WKY and both consomic strains. In addition, a reduction in arterial external and internal diameter and cross-sectional area was detected in MWF compared with WKY, thus exhibiting an inward hypotrophic remodelling. However, these alterations remained unchanged in both consomic strains. These data demonstrate that albuminuria in MWF is associated with increased arterial stiffness due to a reduction of elastin content in the external elastic lamina. Moreover, inward hypotrophic remodelling in MWF is not directly associated with albuminuria. In contrast, we demonstrated that two major genetic loci affect both the development of albuminuria and arterial stiffness, thus linking albuminuria and impairment of mechanical properties of resistance arteries. © 2015 The British Pharmacological Society.

  5. [Clinico-genetical studies of colonic cancer. II. Genetic analysis of predisposition to colonic cancer].

    Science.gov (United States)

    Belev, N F; Gar'kavtseva, R F; Samotyia, E E; Trubnikov, V I; Gindilis, V M

    1986-10-01

    The structure of subjection to different clinical forms of colon cancer and to the morbidity as a whole approximates better the quasi-continued phenotypical model within which the contribution of genetic factors reaches 68-84%, that of incidental medium factors being 16-32%. Genetic study of heterogeneity of colon cancer clinical forms revealed that their pathogenetic community was quite high. However, the origin of colon cancer depends strongly on genetic factors (83.7 +/- 7.3%), in comparison with rectal cancer (67.9 +/- 7.1%). The analysis of colon cancer interrelation with other malignant neoplasms (including specific ones for women--breast and uterus cancer) revealed that the development of another malignant neoplasms was the result of the influence of partially common genes (20-50%) which predetermined the development of colon cancer and other malignant neoplasms. According to the data obtained in this study, the tables of repeated risk have been worked out which may be used for medico-genetic consultation.

  6. Association between Maternal Fish Consumption and Gestational Weight Gain: Influence of Molecular Genetic Predisposition to Obesity.

    Directory of Open Access Journals (Sweden)

    Sofus C Larsen

    Full Text Available Studies suggest that fish consumption can restrict weight gain. However, little is known about how fish consumption affects gestational weight gain (GWG, and whether this relationship depends on genetic makeup.To examine the association between fish consumption and GWG, and whether this relationship is dependent on molecular genetic predisposition to obesity.A nested case-cohort study based on the Danish National Birth Cohort (DNBC sampling the most obese women (n = 990 and a random sample of the remaining participants (n = 1,128. Replication of statistically significant findings was attempted in the Avon Longitudinal Study of Parents and Children (ALSPAC (n = 4,841. We included 32 body mass index (BMI associated single nucleotide polymorphisms (SNPs and 5 SNPs found associated with GWG. BMI associated SNPs were combined in a genetic risk score (GRS. Associations between consumption of fish, GRS or individual variants and GWG were analysed, and interactions between fish and the GRS or individual variants were examined.In the DNBC, each portion/week (150 g of fatty fish was associated with a higher GWG of 0.58 kg (95% CI: 0.16, 0.99, P<0.01. For total fish and lean fish, similar patterns were observed, but these associations were not statistically significant. We found no association between GRS and GWG, and no interactions between GRS and dietary fish on GWG. However, we found an interaction between the PPARG Pro12Ala variant and dietary fish. Each additional Pro12Ala G-allele was associated with a GWG of -0.83 kg (95% CI: -1.29, -0.37, P<0.01 per portion/week of dietary fish, with the same pattern for both lean and fatty fish. In ALSPAC, we were unable to replicate these findings.We found no consistent evidence of association between fish consumption and GWG, and our results indicate that the association between dietary fish and GWG has little or no dependency on GRS or individual SNPs.

  7. Using the molecular genetics methods for studying the peculiarities of muscle activity and inherited predisposition in the sport

    Directory of Open Access Journals (Sweden)

    S.B. Drozdovska

    2013-02-01

    Full Text Available Analyzes of the methods used in sports genetics, and molecular genetics of muscle activity in particular are considered. The historical retrospective review of sports genetics methods was created. Contemporary level sports genetics methods were determined by the scientific literature analysis. The most common molecular genetics techniques that are used for practice and for research into sports were highlighted. It is shown that the main method, which has the greatest practical application in sport, is the method of polymerase chain reaction in various versions. These methods allow genes diagnostic and determine the genetic predisposition to perform of different kinds of physical exercises. The advantages of using these methods in sport, their features and shortcomings, prospects for further research were established.

  8. [Genetic predisposition and Pediatric Acute Respiratory Distress Syndrome: New tools for genetic study].

    Science.gov (United States)

    Erranz, M Benjamín; Wilhelm, B Jan; Riquelme, V Raquel; Cruces, R Pablo

    2015-01-01

    Acute respiratory distress syndrome (ARDS) is the most severe form of respiratory failure. Theoretically, any acute lung condition can lead to ARDS, but only a small percentage of individuals actually develop the disease. On this basis, genetic factors have been implicated in the risk of developing ARDS. Based on the pathophysiology of this disease, many candidate genes have been evaluated as potential modifiers in patient, as well as in animal models, of ARDS. Recent experimental data and clinical studies suggest that variations of genes involved in key processes of tissue, cellular and molecular lung damage may influence susceptibility and prognosis of ARDS. However, the pathogenesis of pediatric ARDS is complex, and therefore, it can be expected that many genes might contribute. Genetic variations such as single nucleotide polymorphisms and copy-number variations are likely associated with susceptibility to ARDS in children with primary lung injury. Genome-wide association (GWA) studies can objectively examine these variations, and help identify important new genes and pathogenetic pathways for future analysis. This approach might also have diagnostic and therapeutic implications, such as predicting patient risk or developing a personalized therapeutic approach to this serious syndrome. Copyright © 2015. Publicado por Elsevier España, S.L.U.

  9. Genetic predisposition to elevated levels of C-reactive protein is associated with a decreased risk for preeclampsia.

    Science.gov (United States)

    Spracklen, Cassandra N; Smith, Caitlin J; Saftlas, Audrey F; Triche, Elizabeth W; Bjonnes, Andrew; Keating, Brendan J; Saxena, Richa; Breheny, Patrick J; Dewan, Andrew T; Robinson, Jennifer G; Hoh, Josephine; Ryckman, Kelli K

    2017-02-01

    To examine the association between genetic predisposition to elevated C-reactive protein (CRP)and risk for preeclampsia using validated genetic loci for C-reactive protein. Preeclampsia cases (n = 177) and normotensive controls (n = 116) were selected from live birth certificates to nulliparous Iowa women during the period August 2002-May 2005. Disease status was verified by the medical chart review. Genetic predisposition to CRP was estimated by a genetic risk score on the basis of established loci for CRP levels. Logistic regression analyses were used to evaluate the relationships between the genotype score and preeclampsia. Replication analyses were performed in an independent, US population of preeclampsia cases (n = 516) and controls (n = 1,097) of European ancestry. The genetic risk score (GRS) related to higher levels of CRP demonstrated a significantly decreased risk of preeclampsia (OR 0.89, 95% CI 0.82-0.96). When the GRS was analyzed by quartile, an inverse linear trend was observed (p = 0.0006). The results were similar after adjustments for the body mass index (BMI), smoking, and leisure-time physical activity. In the independent replication population, the association with the CRP GRS was also marginally significant (OR 0.97, 95% CI 0.92, 1.02). Meta-analysis of the two studies was statistically significant (OR 0.95, 95% CI 0.90, 0.99). Our data suggest an inverse, counterintuitive association between the genetic predisposition to elevated levels of CRP and a decreased risk of preeclampsia. This suggests that the blood CRP level is a marker of preeclampsia, but it does not appear to be a factor on the causal pathway.

  10. Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants.

    Science.gov (United States)

    Drysdale, Simon B; Alcazar, Mireia; Wilson, Theresa; Smith, Melvyn; Zuckerman, Mark; Hodemaekers, Hennie M; Janssen, Riny; Bont, Louis; Johnston, Sebastian L; Greenough, Anne

    2016-12-01

    Term born infants are predisposed to human rhinovirus (HRV) lower respiratory tract infections (LRTI) by reduced neonatal lung function and genetic susceptibility. Our aim was to investigate whether prematurely born infants were similarly predisposed to HRV LRTIs or any other viral LRTIs. Infants born less than 36 weeks of gestational age were recruited. Prior to neonatal/maternity unit discharge, lung function (functional residual capacity by helium gas dilution and multiple breath washout, lung clearance index and compliance (Crs), and resistance (Rrs) of the respiratory system) was assessed and DNA samples assessed for eight single nucleotide polymorphisms (SNPs) in seven genes: ADAM33, IL10, MMP16 NFκB1A,SFTPC, VDR, and NOS2A. Infants were prospectively followed until 1 year corrected age. Nasopharyngeal aspirates (NPAs) were sent whenever an infant developed a LRTI and tested for 13 viruses. One hundred and thirty-nine infants were included in the analysis. Infants who developed HRV LRTIs had reduced Crs (1.6 versus 1.2 mL/cmH2O/kg, p = 0.044) at 36 weeks postmenstrual age. A SNP in the gene coding for the vitamin D receptor was associated with the development of HRV LRTIs and any viral LRTIs (p = 0.02). Prematurely born infants may have both a functional and genetic predisposition to HRV LRTIs. What is Known: • Term born infants are predisposed to rhinovirus lower respiratory tract (HRV LRTIs) infection by reduced neonatal lung function. • Term born infants requiring hospitalisation due to HRV bronchiolitis were more likely to have single nucleotide polymorphism (SNP) in the IL-10 gene. What is New: • Prematurely born infants who developed a HRV LRTI had lower C rs before maternity unit discharge. • A SNP in the gene coding for the vitamin D receptor was associated with the development of HRV LRTIs and overall respiratory viral LRTIs in prematurely born infants.

  11. Integrated screening concept in women with genetic predisposition for breast cancer; Integriertes Frueherkennungskonzept bei Frauen mit genetischer Praedisposition fuer Brustkrebs

    Energy Technology Data Exchange (ETDEWEB)

    Bick, U. [Muenster Univ. (Germany). Inst. fuer Klinische Radiologie

    1997-08-01

    Breast cancer is in 5% of cases due to a genetic disposition. BRCA1 and BRCA2 are by far the most common breast cancer susceptibility genes. For a woman with a genetic predisposition, the individual risk of developing breast cancer sometime in her life is between 70 and 90%. Compared to the spontaneous forms of breast cancer, woman with a genetic predisposition often develop breast cancer at a much younger age. This is why conventional screening programs on the basis of mammography alone cannot be applied without modification to this high-risk group. In this article, an integrated screening concept for women with genetic prodisposition for breast cancer using breast self-examination, clinical examination, ultrasound, mammography and magnetic resonance imaging is introduced. (orig.) [Deutsch] Mammakarzinome sind in etwa 5% auf eine genetische Disposition zurueckzufuehren. Am haeufigsten finden sich Mutationen im Bereich der Gene BRCA1 und BRCA2. Frauen mit einer genetischen Disposition erkranken in etwa 70-90% im Laufe ihres Lebens an einem Mammakarzinom. Das Erkrankungsalter bei diesen Frauen liegt in der Regel deutlich niedriger als bei den spontanen Formen des Mammakarzinoms, so dass vorhandene Frueherkennungskonzepte auf der Basis eines Mammographiescrennings nicht ohne weiteres auf dieses Hochrisikokollektiv uebertragbar sind. Im folgenden wird ein integriertes Konzept zur Frueherkennung bei Frauen mit genetischer Praedisposition fuer ein Mammakarzinom auf der Basis von Brustselbstuntersuchung, klinischer Untersuchung, Sonographie, Mammographie und Magnetresonanztomographie vorgestellt. (orig.)

  12. Habitual coffee consumption and genetic predisposition to obesity: gene-diet interaction analyses in three US prospective studies.

    Science.gov (United States)

    Wang, Tiange; Huang, Tao; Kang, Jae H; Zheng, Yan; Jensen, Majken K; Wiggs, Janey L; Pasquale, Louis R; Fuchs, Charles S; Campos, Hannia; Rimm, Eric B; Willett, Walter C; Hu, Frank B; Qi, Lu

    2017-05-09

    Whether habitual coffee consumption interacts with the genetic predisposition to obesity in relation to body mass index (BMI) and obesity is unknown. We analyzed the interactions between genetic predisposition and habitual coffee consumption in relation to BMI and obesity risk in 5116 men from the Health Professionals Follow-up Study (HPFS), in 9841 women from the Nurses' Health Study (NHS), and in 5648 women from the Women's Health Initiative (WHI). The genetic risk score was calculated based on 77 BMI-associated loci. Coffee consumption was examined prospectively in relation to BMI. The genetic association with BMI was attenuated among participants with higher consumption of coffee than among those with lower consumption in the HPFS (P interaction  = 0.023) and NHS (P interaction  = 0.039); similar results were replicated in the WHI (P interaction  = 0.044). In the combined data of all cohorts, differences in BMI per increment of 10-risk allele were 1.38 (standard error (SE), 0.28), 1.02 (SE, 0.10), and 0.95 (SE, 0.12) kg/m 2 for coffee consumption of  3 cup(s)/day, respectively (P interaction  coffee consumption among participants at lower genetic risk and slightly lower BMI with higher coffee consumption among those at higher genetic risk. Each increment of 10-risk allele was associated with 78% (95% confidence interval (CI), 59-99%), 48% (95% CI, 36-62%), and 43% (95% CI, 28-59%) increased risk for obesity across these subgroups of coffee consumption (P interaction  = 0.008). From another perspective, differences in BMI per increment of 1 cup/day coffee consumption were 0.02 (SE, 0.09), -0.02 (SE, 0.04), and -0.14 (SE, 0.04) kg/m 2 across tertiles of the genetic risk score. Higher coffee consumption might attenuate the genetic associations with BMI and obesity risk, and individuals with greater genetic predisposition to obesity appeared to have lower BMI associated with higher coffee consumption.

  13. Interaction between genetic predisposition to adiposity and dietary protein in relation to subsequent change in body weight and waist circumference.

    Directory of Open Access Journals (Sweden)

    Mikkel Z Ankarfeldt

    Full Text Available Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry.To investigate the interaction between genetic predisposition to higher body mass index (BMI, waist circumference (WC or waist-hip ratio adjusted for BMI (WHRBMI and dietary protein in relation to subsequent change in body weight (ΔBW or change in WC (ΔWC.Three different Danish cohorts were used. In total 7,054 individuals constituted the study population with information on diet, 50 single-nucleotide polymorphisms (SNPs associated with BMI, WC or WHRBMI, as well as potential confounders. Mean follow-up time was ∼5 years. Four genetic predisposition-scores were based on the SNPs; a complete-score including all selected adiposity- associated SNPs, and three scores including BMI, WC or WHRBMI associated polymorphisms, respectively. The association between protein intake and ΔBW or ΔWC were examined and interactions between SNP-score and protein were investigated. Analyses were based on linear regressions using macronutrient substitution models and meta-analyses.When protein replaced carbohydrate, meta-analyses showed no associations with ΔBW (41.0 gram/y/5 energy% protein, [95% CI: -32.3; 114.3] or ΔWC (<-0.1 mm/y/5 energy % protein, [-1.1; 1.1]. Similarly, there were no interactions for any SNP-scores and protein for either ΔBW (complete SNP-score: 1.8 gram/y/5 energy% protein/risk allele, [-7.0; 10.6] or ΔWC (complete SNP-score: <0.1 mm/y/5 energy% protein/risk allele, [-0.1; 0.1]. Similar results were seen when protein replaced fat.This study indicates that the genetic predisposition to general and abdominal adiposity, assessed by gene-scores, does not seem to modulate the influence of dietary protein on ΔBW or ΔWC.

  14. Genetic predisposition to obesity affects behavioural traits including food reward and anxiety-like behaviour in rats.

    Science.gov (United States)

    Vogel, Heike; Kraemer, Maria; Rabasa, Cristina; Askevik, Kaisa; Adan, Roger A H; Dickson, Suzanne L

    2017-06-15

    Here we sought to define behavioural traits linked to anxiety, reward, and exploration in different strains of rats commonly used in obesity research. We hypothesized that genetic variance may contribute not only to their metabolic phenotype (that is well documented) but also to the expression of these behavioural traits. Rat strains that differ in their susceptibility to develop an obese phenotype (Sprague-Dawley, Obese Prone, Obese Resistant, and Zucker rats) were exposed to a number of behavioural tests starting at the age of 8 weeks. We found a similar phenotype in the obesity susceptible models, Obese Prone and Zucker rats, with a lower locomotor activity, exploratory activity, and higher level of anxiety-like behaviour in comparison to the leaner Obese Resistant strain. We did not find evidence that rat strains with a genetic predisposition to obesity differed in their ability to experience reward from chocolate (in a condition place preference task). However, Zucker rats show higher motivated behaviour for sucrose compared to Obese Resistant rats when the effort required to obtain palatable food is relatively low. Together our data demonstrate that rat strains that differ in their genetic predisposition to develop obesity also differ in their performance in behavioural tests linked to anxiety, exploration, and reward and that these differences are independent of body weight. We conclude that genetic variations which determine body weight and the aforementioned behaviours co-exist but that future studies are required to identify whether (and which) common genes are involved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  15. [Genetic analysis of the structure of the predisposition to diabetes mellitus. I. Genetic epidemiological approaches to an analysis of age-dependent multifactorial diseases].

    Science.gov (United States)

    Sergeev, A S

    1983-09-01

    The statistical methods for genetic analysis of multifactorial diseases (MFD) with variable age-at-onset are developed. It is emphasized that the index numbers used in the genetical-epidemiological studies, such as frequency of MFD in the population (qg--incidence) and that among family members (PR), should be independent on the demographic structure of both the population and the families. The mathematical grounds for the estimating methods as well as biological meaning for such index numbers are given. The approach suggested will be used later in analysis of the structure of predisposition to diabetes mellitus.

  16. A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study

    Directory of Open Access Journals (Sweden)

    Schepers Dirk

    2011-10-01

    Full Text Available Abstract Background It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. Methods 935 Coronary artery disease patients (CAD who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS were constructed based on literature and own data and were related to baseline and response VO2 scores. Results Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR and the ciliary neurotrophic factor gene (CNTF had a significantly higher increase in peakVO2 after training (p AMPD1 gene had a significantly lower relative increase (p 2. GPS of data driven models were significantly associated with the increase in peakVO2 after training. Conclusions In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS showed a significant predictive value for the increase in peakVO2.

  17. XX sex reversal, palmoplantar keratoderma, and predisposition to squamous cell carcinoma: genetic analysis in one family.

    Science.gov (United States)

    Radi, Orietta; Parma, Pietro; Imbeaud, Sandrine; Nasca, Maria Rita; Uccellatore, Filippo; Maraschio, Paola; Tiepolo, Luciano; Micali, Giuseppe; Camerino, Giovanna

    2005-10-15

    We describe a large inbred Sicilian family that includes four 46, XX (SRY-) brothers. Palmoplantar hyperkeratosis (PPK) and an associated predisposition to squamous cell carcinoma (SCC) of the skin, segregates as a recessive trait within the family. Interestingly, all the PPK-affected members of the family are phenotypic males (46,XY or 46,XX) while seven XX sibs are healthy phenotypic females with no signs of PPK. We propose that homozygosity for a single mutational event, possibly including contiguous genes, may cause PPK/SCC in both XY or XX individuals and sex reversal in XX individuals. The family is informative for linkage analysis for the PPK trait and allows linkage exclusion for the sex reversal trait. Here we show that 15 loci involved in PPK etiology, skin differentiation, function or malignancy, and nine loci involved in sex determination/differentiation are not implicated in the phenotype of this family.

  18. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    Science.gov (United States)

    Petridis, Christos; Brook, Mark N.; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C.; Hopper, John L.; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A.; Jud, Sebastian M.; Ekici, Arif B.; Beckmann, Matthias W.; Kerin, Michael J.; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Milne, Roger L.; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K.; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A.; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V.; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona A.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S.; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline M.; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J.; Sherman, Mark E.; Hooning, Maartje J.; Hollestelle, Antoinette; van den Ouweland, Ans M. W.; van Deurzen, Carolien H. M.; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J.; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M.; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K.; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10−10; P-het for ILC vs IDC ER+ tumors = 1.8×10−4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at Pbreast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes. PMID:24743323

  19. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Science.gov (United States)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos; Brook, Mark N; Nowinski, Salpie; Papouli, Efterpi; Fletcher, Olivia; Pinder, Sarah; Hanby, Andrew; Kohut, Kelly; Gorman, Patricia; Caneppele, Michele; Peto, Julian; Dos Santos Silva, Isabel; Johnson, Nichola; Swann, Ruth; Dwek, Miriam; Perkins, Katherine-Anne; Gillett, Cheryl; Houlston, Richard; Ross, Gillian; De Ieso, Paolo; Southey, Melissa C; Hopper, John L; Provenzano, Elena; Apicella, Carmel; Wesseling, Jelle; Cornelissen, Sten; Keeman, Renske; Fasching, Peter A; Jud, Sebastian M; Ekici, Arif B; Beckmann, Matthias W; Kerin, Michael J; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara; Guénel, Pascal; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Bojesen, Stig E; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Benitez, Javier; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Meindl, Alfons; Lichtner, Peter; Schmutzler, Rita K; Lochmann, Magdalena; Brauch, Hiltrud; Fischer, Hans-Peter; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Bogdanova, Natalia V; Dörk, Thilo; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Investigators, Kconfab; Lambrechts, Diether; Weltens, Caroline; Van Limbergen, Erik; Hatse, Sigrid; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Volorio, Sara; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; McLean, Catriona A; Haiman, Christopher A; Henderson, Brian E; Schumacher, Fredrick; Le Marchand, Loic; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Kristensen, Vessela; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Tollenaar, Rob A E M; Seynaeve, Caroline M; Kriege, Mieke; Figueroa, Jonine; Chanock, Stephen J; Sherman, Mark E; Hooning, Maartje J; Hollestelle, Antoinette; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Li, Jingmei; Czene, Kamila; Humphreys, Keith; Cox, Angela; Cross, Simon S; Reed, Malcolm W R; Shah, Mitul; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Swerdlow, Anthony; Ashworth, Alan; Orr, Nicholas; Schoemaker, Minouk; Couch, Fergus J; Hallberg, Emily; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Dunning, Alison M; Hall, Per; Easton, Doug; Pharoah, Paul; Schmidt, Marjanka K; Tomlinson, Ian; Garcia-Closas, Montserrat

    2014-04-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09-1.18), P = 6.0 × 10(-10); P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4)). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at Plobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.

  20. [Genetic analysis of precancer-cancer of the stomach system. II. Lactate dehydrogenase in families of the patients: is it a marker of hereditary predisposition?].

    Science.gov (United States)

    Al'tshuller, B A; Bazhenova, M D; Bassalyk, L S; Pashintseva, L P; Bridko, V V

    1986-03-01

    The possibility of using the LDH as a marker of hereditary predisposition to the stomach cancer was analysed by using the genetical correlational analysis. The LDH isoenzymes in the gastric body were studied in 56 pedigrees. Similar LDH alterations were detected in relatives with cancer and precancer (ulcer disease, atrophic gastritis). Relatives with no such pathology had LDH isoenzymes, similar to the control individuals. High and significant coefficients of phenotypic and environmental correlation of LDH and predisposition to the stomach cancer were obtained. The coefficient of genetic correlation was not significant. The problem of the origin of these LDH variances is discussed. The preliminary conclusion is that the LDH isoenzyme changes revealed in patients with stomach cancer appear as a consequence of the disease, and cannot be used as the marker of hereditary predisposition.

  1. Genetic Predisposition to High Blood Pressure and Lifestyle Factors: Associations with Midlife Blood Pressure Levels and Cardiovascular Events.

    Science.gov (United States)

    Pazoki, Raha; Dehghan, Abbas; Evangelou, Evangelos; Warren, Helen; Gao, He; Caulfield, Mark; Elliott, Paul; Tzoulaki, Ioanna

    2017-12-18

    Background -High blood pressure (BP) is a major risk factor for cardiovascular diseases (CVD), the leading cause of mortality worldwide. Both heritable and lifestyle risk factors contribute to elevated BP levels. We aimed to investigate the extent to which lifestyle factors could offset the effect of an adverse BP genetic profile, and its effect on CVD risk. Methods -We constructed a genetic risk score for high BP using 314 published BP loci in 277,005 individuals without previous CVD from the UK Biobank study, a prospective cohort of individuals aged 40 to 69 years, with median 6.11 years of follow-up. We scored participants according to their lifestyle factors including body mass index, healthy diet, sedentary lifestyle, alcohol consumption, smoking, and urinary sodium excretion levels measured at recruitment. We examined the association between tertiles of genetic risk and tertiles of lifestyle score with BP levels and incident CVD using linear regression and Cox regression models respectively. Results -Healthy lifestyle score was strongly associated with BP (PAdvantages and disadvantages of disclosing genetic predisposition to high BP for risk stratification needs careful evaluation.

  2. Genetic predisposition to in situ and invasive lobular carcinoma of the breast.

    Directory of Open Access Journals (Sweden)

    Elinor Sawyer

    2014-04-01

    Full Text Available Invasive lobular breast cancer (ILC accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+ and often associated with lobular carcinoma in situ (LCIS. Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI for ILC = 1.13 (1.09-1.18, P = 6.0 × 10(-10; P-het for ILC vs IDC ER+ tumors = 1.8 × 10(-4. Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03; and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04. In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365 and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7. In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity

  3. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

    Energy Technology Data Exchange (ETDEWEB)

    Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

    2012-08-24

    The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  4. Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

    Directory of Open Access Journals (Sweden)

    Y.D. Apalasamy

    2012-12-01

    Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

  5. Genetic predisposition to colorectal cancer: Where we stand and future perspectives

    OpenAIRE

    Valle, Laura

    2014-01-01

    The development of colorectal cancer (CRC) can be influenced by genetic factors in both familial cases and sporadic cases. Familial CRC has been associated with genetic changes in high-, moderate- and low-penetrance susceptibility genes. However, despite the availability of current gene-identification techniques, the genetic causes of a considerable proportion of hereditary cases remain unknown. Genome-wide association studies of CRC have identified a number of common low-penetrance alleles a...

  6. Development of genetic testing for breast, ovarian and colorectal cancer predisposition: a step closer to targeted cancer prevention.

    Science.gov (United States)

    Eccles, D M

    2011-12-01

    Individuals who inherit a high penetrance cancer susceptibility gene represent a population in which cancer diagnoses occur at younger ages and much more frequently than in the general population. Screening regimens aimed at early detection of cancer may reduce cancer mortality but in order to reduce cancer incidence, surgery and medical therapies have been advocated. In high genetic risk patients, either surgical or medical intervention may provide long term protection against cancer and at young ages co-morbidities will be low. The use of genetic testing for high risk predisposition genes to refine risk estimates and inform choices about cancer prevention is now readily available in many countries and routinely used to target cancer prevention strategies. Surgical approaches to cancer prevention are currently the mainstay in many conditions where a high risk is identified but medical prevention strategies also have demonstrated some efficacy in lowering cancer risk. Using the genetic status of an individual to target cancer treatment and prevent recurrence is increasingly gaining momentum as clinical trials involving known high risk gene carriers are now being conducted using both established cytotoxic drugs and novel targeted agents. Translation of new mechanistic insights into beneficial clinical care strategies requires more research. Robust evidence supporting medical approaches to cancer prevention in particular will require well designed large international collaborative clinical trials.

  7. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation.

    Science.gov (United States)

    Postema, Floor A M; Hopman, Saskia M J; Aalfs, Cora M; Berger, Lieke P V; Bleeker, Fonnet E; Dommering, Charlotte J; Jongmans, Marjolijn C J; Letteboer, Tom G W; Olderode-Berends, Maran J W; Wagner, Anja; Hennekam, Raoul C; Merks, Johannes H M

    2017-07-01

    Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a child for genetic consultation. We performed a PubMed search to review the incidence of TPSs in children for 85 tumour types listed in the International Classification of Childhood Cancer third edition (ICCC-3). The results were discussed during a national consensus meeting with representative clinical geneticists from all six academic paediatric oncology centres in The Netherlands. A TPS incidence of 5% or more was considered a high probability and therefore in itself a reason for referral to a clinical geneticist. The literature search resulted in data on the incidence of a TPS in 26 tumours. For 23/26 tumour types, a TPS incidence of 5% or higher was reported. In addition, during the consensus meeting the experts agreed that children with any carcinoma should always be referred for clinical genetic consultation as well, as it may point to a TPS. We present an overview of 23 paediatric tumours with a high probability of a TPS; this will facilitate paediatric oncologists to decide which patients should be referred for genetic consultation merely based on type of tumour. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genetic mapping of a third Li-Fraumeni syndrome predisposition locus to human chromosome 1q23.

    Science.gov (United States)

    Bachinski, Linda L; Olufemi, Shodimu-Emmanuel; Zhou, Xiaojun; Wu, Chih-Chieh; Yip, Linwah; Shete, Sanjay; Lozano, Guillermina; Amos, Christopher I; Strong, Louise C; Krahe, Ralf

    2005-01-15

    Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous inherited cancer syndrome. Most cases ( approximately 70%) identified and characterized to date are associated with dominantly inherited germ line mutations in the tumor suppressor gene TP53 (p53) in chromosome 17p13.1. In a subset of non-p53 patients with LFS, CHEK2 in chromosome 22q11 has been identified as another predisposing locus. Studying a series of non-p53 LFS kindred, we have shown that there is additional genetic heterogeneity in LFS kindred with inherited predisposition at loci other than p53 or CHEK2. Using a genome-wide scan for linkage with complementing parametric and nonparametric analysis methods, we identified linkage to a region of approximately 4 cM in chromosome 1q23, a genomic region not previously implicated in this disease. Identification ofa third predisposing gene and its underlying mutation(s) should provide insight into other genetic events that predispose to the genesis of the diverse tumor types associated with LFS and its variants.

  9. Prenatal Methylmercury Exposure and Genetic Predisposition to Cognitive Deficit at Age 8 Years

    DEFF Research Database (Denmark)

    Julvez, Jordi; Smith, George Davey; Golding, Jean

    2013-01-01

    Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms.......Cognitive consequences at school age associated with prenatal methylmercury (MeHg) exposure may need to take into account nutritional and sociodemographic cofactors as well as relevant genetic polymorphisms....

  10. Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

    Science.gov (United States)

    Cénit, María Carmen; Márquez, Ana; Cordero-Coma, Miguel; Fonollosa, Alejandro; Adán, Alfredo; Martínez-Berriotxoa, Agustín; Llorenç, Victor; Díaz Valle, David; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; García Serrano, José Luis; de Ramón, Enrique; del Rio, María José; Begoña Gorroño-Echebarría, Marina; Martín-Villa, José Manuel; Ortego-Centeno, Norberto; Martín, Javier

    2013-05-15

    Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

  11. Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.

    Science.gov (United States)

    Du, Mengmeng; Prescott, Jennifer; Cornelis, Marilyn C; Hankinson, Susan E; Giovannucci, Edward; Kraft, Peter; De Vivo, Immaculata

    2013-01-01

    Although cross-sectional studies have linked higher body mass index (BMI) and type 2 diabetes (T2D) to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL). We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D. After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: -0.01; SE: 0.02; P = 0.52). Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: -0.006; SE: 0.02; P = 0.69). In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.

  12. Genetic predisposition to higher body mass index or type 2 diabetes and leukocyte telomere length in the Nurses' Health Study.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Although cross-sectional studies have linked higher body mass index (BMI and type 2 diabetes (T2D to shortened telomeres, whether these metabolic conditions play a causal role in telomere biology is unknown. We therefore examined whether genetic predisposition to higher BMI or T2D was associated with shortened leukocyte telomere length (LTL.We conducted an analysis of 3,968 women of European ancestry aged 43-70 years from the Nurses' Health Study, who were selected as cases or controls in genome-wide association studies and studies of telomeres and disease. Pre-diagnostic relative telomere length in peripheral blood leukocytes, collected in 1989-1990, was measured by quantitative PCR. We combined information from multiple risk variants by calculating genetic risk scores based on 32 polymorphisms near 32 loci for BMI, and 36 polymorphisms near 35 loci for T2D.After adjustment for age and case-control status, there was no association between the BMI genetic risk score and LTL (β per standard deviation increase: -0.01; SE: 0.02; P = 0.52. Similarly, the T2D genetic score was not associated with LTL (β per standard deviation increase: -0.006; SE: 0.02; P = 0.69.In this population of middle-aged and older women of European ancestry, those genetically predisposed to higher BMI or T2D did not possess shortened telomeres. Although we cannot exclude weak or modest effects, our findings do not support a causal relation of strong magnitude between these metabolic conditions and telomere dynamics.

  13. Genome sequencing of Ewing sarcoma patients reveals genetic predisposition | Center for Cancer Research

    Science.gov (United States)

    The largest and most comprehensive genomic analysis of individuals with Ewing sarcoma performed to date reveals that some patients are genetically predisposed to developing the cancer.  Learn more...

  14. Molecular autopsy of sudden unexplained deaths reveals genetic predispositions for cardiac diseases among young forensic cases.

    Science.gov (United States)

    Hellenthal, Nicole; Gaertner-Rommel, Anna; Klauke, Bärbel; Paluszkiewicz, Lech; Stuhr, Markus; Kerner, Thoralf; Farr, Martin; Püschel, Klaus; Milting, Hendrik

    2017-11-01

    Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (forensic department. We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers. The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice.

  15. Development of a communication protocol for telephone disclosure of genetic test results for cancer predisposition.

    Science.gov (United States)

    Patrick-Miller, Linda J; Egleston, Brian L; Fetzer, Dominique; Forman, Andrea; Bealin, Lisa; Rybak, Christina; Peterson, Candace; Corbman, Melanie; Albarracin, Julio; Stevens, Evelyn; Daly, Mary B; Bradbury, Angela R

    2014-10-29

    Dissemination of genetic testing for disease susceptibility, one application of "personalized medicine", holds the potential to empower patients and providers through informed risk reduction and prevention recommendations. Genetic testing has become a standard practice in cancer prevention for high-risk populations. Heightened consumer awareness of "cancer genes" and genes for other diseases (eg, cardiovascular and Alzheimer's disease), as well as the burgeoning availability of increasingly complex genomic tests (ie, multi-gene, whole-exome and -genome sequencing), has escalated interest in and demand for genetic risk assessment and the specialists who provide it. Increasing demand is expected to surpass access to genetic specialists. Thus, there is urgent need to develop effective and efficient models of delivery of genetic information that comparably balance the risks and benefits to the current standard of in-person communication. The aim of this pilot study was to develop and evaluate a theoretically grounded and rigorously developed protocol for telephone communication of BRCA1/2 (breast cancer) test results that might be generalizable to genetic testing for other hereditary cancer and noncancer syndromes. Stakeholder data, health communication literature, and our theoretical model grounded in Self-Regulation Theory of Health Behavior were used to develop a telephone communication protocol for the communication of BRCA1/2 genetic test results. Framework analysis of selected audiotapes of disclosure sessions and stakeholders' feedback were utilized to evaluate the efficacy and inform refinements to this protocol. Stakeholder feedback (n=86) and audiotapes (38%, 33/86) of telephone disclosures revealed perceived disadvantages and challenges including environmental factors (eg, non-private environment), patient-related factors (eg, low health literacy), testing-related factors (eg, additional testing needed), and communication factors (eg, no visual cues

  16. The heterogeneity of genetic predisposition to early-onset colorectal cancer

    NARCIS (Netherlands)

    Hahn, M.M.

    2016-01-01

    Colorectal cancer is one of the major causes of death in developed countries. There is a strong association between genetic factors and the risk of developing colorectal cancer. However, a large fraction of the expected heritability of colorectal cancer still remains unexplained (‘missing

  17. Functional and genetic predisposition to rhinovirus lower respiratory tract infections in prematurely born infants

    NARCIS (Netherlands)

    Drysdale, Simon B.; Alcazar, Mireia; Wilson, Theresa; Smith, Melvyn; Zuckerman, Mark; Hodemaekers, Hennie M.; Janssen, Riny; Bont, Louis; Johnston, Sebastian L.; Greenough, Anne

    2016-01-01

    Term born infants are predisposed to human rhinovirus (HRV) lower respiratory tract infections (LRTI) by reduced neonatal lung function and genetic susceptibility. Our aim was to investigate whether prematurely born infants were similarly predisposed to HRV LRTIs or any other viral LRTIs. Infants

  18. Genetic Addiction Risk Score (GARS): molecular neurogenetic evidence for predisposition to Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Demetrovics, Zsolt; Barh, Debmalya; Gold, Mark S

    2014-12-01

    We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined "Reward Deficiency Syndrome" (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.

  19. Genetic predisposition to breath-hold diving-induced hemoptysis: Preliminary study.

    OpenAIRE

    Cialoni, Danilo; Marabotti, Claudio C; Sponsiello, Nicola; Pieri, Massimo; Balestra, Costantino; Lucchini, Vittorio V; Marroni, Alessandro

    2015-01-01

    Breath-hold diving-induced hemoptysis (BH-DIH) has been reported in about 25% breath-hold divers (BHD) and is characterized by dyspnea, coughing, hemoptysis and chest pain. We investigated whether eNOS G894T, eNOS T786C and ACE insertion/deletion I/D genetic variants, are possible BH-DIH risk factors.

  20. Interactions between Gut Microbiota, Host Genetics and Diet Modulate the Predisposition to Obesity and Metabolic Syndrome.

    Science.gov (United States)

    Ussar, Siegfried; Griffin, Nicholas W; Bezy, Olivier; Fujisaka, Shiho; Vienberg, Sara; Softic, Samir; Deng, Luxue; Bry, Lynn; Gordon, Jeffrey I; Kahn, C Ronald

    2015-09-01

    Obesity, diabetes, and metabolic syndrome result from complex interactions between genetic and environmental factors, including the gut microbiota. To dissect these interactions, we utilized three commonly used inbred strains of mice-obesity/diabetes-prone C57Bl/6J mice, obesity/diabetes-resistant 129S1/SvImJ from Jackson Laboratory, and obesity-prone but diabetes-resistant 129S6/SvEvTac from Taconic-plus three derivative lines generated by breeding these strains in a new, common environment. Analysis of metabolic parameters and gut microbiota in all strains and their environmentally normalized derivatives revealed strong interactions between microbiota, diet, breeding site, and metabolic phenotype. Strain-dependent and strain-independent correlations were found between specific microbiota and phenotypes, some of which could be transferred to germ-free recipient animals by fecal transplantation. Environmental reprogramming of microbiota resulted in 129S6/SvEvTac becoming obesity resistant. Thus, development of obesity/metabolic syndrome is the result of interactions between gut microbiota, host genetics, and diet. In permissive genetic backgrounds, environmental reprograming of microbiota can ameliorate development of metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review.

    Science.gov (United States)

    Colobran, Roger; Giménez-Barcons, Mireia; Marín-Sánchez, Ana; Porta-Pardo, Eduard; Pujol-Borrell, Ricardo

    2016-08-01

    Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  2. Lung cancer, genetic predisposition and smoking: the Nordic Twin Study of Cancer

    DEFF Research Database (Denmark)

    Hjelmborg, Jacob v. B.; Korhonen, Tellervo; Holst, Klaus

    2017-01-01

    Background: We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. Methods: Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time....... The discordant pair analysis confirms that smoking causes lung cancer.......-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status. Results: During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant...

  3. Genetic predisposition to β-thalassemia and sickle cell anemia in Turkey: a molecular diagnostic approach.

    Science.gov (United States)

    Basak, A Nazli; Tuzmen, Sukru

    2011-01-01

    The thalassemia syndromes are a diverse group of inherited disorders that can be characterized according to their insufficient synthesis or absent production of one or more of the globin chains. They are classified in to α, β, γ, δβ, δ, and εγδβ thalassemias depending on the globin chain(s) affected. The β-thalassemias refer to that group of inherited hemoglobin disorders, which are characterized by a reduced synthesis (β(+)-thalassemia) or absence (β(0)-thalassemia) of beta globin (β-globin) chain production (1). Though known as single-gene disorders, hemoglobinopathies such as β-thalassemia and sickle cell anemia are far from being fully resolved in terms of cure, considering the less complex nature of the beta globin (β-globin) gene family compared to more complex multifactorial genetic disorders such as cancer. Currently, there are no definitive therapeutic options for patients with β-thalassemia and sickle cell anemia, and new insights into the pathogenesis of these devastating diseases are urgently needed. Here we address in detail the overall picture utilizing molecular diagnostic approaches that contribute to unraveling the population-specific mutational analysis of β-globin gene. We also present approaches for molecular diagnostic strategies that are applicable to β-thalassemia, sickle cell anemia, and other genetic disorders.

  4. Genetic predisposition to ischaemic stroke byRAGEandHMGB1gene variants in Chinese Han population.

    Science.gov (United States)

    Li, You; Zhu, Jing; Chen, Linfa; Hu, Weidong; Wang, Mengxu; Li, Shengnan; Gu, Xuefeng; Tao, Hua; Zhao, Bin; Ma, Guoda; Li, Keshen

    2017-11-21

    Emerging evidence suggests that the multiligand receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 protein (HMGB1) contribute to the pathophysiology of ischaemic stroke (IS). The present study aimed to investigate the association of RAGE and HMGB1 variants with the risk of IS. A total of 1,034 patients and 1,015 age- and sex-matched healthy controls were genotyped to detect five genetic variants of the RAGE gene and four genetic variants of the HMGB1 gene using the Multiplex SNaPshot assay. We found that the rs2070600 variant of RAGE was associated with an increased risk of IS (OR = 1.19, 95% CI: 1.02-1.38, P = 0.043), whereas the rs2249825 variant of HMGB1 was associated with a decreased risk of IS (OR = 0.83, 95% CI: 0.71-0.98, P = 0.041). Further stratification by IS subtypes revealed that the presence of the TT genotype of the RAGE rs2070600 variant confers a higher risk of the large artery atherosclerosis subtype of IS (P = 0.036). Moreover, patients with the variant T allele of the RAGE rs2070600 variant presented with reduced serum soluble RAGE production. Patients carrying the variant G allele of the HMGB1 rs2249825 variant exhibited significantly lower infarct volumes than those with the major CC genotype. These clues may help in the development of optimal personalized therapeutic approaches for IS patients.

  5. Genetic predisposition to pass the standard SICCT test for bovine tuberculosis in British cattle.

    Directory of Open Access Journals (Sweden)

    William Amos

    Full Text Available Bovine tuberculosis (bTB imposes an important financial burden on the British cattle industry, yet despite intense efforts to control its spread, incidence is currently rising. Surveillance for bTB is based on a skin test that measures an immunological response to tuberculin. Cattle that fail the test are classified as "reactors" and slaughtered. Recent studies have identified genetic markers associated with the reaction of cattle to the tuberculin test. At marker INRA111 a relatively common '22' genotype occurs significantly more frequently in non-reactor cattle. Here we test the possibility that the putative protective '22' genotype does not confer resistance but instead causes cattle that carry it to react less strongly to the prescribed test, and hence avoid slaughter, potentially even though they are infected. We show that, after controlling for age and breed, '22' cattle react less strongly to the immunological challenge and may therefore be less likely to be classified as a reactor. These results highlight the potential discrepancy between infection and test status and imply that the effectiveness of the test-and-slaughter policy may be being compromised by selection for cattle that are genetically predisposed to react less strongly to tuberculin.

  6. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

  7. Genetic predisposition to breath-hold diving-induced hemoptysis: Preliminary study.

    Science.gov (United States)

    Cialoni, Danilo; Marabotti, Claudio; Sponsiello, Nicola; Pieri, Massimo; Balestra, Costantino; Lucchini, Vittorio; Marroni, Alessandro

    2015-01-01

    Breath-hold diving-induced hemoptysis (BH-DIH) has been reported in about 25% breath-hold divers (BHD) and is characterized by dyspnea, coughing, hemoptysis and chest pain. We investigated whether eNOS G894T, eNOS T786C and ACE insertion/deletion I/D genetic variants, are possible BH-DIH risk factors. 108 experienced healthy instructor BHDs with the same minimum requirements (102 male, six female; mean age 43.90 ± 7.49) were studied. We looked for different eNOS G894T, eNOS T786C and ACE insertion/ deletion genetic variants between BH-DIH-positive and BH-DIH-negative subjects to identify the variants most frequently associated with BH-DIH. At least one BH-DIH episode was reported by 22.2% of subjects, while 77.7% never reported BH-DIH. The majority of BH-DIH-positive subjects showed eNOS G894T (p = 0.001) and eNOS-T786C (p = 0.001) genotype "TT" (high-risk profile). Prevalence of BH-DIH was higher in subjects with eNOS G894T TT genotype (50%) than in subjects with GT (9.5%, p < 0.001) and GG (24%, (p = 0.0002) genotype (low-risk profile). Similar results were observed for eNOS T786C: BH-DIH prevalence was higher in the TT genotype (41.2%) group than in the CT (15.4%, p < 0.001) and CC genotype (9.1%, p < 0.001) groups. BH-DIH prevalence was significantly higher in subjects showing ACE ID genotype (34.5%) than II (0%, p < 0.001) and DD (10.5%, p = 0.0002). Of the ACE "II" genotype group, 100% never developed BH-DIH. eNOS-G894T, eNOS-T786C and ACE influence NO availability and regulation of peripheral vascular tone and blood flow. Different genetic variants of eNOS-G894T, eNOS-T786C and ACE appear significantly related to the probability to develop BH-DIH (p < 0.001).

  8. Genetic predisposition to alcoholism, schizophrenia and Alzheimer’s disease with psychodiagnostic characteristics in russian population

    Directory of Open Access Journals (Sweden)

    A. V. Marusin

    2016-01-01

    Full Text Available The purpose of this paper is to identify genetic factors connected with personal features using the panel of 12 polymorphic markers associated with the risk of developing dementia in patients with Alzheimer’s disease, schizophrenia and alcoholism.Materials and methods. The correlation among quantitative traits of personality, temperament and character determined with Cattell’s (the Sixteen personality factor questionnaire (16PF, Leonhard-Schmieschek’s, Spielberger-Khanin’s, and Eysenck’s (IQ tests were analyzed with polymorphic variants of 12 genes involved in the development of severe mental disorders such as alcoholism, schizophrenia and Alzheimer’s disease. DNA samples of 150 students were genotyped using PCR-RPLF method. The data were processed by nonparametric statistical methods.Results. Interallelic nonrandom associations in paired combinations of GABRA2-PICALM, PICALMADCY3, CLU-CBX7 and CLU-ADCY3 polymorphisms were detected. This may indicate the adaptive selection influencing the maintenance of behavioral homeostasis in population. A number of statistically significant associations of genetic variation were found: CLU with perfectionism(Q3 of 16PF and the exaltation of the Leonhard’s tests, PICALM with tension (Q4 of 16PF and the imbalance of Leonhard’s tests, DISC1 with vigilance(L of 16PF, and exaltation, cyclothymia of Leonhard’s tests, ZNF804A with imbalance by Leonhard’s test, SLC6A4 with reasoning(B of 16PF test, ADCY3 with self-reliance(Q2 and extraversion(F2 of 16PF test, MIR9-2 emotional stability(C, liveliness(F, social boldness(H, extraversion(F2 of 16PF, and dysthymia, hyperthymia of Leonhard’s tests, with the personal anxiety of Spielberger-Khanin’s test, CBX7 with vigilance(L, warmth(A of 16PF test, SLC6A3 with IQ.Conclusion. These findings support the idea of overlapping genetic component in common mental and neurological disorders and variability of human cognitive and personality traits.

  9. Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

    Science.gov (United States)

    Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

    2009-01-01

    Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants

  10. Genetic Predisposition To Acquire a Polybasic Cleavage Site for Highly Pathogenic Avian Influenza Virus Hemagglutinin

    Directory of Open Access Journals (Sweden)

    Naganori Nao

    2017-02-01

    Full Text Available Highly pathogenic avian influenza viruses with H5 and H7 hemagglutinin (HA subtypes evolve from low-pathogenic precursors through the acquisition of multiple basic amino acid residues at the HA cleavage site. Although this mechanism has been observed to occur naturally only in these HA subtypes, little is known about the genetic basis for the acquisition of the polybasic HA cleavage site. Here we show that consecutive adenine residues and a stem-loop structure, which are frequently found in the viral RNA region encoding amino acids around the cleavage site of low-pathogenic H5 and H7 viruses isolated from waterfowl reservoirs, are important for nucleotide insertions into this RNA region. A reporter assay to detect nontemplated nucleotide insertions and deep-sequencing analysis of viral RNAs revealed that an increased number of adenine residues and enlarged stem-loop structure in the RNA region accelerated the multiple adenine and/or guanine insertions required to create codons for basic amino acids. Interestingly, nucleotide insertions associated with the HA cleavage site motif were not observed principally in the viral RNA of other subtypes tested (H1, H2, H3, and H4. Our findings suggest that the RNA editing-like activity is the key mechanism for nucleotide insertions, providing a clue as to why the acquisition of the polybasic HA cleavage site is restricted to the particular HA subtypes.

  11. TNF-α Genetic Predisposition and Higher Expression of Inflammatory Pathway Components in Keratoconus.

    Science.gov (United States)

    Arbab, Muneeza; Tahir, Saira; Niazi, Muhammad Khizar; Ishaq, Mazhar; Hussain, Alamdar; Siddique, Pir Muhammad; Saeed, Sadia; Khan, Wajid Ali; Qamar, Raheel; Butt, Azeem Mehmood; Azam, Maleeha

    2017-07-01

    To date keratoconus (KC) pathogenesis is undefined; however, the involvement of inflammatory pathways in disease development is becoming apparent. In the present study, we investigated the role of a promoter region polymorphism rs1800629 (-308G>A) in the inflammatory pathway component TNF-α and its effects on the expression of TNF-α and downstream molecules tumor necrosis factor receptor 1 and 2 (TNFR1 and TNFR2), v-rel avian reticuloendotheliosis viral oncogene homolog A (RELA), and interleukin 6 (IL-6) in KC development. TNF-α promoter polymorphism rs1800629 (-308G>A), was genotyped in 257 sporadic KC patients and 253 healthy controls. Enzyme-linked immunosorbent assay (ELISA) was performed to assess for the -308G>A genotypes. Quantitative polymerase chain reaction (qPCR) was carried out to compare the mRNA expression of TNF-α, TNFR1, TNFR2, RELA, and IL6 in the corneal tissues of 20 KC patients and 20 donor controls. The -308G>A genotype GA was found to be significantly associated with KC development (dominant model [odds ratio (OR) = 6.67 (95% confidence interval [CI] = 4.28-10.42), P A polymorphism is a significant genetic risk factor for the pathogenesis of KC. Moreover, this single nucleotide polymorphism (SNP) was observed to be associated with deregulated expression of downstream molecules, thus further reinforcing the role of the inflammatory pathway components in the development of KC.

  12. Genetic predisposition, parity, age at first childbirth and risk for breast cancer.

    Science.gov (United States)

    Butt, Salma; Harlid, Sophia; Borgquist, Signe; Ivarsson, Malin; Landberg, Göran; Dillner, Joakim; Carlson, Joyce; Manjer, Jonas

    2012-08-07

    Recent studies have identified several single-nucleotide polymorphisms (SNPs) associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. The Malmö Diet and Cancer Study (MDCS) included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR) with 95% confidence intervals (CI). Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2), rs3803662 (TNRC9), rs12443621 (TNRC9), rs889312 (MAP3K1), rs3817198 (LSP1) and rs2107425 (H19). We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons. The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.

  13. Genetic predisposition, parity, age at first childbirth and risk for breast cancer

    Directory of Open Access Journals (Sweden)

    Butt Salma

    2012-08-01

    Full Text Available Abstract Background Recent studies have identified several single-nucleotide polymorphisms (SNPs associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk. Methods The Malmö Diet and Cancer Study (MDCS included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR with 95% confidence intervals (CI. Results Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2, rs3803662 (TNRC9, rs12443621 (TNRC9, rs889312 (MAP3K1, rs3817198 (LSP1 and rs2107425 (H19. We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons. Conclusions The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.

  14. Genetic predisposition to adiposity is associated with increased objectively assessed sedentary time in young children

    DEFF Research Database (Denmark)

    Schnurr, Theresia Maria; Viitasalo, A; Eloranta, A-M

    2018-01-01

    effects of BMI on sedentary time, total physical activity, and moderate-to-vigorous physical activity (MVPA). In fixed effects meta-analyses, the GRS was associated with 0.05 SD/allele increase in sedentary time (P=0.019), but there was no significant association with total physical activity (beta=0.......011 SD/allele, P=0.58) or MVPA (beta=0.001 SD/allele, P=0.96), adjusting for age, sex, monitor wear-time and first three genome-wide principal components. In two-stage least squares regression analyses, each genetically instrumented one unit increase in BMI z-score increased sedentary time by 0.47 SD (P......=0.072). Childhood BMI may have a causal influence on sedentary time but not on total physical activity or MVPA in young children. Our results provide important insights into the regulation of movement behaviour in childhood.International Journal of Obesity accepted article preview online, 26...

  15. Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study.

    Science.gov (United States)

    Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang; Hewitt, Alex W; Wichmann, H-Erich; Yazar, Seyhan; Stambolian, Dwight; Bailey-Wilson, Joan E; Wojciechowski, Robert; Wang, Jie Jin; Mitchell, Paul; Mackey, David A; MacGregor, Stuart

    2016-01-01

    Myopia is the largest cause of uncorrected visual impairments globally and its recent dramatic increase in the population has made it a major public health problem. In observational studies, educational attainment has been consistently reported to be correlated to myopia. Nonetheless, correlation does not imply causation. Observational studies do not tell us if education causes myopia or if instead there are confounding factors underlying the association. In this work, we use a two-step least squares instrumental-variable (IV) approach to estimate the causal effect of education on refractive error, specifically myopia. We used the results from the educational attainment GWAS from the Social Science Genetic Association Consortium to define a polygenic risk score (PGRS) in three cohorts of late middle age and elderly Caucasian individuals (N = 5,649). In a meta-analysis of the three cohorts, using the PGRS as an IV, we estimated that each z-score increase in education (approximately 2 years of education) results in a reduction of 0.92 ± 0.29 diopters (P = 1.04 × 10(-3) ). Our estimate of the effect of education on myopia was higher (P = 0.01) than the observed estimate (0.25 ± 0.03 diopters reduction per education z-score [∼2 years] increase). This suggests that observational studies may actually underestimate the true effect. Our Mendelian Randomization (MR) analysis provides new evidence for a causal role of educational attainment on refractive error. © 2015 WILEY PERIODICALS, INC.

  16. The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease

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    Seoyoung Yoon

    2015-09-01

    Full Text Available Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer

  17. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

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    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  18. Environmental effect and genetic influence: a regional cancer predisposition survey in the Zonguldak region of Northwest Turkey

    Science.gov (United States)

    Kadir, Selahattin; Önen-Hall, A. Piril; Aydin, S. Nihal; Yakicier, Cengiz; Akarsu, Nurten; Tuncer, Murat

    2008-03-01

    The Cretaceous-Eocene volcano-sedimentary units of the Zonguldak region of the western Black Sea consist of subalkaline andesite and tuff, and sandstone dominated by smectite, kaolinite, accessory chlorite, illite, mordenite, and analcime associated with feldspar, quartz, opal-CT, amphibole, and calcite. Kaolinization, chloritization, sericitization, albitization, Fe-Ti-oxidation, and the presence of zeolite, epidote, and illite in andesitic rocks and tuffaceous materials developed as a result of the degradation of a glass shards matrix, enclosed feldspar, and clinopyroxene-type phenocrysts, due to alteration processes. The association of feldspar and glass with smectite and kaolinite, and the suborientation of feldspar-edged, subparallel kaolinite plates to fracture axes may exhibit an authigenic smectite or kaolinite. Increased alteration degree upward in which Al, Fe, and Ti are gained, and Si, Na, K, and Ca are depleted, is due to the alteration following possible diagenesis and hydrothermal activities. Micromorphologically, fibrous mordenite in the altered units and the presence of needle-type chrysotile in the residential buildings in which cancer cases lived were detected. In addition, the segregation pattern of cancer susceptibility in the region strongly suggested an environmental effect and a genetic influence on the increased cancer incidence in the region. The most likely diagnosis was Li-Fraumeni syndrome, which is one of the hereditary cancer predisposition syndromes; however, no mutations were observed in the p53 gene, which is the major cause of Li-Fraumeni syndrome. The micromorphology observed in the altered units in which cancer cases were detected may have a role in the expression of an unidentified gene, but does not explain alone the occurrence of cancer as a primary cause in the region.

  19. [Genetic-statistical analysis of multiple births in humans. I. Genetic analysis of predisposition to multiple birth].

    Science.gov (United States)

    Lil'in, E T; Gindilis, V M

    1976-01-01

    Genetico-statistical analysis was made to check various hypotheses of the tendency to multiple birth inheritance. The material involved was comprised of 115 MZ and 228 DZ twin families burdened by recurrent cases of multiple births in their genealogy. Test data included 516 single birth probands, 5 from which had twins among sibs; this results in p = 0,97% for the evaluation of population frequency of the "affected" couples having twins). Vienberg proband method was applied to check monogenous-autosomal model and Edward & Smith approximating formulae to check additive-polygenous model with liminal results (manifestation). It is shown: 1) that the degree of genetical determination of MZ and DZ twinning is approximately the same for both multiple birth types; H-61 and 53% respectively; 2) in MZ twinning both mother's and father's genotypes perform as multiple birth factors; H-76% for the group of mother's sisters and 64% for that of father's brothers; 3) in case of DZ twinning mother's genotype is much more valid as a multiple birth factor as compared to the father's one; H-68% for the group of mother's sisters and H-25% for father's brothers; 4) at least some genetical factors, involved in multiple birth determination, are common for MZ and DZ twins; the rate of DZ twinning (of different sexes) among sibs of parents of MZ twins is reliable and more than 5-fold increases that in common population. It is suggested that the contradiction of literary data on multiple birth genetics is due to unadequate methods in many early investigations: calculations have been carried out on the basis of twin birth rate, and not on the rate of "affected" (couples having twins); differential Veinberg's method has been used, which is adequate in populational analysis and is unsuitable for genealogical studies for the estimation of MZ and DZ twinning frequency; cases of "sporadic" multiple birth have not been excluded from summary family material. On the basis of the authors' and

  20. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A M; Hopman, Saskia M J; Aalfs, Cora M; Berger, Lieke P V; Bleeker, Fonnet E; Dommering, Charlotte J; Jongmans, Marjolijn C J|info:eu-repo/dai/nl/314344349; Letteboer, Tom G W|info:eu-repo/dai/nl/304815837; Olderode-Berends, Maran J W; Wagner, Anja; Hennekam, Raoul C; Merks, Johannes H M

    2017-01-01

    INTRODUCTION: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a

  1. Childhood tumours with a high probability of being part of a tumour predisposition syndrome; reason for referral for genetic consultation

    NARCIS (Netherlands)

    Postema, Floor A. M.; Hopman, Saskia M. J.; Aalfs, Cora M.; Berger, Lieke P. V.; Bleeker, Fonnet E.; Dommering, Charlotte J.; Jongmans, Marjolijn C. J.; Letteboer, Tom G. W.; Olderode - Berends, Maran J.W.; Wagner, Anja; Hennekam, Raoul C.; Merks, Johannes H. M.

    Introduction: Recognising a tumour predisposition syndrome (TPS) in childhood cancer patients is of major clinical relevance. The presence of a TPS may be suggested by the type of tumour in the child. We present an overview of 23 childhood tumours that in themselves should be a reason to refer a

  2. ANALYSIS OF ACE, ACTN3, ENOS, PPARG, PPARA, HIF-15, PPARGC1B GENE POLYMORPHISMS FOR DETERMINATION A GENETIC PREDISPOSITION TO A VARIETY OF SPORTS

    Directory of Open Access Journals (Sweden)

    S. B. Drozdovska

    2013-05-01

    Full Text Available To establishing the possibility of assessing genetic iinherited predisposition to various sports, the differences in the distribution of genotypes of the complex polymorphisms in groups of athletes, specializing in sports with different types of energy supply of muscular work were studied. The paper examined the DNA 332 persons, of which 110 athletes involved in speed- power sports, 85 - in endurance sports , 51 - in sports that require a combination of strength and endurance, 86 - with no experience regular exercise.

  3. Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study.

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    Shengxu Li

    2010-08-01

    Full Text Available We have previously shown that multiple genetic loci identified by genome-wide association studies (GWAS increase the susceptibility to obesity in a cumulative manner. It is, however, not known whether and to what extent this genetic susceptibility may be attenuated by a physically active lifestyle. We aimed to assess the influence of a physically active lifestyle on the genetic predisposition to obesity in a large population-based study.We genotyped 12 SNPs in obesity-susceptibility loci in a population-based sample of 20,430 individuals (aged 39-79 y from the European Prospective Investigation of Cancer (EPIC-Norfolk cohort with an average follow-up period of 3.6 y. A genetic predisposition score was calculated for each individual by adding the body mass index (BMI-increasing alleles across the 12 SNPs. Physical activity was assessed using a self-administered questionnaire. Linear and logistic regression models were used to examine main effects of the genetic predisposition score and its interaction with physical activity on BMI/obesity risk and BMI change over time, assuming an additive effect for each additional BMI-increasing allele carried. Each additional BMI-increasing allele was associated with 0.154 (standard error [SE] 0.012 kg/m(2 (p = 6.73 x 10(-37 increase in BMI (equivalent to 445 g in body weight for a person 1.70 m tall. This association was significantly (p(interaction = 0.005 more pronounced in inactive people (0.205 [SE 0.024] kg/m(2 [p = 3.62 x 10(-18; 592 g in weight] than in active people (0.131 [SE 0.014] kg/m(2 [p = 7.97 x 10(-21; 379 g in weight]. Similarly, each additional BMI-increasing allele increased the risk of obesity 1.116-fold (95% confidence interval [CI] 1.093-1.139, p = 3.37 x 10(-26 in the whole population, but significantly (p(interaction = 0.015 more in inactive individuals (odds ratio [OR] = 1.158 [95% CI 1.118-1.199; p = 1.93 x 10(-16] than in active individuals (OR = 1.095 (95% CI 1.068-1.123; p = 1

  4. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs.

    Science.gov (United States)

    Hülsmeyer, Velia-Isabel; Fischer, Andrea; Mandigers, Paul J J; DeRisio, Luisa; Berendt, Mette; Rusbridge, Clare; Bhatti, Sofie F M; Pakozdy, Akos; Patterson, Edward E; Platt, Simon; Packer, Rowena M A; Volk, Holger A

    2015-08-28

    Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted.

  5. The altruism of Dona Benigna in Benito Perez Galdós’s Misericordia Religious Morality, Cultural Predisposition or Genetic Inheritance

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    Adel Fartakh,

    2014-06-01

    Full Text Available In the novel Misericordia (2004 by Benito Perez Galdós there is a character, Doña Benigna, who has developed an altruistic behavior in favor of other characters. What is certain is that the origin of this cooperative behavior is unclear. We would think that it emanates either from an acquired moral religious education, or from a cultural predisposition or a genetic inheritance. The moral development of the individual is one of the foundations for the birth of man as free individual during this period of Spanish history. Benito Perez Galdós’s narrative raises a debate about the issue of morality as solidarity action in this critical period of Spain’s evolution.

  6. Genetic screening for the predisposition to venous thromboembolism: a cost-utility analysis of clinical practice in the Italian health care system.

    Science.gov (United States)

    Compagni, Amelia; Melegaro, Alessia; Tarricone, Rosanna

    2013-01-01

    In the Italian health care system, genetic tests for factor V Leiden and factor II are routinely prescribed to assess the predisposition to venous thromboembolism (VTE) of women who request oral contraception. With specific reference to two subpopulations of women already at risk (i.e., familial history or previous event of VTE), the study aimed to assess whether current screening practices in Italy are cost-effective. Two decisional models accrued costs and quality-adjusted life-years (QALY) annually from the perspective of the National Health Service. The two models were derived from a decision analysis exercise concerning testing practices and consequent prescribing behavior for oral contraception conducted with 250 Italian gynecologists. Health care costs were compiled on the basis of 10-year hospital discharge records and the activities of a thrombosis center. Whenever possible, input data were based on the Italian context; otherwise, the data were taken from the international literature. Current testing practices on women with a familial history of VTE generate an incremental cost-effectiveness ratio of €72,412/QALY, which is well above the acceptable threshold of cost-effectiveness of €40,000 to €50,000/QALY. In the case of women with a previous event of VTE, the most frequently used testing strategy is cost-ineffective and leads to an overall loss of QALY. This study represents the first attempt to conduct a cost-utility analysis of genetic screening practices for the predisposition to VTE in the Italian setting. The results indicate that there is an urgent need to better monitor the indications for which tests for factor V Leiden and factor II are prescribed. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

  7. Genetic Predisposition to Polycystic Ovary Syndrome, Postpartum Weight Reduction, and Glycemic Changes: A Longitudinal Study in Women With Prior Gestational Diabetes.

    Science.gov (United States)

    Wang, Tiange; Leng, Junhong; Li, Nan; Martins de Carvalho, Aline; Huang, Tao; Zheng, Yan; Li, Weiqin; Liu, Huikun; Wang, Leishen; Hu, Gang; Qi, Lu

    2015-12-01

    Polycystic ovary syndrome (PCOS) is a common condition in reproductive-aged women and a major female-specific risk factor of obesity, impaired glucose tolerance, and diabetes. We examined whether the genetic variation predisposing to PCOS affected glycemic changes in women with prior gestational diabetes mellitus (GDM) and whether such an effect was modified by changes in body adiposity, especially during and after pregnancy. This is a longitudinal study in Tianjin, China. We genotyped 7 genome-wide association study-identified PCOS single nucleotide polymorphisms and assessed gestational weight gain and changes in glycemic traits and weight at 1 to 5 years postpartum in 1133 women with prior GDM. The main outcome measure was postpartum glycemic changes. The PCOS genetic risk score significantly interacted with postpartum weight reduction on changes in fasting glucose and 2-h glucose (P for interaction = .032 and .007; respectively) after multivariable adjustment. In women with postpartum weight reduction of ≥ 5 kg/y, the genetic risk score was associated with decreased fasting and 2-h glucose, whereas an opposite genetic effect was found in women who lost less weight. The association between postpartum weight reduction and glycemic improvement was more significant among women with a higher genetic risk score. In a large cohort of Chinese women with a history of GDM, our data for the first time indicate that the genetic predisposition to PCOS may interact with postpartum weight reduction on long-term glycemic changes, emphasizing the importance of postpartum weight management in prevention of diabetes in this subgroup of women.

  8. Maternal care affects EEG properties of spike-wave seizures (including pre- and post ictal periods) in adult WAG/Rij rats with genetic predisposition to absence epilepsy.

    Science.gov (United States)

    Sitnikova, Evgenia; Rutskova, Elizaveta M; Raevsky, Vladimir V

    2016-10-01

    WAG/Rij rats have a genetic predisposition to absence epilepsy and develop spontaneous spike-wave discharges in EEG during late ontogenesis (SWD, EEG manifestation of absence epilepsy). Changes in an environment during early postnatal ontogenesis can influence the genetically predetermined absence epilepsy. Here we examined the effect of maternal environment during weaning period on the EEG manifestation of absence epilepsy in adulthood. Experiments were performed in the offspring of WAG/Rij and Wistar rats. The newborn pups were fostered to dams of the same (in-fostering) or another strain (cross-fostering). Age-matched control WAG/Rij and Wistar rats were reared by their biological mothers. Absence seizures were uncommon in Wistar and were not aggravated in both in- and cross-fostered groups. In WAG/Rij rats, fewer SWD were found in the cross-fostered as compared to the in-fostered group. The cross-fostered WAG/Rij rats showed higher percentage of short-lasting SWD with duration EEG at the beginning of SWD in the cross-fostered WAG/Rij rats was lower than in control (8.82 vs 9.25Hz), but it was higher in a period of 1.5s before and after SWD. It was concluded that a healthier maternal environment is able to alleviate genetically predetermined absence seizures in adulthood through changes in EEG rhythmic activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity--a prospective study of three independent cohorts.

    Science.gov (United States)

    Larsen, Sofus C; Angquist, Lars; Ahluwalia, Tarunveer Singh; Skaaby, Tea; Roswall, Nina; Tjønneland, Anne; Halkjær, Jytte; Overvad, Kim; Pedersen, Oluf; Hansen, Torben; Linneberg, Allan; Husemoen, Lise Lotte N; Toft, Ulla; Heitmann, Berit L; Sørensen, Thorkild I A

    2014-05-03

    Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC). A total of 7,569 participants' from MONICA, the Diet Cancer and Health study and the INTER99 study were included in the study. We combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC and WHR) with which the SNPs associate. Linear regression was used to examine the association between ascorbic acid intake and ΔBW or ΔWC. SNP-score × ascorbic acid interactions were examined by adding product terms to the models. We found no significant associations between dietary ascorbic acid and ∆BW or ∆WC. Regarding SNP-score × ascorbic acid interactions, each additional risk allele of the 14 WHR associated SNPs associated with a ∆WC of 0.039 cm/year (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake. However, the association to ∆WC only remained borderline significant after adjustment for ∆BW. In general, our study does not support an association between dietary ascorbic acid and ∆BW or ∆WC, but a diet with a high content of ascorbic acid may be weakly associated to higher WC gain among people who are genetically predisposed to a high WHR. However, given the quite limited association any public health relevance is questionable.

  10. Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity - a prospective study of three independent cohorts

    Science.gov (United States)

    2014-01-01

    Background Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity. Hence, we examined whether dietary ascorbic acid, possibly in interaction with the genetic predisposition to a high BMI, WC or waist-hip ratio adjusted for BMI (WHR), associates with subsequent annual changes in weight (∆BW) and waist circumference (∆WC). Methods A total of 7,569 participants’ from MONICA, the Diet Cancer and Health study and the INTER99 study were included in the study. We combined 50 obesity associated single nucleotide polymorphisms (SNPs) in four genetic scores: a score of all SNPs and a score for each of the traits (BMI, WC and WHR) with which the SNPs associate. Linear regression was used to examine the association between ascorbic acid intake and ΔBW or ΔWC. SNP-score × ascorbic acid interactions were examined by adding product terms to the models. Results We found no significant associations between dietary ascorbic acid and ∆BW or ∆WC. Regarding SNP-score × ascorbic acid interactions, each additional risk allele of the 14 WHR associated SNPs associated with a ∆WC of 0.039 cm/year (P = 0.02, 95% CI: 0.005 to 0.073) per 100 mg/day higher ascorbic acid intake. However, the association to ∆WC only remained borderline significant after adjustment for ∆BW. Conclusion In general, our study does not support an association between dietary ascorbic acid and ∆BW or ∆WC, but a diet with a high content of ascorbic acid may be weakly associated to higher WC gain among people who are genetically predisposed to a high WHR. However, given the quite limited association any public health relevance is questionable. PMID:24886192

  11. [Association of 16189 variant (T-->C transition) of mitochondrial DNA with genetic predisposition to type 2 diabetes in Chinese populations].

    Science.gov (United States)

    Ji, L; Gao, L; Han, X

    2001-06-25

    To assess the prevalence of 16189 variant (T-->C transition) of mitochondrial DNA in Chinese populations and to study the relation between mtDNA 16189 variant and insulin resistance and the role it plays in genetic predisposition to diabetes. PCR and RELP techniques were used to examine 383 unrelated type 2 diabetics and 151 non-diabetic controls selected by random sampling. (1) The prevalence of 16189 variant among type 2 diabetics was significantly higher than that among the controls. (2) The prevalence of 16189 variant was significantly higher among type 2 diabetics with maternal family history than among those without maternal family history. (3) In comparison with the type 2 diabetics without 16189 variant, those with 16189 variant showed higher fasting serum insulin level, decreased insulin sensitivity index, and higher Homa insulin resistance index. (4) In the control group, no significant difference in age, gender, body mass index, waist to hip ratio, serum lipid level, fasting plasma glucose level, fasting serum insulin level, insulin sensitivity index, and Homa insulin resistance index was found between those with 16189 variant and those without 16189 variant. 16189 variant of mitochondrial DNA is one of the genetic predisposing factors for type 2 diabetes mellitus in Chinese populations. It might interfere with the energy metabolism and the production of ATP, thus causing insulin resistance in peripheral tissues.

  12. The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-injuries

    NARCIS (Netherlands)

    Maciejewski, D.F.; Renteria, M.E.; Abdellaoui, A.; Medland, S.E.; Few, L.R.; Gordon, S.D.; Madden, P.A.F.; Montgomery, G.W.; Trull, T.J.; Heath, A.C.; Statham, D.J.; Martin, N.G.; Zietsch, B.P.; Verweij, K.J.H.

    2017-01-01

    Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of

  13. Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.

    Science.gov (United States)

    Aas, M; Melle, I; Bettella, F; Djurovic, S; Le Hellard, S; Bjella, T; Ringen, P A; Lagerberg, T V; Smeland, O B; Agartz, I; Andreassen, O A; Tesli, M

    2018-01-01

    Schizophrenia (SZ) and bipolar disorder (BD) are heritable, polygenic disorders with shared clinical and genetic components, suggesting a psychosis continuum. Cannabis use is a well-documented environmental risk factor in psychotic disorders. In the current study, we investigated the relationship between SZ genetic load and cannabis use before illness onset in SZ and BD spectrums. Since frequent early cannabis use (age cannabis weekly to daily in the period before first illness episode was compared with that of those who never or infrequently used cannabis. Patients with weekly to daily cannabis use before illness onset had the highest SZ-PGRS (p = 0.02, Cohen's d = 0.33). The largest difference was found between patients with daily or weekly cannabis use before illness onset cannabis (p = 0.003, Cohen's d = 0.42). Our study supports an association between high SZ-PGRS and frequent cannabis use before illness onset in psychosis continuum disorders.

  14. Barriers and Motivators for Referral of Patients with Suspected Lynch Syndrome to Cancer Genetic Services: A Qualitative Study

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    Yen Y. Tan

    2014-02-01

    Full Text Available This article explores the views of general practitioners and specialists on their referral of patients with suspected Lynch syndrome to cancer genetic services. Using a purposive maximum variation sampling strategy, we conducted semi-structured interviews face-to-face with 28 general practitioners and specialists in public or private hospitals and specialist clinics between March and August 2011. General practitioners and specialists were recruited in a major metropolitan area in Australia. Interview transcripts were reviewed by two independent researchers, and thematic analysis was performed using NVivo10 software. The main barriers and motivators identified were: (1 clinician-related (e.g., familiarity with Lynch syndrome and family history knowledge; (2 patient-related (e.g., patients’ interests and personal experience with cancer; and (3 organizational-related (e.g., access to services, guidelines and referral pathway. Referral of patients with suspected Lynch syndrome to cancer genetic services is motivated and hindered by a range of individual, interpersonal and organizational factors. In order to improve the care and quality of life of patients and family with suspected Lynch syndrome, further research is needed to develop supportive tools for clinicians.

  15. Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor. alpha. : Relevance to genetic predisposition to systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Jacob, C.O.; Fronek, Z.; Koo, M.; McDevitt, H.O. (Stanford Univ. School of Medicine, CA (USA)); Lewis, G.C. (Genentech Inc., San Francisco, CA (USA)); Hansen, J.A. (Fred Hutchinson Cancer Research Center, Seattle, WA (USA))

    1990-02-01

    The authors report on the production of tumor necrosis factor (TNF)-{alpha} and TNF-{beta} by mitogen-activated peripheral blood lymphocytes or enriched monocyte subpopulations from human leukocyte antigen (HLA)-typed healthy subjects. The results indicate that HLA-DR2- and DQw1-positive donors frequently exhibit low production of TNF-{alpha}, whereas DR3- and DR4-positive subjects show high levels of TNF-{alpha} production. No correlation between TNF-{alpha} levels and HLA-A, -B, and -C genotype was found. The relevance of this quantitative polymorphism to the genetic predisposition to lupus nephritis in systemic lupus erythematosus (SLE) patients was investigated. DR2, DQw1-positive SLE patients show low levels of TNF-{alpha} inducibility; this genotype is also associated with an increased incidence of lupus nephritis. DR3-positive SLE patients, on the other hand, are not predisposed to nephritis, and these patients have high TNF-{alpha} production. DR4 haplotype is associated with high TNF-{alpha} inducibility and is negatively correlated with lupus nephritis. These data may help explain the strong association between HLA-DR2, DQw1 in SLE patients and their susceptibility to nephritis.

  16. Association among genetic predisposition, gut microbiota, and host immune response in the etiopathogenesis of inflammatory bowel disease.

    Science.gov (United States)

    Basso, P J; Fonseca, M T C; Bonfá, G; Alves, V B F; Sales-Campos, H; Nardini, V; Cardoso, C R B

    2014-09-01

    Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a chronic disorder that affects thousands of people around the world. These diseases are characterized by exacerbated uncontrolled intestinal inflammation that leads to poor quality of life in affected patients. Although the exact cause of IBD still remains unknown, compelling evidence suggests that the interplay among immune deregulation, environmental factors, and genetic polymorphisms contributes to the multifactorial nature of the disease. Therefore, in this review we present classical and novel findings regarding IBD etiopathogenesis. Considering the genetic causes of the diseases, alterations in about 100 genes or allelic variants, most of them in components of the immune system, have been related to IBD susceptibility. Dysbiosis of the intestinal microbiota also plays a role in the initiation or perpetuation of gut inflammation, which develops under altered or impaired immune responses. In this context, unbalanced innate and especially adaptive immunity has been considered one of the major contributing factors to IBD development, with the involvement of the Th1, Th2, and Th17 effector population in addition to impaired regulatory responses in CD or UC. Finally, an understanding of the interplay among pathogenic triggers of IBD will improve knowledge about the immunological mechanisms of gut inflammation, thus providing novel tools for IBD control.

  17. Genetic predisposition to fracture non-union: a case control study of a preliminary single nucleotide polymorphisms analysis of the BMP pathway

    Directory of Open Access Journals (Sweden)

    Giannoudis Peter V

    2011-02-01

    Full Text Available Abstract Background Despite the known multi-factorial nature of atrophic fracture non-unions, a possible genetic predisposition for the development of this complication after long bone fractures remains unknown. This pilot study aimed to address this issue by performing a preliminary SNP analysis of specific genes known to regulate fracture healing. Methods A total of fifteen SNPs within four genes of the Bone Morphogenetic Protein (BMP pathway (BMP-2, BMP-7, NOGGIN and SMAD6 were examined, in 109 randomly selected patients with long bone fractures as a result of motor vehicle accident, fall or direct blow. There were sixty-two patients with atrophic non-union and forty-seven patients (54 fractures with uneventful fracture union. Overall SNPs frequencies were computed with respect to patient's age, gender, smoking habits, fracture-associated parameters and the use of nonsteroidal anti-inflammatory drugs (NSAIDs, and tested for their association to the impaired bone healing process, using binary logistic regression (STATA 11.1; StataCorp, Texas USA. Results Statistical analysis revealed age to be an important covariate in the development of atrophic non-union (p = 0.01, OR 1.05 [per year], and two specific genotypes (G/G genotype of the rs1372857 SNP, located on NOGGIN and T/T genotype of the rs2053423 SNP, located on SMAD6 to be associated with a greater risk of fracture non-union (p = 0.02, OR 4.56 and p = 0.04, OR 10.27, respectively, after adjustment for age. Conclusions This is the first clinical study to investigate the potential existence of genetic susceptibility to fracture non-union. Even though no concrete conclusions can be obtained from this pilot study, our results indicate the existence of a potential genetically predetermined impairment within the BMP signalling cascade, initiated after a fracture and when combined with other risk factors could synergistically increase the susceptibility of a patient to develop non-union. Further

  18. Sleep characteristics modify the association of genetic predisposition with obesity and anthropometric measurements in 119,679 UK Biobank participants.

    Science.gov (United States)

    Celis-Morales, Carlos; Lyall, Donald M; Guo, Yibing; Steell, Lewis; Llanas, Daniel; Ward, Joey; Mackay, Daniel F; Biello, Stephany M; Bailey, Mark Es; Pell, Jill P; Gill, Jason Mr

    2017-04-01

    Background: Obesity is a multifactorial condition influenced by genetics, lifestyle, and environment. Objective: We investigated whether the association of a validated genetic profile risk score for obesity (GPRS-obesity) with body mass index (BMI) and waist circumference (WC) was modified by sleep characteristics. Design: This study included cross-sectional data from 119,859 white European adults, aged 37-73 y, participating in the UK Biobank. Interactions of GPRS-obesity and sleep characteristics (sleep duration, chronotype, day napping, and shift work) with their effects on BMI and WC were investigated. Results: β Values are expressed as the change in BMI (in kg/m 2 ) or WC per 1-SD increase in GPRS-obesity. The GPRS-obesity was associated with BMI (β: 0.57; 95% CI: 0.55, 0.60; P = 6.3 × 10 -207 ) and WC (1.21 cm; 95% CI: 1.15, 1.28 cm; P = 4.2 × 10 -289 ). There were significant interactions of GPRS-obesity and a variety of sleep characteristics with their relation with BMI ( P -interaction 9 h daily, the effect of GPRS-obesity on BMI was stronger (β: 0.60; 95% CI: 0.54, 0.65 and β: 0.73; 95% CI: 0.49, 0.97, respectively) than in normal-length sleepers (7-9 h; β: 0.52; 95% CI: 0.49, 0.55). A similar pattern was observed for shift workers (β: 0.68; 95% CI: 0.59, 0.77 compared with β: 0.54; 95% CI: 0.51, 0.58 for non-shift workers) and for night-shift workers (β: 0.69; 95% CI: 0.56, 0.82 compared with β: 0.55; 95% CI: 0.51, 0.58 for non-night-shift workers), for those taking naps during the day (β: 0.65; 95% CI: 0.52, 0.78 compared with β: 0.51; 95% CI: 0.48, 0.55 for those who never or rarely had naps), and for those with a self-reported evening chronotype (β: 0.72; 95% CI: 0.61, 0.82 compared with β: 0.52; 95% CI: 0.47, 0.57 for morning chronotype). Similar findings were obtained by using WC as the outcome. Conclusion: This study shows that the association between genetic risk for obesity and phenotypic adiposity measures is exacerbated by

  19. Improved prediction of genetic predisposition to psychiatric disorders using genomic feature best linear unbiased prediction models

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Demontis, Ditte; Børglum, Anders

    Introduction: Accurate prediction of unobserved phenotypes from observed genotypes is essential for the success in predicting disease risk from genotypes. However, the performance is somewhat limited. Genomic feature best linear unbiased prediction (GFBLUP) models separate the total genomic...... variance into components capturing the variance by a genomic feature (e.g. GO term) and the remaining genomic variance by differential weighting of the genetic variants within the two groups. Previously we have demonstrated (on pigs and fruit flies) increased predictive ability when the genomic feature...... is enriched for causal variants. Here we apply the GFBLUP model to a small schizophrenia case-control study to test the promise of this model on psychiatric disorders, and hypothesize that the performance will be increased when applying the model to a larger ADHD case-control study if the genomic feature...

  20. Genetic Predisposition to Multiple Myeloma at 5q15 Is Mediated by an ELL2 Enhancer Polymorphism

    Directory of Open Access Journals (Sweden)

    Ni Li

    2017-09-01

    Full Text Available Multiple myeloma (MM is a malignancy of plasma cells. Genome-wide association studies have shown that variation at 5q15 influences MM risk. Here, we have sought to decipher the causal variant at 5q15 and the mechanism by which it influences tumorigenesis. We show that rs6877329 G > C resides in a predicted enhancer element that physically interacts with the transcription start site of ELL2. The rs6877329-C risk allele is associated with reduced enhancer activity and lowered ELL2 expression. Since ELL2 is critical to the B cell differentiation process, reduced ELL2 expression is consistent with inherited genetic variation contributing to arrest of plasma cell development, facilitating MM clonal expansion. These data provide evidence for a biological mechanism underlying a hereditary risk of MM at 5q15.

  1. Genetic predisposition to lung adenocarcinoma among never-smoking Chinese with different epidermal growth factor receptor mutation status.

    Science.gov (United States)

    Han, Li; Lee, Cheuk-Kwong; Pang, Herbert; Chan, Hong-Tou; Lo, Iek-Long; Lam, Sze-Kwan; Cheong, Tak-Hong; Ho, James Chung-Man

    2017-12-01

    The inconsistent findings from genetic association studies may be related to the heterogeneity in different molecular subtypes of lung cancer. This study evaluated the predisposing single-nucleotide polymorphisms (SNPs) in epidermal growth factor receptor (EGFR) mutant and EGFR wild-type lung adenocarcinoma separately among never-smokers. This was a two-stage case-control study. Never-smokers with pathologically confirmed lung adenocarcinoma and healthy controls were recruited in Hong Kong and Macau. Genomic DNA was extracted and genotyped by MassARRAY. In the discovery stage, 51 SNPs were investigated at the SNP, gene and pathway level among 103 EGFR mutant and 78 EGFR wild-type lung adenocarcinoma cases compared with matched controls. In the validation stage, SNPs that were identified with significant lung cancer risk were replicated in a separate cohort of 84 lung adenocarcinoma cases and compared with 103 Chinese Han, Beijing and 105 Chinese Han, Southern public controls from the 1000 genome database. The genetic association of IL-6 rs2069840 with EGFR mutant lung adenocarcinoma was ascertained. In the discovery stage, haplotype GGG in three SNPs (rs2069840, rs2069852, rs2066992) of IL-6, synergetic effects of IL-6 rs2069840 and environmental tobacco smoke in the workplace were found to be related to EGFR mutant lung adenocarcinoma. ERCC2 rs238406 showed a marginally significant association with EGFR mutant lung adenocarcinoma in the validation stage (P=0.096). ERCC2 rs50871 and ATM rs611646 showed significant association with EGFR wild-type lung adenocarcinoma in the discovery stage. In conclusion, IL-6 rs2069840 conferred susceptibility to EGFR mutant lung adenocarcinoma in a Hong Kong and Macau never-smoking Chinese population. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Genetic predisposition to low bone mass is paralleled by an enhanced sensitivity to signals anabolic to the skeleton

    Science.gov (United States)

    Judex, Stefan; Donahue, Leah-Rae; Rubin, Clinton

    2002-01-01

    The structure of the adult skeleton is determined, in large part, by its genome. Whether genetic variations may influence the effectiveness of interventions to combat skeletal diseases remains unknown. The differential response of trabecular bone to an anabolic (low-level mechanical vibration) and a catabolic (disuse) mechanical stimulus were evaluated in three strains of adult mice. In low bone-mineral-density C57BL/6J mice, the low-level mechanical signal caused significantly larger bone formation rates (BFR) in the proximal tibia, but the removal of functional weight bearing did not significantly alter BFR. In mid-density BALB/cByJ mice, mechanical stimulation also increased BFR, whereas disuse significantly decreased BFR. In contrast, neither anabolic nor catabolic mechanical signals influenced any index of bone formation in high-density C3H/HeJ mice. Together, data from this study indicate that the sensitivity of trabecular tissue to both anabolic and catabolic stimuli is influenced by the genome. Extrapolated to humans, these results may explain in part why prophylaxes for low bone mass are not universally effective, yet also indicate that there may be a genotypic indication of people who are at reduced risk of suffering from bone loss.

  3. Sex differences in the blood antioxidant defense system in juvenile rats with various genetic predispositions to hypertension.

    Science.gov (United States)

    Horvathova, Martina; Zitnanova, Ingrid; Kralovicova, Zuzana; Balis, Peter; Puzserova, Angelika; Muchova, Jana; Kluknavsky, Michal; Durackova, Zdenka; Bernatova, Iveta

    2016-02-01

    This study investigated the contribution of blood oxidative stress (OS) to the development of hypertension, as well as sex differences in the antioxidant defense system (ADS) in genetic models of hypertension. Nine-week-old normotensive Wistar-Kyoto (WKY) rats, borderline hypertensive rats (BHR) and spontaneously hypertensive rats (SHR) of both sexes were used. Systolic blood pressure (SBP) was determined by tail-cuff plethysmography, the trolox equivalent antioxidant capacity (TEAC) and the concentration of lipid peroxides (LP) were determined in plasma. The activity of the antioxidant enzymes Cu/Zn-superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) was determined in erythrocytes. SBP was significantly elevated in BHR and SHR in both sexes. BHR and SHR males had a higher SBP than the respective females. Sex-dependent differences in the ADS were found only in SHR, in which TEAC, SOD and CAT were significantly higher in males than in females. No differences in TEAC, SOD, CAT and GPx were observed between BHR (males and females) and WKY controls. LP levels were similar in all the groups investigated. Significant positive correlations were observed between SBP and both SOD and CAT. TEAC correlated positively with SOD and LP. As no signs of oxidative damage to lipids were found in young BHR and SHR of either sex, OS in the blood does not seem to be causatively related to the development of hypertension in these rats. However, despite activated antioxidant defenses, the positive correlation between plasma TEAC and LP suggests that oxidative damage is progressing slowly and therefore it seems to be a consequence rather than the cause of hypertension.

  4. [Genetic analysis of TPO, DUOX2 and DUOXA2 genes in children with permanent congenital hypothyroidism suspected dyshormonogenesis].

    Science.gov (United States)

    Huang, Y L; Tan, M Y; Jiang, X; Li, B; Chen, Q Y; Jia, X F; Tang, C F; Liu, J L; Liu, L

    2017-03-02

    Objective: To explore the TPO, DUOX2 and DUOXA2 genotypes and phenotypes of children with permanent congenital hypothyroidism(PCH) suspected dyshormonogenesis in Guangzhou, identified and treated at Guangzhou Newborn Screening Center. Six of them were born between 2011 and 2012. Method: Retrospectively analyzed the clinical data of 9 children with PCH suspected dyshormonogenesis. Genetic analysis of TPO, DUOX2 and DUOXA2 genes were performed with Sanger sequencing. Result: Of the 9 patients, four were identified variants in TPO gene including three cases with biallelic variants and one case with monoallelic variant. Novel c. 1784G>C( p. R595T) variant in TPO was predicted to be damaging by SIFT and PolyPhen-2. Four patients harbored monoallelic known variants in DUOX2 gene and the other one harbored heterozygous known mutation c. 738C>G(p.Y246X) in DUOXA2 gene.Two adolescent patients with biallelic variants in TPO gene showed classical PCH phenotypes with thyroid goiter or nodules. The six patients with monoallelic variant in TPO, DUOX2 or DUOXA2 presented variable phenotypes. Among the 433 578 newborns in the 2011-2012 cohort, there were 156 cases of CH. Six of these cases were PCH suspected dyshormonogenesis, among which 1 case was confirmed TPO biallelic variants and 5 cases were monoallelic variants of TPO, DUOX2, or DUOXA2 genes. Conclusion: TPO and DUOX2 variants are the common molecular pathogenesis in children with PCH suspected dyshormonogenesis. Monoallelic variants in TPO, DUOX2 or DUOXA2 are associated with PCH and showed wide variability in their phenotypes. The novel variant p. R595T in TPO is probably a pathologic variant. The prevalence of PCH caused by TPO gene defects is rare in Guangzhou.

  5. Drug resistance and associated genetic mutations among patients with suspected MDR-TB in Uttar Pradesh, India.

    Science.gov (United States)

    Jain, A; Singh, P K; Chooramani, G; Dixit, P; Malhotra, H S

    2016-07-01

    Programmatic Management of Drug-Resistant Tuberculosis (PMDT) programme in 32 districts of Uttar Pradesh (UP), India. To provide epidemiological status of multidrug-resistant tuberculosis (MDR-TB) and associated microbial genetic mutations among suspected cases in UP. We retrospectively studied and tested using line-probe assay (LPA) 4895 retreatment patients with suspected MDR-TB who were enrolled for PMDT during 2012-2015. The demographic characteristics of cases, LPA-determined drug resistance, the genetic mutation profile, trends in drug resistance over the study period as well as the comparative performance of LPA and phenotypic drug susceptibility testing (DST) were analysed. MDR-TB and rifampicin-resistant TB (RR-TB) were confirmed in respectively 34.5% and 40.3% cases. The RR-TB detection rate (a valid proxy for MDR-TB) initially declined during the study period. Age ⩿30 years and implemented MDR-TB suspicion criteria were independent predictors for RR-TB (P 94.0% agreement with phenotypic DST in determining rifampicin/isoniazid resistance. MDR-TB prevalence in retreatment cases is very high, highlighting the need to reduce the development and transmission of drug-resistant TB.

  6. [Genetic analysis of the structure of predisposition to diabetes mellitus. III. Genetic heterogeneity of diabetes mellitus with different ages of onset].

    Science.gov (United States)

    Sergeev, A S; Kerimi, N B; Mazovetskiĭ, A G; Kuraeva, T L

    1986-02-01

    The results of genetical-epidemiological analysis of the three conventional forms of diabetes mellitus (DM) differentiated for age-at-onset are presented (the form I - from 0 to 29 y. the form II - from 30 to 59 y. the form III - 60 y. and older). The estimates of heritability of liability to the forms I, II and III of DM were 0.57, 0.70 and 0.65, respectively. It was shown that genetic components of the forms I and II are virtually different: genetic correlation between these forms was rA = 0.216 +/- 0.203, which is statistically insignificant. These data support the hypothesis assuming genetic independence of juvenile and adult forms of DM. On the other hand, the forms II and III were found to have an essential number of genes in common: genetic correlation was rA = 0.495 +/- 0.134, being significant at the 5% level. Thus, the forms II and III of DM are not to be considered as two genetically distinct diseases. The low recurrence risks of the form I for siblings (not more than 3.6%) allow to reject the hypothesis of simple monogenic inheritance of juvenile DM and to propose multifactorial nature of the disease.

  7. Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study.

    Directory of Open Access Journals (Sweden)

    Oliver van Hecke

    ]. Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71], angina predicted chronic pain in the other (OR 2·19 [1·63-2·95], and depression, angina (OR 1·98 [1·49-2·65]. Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]; angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95] and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]. In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01. Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23].We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.

  8. Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.

    Science.gov (United States)

    Stratton, Kelly L; Alanee, Shaheen; Glogowski, Emily A; Schrader, Kasmintan A; Rau-Murthy, Rohini; Klein, Robert; Russo, Paul; Coleman, Jonathan; Offit, Kenneth

    2016-05-01

    To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was 5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data

  9. A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

    Science.gov (United States)

    Hampel, Heather; Bennett, Robin L; Buchanan, Adam; Pearlman, Rachel; Wiesner, Georgia L

    2015-01-01

    The practice guidelines of the American College of Medical Genetics and Genomics (ACMG) and the National Society of Genetic Counselors (NSGC) are developed by members of the ACMG and NSGC to assist medical geneticists, genetic counselors, and other health-care providers in making decisions about appropriate management of genetic concerns, including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the ACMG and NSGC joint practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are current only as of their publication date, and are subject to change without notice as advances emerge. In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments, and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health-care provider's best medical judgment based on the clinical circumstances of a particular patient or patient population. Practice guidelines are published by the ACMG or the NSGC for educational and informational purposes only, and neither the ACMG nor the NSGC "approve" or "endorse" any specific methods, practices, or sources of information.Cancer genetic consultation is an important aspect of the care of individuals at increased risk of a hereditary cancer syndrome. Yet several patient, clinician, and system-level barriers hinder identification of individuals appropriate for cancer genetics

  10. Genetic predisposition to coronary heart disease and stroke using an additive genetic risk score: a population-based study in Greece

    Science.gov (United States)

    Objective: To determine the extent to which the risk for incident coronary heart disease (CHD) increases in relation to a genetic risk score (GRS) that additively integrates the influence of high-risk alleles in nine documented single nucleotide polymorphisms (SNPs) for CHD, and to examine whether t...

  11. Ethical issues in the evaluation of adults with suspected genetic neuromuscular disorders.

    Science.gov (United States)

    Su, Xiaowei; Kang, Peter B; Russell, James A; Simmons, Zachary

    2016-12-01

    Genetic testing is rapidly becoming an increasingly significant part of the diagnostic armamentarium of neuromuscular clinicians. Although technically easy to order, the results of such testing, whether positive or negative, have potentially enormous consequences for the individual tested and for family members. As a result, ethical considerations must be in the forefront of the physician's agenda when obtaining genetic testing. Informed consent is an important starting point for discussions between physicians and patients, but the counseling embedded in the informed consent process must be an ongoing part of subsequent interactions, including return of results and follow-up. Patient autonomy, including the right to know and right not-to-know results, must be respected. Considerations of capacity, physician beneficence and nonmaleficence, and privacy all play roles in the process. Muscle Nerve 54: 997-1006, 2016. © 2016 Wiley Periodicals, Inc.

  12. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs

    NARCIS (Netherlands)

    Hülsmeyer, Velia-Isabel; Fischer, Andrea; Mandigers, Paul J J; DeRisio, Luisa; Berendt, Mette; Rusbridge, Clare; Bhatti, Sofie F M; Pakozdy, Akos; Patterson, Edward E; Platt, Simon; Packer, Rowena M A; Volk, Holger A

    2015-01-01

    Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in

  13. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs

    OpenAIRE

    Hülsmeyer, V I; A. Fischer; Mandigers, P.J.J.; De Risio, L.; Berendt, M.; Rusbridge, C; Bhatti, S F M; Pakozdy, A; Patterson, E E; Platt, S.; Packer, R M A; Volk, H. A.

    2015-01-01

    Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevale...

  14. Predisposition assessment modelling

    OpenAIRE

    Esteves, Nuno Jorge Nunes

    2014-01-01

    Dissertation submitted for obtaining the degree of Master in Environmental Engineering Over the last decades outbreaks of the bark beetle Ips typographus (L.) assumed a high importance in forestry due to the economic losses caused, amounting to 3 million m3 the volume of wood damaged in 2009 in Austria. In natural systems, such events result from a dynamic interaction among several factors, the integrated analysis of which can depict the predisposition level of a stand, or site, to I. typo...

  15. Inherited predisposition to chronic lymphocytic leukemia

    OpenAIRE

    Brown, Jennifer R.

    2008-01-01

    Inherited susceptibility to chronic lymphocytic leukemia (CLL) has been recognized for decades. Approximately 10% of individuals with CLL report a family history of CLL or a related lymphoproliferative disorder, and genetic predisposition is the best understood risk factor for CLL. Studies of familial CLL have suggested that the disease features are largely similar to sporadic CLL, although recent data suggest that familial CLL may more commonly show somatic hypermutation of the immunoglobuli...

  16. Contribution of KIR genes, HLA class I ligands, and KIR/HLA class I ligand combinations on the genetic predisposition to celiac disease and coexisting celiac disease and type 1 diabetes mellitus.

    Science.gov (United States)

    Akar, H Haluk; Patiroglu, Turkan; Sevinc, Eylem; Aslan, Duran; Okdemir, Deniz; Kurtoglu, Selim

    2015-09-01

    There are some common genetic features between celiac disease (CD) and diabetes mellitus type 1 (DM). However, the genetic risk factors have not been fully clarified for CD and the co-occurrence of CD and DM. KIR (killer immunoglobulin-like receptor) genes regulate the cytolitic activity of NK-cells and T lymphocytes. The aim of this study is to evaluate the contribution of KIR genes, KIR ligands, and combinations of KIR/ KIR ligands on the genetic predisposition to CD and co-occurrence of CD and DM. Forty six patients with CD (n = 46), 20 patients with CD+DM (n = 20), and 60 healthy controls (n = 60) were included in this study. KIR genes and KIR ligands were investigated with PCR-SSOP and PCR-SSP in all subjects, respectively. This study showed that while the telomeric KIR genes (2DS5 and 3DS1), and combinations of 3DS1+HLA-BBw4-Thrand 3DS1+HLA-BBw4-Iso- (p genes, C1 ligand, and combinations of 3DS1+HLA-BBw4-Thr- and 3DS1+HLA-BBw4-Iso- (p = 0.002, p = 0.004, p = 0.036, p genes, KIR ligands, and KIR/KIR ligand interactions may be responsible for a predisposition to CD and the coexistence of CD and DM. For development of coexisting CD and DM, the 2DS5 and 3DS1 genes, C1 ligand, and combinations of 3DS1+HLA-BBw4-Thr- and 3DS1+HLA-BBw4-Iso- were found to be risk factors.

  17. Predisposition testing for breast and ovarian cancer susceptibility.

    Science.gov (United States)

    Calzone, K A

    1997-05-01

    To provide an overview of breast cancer predisposition syndromes and the breast and Ovarian cancer susceptibility genes identified to date. To describe the clinical implications of genetic testing for breast and ovarian cancer susceptibility. Published research and educational manuscripts, books, conference proceedings, and personal experiences. Nurses must become knowledgeable of predisposition genetic testing for inherited breast cancer risk including: understanding of the gene being analyzed and associated cancer risks, indications for testing, the limitations of the test, the management options for mutation carriers, risks and benefits of testing, and the long-term psychosocial sequelae. Predisposition testing for alterations in breast cancer susceptibility genes is rapidly moving into the general oncology and primary care community where nurses will play a major role in the provision of genetic services. The role of nursing in cancer genetics includes practice and education, nursing research, and policy initiatives.

  18. Hereditary Predispositions to Myelodysplastic Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah A. Bannon

    2016-05-01

    Full Text Available Myelodysplastic syndromes (MDS are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA, dyskeratosis congenita (DC, Diamond–Blackfan anemia (DBA, and Shwachman–Diamond syndrome (SBS, hallmarked by clinically-recognizable phenotypes (e.g., radial ray anomalies in FA and significantly increased risks for MDS and/or acute myeloid leukemia (AML in the setting of bone marrow failure. However, additional families with multiple cases of MDS or AML have long been reported in the medical literature with little known regarding potential hereditary etiologies. Over the last decade, genomic investigation of such families has revealed multiple genes conferring inherited risks for MDS and/or AML as the primary malignancy, including RUNX1, ANKRD26, DDX41, ETV6, GATA2, and SRP72. As these syndromes are increasingly appreciated in even apparently de novo presentations of MDS, it is important for hematologists/oncologists to become familiar with these newly-described syndromes. Herein, we provide a review of familial MDS syndromes and practical aspects of management in patients with predisposition syndromes.

  19. International Szent-Györgyi Prize for Progress in Cancer Research: basic and translational research recognition : Mary-Claire King received the 2016 Prize for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer.

    Science.gov (United States)

    Hartmann, Hali; Zhao, Jie; Ba, Sujuan

    2017-11-21

    The Szent-Györgyi Prize for Progress in Cancer Research is a prestigious scientific award sponsored by the National Foundation for Cancer Research (NFCR)-a leading cancer research charitable organization in the United States that supports innovative cancer research globally with the ultimate goal to cure cancer. The coveted Szent-Györgyi Prize annually honors a scientist whose seminal discovery or body of work has resulted in, or led toward, notable contributions to cancer prevention, diagnosis, or treatment; and the discovery has had a high direct impact of saving people's lives. In addition, the prize promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. In 2016, NFCR's Szent-Györgyi Prize Selection Committee was unanimous in its decision to recognize an icon in human disease genetics, Dr. Mary-Claire King, for her pioneering research that demonstrated the first evidence of genetic predisposition to breast cancer. Her proof of existence of BRCA1 gene and its location has made genetic screening for breast and ovarian cancers possible, saving lives of many people who are at high risk with inherited BRCA1 mutations.

  20. Spooky Suspects

    Science.gov (United States)

    Pacifici, Lara

    2011-01-01

    This activity presents an option for covering biology content while engaging students in an investigation that highlights the spirit of Halloween. Students are engaged in the story line and have fun trying to solve the mystery kidnapping by using science skills to examine the evidence and eliminate some ghoulish suspects. (Contains 1 figure.)

  1. Additive influence of genetic predisposition and conventional risk factors in the incidence of coronary heart disease: a population-based study in Greece

    Science.gov (United States)

    An additive genetic risk score (GRS) for coronary heart disease (CHD) has previously been associated with incident CHD in the population-based Greek European Prospective Investigation into Cancer and nutrition (EPIC) cohort. In this study, we explore GRS-‘environment’ joint actions on CHD for severa...

  2. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition : a meta-analysis

    NARCIS (Netherlands)

    Jansen-van der Weide, Marijke C.; Greuter, Marcel J. W.; Jansen, Liesbeth; Oosterwijk, Jan C.; Pijnappel, Ruud M.; de Bock, Geertruida H.

    2010-01-01

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the

  3. Breed-Predispositions to Cancer in Pedigree Dogs

    OpenAIRE

    Dobson, Jane M.

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared ...

  4. Breed-Predispositions to Cancer in Pedigree Dogs

    OpenAIRE

    Dobson, Jane M.

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared...

  5. Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis.

    Directory of Open Access Journals (Sweden)

    Luca A Lotta

    2016-11-01

    Full Text Available Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question.Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p < 5 × 10-8. The strongest signal was 21 kb upstream of the PPM1K gene (beta in standard deviations [SDs] of leucine per allele = 0.08, p = 3.9 × 10-25, encoding an activator of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD responsible for the rate-limiting step in BCAA catabolism. In another analysis, in up to 47,877 cases of type 2 diabetes and 267,694 controls, a genetically predicted difference of 1 SD in amino acid level was associated with an odds ratio for type 2 diabetes of 1.44 (95% CI 1.26-1.65, p = 9.5 × 10-8 for isoleucine, 1.85 (95% CI 1.41-2.42, p = 7.3 × 10-6 for leucine, and 1.54 (95% CI 1.28-1.84, p = 4.2 × 10-6 for valine. Estimates were highly consistent with those from prospective observational studies of the association between BCAA levels and incident type 2 diabetes in a meta-analysis of 1,992 cases and 4,319 non-cases. Metabolome-wide association analyses of BCAA-raising alleles revealed high specificity to the BCAA pathway and an accumulation of metabolites upstream of branched-chain alpha-ketoacid oxidation, consistent with reduced BCKD activity. Limitations of this study are that, while the association of genetic variants appeared highly specific, the possibility of pleiotropic associations cannot be entirely excluded. Similar to other complex phenotypes, genetic scores used in the study captured a limited proportion of the heritability in BCAA levels. Therefore, it is possible that only some of the mechanisms that increase BCAA levels or affect BCAA metabolism are

  6. Breast cancer predisposition syndromes.

    Science.gov (United States)

    Hemel, Deborah; Domchek, Susan M

    2010-10-01

    A small, but important, percentage of breast cancer cases is caused by the inheritance of a single copy of a mutated gene. BRCA1 and BRCA2 are the genes most commonly associated with inherited breast cancer; however, mutations in TP53 and PTEN cause Li-Fraumeni syndrome and Cowden syndrome, respectively, both of which are associated with high lifetime risks of breast cancer. Advances in the field of breast cancer genetics have led to an improved understanding of detection and prevention strategies. More recently, strategies to target the underlying genetic defects in BRCA1- and BRCA2-associated breast and ovarian cancers are emerging and may have implications for certain types of sporadic breast cancer. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD)

    Science.gov (United States)

    BOUMA, G; OUDKERK POOL, M; CRUSIUS, J B A; SCHREUDER, G M TH; HELLEMANS, H P R; MEIJER, B U G A; KOSTENSE, P J; GIPHART, M J; MEUWISSEN, S G M; PEÑA, A S

    1997-01-01

    Family and epidemiological studies support a genetic susceptibility to UC and CD. Conflicting reports regarding associations between UC and HLA-DR2 and between CD and various HLA alleles have been published. The aim of this study was to determine whether molecularly defined HLA-DR genes are associated with these diseases in a Dutch group of patients. Fifty-nine unrelated Dutch UC patients and 89 CD patients were typed using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB1*15 allele was increased in UC patients compared with controls (42% versus 26% in controls; P= 0.006; odds ratio (OR) = 2.1), and was predominantly found in female patients (53% versus 24%; P= 0.001; OR = 3.5). The DRB1*15 allele was increased in UC patients having a positive family history (P= 0.01; OR = 5.8). Among the 16 patients who showed an increase in extent of disease during follow up, 10 were DRB1*15+ (P= 0.002; OR = 4.8). The frequency of the DRB1*13 allele was decreased in patients with UC (15% versus 28% in controls; P= 0.04; OR = 0.5). In CD, no association was observed between disease or particular clinical subgroups and any allele tested. The present study provides additional evidence for the genetic association between UC and HLA-DRB1*15, and supports recent findings that the susceptibility gene(s) for CD is not located in the HLA class II region. PMID:9218841

  8. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy.

    Science.gov (United States)

    Li, Yadi; Li, Jie; Jia, Xiaoyun; Xiao, Xueshan; Li, Shiqiang; Guo, Xiangming

    2017-01-01

    Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes) and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA) (m.3460G>A, m.11778G>A and m.14484T>C). All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3%) primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations), four at m.3460 (4/89, 4.5%) and nine at m.14484 (9/89, 10.1%). This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.

  9. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy.

    Directory of Open Access Journals (Sweden)

    Yadi Li

    Full Text Available Leber hereditary optic neuropathy (LHON and dominant optic atrophy (DOA, the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA (m.3460G>A, m.11778G>A and m.14484T>C. All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3% primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations, four at m.3460 (4/89, 4.5% and nine at m.14484 (9/89, 10.1%. This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.

  10. Exposure to low-dose radiation and the risk of breast cancer among women with a familial or genetic predisposition: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Jansen-van der Weide, Marijke C. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands); Greuter, Marcel J.W.; Pijnappel, Ruud M. [University Medical Center Groningen, University of Groningen, Department of Radiology, Hanzeplein 1, PO Box 30.001, Groningen (Netherlands); Jansen, Liesbeth [University Medical Center Groningen, University of Groningen, Department of Surgery, Groningen (Netherlands); Oosterwijk, Jan C. [University Medical Center Groningen, University of Groningen, Department of Clinical Genetics, Groningen (Netherlands); Bock, Geertruida H. de [University Medical Center Groningen, University of Groningen, Department of Epidemiology, Groningen (Netherlands)

    2010-11-15

    Women with familial or genetic aggregation of breast cancer are offered screening outside the population screening programme. However, the possible benefit of mammography screening could be reduced due to the risk of radiation-induced tumours. A systematic search was conducted addressing the question of how low-dose radiation exposure affects breast cancer risk among high-risk women. A systematic search was conducted for articles addressing breast cancer, mammography screening, radiation and high-risk women. Effects of low-dose radiation on breast cancer risk were presented in terms of pooled odds ratios (OR). Of 127 articles found, 7 were selected for the meta-analysis. Pooled OR revealed an increased risk of breast cancer among high-risk women due to low-dose radiation exposure (OR = 1.3, 95% CI: 0.9- 1.8). Exposure before age 20 (OR = 2.0, 95% CI: 1.3-3.1) or a mean of {>=}5 exposures (OR = 1.8, 95% CI: 1.1-3.0) was significantly associated with a higher radiation-induced breast cancer risk. Low-dose radiation increases breast cancer risk among high-risk women. When using low-dose radiation among high-risk women, a careful approach is needed, by means of reducing repeated exposure, avoidance of exposure at a younger age and using non-ionising screening techniques. (orig.)

  11. By the pricking of my thumbs, something wicked this way comes: sporadic cancers versus eponymous hereditary cancer predisposition syndromes.

    Science.gov (United States)

    Vaklavas, Christos; Ross, John R; Nabell, Lisle M; Forero, Andres; Heslin, Martin J; Wood, Tina E

    2012-01-01

    Advances in cancer genomics have led to the recognition of a growing number of high-penetrance single-gene cancer predisposition syndromes. Frequently, the suspicion for a hereditary syndrome is raised by a strongly positive family history. However, other features, such as younger-than-usual age at diagnosis and rare histology should also prompt consideration of a genetic syndrome. Common malignancies frequently show a positive family history without an eponymous syndrome being recognized. This article reports on a case with an unusual constellation of malignancies with distinctive pathologies, which raised suspicion for an eponymous cancer pre-disposition syndrome. Absent a positive family history, a de novo mutation-an alteration in a gene that is present for the first time in a family member as a result of a mutation in a germ cell of one of the parents or in the fertilized ovum-was suspected. The authors discuss indications for genetic counseling and testing, limitations, and the evidence that supports the recommendations as formulated by working groups and the NCCN. Most frequently, these recommendations are reasonable statements based on the natural history of the disease, but without population-based studies for many rare syndromes, the actual penetrance, variable expressivity, and actual associated cancer risk are unknown.

  12. A molecular genetic lab to generate inclusive and exclusive forensic evidence: two suspects, a victim, and a bloodstained T-shirt.

    Science.gov (United States)

    Smit, Julie; Heath, Daniel D; Walter, Ryan P

    2014-01-01

    Molecular genetic laboratory exercises can be ineffective due the student's lack of connection to the complex and sequential protocols. In this inquiry-based molecular genetic laboratory exercise, we harness students' fascination with human forensics and provide a real-life scenario using biomolecular techniques to identify "whose blood is on the t-shirt." We use fish blood to create realistic blood stains on clothing and challenge the students to use DNA analyses to clear or implicate suspects. Safety concerns are minimized through the use of fish blood, while maximizing both realism and the likelihood of student success due to fishes' nucleated red blood cells. The goal in designing this laboratory exercise was to create a feasible protocol for large (over 300 students) second year university courses. During two 3 hour laboratory sessions, students learn and apply clean/sterile technique, DNA extraction, polymerase chain reaction, restriction fragment length polymorphisms, and agarose gel electrophoresis. The students also learn to interpret the resulting gel bands in terms of inclusive or exclusive evidence. Students have consistently ranked this lab as their favorite of five taken as part of a second year Genetics course. Copyright © 2013 by The International Union of Biochemistry and Molecular Biology.

  13. Long-term effects of an inpatient weight-loss program in obese children and the role of genetic predisposition-rationale and design of the LOGIC-trial

    Directory of Open Access Journals (Sweden)

    Rank Melanie

    2012-03-01

    measured. Discussion Apart from illustrating the short, middle and long-term effects of an inpatient weight-loss program, this study will contribute to a better understanding of inter-individual differences in the regulation of body weight, taking into account the role of genetic predisposition and lifestyle factors. Trial Registration NCT01067157.

  14. Breed predisposition to canine gastric carcinoma

    DEFF Research Database (Denmark)

    Seim-Wikse, Tonje; Jörundsson, Einar; Nødtvedt, Ane

    2013-01-01

    Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The ai...... of the study was to retrospectively investigate the proportion and possible breed predisposition to canine gastric carcinoma using the Norwegian Canine Cancer Register for calculations of proportional morbidity ratios (PMRs) for the period 1998-2009.......Previous research has indicated a breed predisposition to gastric carcinoma in dogs. However, results to date are inconsistent since several studies have failed to prove such a predisposition. Better knowledge of breeds at risk could facilitate early detection of gastric carcinoma in dogs. The aim...

  15. Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population.

    Science.gov (United States)

    Nissen, Peter H; Christensen, Signe E; Heickendorff, Lene; Brixen, Kim; Mosekilde, Leif

    2007-11-01

    The autosomal dominantly inherited condition familial hypocalciuric hypercalcemia (FHH) is characterized by elevated plasma calcium levels, relative or absolute hypocalciuria, and normal to moderately elevated plasma PTH. The condition is difficult to distinguish clinically from primary hyperparathyroidism and is caused by inactivating mutations in the calcium sensing receptor (CASR) gene. We sought to define the mutation spectrum of the CASR gene in a Danish FHH population and to establish genotype-phenotype relationships regarding the different mutations. A total of 213 subjects clinically suspected to have FHH, and 121 subjects enrolled as part of a family-screening program were studied. Genotype-phenotype relationships were established in 66 mutation-positive index patients and family members. We determined CASR gene mutations, and correlating levels of plasma calcium (albumin corrected), ionized calcium (pH 7.4), and PTH were measured. We identified 22 different mutations in 39 FHH families. We evaluated data on circulating calcium and PTH for 11 different mutations, representing a spectrum of clinical phenotypes, ranging from calcium concentrations moderately above the upper reference limit, to calcium levels more than 20% above the upper reference limit. Furthermore, the mean plasma PTH concentration was within the normal range in eight of 11 studied mutations, but mild to moderately elevated in families with the mutations p.C582Y, p.C582F, and p.G553R. The present data add 19 novel mutations to the catalog of inactivating CASR mutations and illustrate a variety of biochemical phenotypes in patients with the molecular genetic diagnosis FHH.

  16. The Impact of Familial Predisposition to Obesity and Cardiovascular Disease on Childhood Obesity

    Science.gov (United States)

    Nielsen, Louise Aas; Nielsen, Tenna Ruest Haarmark; Holm, Jens-Christian

    2015-01-01

    The prevalence of childhood obesity has reached alarming rates world-wide. The aetiology seems to be an interplay between genetic and environmental factors, and a surrogate measure of this complex interaction is suggested as familial predisposition. Familial predisposition to obesity and related cardiovascular disease (CVD) complications constitute the presence of obesity and/or obesity-related complications in primarily blood-related family members. The approaches of its measurement and applicability vary, and the evidence especially of its influence on obesity and obesity treatment in childhood is limited. Studies have linked a familial predisposition of obesity, CVD (hypertension, dyslipidaemia and thromboembolic events), and type 2 diabetes mellitus to BMI as well as other adiposity measures in children, suggesting degrees of familial aggregation of metabolic derangements. A pattern of predispositions arising from mothers, parents or grandparents as being most influential have been found, but further comprehensive studies are needed in order to specify the exact implications of familial predisposition. In the scope of childhood obesity this article reviews the current literature regarding familial predisposition to obesity and obesity-related complications, and how these familial predispositions may impact obesity in the offspring. PMID:26465142

  17. Breed-Predispositions to Cancer in Pedigree Dogs

    Science.gov (United States)

    Dobson, Jane M.

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies. PMID:23738139

  18. Breed-predispositions to cancer in pedigree dogs.

    Science.gov (United States)

    Dobson, Jane M

    2013-01-01

    Cancer is a common problem in dogs and although all breeds of dog and crossbred dogs may be affected, it is notable that some breeds of pedigree dogs appear to be at increased risk of certain types of cancer suggesting underlying genetic predisposition to cancer susceptibility. Although the aetiology of most cancers is likely to be multifactorial, the limited genetic diversity seen in purebred dogs facilitates genetic linkage or association studies on relatively small populations as compared to humans, and by using newly developed resources, genome-wide association studies in dog breeds are proving to be a powerful tool for unravelling complex disorders. This paper will review the literature on canine breed susceptibility to histiocytic sarcoma, osteosarcoma, haemangiosarcoma, mast cell tumours, lymphoma, melanoma, and mammary tumours including the recent advances in knowledge through molecular genetic, cytogenetic, and genome wide association studies.

  19. Molecular genetic analysis of the calcium sensing receptor gene in patients clinically suspected to have familial hypocalciuric hypercalcemia: phenotypic variation and mutation spectrum in a Danish population

    DEFF Research Database (Denmark)

    Nissen, Peter H; Christensen, Signe E; Heickendorff, Lene

    2007-01-01

    : A total of 213 subjects clinically suspected to have FHH, and 121 subjects enrolled as part of a family-screening program were studied. Genotype-phenotype relationships were established in 66 mutation-positive index patients and family members. MAIN OUTCOME MEASURES: We determined CASR gene mutations...

  20. Assessing Genetic Variants of Uncertain Significance: The Example of Lynch Syndrome

    DEFF Research Database (Denmark)

    Rasmussen, Lene Juel; Heinen, Christopher D.

    2014-01-01

    A significant fraction of cancer is the result of genetic predisposition. Frequently, in patients with suspected cancer predisposition, subtle variations are found in predisposing genes. Currently, it is often not possible to determine whether such variants are pathogenic, thus they are termed...... variants of uncertain significance (VUS). This leads to anxiety in carriers and noncarrying relatives alike, as well as to an unnecessary burden to preventive healthcare. The establishment of procedures that enable the diagnostic assessment of VUSs in individuals are discussed and hereditary colorectal...... cancer syndrome, Lynch syndrome, is used as an example. This challenge is addressed by illustrating the importance of combining genetic and functional data in future strategies to assess VUS. The proposed strategies combine clinical genetic, analytical, functional and in silico approaches....

  1. Hereditary Predispositions to Myelodysplastic Syndrome

    OpenAIRE

    Sarah A. Bannon; Courtney D. DiNardo

    2016-01-01

    Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dysker...

  2. Validation of a clinical screening instrument for tumour predisposition syndromes in patients with childhood cancer (TuPS): protocol for a prospective, observational, multicentre study.

    Science.gov (United States)

    Postema, Floor A M; Hopman, Saskia M J; de Borgie, Corianne A J M; Hammond, Peter; Hennekam, Raoul C; Merks, Johannes H M; Aalfs, Cora M; Anninga, Jakob K; Berger, Lieke Pv; Bleeker, Fonnet E; de Bont, Eveline Sjm; de Borgie, Corianne Ajm; Dommering, Charlotte J; van Eijkelenburg, Natasha Ka; Hammond, Peter; Hennekam, Raoul C; van den Heuvel-Eibrink, Marry M; Hopman, Saskia Mj; Jongmans, Marjolijn Cj; Kors, Wijnanda A; Letteboer, Tom Gw; Loeffen, Jan Lcm; Merks, Johannes Hm; Olderode-Berends, Maran Jw; Postema, Floor Am; Wagner, Anja

    2017-01-20

    Recognising a tumour predisposition syndrome (TPS) in patients with childhood cancer is of significant clinical relevance, as it affects treatment, prognosis and facilitates genetic counselling. Previous studies revealed that only half of the known TPSs are recognised during standard paediatric cancer care. In current medical practice it is impossible to refer every patient with childhood cancer to a clinical geneticist, due to limited capacity for routine genetic consultation. Therefore, we have developed a screening instrument to identify patients with childhood cancer with a high probability of having a TPS. The aim of this study is to validate the clinical screening instrument for TPS in patients with childhood cancer. This study is a prospective nationwide cohort study including all newly diagnosed patients with childhood cancer in the Netherlands. The screening instrument consists of a checklist, two- and three-dimensional photographic series of the patient. 2 independent clinical geneticists will assess the content of the screening instrument. If a TPS is suspected based on the instrument data and thus further evaluation is indicated, the patient will be invited for full genetic consultation. A negative control group consists of 20% of the patients in whom a TPS is not suspected based on the instrument; they will be randomly invited for full genetic consultation. Primary outcome measurement will be sensitivity of the instrument. The Medical Ethical Committee of the Academic Medical Centre stated that the Medical Research Involving Human Subjects Act does not apply to this study and that official approval of this study by the Committee was not required. The results will be offered for publication in peer-reviewed journals and presented at International Conferences on Oncology and Clinical Genetics. The clinical data gathered in this study will be available for all participating centres. NTR5605. Published by the BMJ Publishing Group Limited. For permission to

  3. American College of Medical Genetics and Genomics: standards and guidelines for documenting suspected consanguinity as an incidental finding of genomic testing.

    Science.gov (United States)

    Rehder, Catherine W; David, Karen L; Hirsch, Betsy; Toriello, Helga V; Wilson, Carolyn M; Kearney, Hutton M

    2013-02-01

    Genomic testing, including single-nucleotide polymorphism-based microarrays and whole-genome sequencing, can detect long stretches of the genome that display homozygosity. The presence of these segments, when distributed across multiple chromosomes, can indicate a familial relationship between the proband's parents. This article describes the detection of possible consanguinity by genomic testing and the factors confounding the inference of a specific p-arental relationship. It is designed to guide the documentation of suspected consanguinity by clinical laboratory professionals and to alert laboratories to the need to establish a reporting policy in conjunction with their ethics review committee and legal counsel.

  4. A Molecular Genetic Lab to Generate Inclusive and Exclusive Forensic Evidence: Two Suspects, a Victim, and a Bloodstained T-Shirt

    Science.gov (United States)

    Smit, Julie; Heath, Daniel D.; Walter, Ryan P.

    2014-01-01

    Molecular genetic laboratory exercises can be ineffective due the student's lack of connection to the complex and sequential protocols. In this inquiry-based molecular genetic laboratory exercise, we harness students' fascination with human forensics and provide a real-life scenario using biomolecular techniques to identify "whose…

  5. Suspected Lynch syndrome associated MSH6 variants: A functional assay to determine their pathogenicity.

    Directory of Open Access Journals (Sweden)

    Hellen Houlleberghs

    2017-05-01

    Full Text Available Lynch syndrome (LS is a hereditary cancer predisposition caused by inactivating mutations in DNA mismatch repair (MMR genes. Mutations in the MSH6 DNA MMR gene account for approximately 18% of LS cases. Many LS-associated sequence variants are nonsense and frameshift mutations that clearly abrogate MMR activity. However, missense mutations whose functional implications are unclear are also frequently seen in suspected-LS patients. To conclusively diagnose LS and enroll patients in appropriate surveillance programs to reduce morbidity as well as mortality, the functional consequences of these variants of uncertain clinical significance (VUS must be defined. We present an oligonucleotide-directed mutagenesis screen for the identification of pathogenic MSH6 VUS. In the screen, the MSH6 variant of interest is introduced into mouse embryonic stem cells by site-directed mutagenesis. Subsequent selection for MMR-deficient cells using the DNA damaging agent 6-thioguanine (6TG allows the identification of MMR abrogating VUS because solely MMR-deficient cells survive 6TG exposure. We demonstrate the efficacy of the genetic screen, investigate the phenotype of 26 MSH6 VUS and compare our screening results to clinical data from suspected-LS patients carrying these variant alleles.

  6. Familial Investigations of Childhood Cancer Predisposition

    Science.gov (United States)

    2018-01-03

    Acute Leukemia; Adenomatous Polyposis; Adrenocortical Carcinoma; AML; BAP1 Tumor Predisposition Syndrome; Carney Complex; Choroid Plexus Carcinoma; Constitutional Mismatch Repair Deficiency Syndrome; Diamond-Blackfan Anemia; DICER1 Syndrome; Dyskeratosis Congenita; Emberger Syndrome; Familial Acute Myeloid Leukemia; Familial Adenomatous Polyposis; Fanconi Anemia; Familial Cancer; Familial Wilms Tumor; Familial Neuroblastoma; GIST; Hereditary Breast and Ovarian Cancer; Hereditary Paraganglioma-Pheochromocytoma Syndrome; Hodgkin Lymphoma; Juvenile Polyposis; Li-Fraumeni Syndrome; Lynch Syndrome; MDS; Melanoma Syndrome; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2; Neuroblastoma; Neurofibromatosis Type 1; Neurofibromatosis Type II; Nevoid Basal Cell Carcinoma Syndrome; Non Hodgkin Lymphoma; Noonan Syndrome and Other Rasopathy; Overgrowth Syndromes; Pancreatic Cancer; Peutz-Jeghers Syndrome; Pheochromocytoma/Paraganglioma; PTEN Hamartoma Tumor Syndrome; Retinoblastoma; Rhabdoid Tumor Predisposition Syndrome; Rhabdomyosarcoma; Rothmund-Thomson Syndrome; Tuberous Sclerosis; Von Hippel-Lindau Disease

  7. Clinical Assessment and Diagnosis of Germline Predisposition to Hematopoietic Malignancies: The University of Chicago Experience

    Directory of Open Access Journals (Sweden)

    Ami V. Desai

    2017-12-01

    Full Text Available With the increasing use of clinical genomics to guide cancer treatment and management, there is a rise in the identification of germline cancer predisposition syndromes and a critical need for patients with germline findings to be referred for surveillance and care. The University of Chicago Hematopoietic Malignancies Cancer Risk Team has established a unique approach to patient care for individuals with hereditary hematologic malignancies through close communication and coordination between our pediatric and adult programs. Dedicated program members, including physicians, nurses, genetic counselors, and clinical research assistants, screen individuals for cancer predisposition at initial diagnosis through survivorship, in addition to testing individuals with an established family history of a cancer predisposition syndrome. Sample procurement, such as a skin biopsy at the time of bone marrow aspirate/biopsy in individuals with a positive screen, has facilitated timely identification of clinical germline findings or has served as a pipeline for translational research. Our integrated translational research program has led to the identification of novel syndromes in collaboration with other investigators, which have been incorporated iteratively into our clinical pipeline. Individuals are referred for clinical assessment based on personal and family history, identification of variants in susceptibility genes via molecular tumor testing, and during evaluation for matched related allogeneic stem cell transplantation. Upon referral, genetic counseling incorporates education with mindfulness of the psychosocial issues surrounding germline testing at different ages. The training and role of genetic counselors continues to grow, with the discovery of new predisposition syndromes, in the age of improved molecular diagnostics and new models for service delivery, such as telemedicine. With the identification of new syndromes that may predispose individuals

  8. Predisposición genética para el cáncer de mama: genes BRCA1 y BRCA2 Genetic predisposition for breast cancer: BRCA1 and BRCA2 genes

    Directory of Open Access Journals (Sweden)

    Steven A Narod

    2011-10-01

    Full Text Available El descubrimiento de los genes BRCA1 y BRCA2 ha llevado a la introducción de pruebas genéticas cada vez más sofisticadas para medir el riesgo de cáncer de mama de origen hereditario, entre otras cosas. En el presente artículo exploramos los criterios a seguir para realizar pruebas para estos genes, así como las implicaciones en el tratamiento para los pacientes en caso de identificarlos.The discovery of genes BRCA1 and BRCA2 has led to the introduction of genetic tests more complex every time for the evaluation ofthehereditarycancerrisk,amongothers.In the present paper we explore the criteria to decide when to run the testing for the genes, as well as the implications for the treatment of patients who are identified with them.

  9. Familial predisposition to anterior cruciate ligament injury

    Directory of Open Access Journals (Sweden)

    Kenichi Goshima

    2014-04-01

    Full Text Available Although several risk factors for anterior cruciate ligament (ACL injury have been evaluated in the literature, there are few reports on familial predisposition. This study investigated the familial predisposition to ACL injury. The study included 350 patients who underwent ACL reconstruction between January 2005 and September 2008. All patients were surveyed by telephone or a written questionnaire about family history (FH of ACL injury, sports played by family members, and mechanisms of injury. We also compared age, sex, height, weight, body mass index, Tegner activity score, general joint laxity, and tibial slope between an FH group (with FH and a control group (without FH. In addition, we compared the incidence of ACL graft rupture and contralateral ACL rupture 2 years after primary surgery. Complete information was obtained from 316 patients, 38 (12.0% of whom had FH of ACL injury. Two families had three members with ACL injuries. Of the 40 family members with ACL injuries, 38 (95% had noncontact injuries and 34 (85% shared a similar mechanism of injury with the related patient. No significant differences were identified between the two groups, except that tibial slope was significantly greater in the FH group than in the control group. Although the incidence of repeat ACL injury was greater in the FH group (23.7% than in the control group (16.4%, there was no significant difference. Our results indicated a high probability of familial predisposition to many of the identified risk factors for ACL injury. In addition, patients with FH of ACL injury might be at high risk for initial and repeat ACL injuries. Therefore, prevention programs should be implemented for patients with FH of ACL injury in order to decrease the risk of these injuries.

  10. “Liking” and “wanting” of sweet and oily food stimuli as affected by high-fat diet-induced obesity, weight loss, leptin, and genetic predisposition

    Science.gov (United States)

    Shin, Andrew C.; Townsend, R. Leigh; Patterson, Laurel M.

    2011-01-01

    Cross-sectional studies in both humans and animals have demonstrated associations between obesity and altered reward functions at the behavioral and neural level, but it is unclear whether these alterations are cause or consequence of the obese state. Reward behaviors were quantified in male, outbred Sprague-Dawley (SD) and selected line obesity-prone (OP) and obesity-resistant (OR) rats after induction of obesity by high-fat diet feeding and after subsequent loss of excess body weight by chronic calorie restriction. As measured by the brief access lick and taste-reactivity paradigms, both obese SD and OP rats “liked” low concentrations of sucrose and corn oil less, but “liked” the highest concentrations more, compared with lean rats, and this effect was fully reversed by weight loss in SD rats. Acute food deprivation was unable to change decreased responsiveness to low concentrations but eliminated increased responsiveness to high concentrations in obese SD rats, and leptin administration in weight-reduced SD rats shifted concentration-response curves toward that seen in the obese state in the brief access lick test. “Wanting” and reinforcement learning as assessed in the incentive runway and progressive ratio lever-pressing paradigms was paradoxically decreased in both obese (compared with lean SD rats) and OP (compared with OR rats). Thus, reversible, obesity-associated, reduced “liking” and “wanting” of low-calorie foods in SD rats suggest a role for secondary effects of the obese state on reward functions, while similar differences between select lines of OP and OR rats before induction of obesity indicate a genetic component. PMID:21849633

  11. From clinical suspect to molecular confirmation of noonan syndrome; contribution of “best practice” genetic counseling and new technical possibilities

    Directory of Open Access Journals (Sweden)

    Bukvic Nenad

    2015-01-01

    Full Text Available Noonan syndrome (NS is an autosomal dominant disorder, characterized by variable expressivity of clinical features such as: postnatal growth reduction, congenital heart disease, characteristic facial dysmorphisms and development delay. In ~75% of all NS cases, germline mutations involving RAS-MAPK signaling pathway genes (PTPN11, SOS1, RAF1, KRAS, NRAS, BRAF, SHOC2, MEK1, CBL are causative. We reported a case of 13-year-old girl [born at 36w by CS (BW 3250 g (~95°, BL 48 cm (~75°] referred for genetic counseling due to growth retardation, facial dysmorphisms, development delay and learning disability. After birth she presented frequent vomiting, with failure to thrive and at 5 months of age underwent surgery for intestinal malrotation. Because of short stature, Growth Hormone (GH therapy have been introduced at age of 3yrs up to 11yrs. Negative molecular testing for PTPN11 and SOS1 genes, normal female karyotype and aCGH analysis were observed. Objective examination: H 138 cm, (A; p.Val14Ile has been identified. Even though KRAS mutations are usually associated with NS severe phenotype with cardiac involvement (hypertrophic cardiomyopathy, this finding is not present in our patient.

  12. Pediatric glaucoma suspects

    Directory of Open Access Journals (Sweden)

    Kooner K

    2014-06-01

    Full Text Available Karanjit Kooner,1 Matthew Harrison,1 Zohra Prasla,1 Mohannad Albdour,1 Beverley Adams-Huet21Department of Ophthalmology, 2Department of Clinical Sciences, Division of Biostatistics, University of Texas Southwestern Medical Center, Dallas, TX, USAPurpose: To report demographic and ocular features of pediatric glaucoma suspects in an ethnically diverse population of North Central Texas.Design: Retrospective cross-sectional chart review.Participants: Subjects included 75 (136 eyes pediatric glaucoma suspects. Patients with one or more of the following risk factors were included: cup-to disc (C/D ratio of ≥0.6; intraocular pressure (IOP ≥21 mmHg; family history of glaucoma; congenital glaucoma in the opposite eye; history of blunt trauma to either eye; and presence of either Sturge–Weber or Axenfeld–Rieger syndrome, or oculodermal melanocytosis.Methods: Data were extracted from electronic patient medical records. Patient records with incomplete data were excluded. The main outcome measures were race, sex, age, IOP, C/D, family history of glaucoma; and glaucoma treatment.Results: Subjects included 28 (37.3% Hispanics, 20 (26.6% African Americans, 20 (26.6% Caucasians, and seven (9.3% Asians. Forty (53.3% of the patients were male. Suspicious optic disc was seen in 57 (76%; elevated IOP in 25 (33.3%; presence of family history in 13 (17.3%, and Sturge–Weber syndrome in nine (12% patients. The average C/D ratio was 0.58±0.2. The C/D ratios of African American (0.65±0.2, Hispanic (0.63±0.2, and Asian (0.62±0.15 patients were significantly greater than those of Caucasians (0.43±0.18; P=0.0004, 0.0003, and 0.0139, respectively. Caucasian patients were the youngest (7.9±4.8 years. Eleven cases (14.7% required medication.Conclusion: Thirty-three point seven percent of patients seen in the glaucoma clinic were glaucoma suspects. The most common risk factors for suspected glaucoma were suspicious optic discs, elevated IOP, and family history

  13. Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects.

    Science.gov (United States)

    Inoue, Takanobu; Nakamura, Akie; Fuke, Tomoko; Yamazawa, Kazuki; Sano, Shinichiro; Matsubara, Keiko; Mizuno, Seiji; Matsukura, Yoshika; Harashima, Chie; Hasegawa, Tatsuji; Nakajima, Hisakazu; Tsumura, Kumi; Kizaki, Zenro; Oka, Akira; Ogata, Tsutomu; Fukami, Maki; Kagami, Masayo

    2017-01-01

    Silver-Russell syndrome (SRS) is a rare congenital disorder characterized by pre- and postnatal growth failure and dysmorphic features. Recently, pathogenic copy number variations (PCNVs) and imprinting defects other than hypomethylation of the H19-differentially methylated region (DMR) and maternal uniparental disomy chromosome 7 have been reported in patients with the SRS phenotype. This study aimed to clarify the frequency and clinical features of patients with SRS phenotype caused by PCNVs. We performed array comparative genomic hybridization analysis using a catalog array for 54 patients satisfying the Netchine-Harbison clinical scoring system (NH-CSS) (SRS-compatible) and for 28 patients presenting with three NH-CSS items together with triangular face and/or fifth finger clinodactyly and/or brachydactyly (SRS-like) without abnormal methylation levels of 9 DMRs related to known imprinting disorders. We then investigated the clinical features of patients with PCNVs. Three of the 54 SRS-compatible patients (5.6%) and 2 of the 28 SRS-like patients (7.1%) had PCNVs. We detected 3.5 Mb deletion in 4p16.3, mosaic trisomy 18, and 3.77-4.00 Mb deletion in 19q13.11-12 in SRS-compatible patients, and 1.41-1.97 Mb deletion in 7q11.23 in both SRS-like patients. Congenital heart diseases (CHDs) were identified in two patients and moderate to severe global developmental delay was observed in four patients. Of the patients in our study, 5.6% of SRS-compatible and 7.1% of SRS-like patients had PCNVs. All PCNVs have been previously reported for genetic causes of contiguous deletion syndromes or mosaic trisomy 18. Our study suggests patients with PCNVs, who have a phenotype resembling SRS, show a high tendency towards CHDs and/or apparent developmental delay.

  14. Predisposition Locus for Major Depression at Chromosome 12q22-12q23.2

    Science.gov (United States)

    Abkevich, Victor; Camp, Nicola J.; Hensel, Charles H.; Neff, Chris D.; Russell, Deanna L.; Hughes, Dana C.; Plenk, Agnes M.; Lowry, Michael R.; Richards, R. Lynn; Carter, Catherine; Frech, Georges C.; Stone, Steven; Rowe, Kerry; Chau, Chi Ai; Cortado, Kathleen; Hunt, Angelene; Luce, Karanina; O’Neil, Gayanne; Poarch, Jeff; Potter, Jennifer; Poulsen, Gregg H.; Saxton, Heidi; Bernat-Sestak, Michelle; Thompson, Victor; Gutin, Alexander; Skolnick, Mark H.; Shattuck, Donna; Cannon-Albright, Lisa

    2003-01-01

    Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2. PMID:14606042

  15. Genetic predisposition to ductal carcinoma in situ of the breast

    NARCIS (Netherlands)

    C. Petridis (Christos); R.H. Brook; V. Shah (Vandna); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); D. Levi (Dina); E. Papouli (Efterpi); N. Orr (Nick); A. Cox (Angela); S.S. Cross (Simon); I. dos Santos Silva (Isabel); J. Peto (Julian); A.J. Swerdlow (Anthony ); M. Schoemaker (Minouk); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); J. Benítez (Javier); A. González-Neira (Anna); D.C. Tessier (Daniel C.); D. Vincent (Daniel); J. Li (Jingmei); J.D. Figueroa (Jonine); V. Kristensen (Vessela); A.-L. Borresen-Dale (Anne-Lise); P. Soucy (Penny); J. Simard (Jacques); R.L. Milne (Roger); G.G. Giles (Graham); S. Margolin (Sara); A. Lindblom (Annika); T. Brüning (Thomas); H. Brauch (Hiltrud); M.C. Southey (Melissa); J.L. Hopper (John); T. Dörk (Thilo); N.V. Bogdanova (Natalia); M. Kabisch (Maria); U. Hamann (Ute); R.K. Schmutzler (Rita); A. Meindl (Alfons); H. Brenner (Hermann); V. Arndt (Volker); R. Winqvist (Robert); K. Pykäs (Katri); P.A. Fasching (Peter); M.W. Beckmann (Matthias); J. Lubinski (Jan); A. Jakubowska (Anna); A.M. Mulligan (Anna Marie); I.L. Andrulis (Irene); R.A.E.M. Tollenaar (Rob); P. Devilee (Peter); L. Le Marchand (Loic); C.A. Haiman (Christopher); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); P. Radice (Paolo); P. Peterlongo (Paolo); F. Marme (Federick); B. Burwinkel (Barbara); C.H.M. van Deurzen (Carolien); A. Hollestelle (Antoinette); N. Miller (Nicola); M. Kerin (Michael); D. Lambrechts (Diether); O.A.M. Floris; J. Wesseling (Jelle); H. Flyger (Henrik); S.E. Bojesen (Stig); S. Yao (Song); C.B. Ambrosone (Christine); G. Chenevix-Trench (Georgia); T. Truong (Thérèse); P. Guénel (Pascal); A. Rudolph (Anja); J. Chang-Claude (Jenny); H. Nevanlinna (Heli); C. Blomqvist (Carl); K. Czene (Kamila); J.S. Brand (Judith S.); J.E. Olson (Janet); F.J. Couch (Fergus); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); S. Pinder (Sarah); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); R. Roylance (Rebecca); M. García-Closas (Montserrat); E.J. Sawyer (Elinor)

    2016-01-01

    textabstractBackground: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk

  16. Genetic predisposition to schizophrenia associated with increased use of cannabis

    NARCIS (Netherlands)

    Power, R.A.; Verweij, K.J.H.; Zuhair, M.; Montgomery, G.W.; Henders, A.K.; Heath, A.C.; Madden, P.A.F.; Medland, S.E.; Wray, N.R.; Martin, N.G.

    2014-01-01

    Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric

  17. Genetic predisposition to schizophrenia associated with increased use of cannabis.

    NARCIS (Netherlands)

    Power, R.A.; Verweij, C.J.H.; Zuhair, M.; Montgomery, G.W.; Henders, A.K.; Heath, A.C.; Madden, P.A.F.; Medland, S.E.; Wray, N.R.; Martin, N.G.

    2014-01-01

    Cannabis is the most commonly used illicit drug worldwide. With debate surrounding the legalization and control of use, investigating its health risks has become a pressing area of research. One established association is that between cannabis use and schizophrenia, a debilitating psychiatric

  18. Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use

    OpenAIRE

    Martínez, Carmen; Blanco, Gerardo; Ladero, José M; García-Martín, Elena; Taxonera, Carlos; Gamito, Francisco G; Diaz-Rubio, Manuel; Agúndez, José A G

    2004-01-01

    Impaired drug metabolism is a major cause of adverse drug reactions, and it is often caused by mutations at genes coding for drug-metabolising enzymes. Two amino-acid polymorphisms of cytochrome P4502C9 (CYP2C9), an enzyme involved in the metabolism of several nonsteroidal anti-inflammatory drugs (NSAIDs), were studied in 94 individuals with acute bleeding after NSAIDs use and 124 individuals receiving NSAIDs with no adverse effects. The frequency of CYP2C9 variant alleles was increased in ov...

  19. Female alcoholism: Gender differences as victimogenic predispositions

    Directory of Open Access Journals (Sweden)

    Konstantinović-Vilić Slobodanka

    2014-01-01

    Full Text Available The subject matter of this paper is an analysis of stereotypical social reactions to women’s alcoholism in the micro and macro social and cultural environment. The social stigma and blame that female alcohol abusers are exposed to have become part of deeply rooted gender-related labels. In a broader social context, they lead to discrimination and social exclusion. In the contemporary society, female alcoholism is turning into a growing social and health problem and because of that it is essential to make the social environment more sensitive to the issue of female alcoholism in order to eliminate the causes of female alcoholism and fully support women’s medical treatment,. It would have a preventive effect in suppressing female alcoholism and it would significantly reduce victimization of women who are, in such circumstances, much more vulnerable and exposed to physical and sexual violence. The aim of this paper is to point out to the basic phenomenological and etiological feature of female alcoholism, prejudices and stereotypical attitudes they are exposed to, social and cultural implications of female alcoholism, which is perceived as a predisposition for women’s victimization and exposure to violence, so as to promote a different social approach to female alcoholism and advocate for instituting social and educational policy based on the concept of gender equality and support of social control measures.

  20. Disparities in Genetic Testing: Thinking Outside the BRCA Box

    National Research Council Canada - National Science Library

    Michael J. Hall; Olufunmilayo I. Olopade

    2006-01-01

    .... Nonetheless, differential access to and utilization of genetic counseling and cancer predisposition testing among underserved racial and ethnic minorities compared with the white population has led...

  1. How Are Genetic Conditions Diagnosed?

    Science.gov (United States)

    ... Consultation How are genetic conditions diagnosed? How are genetic conditions diagnosed? A doctor may suspect a diagnosis ... and advocacy resources. For more information about diagnosing genetic conditions: Genetics Home Reference provides information about genetic ...

  2. Technology and the Glaucoma Suspect

    National Research Council Canada - National Science Library

    Blumberg, Dana M; De Moraes, Carlos Gustavo; Liebmann, Jeffrey M; Garg, Reena; Chen, Cynthia; Theventhiran, Alex; Hood, Donald C

    2016-01-01

    ...), stereoscopic disc photographs, and automated perimetry as assessed by a group of glaucoma specialists in differentiating individuals with early glaucoma from suspects. Forty-six eyes (46 patients...

  3. A Major Predisposition Locus for Severe Obesity, at 4p15-p14

    Science.gov (United States)

    Stone, Steven; Abkevich, Victor; Hunt, Steven C.; Gutin, Alexander; Russell, Deanna L.; Neff, Chris D.; Riley, Robyn; Frech, Georges C.; Hensel, Charles H.; Jammulapati, Srikanth; Potter, Jennifer; Sexton, David; Tran, Thanh; Gibbs, Drew; Iliev, Diana; Gress, Richard; Bloomquist, Brian; Amatruda, John; Rae, Peter M. M.; Adams, Ted D.; Skolnick, Mark H.; Shattuck, Donna

    2002-01-01

    Although the predisposition to morbid obesity is heritable, the identities of the disease-causing genes are largely unknown. Therefore, we have conducted a genomewide search with 628 markers, using multigenerational Utah pedigrees to identify genes involved in predisposition to obesity. In the genomewide search, we identified a highly significant linkage to high body-mass index in female patients, at D4S2632, with a multipoint heterogeneity LOD (HLOD) score of 6.1 and a nonparametric linkage (NPL) score of 5.3. To further delineate the linkage, we increased both the marker density around D4S2632 and the size of our pedigree data set. As a result, the linkage evidence increased to a multipoint HLOD score of 9.2 (at D4S3350) and an NPL score of 11.3. Evidence from almost half of the families in this analysis support this linkage, and therefore the gene in this region might account for a significant percentage of the genetic predisposition to severe obesity in females. However, further studies are necessary to clarify the effect that this gene has in males and in the general population. PMID:11957135

  4. [Predisposition and phenotypes of gestational diabetes].

    Science.gov (United States)

    Kleinwechter, H; Demandt, N; Schäfer-Graf, U

    2014-05-01

    Gestational diabetes (GDM) is defined as glucose intolerance first diagnosed with a 75 gram oral glucose tolerance test based on IADPSG criteria which had been recently adopted by WHO. In industrial countries GDM is one of the most frequent pregnancy complications. In 2012, in Germany GDM had been diagnosed in 4,3 % of all births, overall 27,700 cases. GDM has to be considered as a preliminary stage of type 2 diabetes with insulin resistance and inadequate β-cell-compensation. Additionally, adverse metabolic profile, associations with inflammatory parameters, with D vitamin metabolism, and insufficient decline of renal threshold for glucose had been identified in women with GDM. Within 10 years after GDM roughly 50 % of the women convert to overt diabetes, mostly type 2. GDM and type 2 diabetes share potential candidate genes. In about 1 % of GDM in Caucasian women a mutation in glucokinase gene had been found (GCK-MODY). Predisposition to GDM is predominantly characterized by family history of diabetes, previous GDM in pregnancies, factors of metabolic syndrome, and unfavorable life style. The probability for GDM rises with increasing mother's age and preconceptional BMI. Via fetal programming GDM dispones to offspring obesity as early as school entry. Prevention of GDM focus on regular physical exercise, normalizing body weight before conception, reducing excess intake of animal protein and soft drinks, planning of pregnancy in younger ages, and avoiding pollutant exposition as well as smoking cessation. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Epigenetics of drug abuse: predisposition or response

    OpenAIRE

    Nielsen, David A.; Utrankar, Amol; Reyes, Jennifer A.; Simons, Daniel D; Kosten, Thomas R.

    2012-01-01

    Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversib...

  6. Myeloid Neoplasms with Germline Predisposition: A New Provisional Entity Within the World Health Organization Classification.

    Science.gov (United States)

    Czuchlewski, David R; Peterson, LoAnn C

    2016-03-01

    The forthcoming update of the World Health Organization (WHO) classification of hematopoietic neoplasms will feature "Myeloid Neoplasms with Germline Predisposition" as a new provisional diagnostic entity. This designation will be applied to some cases of acute myeloid leukemia and myelodysplastic syndrome arising in the setting of constitutional mutations that render patients susceptible to the development of myeloid malignancies. For the diagnostic pathologist, recognizing these cases and confirming the diagnosis will demand a sophisticated grasp of clinical genetics and molecular techniques. This article presents a concise review of this new provisional WHO entity, including strategies for clinical practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Scott, D. [Christie Hospital, Manchester (United Kingdom). Paterson Inst. for Cancer Research

    2000-05-01

    Aim: This paper briefly summarizes the research on this topic, undertaken in the Department of Cancer Genetics, Paterson Institute for Cancer Research, Manchester, England, over the previous 6 years. We have investigated the possible role of radiosensitivity as a marker of cancer predisposition and response to radiotherapy in the general population. Results: We found that 42% (57/135) of breast cancer patients exhibit chromosomal radiosensitivity when lymphocytes are irradiated in the G{sub 2} phase of the cell cycle, compared with 6% (6/105) of healthy controls. These figures are much higher than the estimated frequencies of carriers of the ataxia-telangiectasia gene (heterozygotes) amongst breast cancer patients (<5%) and control (0.5%). We have also obtained evidence of heritability of G{sub 2} sensitivity by studying relatives of breast cancer cases. The pattern of inheritance is relatively simple and attributable to 1 or 2 genes segregating in each family. In a prospective study of 123 breast cancer patients, 9 (7%) had severe acute reactions to radiotherapy and their mean G{sub 2} sensitivity was significantly greater (p=0.001) than that of the remaining patients. In 16 patients with adverse acute reactions we found no mutations of the ataxia-telangiectasia gene (ATM). Using another chromosomal assay (micronucleus induction in G{sub 0} lymphocytes) we found that the mean radiosensitivity of patients with severe late reactions was higher than that of normal reactors. For example, 8 patients with severe fibrosis were more sensitive (p=0.055) than 39 patients with a normal response. However, the discriminatory power of these chromosomal assays is too low for them to be used alone in a clinical setting. Conclusion: Our results provide good evidence that genes other than ATM, that confer chromosomal radiosensitivity, are involved in low penetrance predisposition to breast cancer in a high proportion of cases and contribute to adverse reactions after radiotherapy

  8. Epigenetics of drug abuse: predisposition or response.

    Science.gov (United States)

    Nielsen, David A; Utrankar, Amol; Reyes, Jennifer A; Simons, Daniel D; Kosten, Thomas R

    2012-07-01

    Drug addiction continues to be a serious medical and social problem. Vulnerability to develop an addiction to drugs is dependent on genetic, environmental, social and biological factors. In particular, the interactions of environmental and genetic factors indicate the significance of epigenetic mechanisms, which have been found to occur in response to illicit drug use or as underlying factors in chronic substance abuse and relapse. Epigenetics is defined as the heritable and possibly reversible modifications in gene expression that do not involve alterations in the DNA sequence. This review discusses the various types of epigenetic modifications and their relevance to drug addiction to elucidate whether epigenetics is a predisposing factor, or a response to, developing an addiction to drugs of abuse.

  9. Biomarkers and genes predictive of disease predisposition and ...

    African Journals Online (AJOL)

    Biomarkers and genes predictive of disease predisposition and prognosis in rheumatoid arthritis. Rheumatoid arthritis is a debilitating disease which often progresses to relentlessly severe disease. Pieter W A Meyer, NHDip Med Tech, MTech, PhD. Medical Research Council Unit for Inflammation and Immunity, Department ...

  10. Content, Structure, and Usefulness of Juvenile Predisposition Psychological Evaluations

    Science.gov (United States)

    Morin, Samantha L.; Cruise, Keith R.; Hinz, Holly; Holloway, Evan D.; Chapman, John F.

    2015-01-01

    Background: There is a dearth of research regarding the content and structure of juvenile predisposition psychological evaluations. Limited research suggests that key mental health domains are insufficiently represented and judges use evaluator recommendations regarding legal outcomes more often than clinical outcomes. Studies have not addressed…

  11. A New View of Health: Genetics and Environment

    Science.gov (United States)

    Childs, Barton

    1978-01-01

    Discusses the importance of and need for genetics education for both medical professionals and the public. The nature nurture controversy is included in terms of environmental conditions causing the expression of certain genetic predispositions. (MA)

  12. Inherited predisposition to breast and ovarian cancer in non-Jewish populations in Israel.

    Science.gov (United States)

    Zidan, Jamal; Zhou, Alicia Y; van den Akker, Jeroen; Laitman, Yael; Schayek, Hagit; Schnaider, Julia; Friedman, Eitan

    2017-08-21

    The contribution of genetic factors to cancer in non-Jewish populations in Israel is understudied. Yet the early, mostly premenopausal age at breast cancer diagnosis is suggestive of an inherited predisposition. High-risk cancer cases of non-Jewish origin who were counseled at the Oncogenetics unit, Sheba Medical Center and the oncology institute at the Ziv medical center from January 1, 2000 to December 31 2016 were eligible. DNA extracted from leukocytes was subjected to massive parallel, next-generation sequencing using the Color Genomics platform. Data were analyzed for pathogenic and likely pathogenic mutations using existing pipelines. Overall, 68 cases, each representing a unique high-risk breast/ovarian family, were genotyped: 32 Druze, 26 Muslim Arabs, and 10 Christian Arabs. Fifty-nine had breast cancer (mean age at diagnosis 42.7 ± 7.6 years), and 9 had ovarian cancer (51.6 ± 9.7 years). Overall three pathogenic mutations one each in BRCA1, PALB2, and BRIP1 genes were detected mostly in Druze families. In addition, 29 variants of unknown significance were also detected, and in 36 cases no sequence variants were noted in any of the genotyped genes. The contribution of the known cancer susceptibility genes to the burden of inherited breast/ovarian cancer predisposition in non-Jews in Israel is modest. Other genes or molecular mechanisms account for the familial breast/ovarian cancer clustering in this population.

  13. [Inherited colorectal cancer predisposition syndromes identified in the Instituto Nacional de Enfermedades Neoplasicas (INEN), Lima, Peru;].

    Science.gov (United States)

    Castro-Mujica, María del Carmen; Sullcahuamán-Allende, Yasser; Barreda-Bolaños, Fernando; Taxa-Rojas, Luis

    2014-04-01

    Colorectal cancer (CRC) is the fourth most common cancer in the world and is classified according to their origin in sporadic CRC (~ 70%) and genetic CRC (~ 30%), this latter involves cases of familial aggregation and inherited síndromes that predispose to CRC. To describe inherited CRC predisposition syndromes, polyposic and non-polyposic, identified in the Oncogenetics Unit at National Institute of Cancer Disease (INEN). A descriptive observational record from the attentions of the Oncogenetics Unit at INEN during 2009 to 2013. We included patients with personal or familiar history of CRC and/or colonic polyposis who were referred for clinical assessment to the Oncogenetics Unitat INEN. 59.3 % were female, 40.7 % male, 69.8% under 50 years old, 60.5% had a single CRC, 23.2% had more than one CRC or CRC associated with other extracolonic neoplasia and 32.6% had a familiar history of cancer with autosomal dominant inheritance. According to the clinical genetic diagnosis, 93.1% of the included cases were inherited syndromes that predispose to CRC, with 33.8% of colonic polyposis syndromes, 23.3% of hereditary nonpolyposis CRC syndromes (HNPCC) and 36.0% of CCRHNP probable cases. Clinical genetic evaluation of patients with personal or familiar history of CRC and/or colonic polyposis can identify inherited colorectal cancer predisposition syndromes and provide an appropriategenetic counseling to patients and relatives at risk, establishing guidelines to follow-up and prevention strategies to prevent morbidity and mortality by cancer.

  14. Atopic predisposition in cholinergic urticaria patients and its implications.

    Science.gov (United States)

    Altrichter, S; Koch, K; Church, M K; Maurer, M

    2016-12-01

    Cholinergic urticaria (CholU) is a frequent chronic urticaria disorder with itchy weal and flare-type skin reactions in response to physical exercise or passive warming. A higher frequency of atopy among CholU patients has been reported, but the significance of this observation is unclear. To assess the prevalence and relevance of atopy in CholU patients. Thirty CholU patients were assessed for atopic skin diathesis (atopic predisposition) by use of the Erlangen Atopy Score and divided into atopic and non-atopic predisposed CholU individuals. Both groups were assessed for disease severity (CholUSI) and activity (CholUAS7), quality of life impairment [Dermatology Life Quality Index (DLQI) and CU-Q2 OL], seasonal exacerbation, total and specific serum IgE and comorbidities. CholU patients were found to exhibit high rates of atopic predisposition (57%), with higher prevalence and scores in female than in male patients. High Erlangen Atopy Scores were linked to high CholU severity, activity and impact on QoL. Atopic predisposed CholU patients show different seasonal exacerbation patterns, IgE specificity and comorbidity profiles as compared to non-atopic CholU patients. Atopic predisposition and cholinergic urticaria appear to be linked more closely than previously thought, which suggests shared pathogenetic mechanisms. Atopic patients with cholinergic urticaria have more severe disease and poorer quality of life than those who do not. Thus, all cholinergic urticaria patients should be assessed for atopic predisposition. © 2016 European Academy of Dermatology and Venereology.

  15. River predisposition to ice jams: a simplified geospatial model

    Science.gov (United States)

    De Munck, Stéphane; Gauthier, Yves; Bernier, Monique; Chokmani, Karem; Légaré, Serge

    2017-07-01

    Floods resulting from river ice jams pose a great risk to many riverside municipalities in Canada. The location of an ice jam is mainly influenced by channel morphology. The goal of this work was therefore to develop a simplified geospatial model to estimate the predisposition of a river channel to ice jams. Rather than predicting the timing of river ice breakup, the main question here was to predict where the broken ice is susceptible to jam based on the river's geomorphological characteristics. Thus, six parameters referred to potential causes for ice jams in the literature were initially selected: presence of an island, narrowing of the channel, high sinuosity, presence of a bridge, confluence of rivers, and slope break. A GIS-based tool was used to generate the aforementioned factors over regular-spaced segments along the entire channel using available geospatial data. An ice jam predisposition index (IJPI) was calculated by combining the weighted optimal factors. Three Canadian rivers (province of Québec) were chosen as test sites. The resulting maps were assessed from historical observations and local knowledge. Results show that 77 % of the observed ice jam sites on record occurred in river sections that the model considered as having high or medium predisposition. This leaves 23 % of false negative errors (missed occurrence). Between 7 and 11 % of the highly predisposed river sections did not have an ice jam on record (false-positive cases). Results, limitations, and potential improvements are discussed.

  16. River predisposition to ice jams: a simplified geospatial model

    Directory of Open Access Journals (Sweden)

    S. De Munck

    2017-07-01

    Full Text Available Floods resulting from river ice jams pose a great risk to many riverside municipalities in Canada. The location of an ice jam is mainly influenced by channel morphology. The goal of this work was therefore to develop a simplified geospatial model to estimate the predisposition of a river channel to ice jams. Rather than predicting the timing of river ice breakup, the main question here was to predict where the broken ice is susceptible to jam based on the river's geomorphological characteristics. Thus, six parameters referred to potential causes for ice jams in the literature were initially selected: presence of an island, narrowing of the channel, high sinuosity, presence of a bridge, confluence of rivers, and slope break. A GIS-based tool was used to generate the aforementioned factors over regular-spaced segments along the entire channel using available geospatial data. An ice jam predisposition index (IJPI was calculated by combining the weighted optimal factors. Three Canadian rivers (province of Québec were chosen as test sites. The resulting maps were assessed from historical observations and local knowledge. Results show that 77 % of the observed ice jam sites on record occurred in river sections that the model considered as having high or medium predisposition. This leaves 23 % of false negative errors (missed occurrence. Between 7 and 11 % of the highly predisposed river sections did not have an ice jam on record (false-positive cases. Results, limitations, and potential improvements are discussed.

  17. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); Kerr, Iain D., E-mail: ikerr@myriad.com [Myriad Genetic Laboratories Inc., 320 Wakara Way, Salt Lake City, UT 84108 (United States); Min, Jinrong, E-mail: ikerr@myriad.com [University of Toronto, 101 College Street, Toronto, ON M5G 1L7 (Canada); University of Toronto, Toronto, ON M5G 1L7 (Canada)

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  18. Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing.

    Science.gov (United States)

    Ng, P S; Wen, W X; Fadlullah, M Z H; Yoon, S Y; Lee, S Y; Thong, M K; Yip, C H; Mohd Taib, N A; Teo, S H

    2016-10-01

    Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Genetics

    Science.gov (United States)

    ... Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... mother and medications). These include: Asthma Cancer Coronary heart disease Diabetes Hypertension Stroke MITOCHONDRIAL DNA-LINKED DISORDERS Mitochondria ...

  20. Functional analysis in mouse embryonic stem cells reveals wild-type activity for three MSH6 variants found in suspected Lynch syndrome patients.

    Directory of Open Access Journals (Sweden)

    Eva A L Wielders

    Full Text Available Lynch syndrome confers an increased risk to various types of cancer, in particular early onset colorectal and endometrial cancer. Mutations in mismatch repair (MMR genes underlie Lynch syndrome, with the majority of mutations found in MLH1 and MSH2. Mutations in MSH6 have also been found but these do not always cause a clear cancer predisposition phenotype and MSH6-defective tumors often do not show the standard characteristics of MMR deficiency, such as microsatellite instability. In particular, the consequences of MSH6 missense mutations are challenging to predict, which further complicates genetic counseling. We have previously developed a method for functional characterization of MSH2 missense mutations of unknown significance. This method is based on endogenous gene modification in mouse embryonic stem cells using oligonucleotide-directed gene targeting, followed by a series of functional assays addressing the MMR functions. Here we have adapted this method for the characterization of MSH6 missense mutations. We recreated three MSH6 variants found in suspected Lynch syndrome families, MSH6-P1087R, MSH6-R1095H and MSH6-L1354Q, and found all three to behave like wild type MSH6. Thus, despite suspicion for pathogenicity from clinical observations, our approach indicates these variants are not disease causing. This has important implications for counseling of mutation carriers.

  1. Mitochondrial BAX Determines the Predisposition to Apoptosis in Human AML.

    Science.gov (United States)

    Reichenbach, Frank; Wiedenmann, Cornelius; Schalk, Enrico; Becker, Diana; Funk, Kathrin; Scholz-Kreisel, Peter; Todt, Franziska; Wolleschak, Denise; Döhner, Konstanze; Marquardt, Jens U; Heidel, Florian; Edlich, Frank

    2017-08-15

    Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death.Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort.Results: This study shows that relative BAX localization determines the predisposition of different AML cell lines to apoptosis. Human AML displays a surprising variety of relative BAX localizations. In a test cohort of 48 patients with AML, mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients treated with myelosuppressive chemotherapy confirmed that relative BAX localization correlates with probability of disease progression, FLT3-ITD status, and leukocytosis. Relative BAX localization could therefore be helpful to identify elderly or frail patients who may benefit from cytotoxic therapy.Conclusions: In this retrospective analysis of two independent AML cohorts, our data suggest that Bax localization may predict prognosis of patients with AML and cellular predisposition to apoptosis, combining the actual contribution of known and unknown factors to a final "common path." Clin Cancer Res; 23(16); 4805-16. ©2017 AACR. ©2017 American Association for Cancer Research.

  2. [Individual alpha frequency EEG as neurophysiological endophenotype of affective predispositions].

    Science.gov (United States)

    Aftanas, L I; Tumialis, A V

    2013-01-01

    Individual alpha frequency (IAF) of electroencephalogram (EEG) is regarded as a neurophysiological endophenotypic indicator of cognitive activity featuring individual propensity to efficient cognitive performance and creativity. Considering that cognitive coping style is intrinsic part of emotional regulation, defining medical aspects of individual health as well as risks of psychosomatic diseases, we intended to assess IAF contribution into mechanisms of individual emotional reactivity. As participants was healthy man subjects (n = 62). Three models of laboratory induced emotions were used: emotional perception (1); anxious apprehension (awaiting of inescapable aversive punishment) (2); experience of discrete emotions of anger and joy (3). It was revealed that high IAF individuals exhibit predisposition to prevalence of parasympathetic activity in the global circuit of autonomous regulation, proactive-like coping with inescapable threat, prevailing contribution of the positive emotional stance and better accessibility of recent positive memories. By contrast, low IAF subjects manifested predisposition to prevalence of sympathetic activity in the global circuit of autonomous regulation, maladaptive avoidance-like coping with inescapable threat, insufficiency positive emotional arousal mechanisms. It is suggested that IAF creates a "hardware" construct featuring individual emotional space and adaptability of coping styles to emotional challenges.

  3. Predisposição genética, hereditariedade e reabsorções radiculares em Ortodontia: cuidados com interpretações precipitadas: uma análise crítica do trabalho de Al-Qawasmi et al Genetics predisposition, heredity and radicular resorption, in Orthodontics: cares with precipitated interpretations and a critical analysis of Al-Qawasmi´s work

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    2004-05-01

    Full Text Available O trabalho de Al-Qawasmi et al.¹, publicado em março de 2003 pelo American Journal of Orthodontics and Dentofacial Orthopedics, procurou estabelecer uma predisposição genética para justificar as reabsorções dentárias em Ortodontia, mas apresentou algumas limitações metodológicas e equívocos na interpretação de seus resultados. A análise criteriosa deste artigo ressalta que, na maioria, estas limitações foram mencionadas e reconhecidas pelos autores na discussão do trabalho, mas o seu resumo e título foram muito taxativos e conclusivos. A linguagem de estudos genéticos nem sempre é familiar a todos os clínicos e isto também requer uma análise esclarecedora à luz de uma visão mais aplicada ao cotidiano ortodôntico. Referenciar ou citar este trabalho de Al-Qawasmi et al.¹, para afirmar de forma taxativa que se demonstrou a natureza hereditária das reabsorções dentárias em Ortodontia, pode denotar falta de conhecimento sobre o assunto ou uma leitura ou compreensão apenas do seu título. Ou ainda, a citação deste trabalho como prova definitiva de associação entre hereditariedade e reabsorções dentárias em Ortodontia pode traduzir também o desejo de excluir da prática clínica a responsabilidade de planejar de forma individualizada e detalhada cada tratamento com base no conhecimento das possibilidades e limitações técnicas oferecidas pela ciência ortodôntica, bem como nas suas bases biológicas, por exemplo, valorizando a morfologia radicular e da crista óssea alveolar e o papel dos cementoblastos na proteção da superfície radicular.The study published in the American Journal of Orthodontics and Dentofacial Orthopedics last March by Al-Qawasmi et al. tried to implicate dental resorption during orthodontic treatment to genetic predisposition. The methodology used, however, presents limitations and interpretative mistakes of the results. When analyzing the article sensibly, one is able to find that

  4. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  5. Suspected levamisole intoxication in calves.

    Science.gov (United States)

    Müller, K R; Dwyer, C

    2016-07-01

    A group of 32 Friesian and four Hereford calves, 3-4 months old with body weights between 100-120 kg, were purchased from a weaner sale. On arrival at the property the Hereford calves were treated with a combination anthelmintic containing 2 g/L abamectin and 80 g/L levamisole hydrochloride. Shortly afterwards they developed tremors and frothing from the mouth, and two died overnight. The Friesian calves were treated with the same anthelmintic on the following day, when some showed hypersalivation and frothing from the mouth. Examination of the three most severely affected Friesian calves revealed severe nicotinic-type symptoms including hypersalivation, frothing from the mouth, muscle tremors, recumbency, rapid respiration, hyperaesthesia, and central nervous system depression. Other calves showed mild to moderate signs of intoxication including restlessness, tail switching, salivation, tremors, frequent defaecation, mild colic and jaw chomping. Two calves died shortly afterwards. An adverse drug event investigation revealed that the formulation and quality of the anthelmintic was within the correct specification, and that the drench gun was functioning correctly. Suspected levamisole intoxication due to a combination of possible overdosing, dehydration, and stress caused by transportation and prolonged yarding. Susceptibility to levamisole toxicity in New Zealand calves can be increased if factors like dehydration or stress are present. Levamisole has a narrow margin of safety, and overdosing in calves can easily occur if the dose rate is not based on their actual weight or health status.

  6. River channel's predisposition to ice jams: a geospatial model

    Science.gov (United States)

    De Munck, S.; Gauthier, Y.; Bernier, M.; Légaré, S.

    2012-04-01

    When dynamic breakup occurs on rivers, ice moving downstream may eventually stop at an obstacle when the volume of moving ice exceeds the transport capacity of the river, resulting into an ice jam. The suddenness and unpredictability of these ice jams are a constant danger to local population. Therefore forecasting methods are necessary to provide an early warning to these population. Nonetheless the morphological and hydrological factors controlling where and how the ice will jam are numerous and complex. Existing studies which exist on this topic are highly site specific. Therefore, the goal of this work is to develop a simplified geospatial model that would estimate the predisposition of any river channel to ice jams. The question here is not to predict when the ice will break up but rather to know where the released ice would be susceptible to jam. This paper presents the developments and preliminary results of the proposed approach. The initial step was to document the main factors identified in the literature, as potential cause for an ice jam. First, several main factors identified in the literature as potential cause for an ice jam have been selected: presence of an island, narrowing of the channel, sinuosity, presence of a bridge, confluence of rivers and slope break. The second step was to spatially represent, in 2D, the physical characteristics of the channel and to translate these characteristics into potential ice jamming factors. The Chaudiere River, south of Quebec City (Canada), was chosen as a test site. Tools from the GIS-based FRAZIL system have been used to generate these factors from readily available geospatial data and calcutate an "ice jam predisposition index" over regular-spaced segments along the entire channel. The resulting map was validated upon historical observations and local knowledge, collected in relationship with the Minister of Public Security.

  7. Methylation of Breast Cancer Predisposition Genes in Early-Onset Breast Cancer: Australian Breast Cancer Family Registry.

    Directory of Open Access Journals (Sweden)

    Cameron M Scott

    Full Text Available DNA methylation can mimic the effects of both germline and somatic mutations for cancer predisposition genes such as BRCA1 and p16INK4a. Constitutional DNA methylation of the BRCA1 promoter has been well described and is associated with an increased risk of early-onset breast cancers that have BRCA1-mutation associated histological features. The role of methylation in the context of other breast cancer predisposition genes has been less well studied and often with conflicting or ambiguous outcomes. We examined the role of methylation in known breast cancer susceptibility genes in breast cancer predisposition and tumor development. We applied the Infinium HumanMethylation450 Beadchip (HM450K array to blood and tumor-derived DNA from 43 women diagnosed with breast cancer before the age of 40 years and measured the methylation profiles across promoter regions of BRCA1, BRCA2, ATM, PALB2, CDH1, TP53, FANCM, CHEK2, MLH1, MSH2, MSH6 and PMS2. Prior genetic testing had demonstrated that these women did not carry a germline mutation in BRCA1, ATM, CHEK2, PALB2, TP53, BRCA2, CDH1 or FANCM. In addition to the BRCA1 promoter region, this work identified regions with variable methylation at multiple breast cancer susceptibility genes including PALB2 and MLH1. Methylation at the region of MLH1 in these breast cancers was not associated with microsatellite instability. This work informs future studies of the role of methylation in breast cancer susceptibility gene silencing.

  8. Melanoma genetics.

    Science.gov (United States)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2016-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of heritable melanoma risk genes is an important component of disease occurrence. Susceptibility for some families is due to mutation in one of the known high penetrance melanoma predisposition genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP and TERT. However, despite such mutations being implicated in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed in melanoma families at rates greater than expected by chance. The most extensively documented association is between CDKN2A germ line mutations and pancreatic cancer, and a cancer syndrome including cutaneous melanoma, uveal melanoma and mesothelioma has been proposed for BAP1 germ line mutations. Other medium to high penetrance melanoma predisposition genes have been associated with renal cell carcinoma (MITF, BAP1) and glioma (POT1). These associations between melanoma and other cancers hint at the possibility of common pathways for oncogenesis, and better knowledge of these pathways may improve understanding of the genetic basis underpinning familial melanoma. It is likely that 'melanoma' risk genes will impact on mutation screening and genetic counselling not only for melanoma but

  9. Genetic association studies in lumbar disc degeneration

    DEFF Research Database (Denmark)

    Eskola, Pasi J; Lemmelä, Susanna; Kjaer, Per

    2012-01-01

    Low back pain is associated with lumbar disc degeneration, which is mainly due to genetic predisposition. The objective of this study was to perform a systematic review to evaluate genetic association studies in lumbar disc degeneration as defined on magnetic resonance imaging (MRI) in humans....

  10. The influence of familial predisposition to cardiovascular complications upon childhood obesity treatment.

    Science.gov (United States)

    Nielsen, Louise A; Bøjsøe, Christine; Kloppenborg, Julie T; Trier, Cæcilie; Gamborg, Michael; Holm, Jens-Christian

    2015-01-01

    The aim was to investigate whether a familial predisposition to obesity related cardiovascular complications was associated with the degree of obesity at baseline and/or changes in the degree of obesity during a multidisciplinary childhood obesity treatment program. The study included 1421 obese children (634 boys) with a median age of 11.5 years (range 3.1-17.9 years), enrolled in treatment for 0.04 to 5.90 years (median 1.3 years) at the Children's Obesity Clinic, Denmark. At baseline, weight and height were measured, body mass index (BMI) standard deviation score (SDS) calculated, and self-reported information on familial predisposition to obesity, hypertension, type 2 diabetes mellitus (T2DM), thromboembolic events, and dyslipidaemia were obtained. A familial predisposition included events in biological parents, siblings, grandparents, uncles, and aunts. The treatment outcomes were categorically analysed according to the prevalence of familial predispositions. The median BMI SDS at enrollment was 3.2 in boys and 2.8 in girls. One-thousand-and-forty-one children had obesity in their family, 773 had hypertension, 551 had T2DM, 568 had thromboembolic events, and 583 had dyslipidaemia. Altogether, 733 had three or more predispositions. At baseline, familial T2DM was associated with a higher mean BMI SDS (p = 0.03), but no associations were found between the other predispositions and the children's degree of obesity. During treatment, girls with familial obesity lost more weight, compared to girls without familial obesity (p = 0.04). No other familial predispositions were associated with changes in BMI SDS during treatment. Obese children with a familial predisposition to T2DM showed a significantly higher degree of obesity at baseline and girls with familial obesity responded better to treatment. Besides these findings, no other associations were found between the occurrence of familial predispositions and the degree of obesity or changes herein during

  11. A case of suspect “cyanosis”

    OpenAIRE

    Elisabetta Antonucci; Matteo Conte; Michele Di Pumpo; Giuseppe Antonucci

    2013-01-01

    CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO). Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed...

  12. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people.

    NARCIS (Netherlands)

    Henquet, C.J.; Krabbendam, L.; Spauwen, P.H.M.; Kaplan, C.; Lieb, R.; Wittchen, H.U.; Os, J. van

    2005-01-01

    OBJECTIVE: To investigate the relation between cannabis use and psychotic symptoms in individuals with above average predisposition for psychosis who first used cannabis during adolescence. DESIGN: Analysis of prospective data from a population based sample. Assessment of substance use,

  13. Verification of the model of predisposition in triathlon – structural model of confirmative factor analysis

    Directory of Open Access Journals (Sweden)

    Lenka Kovářová

    2012-09-01

    Full Text Available BACKGROUND: The triathlon is a combination of three different types of sport – swimming, cycling, and running. Each of these requires different top level predispositions and complex approach to talent selection is a rather difficult process. Attempts to identify assumptions in the triathlon have so far been specific and focused only on some groups of predispositions (physiology, motor tests, and psychology. The latest studies missed the structural approach and were based on determinants of sport performance, theory of sports training and expert assessment. OBJECTIVE: The aim of our study was to verify the model of predisposition in the short triathlon for talent assessment of young male athletes age 17–20 years. METHODS: The research sample consisted of 55 top level triathletes – men, who were included in the Government supported sports talent programme in the Czech Republic at the age of 17–20 years. We used a confirmative factor analysis (FA and Path diagram to verify the model, which allow us to explain mutual relationships among observed variables. For statistical data processing we used a structure equating modeling (SEM by software Lisrel L88. RESULTS: The study confirms best structural model for talent selection in triathlon at the age of 17–20 years old men, which composed seventeen indicators (tests and explained 91% of all cross-correlations (Goodness of Fit Index /GFI/ 0.91, Root Mean Square Residual /RMSR/ 0.13. Tests for predispositions in triathlons were grouped into five items, three motor predispositions (swimming, cycling and running skills, aerobic and psychological predispositions. Aerobic predispositions showed the highest importance to the assumptions to the general factor (1.00; 0. Running predispositions were measured as a very significant factor (–0.85; 0.28 which confirms importance of this critical stage of the race. Lower factor weight showed clusters of swimming (–0.61; 0.63 and cycling (0.53; 0

  14. The phenomenology of specialization of criminal suspects.

    Directory of Open Access Journals (Sweden)

    Michele Tumminello

    Full Text Available A criminal career can be either general, with the criminal committing different types of crimes, or specialized, with the criminal committing a specific type of crime. A central problem in the study of crime specialization is to determine, from the perspective of the criminal, which crimes should be considered similar and which crimes should be considered distinct. We study a large set of Swedish suspects to empirically investigate generalist and specialist behavior in crime. We show that there is a large group of suspects who can be described as generalists. At the same time, we observe a non-trivial pattern of specialization across age and gender of suspects. Women are less prone to commit crimes of certain types, and, for instance, are more prone to specialize in crimes related to fraud. We also find evidence of temporal specialization of suspects. Older persons are more specialized than younger ones, and some crime types are preferentially committed by suspects of different ages.

  15. From predisposition to psychosis: progression of symptoms in schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef

    1999-01-01

    Schizophrenia is increasingly viewed as a neurodevelopmental process caused by an interaction between genetic factors and environmental stressors. Prospective studies and retrospective research using objective data indicate that behavioural deviations can be dated to early infancy and cut across...

  16. A case of suspect “cyanosis”

    Directory of Open Access Journals (Sweden)

    Elisabetta Antonucci

    2013-05-01

    Full Text Available CLINICAL CASE A 70-year old woman was admitted to our hospital because of fever, asthenia and a suspected stroke. Her medical history showed a congenital cardiopathy (Patent Foramen Ovale, PFO. Skin and oral mucosa pigmentation, orthostatic hypotension, hypoglycemia and hyponatriemia arose the suspect of Addison’s disease. The diagnosis was confirmed by the evaluation of basal levels of plasma ACTH and serum cortisol, and serum cortisol levels after ACTH stimulation. Abdominal CT scan showed atrophy and calcification of adrenal glands. CONCLUSIONS In most cases, Addison’s disease is provoked by autoimmune destruction of the adrenal cortex; however, in our reported patient, tuberculosis could be a possible cause.

  17. Chronotype and personality factors of predisposition to seasonal affective disorder.

    Science.gov (United States)

    Oginska, Halszka; Oginska-Bruchal, Katarzyna

    2014-05-01

    The study aimed to recognize the personality factors of a predisposition to seasonal mood fluctuations in a non-clinical sample. A group of 101 subjects (57 women, 44 men; mean age 26.4 ± 6.5 years) completed a battery of tests comprising a Seasonal Pattern Assessment Questionnaire (SPAQ), Chronotype Questionnaire (ChQ), a NEO-Five Factor Inventory and a Coping Inventory for Stressful Situations (CISS). A smaller sample (n = 44) completed a Winter Blues Scale (WBS). Women scored significantly higher than men in seasonality (p = 0.014), neuroticism (p = 0.049), agreeableness (p = 0.010), and avoidance-oriented coping style (p = 0.041). Subjects with seasonal affective disorder (SAD) (n = 41) or sub-SAD (n = 33), as diagnosed with SPAQ, exhibited higher levels of neuroticism (p = 0.017) and openness (p = 0.016) in comparison to non-SAD individuals. The latter declared a less frequent avoidance coping style. Both measures of seasonality, i.e. the SPAQ Global Seasonality Score and WBS, correlated significantly (r = 0.28 and 0.44, respectively) with the subjective amplitude of the circadian rhythm, as described with the "distinctness" scale of ChQ. Female gender, neuroticism and openness were confirmed as factors linked to seasonal mood variability. Additionally, the study revealed an association between susceptibility to mild winter depression and an avoidance-oriented coping style. The avoidance coping style was correlated positively with all the aspects of seasonality described by SPAQ (correlation coefficients from 0.21 to 0.34). Both sub-types of avoidance-oriented style, i.e. distraction and social diversion, were associated with marked subjective seasonal changes in sleep length, mood and the energy level. While the subjective amplitude of circadian rhythm proved to be connected with seasonality, the subjective acrophase of the rhythm (morningness-eveningness preference) did not. It may be hypothesized that sensitivity

  18. CLINICAL AND GENETIC PARALLELS ALONG CELIAC DISEASE AMONG TOMSK CHILDREN

    OpenAIRE

    E.I. Kondrat’eva; Puzyrev, V.P.; L.P. Nazarenko; A. A. Rudko; G.N. Yankina; E.V. Loshkova

    2007-01-01

    The article is devoted to the analysis of the genetic predisposition to celiac disease. The authors studied the associations of the HLA genes and modifier genes of the immune response (interleukine 1, inter leukine 1 receptor antagonist, inter leukine 4, α-subunits of interleukine 4 receptor, receptor to D vitamin) along with predisposition to the disease, as well as the variants of its run and accompanied autoimmune diseases (autoimmune thyroiditis, insular diabetes type 1).Key words: celiac...

  19. Gene Expression Profiling of Dendritic Cells Reveals Important Mechanisms Associated with Predisposition to Staphylococcus Infections

    Science.gov (United States)

    Toufeer, Mehdi; Bonnefont, Cécile M. D.; Foulon, Eliane; Caubet, Cécile; Tasca, Christian; Aurel, Marie-Rose; Robert-Granié, Christèle; Rupp, Rachel; Foucras, Gilles

    2011-01-01

    Background Staphylococcus aureus is a major pathogen of humans and animals and emerging antibiotic-resistant strains have further increased the concern of this health issue. Host genetics influence susceptibility to S. aureus infections, and the genes determining the outcome of infections should be identified to find alternative therapies to treatment with antibiotics. Here, we used outbred animals from a divergent selection based on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals showing different degrees of susceptibility had distinct gene expression profiles. We measured gene expression levels of in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hrs) by using 15 k ovine Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes involved in the inflammatory process and T helper cell polarization were highly up-regulated upon stimulation. Moreover, a set of 204 genes were statistically differentially expressed between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, over-expression of the C1q and Ido1 genes was observed in the resistant line and suggested a role of classical pathway of complement and early regulation of inflammation pathways, respectively. On the contrary, over expression of genes involved in the IL1R pathway was observed in susceptible animals. Furthermore, the leucocyte extravasation pathway was also found to be dominant in the susceptible line. Conclusion/Significance We successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8-hour kinetics experiment. The distinct

  20. Hereditary predisposition to ovarian cancer, looking beyond BRCA1/BRCA2.

    Science.gov (United States)

    Minion, Lindsey E; Dolinsky, Jill S; Chase, Dana M; Dunlop, Charles L; Chao, Elizabeth C; Monk, Bradley J

    2015-04-01

    Genetic predisposition to ovarian cancer is well documented. With the advent of next generation sequencing, hereditary panel testing provides an efficient method for evaluating multiple genes simultaneously. Therefore, we sought to investigate the contribution of 19 genes identified in the literature as increasing the risk of hereditary breast and ovarian cancer (HBOC) in a BRCA1 and BRCA2 negative population of patients with a personal history of breast and/or ovarian cancer by means of a hereditary cancer panel. Subjects were referred for multi-gene panel testing between February 2012 and March 2014. Clinical data was ascertained from requisition forms. The incidence of pathogenic mutations (including likely pathogenic), and variant of unknown significance were then calculated for each gene and/or patient cohort. In this cohort of 911 subjects, panel testing identified 67 mutations. With 7.4% of subjects harboring a mutation on this multi-gene panel, the diagnostic yield was increased, compared to testing for BRCA1 and BRCA2 mutations alone. In the ovarian cancer probands, the most frequently mutated genes were BRIP1 (n=8; 1.72%) and MSH6 (n=6; 1.29%). In the breast cancer probands, mutations were most commonly observed in CHEK2 (n=9; 2.54%), ATM (n=3; 0.85%), and TP53 (n=3; 0.85%). Although further studies are needed to clarify the exact management of patients with a mutation in each gene, this study highlights information that can be captured with panel testing and provides support for incorporation of panel testing into clinical practice. Copyright © 2015. Published by Elsevier Inc.

  1. Neurological soft signs: Effects of trait schizotypy, psychological distress and auditory hallucination predisposition

    Directory of Open Access Journals (Sweden)

    Saskia de Leede-Smith

    2017-03-01

    Full Text Available Schizotypy is regarded as a trait vulnerability for psychotic disorders, yet alone is insufficient for development of a diagnosable disorder. Additional symptoms and psychological distress are necessary for help seeking and transition from an at risk mental state to a clinical diagnosis. The present study investigated the interaction between trait schizotypy, state auditory verbal hallucination (AVH predisposition, distress and handedness for the expression of neurological soft signs (NSS, a neurodevelopmental vulnerability factor for psychosis. Cluster analysis formed schizotypy groups statistically across the dimensions captured by the SPQ. It was hypothesized that schizotypy and AVH predisposition would interact, resulting in significantly greater NSS. Psychological distress and handedness were hypothesized to be significant covariates, accounting for some variance in the expression of NSS between the groups. A sample of University students (n = 327 completed the Schizotypal Personality Questionnaire, Launay-Slade Hallucination Scale, General Health Questionnaire and the Neurological Evaluation Scale (NES. Cluster Analysis revealed four schizotypy groups. Distress was not a significant covariate in any analysis. As expected, those with high overall schizotypy and high AVH predisposition expressed significantly greater Motor-Coordination NSS compared to those with high schizotypy and low AVH predisposition. Within the Mixed Interpersonal and Cognitive-Perceptual Schizotypy cluster, those with low AVH predisposition expressed significantly more Motor-Coordination NSS than those with high AVH predisposition. These findings suggest motor coordination NSS are detectable in schizotypy, and AVH predisposition appears to interact with these traits. This study highlights the importance of considering both trait and subclinical state risk factors when investigating risk for psychosis.

  2. Congenital Malaria Among Newborns Admitted for Suspected ...

    African Journals Online (AJOL)

    Background: Signs and symptoms of congenital malaria do not differ much from those of neonatal sepsis: both can co-exist, and most times very difficult to differentiate clinically. Objective: To document the prevalence, risk factors for congeni tal malar ia among neonates admitted for suspected neonatal sepsis, and ...

  3. Congenital Malaria Among Newborns Admitted for Suspected ...

    African Journals Online (AJOL)

    None of the clinical feature had good sensitivity, specificity or predictive value for congenital malaria, and only 1.6% death was recorded in a baby with high parasite density. Conclusion: Congenital malaria is common in newborns with suspected neonatal sepsis. History of peripartum pyrexia, prematurity and intrauterine ...

  4. MRI for clinically suspected appendicitis during pregnancy.

    NARCIS (Netherlands)

    Cobben, L.P.; Groot, I.; Haans, L.; Blickman, J.G.; Puylaert, J.

    2004-01-01

    OBJECTIVE: The purpose of this study was to evaluate whether MRI can be used to accurately diagnose or exclude appendicitis in pregnant patients with clinically suspected appendicitis. CONCLUSION: Our results suggest that MRI is helpful in the examination and diagnosis of acute appendicitis in

  5. Biomechanical properties of keratoconus suspect eyes.

    Science.gov (United States)

    Saad, Alain; Lteif, Yara; Azan, Elodie; Gatinel, Damien

    2010-06-01

    Measuring corneal biomechanical properties may help detect keratoconus suspect corneas and eliminate the risk of ectasia after LASIK. Data of 504 eyes separated into three groups were retrospectively reviewed: normal (n = 252), keratoconus suspect (n = 80), and keratoconus (n = 172). Corneal hysteresis (CH) and corneal resistance factor (CRF) were measured with an ocular biomechanics analyzer. Mean corneal hysteresis was 10.6 +/- 1.4 (SD) mm Hg in the normal group, compared with 10.0 +/- 1.6 mm Hg in the keratoconus suspect group and 8.1 +/- 1.4 mm Hg in the keratoconus group. The mean CRF was 10.6 +/- 1.6 mm Hg in the normal group compared with 9.7 +/- 1.7 in the keratoconus suspect group and 7.1 +/- 1.6 mm Hg in the keratoconus group. Mean CH and CRF were significantly different between the three groups (P corneas. Analyzing signal curves obtained with the biomechanics analyzer may provide additional valuable information for selecting qualified patients for refractive surgery.

  6. Characterization of suspected illegal skin whitening cosmetics.

    Science.gov (United States)

    Desmedt, B; Van Hoeck, E; Rogiers, V; Courselle, P; De Beer, J O; De Paepe, K; Deconinck, E

    2014-03-01

    An important group of suspected illegal cosmetics consists of skin bleaching products, which are usually applied to the skin of the face, hands and décolleté for local depigmentation of hyper pigmented regions or more importantly, for a generalized reduction of the skin tone. These cosmetic products are suspected to contain illegal active substances that may provoke as well local as systemic toxic effects, being the reason for their banning from the EU market. In that respect, illegal and restricted substances in cosmetics, known to have bleaching properties, are in particular hydroquinone, tretinoin and corticosteroids. From a legislative point of view, all cosmetic products containing a prohibited whitening agent are illegal and must be taken off the EU market. A newly developed screening method using ultra high performance liquid chromatography-time off flight-mass spectrometry allows routine analysis of suspected products. 163 suspected skin whitening cosmetics, collected by Belgian inspectors at high risk sites such as airports and so-called ethnic cosmetic shops, were analyzed and 59% were classified as illegal. The whitening agents mostly detected were clobetasol propionate and hydroquinone, which represent a serious health risk when repeatedly and abundantly applied to the skin. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Suspecting Neurological Dysfunction From E Mail Messages ...

    African Journals Online (AJOL)

    A non medical person suspected and confirmed neurological dysfunction in an individual, based only on e mail messages sent by the individual. With email communication becoming rampant “peculiar” email messages may raise the suspicion of neurological dysfunction. Organic pathology explaining the abnormal email ...

  8. Familial predisposition to developmental dysplasia of the hip.

    Science.gov (United States)

    Stevenson, David A; Mineau, Geraldine; Kerber, Richard A; Viskochil, David H; Schaefer, Carole; Roach, James W

    2009-01-01

    Developmental dysplasia of the hip (DDH) is a common birth defect and is thought to have genetic contributions to the phenotype. It is likely that DDH is genetically heterogeneous with environmental modifiers. The Utah Population Database (UPDB) is a computerized integration of pedigrees, vital statistics, and medical records representing over 6 million individuals, and is a unique resource providing the ability to search for familial factors beyond the nuclear family, decreasing the effect of a shared environment. The purpose of this study is to assess the degree of relationship between individuals with DDH. Datasets were created from UPDB statewide birth certificates and from the University of Utah Health Sciences Center enterprise data warehouse using records for DDH and linked to the UPDB. Controls for the dataset were selected that matched cases on birth year and sex and 10 controls were selected per case. Statistics computed for each family were the number of descendants, the observed number of affected, the expected number of affected, P value, familial standardize incidence ratio, relative risks (RRs), and standard error. A kinship analysis tool was used to find pedigrees with excess DDH. The combined data resulted in 1649 distinct individuals with DDH. RR was significantly increased in first-degree relatives (RR=12.1; Pdata suggest a genetic contribution to DDH with a 12-fold increase in risk for first-degree relatives. Better phenotypic characterization and classification will be critical for future genetic analyses.

  9. Identification of pathogenic retrotransposon insertions in cancer predisposition genes.

    Science.gov (United States)

    Qian, Yaping; Mancini-DiNardo, Debora; Judkins, Thaddeus; Cox, Hannah C; Brown, Krystal; Elias, Maria; Singh, Nanda; Daniels, Courtney; Holladay, Jayson; Coffee, Bradford; Bowles, Karla R; Roa, Benjamin B

    2017-10-01

    Cancer risks have been previously reported for some retrotransposon element (RE) insertions; however, detection of these insertions is technically challenging and very few oncogenic RE insertions have been reported. Here we evaluate RE insertions identified during hereditary cancer genetic testing using a comprehensive testing strategy. Individuals who had single-syndrome or pan-cancer hereditary cancer genetic testing from February 2004 to March 2017 were included. RE insertions were identified using Sanger sequencing, Next Generation Sequencing, or multiplex quantitative PCR, and further characterized using targeted PCR and sequencing analysis. Personal cancer history, ancestry, and haplotype were evaluated. A total of 37 unique RE insertions were identified in 10 genes, affecting 211 individuals. BRCA2 accounted for 45.9% (17/37) of all unique RE insertions. Several RE insertions were detected with high frequency in populations of conserved ancestry wherein up to 100% of carriers shared a high degree of haplotype conservation, suggesting founder effects. Our comprehensive testing strategy resulted in a substantial increase in the number of reported oncogenic RE insertions, several of which may have possible founder effects. Collectively, these data show that the detection of RE insertions is an important component of hereditary cancer genetic testing and may be more prevalent than previously reported. Copyright © 2017 Myriad Genetics, Inc. Published by Elsevier Inc. All rights reserved.

  10. Evaluation of Patients and Families With Concern for Predispositions to Hematologic Malignancies Within the Hereditary Hematologic Malignancy Clinic (HHMC).

    Science.gov (United States)

    DiNardo, Courtney D; Bannon, Sarah A; Routbort, Mark; Franklin, Anna; Mork, Maureen; Armanios, Mary; Mace, Emily M; Orange, Jordan S; Jeff-Eke, Meselle; Churpek, Jane E; Takahashi, Koichi; Jorgensen, Jeffrey L; Garcia-Manero, Guillermo; Kornblau, Steve; Bertuch, Alison; Cheung, Hannah; Bhalla, Kapil; Futreal, Andrew; Godley, Lucy A; Patel, Keyur P

    2016-07-01

    Although multiple predispositions to hematologic malignancies exist, evaluations for hereditary cancer syndromes (HCS) are underperformed by most hematologist/oncologists. Criteria for initiating HCS evaluation are poorly defined, and results of genetic testing for hereditary hematologic malignancies have not been systematically reported. From April 2014 to August 2015, 67 patients were referred to the Hereditary Hematologic Malignancy Clinic (HHMC). Referral reasons included (1) bone marrow failure or myelodysplastic syndrome in patients ≤ 50 years, (2) evaluation for germ-line inheritance of identified RUNX1, GATA2, or CEBPA mutations on targeted next-generation sequencing panels, and (3) strong personal and/or family history of malignancy. Cultured skin fibroblasts were utilized for germ-line DNA in all patients with hematologic malignancy. Eight patients (12%) were clinically diagnosed with a HCS: 4 patients with RUNX1-related familial platelet disorder (FPD)/acute myeloid leukemia (AML), and 1 patient each with dyskeratosis congenita, Fanconi anemia, germ-line DDX41, and Li-Fraumeni syndrome (LFS). Two patients with concern for FPD/AML and LFS, respectively, had RUNX1 and TP53 variants of unknown significance. Additionally, 4 patients with prior HCS diagnosis (1 LFS, 3 FPD/AML) were referred for further evaluation and surveillance. In this HHMC-referred hematologic malignancy cohort, HCS was confirmed in 12 patients (18%). HCS identification provides insight for improved and individualized treatment, as well as screening/surveillance opportunities for family members. The HHMC has facilitated HCS diagnosis; with increased clinical awareness of hematologic malignancy predisposition syndromes, more patients who may benefit from evaluation can be identified. Mutation panels intended for prognostication may provide increased clinical suspicion for germ-line testing. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Suspected poisoning of domestic animals by pesticides.

    Science.gov (United States)

    Caloni, Francesca; Cortinovis, Cristina; Rivolta, Marina; Davanzo, Franca

    2016-01-01

    A retrospective study was carried out by reviewing all suspected cases of domestic animal poisoning attributed to pesticides, reported to the Milan Poison Control Centre (MPCC) between January 2011 and December 2013. During this period, pesticides were found to be responsible for 37.3% of all suspected poisoning enquiries received (815). The most commonly species involved was the dog (71.1% of calls) followed by the cat (15.8%), while a limited number of cases involved horses, goats and sheep. Most cases of exposure (47.1%) resulted in mild to moderate clinical signs. The outcome was reported in 59.9% of these cases, with death occurring in 10.4% of them. Insecticides (40.8%) proved to be the most common group of pesticides involved and exposure to pyrethrins-pyrethroids accounted for the majority of calls. According to the MPCC data, there has been a decrease in the number of suspected poisonings cases attributed to pesticides that have been banned by the EU, including aldicarb, carbofuran, endosulfan and paraquat. In contrast, there has been an increase of suspected poisoning cases attributed to the neonicotinoids, imidacloprid and acetamiprid, probably due to their widespread use in recent years. Cases of suspected poisoning that involved exposure to rodenticides accounted for 27.6% of calls received by the MPCC and anticoagulant rodenticides were the primary cause of calls, with many cases involving brodifacoum and bromadiolone. Herbicides were involved in 14.2% of calls related to pesticides and glyphosate was the main culprit in cases involving dogs, cats, horses, goats and sheep. As far as exposure to molluscicides (11.5%) and fungicides (5.9%), most of the cases involved dogs and the suspected poisoning agents were metaldehyde and copper compounds respectively. The data collected are useful in determining trends in poisoning episodes and identifying newly emerging toxicants, thus demonstrating the prevalence of pesticides as causative agents in animal

  12. From predisposition to psychosis: progression of symptoms in schizophrenia

    DEFF Research Database (Denmark)

    Parnas, Josef

    1999-01-01

    Schizophrenia is increasingly viewed as a neurodevelopmental process caused by an interaction between genetic factors and environmental stressors. Prospective studies and retrospective research using objective data indicate that behavioural deviations can be dated to early infancy and cut across...... multiple behavioural domains. In adolescence, preschizophrenics exhibit subtle changes in cognition and affect as well as a variety of anomalous subjective experiences (so-called 'basic symptoms'), suggesting 'trait' status of these features. Prodromal symptoms occur in a substantial proportion...

  13. Cannabis use and genetic predisposition for schizophrenia : a case-control study

    NARCIS (Netherlands)

    Veling, W; Mackenbach, J P; van Os, J; Hoek, H W

    BACKGROUND: Cannabis use may be a risk factor for schizophrenia. Part of this association may be explained by genotype-environment interaction, and part of it by genotype-environment correlation. The latter issue has not been explored. We investigated whether cannabis use is associated with

  14. Women's acceptance of MRI in breast cancer surveillance because of a familial or genetic predisposition

    NARCIS (Netherlands)

    Essink-Bot, M. L.; Rijnsburger, A. J.; van Dooren, S.; de Koning, H. J.; Seynaeve, C.

    2006-01-01

    Magnetic resonance imaging (MRI) of the breasts is a promising screening modality for early detection in women at increased breast cancer risk. We investigated the subjective experiences with MRI and the preferences for MRI, mammography or clinical breast examination in 178 high-risk women adhering

  15. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    NARCIS (Netherlands)

    E.J. Sawyer (Elinor); R. Roylance (Rebecca); C. Petridis (Christos); R.H. Brook; S. Nowinski (Salpie); E. Papouli (Efterpi); O. Fletcher (Olivia); S. Pinder (Sarah); A. Hanby (Andrew); K. Kohut (Kelly); P. Gorman (Patricia); M. Caneppele (Michele); J. Peto (Julian); I. dos Santos Silva (Isabel); N. Johnson (Nichola); R. Swann (Ruth); M. Dwek (Miriam); K.-A. Perkins (Katherine-Anne); C. Gillett (Cheryl); R. Houlston (Richard); G. Ross (Gillian); P. de Ieso (Paolo); M.C. Southey (Melissa); J.L. Hopper (John); E. Provenzano (Elena); C. Apicella (Carmel); J. Wesseling (Jelle); S. Cornelissen (Sten); J.N. Keeman; P.A. Fasching (Peter); S.M. Jud (Sebastian); A.B. Ekici (Arif); M.W. Beckmann (Matthias); M. Kerin (Michael); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); B. Burwinkel (Barbara); P. Guénel (Pascal); T. Truong (Thérèse); P. Laurent-Puig (Pierre); P. Kerbrat (Pierre); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); S.F. Nielsen (Sune); H. Flyger (Henrik); R.L. Milne (Roger); J.I.A. Perez (Jose Ignacio Arias); P. Menéndez (Primitiva); J. Benítez (Javier); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Meindl (Alfons); P. Lichtner (Peter); R.K. Schmutzler (Rita); M. Lochmann (Magdalena); H. Brauch (Hiltrud); H.-P. Fischer; Y-D. Ko (Yon-Dschun); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Lindblom (Annika); S. Margolin (Sara); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); G. Chenevix-Trench (Georgia); D. Lambrechts (Diether); C. Weltens (Caroline); E. van Limbergen (Erik); S. Hatse (Sigrid); J. Chang-Claude (Jenny); A. Rudolph (Anja); P. Seibold (Petra); D. Flesch-Janys (Dieter); P. Radice (Paolo); P. Peterlongo (Paolo); B. Bonnani (Bernardo); S. Volorio (Sara); G.G. Giles (Graham); G. Severi (Gianluca); L. Baglietto (Laura); C.A. McLean (Catriona Ann); C.A. Haiman (Christopher); B.E. Henderson (Brian); F.R. Schumacher (Fredrick); L. Le Marchand (Loic); J. Simard (Jacques); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); V. Kristensen (Vessela); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); S. Kauppila (Saila); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); P. Devillee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); M. Kriege (Mieke); J.D. Figueroa (Jonine); S.J. Chanock (Stephen); M.E. Sherman (Mark); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); A.M.W. van den Ouweland (Ans); C.H.M. van Deurzen (Carolien); J. Li (Jingmei); K. Czene (Kamila); M.K. Humphreys (Manjeet); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); M. Shah (Mitul); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska-Bieniek (Katarzyna); K. Durda (Katarzyna); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); F.J. Couch (Fergus); B. Hallberg (Boubou); A. González-Neira (Anna); G. Pita (G.); M.R. Alonso (M Rosario); Y. Tessier (Yann); D. Vincent (Daniel); F. Bacot (Francois); M.K. Bolla (Manjeet); Q. Wang (Qing); J. Dennis (Joe); K. Michailidou (Kyriaki); A.M. Dunning (Alison); P. Hall (Per); D.F. Easton (Douglas); P.D.P. Pharoah (Paul); M.K. Schmidt (Marjanka); I.P. Tomlinson (Ian); M. García-Closas (Montserrat)

    2014-01-01

    textabstractInvasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to

  16. Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond.

    Science.gov (United States)

    Hall, M J; Obeid, E I; Schwartz, S C; Mantia-Smaldone, G; Forman, A D; Daly, M B

    2016-03-01

    Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multi-gene panel tests is critical for providers on the front-line of women's health. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Genetic testing for hereditary cancer predisposition: BRCA1/2, Lynch syndrome, and beyond

    Science.gov (United States)

    Hall, MJ; Obeid, EI; Schwartz, SC; Mantia-Smaldone, G; Forman, AD; Daly, MB

    2016-01-01

    Obstetrician/gynecologists and gynecologic oncologists serve an integral role in the care of women at increased hereditary risk of cancer. Their contribution includes initial identification of high risk patients, screening procedures like bimanual exam, trans-vaginal ultrasound and endometrial biopsy, prophylaxis via TAH and/or BSO, and chemoprevention. Further, gynecologists also serve a central role in the management of the secondary repercussions of efforts to mitigate increased cancer risks, including vasomotor symptoms, sexual function, bone health, cardiovascular disease, and mental health. The past several years has seen multiple new high and moderate penetrance genes introduced into the clinical care of women at increased risk of gynecologic malignancy. Awareness of these new genes and the availability of new multigene panel tests is critical for providers on the front-line of women’s health. PMID:26812021

  18. Effect of team sport participation on genetic predisposition to adolescent smoking progression.

    Science.gov (United States)

    Audrain-McGovern, Janet; Rodriguez, Daniel; Wileyto, E Paul; Schmitz, Kathryn H; Shields, Peter G

    2006-04-01

    There is much to be learned about why some adolescents progress to a regular smoking habit and others do not. To evaluate whether (1) team sport participation buffers the effect of having 2 smoking risk genotypes (the dopamine reuptake transporter [SLC6A3] and the dopamine D(2) receptor [DRD2]) or 1 of these risk genotypes vs having none on adolescent smoking progression and (2) the buffering effects of team sports were due to physical activity associated with team sport participation. Longitudinal cohort study. Survey data were collected annually from grade 9 to the end of grade 12. Self-report measures included smoking, team sport participation, physical activity, depression, smoking exposure, and alcohol and marijuana use. DNA was collected via buccal swabs. Data were analyzed using latent growth modeling. Five public high schools in Virginia. A total of 361 students of European ancestry. Main Outcome Measure Smoking progression. For adolescents participating in at least 1 team sport, but not for adolescents with no team sport participation, physical activity had a significant negative effect on smoking progression (z = -3.85, Psport but not for adolescents with no team sport participation. This study provides the first evidence of an interaction between environmental influences and specific genes on adolescent smoking and may promote an understanding of important protective relationships in the environment.

  19. [The wakefulness-sleep cycle in rats with a genetic predisposition to catalepsy].

    Science.gov (United States)

    Oganesian, G A; Khomutetskaia, O E; Bogoslovskiĭ, M M; Karmanova, I G; Kolpakov, V G; Barykina, N N

    1990-01-01

    Neurophysiological studies on wakefulness-sleep cycle have been made in rats selected for hereditary inclination to catalepsy. It was shown that in these animals, the stage of delta-sleep is significantly reduced, whereas the duration of a superficial slow-wave sleep is increased. In a sleeping phase of the cycle, large amount of spindles in the range of alpha- and beta 1-oscillations was observed, especially significant in electrograms of n. caudatum and sensorimotor cortex. This activity is considered as a pathological manifestation of a transient hypnotic phase which includes the increase in immobilization of a cataleptic type.

  20. Genetic predisposition to fiber carcinogenesis causes a mesothelioma epidemic in Turkey.

    OpenAIRE

    Dogan, A. Umran; Baris, Y. Izzettin; Dogan, Meral; Emri, Salih; Steele, Ian; Elmishad, Amira G.; Carbone, Michele

    2006-01-01

    Cancer type: Malignant mesotheliomaStudy design: cohort studyStudy size: 24 family pedigreesDescription of cohort(s) studied: people born in three villages in Cappadocia (Turkey): villages of Tuzkoy, Karain, and 'Old' Sarihidir, where approximately 50% of deaths are caused by malignant mesotheliomaExposure(s) evaluated: erioniteImpact on risk: The X-ray diffraction pattern and the crystal structure of erionite from malignant mesothelioma villages were determined and compared the results with ...

  1. Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy

    NARCIS (Netherlands)

    Wasielewski, Marijke; van Spaendonck-Zwarts, Karin Y; Westerink, Nico-Derk L; Jongbloed, Jan D H; Postma, Aleida; Gietema, Jourik A; van Tintelen, J Peter; van den Berg, Maarten P

    2014-01-01

    OBJECTIVE: Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that

  2. Genetic predisposition to ductal carcinoma in situ of the breast

    DEFF Research Database (Denmark)

    Petridis, Christos; Brook, Mark N; Shah, Vandna

    2016-01-01

    BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, o...

  3. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism.

    Science.gov (United States)

    Oldridge, Derek A; Wood, Andrew C; Weichert-Leahey, Nina; Crimmins, Ian; Sussman, Robyn; Winter, Cynthia; McDaniel, Lee D; Diamond, Maura; Hart, Lori S; Zhu, Shizhen; Durbin, Adam D; Abraham, Brian J; Anders, Lars; Tian, Lifeng; Zhang, Shile; Wei, Jun S; Khan, Javed; Bramlett, Kelli; Rahman, Nazneen; Capasso, Mario; Iolascon, Achille; Gerhard, Daniela S; Guidry Auvil, Jaime M; Young, Richard A; Hakonarson, Hakon; Diskin, Sharon J; Look, A Thomas; Maris, John M

    2015-12-17

    Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells. Here we investigate the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation and transcription factor binding sites. We show that SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 × 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding (P neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumour cells.

  4. Prevalence of Hyperinsulinemia Associated with Body Mass Index, Genetic Predisposition, and Lifestyle in College Freshmen Students

    Science.gov (United States)

    Hopper, Mari K.; Brown, Gordon W.; Funke, Katharine A.; Pike Brown, Leslie R.

    2012-01-01

    Objective: College lifestyle places an individual at greater risk for the development of insulin resistance (IR) and disease. The aim of this study was to establish a baseline measurement of insulin, and other variables influencing IR in college freshmen. Participants: Twenty-two men and women, 18 to 19 years of age, during first month of college.…

  5. A possible association between the genetic predisposition for dizygotic twinning and schizophrenia

    DEFF Research Database (Denmark)

    Kläning, Ulla; Pedersen, Carsten Bøcker; Mortensen, Preben Bo

    2002-01-01

    BACKGROUND: A previous study demonstrated a 40% higher rate of schizophrenia in dizygotic twins than in the general population. The aim of the present study is to evaluate whether genes influencing the rate of dizygotic twinning and genes of importance for developing schizophrenia can be associat...

  6. Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast

    DEFF Research Database (Denmark)

    Sawyer, Elinor; Roylance, Rebecca; Petridis, Christos

    2014-01-01

    Invasive lobular breast cancer (ILC) accounts for 10-15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast can...

  7. Syndromic Gastric Polyps : At the Crossroads of Genetic and Environmental Cancer Predisposition

    NARCIS (Netherlands)

    Brosens, Lodewijk A A|info:eu-repo/dai/nl/314060944; Giardiello, Francis M; Offerhaus, G Johan|info:eu-repo/dai/nl/070543283; Montgomery, Elizabeth A

    2016-01-01

    Gastric polyps occur in 1-4 % of patients undergoing gastroscopy. Although most are sporadic, some gastric polyps are part of an underlying hereditary syndrome. Gastric polyps can be seen in each of the well-known gastrointestinal polyposis syndromes, but also in Lynch syndrome and in several rare

  8. Research Directions in Genetic Predispositions to Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis.

    Science.gov (United States)

    Manolio, Teri A; Hutter, Carolyn M; Avigan, Mark; Cibotti, Ricardo; Davis, Robert L; Denny, Joshua C; Grenade, Lois La; Wheatley, Lisa M; Carrington, Mary N; Chantratita, Wasun; Chung, Wen-Hung; Dalton, Andrea D; Hung, Shuen-Iu; Lee, Ming Ta Michael; Leeder, J Steven; Lertora, Juan J L; Mahasirimongkol, Surakameth; McLeod, Howard L; Mockenhaupt, Maja; Pacanowski, Michael; Phillips, Elizabeth J; Pinheiro, Simone; Pirmohamed, Munir; Sung, Cynthia; Suwankesawong, Wimon; Trepanier, Lauren; Tumminia, Santa J; Veenstra, David; Yuliwulandari, Rika; Shear, Neil H

    2018-03-01

    Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is one of the most devastating of adverse drug reactions (ADRs) and was, until recently, essentially unpredictable. With the discovery of several risk alleles for drug-induced SJS/TEN and the demonstration of effectiveness of screening in reducing incidence, the stage is set for implementation of preventive strategies in populations at risk. Yet much remains to be learned about this potentially fatal complication of commonly used drugs. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  9. Exploring predisposition and treatment response--the promise of genomics.

    Science.gov (United States)

    Pan, Stephen; Knowles, Joshua W

    2012-01-01

    Spurred by large-scale public and private efforts as well as technological developments, the last few years have seen a major leap forward in our understanding of the genetic basis of cardiovascular disease. This revolution is in its infancy and will continue to alter the medical landscape for years to come. There is a need within the general cardiology community to develop a better understanding about how these developments may alter routine clinical care. In this review, we will provide an overview of the current state of genetics as pertains to rare cardiovascular diseases and then review advances in the discovery of the genetic basis of common disease with the potential for improved risk assessment and drug development. We will also outline a few recent examples of pharmacogenetic advances that are already starting to become a part of clinical management and finally discuss the promise as well as the challenges in using next-generation sequencing technologies to provide personalized cardiovascular care. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. The Influence of Familial Predisposition to Cardiovascular Complications upon Childhood Obesity Treatment

    DEFF Research Database (Denmark)

    Nielsen, Louise A; Bøjsøe, Christine; Kloppenborg, Julie T

    2015-01-01

    INTRODUCTION: The aim was to investigate whether a familial predisposition to obesity related cardiovascular complications was associated with the degree of obesity at baseline and/or changes in the degree of obesity during a multidisciplinary childhood obesity treatment program. METHODS: The study...... included 1421 obese children (634 boys) with a median age of 11.5 years (range 3.1-17.9 years), enrolled in treatment for 0.04 to 5.90 years (median 1.3 years) at the Children's Obesity Clinic, Denmark. At baseline, weight and height were measured, body mass index (BMI) standard deviation score (SDS......) calculated, and self-reported information on familial predisposition to obesity, hypertension, type 2 diabetes mellitus (T2DM), thromboembolic events, and dyslipidaemia were obtained. A familial predisposition included events in biological parents, siblings, grandparents, uncles, and aunts. The treatment...

  11. The evaluation of suspected child physical abuse.

    Science.gov (United States)

    Christian, Cindy W

    2015-05-01

    Child physical abuse is an important cause of pediatric morbidity and mortality and is associated with major physical and mental health problems that can extend into adulthood. Pediatricians are in a unique position to identify and prevent child abuse, and this clinical report provides guidance to the practitioner regarding indicators and evaluation of suspected physical abuse of children. The role of the physician may include identifying abused children with suspicious injuries who present for care, reporting suspected abuse to the child protection agency for investigation, supporting families who are affected by child abuse, coordinating with other professionals and community agencies to provide immediate and long-term treatment to victimized children, providing court testimony when necessary, providing preventive care and anticipatory guidance in the office, and advocating for policies and programs that support families and protect vulnerable children. Copyright © 2015 by the American Academy of Pediatrics.

  12. Suspects in criminal investigations of rape

    Directory of Open Access Journals (Sweden)

    Marinković Darko

    2014-01-01

    Full Text Available Investigations of sexual assaults mostly focus on victims and their credibility, which may cause lack of firm evidence in relation to suspects. Given the fact that the criminal offence of rape is characterised by a high incidence of false reports and accusations, frequently indicating specific persons as the perpetrators, certain caution is necessary in the investigation in order to avoid false accusations and/or convictions. As regards the personality of the rapist and motives for committing a forcible sexual act, certain types or rather certain categories of perpetrators can be distinguished, although it should be noted that a large number of rapists do not belong to one category only, but rather combine characteristics of several different types. During a criminal investigation it is of vital importance to differentiate between a rape as a surprise attack and a rape as abuse of trust, as they are compatible with the nature of the suspect's defence. The suspect shall be subjected to a forensic examination in the course of the investigation in order to find traces which prove vaginal, anal or oral penetration, coerced sexual intercourse and identity of the rapist. While conducting an interrogation of a suspected rapist, a crime investigating officer shall use either factual or emotional approach to his interviewee, depending on his psychological and motivational characteristics. In this regard, the factual approach is believed to be more efficient with anger rapists and sadistic rapists, whereas the compassionate approach gives good results with the gentlemen-rapists and partly with the power asserting rapists.

  13. Glaucoma suspect & Humphrey Field Analyzer a correlation

    Directory of Open Access Journals (Sweden)

    P Dahal

    2012-09-01

    Full Text Available Glaucoma originally meant "clouded", in Greek.The term glaucoma refers to a group of diseases that have in common characteristic optic neuropathy with associated visual field loss for which elevated intraocular pressure is one of the primary risk factor. The purpose of the study is to correlate the clinically diagnosed cases of glaucoma suspect with the Humphrey Field Analyzer (HFA. Fifty cases of glaucoma suspect who attended the glaucoma clinic of Nepal Eye Hospital Tripureswor, Kathmandu, Nepal and who meets at least two criteria, among the four types of glaucoma suspects were advised for the HFA for the study. In this study out of 50 patient, 36 (72% patients had normal visual field. 14 (28% patients had thinning of the neural retinal rim (NRR in both eyes. The significant relation with thinning of neural retina rim and glaucomatous hemifield test was found in the study. Journal of College of Medical Sciences-Nepal,2012,Vol-8,No-1, 23-28 DOI: http://dx.doi.org/10.3126/jcmsn.v8i1.6822

  14. Tocolytics for suspected intrapartum fetal distress.

    Science.gov (United States)

    Kulier, R; Hofmeyr, G J

    2000-01-01

    Prophylactic tocolysis with betamimetics and other agents has become widespread as a treatment for fetal distress. Uterine relaxation may improve placental blood flow and therefore fetal oxygenation. However there may also be adverse maternal cardiovascular effects. The objective of this review was to assess the effects of tocolytic therapy for suspected fetal distress on fetal, maternal and perinatal outcomes. We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: February 1999. Randomised trials comparing tocolytic therapy with no treatment or treatment with another tocolytic agent for suspected fetal distress. Two reviewers assessed trial quality and extracted data. Three studies were included. Compared with no treatment, there were fewer failed improvements in fetal heart rate abnormalities with tocolytic therapy (relative risk 0.26, 95% 0.13 to 0.53). Betamimetic therapy compared with magnesium sulphate showed a non-significant trend towards reduced uterine activity (relative risk 0.07, 95% confidence interval 0.00 to 1.10). Betamimetic therapy appears to be able to reduce the number of fetal heart rate abnormalities and perhaps reduce uterine activity. However there is not enough evidence based on clinically important outcomes to evaluate the use of betamimetics for suspected fetal distress.

  15. TLR2-TLR4/CD14 polymorphisms and predisposition to severe invasive infections by Neisseria meningitidis and Streptococcus pneumoniae.

    Science.gov (United States)

    Tellería-Orriols, J J; García-Salido, A; Varillas, D; Serrano-González, A; Casado-Flores, J

    2014-01-01

    Streptococcus pneumoniae and Neisseria meningitidis are major causes of severe invasive bacterial infections in some individuals. Apparently the genetic is a major susceptibility determinant to these infectious diseases. We study if the functional polymorphisms within genes of the innate immune system (TLR2-TLR4 and CD14) are related to the predisposition to severe invasive infections caused by S. pneumoniae and N. meningitidis. Prospective descriptive study. Sixty-six Caucasian healthy children and 173 consecutive Caucasian children with invasive bacterial infections by N. meningitidis (n=59) and S. pneumoniae (n=114) were enrolled between January 1, 2008 and December 31, 2010. All blood samples were genotyped with description of the coding polymorphisms in p.R753Q of TLR2 gene and p.D299G of TLR4 gene as well as the promotor polymorphism c.-159C>T of the CD14 gene. Compared to the controls the p.753Q allele of TLR2 and the allele c.-159T of CD14 were more frequent in patients with S. pneumoniae (pGenetical variations in the innate immune system by polymorphisms in the TLR2 and CD14, could be related with an increases susceptibility to severe invasive infections by S. pneumoniae and N. meningitidis. Copyright © 2013 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  16. Tuberous breast and predisposition to breast deformity in consanguineous.

    Science.gov (United States)

    Dessy, Luca Andrea; De Santo, Liliana; Onesti, Maria Giuseppina; Fallico, Nefer; Mazzocchi, Marco

    2018-01-01

    Tuberous breast deformity is a pathologic condition of the breast consisting of a constricting ring at the breast base, reduction in the volume of the breast parenchyma, and herniation of breast tissue through the nipple-areola complex with areola enlargement. This pathology is generally congenital and has an unknown etiopathogenesis. We report the first observation of tuberous breast deformity in consanguineous. This report suggests the potential role of a genetic base in the development of this deformity. Between May 2008 and March 2011, we observed six female patients from two different families, aged between 18 and 55 years, affected by tuberous breast deformity. The breast deformity was characterized by breast asymmetry in all six cases. Four patients underwent surgery to correct the deformity. Standardized objective measurements of breast and chest were taken. A Visual Analog Scale was used to evaluate patients' and physicians' satisfaction. The first three patients were consanguineous; two were first cousins, and the third was second cousin with one of the above. The other three patients were also from the same family: two sisters and their mother. According to Von Heimburg's classification, the patients presented different degrees of breast deformity. In all operated cases, a good esthetic result with a high satisfaction (average visual analog scale score 9) was achieved. The results remained stable over time and no revisions were needed after the 1-year follow-up. The possibility of a parental consanguinity for breast deformities such tuberous breast has never been described in the literature. This report suggests the possible genetic role in the development of tuberous breast deformity. Further studies and genetic tests are required to prove this hypothesis. © 2017 Wiley Periodicals, Inc.

  17. Clinical characteristics, management and long-term outcome of suspected rapid eye movement sleep behaviour disorder in 14 dogs.

    Science.gov (United States)

    Schubert, T A; Chidester, R M; Chrisman, C L

    2011-02-01

    To describe the clinical characteristics, management and long-term outcome in dogs with suspected rapid eye movement sleep behaviour disorder. Medical records and video recordings of 14 dogs with suspected rapid eye movement sleep behaviour disorder were reviewed and the owners were contacted via telephone or email for further information. Clinical signs included episodes of violent limb movements, howling, barking, growling, chewing, or biting during sleep. Episodes occurred at night and during daytime naps. The age at onset ranged from 8 weeks to 7·5 years with a median of 6 years but 64% of dogs were one year or less. There was no apparent sex or breed predisposition. Rapid eye movement sleep behaviour disorder events were reduced in severity and frequency in 78% of the dogs treated with 40 mg/kg/day oral potassium bromide. One dog was euthanized within 3 months of the onset of signs because of their severity. The duration of the disorder in the 13 surviving dogs ranged from 1·5 to 9 years. None of the dogs spontaneously recovered. Rapid eye movement sleep behaviour disorder is suspected to occur in dogs, as it does in human beings. It causes concern to the owners and disrupts the home environment. Unlike human beings, rapid eye movement sleep behaviour disorder of dogs often has a juvenile onset. © 2011 British Small Animal Veterinary Association.

  18. [Review of genetic research and testing in sport].

    Science.gov (United States)

    Marosi, Krisztina; Horváth, Endre; Nagy, Péter; Köles, Bernadett; Nagy, Zsolt B

    2012-08-12

    There is compelling evidence for a genetic contribution to physical performance. In addition, there is an advanced scientific knowledge on the predisposition to sports-related diseases and injuries. Genetic testing of performance related polymorphisms can serve as a new opportunity for developing the process of talent selection. Sport-related genetic information may also allow for individualization of the training and improve performance. Genetic testing may also play an important role in the pre-participation screening for injuries and disease risks.

  19. Personality Predispositions to Depression in Children of Affectively-Ill Parents: The Buffering Role of Self-Esteem

    Science.gov (United States)

    Abela, John R. Z.; Fishman, Michael B.; Cohen, Joseph R.; Young, Jami F.

    2012-01-01

    A major theory of personality predispositions to depression posits that individuals who possess high levels of self-criticism and/or dependency are vulnerable to developing depression following negative life events. The goal of the current study was to test this theory of personality predispositions and the self-esteem buffering hypothesis in a…

  20. The Role of Social Factors in Iranian University Students' Predispositions towards Autonomous Language Learning

    Science.gov (United States)

    Naeeini, Sara Kashefian; Riazi, Abdolmehdi; Salehi, Hadi

    2012-01-01

    In order to meet the demands of the changing world, students should become endowed with the ability to learn perpetually and regard learning as a life-long enterprise. This study investigated those learners belief which showed learners' predispositions toward autonomy and some social factors such as gender, academic achievement, marital status and…

  1. The influence of water table depth and the free atmospheric state on convective rainfall predisposition

    Science.gov (United States)

    Sara Bonetti; Gabriele Manoli; Jean-Christopher Domec; Mario Putti; Marco Marani; Gabriel G. Katul

    2015-01-01

    A mechanistic model for the soil-plant system is coupled to a conventional slab representation of the atmospheric boundary layer (ABL) to explore the role of groundwater table (WT) variations and free atmospheric (FA) states on convective rainfall predisposition (CRP) at a Loblolly pine plantation site situated in the lower coastal plain of North Carolina....

  2. Whole-exome sequencing identifies rare pathogenic variants in new predisposition genes for familial colorectal cancer.

    Science.gov (United States)

    Esteban-Jurado, Clara; Vila-Casadesús, Maria; Garre, Pilar; Lozano, Juan José; Pristoupilova, Anna; Beltran, Sergi; Muñoz, Jenifer; Ocaña, Teresa; Balaguer, Francesc; López-Cerón, Maria; Cuatrecasas, Miriam; Franch-Expósito, Sebastià; Piqué, Josep M; Castells, Antoni; Carracedo, Angel; Ruiz-Ponte, Clara; Abulí, Anna; Bessa, Xavier; Andreu, Montserrat; Bujanda, Luis; Caldés, Trinidad; Castellví-Bel, Sergi

    2015-02-01

    Colorectal cancer is an important cause of mortality in the developed world. Hereditary forms are due to germ-line mutations in APC, MUTYH, and the mismatch repair genes, but many cases present familial aggregation but an unknown inherited cause. The hypothesis of rare high-penetrance mutations in new genes is a likely explanation for the underlying predisposition in some of these familial cases. Exome sequencing was performed in 43 patients with colorectal cancer from 29 families with strong disease aggregation without mutations in known hereditary colorectal cancer genes. Data analysis selected only very rare variants (0-0.1%), producing a putative loss of function and located in genes with a role compatible with cancer. Variants in genes previously involved in hereditary colorectal cancer or nearby previous colorectal cancer genome-wide association study hits were also chosen. Twenty-eight final candidate variants were selected and validated by Sanger sequencing. Correct family segregation and somatic studies were used to categorize the most interesting variants in CDKN1B, XRCC4, EPHX1, NFKBIZ, SMARCA4, and BARD1. We identified new potential colorectal cancer predisposition variants in genes that have a role in cancer predisposition and are involved in DNA repair and the cell cycle, which supports their putative involvement in germ-line predisposition to this neoplasm.

  3. Bridging Home and Host Country: Educational Predispositions of Chinese and Indian Recent Immigrant Families

    Science.gov (United States)

    Gordon, June A.; Liu, Xiangyan

    2015-01-01

    This research focuses on the predispositions that recent Chinese and Indian immigrant families bring with them to the United States and how these are reinforced by the communities in which they locate. The findings draw from 144 interviews in California. Three themes dominate: positioning through schooling, transnational family, and extended…

  4. Exploring culture: audience predispositions and consequent effects on audience behavior in a mass-gathering setting.

    Science.gov (United States)

    Hutton, Alison; Brown, Steve; Verdonk, Naomi

    2013-06-01

    The purpose of this critical review is to look at the current literature regarding mass gatherings and to create further understanding of this area with a particular focus on what the audience brings with them to the event, particularly in a planned event with a cultural theme or focus. Through an understanding of these predispositions and consequent effects on audience behavior in a mass-gathering setting, a more complete understanding of motivation factors of crowds and audiences can also be found. A critical review of mass-gathering literature was undertaken by searching various online academic databases. Peer-reviewed scholarly articles relevant to the cultural aspects associated with religious, sporting and music mass gatherings were also analyzed. Results from the review show that the word "culture" is often used to explain what happens at the event without reflecting how the motivations or behaviors of audiences at an event are influenced by the cultural predispositions of the audience. By understanding the cultural predispositions of the audience, event planners and designers, event risk managers and event safety personnel are able to better understand the motivation of the audience and how this might impact on audience behavior at the event. Further work needs to be done, however, to investigate the broader range of predispositions. The ultimate aim of developing this understanding is to better inform the health promotion and public health messages that can be developed for a particular type of event based on the likely composition of the audience in attendance.

  5. The Perceived Reality of Television and Aggressive Predispositions Among Children in Mexico.

    Science.gov (United States)

    Korzenny, Felipe

    The purpose of this study was to assess the effectiveness of several independent variables in predicting the perception of television's content as real. The relationship between the perception of television violence as real and agressive predispositions of young viewers was analyzed. Two hundred seventy-three Mexican children in the third and…

  6. Predisposition Factors of Career and Technical Education Transfer Students: A Hermeneutic Phenomenology Study

    Science.gov (United States)

    Hioki, Warren; Lester, Derek; Martinez, Mario

    2015-01-01

    Six college students, who were career and technical education (CTE) transfer students in the state of Nevada, were interviewed Spring Semester of 2009. The study used a hermeneutic phenomenology framework as the method to identify those predisposition variables that heavily influenced the students in their decision to transfer to a senior…

  7. Prevalence of glaucoma suspects and pattern of intra-ocular ...

    African Journals Online (AJOL)

    Background: Glaucoma is the commonest cause of irreversible blindness in the world. Some glaucoma patients start out as glaucoma suspects for years. Aim: To determine the prevalence of glaucoma suspects and pattern of intra-ocular pressure distribution in glaucoma suspects. Methods: This survey was carried out in ...

  8. Nuclear Pedigree Criteria of Suspected HNPCC

    Directory of Open Access Journals (Sweden)

    Kładny Józef

    2003-01-01

    Full Text Available Abstract The criteria for the diagnosis of HNPCC established by the ICG-HNPCC are very restrictive as they do not allow for the diagnosis of a large number of "suspected HNPCC" cases - these are families which do no fulfill the strict diagnostic "Amsterdam criteria", but do present with several pedigree and clinical features characteristic for HNPCC. Several series of families suspected of harboring germline mutations in DNA mismatch repair genes have been studied for germline changes in DNA mismatch repair genes and a mutation rate of somewhere between 8-60% was found. Therefore a subgroup of members of the ICG-HNPCC has been working on pedigree/clinical diagnostic criteria for suspected HNPCC. Materials and methods Part I The study was based on two series of colorectal cancer (CRC cases: 1 HNPCC - this group comprised 190 patients affected by CRC from randomly selected families which fulfilled the Amsterdam II criteria registered in Düsseldorf, Germany (102 cases of CRC, Denmark (18 CRCs, Leiden, Holland (23 CRCs and Szczecin, Poland (47 CRCs. 2 Consecutive CRCs - this group comprised 629 (78.0% of 806 individuals with CRC diagnosed in 1991-1997 in the city of Szczecin (ca. 400,000 of inhabitants, Poland. Nuclear pedigrees in both groups were compared for frequency of occurrence of clinical features, that have been shown to be associated with HNPCC. Part II 52 consecutive CRC cases from Szczecin, matching the criteria recognized in part I as appropriate for diagnosis of cases "suspected of HNPCC" were studied for the occurrence of germline hMSH2/hMLH1 constitutional mutations using "exon by exon" sequencing. Results The combination of features - i.e. the occurrence of an HNPCC associated cancer (CRC or cancer of the endometrium, small bowel or urinary tract in a 1st degree relative of a CRC patient; at least one of the patients being diagnosed under age of 50 - appeared to be strongly associated to HNPCC with an OR - 161. Constitutional

  9. Identification of ALK as a major familial neuroblastoma predisposition gene.

    Science.gov (United States)

    Mossé, Yaël P; Laudenslager, Marci; Longo, Luca; Cole, Kristina A; Wood, Andrew; Attiyeh, Edward F; Laquaglia, Michael J; Sennett, Rachel; Lynch, Jill E; Perri, Patrizia; Laureys, Geneviève; Speleman, Frank; Kim, Cecilia; Hou, Cuiping; Hakonarson, Hakon; Torkamani, Ali; Schork, Nicholas J; Brodeur, Garrett M; Tonini, Gian P; Rappaport, Eric; Devoto, Marcella; Maris, John M

    2008-10-16

    Neuroblastoma is a childhood cancer that can be inherited, but the genetic aetiology is largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase (ALK) gene explain most hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at chromosome bands 2p23-24 using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate germline missense mutations in the tyrosine kinase domain of ALK that segregated with the disease in eight separate families. Resequencing in 194 high-risk neuroblastoma samples showed somatically acquired mutations in the tyrosine kinase domain in 12.4% of samples. Nine of the ten mutations map to critical regions of the kinase domain and were predicted, with high probability, to be oncogenic drivers. Mutations resulted in constitutive phosphorylation, and targeted knockdown of ALK messenger RNA resulted in profound inhibition of growth in all cell lines harbouring mutant or amplified ALK, as well as in two out of six wild-type cell lines for ALK. Our results demonstrate that heritable mutations of ALK are the main cause of familial neuroblastoma, and that germline or acquired activation of this cell-surface kinase is a tractable therapeutic target for this lethal paediatric malignancy.

  10. Identification of ALK as the Major Familial Neuroblastoma Predisposition Gene

    Science.gov (United States)

    Mossë, Yalë P; Laudenslager, Marci; Longo, Luca; Cole, Kristina A; Wood, Andrew; Attiyeh, Edward F; Laquaglia, Michael J; Sennett, Rachel; Lynch, Jill E; Perri, Patrizia; Laureys, Geneviève; Speleman, Frank; Hakonarson, Hakon; Torkamani, Ali; Schork, Nicholas J; Brodeur, Garrett M; Tonini, Gian Paolo; Rappaport, Eric; Devoto, Marcella; Maris, John M

    2009-01-01

    SUMMARY Survival rates for the childhood cancer neuroblastoma have not substantively improved despite dramatic escalation in chemotherapy intensity. Like most human cancers, this embryonal malignancy can be inherited, but the genetic etiology of familial and sporadically occurring neuroblastoma was largely unknown. Here we show that germline mutations in the anaplastic lymphoma kinase gene (ALK) explain the majority of hereditary neuroblastomas, and that activating mutations can also be somatically acquired. We first identified a significant linkage signal at the short arm of chromosome 2 (maximum nonparametric LOD=4.23 at rs1344063) using a whole-genome scan in neuroblastoma pedigrees. Resequencing of regional candidate genes identified three separate missense mutations in the tyrosine kinase domain of ALK (G1128A, R1192P and R1275Q) that segregated with the disease in eight separate families. Examination of 491 sporadically occurring human neuroblastoma samples showed that the ALK locus was gained in 22.8%, and highly amplified in an additional 3.3%, and that these aberrations were highly associated with death from disease (P=0.0003). Resequencing of 194 high-risk neuroblastoma samples showed somatically acquired mutations within the tyrosine kinase domain in 12.4%. Nine of the ten mutations map to critical regions of the kinase domain and were predicted to be oncogenic drivers with high probability. Mutations resulted in constitutive phosphorylation consistent with activation, and targeted knockdown of ALK mRNA resulted in profound growth inhibition of 4 of 4 cell lines harboring mutant or amplified ALK, as well as 2 of 6 wild type for ALK. Our results demonstrate that heritable mutations of ALK are the major cause of familial neuroblastoma, and that germline or acquired activation of this cell surface kinase is a tractable therapeutic target for this lethal pediatric malignancy. PMID:18724359

  11. A brief history of the political work of genetics.

    Science.gov (United States)

    Nelkin, Dorothy

    2002-01-01

    The biological sciences have long been used to define distinctions between people and to define inequalities as a natural consequence of essential biological traits. Today, geneticists draw distinctions on the basis of genetic predispositions. Their population-based methods can reinforce stereotypes about race and ethnic differences, providing concepts, validated by science, through which group differences can be interpreted as biologically ordained. Cases suggest how genetic variants can be used in social policies as individuals are differentially treated, not on the basis of their individual condition, but because of predispositions attributed to their group.

  12. Correlation between mutations and mRNA expression of APC and MUTYH genes: new insight into hereditary colorectal polyposis predisposition.

    Science.gov (United States)

    Aceto, Gitana Maria; Fantini, Fabiana; De Iure, Sabrina; Di Nicola, Marta; Palka, Giandomenico; Valanzano, Rosa; Di Gregorio, Patrizia; Stigliano, Vittoria; Genuardi, Maurizio; Battista, Pasquale; Cama, Alessandro; Curia, Maria Cristina

    2015-10-28

    Transcript dosage imbalance may influence the transcriptome. To gain insight into the role of altered gene expression in hereditary colorectal polyposis predisposition, in the present study we analyzed absolute and allele-specific expression (ASE) of adenomatous polyposis coli (APC) and mutY Homolog (MUTYH) genes. We analyzed DNA and RNA extracted from peripheral blood mononuclear cells (PBMC) of 49 familial polyposis patients and 42 healthy blood donors selected according similar gender and age. Patients were studied for germline alterations in both genes using dHPLC, MLPA and automated sequencing. APC and MUTYH mRNA expression levels were investigated by quantitative Real-Time PCR (qRT-PCR) analysis using TaqMan assay and by ASE assays using dHPLC-based primer extension. Twenty out of 49 patients showed germline mutations: 14 in APC gene and six in MUTYH gene. Twenty-nine patients did not show mutations in both genes. Results from qRT-PCR indicated that gene expression of both APC and MUTYH was reduced in patients analyzed. In particular, a significant reduction in APC expression was observed in patients without APC germline mutation vs control group (P mutation carrier patients, although lower compared to control individuals, did not show statistical significance. On the other hand a significant reduced MUTYH expression was detected in patients with MUTYH mutations vs control group (P mutation carriers. In particular one case showed a complete loss of one allele. Among APC mutation negative cases, 4 out of 13 showed a moderate ASE. ASE of MUTYH did not show any altered expression in the cases analyzed. Spearman's Rho Test analysis showed a positive and significant correlation between APC and MUTYH genes both in cases and in controls (P = 0.020 and P gene mutation. Expression of APC is decreased in mutation negative cases and this appears to be a promising indicator of FAP predisposition, while for MUTYH gene, mutation is associated to reduced m

  13. Prevalence of Malassezia pachydermatis in dogs with suspected Malassezia dermatitis or otitis in Slovakia

    Directory of Open Access Journals (Sweden)

    Eva Čonková

    2011-01-01

    Full Text Available The aim of the study was to evaluate the prevalence of yeast Malassezia pachydermatis in dogs from Slovakia in relation to different predisposition factors (sex, age, body localisation, hair type, and season. Samples of ear swabs (58 and dermal swabs (131 from 147 dogs with clinical symptoms of suspected yeast dermatitis and/or otitis, were examined between June 2005 to June 2007. Relatively higher prevalence of M. pachydermatis was found in samples taken from males (45.2% than in females (35.2%, and in geriatric dogs (63.6% than in young (42.5% or adult (38.5% dogs. Malassezia pachydermatis was isolated more often from ear swabs (44.8% than from skin swabs (38.9%. Prevalence of M. pachydermatis was significantly higher (p Malassezia pachydermatis is one of the most frequent yeasts isolated in dogs. Knowledge of factors predisposing to development of infection is valuable attribute of the correct diagnostic approach and case management.

  14. A genetical approach to deep venous thrombosis

    Directory of Open Access Journals (Sweden)

    Celal Yavuz

    2012-06-01

    Full Text Available Deep venous thrombosis (DVT is a common disorderthat frequently occurs after surgical procedures andtrauma and in the presence of cancer or immobilizationconditions. However, it can also develop without any ofthese predisposing factors. This condition directs theresearcher’s enquiry to investigating the basis of organismalthrombotic predisposition. The common prothromboticgenetic mutations include factor V Leiden, factor IIG20210 A, plasminogen activator inhibitor-1, prothrombinA20210, and factor XIII - VIII. Nevertheless, current studiessuggest that the thrombotic events are not connectedwith single gene deletion or homeostatic regulation is alsoaffected by other genetic risk factors. Complex interactionsof genetic mutations can be affects different levels ofthrombotic system or reinforce each other’s effects on homeostaticmechanisms. The analysis of literature, togetherwith the action mechanisms of the classic geneticalfactors and new suggestions, may contribute significantlyto our understanding of the genetic predisposition to venousthrombosis. J Clin Exp Invest 2012; 3(2: 303-306

  15. Mechanism of Ovarian Epithelial Tumor Predisposition in Individuals Carrying Germline BRCA1 Mutations

    Science.gov (United States)

    2006-12-01

    cystadenomas , which are benign tumors made up of the same cell type as ovarian serous carcinomas. We confirmed that these tumors carried only the wild type... cystadenomas in strong support of our hypothesis. We proposed to elucidate the mechanism of tumor predisposition in this mouse model by identifying the...Maxson R, Dubeau L: Inactivation of Brca1 in mouse ovarian granulosa cells causes serous epithelial cystadenomas carrying functional Brca1alleles in

  16. Evaluation criteria of the individual motor predisposition of female sport gymnastics

    Directory of Open Access Journals (Sweden)

    Boraczynski T.

    2010-10-01

    Full Text Available In the paper were presented the results of research, aimed to improve criteria for assessing the motor predisposition of girls in sports gymnastics at the initial stage of training. The studies included 24 gymnasts divided into two age groups: A 6,0-7,5 years of age and B (8,3-13,0. The level of physical fitness was assessed with the use of the EUROFIT battery tests. easurements of the maximum moment of muscle strength in the bending forearm in the elbow joint in terms of isometric contraction were also performed. Assessment f the level of individual strengthspeed and coordination abilities and physical fitness structure including the pace of biological development were the basis for the development of objective criteria for assessing the sports predispositions of young gymnasts at the initial stage of training. Our results provide the basis for improving the control system and optimization of assessment criteria in women gymnastics, including age, training experience and sports level. The results presented in this paper demonstrated the usefulness of the research methodology used to assess the physical fitness and predispositions of gymnasts at the initial stage of training, what enables individualization of training process.

  17. Psychological predispositions of teachers for encouraging the pluralist cognitive style in teaching

    Directory of Open Access Journals (Sweden)

    Đurišić-Bojanović Mirosava

    2008-01-01

    Full Text Available The aim of the presented research was to determine in which measure teachers possess the psychological predispositions for democratic functioning as a condition for education for democracy. Two groups of personal characteristics were singled out: (a predispositions for anti-democratic behavior, arbitrarily labeled weak ego characteristics, and (b strong ego characteristics as predispositions for democratic behavior. The readiness of teachers to develop the democratic style of teaching was tested via their readiness to accept plurality of ideas, as the acceptance of legitimacy of the existence of different explanations of many phenomena and readiness to consider the argumentation for disagreeing or opposed views within controversial issues. The research was conducted on the purposeful, convenient sample during the school year 2006/2007 in primary and secondary schools in several towns in Serbia (N=158. The scales in accordance with Likert's procedure were applied for each individual characteristic. The results show that the majority of teachers have a positive attitude towards the acceptance of plurality of ideas. The assumptions about a significant negative correlation between the acceptance of plurality of ideas and weak ego characteristics were confirmed, as well as about a significant positive correlation with strong ego characteristics. This paper discusses the pedagogical implications of the obtained findings.

  18. An Xpd mouse model for the combined xeroderma pigmentosum/Cockayne syndrome exhibiting both cancer predisposition and segmental progeria.

    NARCIS (Netherlands)

    Andressoo, Jaan-Olle; Mitchell, James R; Wit, Jan de; Hoogstraten, Deborah; Volker, Marcel; Toussaint, Wendy; Speksnijder, Ewoud; Beems, Rudolf B; Steeg, Harry van; Jans, Judith; Zeeuw, Chris I de; Jaspers, Nicolaas G J; Raams, Anja; Lehmann, Alan R; Vermeulen, Wim; Hoeijmakers, Jan H J; Horst, Gijsbertus T J van der

    2006-01-01

    Inborn defects in nucleotide excision DNA repair (NER) can paradoxically result in elevated cancer incidence (xeroderma pigmentosum [XP]) or segmental progeria without cancer predisposition (Cockayne syndrome [CS] and trichothiodystrophy [TTD]). We report generation of a knockin mouse model for the

  19. Exploring the Effects of Macro-Environment on the Predisposition to Adopt Strategic Orientation among Small Medium Size Hotel Entrepreneurs

    National Research Council Canada - National Science Library

    Azilah Kasim; Hisham Dzakiria

    2016-01-01

      This paper looks at the effect of macro-environment context on small and medium size hotels' predisposition to adopt strategic orientation using a qualitative approach in its research methodology...

  20. Cholesterol-Induced Hepatic Inflammation Does Not Underlie the Predisposition to Insulin Resistance in Dyslipidemic Female LDL Receptor Knockout Mice

    NARCIS (Netherlands)

    Gruben, Nanda; Funke, Anouk; Kloosterhuis, Niels J.; Schreurs, Marijke; Sheedfar, Fareeba; Havinga, Rick; Houten, Sander M.; Shiri-Sverdlov, Ronit; van de Sluis, Bart; Kuivenhoven, Jan Albert; Koonen, Debby P. Y.; Hofker, Marten H.

    2015-01-01

    Chronic inflammation is considered a causal risk factor predisposing to insulin resistance. However, evidence is accumulating that inflammation confined to the liver may not be causal to metabolic dysfunction. To investigate this, we assessed if hepatic inflammation explains the predisposition

  1. Are Genetics and Environment Substitutes or Complements in Affecting Entrepreneurial Choice?

    DEFF Research Database (Denmark)

    Zunino, Diego

    whether the genetic effect is different across genders, based on the stylized fact that barriers to entrepreneurship entry are stronger for females than for males. Using regression analysis, the study confirms earlier findings showing substantial genetic effects. More interestingly, the study finds...... that the genetic effect drops when the environment is less favorable – namely when the individual is female. The result of a positive interaction between predisposition and environment implies that the environment and predisposition can be considered complements rather than substitutes, that institutions play......Recent twin and adoption studies have shown that genes matter for entrepreneurial choice. This related study addresses how a genetic predisposition to entrepreneurship interacts with the (entrepreneurship friendliness of the) environment, using a dataset of Italian twins. In particular, we study...

  2. Hereditariedade e suscetibilidade à reabsorção radicular em Ortodontia não se fundamentam: erros metodológicos e interpretativos repetidamente publicados podem gerar falsas verdades. Análise crítica do trabalho de Al-Qawasmi et al.² sobre a predisposição genética à reabsorção radicular de natureza ortodôntica Heredity and susceptibility to radicular resorption in Odontology do not base: methodological and interpretative repeatedly published mistakes can generate false truths. Critical analysis of Al-Qawasmi work about genetics predisposition to radicular reabsorption of orthodontic kind

    Directory of Open Access Journals (Sweden)

    Alberto Consolaro

    2004-05-01

    Full Text Available O trabalho de Al-Qawasmi et al.², publicado em agosto de 2003 no periódico Journal of Dental Research, procurou estabelecer um gene candidato para a hereditariedade e predisposição genética nas reabsorções dentárias em Ortodontia, mas apresentou e repetiu algumas limitações metodológicas e equívocos na interpretação de seu trabalho anterior de março de 2003¹. Nas conclusões afirmam explicitamente que os achados são preliminares e sugestivos, necessitando de confirmação por meio de estudos adicionais. Os resultados são correlacionados fundamentando-se em dados de outros autores sobre síndromes ósseas associadas a reabsorções por substituição, cervicais externas e não com as reabsorções radiculares externas apicais induzidas ortodonticamente. O gene da reabsorção radicular externa apical relacionada a tratamentos ortodônticos não foi determinado e muito menos a sua natureza hereditária. Nem tampouco, a suscetibilidade à reabsorção radicular em Ortodontia foi detectada ou provada. O trabalho analisado e os demais relacionados com o mesmo tema não conseguiram comprovar suas hipóteses porque ignoram que o primeiro passo para a reabsorção radicular externa é a destruição da camada cementoblástica e isto apenas ocorre a partir da ação de fatores locais. Analisando criticamente estes trabalhos podemos afirmar que procurar o gene da reabsorção radicular e da suscetibilidade a partir de pesquisas em mediadores e células clásticas demonstra a falta de um conhecimento completo e amplo da etiopatogenia deste importante fenômeno biológico, imprescindível para o estabelecimento da premissa dos trabalhos.The study of Al-Qawasmi et al.² published in August 2003 on Journal of Dental Research, aimed to establish a candidate gene for heritability and genetic predisposition to external root resorption in orthodontic patients. This paper, however, presents and repeated some methodological faults and equivocated

  3. Magnetic resonance imaging of suspected atrial tumors.

    Science.gov (United States)

    Menegus, M A; Greenberg, M A; Spindola-Franco, H; Fayemi, A

    1992-05-01

    Two-dimensional echocardiography has become the standard technique for evaluation of cardiac and paracardiac mass lesions. We have used magnetic resonance imaging (MRI) as an independent assessment of cardiac-associated masses in patients with echocardiograms demonstrating sessile atrial tumors. MRI was performed in seven patients, ages 33 to 84, whose echocardiographic diagnoses included left atrial mass (five), right atrial mass (one), and interatrial mass (one). In four of the patients with a diagnosis of left atrial mass, MRI showed extracardiac compression of the atrium, simulating a tumor (hiatal hernia, tortuous descending aorta, bronchogenic cyst). MRI was entirely normal in one patient with an apparent left atrial mass. MRI elucidated extension of an extracavitary mass into the interatrial septum in two patients. One of these patients with an echocardiographic right atrial mass had extension of a lipoma into the interatrial septum without atrial tumor. MRI confirmed the echocardiographic diagnosis of an interatrial mass in the other patient. We conclude that MRI, because of its ability to define anatomic relationships and tissue characteristics, is a powerful noninvasive tool for evaluating suspected cardiac mass lesions. Although echocardiography remains the primary screening test for the detection of cardiac masses, MRI is a more specific modality for precise diagnosis. Correct MRI interpretation may obviate the need for invasive studies or surgery.

  4. Attitude towards pre-implantation genetic diagnosis for hereditary cancer

    NARCIS (Netherlands)

    Lammens, Chantal; Bleiker, Eveline; Aaronson, Neil; Vriends, Annette; Ausems, Margreet; Jansweijer, Maaike; Wagner, Anja; Sijmons, Rolf; van den Ouweland, Ans; van der Luijt, Rob; Spruijt, Liesbeth; Garcia, Encarna Gomez; Ruijs, Marielle; Verhoef, Senno

    2009-01-01

    The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition.

  5. Genetic susceptibility to head and neck squamous cell carcinoma

    NARCIS (Netherlands)

    Lacko, M.; Braakhuis, B.J.M.; Sturgis, E.M.; Boedeker, C.C.; Suarez, C.; Rinaldo, A.; Ferlito, A.; Takes, R.P.

    2014-01-01

    Head-and-neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, and its incidence is growing. Although environmental carcinogens and carcinogenic viruses are the main etiologic factors, genetic predisposition obviously plays a risk-modulating role, given that not all

  6. Preventing organ damage by genetic testing for hereditary ...

    African Journals Online (AJOL)

    A genetic predisposition for this relatively common autosomal recessive disease has been identified in approximately 1 in 100 South Africans of European descent. If left untreated, this condition may lead to organ damage presenting as cirrhosis, liver cancer, diabetes, arthritis, impotence, sterility and/or cardiac disease.

  7. Detection of Rabies antigen in brains of suspected Rabid dogs ...

    African Journals Online (AJOL)

    Objective: To detect the presence of rabies antigen in brains of suspected rabid dogs. Materials and Methods: Ninety six (96) brain specimens from suspected rabid dogs were examined for the presence of rabies antigen using Seller's staining technique and enzyme immunoassay. Results: The two techniques were both ...

  8. 48 CFR 803.806 - Processing suspected violations.

    Science.gov (United States)

    2010-10-01

    ... GENERAL IMPROPER BUSINESS PRACTICES AND PERSONAL CONFLICTS OF INTEREST Limitation on the Payment of Funds to Influence Federal Transactions 803.806 Processing suspected violations. A VA employee must report suspected violations of 31 U.S.C. 1352, Limitation on Use of Appropriated Funds to Influence Certain Federal...

  9. The clinical course of patients with suspected pulmonary embolism

    NARCIS (Netherlands)

    van Beek, E. J.; Kuijer, P. M.; Büller, H. R.; Brandjes, D. P.; Bossuyt, P. M.; ten Cate, J. W.

    1997-01-01

    BACKGROUND: The outcome of patients with suspected pulmonary embolism is known to a limited extent only. OBJECTIVE: To address this limited knowledge in a cohort in whom pulmonary embolism was proved or ruled out. METHODS: Consecutive patients with clinically suspected pulmonary embolism underwent

  10. Phenotype-Environment Interactions in Genetic Syndromes Associated with Severe or Profound Intellectual Disability

    Science.gov (United States)

    Tunnicliffe, Penny; Oliver, Chris

    2011-01-01

    The research literature notes both biological and operant theories of behavior disorder in individuals with intellectual disabilities. These two theories of genetic predisposition and operant reinforcement remain quite distinct; neither theory on its own is sufficient to explain challenging behavior in genetic syndromes and an integrated approach…

  11. Genetic Determinants of Macrovascular Complications and Mortality in Type 2 Diabetes

    NARCIS (Netherlands)

    M. Yazdanpanah (Mojgan)

    2006-01-01

    textabstractEvidence is accumulating that there is a genetic predisposition for the development of vascular complications of type 2 diabetes. There is a large variation in the risk and onset of complication in patients, which may partly be explained by genetic susceptibility. Most likely

  12. [Information for family members with an increased risk for a genetic disease

    NARCIS (Netherlands)

    Gordijn, B.

    2006-01-01

    After a genetic diagnosis a physician might deem it important to inform family members of his counselee who might have an increased risk of having a certain genetic predisposition. Against this background this contribution analyzes the following ethical questions: 1. To what extent is the physician

  13. Seasonal variation among tuberculosis suspects in four countries

    DEFF Research Database (Denmark)

    Mabaera, Biggie; Naranbat, Nymadawa; Katamba, Achilles

    2009-01-01

    The objective of the study was to analyze monthly trends across a calendar year in tuberculosis suspects and sputum smear-positive cases based on nationally representative samples of tuberculosis laboratory registers from Moldova, Mongolia, Uganda and Zimbabwe. Out of the 47 140 suspects registered...... in the tuberculosis laboratory registers, 13.4% (6312) were cases. The proportion varied from country to country, Moldova having the lowest (9%) and Uganda the highest (21%). From the monthly proportion of suspects and cases among total suspects and cases, seasonal variations were most marked in Mongolia which, among...... attendance to diagnostic laboratory services, evidenced by the contrasting findings of Mongolia (extreme continental northern climate) compared to Uganda (equatorial climate). A combination of external and possibly endogenous factors seems to determine whether tuberculosis suspects and cases present...

  14. [Cancer genetic screening for patient with multiple renal tumors: What is the current practice for what results?].

    Science.gov (United States)

    Beaugerie, A; Verkarre, V; Audenet, F; Le Guilchet, T; Hurel, S; Richard, S; Corréas, J M; Fontaine, E; Méjean, A; Timsit, M O

    2016-06-01

    To evaluate in a high volume center the practice and the performance of cancer genetic screening for patients with multiple renal tumors without a predisposition to kidney tumors known at the time of surgery. All patients treated for multiple renal tumors from January 2000 to December 2013 in our center were included. Patients with a family history of renal cell carcinoma, a kidney disease or a genetic predisposition to renal cancer known at the time of surgery were excluded from the analysis. Our list of patients was retrospectively compared to the records from PREDIR (PREDisposition to Kidney Tumors) center of Île-de-France, which regionally centralizes the care of patients with kidney tumors associated with a genetic predisposition. One hundred and thirty-six patients were included. Twenty-six patients of 136 (19%) were referred to PREDIR center: 23 followed the screening and 3 did not show up in consultation. Of the 23 patients screened, three genetic predispositions to kidney tumors were identified (13%). Of the 95 patients with synchronous tumors, 48% with more than 3 tumors benefited from cancer genetics investigation against 13% of those presenting only two tumors. Our study shows that cancer genetic investigations are not routinely offered to patients with multiple kidney tumors, conversely to existing guidelines. Urologists must be aware of this screening. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  15. Race and ethnicity as a victimogenic predisposition of exceeding and abuse of police authority

    Directory of Open Access Journals (Sweden)

    Kesić Zoran

    2012-01-01

    Full Text Available The unique position in society and the specific functions make the police one of the key holders of protection of the fundamental rights and freedoms of citizens. At the same time, their position and function provide police officers significant opportunities to violate the same freedoms and rights, by resorting to various forms of violation and abuse of power. This dual nature of the police authority gives us reason to question the police from a completely different angle - as a source of a specific form of victimization. The risk degree of victimization by police authority is determined by the different predispositions, and above all by the victim’s behavior. However, some individual characteristics (gender, age, sexual orientation, ethnic and social origin are also a kind of victimogenic predisposition, as they contribute to the process of victimization independently or in combination with the behavior of the victim. In this work we draw attention to the fact that race (ethnicity often makes an independent criterion which the police use when deciding how to act in the concrete case. This circumstance contributes to a distinctive form of police procedure, known as racial profiling. The fact that the race of a person is taken as a criterion for treatment suggests the conclusion that here is actually about a form of discriminatory behavior. Considered in this context, race may be treated as victimogenic predisposition of police authority, and racial profiling as a process of victimization. [Projekat Ministarstva nauke Republike Srbije, br. 179045: Razvoj institucionalnih kapaciteta, standarda i procedura za suprotstavljanje organizovanom kriminalu i terorizmu u uslovima međunarodnih integracija

  16. Complicated Lemierre Syndrome Caused by Streptococcus gordonii and Possible Rickettsial Co-Infection in a Patient with Thrombophilia Predisposition

    Directory of Open Access Journals (Sweden)

    Antreas Iacovou Ioannou

    2017-06-01

    Full Text Available Aims: Lemierre syndrome is a life-threating condition characterized by recent oropharyngeal infection, internal jugular vein thrombosis, and anaerobic septicemia. It is usually caused by Fusobacterium necrophorum. Methods: A young Romanian male presented with fever and rigors, mild tachypnea, hypoxia, sore throat, decayed teeth, and tenderness of the left carotid triangle. Laboratory examination indicated severe sepsis with disseminated intravascular coagulation, acute renal failure, and acute respiratory distress syndrome while the Doppler ultrasonography of the carotids revealed left internal jugular venous thrombosis. The patient was administered piperacillin/tazobactam and vancomycin intravenously, doxycycline orally, and anti-coagulation by enoxaparin based on the diagnosis of Lemierre syndrome. Meanwhile, he was complicated by bilateral diffuse pulmonary cavities and encapsulated pleural effusions and so transcutaneous drainage was performed. The patient was discharged after a month and continued his treatment with oral phenoxypenicillin and doxycycline until full radiographic improvement. He was switched to oral anti-coagulation by vitamin-K antagonists and was referred to a hematologist, a vascular-surgeon, and a dentist. Results: Streptococcus gordonii was isolated from the patient’s blood and pleural fluid cultures and serology for Rickettsial spp. IgM was positive. Thrombophilia genetic tests revealed three minor mutations for fibrinogen-455, plasminogen activator inhibitor-1, and methylenetetrahydrofolate reductase. According to the literature, S. gordonii is not usually a causative agent and Rickettsial spp. have as yet not been correlated with Lemierre syndrome. The failure of left jugular vein recanalization shows a possible causative role of the underlying thrombophilic predisposition. Discussion: Because of the syndrome’s rarity and the atypical microorganisms isolated in this case, increased awareness is advised for its

  17. The Influence of Familial Predisposition to Cardiovascular Complications upon Childhood Obesity Treatment

    OpenAIRE

    Nielsen, Louise A.; Christine Bøjsøe; Julie T Kloppenborg; Cæcilie Trier; Michael Gamborg; Jens-Christian Holm

    2015-01-01

    Introduction The aim was to investigate whether a familial predisposition to obesity related cardiovascular complications was associated with the degree of obesity at baseline and/or changes in the degree of obesity during a multidisciplinary childhood obesity treatment program. Methods The study included 1421 obese children (634 boys) with a median age of 11.5 years (range 3.1?17.9 years), enrolled in treatment for 0.04 to 5.90 years (median 1.3 years) at the Children's Obesity Clinic, Denma...

  18. Personal genetics: sports utility vehicle?

    Science.gov (United States)

    Grimaldi, Keith Anthony; Paoli, Antonio; Smith, Graeme John

    2012-12-01

    Personal genetic testing which is not strictly related to medicine or health is becoming more and more popular covering areas from ancestry, genealogy, nutrition& lifestyle and more recently sports and exercise. The reasons are compelling - if it were possible to read in our genes our potential sporting attributes and how to achieve them it would be valuable information. But is it possible? This overview will look at the current situation and future prospects the authors believe that there is utility in sports genetic testing exactly what can be interpreted from our genetic results needs to be precisely defined and limited to what has been demonstrated by repeated scientific studies. Current areas of interest include optimizing exercise/training routines, VO2max improvement and predisposition to some common sports related injuries such as tendonitis. The interest and the scientific progress is reflected both in increasing rate of publication of geneexercise studies as well as in patent applications concerning genetic associations with commercial potential.

  19. Genetics of Behçet's Disease

    Directory of Open Access Journals (Sweden)

    Tamer İrfan Kaya

    2012-01-01

    Full Text Available Behçet's disease (BD is a systemic inflammatory disorder characterized mainly by recurrent oral and genital ulcers and eye involvement. Although the pathogenesis remains poorly understood, a variety of studies have demonstrated that genetic predisposition is a major factor in disease susceptibility. Peculiar geographical distribution of BD along the ancient Silk Road has been regarded as evidence supporting genetic influence. The observed aggregation of BD in families of patients with BD is also supportive for a genetic component in its etiology. HLA-B51 (B510101 subtype is the most strongly associated genetic marker for BD in countries on the Silk Road. In recent years, several genome-wide association studies and genetic polymorphism studies have also found new genetic associations with BD, which may have a supplementary role in disease susceptibility and/or severity. The author reviewed the HLA and non-HLA genetic association studies.

  20. [Genetic classification of clinical forms of childhood schizophrenia].

    Science.gov (United States)

    Kozlova, I A; Trubnikov, V I

    1989-01-01

    In an analysis of 225 families of probands with different forms of the course of children's schizophrenia, a hypothesis on the degree of their genetical similarity (or dissimilarity) was tested. Malignant and slow progredient form of children schizophrenia showed major genetical similarity (correlation coefficient 1.0) with the recurrent schizophrenia occupying a separate position having no common genetical predisposition factors with nuclear forms of schizophrenia. Paroxysmal progredient schizophrenia displayed a distinct genetical relation to any other form (genetical correlation coefficient ranging in 0.5-0.7).

  1. Prediction of Suspect Location Based on Spatiotemporal Semantics

    Directory of Open Access Journals (Sweden)

    Lian Duan

    2017-06-01

    Full Text Available The prediction of suspect location enables proactive experiences for crime investigations and offers essential intelligence for crime prevention. However, existing studies have failed to capture the complex social location transition patterns of suspects and lack the capacity to address the issue of data sparsity. This paper proposes a novel location prediction model called CMoB (Crime Multi-order Bayes model based on the spatiotemporal semantics to enhance the prediction performance. In particular, the model groups suspects with similar spatiotemporal semantics as one target suspect. Then, their mobility data are applied to estimate Markov transition probabilities of unobserved locations based on a KDE (kernel density estimating smoothing method. Finally, by integrating the total transition probabilities, which are derived from the multi-order property of the Markov transition matrix, into a Bayesian-based formula, it is able to realize multi-step location prediction for the individual suspect. Experiments with the mobility dataset covering 210 suspects and their 18,754 location records from January to June 2012 in Wuhan City show that the proposed CMoB model significantly outperforms state-of-the-art algorithms for suspect location prediction in the context of data sparsity.

  2. A Genetical approach to deep venous thrombosis

    OpenAIRE

    Yavuz, Celal

    2012-01-01

    Deep venous thrombosis (DVT) is a common disorder that frequently occurs after surgical procedures and trauma and in the presence of cancer or immobilization conditions. However, it can also develop without any of these predisposing factors. This condition directs the researcher's enquiry to investigating the basis of organismal thrombotic predisposition. The common prothrombotic genetic mutations include factor V Leiden, factor II G20210 A, plasminogen activator inhibitor-1, prot...

  3. B Plant/WESF suspect/counterfeit parts identification program

    Energy Technology Data Exchange (ETDEWEB)

    Mertz, D.W.

    1996-01-12

    This document describes a suspect/counterfeit parts inspection program required by DOE conducted in accordance with Internal Memo 16710-94-DWM-048, J.A. O`Brien to J. N. Nansen, B Plant Suspect/ Counterfeit Parts Action Plan, dated May 24, 1994. The program included: physical inspection of all spare parts inventories within the plant; screening of installed B Plant/WESF (Waste Encapsulation and Storage Facility) systems for applications where the use and subsequent potential failure of suspect/counterfeit parts could have critical consequences; and a physical inspection based upon this screening.

  4. [Predisposition of citizens to use Internet-based channels to communicate with doctors in Spain].

    Science.gov (United States)

    Herrera-Usagre, Manuel; Reyes-Alcázar, Víctor; Valverde, José A

    2014-01-01

    Analyze factors affecting the predisposition of Spanish citizens to use Internet-based communication channels (E-mail, blogs, social networks, and online recommendations). Secondary data were analyzed by applying a boosted regression tree (BRT) to the results obtained from the survey "Use and Applications of Information and Communications Technology in Health," administered to a representative sample of the Spanish population between 16 and 85 years of age who use the Internet. Model forecasts achieved different degrees of precision for each of the communication channels: for E-mail, AUC (area under the curve) = 0.79; for the physician's blog or personal website, AUC = 0.736; for social networks, AUC = 0.73; for recommendations of websites related to health problems, AUC = 0.768. Being young was the most important parameter in citizen predisposition to communicate through social networks (relative influence; RI = 21.05%), while population density was the most important parameter in likelihood that the physician would have a blog or personal health-related website (RI = 19.48%). Having a positive perception of the technology when facilitating health-related transactions was the most important characteristic in wanting to receive recommendations on health-related Internet resources (RI = 18.66%), while having a higher level of education was the best predictor of wanting to establish E-mail communication (RI = 18.98%). Many of Spanish people are open to using physician-patient interaction channels on the Internet.

  5. General lessons from large-scale studies to identify human cancer predisposition genes.

    Science.gov (United States)

    Cazier, Jean-Baptiste; Tomlinson, Ian

    2010-01-01

    There are now about 100 genes known to cause Mendelian inherited cancer syndromes, but these only explain a minor part of the familial clustering of the common cancers. The increased familial relative risk of cancer in the general population must largely involve genes of low- or moderate-penetrance. Until recently, attempts to identify cancer predisposition genes with low penetrance had proved similarly unrewarding. However, in the past 2 years, developments in this area have been rapid. In particular, the 'common disease-common variant' model of predisposition has come to the fore. In this model, alleles of high frequency (typically > 10%) and low penetrance (typically cancers. Many common risk alleles for cancer have been found by genome-wide association studies (GWASs) in the form of tagging SNPs, although identification of the disease-causing variants generally remains a difficult problem. The 'common disease-common variant' model has recently been criticized by proponents of a 'common disease-rare variant' model. In fact, the conflict between the models is false and a more continuous approach, bounded only by technical limitations and sample sizes, appears to be more appropriate. In this review, we summarize the general findings from cancer GWASs and their problems, and discuss the issues of finding rarer variants and other forms of cancer-predisposing variation, such as copy number polymorphisms.

  6. Impaired mucociliary clearance in allergic rhinitis patients is related to a predisposition to rhinosinusitis.

    Science.gov (United States)

    Vlastos, Ioannis; Athanasopoulos, Ioannis; Mastronikolis, Nicholas S; Panogeorgou, Theodora; Margaritis, Vassilios; Naxakis, Stefanos; Goumas, Panos D

    2009-04-01

    Although mucociliary clearance has been shown to be impaired in patients with allergic rhinitis and chronic rhinosinusitis, its exact role in relation to a predisposition to rhinosinusitis is unknown. To investigate this possible association, we conducted a prospective study of 125 patients with allergic rhinitis. Of this group, 23 patients were classified as being sinusitis-prone based on their history of antibiotic consumption for the treatment of rhinosinusitis; the remaining 102 patients were deemed to be not sinusitis-prone. The saccharine test was used to evaluate mucociliary clearance in all patients. Several variables-age, sex, smoking habits, rhinitis severity, and medication history-were examined. We found that the sinusitis-prone patients had a significantly greater mucociliary clearance time than did those who were not prone (median: 15 and 12 min, respectively; p = 0.02). No other statistically significant differences were seen between the 2 groups with respect to any other variables that might have affected mucociliary clearance. We conclude that impaired mucociliary clearance in allergic rhinitis patients is associated with a predisposition to rhinosinusitis.

  7. Social predisposition dependent neuronal activity in the intermediate medial mesopallium of domestic chicks (Gallus gallus domesticus).

    Science.gov (United States)

    Mayer, Uwe; Rosa-Salva, Orsola; Lorenzi, Elena; Vallortigara, Giorgio

    2016-09-01

    Species from phylogenetically distant animal groups, such as birds and primates including humans, share early experience-independent social predispositions that cause offspring, soon after birth, to attend to and learn about conspecifics. One example of this phenomenon is provided by the behaviour of newly-hatched visually-naïve domestic chicks that preferentially approach a stimulus resembling a conspecific (a stuffed fowl) rather than a less naturalistic object (a scrambled version of the stuffed fowl). However, the neuronal mechanisms underlying this behaviour are mostly unknown. Here we analysed chicks' brain activity with immunohistochemical detection of the transcription factor c-Fos. In a spontaneous choice test we confirmed a significant preference for approaching the stuffed fowl over a texture fowl (a fowl that was cut in small pieces attached to the sides of a box in scrambled order). Comparison of brain activation of a subgroup of chicks that approached either one or the other stimulus revealed differential activation in an area relevant for imprinting (IMM, intermediate medial mesopallium), suggesting that a different level of plasticity is associated with approach to naturalistic and artificial stimuli. c-Fos immunoreactive neurons were present also in the intermediate layers of the optic tectum (a plausible candidate for processing early social predispositions) showing a trend similar to the results for the IMM. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. New voters, new outlook? Predispositions, social networks, and the changing politics of gay civil rights.

    Science.gov (United States)

    Becker, Amy B; Scheufele, Dietram A

    2011-01-01

    Objectives. This study examines the factors that shape public acceptance of homosexuality and support for same-sex marriage across age cohorts.Methods. We analyzed data from two national surveys. We constructed hierarchical logistic and hierarchical ordinary least squares regressions for relevant age cohorts in order to test our hypotheses and explore our research questions.Results. Our models suggest that personal contact has a greater impact on the attitudes of younger respondents, positively influencing public acceptance of homosexuality. Alternatively, religious and ideological predispositions have a greater impact on the attitudes of older individuals. When examining public support for gay marriage, we find that younger individuals have higher levels of deliberative engagement with the issue debate, while older individuals rely more heavily on their predispositions when determining issue stance. Interestingly, measures of media exposure are not significantly related to either public acceptance of homosexuality or support for same-sex marriage, suggesting that other factors may have a greater impact on public attitudes at this point in time.Conclusion. The implications of these findings are discussed in light of the emergence of a new political generation and the continuing struggle for gay civil rights.

  9. PERSONALITY PREDISPOSITIONS IN CHINESE ADOLESCENTS: THE RELATION BETWEEN SELF-CRITICISM, DEPENDENCY, AND PROSPECTIVE INTERNALIZING SYMPTOMS

    Science.gov (United States)

    Cohen, Joseph R.; Young, Jami F.; Hankin, Benjamin L.; Yao, Shuqiao; Zhu, Xiong Zhao; Abela, John R.Z.

    2015-01-01

    The present study examined the prospective relation between two personality predispositions, self-criticism and dependency, and internalizing symptoms. Specifically, it was examined whether self-criticism and dependency predicted symptoms of depression and social anxiety, and if a moderation (e.g. diathesis-stress) or mediation model best explained the relation between the personality predispositions and emotional distress in Chinese adolescents. Participants included 1,150 adolescents (597 females and 553 males) from mainland China. Participants completed self-report measures of self-criticism, dependency, and neuroticism at baseline, and self-report measures of negative events, depressive symptoms, and social anxiety symptoms once a month for six months. Findings showed that self-criticism predicted depressive symptoms, while dependency predicted social anxiety symptoms. In addition, support was found for a mediation model, as opposed to a moderation model, with achievement stressors mediating the relation between self-criticism and depressive symptoms. Overall, these findings highlight new developmental pathways for the development of depression and social anxiety symptoms in mainland Chinese adolescents. Implications for cross-cultural developmental psychopathology research are discussed. PMID:25798026

  10. Maternal smoking increases risk of allergic sensitization and wheezing only in children with allergic predisposition: longitudinal analysis from birth to 10 years

    National Research Council Canada - National Science Library

    Keil, T; Lau, S; Roll, S; Grüber, C; Nickel, R; Niggemann, B; Wahn, U; Willich, S N; Kulig, M

    2009-01-01

    .... To examine the interaction of passive smoking and an allergic predisposition regarding allergic sensitization, allergic airway symptoms and respiratory infections during the first 10 years of life...

  11. Stopping and Questioning Suspected Shoplifters Without Creating Civil Liability

    Science.gov (United States)

    Reed, Jack R., Jr.

    1977-01-01

    Legal problems concerned with shoplifting suspects are addressed, including common law, criminal penalties, and the merchant's liability. Tangential questions and answers are presented along with discussion of pertinent court cases. (LBH)

  12. ALGORITHM OF MANAGEMENT OF PATIENTS WITH SUSPECTED BLUNT CARDIAC TRAUMA

    Directory of Open Access Journals (Sweden)

    S. R. Gilarevsky

    2013-01-01

    Full Text Available Abstract. Contemporary algorithm of diagnostic examination of patients with suspected blunt cardiac trauma is presented. General aspects of monitoring and treatment of such patients are also discussed. 

  13. Suspect confession of child sexual abuse to investigators.

    Science.gov (United States)

    Lippert, Tonya; Cross, Theodore P; Jones, Lisa; Walsh, Wendy

    2010-05-01

    Increasing the number of suspects who give true confessions of sexual abuse serves justice and reduces the burden of the criminal justice process on child victims. With data from four communities, this study examined confession rates and predictors of confession of child sexual abuse over the course of criminal investigations (final N = 282). Overall, 30% of suspects confessed partially or fully to the crime. This rate was consistent across the communities and is very similar to the rates of suspect confession of child sexual abuse found by previous research, although lower than that from a study focused on a community with a vigorous practice of polygraph testing. In a multivariate analysis, confession was more likely when suspects were younger and when more evidence of abuse was available, particularly child disclosure and corroborative evidence. These results suggest the difficulty of obtaining confession but also the value of methods that facilitate child disclosure and seek corroborative evidence, for increasing the odds of confession.

  14. Updates on breast cancer genetics: Clinical implications of detecting syndromes of inherited increased susceptibility to breast cancer.

    Science.gov (United States)

    Cobain, Erin F; Milliron, Kara J; Merajver, Sofia D

    2016-10-01

    Since the initial discovery that pathogenic germline alterations in BRCA 1/2 increase susceptibility to breast and ovarian cancer, many additional genes have now been discovered that also increase breast cancer risk. Given that several more genes have now been implicated in hereditary breast cancer syndromes, there is increased clinical use of multigene panel testing to evaluate patients with a suspected genetic predisposition to breast cancer. While this is most certainly a cost-effective approach, broader testing strategies have resulted in a higher likelihood of identifying moderate-penetrance genes, for which management guidelines regarding breast cancer risk reduction have not been firmly established. In addition, the testing of more genes has led to increased detection of variants of uncertain significance. We review the current knowledge regarding both high- and moderate-risk hereditary breast cancer syndromes, as well as additional genes implicated in hereditary breast cancer for which there is limited data. Furthermore, strategies for cancer risk reduction in mutation carriers as well as therapeutic implications for those patients who harbor pathogenic germline alterations are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Assimetria cerebral e lateralização da linguagem: déficits nucleares na esquizofrenia como indicadores da predisposição genética Asimetría cerebral y lateralización del lenguaje: déficits nucleares en la esquizofrenia como indicadores de predisposición genética Cerebral asymmetry and the lateralization of language: core deficits in schizophrenia as pointers to the genetic predisposition

    Directory of Open Access Journals (Sweden)

    Timothy J. Crow

    2004-08-01

    anatómicos, funcionales y genéticos. HALLAZGOS RECIENTES: Estudios de imagen, post mortem y anatómicos, demuestran evidencias de una reducción o reversión de aspectos de asimetría, particularmente en la corteza de asociación occipito-temporo-parietal. En algunos estudios, hay interacción con el sexo. Hay evidencias de que una alteración en el lóbulo temporal izquierdo es, a veces, progresiva. Estudios funcionales agregan credibilidad al concepto de que la lateralización del lenguaje es reducida y, en algunos casos, revertida. RESUMEN: La dimensión de la asimetría se destaca como la variable que puede dar significación a las observaciones entre campos de investigación y que proporciona una solución para la base genética de la psicosis. Estudios de gemelos monocigóticos discordantes vienen presentando fuertes indicaciones de que la variación relevante es epigenética; ello es consistente con la posibilidad de que la variación esté relacionada a alteraciones estructurales recientes (la trasposición replicativa Xq21.3/Yp de los cromosomas sexuales.PURPOSE OF REVIEW: Cerebral asymmetry (the torque from right frontal to left occipital is the defining feature of the human brain, and as Broca proposed, the putative neural correlate of language. If as has been suggested schizophrenia is the price that Homo sapiens pays for language, the torque together with its functional correlates is of central significance. Recent evidence from anatomical, functional and genetic studies is reviewed. RECENT FINDINGS: Both post-mortem and anatomical imaging studies show evidence of a reduction or reversal of aspects of asymmetry particularly in the occipito-temporo-parietal association cortex. In some studies there is an interaction with sex. There is evidence that change in the left temporal lobe is sometimes progressive. Functional studies add substance to the concept that the lateralization of language is reduced and in some aspects reversed. SUMMARY: The dimension of

  16. Suspect aggression and victim resistance in multiple perpetrator rapes.

    Science.gov (United States)

    Woodhams, Jessica; Cooke, Claire

    2013-11-01

    Several research studies have reported an elevated level of aggression in rapes committed by multiple perpetrators compared to rapes committed by lone suspects. Several factors that have been linked to elevated aggression in generic samples of rape were examined for the first time with a sample of multiple perpetrator rapes. Factors that might be associated with victim resistance were also investigated. Victim and offender characteristics, as well as the behaviors displayed by victims and offenders, were extracted from the police files of 89 multiple perpetrator stranger rapes perpetrated against female victims in the United Kingdom. These behaviors were rated for their level of suspect (non-sexual) aggression and victim resistance, respectively. Degree of victim resistance was significantly and positively associated with suspect aggression. Older victims were the recipients of significantly higher levels of suspect aggression. Victims who were incapacitated from drugs and/or alcohol were less likely to be the recipients of suspect aggression. Group leaders displayed more aggression towards the victim than the followers in the groups. The number of perpetrators was significantly related to the degree of resistance displayed by the victim with offences perpetrated by fewer suspects being characterized by more victim resistance. Research regarding cognitive appraisal during criminal interactions and the respective roles of offenders is referred to in considering these relationships.

  17. Interviewing strategically to elicit admissions from guilty suspects.

    Science.gov (United States)

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-06-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects' perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects' counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects' perception by confronting them with statement-evidence inconsistencies. Participants (N = 90) were asked to perform several mock criminal tasks before being interviewed using 1 of 3 interview techniques: (a) SUE-Confrontation, (b) Early Disclosure of Evidence, or (c) No Disclosure of Evidence. As predicted, the SUE-Confrontation interview generated more statement-evidence inconsistencies from suspects than the Early Disclosure interview. Importantly, suspects in the SUE-Confrontation condition (vs. Early and No disclosure conditions) admitted more self-incriminating information and also perceived the interviewer to have had more information about the critical phase of the crime (the phase where the interviewer lacked evidence). The findings show the adaptability of the SUE-technique and how it may be used as a tool for eliciting admissions. (c) 2015 APA, all rights reserved).

  18. Examining the Use of Distance-Mediated Case Conferencing for Case-Based Training in Clinical Cancer Genetics

    Science.gov (United States)

    Blazer, Kathleen R.

    2010-01-01

    Individuals with a cancer-predisposing genetic trait have a lifetime risk to develop cancer approaching 100 percent, and cancer often strikes early in age, before standard recommended cancer screening begins. Identifying hereditary cancer predisposition through genetic cancer risk assessment (GCRA) allows for intensified measures to prevent…

  19. Predicting attitudes toward nanotechnology: The influence of cultural and predispositional values

    Science.gov (United States)

    Shih, Tsung-Jen

    Past experience in dealing with biotechnology has suggested that public opinion plays an important role in determining the prosperity of emerging technologies. A great amount of money and energy, therefore, were invested to understand nanotechnology's impact on the society and the public, in addition to the technical advancement of the technology. However, most studies examining public opinion have focused on personal level factors and have ignored the potential influence of cultural factors. This study addresses this gap by analyzing public opinion in 21 countries, including the US and 20 European countries. Specifically, this study examines the impact of predispositional and cultural values on public support for nanotechnology, with the mediating roles of moral judgment and risk perception accounted for. This study also looks into the dynamics between cultural values and predispositional values; that is, how cultural values may moderate the effects of predispositional values in affecting attitudes toward nanotechnology. The results indicate that people rely on "information shortcuts," such as confidence and religious belief, for decision making. Individual-level factors still play an important role in shaping public attitudes even after country-level factors are controlled. Furthermore, aggregate cultural values provide people with important "mental programs" to interpret nanotechnology. They explain why people in different cultures have different moral and risk perceptions. However, most of the cultural values do not affect public support directly, suggesting that public support is contingent greatly on the core characteristics of nanotechnology, such as its usefulness, risk, and moral acceptability, which, in turn, is influenced by personal beliefs and cultural givens. The results also suggest that people in different cultures respond to survey questions in different manners. People living in cultures emphasizing uncertainty avoidance and individualism are more

  20. Presumed prevalence analysis on suspected and highly suspected breast cancer lesions in São Paulo using BIRADS® criteria

    Directory of Open Access Journals (Sweden)

    Vivian Milani

    Full Text Available CONTEXT AND OBJECTIVE: Breast cancer screening programs are critical for early detection of breast cancer. Early detection is essential for diagnosing, treating and possibly curing breast cancer. Since there are no data on the incidence of breast cancer, nationally or regionally in Brazil, our aim was to assess women by means of mammography, to determine the prevalence of this disease. DESIGN AND SETTING: The study protocol was designed in collaboration between the Department of Diagnostic Imaging (DDI, Institute of Diagnostic Imaging (IDI and São Paulo Municipal Health Program. METHODS: A total of 139,945 Brazilian women were assessed by means of mammography between April 2002 and September 2004. Using the American College of Radiology (ACR criteria (Breast Imaging Reporting and Data System, BIRADS®, the prevalence of suspected and highly suspected breast lesions were determined. RESULTS: The prevalence of suspected (BIRADS® 4 and highly suspected (BIRADS® 5 lesions increased with age, especially after the fourth decade. Accordingly, BIRADS® 4 and BIRADS® 5 lesions were more prevalent in the fourth, fifth, sixth and seventh decades. CONCLUSION: The presumed prevalence of suspected and highly suspected breast cancer lesions in the population of São Paulo was 0.6% and it is similar to the prevalence of breast cancer observed in other populations.

  1. Difference in Visual Social Predispositions Between Newborns at Low- and High-risk for Autism

    Science.gov (United States)

    Di Giorgio, Elisa; Frasnelli, Elisa; Rosa Salva, Orsola; Maria Luisa, Scattoni; Puopolo, Maria; Tosoni, Daniela; Apicella, Fabio; Gagliano, Antonella; Guzzetta, Andrea; Molteni, Massimo; Persico, Antonio; Pioggia, Giovanni; Valeri, Giovanni; Vicari, Stefano; Simion, Francesca; Vallortigara, Giorgio

    2016-01-01

    Some key behavioural traits of Autism Spectrum Disorders (ASD) have been hypothesized to be due to impairments in the early activation of subcortical orienting mechanisms, which in typical development bias newborns to orient to relevant social visual stimuli. A challenge to testing this hypothesis is that autism is usually not diagnosed until a child is at least 3 years old. Here, we circumvented this difficulty by studying for the very first time, the predispositions to pay attention to social stimuli in newborns with a high familial risk of autism. Results showed that visual preferences to social stimuli strikingly differed between high-risk and low-risk newborns. Significant predictors for high-risk newborns were obtained and an accurate biomarker was identified. The results revealed early behavioural characteristics of newborns with familial risk for ASD, allowing for a prospective approach to the emergence of autism in early infancy. PMID:27198160

  2. Difference in Visual Social Predispositions Between Newborns at Low- and High-risk for Autism.

    Science.gov (United States)

    Di Giorgio, Elisa; Frasnelli, Elisa; Rosa Salva, Orsola; Maria Luisa, Scattoni; Puopolo, Maria; Tosoni, Daniela; Simion, Francesca; Vallortigara, Giorgio

    2016-05-20

    Some key behavioural traits of Autism Spectrum Disorders (ASD) have been hypothesized to be due to impairments in the early activation of subcortical orienting mechanisms, which in typical development bias newborns to orient to relevant social visual stimuli. A challenge to testing this hypothesis is that autism is usually not diagnosed until a child is at least 3 years old. Here, we circumvented this difficulty by studying for the very first time, the predispositions to pay attention to social stimuli in newborns with a high familial risk of autism. Results showed that visual preferences to social stimuli strikingly differed between high-risk and low-risk newborns. Significant predictors for high-risk newborns were obtained and an accurate biomarker was identified. The results revealed early behavioural characteristics of newborns with familial risk for ASD, allowing for a prospective approach to the emergence of autism in early infancy.

  3. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition.

    Science.gov (United States)

    van der Horst, G T; van Steeg, H; Berg, R J; van Gool, A J; de Wit, J; Weeda, G; Morreau, H; Beems, R B; van Kreijl, C F; de Gruijl, F R; Bootsma, D; Hoeijmakers, J H

    1997-05-02

    A mouse model for the nucleotide excision repair disorder Cockayne syndrome (CS) was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient. CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV) sensitivity, inactivation of transcription-coupled repair, unaffected global genome repair, and inability to resume RNA synthesis after UV exposure. Other CS features thought to involve the functioning of basal transcription/repair factor TFIIH, such as growth failure and neurologic dysfunction, are present in mild form. In contrast to the human syndrome, CSB-deficient mice show increased susceptibility to skin cancer. Our results demonstrate that transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers contributes to the prevention of carcinogenesis in mice. Further, they suggest that the lack of cancer predisposition in CS patients is attributable to a global genome repair process that in humans is more effective than in rodents.

  4. Characteristics of benzodiazepine receptors in rats differing in predisposition to experimental alcoholism

    Energy Technology Data Exchange (ETDEWEB)

    Burov, Yu.V.; Maiskii, A.I.; Yukhananov, R.Yu.

    1986-02-01

    This paper studies the number and affinity of benzodiazepine receptors for diazepam in the cerebral cortex and hippocampus of rats differently predisposed to the development of experimental alcoholism. Ethanol was injected once intraperitoneally, in a dose of 2.5 g/kg. Control animals received the same volume of physiological saline. Bound and free N-methyl-tritium-diazepam were separated by means of GF/B filters. The characteristics of benzodiazepine receptors are shown in rats differing in predisposition to the development of experimental alcoholism and in rats during voluntary chronic alcoholization. It is shown that weakening of functional acitivity of the GABA-benzodiazepam complex in animals predisposed to the development of experimental alcoholism is one of the neurochemical mechanisms of development of the abstinence syndrome.

  5. Predisposition to essential hypertension and development of diabetic nephropathy in IDDM patients

    DEFF Research Database (Denmark)

    Fagerudd, J A; Tarnow, L; Jacobsen, P

    1998-01-01

    of hypertension in this group. However, the difference in prevalence of parental hypertension was not evident using office blood pressure measurements (64 vs. 57%; NS; difference 7% [-5.8-20%). Furthermore, patients with DN+ and with antihypertensive therapy in both parents were themselves more frequently treated......Conflicting results have been reported on the relationship between familial predisposition to hypertension and development of diabetic nephropathy in IDDM. In our case-control study, we assessed the prevalence of hypertension among parents of 73 IDDM patients with diabetic nephropathy (DN......+; persistent albuminuria > 200 microg/min or > 300 mg/24 h) and 73 IDDM patients without diabetic nephropathy (DN-; urinary albumin excretion pressure (SpaceLabs 90207) > or = 135/85 mm...

  6. Predisposition in plant disease: exploiting the nexus in abiotic and biotic stress perception and response.

    Science.gov (United States)

    Bostock, Richard M; Pye, Matthew F; Roubtsova, Tatiana V

    2014-01-01

    Predisposition results from abiotic stresses occurring prior to infection that affect susceptibility of plants to disease. The environment is seldom optimal for plant growth, and even mild, episodic stresses can predispose plants to inoculum levels they would otherwise resist. Plant responses that are adaptive in the short term may conflict with those for resisting pathogens. Abiotic and biotic stress responses are coordinated by complex signaling networks involving phytohormones and reactive oxygen species (ROS). Abscisic acid (ABA) is a global regulator in stress response networks and an important phytohormone in plant-microbe interactions with systemic effects on resistance and susceptibility. However, extensive cross talk occurs among all the phytohormones during stress events, and the challenge is discerning those interactions that most influence disease. Identifying convergent points in the stress response circuitry is critically important in terms of understanding the fundamental biology that underscores the disease phenotype as well as translating research to improve stress tolerance and disease management in production systems.

  7. Hindlimb unloading results in increased predisposition to cardiac arrhythmias and alters left ventricular connexin 43 expression.

    Science.gov (United States)

    Moffitt, Julia A; Henry, Matthew K; Welliver, Kathryn C; Jepson, Amanda J; Garnett, Emily R

    2013-03-01

    Hindlimb unloading (HU) is a well-established animal model of cardiovascular deconditioning. Previous data indicate that HU results in cardiac sympathovagal imbalance. It is well established that cardiac sympathovagal imbalance increases the risk for developing cardiac arrhythmias. The cardiac gap junction protein connexin 43 (Cx43) is predominately expressed in the left ventricle (LV) and ensures efficient cell-to-cell electrical coupling. In the current study we wanted to test the hypothesis that HU would result in increased predisposition to cardiac arrhythmias and alter the expression and/or phosphorylation of LV-Cx43. Electrocardiographic data using implantable telemetry were obtained over a 10- to 14-day HU or casted control (CC) condition and in response to a sympathetic stressor using isoproterenol administration and brief restraint. The arrhythmic burden was calculated using a modified scoring system to quantify spontaneous and provoked arrhythmias. In addition, Western blot analysis was used to measure LV-Cx43 expression in lysates probed with antibodies directed against the total and an unphosphorylated form of Cx43 in CC and HU rats. HU resulted in a significantly greater total arrhythmic burden during the sympathetic stressor with significantly more ventricular arrhythmias occurring. In addition, there was increased expression of total LV-Cx43 observed with no difference in the expression of unphosphorylated LV-Cx43. Specifically, the increased expression of LV-Cx43 was consistent with the phosphorylated form. These data taken together indicate that cardiovascular deconditioning produced through HU results in increased predisposition to cardiac arrhythmias and increased expression of phosphorylated LV-Cx43.

  8. Personality and predisposition to form habit behaviours during instrumental conditioning in horses (Equus caballus).

    Science.gov (United States)

    Lansade, Léa; Marchand, Alain R; Coutureau, Etienne; Ballé, Cyrielle; Polli, Floriane; Calandreau, Ludovic

    2017-01-01

    The relationship between personality and learning abilities has become a growing field of interest. Studies have mainly focused on the relationship with performance, such as the speed of acquisition. In this study, we hypothesised that personality could in part also be related to a certain predisposition of an individual to switch more easily from a goal-directed process to a habit process during learning. To identify these processes, we conducted a contingency degradation protocol. This study investigated 1/ whether in general horses are able to adjust their response according to the contingency between their action and the reward, 2/ whether there are any relationships between certain personality profiles and a predisposition to switch more rapidly to habitual processes, and 3/ whether emotional states experienced during the learning procedure play a role in this switching. Personality tests were conducted on 29 horses, followed by a degradation contingency protocol. Overall, results show that horses were sensitive to contingency degradation between their action and the reward. Nevertheless, there was inter-individual variability: the horses presenting high fearfulness, and to a lesser extent low sensory sensitivity and low gregariousness were less sensitive to the degradation, demonstrating that they were more likely to switch to a habitual process. Contrary to our expectations, the emotional state experienced during the procedure did not seem to explain this switching. We conclude that personality is not only related to learning performance, but also in part to the process involved during learning, independently of the emotion experienced during the process. This study provides new theoretical knowledge on cognitive skills in ungulates.

  9. [Genetics in scleroderma].

    Science.gov (United States)

    Bossini-Castillo, Lara; Martín, José-Ezequiel; Díaz-Gallo, Lina Marcela; Rueda, Blanca; Martín, Javier

    2010-09-01

    Systemic sclerosis or scleroderma (SSc) is an autoimmune pathology with a variable clinical expression grouped within genetically complex diseases, in which environmental and genetical factors combine. Genes of the HLA regions were those first associated with susceptibility to present SSc, mainly the HLA-DRB1⁎11/⁎06/⁎16 allelles. However, through association studies, different candidate genes that belong to the triad of autoimmunity, endothelial disfunction and fibrosis have been proposed as genes implicated in the predisposition to disease. In spite of these initial advances, up until recently most studies have had little statistical power, due to the small number of patients included and the lack of reproduction in independent populations. Recently, the development of genotyping platforms and data analysis has allowed for the application of a new type of strategy known as «genome wide association studies» the analysis of the genetics to complex diseases, which are potent tools in the study of these multifactorial diseases. This paper pretends to perform a review of the recent advances in the study of the genetics of scleroderma, presenting results obtained in the analysis of the main candidate genes outside the HLA regions and the contribution of GWAS to the understanding of the molecular mechanisms of this disease. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  10. Genetic variants associated with drugs-induced immediate hypersensitivity reactions: a PRISMA-compliant systematic review

    OpenAIRE

    Oussalah, A.; Mayorga, C.; Blanca, M.; Barbaud, A.; Nakonechna, A.; Cernadas, J.; Gotua, M.; Brockow, K.; Caubet, Jean-Christoph Roger J-P; Bircher, A.; Atanaskovic, M.; Demoly, P.; K. Tanno, L.; Terreehorst, I.; Laguna, J. J.

    2016-01-01

    Drug hypersensitivity includes allergic (AR) and nonallergic reactions (NARs) influenced by genetic predisposition. We performed a systematic review of genetic predictors of IgE-mediated AR and NAR with MEDLINE and PubMed search engine between January 1966 and December 2014. Among 3110 citations, the search selected 53 studies, 42 of which remained eligible. These eligible studies have evaluated genetic determinants of immediate reactions (IR) to beta-lactams (n = 19), NAR against aspirin (n ...

  11. Predisposition to insulin resistance and obesity due to staple consumption of rice: Amylose content versus germination status.

    Science.gov (United States)

    Abubakar, Bilyaminu; Zawawi, Norhasnida; Omar, Abdul Rahman; Ismail, Maznah

    2017-01-01

    Type 2 diabetes is a metabolic disorder with established, well-defined precursors. Obesity and insulin resistance are amongst most important factors in predisposition to diabetes. Rice is a staple for about half the global population and its consumption has been strongly linked with diabetogenesis. We assert that tackling the prevalence of predisposing factors by modifying certain rice cultivars could reduce the global burden of obesity and insulin resistance, and by extension type 2 diabetes. Several rice cultivars with various properties were fed to nulliparous rats (five weeks old at the start of the experiment) for 90 days. They were then returned to a diet of standard pellets and mated with males raised on a standard diet. The resulting pups and dams were investigated for obesity and insulin resistance markers. We found that germination did more to reduce predisposition to obesity and insulin resistance than high amylose content. The combined reducing effect of germination and high amylose content on predisposition to obesity and insulin resistance was greater than the sum of their independent effects. Polished (white) rice with a low amylose content predisposed dams on a high-fat diet to markers of insulin resistance and obesity and this predisposition was inherited (in biochemical terms) by their F1 offspring. Overall, the results suggest that harnessing the beneficial properties of germination and amylose in rice would reduce the burden of obesity and insulin resistance, which are known to be key risk factors for development of type 2 diabetes.

  12. Improving Students' Predisposition towards Physical Education by Optimizing Their Motivational Processes in an Acrosport Unit

    Science.gov (United States)

    Abós, Ángel; Sevil, Javier; Julián, José Antonio; Abarca-Sos, Alberto; García-González, Luis

    2017-01-01

    Grounded in self-determination theory and achievement goal theory, this quasi-experimental study evaluated the effectiveness of a teaching intervention programme to improve predisposition towards physical education based on developing a task-oriented motivational climate and supporting basic psychological needs. The final sample consisted of 35…

  13. Climate change induced effects on the predisposition of forests of the water protection zone Wildalpen to disturbances by bark beetles

    Science.gov (United States)

    Baier, P.; Pennerstorfer, J.; Schopf, A.

    2012-04-01

    The provision of drinking water of high quality is a precious service of forests. Large-scale disturbances like forest fires, wind throws, pest outbreaks and subsequent clear cutting may lead to changes in hydrology (runoff as well as percolation). Furthermore, water quality can be negatively influenced by increased erosion, increased decomposition of litter and humus and leaching of nitrate. Large-scale epidemics of forest pests may induce forest decline at landscape scale with subsequent long-lasting negative effects on water quality. The European spruce bark beetle, Ips typographus (L.), is one of the most significant sources of mortality in mature spruce forest ecosystems in Eurasia. The objective of this study was to apply a complex predisposition assessment system for hazard rating and for the evaluation of climate change impacts for the water protection forests of the City of Vienna in Wildalpen. The following steps have been done to adapt/apply the bark beetle phenology model and the hazard rating system: -application, adaptation and validation of the bark beetle phenology model PHENIPS concerning start of dispersion, brood initiation, duration of development, beginning of sister broods, voltinism and hibernation - spatial/temporal modelling of the phenology and voltinism of I. typographus using past, present as well as projected climate data - application and validation of the stand- and site related long-term predisposition assessment system using forest stand/site data, annual damage reports and outputs of phenology modelling as data input - mapping of endangered areas and assessment of future susceptibility to infestations by I. typographus and other disturbing agents based on climate scenarios using GIS. The assessment of site- and stand-related predisposition revealed that the forest stands in Wildalpen are highly susceptible to bark beetle infestation. More than 65% of the stands were assigned to the predisposition classes high/very high. Only 10% of

  14. New insights into the genetics of fibromyalgia.

    Science.gov (United States)

    Park, Dong-Jin; Lee, Shin-Seok

    2017-11-01

    Although debate on the concept of fibromyalgia (FM) has been vigorous ever since the classification criteria were first published, FM is now better understood and has become recognized as a disorder. Recently, FM has come to be considered a major health problem, affecting 1% to 5% of the general population. As familial aggregations have been observed among some FM patients, genetic research on FM is logical. In fact, genome-wide association studies and linkage analysis, and studies on candidate genes, have uncovered associations between certain genetic factors and FM. Genetic susceptibility is now considered to influence the etiology of FM. At the same time, novel genetic techniques, such as microRNA analysis, have been used in attempts to improve our understanding of the genetic predisposition to FM. In this article, we review recent advances in, and continuing challenges to, the identification of genes contributing to the development of, and symptom severity in, FM.

  15. Clinical and microbiological features of dientamoebiasis in patients suspected of suffering from a parasitic gastrointestinal illness: a comparison of Dientamoeba fragilis and Giardia lamblia infections

    NARCIS (Netherlands)

    Vandenberg, Olivier; Peek, Ron; Souayah, Hichem; Dediste, Anne; Buset, Michel; Scheen, Robert; Retore, Patricia; Zissis, Georges; van Gool, Tom

    2006-01-01

    To describe the clinical and microbiological features of Dientamoeba fragilis and Giardia lamblia infected patients, and to analyze the genetic variation of D. fragilis strains. For a period of two years, all stool samples collected from patients suspected of having a parasitic gastrointestinal

  16. The use of psychoactive prescription drugs among DUI suspects.

    Science.gov (United States)

    Karjalainen, Karoliina; Haukka, Jari; Lintonen, Tomi; Joukamaa, Matti; Lillsunde, Pirjo

    2015-10-01

    The study seeks to increase understanding of the use of psychoactive prescription drugs among persons suspected of driving under the influence (DUI). We studied whether the use of prescribed psychoactive medication was associated with DUI, and examined the difference in the use of prescription drugs between DUI recidivists and those arrested only once. In this register-based study, persons suspected of DUI (n=29470) were drawn from the Register of DUI suspects, and an age- and gender-matched reference population (n=30043) was drawn from the Finnish general population. Data on prescription drug use was obtained by linkage to the National Prescription Register. The associations of DUI arrest and use of psychoactive prescription drugs in different DUI groups (findings for alcohol only, prescription drugs, prescription drugs and alcohol, illicit drugs) were estimated by using mixed-effect logistic regression. The use of psychoactive prescription drugs and DUI appeared to be strongly associated, with DUI suspects significantly more likely to use psychoactive prescription drugs compared to the reference population. Gender differences existed, with the use of benzodiazepines being more common among female DUI suspects. Moreover, DUI recidivists were more likely to use psychoactive prescription drugs compared to those arrested only once. In addition to alcohol and/or illicit drug use, a significant proportion of DUI suspects were using psychoactive prescription drugs. When prescribing psychoactive medication, especially benzodiazepines, physicians are challenged to screen for possible substance use problems and also to monitor for patients' alcohol or illicit drug use while being medicated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Book Review: Placing the Suspect behind the Keyboard: Using Digital Forensics and Investigative Techniques to Identify Cybercrime Suspects

    Directory of Open Access Journals (Sweden)

    Thomas Nash

    2013-06-01

    Full Text Available Shavers, B. (2013. Placing the Suspect behind the Keyboard: Using Digital Forensics and Investigative Techniques to Identify Cybercrime Suspects. Waltham, MA: Elsevier, 290 pages, ISBN-978-1-59749-985-9, US$51.56. Includes bibliographical references and index.Reviewed by Detective Corporal Thomas Nash (tnash@bpdvt.org, Burlington Vermont Police Department, Internet Crime against Children Task Force. Adjunct Instructor, Champlain College, Burlington VT.In this must read for any aspiring novice cybercrime investigator as well as the seasoned professional computer guru alike, Brett Shaver takes the reader into the ever changing and dynamic world of Cybercrime investigation.  Shaver, an experienced criminal investigator, lays out the details and intricacies of a computer related crime investigation in a clear and concise manner in his new easy to read publication, Placing the Suspect behind the Keyboard. Using Digital Forensics and Investigative techniques to Identify Cybercrime Suspects. Shaver takes the reader from start to finish through each step of the investigative process in well organized and easy to follow sections, with real case file examples to reach the ultimate goal of any investigation: identifying the suspect and proving their guilt in the crime. Do not be fooled by the title. This excellent, easily accessible reference is beneficial to both criminal as well as civil investigations and should be in every investigator’s library regardless of their respective criminal or civil investigative responsibilities.(see PDF for full review

  18. Apparent predisposition to systemic lupus erythematosus in Chinese patients in West Malaysia.

    Science.gov (United States)

    Frank, A O

    1980-06-01

    In the first 9 years following the opening of the University Hospital in kuala Lumpur nearly 130,000 patients have been admitted (excluding obstetric patients), and, of these, 175 fulfilled the American Rheumatism Association criteria for the diagnosis of systemic lupus erythematosus. This diagnosis was made significantly more frequently in Chinese patients than in other races. SLE is more often reported from Chinese communities in Asia than from India and tropical Africa. There may be a lower susceptibility to autoimmune disease in black Africans than the suspected increased susceptibility to autoimmune disease in black Africans than the suspected increased susceptibility in their American Negro and West Indian descendants. A careful study of racial and geograhical factors in autoimmune disease should throw further light on the interaction between the host and his environment which results in autoimmune disease.

  19. Suspected Rhinolithiasis Associated With Endodontic Disease in a Cat.

    Science.gov (United States)

    Ng, Kevin; Fiani, Nadine; Peralta, Santiago

    2017-12-01

    Rhinoliths are rare, intranasal, mineralized masses formed via the precipitation of mineral salts around an intranasal nidus. Clinical signs are typically consistent with inflammatory rhinitis and nasal obstruction, but asymptomatic cases are possible. Rhinoliths may be classified as exogenous or endogenous depending on the origin of the nidus, with endogenous rhinoliths reportedly being less common. This case report describes a suspected case of endogenous rhinolithiasis in a cat which was detected as an incidental finding during radiographic assessment of a maxillary canine tooth with endodontic disease. Treatment consisted of removal of the suspected rhinolith via a transalveolar approach after surgical extraction of the maxillary canine tooth.

  20. Cholescintigraphy and ultrasonography in patients suspected of having acute cholecystitis

    DEFF Research Database (Denmark)

    Lauritsen, K B; Sommer, W; Hahn, L

    1988-01-01

    The diagnostic power of combined cholescintigraphy and ultrasonography was tested in 67 patients suspected of having acute cholecystitis; of these, 42 (63%) had acute cholecystitis. The predictive value of a positive scintigraphy (PVpos) was 95% and that of a negative (PVneg) was 91% (n = 67...... that in patients suspected of having acute cholecystitis cholescintigraphy should be the first diagnostic procedure performed. If the scintigraphy is positive, additional ultrasonographic detection of gallstones makes the diagnosis almost certain. If one diagnostic modality is inconclusive, the other makes a fair...

  1. Symptomatic Patency Capsule Retention in Suspected Crohn's Disease

    DEFF Research Database (Denmark)

    Rasmussen, Bjørn; Nathan, Torben; Jensen, Michael Dam

    2016-01-01

    The main limitation of capsule endoscopy is the risk of capsule retention. In patients with suspected Crohn's disease, however, this complication is rare, and if a small bowel stenosis is not reliably excluded, small bowel patency can be confirmed with the Pillcam patency capsule. We present two...... patients examined for suspected Crohn's disease who experienced significant symptoms from a retained patency capsule. Both patients had Crohn's disease located in the terminal ileum. In one patient, the patency capsule caused abdominal pain and vomiting and was visualized at magnetic resonance enterography...

  2. Fluorescence in situ hybridization (FISH) using non-commercial probes in the diagnosis of clinically suspected microdeletion syndromes.

    Science.gov (United States)

    Halder, Ashutosh; Jain, Manish; Chaudhary, Isha; Gupta, Neerja; Kabra, Madhulika

    2013-01-01

    Microdeletion syndromes are characterized by small (Fluorescence in situ hybridization (FISH) technique is commonly used for precise genetic diagnosis of microdeletion syndromes. This study was conducted to assess the role of FISH in the diagnosis of suspected microdeletion syndrome. FISH was carried out on 301 clinically suspected microdeletion syndrome cases for the confirmation of clinical diagnosis using non-commercial probes. Of these, 177 cases were referred for 22q11.2 microdeletion, 42 cases were referred for William syndrome, 38 cases were referred for Prader Willi/Angelman and 44 cases were referred for other suspected microdeletion syndromes. FISH was confirmatory in 23 cases only (7.6%). There were 17 cases of 22q11.2 microdeletion, four cases of Prader Willi syndrome and two cases of William syndrome. We conclude that FISH should not be the method of choice for clinically suspected microdeletion syndromes. We propose to follow strict clinical criteria for FISH testing or preferably to follow better methods (genotype first approach). Whole genome screening may be used as first line of test and FISH may be used for confirmation of screening result, screening of family members and prenatal diagnosis.

  3. Knee complaints and prognosis of osteoarthritis at 10 years : impact of ACL ruptures, meniscal tears, genetic predisposition and surgery

    NARCIS (Netherlands)

    Huetink, Kasper

    2015-01-01

    In this thesis we demonstrated that several known risk factors for knee OA development i.e. ACL ruptures, meniscal tears, the presence of hand OA and increased BMI, are already associated with knee OA development as demonstrated on radiographs and MR images early in life. Identifying these factors

  4. MRI screening for breast cancer in women with familial or genetic predisposition : design of the Dutch National Study (MRISC)

    NARCIS (Netherlands)

    Kriege, M; Brekelmans, C T; Boetes, C; Rutgers, E J; Oosterwijk, J C; Tollenaar, R A; Manoliu, R A; Holland, R; de Koning, H J; Klijn, J G

    2001-01-01

    Mammography screening of women aged 50-70 years for breast cancer has proven to be effective in reducing breast cancer mortality. There is no consensus about the value of breast cancer screening in women aged 40-49 years. Five to ten per cent of all breast cancers are hereditary. One of the options

  5. Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism | Office of Cancer Genomics

    Science.gov (United States)

    Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells.

  6. [Issues on business of genetic testing in near future].

    Science.gov (United States)

    Takada, Fumio

    2009-06-01

    Since 1990's, a business condition that company sells genetic testing services directly to consumers without through medical facility, so called "direct-to-consumers (DTC) genetic testing", has risen. They provide genetic testing for obesity, disease susceptibility or paternity, etc. There are serious problems in this kind of business. Most of the providers do not make sales with face-to-face selling, and do through internet instead. They do not provide genetic counseling by certified genetic counselor or clinical geneticist. Most DTC genetic testing services for disease susceptibility or predispositions including obesity, lack scientific validity, clinical validity and clinical utility. And also including paternity genetic testing, they all have risks of ethical legal and social issues (ELSI) in genetic discrimination and/or eugenics. The specific problem in Japan is that the healthcare section of the government still has not paid attention and not taken seriously the requirement to deploy safety net.

  7. Dopamine and the management of attentional resources: genetic markers of striatal D2 dopamine predict individual differences in the attentional blink.

    Science.gov (United States)

    Colzato, Lorenza S; Slagter, Heleen A; de Rover, Mischa; Hommel, Bernhard

    2011-11-01

    The attentional blink (AB)--a deficit in reporting the second of two target stimuli presented in close succession in a rapid sequence of distracters--has been related to processing limitations in working memory. Given that dopamine (DA) plays a crucial role working memory, the present study tested whether individual differences in the size of the AB can be predicted by differences in genetic predisposition related to the efficiency of dopaminergic pathways. Polymorphisms related to mesocortical and nigrostriatal dopaminergic pathways were considered, as well as polymorphisms related to norepinephrine (NE), a transmitter system that has also been suspected to play a role in the AB. In a sample of 157 healthy adults, we studied the dependency of the individual magnitude of the AB and the C957T polymorphism at the DRD2 gene (associated with striatal DA/D2 receptors), the DARPP32 polymorphism (associated with striatal DA/D1), the COMT Val(158)Met polymorphism (associated with frontal DA), DBH444 g/a and DBH5'-ins/del polymorphisms (polymorphisms strongly correlated with DA beta hydroxylase, the enzyme catalyzing the DA-NE conversion) and NET T-182C (a polymorphism related to the NE transporter). DRD2 C957T T/T homozygotes showed a significantly smaller AB, whereas polymorphisms associated with frontal DA and NE were unrelated to performance. This outcome pattern suggests a crucial role of the nigrostriatal dopaminergic pathway and of nigrostriatal D2 receptors, in particular, in the management of attentional resources.

  8. PMS2 Involvement in Patients Suspected of Lynch Syndrome

    NARCIS (Netherlands)

    Niessen, Renee C.; Kleibeuker, Jan H.; Westers, Helga; Jager, Paul O. J.; Rozeveld, Dennie; Bos, Krista K.; Boersma-van Ek, Wytske; Hollema, Harry; Sijmons, Rolf H.; Hofstra, Robert M. W.

    It is well-established that germline mutations in the mismatch repair genes MLH1, MSH2, and MSH6 cause Lynch syndrome. However, mutations in these three genes do not account for all Lynch syndrome (suspected) families. Recently, it was shown that germline mutations in another mismatch repair gene,

  9. Faecal Calprotectin in Suspected Paediatric Inflammatory Bowel Disease

    NARCIS (Netherlands)

    Degraeuwe, Pieter L. J.; Beld, Monique P. A.; Ashorn, Merja; Canani, Roberto Berni; Day, Andrew S.; Diamanti, Antonella; Fagerberg, Ulrika L.; Henderson, Paul; Kolho, Kaija-Leena; Van de Vijver, Els; van Rheenen, Patrick F.; Wilson, David C.; Kessels, Alfons G. H.

    Objectives: The diagnostic accuracy of faecal calprotectin (FC) concentration for paediatric inflammatory bowel disease (IBD) is well described at the population level, but not at the individual level. We reassessed the diagnostic accuracy of FC in children with suspected IBD and developed an

  10. Stabilization of the spine in patients with suspected cervical spine ...

    African Journals Online (AJOL)

    Stabilization of the spine in patients with suspected cervical spine injury in Mulago Hospital. BM Ndeleva, T Beyeza. Abstract. No Abstract. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT · http://dx.doi.org/10.4314/eaoj.v5i1.67487 · AJOL African Journals ...

  11. Talking heads : interviewing suspects from a cultural perspective

    NARCIS (Netherlands)

    Beune, K.

    2009-01-01

    Although the literature on the interviewing of suspects has increased over the past decade, research on the use and effectiveness of police strategies and their boundary conditions is very rare. The present dissertation aims to fill this void by identifying behaviors that appeal to and persuade

  12. Nonreferral of Nursing Home Patients With Suspected Breast Cancer

    NARCIS (Netherlands)

    Hamaker, Marije E.; Hamelinck, Victoria C.; van Munster, Barbara C.; Bastiaannet, Esther; Smorenburg, Carolien H.; Achterberg, Wilco P.; Liefers, Gerrit-Jan; de Rooij, Sophia E.

    2012-01-01

    Introduction: People with suspected breast cancer who are not referred for diagnostic testing remain unregistered and are not included in cancer statistics. Little is known about the extent of and motivation for nonreferral of these patients. Methods: A Web-based survey was sent to all elderly care

  13. DNA typing from vaginal smear slides in suspected rape cases

    Directory of Open Access Journals (Sweden)

    Dayse Aparecida da Silva

    Full Text Available In an investigation of suspected rape, proof of sexual assault with penetration is required. In view of this, detailed descriptions of the genitalia, the thighs and pubic region are made within the forensic medical service. In addition, vaginal swabs are taken from the rape victim and some of the biological material collected is then transferred to glass slides. In this report, we describe two rape cases solved using DNA typing from cells recovered from vaginal smear slides. In 1999, two young women informed the Rio de Janeiro Police Department that they had been victims of sexual assaults. A suspect was arrested and the victims identified him as the offender. The suspect maintained that he was innocent. In order to elucidate these crimes, vaginal smear slides were sent to the DNA Diagnostic Laboratory for DNA analysis three months after the crimes, as unique forensic evidence. To get enough epithelial and sperm cells to perform DNA analysis, we used protocols modified from the previously standard protocols used for DNA extraction from biological material fixed on glass slides. The quantity of cells was sufficient to perform human DNA typing using nine short tandem repeat (STR loci. It was 3.3 billion times more probable that it was the examined suspect who had left sperm cells in the victims, rather than any other individual in the population of Rio de Janeiro.

  14. Cognitive Linguistic Performances of Multilingual University Students Suspected of Dyslexia

    Science.gov (United States)

    Lindgren, Signe-Anita; Laine, Matti

    2011-01-01

    High-performing adults with compensated dyslexia pose particular challenges to dyslexia diagnostics. We compared the performance of 20 multilingual Finnish university students with suspected dyslexia with 20 age-matched and education-matched controls on an extensive test battery. The battery tapped various aspects of reading, writing, word…

  15. Differential Diagnosis of Children with Suspected Childhood Apraxia of Speech

    Science.gov (United States)

    Murray, Elizabeth; McCabe, Patricia; Heard, Robert; Ballard, Kirrie J.

    2015-01-01

    Purpose: The gold standard for diagnosing childhood apraxia of speech (CAS) is expert judgment of perceptual features. The aim of this study was to identify a set of objective measures that differentiate CAS from other speech disorders. Method: Seventy-two children (4-12 years of age) diagnosed with suspected CAS by community speech-language…

  16. A suspected case of Addison’s disease in cattle

    OpenAIRE

    Lambacher, Bianca; Wittek, Thomas

    2015-01-01

    A 4.75-year old Simmental cow was presented with symptoms of colic and ileus. The clinical signs and blood analysis resulted in the diagnosis of suspected primary hypoadrenocorticism (Addison’s disease). Although Addison’s disease has been frequently described in other domestic mammals, to our knowledge, this disease has not previously been reported in cattle.

  17. Is extended biopsy protocol justified in all patients with suspected ...

    African Journals Online (AJOL)

    Objective: To determine the significance of an extended 10-core transrectal biopsy protocol in different categories of patients with suspected prostate cancer using digital guidance. Materials and Methods: We studied 125 men who were being evaluated for prostate cancer. They all had an extended 10-core digitally guided ...

  18. Correlates and Suspected Causes of Obesity in Children

    Science.gov (United States)

    Crothers, Laura M.; Kehle, Thomas J.; Bray, Melissa A.; Theodore, Lea A.

    2009-01-01

    The correlates and suspected causes of the intractable condition obesity are complex and involve environmental and heritable, psychological and physical variables. Overall, the factors associated with and possible causes of it are not clearly understood. Although there exists some ambiguity in the research regarding the degree of happiness in…

  19. Medical Evaluation of Suspected Child Sexual Abuse: 2011 Update

    Science.gov (United States)

    Adams, Joyce A.

    2011-01-01

    The medical evaluation of children with suspected sexual abuse includes more than just the physical examination of the child. The importance of taking a detailed medical history from the parents and a history from the child about physical sensations following sexual contact has been emphasized in other articles in the medical literature. The…

  20. Selective screening in neonates suspected to have inborn errors of ...

    African Journals Online (AJOL)

    Background: Inborn errors of metabolism (IEM) have a high morbidity and mortality in neonates. Unfortunately, there is no nationwide neonatal screen in Egypt, so several cases may be missed. Objective: The aim of this work was to detect the prevalence of IEM among neonates with suspected IEM, and to diagnose IEM as ...

  1. Sexual Health Before Treatment in Women with Suspected Gynecologic Malignancy.

    Science.gov (United States)

    Bretschneider, C Emi; Doll, Kemi M; Bensen, Jeannette T; Gehrig, Paola A; Wu, Jennifer M; Geller, Elizabeth J

    2017-08-22

    Sexual health in survivors of gynecologic cancer has been studied; however, sexual health in these women before treatment has not been thoroughly evaluated. The objective of our study was to describe the pretreatment characteristics of sexual health of women with suspected gynecologic cancer before cancer treatment. We performed a cross-sectional analysis of women with a suspected gynecologic cancer, who were prospectively enrolled in a hospital-based cancer survivorship cohort from August 2012 to June 2013. Subjects completed the validated Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire. Pretreatment sexual health was assessed in terms of sexual interest, desire, lubrication, discomfort, orgasm, enjoyment, and satisfaction. Of 186 eligible women with suspected gynecologic cancer, 154 (82%) completed the questionnaire pretreatment. Mean age was 58.1 ± 13.3 years. Sexual health was poor: 68.3% reported no sexual activity, and 54.7% had no interest in sexual activity. When comparing our study population to the general U.S. population, the mean pretreatment scores for the subdomains of lubrication and vaginal discomfort were similar, while sexual interest was significantly lower and global satisfaction was higher. In a linear regression model, controlling for cancer site, age remained significantly associated with sexual function while cancer site did not. Problems with sexual health are prevalent in women with suspected gynecologic malignancies before cancer treatment. Increasing awareness of the importance of sexual health in this population will improve quality of life for these women.

  2. Use of budesonide Turbuhaler in young children suspected of asthma

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S; Nikander, K

    1994-01-01

    The question addressed in this study was the ability of young children to use a dry-powder inhaler, Turbuhaler. One hundred and sixty five children suspected of asthma, equally distributed in one year age-groups from 6 months to 8 yrs, inhaled from a Pulmicort Turbuhaler, 200 micrograms budesonid...

  3. Doppler ultrasound in the assessment of suspected intra-uterine ...

    African Journals Online (AJOL)

    Ramakantb

    obesity with hypertension and non-insulin-dependent diabetes mellitus.[3] In this review, a brief discussion about the ultrasound diagnosis of suspected IUGR, and thereafter about the use of Doppler ultrasound in the diagnosis of IUGR, will be ... before that, all fetuses have relatively larger heads, which will mask the brain-.

  4. Candida meningitis in a suspected immunosuppressive patient - A ...

    African Journals Online (AJOL)

    Candida meningitis in a suspected immunosuppressive patient - A case report. EO Sanya, NB Ameen, BA Onile. Abstract. No Abstract. West African Journal of Medicine Vol. 25 (1) 2006: pp.79-81. Full Text: EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT.

  5. Ajmaline challenge in young individuals with suspected Brugada syndrome

    NARCIS (Netherlands)

    Sorgente, A.; Sarkozy, A.; Asmundis, C. de; Chierchia, G.B.; Capulzini, L.; Paparella, G.; Henkens, S.; Brugada, P.

    2011-01-01

    BACKGROUND: The clinical characteristics and the results of ajmaline challenge in young individuals with suspected Brugada syndrome (BS) have not been systematically investigated. METHODS: Among a larger series of patients included in the BS database of our Department, 179 patients undergoing

  6. A Diagnostic Program for Patients Suspected of Having Lung Cancer

    NARCIS (Netherlands)

    Stigt, Jos A.; Uil, Steven M.; Oostdijk, Ad H.; Boers, James E.; van den Berg, Jan-Willem K.; Groen, Harry J. M.

    2012-01-01

    In 297 patients suspected of having lung cancer, invasive diagnostic procedures followed positron emission tomography/computed tomography (PET-CT) on the same day. For patients with a diagnosis of malignancy (215/297), investigations were finalized on 1 day in 85%, and bronchoscopy was performed in

  7. Use of Chest Radiography In Patients Suspected of Pulmonary ...

    African Journals Online (AJOL)

    may be rushed into treatfng all cases of cough, fever and weight loss with negative sputums as PTB, and other diagnoses may be overlooked. A cheaper, quicker way of screening TB suspects would help con- siderably in this common problem. In Febuary 1991, the Norwegian Government do- nated two Odelka camer;l,s to ...

  8. Opioid analgesic administration in patients with suspected drug use.

    Science.gov (United States)

    Kreling, Maria Clara Giorio Dutra; Mattos-Pimenta, Cibele Andrucioli de

    2017-01-01

    To identify the prevalence of patients suspected of drug use according to the nursing professionals' judgement, and compare the behavior of these professionals in opioid administration when there is or there is no suspicion that patient is a drug user. A cross-sectional study with 507 patients and 199 nursing professionals responsible for administering drugs to these patients. The Chi-Square test, Fisher's Exact and a significance level of 5% were used for the analyzes. The prevalence of suspected patients was 6.7%. The prevalence ratio of administration of opioid analgesics 'if necessary' is twice higher among patients suspected of drug use compared to patients not suspected of drug use (p = 0.037). The prevalence of patients suspected of drug use was similar to that of studies performed in emergency departments. Patients suspected of drug use receive more opioids than patients not suspected of drug use. Identificar a prevalência de pacientes com suspeita de uso de drogas conforme opinião de profissionais de enfermagem e comparar a conduta desses profissionais na administração de opioides quando há ou não suspeita de que o paciente seja usuário de drogas. Estudo transversal com 507 pacientes e 199 profissionais de enfermagem responsáveis pela administração de medicamentos a esses pacientes. Para as análises foram utilizados os testes de Qui-Quadrado, Exato de Fisher e um nível de significância de 5%. A prevalência de pacientes suspeitos foi 6,7%. A razão de prevalência de administração de analgésicos opioides "se necessário" é duas vezes maior entre os pacientes suspeitos em relação aos não suspeitos (p=0,037). A prevalência de suspeitos foi semelhante à de estudos realizados em departamentos de emergência. Os suspeitos de serem usuários de drogas recebem mais opioides do que os não suspeitos.

  9. Suspectable Risk Factors of Congenital Anomaly in Dr. Hasan Sadikin General Hospital Bandung, Indonesia

    Directory of Open Access Journals (Sweden)

    Pradistya Syifa Yudiasari

    2017-06-01

    Full Text Available Background: Congenital anomaly is a disease of structural or functional alteration since birth. The cause of congenital anomaly is genetic, environtment, and unknown. The cause of congenital anomaly is unknown, made congenital anomaly is difficult to detect. Therefore, the objective of this study was to identify the suspectable risk factors of congenital anomaly. Methods: This was a descriptive study. About 78 samples were taken by purposive sampling from medical records of patients with congenital anomaly in pediatric surgery ambulatory unit at Dr. Hasan Sadikin General Hospital (RSHS, Bandung from September to November 2014. From the selected medical records, an interview was carried out to the parents’ patient to identify some suspectable risk factors. The collected data were analyzed and presented in tables. Results: From 78 medical records,  hirschprung disease was the highest among all type of congenital anomaly (29%. The characteristic of congenital anomaly was mothers in the age of 20–35 years (65%, fathers’ age was  more than 20 years old, family history of congenital anomaly was 1%, there was no history of previous congenital anomaly in previous pregnancy, infection history was 3%, history of medication was 11.5%, mother’s BMI was in normal term (18.5─24.9 as much as 65%, no history of radiation, there was no history of chronic alcohol. History of smoking/passive smoking was high (65%. Conclusions: Hirschprung disease is the highest rate disease in congenital anomaly and smoking is a highest suspectable risk factor contribute to congenital anomaly.   DOI: 10.15850/amj.v4n2.1095

  10. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease

    NARCIS (Netherlands)

    van der Sloot, Kimberley; Ziad Alizadeh, Behrooz

    INTRODUCTION: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn's disease (CD) progression. METHODS: Our study population included

  11. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease

    NARCIS (Netherlands)

    Van Der Sloot, Kimberley W. J.; Joshi, Amit D.; Bellavance, Danielle R.; Gilpin, Katherine K.; Stewart, Kathleen O.; Lochhead, Paul; Garber, John J.; Giallourakis, Cosmas; Yajnik, Vijay; Ananthakrishnan, Ashwin N.; Alizadeh, Behrooz Z.; Xavier, Ramnik J.; Khalili, Hamed

    Introduction: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation. However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition in Crohn's disease (CD) progression. Methods: Our study population included

  12. A Specific Pathway Can Be Identified between Genetic Characteristics and Behaviour Profiles in Prader-Willi Syndrome via Cognitive, Environmental and Physiological Mechanisms

    Science.gov (United States)

    Woodcock, K. A.; Oliver, C.; Humphreys, G. W.

    2009-01-01

    Background: Behavioural phenotypes associated with genetic syndromes have been extensively investigated in order to generate rich descriptions of phenomenology, determine the degree of specificity of behaviours for a particular syndrome, and examine potential interactions between genetic predispositions for behaviour and environmental influences.…

  13. Magnetic resonance imaging versus bone scintigraphy in suspected scaphoid fracture

    Energy Technology Data Exchange (ETDEWEB)

    Tiel-van Buul, M.M.C. [Dept. of Nuclear Medicine, Academic Medical Center, Univ. of Amsterdam (Netherlands); Roolker, W. [Dept. of Nuclear Medicine, Academic Medical Center, Univ. of Amsterdam (Netherlands); Verbeeten, B.W.B. Jr. [Dept. of Radiology, Academic Medical Center, Univ. of Amsterdam (Netherlands); Broekhuizen, A.H. [Dept. of Traumatology, Academic Medical Center, Univ. of Amsredam (Netherlands)

    1996-08-01

    Magnetic resonance imaging (MRI) has become increasingly useful in the evaluation of musculoskeletal problems, including those of the wrist. In patients with a wrist injury, MRI is used mainly to assess vascularity of scaphoid non-union. However, the use of MRI in patients in the acute phase following carpal injury is not common. Three-phase bone scintigraphy is routinely performed from at least 72 h after injury in patients with suspected scaphoid fracture and negative initial radiographs. We evaluated MRI in this patient group. The bone scan was used as the reference method. Nineteen patients were included. Bone scintigraphy was performed in all 19 patients, but MRI could be obtained in only 16 (in three patients, MRI was stopped owing to claustrophobia). In five patients, MRI confirmed a scintigraphically suspected scaphoid fracture. In one patient, a perilunar luxation, without a fracture, was seen on MRI, while bone scintigraphy showed a hot spot in the region of the lunate bone, suspected for fracture. This was confirmed by surgery. In two patients, a hot spot in the scaphoid region was suspected for scaphoid fracture, and immobilization and employed for a period of 12 weeks. MRI was negative in both cases; in one of them a scaphoid fracture was retrospectively proven on the initial X-ray series. In another two patients, a hot spot in the region of MCP I was found with a negative MRI. In both, the therapy was adjusted. In the remaining six patients, both modalities were negative. We conclude that in the diagnostic management of patients with suspected scaphoid fracture and negative initial radiographs, the use of MRI may be promising, but is not superior to three-phase bone scintigraphy. (orig.)

  14. Genetic aspects of human obesity.

    Science.gov (United States)

    Larder, Rachel; Lim, Chung Thong; Coll, Anthony P

    2014-01-01

    Obesity and its related metabolic consequences represent a major public health problem. Huge changes within the environment have undoubtedly contributed to the increased prevalence of obesity but genetic factors are also critical in determining an individual's predisposition to gain weight. The last two decades have seen a huge increase in the understanding of the mechanisms controlling appetitive behavior, body composition, and energy expenditure. Many regions throughout the central nervous system play critical roles in these processes but the hypothalamus, in particular, receives and orchestrates a variety of signals to bring about coordinated changes in energy balance. Reviewing data from human genetic and model organism studies, we consider how disruptions of hypothalamic pathways evolved to maintain energy homeostasis and go on to cause obesity. We highlight ongoing technological developments which continue to lead to novel insights and discuss how this increased knowledge may lead to effective therapeutic interventions in the future. © 2014 Elsevier B.V. All rights reserved.

  15. Arousal Predisposition as a Vulnerability Indicator for Psychosis: A General Population Online Stress Induction Study

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    Annika Clamor

    2015-01-01

    Full Text Available Explanatory models ascribe to arousability a central role for the development of psychotic symptoms. Thus, a disposition to hyperarousal (i.e., increased arousal predisposition (AP may serve as an underlying vulnerability indicator for psychosis by interacting with stressors to cause symptoms. In this case, AP, stress-response, and psychotic symptoms should be linked before the development of a diagnosable psychotic disorder. We conducted a cross-sectional online study in a population sample (N=104; Mage=27.7 years, SD=11.2, range 18–70. Participants rated their AP and subclinical psychotic symptoms. Participants reported their stress-levels before and after two stress inductions including an arithmetic and a social stressor. The participants with an increased AP generally felt more stressed. However, AP was not associated with the specific stress-response. As expected, positive psychotic symptoms were significantly associated with AP, but this was not mediated by general stress-levels. Its association to subtle, nonclinical psychotic symptoms supports our assumption that AP could be a vulnerability indicator for psychosis. The trait is easily accessible via a short self-report and could facilitate the identification of people at risk and be a promising target for early stress-management. Further research is needed to clarify its predictive value for stress-responses.

  16. Impact of “noncaloric” activity-related factors on the predisposition to obesity in children

    Directory of Open Access Journals (Sweden)

    Angelo Tremblay

    2010-07-01

    Full Text Available Angelo Tremblay, Émilie Pérusse-Lachance, Patrice BrassardDivision de Kinésiologie, PEPS, Université Laval and Centre de Recherche de l’Institut Universitaire en Cardiologie et Pneumologie de Québec, Québec, CanadaAbstract: The research related to childhood obesity generally emphasizes the impact of unhealthy eating and sedentary behavior as the main determinants of the predisposition to the positive energy balance that underlies excess body fat accumulation. Recent investigations have, however, demonstrated that “noncaloric” activity-related factors can induce a significant imbalance between spontaneous energy intake and energy expenditure. This is the case for short sleep duration that favors hormonal changes that increase hunger and energy intake. This agrees with our research experience demonstrating that short sleeping predicts the risk of obesity in children to a greater extent than sedentary behavior. Recent research by our team has also showed that demanding mental work promotes a substantial increase in energy intake without altering energy expenditure. In addition, our preliminary data suggest that the regular practice of school-related cognitive efforts is predictive of an increase in abdominal fat accumulation. As discussed in this paper, individual variations in brain oxygenation and its related cerebral aerobic fitness might play a role in the relationship between mental work, energy intake, and the risk of excess body weight.Keywords: sleep duration, mental work, brain oxygenation, energy intake, energy expenditure

  17. Tumor susceptibility gene 101 regulates predisposition to apoptosis via ESCRT machinery accessory proteins

    Science.gov (United States)

    Kaul, Zenia; Chakrabarti, Oishee

    2017-01-01

    ESCRT proteins are implicated in myriad cellular processes, including endosome formation, fusion of autophagosomes/amphisomes with lysosomes, and apoptosis. The role played by these proteins in either facilitating or protecting against apoptosis is unclear. In this study, while trying to understand how deficiency of Mahogunin RING finger 1 (MGRN1) affects cell viability, we uncovered a novel role for its interactor, the ESCRT-I protein TSG101: it directly participates in mitigating ER stress–mediated apoptosis. The association of TSG101 with ALIX prevents predisposition to apoptosis, whereas ALIX–ALG-2 interaction favors a death phenotype. Altered Ca2+ homeostasis in cells and a simultaneous increase in the protein levels of ALIX and ALG-2 are required to elicit apoptosis by activating ER stress–associated caspase 4/12. We further demonstrate that in the presence of membrane-associated, disease-causing prion protein CtmPrP, increased ALIX and ALG-2 levels are detected along with ER stress markers and associated caspases in transgenic brain lysates and cells. These effects were rescued by overexpression of TSG101. This is significant because MGRN1 deficiency is closely associated with neurodegeneration and prenatal and neonatal mortality, which could be due to excess cell death in selected brain regions or myocardial apoptosis during embryonic development. PMID:28539405

  18. Overexpression of the transcription factor Hand1 causes predisposition towards arrhythmia in mice.

    Science.gov (United States)

    Breckenridge, Ross A; Zuberi, Zia; Gomes, John; Orford, Robert; Dupays, Laurent; Felkin, Leanne E; Clark, James E; Magee, Anthony I; Ehler, Elisabeth; Birks, Emma J; Barton, Paul J R; Tinker, Andrew; Mohun, Timothy J

    2009-07-01

    Elevated levels of the cardiac transcription factor Hand1 have been reported in several adult cardiac diseases but it is unclear whether this change is itself maladaptive with respect to heart function. To test this possibility, we have developed a novel, inducible transgenic system, and used it to overexpress Hand1 in adult mouse hearts. Overexpression of Hand1 in the adult mouse heart leads to mild cardiac hypertrophy and a reduction in life expectancy. Treated mice show no significant fibrosis, myocyte disarray or congestive heart failure, but have a greatly reduced threshold for induced ventricular tachycardia, indicating a predisposition to cardiac arrhythmia. Within 48 h, they show a significant loss of connexin43 protein from cardiac intercalated discs, with increased intercalated disc beta-catenin expression at protein and RNA levels. These changes are sustained during prolonged Hand1 overexpression. We propose that cardiac overexpression of Hand1 offers a useful mouse model of arrhythmogenesis and elevated HAND1 may provide one of the molecular links between the failing heart and arrhythmia.

  19. The Role of PALB2 in the DNA Damage Response and Cancer Predisposition.

    Science.gov (United States)

    Nepomuceno, Thales C; De Gregoriis, Giuliana; de Oliveira, Francisco M Bastos; Suarez-Kurtz, Guilherme; Monteiro, Alvaro N; Carvalho, Marcelo A

    2017-08-31

    The deoxyribonucleic acid (DNA) damage response (DDR) is a major feature in the maintenance of genome integrity and in the suppression of tumorigenesis. PALB2 (Partner and Localizer of Breast Cancer 2 (BRCA2)) plays an important role in maintaining genome integrity through its role in the Fanconi anemia (FA) and homologous recombination (HR) DNA repair pathways. Since its identification as a BRCA2 interacting partner, PALB2 has emerged as a pivotal tumor suppressor protein associated to hereditary cancer susceptibility to breast and pancreatic cancers. In this review, we discuss how other DDR proteins (such as the kinases Ataxia Telangiectasia Mutated (ATM) and ATM- and Rad3-Related (ATR), mediators BRCA1 (Breast Cancer 1)/BRCA2 and effectors RAD51/DNA Polymerase η (Polη) interact with PALB2 to orchestrate DNA repair. We also examine the involvement of PALB2 mutations in the predisposition to cancer and the role of PALB2 in stimulating error-free DNA repair through the FA/HR pathway.

  20. Pre-disposition and epigenetics govern variation in bacterial survival upon stress.

    Directory of Open Access Journals (Sweden)

    Ming Ni

    Full Text Available Bacteria suffer various stresses in their unpredictable environment. In response, clonal populations may exhibit cell-to-cell variation, hypothetically to maximize their survival. The origins, propagation, and consequences of this variability remain poorly understood. Variability persists through cell division events, yet detailed lineage information for individual stress-response phenotypes is scarce. This work combines time-lapse microscopy and microfluidics to uniformly manipulate the environmental changes experienced by clonal bacteria. We quantify the growth rates and RpoH-driven heat-shock responses of individual Escherichia coli within their lineage context, stressed by low streptomycin concentrations. We observe an increased variation in phenotypes, as different as survival from death, that can be traced to asymmetric division events occurring prior to stress induction. Epigenetic inheritance contributes to the propagation of the observed phenotypic variation, resulting in three-fold increase of the RpoH-driven expression autocorrelation time following stress induction. We propose that the increased permeability of streptomycin-stressed cells serves as a positive feedback loop underlying this epigenetic effect. Our results suggest that stochasticity, pre-disposition, and epigenetic effects are at the source of stress-induced variability. Unlike in a bet-hedging strategy, we observe that cells with a higher investment in maintenance, measured as the basal RpoH transcriptional activity prior to antibiotic treatment, are more likely to give rise to stressed, frail progeny.

  1. Predisposition for borderline personality disorder with comorbid major depression is associated with that for polycystic ovary syndrome in female Japanese population

    Directory of Open Access Journals (Sweden)

    Kawamura S, Maesawa C, Nakamura K, Nakayama K, Morita M, Hiruma Y, Yoshida T, Sakai A, Masuda T

    2011-11-01

    Full Text Available Satoshi Kawamura1, Chihaya Maesawa2, Koji Nakamura1, Kazuhiko Nakayama1, Michiaki Morita1, Yohei Hiruma1, Tomoyuki Yoshida3, Akio Sakai3, Tomoyuki Masuda41Department of Psychiatry, Tokyo Jikei University school of Medicine, Tokyo, Japan; 2Department of Tumor Biology, Division of Bioscience, center for Advanced Medical science, Iwate Medical University school of Medicine, Morioka, Japan; 3Department of Neuropsychiatry, Iwate Medical University school of Medicine, Morioka, Japan; 4Department of Pathology, Iwate Medical University school of Medicine, Morioka, JapanAbstract: Polycystic ovary syndrome (PCOS is a common lifestyle-related endocrinopathy in women of reproductive age and is associated with several mental health problems. We examined the genotypic distributions of IRS-1 Gly972Arg and CYP11B2 -344T/C, which were previously described as influencing PCOS, and assayed the serum levels of interleukin-6 (IL-6 and tumor necrosis factor-alpha (TNF-α, in a set of female patients with borderline personality disorder (BPD with comorbid major depressive disorder (MDD (n = 50 and age-matched control subjects (n = 100, to investigate the predisposition for BPD with MDD. The results showed that the patients were more frequently IRS-1 972Arg variant allele carriers (P = 0.013; OR 6.68; 95% CI = 1.30-34.43 and homozygous for the CYP11B2 -344C variant allele (P = 0.022; OR = 3.32; 95% CI = 1.18-9.35 than the control subjects. The IL-6 level was significantly higher in the patients than in the controls (P < 0.0001. There was no significant difference in the serum TNF-α level between patients with BPD with MDD and the healthy comparison group (P = 0.5273. In conclusion, the predisposition for BPD with MDD is associated with that for PCOS, in the female Japanese population. An elevated serum IL-6 level is considered to be a possible biomarker of BPD with MDD.Keywords: borderline personality disorder, depression, polycystic ovary syndrome, genetic

  2. Genetic risk of breast cancer.

    Science.gov (United States)

    Nasir, A; Shackelford, R E; Anwar, F; Yeatman, T J

    2009-12-01

    Several cutting-edge strategies are being used to evaluate candidate genetic risk factors for breast cancer. These include linkage analysis for mapping out BRCA1 and BRCA2, mutational screening of candidate risk genes like CHEK2, ATM, BRIP1 and PALB2, which are associated with an intermediate level of breast cancer risk. Genome-wide association studies have revealed several low-penetrance breast cancer risk alleles. The predisposition factors are associated with different levels of breast cancer risk. Relative to control population, the risk in patients harboring high-risk BRCA1 and 2 mutations is over 10-fold, with intermediate penetrance genes 2 to 4-fold and with low penetrance alleles less than 1.5-fold. Overall, these factors account for about 25% of the genetic risk for breast cancer. In the remainder, genetic factors to contribute to the risk of breast cancer remain unknown and are a subject of current investigation. With discovery and validation of newer and clinically relevant predisposition factors, additional breast cancer risk categories may be recognized. BRCA1 and BRCA2 mutation testing allows identification of individuals at increased risk of breast cancer who are offered risk-reducing interventions. Targeted therapies are being developed that may refine management of patients with BRCA1 and BRCA2 mutations. Further genome-wide studies are required to identify clinically relevant molecular factors that will allow more accurate and widely applicable genetic risk stratification. Current efforts in discovery, validation and qualification of molecular markers of breast cancer risk offer considerable promise in the future to develop more accurate breast cancer risk assessment along with development of more effective chemopreventive and therapeutic strategies.

  3. The genetic basis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    A. A. Tappakhov

    2017-01-01

    Full Text Available Parkinson's disease (PD is a multifactorial disease that develops in the presence of both genetic and environmental factors. In recent years, there has been sufficient information on the role of genetic predisposition in the development of not only familial cases, but also sporadic ones. A hereditary burden in PD may not be traced in cases of recessive inheritance with a low gene penetrance, as well as in a patient's death before the onset of the disease. Active introduction of molecular genetic methods, including next generation sequencing, can annually identify new gene mutations that underlie sporadic PD cases. This paper provides an overview of the current literature on the genetic aspects of PD with emphasis on the ethnic characteristics of the disease.

  4. The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels

    Science.gov (United States)

    Sung, Pi-Lin; Wen, Kuo-Chang; Chen, Yi-Jen; Chao, Ta-Chung; Tsai, Yi-Fang; Tseng, Ling-Ming; Qiu, Jian-Tai Timothy; Chao, Kuan-Chong; Wu, Hua-Hsi; Chuang, Chi-Mu

    2017-01-01

    An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes. PMID:28961279

  5. The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels.

    Science.gov (United States)

    Sung, Pi-Lin; Wen, Kuo-Chang; Chen, Yi-Jen; Chao, Ta-Chung; Tsai, Yi-Fang; Tseng, Ling-Ming; Qiu, Jian-Tai Timothy; Chao, Kuan-Chong; Wu, Hua-Hsi; Chuang, Chi-Mu; Wang, Peng-Hui; Huang, Chi-Ying F

    2017-01-01

    An important role of genetic factors in the development of breast cancer (BC) or ovarian cancer (OC) in Taiwanese (ethnic Chinese) patients has been suggested. However, other than germline BRCA1 or BRCA2 mutations, which are related to hereditary breast-ovarian cancer (HBOC), cancer-predisposition genes have not been well studied in this population. The aim of the present study was to more accurately summarize the prevalence of genetic mutations in HBOC patients using various gene panels ranging in size from BRCA1/2 alone to multi-gene panels. Among 272 HBOC patients analyzed, the prevalence of BRCA1, BRCA2 and non-BRCA1/2 pathogenic mutations was 7.7% (21/272), 6.8% (16/236) and 8.2% (13/159), respectively. The total mutation rate was 18.4% (50/272). Although no founder mutations were identified in this study, two recurrent mutations, BRCA1 (c.3607C>T) and BRCA2 (c.5164_5165 delAG), were found. The main pathogenic/likely pathogenic mutations in non-BRCA1/2 genes included ATM, BRIP1, FANCI, MSH2, MUYTH, RAD50, RAD51C and TP53. The prevalence rate of gene mutations in HBOC patients did not differ with respect to whether BC or OC was the first diagnosis or they presented a family history of the disease or their age at diagnosis. HBOC patients with both BC and OC exhibited a higher prevalence rate of mutations (50.0%) than patients with OC (25.0%) or BC (8.6%) alone. In conclusion, evaluation of hereditary cancer risk in Taiwan HBOC patients, particularly individuals with double cancer, is strongly encouraged. Panel testing can yield additional genomic information, and widespread and well-designed panel testing will help in assessing more accurate mutational prevalence of risk genes.

  6. Differential diagnosis of Mendelian and mitochondrial disorders in patients with suspected multiple sclerosis

    Science.gov (United States)

    Katz Sand, Ilana B.; Honce, Justin M.; Lublin, Fred D.

    2015-01-01

    Several single gene disorders share clinical and radiologic characteristics with multiple sclerosis and have the potential to be overlooked in the differential diagnostic evaluation of both adult and paediatric patients with multiple sclerosis. This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. Recognition of a single-gene disorder as causal for a patient’s ‘multiple sclerosis-like’ phenotype is critically important for accurate direction of patient management, and evokes broader genetic counselling implications for affected families. Here we review single gene disorders that have the potential to mimic multiple sclerosis, provide an overview of clinical and investigational characteristics of each disorder, and present guidelines for when clinicians should suspect an underlying heritable disorder that requires diagnostic confirmation in a patient with a definite or probable diagnosis of multiple sclerosis. PMID:25636970

  7. Saturated Fat Intake Modulates the Association between an Obesity Genetic Risk Score and Body Mass Index in Two US Populations

    OpenAIRE

    P. Casas-Agustench; Arnett, Dk; Smith, CE; Lai, CQ; Parnell, LD; Borecki, IB; Frazier-Wood, AC; Allison, M; Chen, YDI; Taylor, Kd; Rich, SS; Rotter, JI; Lee, YC; Ordovás, JM

    2014-01-01

    © 2014 Academy of Nutrition and Dietetics. Combining multiple genetic variants related to obesity into a genetic risk score (GRS) might improve identification of individuals at risk of developing obesity. Moreover, characterizing gene-diet interactions is a research challenge to establish dietary recommendations to individuals with higher predisposition to obesity. Our objective was to analyze the association between an obesity GRS and body mass index (BMI) in the Genetics of Lipid Lowering D...

  8. A Systems Genetic Analysis of Alcohol Drinking by Mice, Rats and Men: Influence of Brain GABAergic Transmission

    OpenAIRE

    Saba, Laura M.; Bennett, Beth; Hoffman, Paula L; Barcomb, Kelsey; Ishii, Takao; Kechris, Katerina; Tabakoff, Boris

    2010-01-01

    Genetic influences on the predisposition to complex behavioral or physiological traits can reflect genetic polymorphisms that lead to altered gene product function, and/or variations in gene expression levels. We have explored quantitative variations in an animal's alcohol consumption, using a genetical genomic/phenomic approach. In our studies, gene expression is correlated with amount of alcohol consumed, and genomic regions that regulate the alcohol consumption behavior and the quantitativ...

  9. Genetics and sports.

    Science.gov (United States)

    Lippi, Giuseppe; Longo, Umile Giuseppe; Maffulli, Nicola

    2010-01-01

    The limit of each individual to perform a given type of exercise depends on the nature of the task, and is influenced by a variety of factors, including psychology, environment and genetic make up. Genetics provide useful insights, as sport performances can be ultimately defined as a polygenic trait. We searched PubMed using the terms 'sports' and 'genetics' over the period 1990 to present. The physical performance phenotypes for which a genetic basis can be suspected include endurance capacity, muscle performance, physiological attitude to train and ability of tendons and ligaments to withstand injury. Genetic testing in sport would permit to identify individuals with optimal physiology and morphology, and also those with a greater capacity to respond/adapt to training and a lesser chance of suffering from injuries. Ethical and practical caveats should be clearly emphasized. The translation of an advantageous genotype into a champion's phenotype is still influenced by environmental, psychological and sociological factors. The current scientific evidence on the relationship between genetics and sports look promising. There is a need for additional studies to determine whether genome-wide genotyping arrays would be really useful and cost-effective. Since exercise training regulates the expression of genes encoding various enzymes in muscle and other tissues, genetic research in sports will help clarify several aspects of human biology and physiology, such as RNA and protein level regulation under specific circumstances.

  10. A rational clinical approach to suspected insulin allergy

    DEFF Research Database (Denmark)

    Bødtger, Uffe; Wittrup, M

    2005-01-01

    AIMS: Allergy to recombinant human (rDNA) insulin preparations is a rare complication of insulin therapy. However, insulin preparations contain several allergens, and several disorders can resemble insulin allergy. Studies evaluating the diagnostic procedures on suspected insulin allergy...... technique (n = 5), skin disease (n = 3) and other systemic allergy (n = 1). Nine other patients were found to be allergic to protamine (n = 3) or rDNA insulin (n = 6), and specific treatment was associated with relief in 8 patients (89%). Four patients had local reactions of unknown causes but symptom...... relief was obtained in three cases by unspecific therapy. Overall, 20 (91%) reported relief of symptoms. CONCLUSION: Our standardized investigative procedure of suspected insulin preparation (IP) allergy was associated with relief of symptoms in > 90% of patients. IP allergy was diagnosed in 41...

  11. Interdisciplinary action of nurses to children with suspected sexual abuse

    Directory of Open Access Journals (Sweden)

    Lia Leão Ciuffo

    2014-04-01

    Full Text Available Objective. Understanding the role of nurses as members of interdisciplinary teams in the care of children with suspected sexual abuse. Methodology. This is a qualitative research based on the sociological phenomenology of Alfred Schutz. In 2008 were interviewed eleven nurses who worked in reference institutions for the care of child victims of sexual abuse in Rio de Janeiro. Results. The category called 'Interacting with other professionals in child care' emerged from the analysis of performance of professionals. The intersubjective relations between the nurses and the interdisciplinary team will enable to understand the intent of care from the perspective of social, emotional and psychological needs of children and their families. Conclusion. Interdisciplinarity favored the development of actions based on acceptance, listening and agreements on possible solutions in the care of children with suspected sexual abuse.

  12. Atlantoaxial subluxation and nasopharyngeal necrosis complicating suspected granulomatosis with polyangiitis.

    Science.gov (United States)

    Mohapatra, Anand; Holekamp, Terrence F; Diaz, Jason A; Zebala, Lukas; Brasington, Richard

    2015-04-01

    Granulomatosis polyangiitis (GPA, formerly Wegener granulomatosis) is a vasculitis that typically involves the upper respiratory tract, lungs, and kidneys. The 2 established methods to confirm a suspicion of GPA are the antineutrophil cytoplasmic antibody (ANCA) test and biopsy. However, ANCA-negative cases have been known to occur, and it can be difficult to find biopsy evidence of granulomatous disease.We report a case of suspected granulomatosis with polyangiitis limited to the nasopharynx. With a negative ANCA and no histological evidence, our diagnosis was founded on the exclusion of other diagnoses and the response to cyclophosphamide therapy. This case is unique because the patient's lesion resulted in atlantoaxial instability, which required a posterior spinal fusion at C1-C2. This is the first reported case of suspected GPA producing damage to the cervical spine and threatening the spinal cord.

  13. Suspected side effects to the quadrivalent human papilloma vaccine

    DEFF Research Database (Denmark)

    Brinth, Louise; Theibel, Ann Cathrine; Pors, Kirsten

    2015-01-01

    INTRODUCTION: The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous...... system dysfunction have been described as suspected side effects to the Q-HPV vaccine. METHODS: We present a description of suspected side effects to the Q-HPV vaccine in 53 patients referred to our Syncope Unit for tilt table test and evaluation of autonomic nervous system function. RESULTS: All...... consistency in the reported symptoms as well as between our findings and those described by others. Our findings neither confirm nor dismiss a causal link to the Q-HPV vaccine, but they suggest that further research is urgently warranted to clarify the pathophysiology behind the symptoms experienced...

  14. Radiological (scintigraphic) evaluation of patients with suspected pulmonar thromboembolism

    Energy Technology Data Exchange (ETDEWEB)

    Biello, D.R.

    1987-06-19

    The optimal strategy for diagnostic evaluation of patients with suspected pulmonary thromboembolism (PE) is subject of controversial and often conflicting opinions. If untreated, as many as 30% of patients with PE may die. Conversely, anticoagulant therapy significantly decreases mortality from PE, but bleeding complications occur. Underdiagnosis may result in a preventable death, and overdiagnosis may lead to significant hemorrhage from unnecessary anticoagulant therapy. This article outlines a practical guide for the use of pulmonary ventilation-perfusion (V-P) scintigraphy in patients with suspected PE. Perfusion imaging involves the intravenous injection of radiolabeled particles ranging from 10 to 60 ..mu..m in diameter (technetium Tc 99m macroaggregated albumin or technetium Tc 99m serum albumin microspheres); these particles are trapped in the capillaries and precapillary arterioles of the lung. The radiolabeled particles are distributed to the lungs in proportion to regional pulmonary blood flow. The correspondence of perfusion defects to bronchopulmonary segments is best appreciated in the posterior oblique views.

  15. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  16. Radiotherapy in three suspect cases of feline thymoma.

    Science.gov (United States)

    Kaser-Hotz, B; Rohrer, C R; Fidel, J L; Nett, C S; Hörauf, A; Hauser, B

    2001-01-01

    Radiation therapy for three cases of suspect feline thymoma is described. The thymoma was controlled for 4 years in case no. 1. Case no. 2 responded well to radiation therapy but was euthanized after 2 months because of a nasal adenocarcinoma. Case no. 3 continues to do well more than 8 months after radiotherapy. Difficulties in diagnosing feline thymomas are discussed, and biological behavior as well as different treatment modalities of feline and human thymomas are compared.

  17. Percutaneous cholecystocentesis in cats with suspected hepatobiliary disease.

    Science.gov (United States)

    Byfield, Victoria L; Callahan Clark, Julie E; Turek, Bradley J; Bradley, Charles W; Rondeau, Mark P

    2017-12-01

    Objectives The objective was to evaluate the safety and diagnostic utility of percutaneous ultrasound-guided cholecystocentesis (PUC) in cats with suspected hepatobiliary disease. Methods Medical records of 83 cats with suspected hepatobiliary disease that underwent PUC were retrospectively reviewed. Results At the time of PUC, at least one additional procedure was performed in 79/83 cats, including hepatic aspiration and/or biopsy (n = 75) and splenic aspiration (n = 18). Complications were noted in 14/83 cases, including increased abdominal fluid (n = 11), needle-tip occlusion (n = 1), failed first attempt to penetrate the gall bladder wall (n = 1) and pneumoperitoneum (n = 1). There were no reports of gall bladder rupture, bile peritonitis or hypotension necessitating treatment with vasopressor medication. Blood products were administered to 7/83 (8%) cats. Seventy-two cats (87%) survived to discharge. Of the cats that were euthanized (9/83) or died (2/83), none were reported as a definitive consequence of PUC. Bacteria were identified cytologically in 10/71 samples (14%); all 10 had a positive aerobic bacterial culture. Bile culture was positive in 11/80 samples (14%). Of the cases with a positive bile culture, cytological description of bacteria corresponded to the organism cultured in fewer than 50% of cases. The most common cytologic diagnosis was hepatic lipidosis (49/66). The most common histopathologic diagnosis was cholangitis (10/21). Conclusions and relevance PUC was safe in this group of cats with suspected hepatobiliary disease. Complications were likely associated with ancillary procedures performed at the time of PUC. Bile analysis yielded an abnormal result in nearly one-third of cats with suspected hepatobiliary disease. Complete agreement between bile cytology and culture was lacking. Further evaluation of the correlation between bile cytology and bile culture is warranted.

  18. Interviewing strategically to elicit admissions from guilty suspects

    OpenAIRE

    Tekin, Serra; Granhag, Pär Anders; Strömwall, Leif; Giolla, Erik Mac; Vrij, Aldert; Hartwig, Maria

    2015-01-01

    In this article we introduce a novel interviewing tactic to elicit admissions from guilty suspects. By influencing the suspects’ perception of the amount of evidence the interviewer holds against them, we aimed to shift the suspects’ counterinterrogation strategies from less to more forthcoming. The proposed tactic (SUE-Confrontation) is a development of the Strategic Use of Evidence (SUE) framework and aims to affect the suspects’ perception by confronting them with statement-evidence incons...

  19. MRI for clinically suspected pediatric appendicitis: case interpretation

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael M.; Brian, James M.; Methratta, Sosamma T.; Hulse, Michael A.; Choudhary, Arabinda K.; Eggli, Kathleen D.; Boal, Danielle K.B. [Penn State Milton S. Hershey Medical Center, Division of Pediatric Radiology, Department of Radiology, Hershey, PA (United States)

    2014-05-15

    As utilization of MRI for clinically suspected pediatric appendicitis becomes more common, there will be increased focus on case interpretation. The purpose of this pictorial essay is to share our institution's case interpretation experience. MRI findings of appendicitis include appendicoliths, tip appendicitis, intraluminal fluid-debris level, pitfalls of size measurements, and complications including abscesses. The normal appendix and inguinal appendix are also discussed. (orig.)

  20. MRI for clinically suspected pediatric appendicitis: an implemented program

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Michael M.; Gustas, Cristy N.; Choudhary, Arabinda K.; Methratta, Sosamma T.; Hulse, Michael A.; Eggli, Kathleen D.; Boal, Danielle K.B. [Penn State Milton S. Hershey Medical Center, Department of Radiology, Mail Code H066, 500 University Drive, P.O. Box 850, Hershey, PA (United States); Geeting, Glenn [Penn State Milton S. Hershey Medical Center, Department of Emergency Medicine, Hershey, PA (United States)

    2012-09-15

    Emergent MRI is now a viable alternative to CT for evaluating appendicitis while avoiding the detrimental effects of ionizing radiation. However, primary employment of MRI in the setting of clinically suspected pediatric appendicitis has remained significantly underutilized. To describe our institution's development and the results of a fully implemented clinical program using MRI as the primary imaging evaluation for children with suspected appendicitis. A four-sequence MRI protocol consisting of coronal and axial single-shot turbo spin-echo (SS-TSE) T2, coronal spectral adiabatic inversion recovery (SPAIR), and axial SS-TSE T2 with fat saturation was performed on 208 children, ages 3 to 17 years, with clinically suspected appendicitis. No intravenous or oral contrast material was administered. No sedation was administered. Data collection includes two separate areas: time parameter analysis and MRI diagnostic results. Diagnostic accuracy of MRI for pediatric appendicitis indicated a sensitivity of 97.6% (CI: 87.1-99.9%), specificity 97.0% (CI: 93.2-99.0%), positive predictive value 88.9% (CI: 76.0-96.3%), and negative predictive value 99.4% (CI: 96.6-99.9%). Time parameter analysis indicated clinical feasibility, with time requested to first sequence obtained mean of 78.7 +/- 52.5 min, median 65 min; first-to-last sequence time stamp mean 14.2 +/- 8.8 min, median 12 min; last sequence to report mean 57.4 +/- 35.2 min, median 46 min. Mean age was 11.2 +/- 3.6 years old. Girls represented 57% of patients. MRI is an effective and efficient method of imaging children with clinically suspected appendicitis. Using an expedited four-sequence protocol, sensitivity and specificity are comparable to CT while avoiding the detrimental effects of ionizing radiation. (orig.)

  1. Epidemiology of suspected wrist joint infection versus inflammation.

    Science.gov (United States)

    Skeete, Kshamata; Hess, Erik P; Clark, Tod; Moran, Steven; Kakar, Sanjeev; Rizzo, Marco

    2011-03-01

    To determine the cumulative prevalence of septic arthritis presenting to the emergency department of an academic medical center and evaluate the use of clinical data to diagnose infection versus inflammation. We conducted a records review of a single institution with 80,000 annual emergency room visits. We included a consecutive series of patients with suspected wrist infection from January 1, 2007, to December 31, 2008. Adults complaining of atraumatic wrist pain with either erythema or swelling on physical examination or a final diagnosis of septic arthritis, gout, pseudogout, cellulitis, wrist hematoma/edema, or wrist arthritic flare were suspected to have infection. We collected data using a standardized data abstraction form. We reviewed 804 patient records. A total of 104 patients meeting inclusion criteria for suspected wrist joint infection during the 2-year study period were included. Mean age was 62.5 years (SD, 20.2 y); 63 were men. There were 12 patients with a history of gout, 4 with a history of pseudogout, and 19 with a history of diabetes. Wrist arthrocentesis was performed in 31 patients, and 11 underwent surgical treatment. There were 16 patients with a final diagnosis of gout, 11 with pseudogout, 43 with cellulitis, 13 with upper extremity hematoma/edema, and 15 with wrist arthritic flare. The cumulative prevalence of septic arthritis was 5%. In this series of emergency department patients with suspected wrist joint infection, gout, pseudogout, and cellulitis were the most common etiologies. The cumulative incidence of septic wrist arthritis was low. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  2. Suspected spinocellular carcinoma of the inferior eyelid resulted multiple chalazion.

    Science.gov (United States)

    Onesti, Maria Giuseppina; Troccola, Antonietta; Maruccia, Michele; Conversi, Andrea; Scuderi, Gianluca

    2013-01-01

    Chalazion is a subacute granulomatous inflammation of the eyelid caused by retention of tarsal gland secretions and it's the most common inflammatory lesion of the eyelid. In cases of doubtful clinical presentation the diagnosis with a biopsy and a histopathological examination is important because it can orientate an appropriate surgical treatment. We report a case of a 64-years-old diabetic man, suspected for a spinocellular lesion of the inferior eyelid of the left eye, it resulted unexpectedly a chalazion.

  3. CT-guided biopsy of suspected malignancy: A potential pitfall

    Directory of Open Access Journals (Sweden)

    Steven Henderson

    2013-11-01

    Full Text Available Paragangliomas are rare catecholamine-secreting neuro-endocrine tumours that can arise from sympathetic or parasympathetic tissue. Any manipulation of these tumours, without appropriate medical therapy, can result in excess catecholamine release leading to a catecholamine crisis. Neuro-endocrine tumours must be considered prior to interventional biopsy of an unknown soft-tissue mass, and appropriate biochemical investigations should be performed in suspected cases to prevent catastrophic complications.

  4. No (Wo)Man Is an Island-The Influence of Physicians' Personal Predisposition to Labia Minora Appearance on Their Clinical Decision Making : A Cross-Sectional Survey

    NARCIS (Netherlands)

    Reitsma, Welmoed; Mourits, Marian J. E.; Koning, Merel; Pascal, Astrid; van der Lei, Berend

    Introduction. Physicians are increasingly presented with women requesting a labia minora reduction procedure. Aim. To assess the influencing factor of personal predisposition in general practitioners, gynecologists, and plastic surgeons to labia minora appearance in relation to their willingness to

  5. [Three cases of suspected re-infection of mumps virus].

    Science.gov (United States)

    Hatanaka, Akio; Kamada, Tomoko; Honda, Keiji; Tazaki, Akihisa; Kishine, Naomi; Kawashima, Yoshiyuki

    2012-08-01

    A 32-year-old woman, 5-year-old girl, and 33-year-old man visited our otorhinolaryngology outpatient clinic with tumentia of the unilateral parotid gland. A high titer of serum IgG antibodies against the mumps virus was detected. Around the same time, other members of their families had the same parotid tumentia, and they were diagnosed as having their first mumps infection. Therefore, the diagnosis of the three cases was strongly suspected to be re-infection with mumps. In Japan, it was classically believed that the mumps virus infection occurs only once in patients and reinfection doesn't occur. However, some pediatricians in Japan have reported that re-infection with mumps is strongly suspected when high titers of serum IgG antibodies against the mumps virus are found at the initial visit. It is now believed many more examples of mumps re-infection cases have existed than we previously believed. When high titers of serum IgG antibodies against the mumps virus are detected at an initial visit in patients who have had mumps previously, re-infection should be strongly suspected. And to make it certain, we suggest that the mumps IgG antibodies should be checked twice to confirm the diagnosis. If elevation of the IgG antibodies persist, the diagnosis will be much more certain.

  6. Ten-day observation of live rabies suspected dogs.

    Science.gov (United States)

    Tepsumethanon, V; Wilde, H; Sitprija, V

    2008-01-01

    This study aimed at analyzing a ten-day observation period of rabies suspected dogs and cats according to six criteria. Dogs and cats suspected of being rabid were brought for observation when they had either bitten a person or another animal or when abnormal behaviour or unusual illness was observed. Between 1985 and 2005, retrospective and prospective data from 1,222 dogs and 303 cats was collected during the ten-day observation period. If an animal had died, brain examination using fluorescent antibody testing was routinely performed. If an animal had survived for > or =10 days, it was released to its owner or transferred to the municipal dog shelter. A total of 644 dogs and 58 cats found rabid died within 10 days of observation. In addition, for 208 dogs confirmed rabid with laboratory tests between 1997 and 2005, six criteria were analysed from the day of submission. This experience with the implemented 10-day observation period confirms the WHO recommendation on identifying suspected rabid dogs or cats under veterinary supervision following a human exposure.

  7. MR delayed enhancement imaging findings in suspected acute myocarditis

    Energy Technology Data Exchange (ETDEWEB)

    Gahide, Gerald [CHU de Montpellier, Radiologie centrale - Pole Cardiovasculaire et Thoracique, Montpellier (France); Centre Hospitalo-Universitaire de Montpellier, Hopital A de Villeneuve, Montpellier (France); Bertrand, D.; Dacher, J.N. [CHU de Rouen, Radiologie centrale - Hopital Charles Nicolle, Rouen (France); Roubille, F.; Skaik, S.; Piot, C.; Leclerq, F. [CHU de Montpellier, Departement de Cardiologie - Pole Cardiovasculaire et Thoracique, Montpellier (France); Tron, C.; Cribier, A. [CHU de Rouen, Departement de Cardiologie - Hopital Charles Nicolle, Rouen (France); Vernhet, H. [CHU de Montpellier, Radiologie centrale - Pole Cardiovasculaire et Thoracique, Montpellier (France)

    2010-01-15

    The purpose of the study was to prospectively assess the clinical impact of routinely performed delayed enhancement imaging in suspected acute myocarditis. A two-centre prospective study was performed in patients with suspected acute myocarditis. The protocol included horizontal long axis, vertical long axis and short axis cine MR and delayed enhancement imaging after Gd-DTPA infusion (0.2 mmol/kg). Sixty consecutive patients were enrolled (aged 49.4{+-}17.8 years). MRI demonstrated delayed enhancement sparing the subendocardicardial layer in 51.6% of patients, concordant with the diagnosis of acute myocarditis; 16.7% of patients exhibited delayed enhancement involving the subendocardial layer with irregular margins, concordant with the diagnosis of acute myocardial infarction; 31.7% of patients had delayed enhancement imaging that was considered normal. Routine imaging to identify delayed enhancement provided crucial information in suspected acute myocarditis by reinforcing the diagnosis in 51.6% of patients and correcting a misdiagnosed acute myocardial infarction in 16.7% of patients. (orig.)

  8. Low dose computed tomography in suspected acute renal colic.

    Science.gov (United States)

    Meagher, T; Sukumar, V P; Collingwood, J; Crawley, T; Schofield, D; Henson, J; Lakin, K; Connolly, D; Giles, J

    2001-11-01

    To evaluate whether computed tomography (CT) of the renal tract in suspected renal colic using reduced exposure factors maintains diagnostic accuracy. Prospective multi-centre cohort study. Patients with suspected renal colic were examined using computed tomography (CT) of the renal tract followed by intravenous urography (IVU) in four different centres with five different CT systems. Sixty-nine patients with suspected renal colic had CT of the renal tract followed by IVU. CT was performed with reduced exposure factors, giving a mean CT effective dose of 3.5 (range 2.8-4.5) mSv compared with 1.5 mSv for IVU. Ureteric calculi were detected in 43 patients: CT and IVU detected 40 (93%) ureteric calculi. CT identified other lesions causing symptoms in five patients and identified renal calculi in 24 patients. IVU identified renal calculi in six patients and made false positive diagnosis of renal calculi in seven patients. Mean examination time for CT was 5 minutes and for IVU was 80 minutes. CT examination at reduced exposure factors maintains the diagnostic accuracy recorded in other series. Copyright 2001 The Royal College of Radiologists.

  9. The economics of cardiac biomarker testing in suspected myocardial infarction.

    Science.gov (United States)

    Goodacre, Steve; Thokala, Praveen

    2015-03-01

    Suspected myocardial infarction (MI) is a common reason for emergency hospital attendance and admission. Cardiac biomarker measurement is an essential element of diagnostic assessment of suspected MI. Although the cost of a routinely available biomarker may be small, the large patient population and consequences in terms of hospital admission and investigation mean that the economic impact of cardiac biomarker testing is substantial. Economic evaluation involves comparing the estimated costs and effectiveness (outcomes) of two or more interventions or care alternatives. This process creates some difficulties with respect to cardiac biomarkers. Estimating the effectiveness of cardiac biomarkers involves identifying how they help to improve health and how we can measure this improvement. Comparison to an appropriate alternative is also problematic. New biomarkers may be promoted on the basis of reducing hospital admission or length of stay, but hospital admission for low risk patients may incur significant costs while providing very little benefit, making it an inappropriate comparator. Finally, economic evaluation may conclude that a more sensitive biomarker strategy is more effective but, by detecting and treating more cases, is also more expensive. In these circumstances it is unclear whether we should use the more effective or the cheaper option. This article provides an introduction to health economics and addresses the specific issues relevant to cardiac biomarkers. It describes the key concepts relevant to economic evaluation of cardiac biomarkers in suspected MI and highlights key areas of uncertainty and controversy. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Limitation of personal freedom by detention of suspect

    Directory of Open Access Journals (Sweden)

    Knežević Saša

    2011-01-01

    Full Text Available The right of personal freedom is one of the most important right from the set of basic human rights and freedoms, contained in the most important acts of international legal character, and the constitutions of states based on the rule of law. This right is directly related to the very human existence, and, therefore, it is necessary to make its legal articulation. Personal freedom means the right to security of the citizen, that he will not be arrested and detained in prison by the state authorities, as well as the right to be free to move and inhabit. However, from the very nature of Criminal Law protection of social values, arises the need to limit the right to personal freedom in exceptional circumstances, including the detention of the suspect. Keeping the suspect is a measure of procedural compulsion, by which, through the police decision, detained prison is temporarily imprisoned, for gathering information and hearing. The basic principles of humanity require that the detained suspect retains all the rights, derived from the principle of personal liberty.

  11. MIBG in the evaluation of suspected pheochromocytoma: Mayo Clinic experience

    Energy Technology Data Exchange (ETDEWEB)

    Brown, M.L.; Sheps, S.G.; Sizemore, G.; Swensen, S.J.; Gharib, H.; Grant, C.S.; van Heerden, J.A.

    1984-01-01

    Work done at the University of Michigan has shown that I-131 metaiodobenzylguanidine (MIBG) is an effective agent for the diagnosis and localization of pheochromocytoma. A recent report questioned the sensitivity of this test. In 1983, 40 patients at Mayo Clinic had 42 scans during the workup of suspected spontaneous pheochromocytoma or metastatic pheochromocytoma. All patients were given 500 ..mu..Ci I-131 MIBG supplied by the University of Michigan. The final diagnosis of pheochromocytoma (true positive (TP) and false negative (FN) and false positive (FP)) was made by surgery and pathology. True negative (TN) diagnosis was made by normal plasma and urinary catecholamines, and in many patients CT. There were 15 TP studies (six spontaneous pheochrocytoma, nine metastatic or recurrent pheochromoctyoma), and 22 TN studies. There was one FP study of recurrent paraganglioma near the bladder (CT was also FP) and four FN studies (two spontaneous and two metastatic) where one CT was also FN. This results in a sensitivity of 79%, specificity of 96%, and accuracy of 88%. MIBG is very useful in the workup of patients with known or suspected recurrent or metastatic pheochromocytoma and is helpful in the evaluation of the patient suspected of having a spontaneous pheochromocytoma when CT is normal.

  12. The Effect of Nutrition and Sleep Habits on Predisposition for Metabolic Syndrome in Greek Children.

    Science.gov (United States)

    Katsa, Maria Efthymia; Ioannidis, Anastasios; Zyga, Sofia; Tsironi, Maria; Koutsovitis, Paraskevas; Chatzipanagiotou, Stylianos; Panagiotakos, Demosthenes; Sachlas, Athanasios; Kolovos, Petros; Routsi, Kleopatra; Pistikou, Anna Maria; Kougioumtzi Dimoliani, Dafni Eleni; Rojas Gil, Andrea Paola

    2018-02-02

    To investigate the effect of lifestyle habits in childhood Metabolic Syndrome (MTS). Descriptive correlation study with 480 participants (5-12 years old) using a specially designed questionnaire was conducted. Anthropometric and biochemical analyses were performed. Fifteen percent of children exhibited predisposition for MTS. Regarding sleep habits, logistic regression analysis (LRA) showed that hour of sleep -before 22:00- was associated with decreased waist circumference (WC%) (p = .026). Midday siesta was negatively correlated with systolic (SBP) (p = .001) and diastolic blood pressure (DBP) (p = .046). In children without MTS, lack of sleep and night time sleep was positively correlated with DBP (p = .044) and fasting blood glucose (FBG) (p = .005). Regarding nutrition habits, fast food consumption was positively correlated with SBP (p = .006) and meat consumption was positively correlated with both Body Mass Index% (BMI%) (p = .038) and WC% (p = .023). LRA showed that fruit (p = .001) and legume (p = .040) consumption was associated with decreased FBG; fish consumption with decreased Low Density Lipoprotein (LDL) cholesterol (p = .031), vegetable (p = .054) and cereal consumption (p = .012) with decreased DBP. In children with MTS, fruits were associated with increased FBG (p = .034). In children without MTS, meat consumption was associated with increased LDL (p = .024), cereal with increased WC% (p = .002) and olive products with increased High Density Lipoprotein (HDL) cholesterol and BMI% (p = .037). The adoption of both balanced diet and sleep habits seemed to be crucial for the prevention of MTS. Clinical health nurses could develop and implement preventive intervention programs in order to avoid metabolic complications in adulthood. Copyright © 2018. Published by Elsevier Inc.

  13. Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets and laptops at night

    Directory of Open Access Journals (Sweden)

    Seyed Ali Reza Mortazavi

    2018-02-01

    Full Text Available Breast cancer is the most common malignancy among women, both in the developed and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have an increased risk of breast and ovarian cancers. Recent studies show that short-wavelength visible light disturb the secretion of melatonin and causes circadian rhythm disruption. We have previously studied the health effects of exposure to different levels of radiofrequency electromagnetic fields (RF-EMFs such as mobile phones, mobile base stations, mobile phone jammers, laptop computers, and radars. Moreover, over the past several years, we investigated the health effects of exposure to the short wavelength visible light in the blue region emitted from digital screens. The reduction of melatonin secretion after exposure to blue light emitted from smartphone’s screen has been reported to be associated with the negative impact of smartphone use at night on sleep. We have shown that both the blue light and RF-EMFs generated by mobile phones are linked to the disruption of the circadian rhythm in people who use their phones at night. Therefore, if women with hereditary breast cancer predispositions use their smartphones, tablets and laptops at night, disrupted circadian rhythms (suppression of melatonin caused by exposure to blue light emitted from the digital screens, amplifies the risk of breast cancer. It can be concluded that women who carry mutated BRCA1 or BRCA2, or women with family history of breast cancer should avoid using their smartphones, tablets and laptops at night. Using sunglasses with amber lenses, or smartphone applications which decrease the users’ exposure to blue light before sleep, at least to some extent, can decrease the risk of circadian rhythm disruption and breast cancer.

  14. Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets, and laptops at night.

    Science.gov (United States)

    Mortazavi, Seyed Ali Reza; Mortazavi, Seyed Mohammad Javad

    2018-02-01

    Breast cancer is the most common malignancy among women, both in the developed and developing countries. Women with mutations in the BRCA1 and BRCA2 genes have an increased risk of breast and ovarian cancers. Recent studies show that short-wavelength visible light disturb the secretion of melatonin and causes circadian rhythm disruption. We have previously studied the health effects of exposure to different levels of radiofrequency electromagnetic fields (RF-EMFs) such as mobile phones, mobile base stations, mobile phone jammers, laptop computers, and radars. Moreover, over the past several years, we investigated the health effects of exposure to the short wavelength visible light in the blue region emitted from digital screens. The reduction of melatonin secretion after exposure to blue light emitted from smartphone's screen has been reported to be associated with the negative impact of smartphone use at night on sleep. We have shown that both the blue light and RF-EMFs generated by mobile phones are linked to the disruption of the circadian rhythm in people who use their phones at night. Therefore, if women with hereditary breast cancer predispositions use their smartphones, tablets and laptops at night, disrupted circadian rhythms (suppression of melatonin caused by exposure to blue light emitted from the digital screens), amplifies the risk of breast cancer. It can be concluded that women who carry mutated BRCA1 or BRCA2, or women with family history of breast cancer should avoid using their smartphones, tablets and laptops at night. Using sunglasses with amber lenses, or smartphone applications which decrease the users' exposure to blue light before sleep, at least to some extent, can decrease the risk of circadian rhythm disruption and breast cancer.

  15. Personality Factors Predicting Smartphone Addiction Predisposition: Behavioral Inhibition and Activation Systems, Impulsivity, and Self-Control.

    Science.gov (United States)

    Kim, Yejin; Jeong, Jo-Eun; Cho, Hyun; Jung, Dong-Jin; Kwak, Minjung; Rho, Mi Jung; Yu, Hwanjo; Kim, Dai-Jin; Choi, In Young

    2016-01-01

    The purpose of this study was to identify personality factor-associated predictors of smartphone addiction predisposition (SAP). Participants were 2,573 men and 2,281 women (n = 4,854) aged 20-49 years (Mean ± SD: 33.47 ± 7.52); participants completed the following questionnaires: the Korean Smartphone Addiction Proneness Scale (K-SAPS) for adults, the Behavioral Inhibition System/Behavioral Activation System questionnaire (BIS/BAS), the Dickman Dysfunctional Impulsivity Instrument (DDII), and the Brief Self-Control Scale (BSCS). In addition, participants reported their demographic information and smartphone usage pattern (weekday or weekend average usage hours and main use). We analyzed the data in three steps: (1) identifying predictors with logistic regression, (2) deriving causal relationships between SAP and its predictors using a Bayesian belief network (BN), and (3) computing optimal cut-off points for the identified predictors using the Youden index. Identified predictors of SAP were as follows: gender (female), weekend average usage hours, and scores on BAS-Drive, BAS-Reward Responsiveness, DDII, and BSCS. Female gender and scores on BAS-Drive and BSCS directly increased SAP. BAS-Reward Responsiveness and DDII indirectly increased SAP. We found that SAP was defined with maximal sensitivity as follows: weekend average usage hours > 4.45, BAS-Drive > 10.0, BAS-Reward Responsiveness > 13.8, DDII > 4.5, and BSCS > 37.4. This study raises the possibility that personality factors contribute to SAP. And, we calculated cut-off points for key predictors. These findings may assist clinicians screening for SAP using cut-off points, and further the understanding of SA risk factors.

  16. Personality Factors Predicting Smartphone Addiction Predisposition: Behavioral Inhibition and Activation Systems, Impulsivity, and Self-Control.

    Directory of Open Access Journals (Sweden)

    Yejin Kim

    Full Text Available The purpose of this study was to identify personality factor-associated predictors of smartphone addiction predisposition (SAP. Participants were 2,573 men and 2,281 women (n = 4,854 aged 20-49 years (Mean ± SD: 33.47 ± 7.52; participants completed the following questionnaires: the Korean Smartphone Addiction Proneness Scale (K-SAPS for adults, the Behavioral Inhibition System/Behavioral Activation System questionnaire (BIS/BAS, the Dickman Dysfunctional Impulsivity Instrument (DDII, and the Brief Self-Control Scale (BSCS. In addition, participants reported their demographic information and smartphone usage pattern (weekday or weekend average usage hours and main use. We analyzed the data in three steps: (1 identifying predictors with logistic regression, (2 deriving causal relationships between SAP and its predictors using a Bayesian belief network (BN, and (3 computing optimal cut-off points for the identified predictors using the Youden index. Identified predictors of SAP were as follows: gender (female, weekend average usage hours, and scores on BAS-Drive, BAS-Reward Responsiveness, DDII, and BSCS. Female gender and scores on BAS-Drive and BSCS directly increased SAP. BAS-Reward Responsiveness and DDII indirectly increased SAP. We found that SAP was defined with maximal sensitivity as follows: weekend average usage hours > 4.45, BAS-Drive > 10.0, BAS-Reward Responsiveness > 13.8, DDII > 4.5, and BSCS > 37.4. This study raises the possibility that personality factors contribute to SAP. And, we calculated cut-off points for key predictors. These findings may assist clinicians screening for SAP using cut-off points, and further the understanding of SA risk factors.

  17. Predisposition Factors of Students’ Choice in Agriculture, Fisheries and Natural Resources (AFNR Courses (Luzon Area

    Directory of Open Access Journals (Sweden)

    DR. ROMEO C. CLEMENTE

    2014-02-01

    Full Text Available This study is an inquiry into the motivational, personality, and extrinsic variables as factors affecting students’ predisposition in their career choice for agriculture, fisheries and forestry. It features empirical facts generally reflective of the recent conditions of public and private Higher Education Institutions (as NUCAFs, PIAs and PIFs identified by NAFES-CHED and DA of Luzon, Philippines vis-à-vis problems and reasons of continuous decline in the subscription of Filipino students for AFNR courses. Subsumed in the notable findings for Luzon area (i.e., most enrollees and their parents are marginalized; most mothers who are mere housekeepers heavily influence children’s disposition; most professional AFNR parents and enrollees’ siblings who are now AFNR professionals poorly influence them to take the same course; scholarship grants or free tuition fee as a prime way out to finish college education; personal ideal expectation of students for the government to provide promising local employment; common social motive to participate in addressing problems on food security for the continuously increasing population; economic motive to shorter waiting time for employment; SUCs feel obliged to expand curriculum offering to non-AFNR courses to survive institutional fiscal constraints; dearth of educationally qualified faculty and administrators; campaign for the AFNR curriculum programs as effective strategy to improve enrolment rate; low passing rate in AFNR board examinations due to low participation rate, expensive requirements of review, generic contents of examination, and deficiency on the quality and quantity of facilities/equipment and library holdings in most AFNR State Colleges/Universities served as framework of reference for the formulation of proposed education policy reforms/measures and advocacy interventions designed to spur interest in AFNR courses.

  18. Prevalence and breed predisposition for thoracolumbar intervertebral disc disease in cats.

    Science.gov (United States)

    De Decker, Steven; Warner, Anne-Sophie; Volk, Holger A

    2017-04-01

    Objectives The objective was to evaluate the prevalence and possible breed predilections for thoracolumbar intervertebral disc disease (IVDD) in cats. Methods Medical records and imaging studies of cats diagnosed with thoracolumbar IVDD between January 2008 and August 2014 were retrospectively reviewed and compared with the general hospital population. The association between type of IVDD (ie, intervertebral disc extrusion [IVDE] or intervertebral disc protrusion [IVDP]) and breed, age, sex, and duration and severity of clinical signs was also evaluated. Results Of 12,900 cats presented during the study period, 31 (0.24%) were diagnosed with IVDD, including 17 purebred and 14 non-purebred cats. Of all presented purebred cats, 0.52% were diagnosed with thoracolumbar IVDD. More specifically, 1.29% of all British Shorthairs and 1.83% of all presented Persians were diagnosed with IVDD. Compared with the general hospital population, purebred cats ( P = 0.0001), British Shorthairs ( P cats were younger than affected non-purebred cats ( P = 0.02). Of 31 cats with IVDD, 19 were diagnosed with IVDE and 12 with IVDP. Cats with IVDE had a significantly shorter duration of clinical signs ( P = 0.0002) and demonstrated more severe neurological deficits ( P = 0.04) than cats with IVDP. Conclusions and relevance Although thoracolumbar IVDD is an uncommon condition in cats, purebred cats, British Shorthairs and Persians, were overrepresented. It is currently unclear if this represents a true breed predisposition or a higher likelihood of owners of purebred cats seeking referral for advanced diagnostic imaging procedures.

  19. Allergic predisposition modifies the effects of pet exposure on respiratory disease in boys and girls: the seven northeast cities of china (snecc study

    Directory of Open Access Journals (Sweden)

    Dong Guang-Hui

    2012-07-01

    Full Text Available Abstract Background The relationship between pet exposure and the respiratory disease in childhood has been a controversial topic, much is still unknown about the nature of the associations between pet exposure and children’s respiratory health stratified by gender and allergic predisposition. The objective of the present study was to assess the relationship between pet exposure and respiratory symptoms in Chinese children, and to investigate the modified effects of gender and allergic predisposition on such relationship. Methods 31,049 children were selected from 25 districts of 7 cities in Northeast China in 2009. Information on respiratory health and exposure to home environmental factors was obtained via a standard questionnaire designed by the American Thoracic Society. Results Children with an allergic predisposition were found to have more frequent exposure to pets than those without an allergic predisposition (18.5% vs. 15.4%. In children without an allergic predisposition, pet exposure was associated with increased susceptibility to respiratory symptoms/diseases, with girls being more susceptible than boys. No association was found between pet exposure and respiratory symptoms/diseases in boys with an allergic predisposition. In girls with an allergic predisposition, association was found between doctor-diagnosed asthma and pet exposure of their mother during pregnancy (adjusted odds ratio (ORs = 2.03; 95% confidence interval (CI: 1.01-4.33, and their current pet exposure (ORs = 1.37; 95%CI: 1.00-1.88. Conclusions Pet exposure in children without an allergic predisposition was associated with increased susceptibility to respiratory disease, with girls being more susceptible than boys.

  20. Imaging trends in suspected appendicitis-a Canadian perspective.

    Science.gov (United States)

    Tan, Victoria F; Patlas, Michael N; Katz, Douglas S

    2017-06-01

    The purpose of our study was to assess trends in the imaging of suspected appendicitis in adult patients in emergency departments of academic centers in Canada. A questionnaire was sent to all 17 academic centers in Canada to be completed by a radiologist who works in emergency radiology. The questionnaires were sent and collected over a period of 4 months from October 2015 to February 2016. Sixteen centers (94%) responded to the questionnaire. Eleven respondents (73%) use IV contrast-enhanced computed tomography (CT) as the imaging modality of choice for all patients with suspected appendicitis. Thirteen respondents (81%) use ultrasound as the first modality of choice in imaging pregnant patients with suspected appendicitis. Eleven respondents (69%) use ultrasound (US) as the first modality of choice in patients younger than 40 years of age. Ten respondents (67%) use ultrasound as the first imaging modality in female patients younger than 40 years of age. When CT is used, 81% use non-focused CT of the abdomen and pelvis, and 44% of centers use oral contrast. Thirteen centers (81%) have ultrasound available 24 h a day/7 days a week. At 12 centers (75%), ultrasound is performed by ultrasound technologists. Four centers (40%) perform magnetic resonance imaging (MRI) in suspected appendicitis in adult patients at the discretion of the attending radiologist. Eleven centers (69%) have MRI available 24/7. All 16 centers (100%) use unenhanced MRI. Various imaging modalities are available for the work-up of suspected appendicitis. Although there are North American societal guidelines and recommendations regarding the appropriateness of the multiple imaging modalities, significant heterogeneity in the first-line modalities exist, which vary depending on the patient demographics and resource availability. Imaging trends in the use of the first-line modalities should be considered in order to plan for the availability of the imaging examinations and to consider plans for

  1. Predictors of bacteremia in emergency department patients with suspected infection.

    Science.gov (United States)

    Chase, Maureen; Klasco, Richard S; Joyce, Nina R; Donnino, Michael W; Wolfe, Richard E; Shapiro, Nathan I

    2012-11-01

    The goal of this study is to identify clinical variables associated with bacteremia. Such data could provide a rational basis for blood culture testing in emergency department (ED) patients with suspected infection. This is a secondary analysis of a prospective cohort of ED patients with suspected infection. Data collected included demographics, vital signs, medical history, suspected source of infection, laboratory and blood culture results and outcomes. Bacteremia was defined as a positive blood culture by Centers for Disease Control criteria. Clinical variables associated with bacteremia on univariate logistic regression were entered into a multivariable model. There were 5630 patients enrolled with an average age of 59.9 ± 19.9 years, and 54% were female. Blood cultures were obtained on 3310 (58.8%). There were 409 (12.4%) positive blood cultures, of which 68 (16.6%) were methicillin-resistant Staphylococcus aureus (MRSA) and 161 (39.4%) were Gram negatives. Ten covariates (respiratory failure, vasopressor use, neutrophilia, bandemia, thrombocytopenia, indwelling venous catheter, abnormal temperature, suspected line or urinary infection, or endocarditis) were associated with all-cause bacteremia in the final model (c-statistic area under the curve [AUC], 0.71). Additional factors associated with MRSA bacteremia included end-stage renal disease (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.9-7.8) and diabetes (OR, 2.0; 95% CI, 1.1-3.6) (AUC, 0.73). Factors strongly associated with Gram-negative bacteremia included vasopressor use in the ED (OR, 2.8; 95% CI, 1.7-4.6), bandemia (OR, 3.5; 95% CI, 2.3-5.3), and suspected urinary infection (OR, 4.0; 95% CI, 2.8-5.8) (AUC, 0.75). This study identified several clinical factors associated with bacteremia as well as MRSA and Gram-negative subtypes, but the magnitude of their associations is limited. Combining these covariates into a multivariable model moderately increases their predictive value. Copyright

  2. Interactions between genetic variants associated with adiposity traits and soft drinks in relation to longitudinal changes in body weight and waist circumference

    DEFF Research Database (Denmark)

    Olsen, Nanna J; Ängquist, Lars; Larsen, Sofus C

    2016-01-01

    Background: Intake of sugar-sweetened beverages is associated with obesity, and this association may be modified by a genetic predisposition to obesity. Objective: We examined the interactions between a molecular genetic predisposition to various aspects of obesity and the consumption of soft...... drinks, which are a major part of sugar-sweetened beverages, in relation to changes in adiposity measures. Design: A total of 4765 individuals were included in the study. On the basis of 50 obesity- Associated single nucleotide polymorphisms that are associated with body mass index (BMI), waist...

  3. Differential Regulation of Cryptic Genetic Variation Shapes the Genetic Interactome Underlying Complex Traits.

    Science.gov (United States)

    Yadav, Anupama; Dhole, Kaustubh; Sinha, Himanshu

    2016-12-01

    Cryptic genetic variation (CGV) refers to genetic variants whose effects are buffered in most conditions but manifest phenotypically upon specific genetic and environmental perturbations. Despite having a central role in adaptation, contribution of CGV to regulation of quantitative traits is unclear. Instead, a relatively simplistic architecture of additive genetic loci is known to regulate phenotypic variation in most traits. In this paper, we investigate the regulation of CGV and its implication on the genetic architecture of quantitative traits at a genome-wide level. We use a previously published dataset of biparental recombinant population of Saccharomyces cerevisiae phenotyped in 34 diverse environments to perform single locus, two-locus, and covariance mapping. We identify loci that have independent additive effects as well as those which regulate the phenotypic manifestation of other genetic variants (variance QTL). We find that whereas additive genetic variance is predominant, a higher order genetic interaction network regulates variation in certain environments. Despite containing pleiotropic loci, with effects across environments, these genetic networks are highly environment specific. CGV is buffered under most allelic combinations of these networks and perturbed only in rare combinations resulting in high phenotypic variance. The presence of such environment specific genetic networks is the underlying cause of abundant gene–environment interactions. We demonstrate that overlaying identified molecular networks on such genetic networks can identify potential candidate genes and underlying mechanisms regulating phenotypic variation. Such an integrated approach applied to human disease datasets has the potential to improve the ability to predict disease predisposition and identify specific therapeutic targets.

  4. Genetic heterogeneity in hereditary haemorrhagic telangiectasia.

    Science.gov (United States)

    Porteous, M E; Curtis, A; Williams, O; Marchuk, D; Bhattacharya, S S; Burn, J

    1994-01-01

    A locus causing hereditary haemorrhagic telangiectasia (HHT) has recently been mapped to 9q34 in four families and designated HHT1. In this paper, the results of a linkage study showing genetic heterogeneity in four families in whom HHT is segregating are reported. All the previously reported 9q34 linked families contain at least one affected member with a symptomatic pulmonary arteriovenous malformation. We postulate that clinical heterogeneity may also be a feature of HHT with a significantly higher predisposition to symptomatic PAVMs associated with the HHT1 linked families. PMID:7891373

  5. Quantitative integration of genetic factors in the learning and production of canary song.

    Science.gov (United States)

    Mundinger, Paul C; Lahti, David C

    2014-04-22

    Learned bird song is influenced by inherited predispositions. The canary is a model system for the interaction of genes and learning on behaviour, especially because some strains have undergone artificial selection for song. In this study, roller canaries (bred for low-pitched songs) and border canaries (whose song is higher pitched, similar to the wild-type) were interbred and backcrossed to produce 58 males that sorted into seven genetically distinct groups. All males were tutored with the same set of songs, which included both low- and high-pitched syllables. Individuals were consistent within genetic groups but differed between groups in the proportion of low- versus high-pitched syllables they learned and sang. Both sex-linked and autosomal factors affected song learning and song production, in an additive manner. Dominant Z-chromosome factors facilitated high-pitched syllable learning and production, whereas the sex-linked alleles associated with the switch to low-pitched syllables under artificial selection were largely recessive. With respect to autosomal effects, the most surprising result is that males in the same genetic group had almost identical repertoires. This result challenges two common preconceptions: that genetic changes at different loci lead to distinct phenotypic changes, and that genetic predispositions affect learning in simple and general ways. Rather, different combinations of genetic changes can be associated with the same phenotypic effect; and predispositions can be remarkably specific, such as a tendency to learn and sing one song element rather than another.

  6. Prognostic importance of quantitative echocardiographic evaluation in patients suspected of first non-massive pulmonary embolism

    DEFF Research Database (Denmark)

    Kjaergaard, Jesper; Schaadt, Bente Krogsgaard; Lund, Jens Otto

    2008-01-01

    AIMS: Patients suspected of acute pulmonary embolism (PE) frequently undergo echocardiography as a part of the initial work-up. Prognostic implication of routine echocardiography in patients suspected of PE remain to be established. METHODS AND RESULTS: Transthoracic echocardiography, including...

  7. Androgenetic Alopecia: Identification of Four Genetic Risk Loci and Evidence for the Contribution of WNT Signaling to Its Etiology

    NARCIS (Netherlands)

    Heilmann, S.; Kiefer, A.K.; Fricker, N.; Drichel, D.; Hillmer, A.M.; Herold, C.; Tung, J.Y.; Eriksson, N.; Redler, S.; Betz, R.C.; Li, R.; Karason, A.; Nyholt, D.R.; Song, K.; Vermeulen, S.; Kanoni, S.; Dedoussis, G.; Martin, N.G.; Kiemeney, L.A.L.M.; Mooser, V.; Stefansson, K.; Richards, J.B.; Becker, T.; Brockschmidt, F.F.; Hinds, D.A.; Nothen, M.M.

    2013-01-01

    The pathogenesis of androgenetic alopecia (AGA, male-pattern baldness) is driven by androgens, and genetic predisposition is the major prerequisite. Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms (SNPs) at eight different genomic loci are

  8. Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations

    Directory of Open Access Journals (Sweden)

    Jun Kanazawa

    2017-10-01

    Conclusions: Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.

  9. Clinical and Genetic Characterization of Patients with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Caused by a Plakophilin-2 Splice Mutation

    NARCIS (Netherlands)

    van der Smagt, Jasper J.; van der Zwaag, Paul A.; van Tintelen, J. Peter; Cox, Moniek G. P. J.; Wilde, Arthur A. M.; van Langen, Irene M.; Ummels, Amber; Hennekam, F. A. M.; Dooijes, Dennis; Gerbens, Frans; Bikker, Hennie; Hauer, Richard N. W.; Doevendans, Pieter A.

    2012-01-01

    Objectives: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is characterized by fibrofatty replacement of cardiomyocytes. In around 50% of index patients, a genetic predisposition is demonstrated. The purpose of this study was to examine a plakophilin-2 (PKP2) splice site

  10. DNA demethylation in normal colon tissue predicts predisposition to multiple cancers

    Science.gov (United States)

    Kamiyama, H; Suzuki, K; Maeda, T; Koizumi, K; Miyaki, Y; Okada, S; Kawamura, YJ; Samuelsson, JK; Alonso, S; Konishi, F; Perucho, M

    2014-01-01

    demethylation in NCM with multiple CC risk from younger patients also suggests an inherited predisposition for the apparent field cancerization effect of somatic demethylation. PMID:22310288

  11. Icare rebound tonometry in children with known and suspected glaucoma.

    Science.gov (United States)

    Flemmons, Meghan S; Hsiao, Ya-Chuan; Dzau, Jacqueline; Asrani, Sanjay; Jones, Sarah; Freedman, Sharon F

    2011-04-01

    Accurate intraocular pressure (IOP) measurement, important in managing pediatric glaucoma, often presents challenges. The Icare rebound tonometer shows promise for screening healthy children and has been reported comparable with Goldmann applanation in adults with glaucoma. The purpose of this study was to evaluate the Icare tonometer against Goldmann applanation for clinic IOP measurement in pediatric glaucoma. This was a prospective study comparing Icare versus Goldmann tonometry in pediatric glaucoma. Children with known or suspected glaucoma were recruited from scheduled clinic visits. IOP was measured with the Icare tonometer by a clinician and subsequently measured with Goldmann applanation tonometry (GAT) by a different single masked clinician. A total of 71 eyes of 71 children with known or suspected glaucoma were included. IOP by GAT ranged from 9 to 36 mm Hg. Icare readings ranged from 11 to 44 mm Hg. Mean difference between Icare and GAT was 2.3 ± SD 3.7 mm Hg, p IOPs were within ± 3 mm Hg of GAT in 63%. Icare IOPs were ≥GAT IOPs in 75%. The following factors were not associated with Icare IOPs greater than GAT: child's age, glaucoma diagnosis, strabismus, nystagmus, central corneal thickness, Icare instrument-reported reliability, number of glaucoma surgeries or medications, corneal abnormalities, and visual acuity. IOP by Icare tonometry was within 3 mm Hg of IOP by GAT in 63% and greater than GAT in 75%. This device may be reasonable to estimate IOP in selected children with known or suspected glaucoma whose IOP cannot otherwise be obtained in clinic; however, correlation of Icare IOPs with clinical findings must continue to be considered in each case. Copyright © 2011 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  12. Herbal hepatotoxicity: suspected cases assessed for alternative causes.

    Science.gov (United States)

    Teschke, Rolf; Schulze, Johannes; Schwarzenboeck, Alexander; Eickhoff, Axel; Frenzel, Christian

    2013-09-01

    Alternative explanations are common in suspected drug-induced liver injury (DILI) and account for up to 47.1% of analyzed cases. This raised the question of whether a similar frequency may prevail in cases of assumed herb-induced liver injury (HILI). We searched the Medline database for the following terms: herbs, herbal drugs, herbal dietary supplements, hepatotoxic herbs, herbal hepatotoxicity, and herb-induced liver injury. Additional terms specifically addressed single herbs and herbal products: black cohosh, Greater Celandine, green tea, Herbalife products, Hydroxycut, kava, and Pelargonium sidoides. We retrieved 23 published case series and regulatory assessments related to hepatotoxicity by herbs and herbal dietary supplements with alternative causes. The 23 publications comprised 573 cases of initially suspected HILI; alternative causes were evident in 278/573 cases (48.5%). Among them were hepatitis by various viruses (9.7%), autoimmune diseases (10.4%), nonalcoholic and alcoholic liver diseases (5.4%), liver injury by comedication (DILI and other HILI) (43.9%), and liver involvement in infectious diseases (4.7%). Biliary and pancreatic diseases were frequent alternative diagnoses (11.5%), raising therapeutic problems if specific treatment is withheld; pre-existing liver diseases including cirrhosis (9.7%) were additional confounding variables. Other diagnoses were rare, but possibly relevant for the individual patient. In 573 cases of initially assumed HILI, 48.5% showed alternative causes unrelated to the initially incriminated herb, herbal drug, or herbal dietary supplement, calling for thorough clinical evaluations and appropriate causality assessments in future cases of suspected HILI.

  13. Role of genetic in periodontal disease

    Directory of Open Access Journals (Sweden)

    Anand Narayanrao Wankhede

    2017-01-01

    Full Text Available Genetics is the study and understanding of the phenomena of heredity and variation. A large number of genes are associated with many systemic conditions. Periodontitis is inflammatory condition of periodontium. Periodontium consists of gingiva, periodontal ligament, cementum, and alveolar bone. It is considered being a multifactorial disease. Studies of animals and humans support the concept that a large number of genes' factor may be associated with periodontitis and clearly play a role in the predisposition and progression of periodontal diseases. It has been proven that genetic factors impair inflammatory and immune responses during periodontal diseases. Research on identifying specific genes causing periodontitis may improve and prevent the disease progression. The aim of this article is to focus on genetic risk factors and its influence for the various forms of periodontal disease.

  14. Benefits of sonography in diagnosing suspected uncomplicated acute diverticulitis.

    Science.gov (United States)

    King, Welfur C; Shuaib, Waqas; Vijayasarathi, Arvind; Fajardo, Carlos G; Cabrera, Waldo E; Costa, Juan L

    2015-01-01

    Despite evidence demonstrating equivalent accuracy of sonography and computed tomography (CT) in the workup of mild/uncomplicated acute diverticulitis, CT is overwhelmingly performed as the initial diagnostic test, particularly in the acute setting. Our study evaluated potential radiation and turnaround time savings associated with performing sonography instead of CT as the initial diagnostic examination in the workup of suspected uncomplicated acute diverticulitis. We retrospectively reviewed medical records from January 2010 to December 2012 for patients presenting with clinical symptoms of acute diverticulitis. Patients were categorized as a whole and subgrouped by age (>40 and 40 years and 121 diverticulitis. © 2015 by the American Institute of Ultrasound in Medicine.

  15. A Suspected Pelvic Aneurysmal Bone Cyst in Pregnancy

    Directory of Open Access Journals (Sweden)

    Rayan Elkattah

    2013-01-01

    Full Text Available Albeit rare, the majority of identified bone lesions in pregnancy spare the pelvis. Once encountered with a pelvic bone lesion in pregnancy, the obstetrician may face a challenging situation as it is difficult to determine and predict the effects that labor and parturition impart on the pelvic bones. Bone changes and pelvic bone fractures have been well documented during childbirth. The data regarding clinical outcomes and management of pregnancies complicated by pelvic ABCs is scant. Highly suspected to represent an aneurysmal bone cyst, the clinical evaluation of a pelvic lesion in the ilium of a pregnant individual is presented, and modes of delivery in such a scenario are discussed.

  16. Patch Testing in Suspected Allergic Contact Dermatitis to Cosmetics

    OpenAIRE

    Pramod Kumar; Rekha Paulose

    2014-01-01

    Background. Increasing use of cosmetics has contributed to a rise in the incidence of allergic contact dermatitis (ACD) to cosmetics. It is estimated that 1–5.4% of the population is sensitized to a cosmetic ingredient. Patch testing helps to confirm the presence of an allergy and to identify the actual allergens which are chemical mixtures of various ingredients. Objectives. The aims of this study are to perform patch testing in suspected ACD to cosmetics and to identify the most common alle...

  17. Familial Isolated Pituitary Adenomas (FIPA) and the Pituitary Adenoma Predisposition due to Mutations in the Aryl Hydrocarbon Receptor Interacting Protein (AIP) Gene

    Science.gov (United States)

    Aaltonen, Lauri A.; Daly, Adrian F.

    2013-01-01

    Pituitary adenomas are one of the most frequent intracranial tumors and occur with a prevalence of approximately 1:1000 in the developed world. Pituitary adenomas have a serious disease burden, and their management involves neurosurgery, biological therapies, and radiotherapy. Early diagnosis of pituitary tumors while they are smaller may help increase cure rates. Few genetic predictors of pituitary adenoma development exist. Recent years have seen two separate, complimentary advances in inherited pituitary tumor research. The clinical condition of familial isolated pituitary adenomas (FIPA) has been described, which encompasses the familial occurrence of isolated pituitary adenomas outside of the setting of syndromic conditions like multiple endocrine neoplasia type 1 and Carney complex. FIPA families comprise approximately 2% of pituitary adenomas and represent a clinical entity with homogeneous or heterogeneous pituitary adenoma types occurring within the same kindred. The aryl hydrocarbon receptor interacting protein (AIP) gene has been identified as causing a pituitary adenoma predisposition of variable penetrance that accounts for 20% of FIPA families. Germline AIP mutations have been shown to associate with the occurrence of large pituitary adenomas that occur at a young age, predominantly in children/adolescents and young adults. AIP mutations are usually associated with somatotropinomas, but prolactinomas, nonfunctioning pituitary adenomas, Cushing disease, and other infrequent clinical adenoma types can also occur. Gigantism is a particular feature of AIP mutations and occurs in more than one third of affected somatotropinoma patients. Study of pituitary adenoma patients with AIP mutations has demonstrated that these cases raise clinical challenges to successful treatment. Extensive research on the biology of AIP and new advances in mouse Aip knockout models demonstrate multiple pathways by which AIP may contribute to tumorigenesis. This review assesses

  18. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens.

    Science.gov (United States)

    Giménez-Barcons, Mireia; Casteràs, Anna; Armengol, Maria del Pilar; Porta, Eduard; Correa, Paula A; Marín, Ana; Pujol-Borrell, Ricardo; Colobran, Roger

    2014-10-15

    Down syndrome (DS), or trisomy of chromosome 21, is the most common genetic disorder associated with autoimmune diseases. Autoimmune regulator protein (AIRE), a transcription factor located on chromosome 21, plays a crucial role in autoimmunity by regulating promiscuous gene expression (pGE). To investigate if autoimmunity in DS is promoted by the reduction of pGE owing to dysregulation of AIRE, we assessed the expression of AIRE and of several peripheral tissue-restricted Ag genes by quantitative PCR in thymus samples from 19 DS subjects and 21 euploid controls. Strikingly, despite the 21 trisomy, AIRE expression was significantly reduced by 2-fold in DS thymuses compared with controls, which was also confirmed by fluorescent microscopy. Allele-specific quantification of intrathymic AIRE showed that despite its lower expression, the three copies are expressed. More importantly, decreased expression of AIRE was accompanied by a reduction of pGE because expression of tissue-restricted Ags, CHRNA1, GAD1, PLP1, KLK3, SAG, TG, and TSHR, was reduced. Of interest, thyroid dysfunction (10 cases of hypothyroidism and 1 of Graves disease) developed in 11 of 19 (57.9%) of the DS individuals and in none of the 21 controls. The thymuses of these DS individuals contained significantly lower levels of AIRE and thyroglobulin, to which tolerance is typically lost in autoimmune thyroiditis leading to hypothyroidism. Our findings provide strong evidence for the fundamental role of AIRE and pGE, namely, central tolerance, in the predisposition to autoimmunity of DS individuals. Copyright © 2014 by The American Association of Immunologists, Inc.

  19. THERAPEUTIC IMPLICATIONS OF GENETIC RISK VARIANTS FOR CORONARY ARTERY DISEASE

    Directory of Open Access Journals (Sweden)

    Rajiv Kumar Srivastava

    2017-02-01

    Full Text Available BACKGROUND This review covers therapeutic implication of genetic risk variant responsible for coronary artery disease by utilising the highdensity single-nucleotide microarrays to screen the entire human genome. The sequence of the human genome provides the blueprint for life. Approximately, 99.5% of the human genome Deoxyribonucleic Acid (DNA sequence is identical among humans with 0.5% of the genome sequence (15 million bps accounting for all individual differences. MATERIALS AND METHODS The new technology of the computerised chip array of millions of Single-Nucleotide Polymorphisms (SNPs as Deoxyribonucleic Acid (DNA markers makes it possible to study and detect genetic predisposition to common polygenic disorders such as Coronary Artery Disease (CAD. The sample sizes required for these studies are massive and large; worldwide consortiums such as Coronary Artery Disease Genome-wide Replication and Meta-Analysis (CARDIoGRAM study have been formed to accommodate this requirement. After the identification of 9p21 progress to detect genetic predisposition has been remarkable. RESULTS There are currently a total of 50 genetic risk variants predisposing to CAD of genome-wide significance with confirmation in independent populations. Rare variants (Minor Allele Frequency, MAF <5% will require direct sequencing to detect genetic predisposition. CONCLUSION We can develop new biomarkers for detecting early CAD as well as unique targets for novel therapy. The challenge for the future will be to identify the molecular mechanisms mediating the risk of those genetic risk variants that act through nonconventional risk factors. The ultimate objective for the future is the sequencing and functional analysis of the causative polymorphisms for its therapeutic implications.

  20. Genetic and diet effects on Ppar-α and Ppar-γ signaling pathways in the Berlin Fat Mouse Inbred line with genetic predisposition for obesity

    Directory of Open Access Journals (Sweden)

    Wagener Asja

    2010-09-01

    Full Text Available Abstract Background The Berlin Fat Mouse Inbred (BFMI line is a new mouse model for obesity, which was long-term selected for high fatness. Peroxisome proliferator-activated receptors (PPARs are involved in the control of energy homeostasis, nutrient metabolism and cell proliferation. Here, we studied the expression patterns of the different Ppar genes and the genes in the PPAR pathway in the BFMI line in comparison to physiological changes. Results At the age of 10 weeks, the BFMI mice exhibited marked obesity with enlarged adipocytes and high serum triglycerides concentrations in comparison to the often used mouse line C57BL/6 (B6. Between these two lines, gene expression analyses revealed differentially expressed genes belonging to the PPAR pathway, in particular genes of the lipogenesis and the fatty acid transport. Conclusion Surprisingly, the Ppar-α gene expression was up-regulated in liver and Ppar-γ gene expression was down-regulated in the white adipose tissue, indicating the activation of a mechanism that counteracts the rise of obesity.

  1. Role of genetic factors in the pathogenesis of aggressive periodontitis.

    Science.gov (United States)

    Vieira, Alexandre R; Albandar, Jasim M

    2014-06-01

    This article critically reviews the evidence for a role of genetic factors in the pathogenesis of aggressive periodontitis and discusses the study approaches commonly used to identify genetic risk factors of this disease. Available data suggest that aggressive periodontitis is caused by mutations in multiple genes, combined with environmental effects. Syndromic periodontal diseases include certain monogenic disorders that express phenotypes showing aggressive forms of periodontitis, and the genetic triggering factors of most of these syndromes have been identified. Other periodontal disease phenotypes seem to occur through different genetic predisposition patterns. Case-control and genome-wide studies have been used to investigate the association with gene polymorphisms. Association studies and the familial aggregation of aggressive periodontitis suggest a significant genetic component in the increased predisposition to this disease. There is evidence to support the contribution of a few major genes or of multiple small-effects genes. In addition, there is evidence of gene-gene and gene-environment interaction effects. Early studies suggested an X-linked mode of transmission of aggressive periodontitis, and subsequent studies support an autosomal mode. Genetic studies have the potential to improve the screening programs of subjects at risk for developing aggressive periodontitis and may enhance treatment outcome through gene therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs.

    Science.gov (United States)

    Kim, Seung-Hyun; Sanak, Marek; Park, Hae-Sim

    2013-05-01

    Various hypersensitivity reactions have been reported with aspirin and nonsteroidal anti-inflammatory drugs. Hypersensitivity can occur regardless of a chemical drug structure or its therapeutic potency. Allergic conditions include aspirin-exacerbated respiratory disease (AERD or aspirin-induced asthma), aspirin-induced urticaria/angioedema (AIU), and anaphylaxis. Several genetic studies on aspirin hypersensitivity have been performed to discover the genetic predisposition to aspirin hypersensitivity and to gain insight into the phenotypic diversity. This article updates data on the genetic mechanisms that govern AERD and AIU and summarizes recent findings on the molecular genetic mechanism of aspirin hypersensitivity. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Immunology and Genetic of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Norma C. Serrano

    2006-01-01

    Full Text Available Preeclampsia is a disease characterized by hypertension and proteinuria in the third trimester of pregnancy. Preeclampsia is a major cause of maternal mortality, and fetal death, especially in developing countries, but its aetiology remains unclear. Key findings support a causal role of superficial placentation driven by immune mal maladaptation, which then lead to reduced concentrations of angiogenic growth factors and to an increase in placental debris in the maternal circulation resulting in a maternal inflammatory response. Epidemiological research has consistently demonstrated a substantial familial predisposition to preeclampsia. Unfortunately, the conquest of the genes explaining such a individual susceptibility has been proved to be a hard task. However, genetics will also inform us about causality of environmental factors, and then serve as a tool to prioritize therapeutic targets for preventive strategies.

  4. Profile of genetic disorders prevalent in northeast region of Cairo ...

    African Journals Online (AJOL)

    As clinical geneticists, we recently reviewed our 43 years experience in an attempt to represent the frequency of genetic disorders in the Division of Genetics at Pediatric Hospital, Faculty of Medicine, Ain-Shams University, Cairo, Egypt, during the period from 1966 to 2009. All patients (from birth up to 18 years) suspected of ...

  5. Investigation of suspected chronic fatigue syndrome/myalgic encephalopathy.

    Science.gov (United States)

    Owe, Jone Furlund; Næss, Halvor; Gjerde, Ivar Otto; Bødtker, Jørn Eilert; Tysnes, Ole-Bjørn

    2016-02-09

    Chronic fatigue is a frequently occurring problem in both the primary and specialist health services. The Department of Neurology at Haukeland University Hospital has established a standard assessment for patients referred with suspected CFS/ME. This study reports diagnoses and findings upon assessment, and considers the benefit of supplementary examinations. Diagnoses and findings from examinations of 365 patients assessed for suspected CFS/ME are retrospectively reported. A total of 48 patients (13.2%) were diagnosed with CFS/ME, while a further 18 patients (4.9%) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3%), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients. Fatigue is a frequently occurring symptom in the population. Thorough somatic and psychiatric investigation is necessary before referral to the specialist health services. Mental disorders and reactions to life crises are common and important differential diagnoses for CFS/ME. Long waiting times in the specialist health services may result in delayed diagnosis for these patients.

  6. Perioperative sexual interest in women with suspected gynecologic malignancies.

    Science.gov (United States)

    Bretschneider, C E; Bensen, Jeannette T; Geller, Elizabeth J; Gehrig, Paola A; Wu, Jennifer M; Doll, Kemi M

    2017-07-01

    For women with gynecologic cancer, the impact of surgery on sexual interest and desire in the immediate and later postoperative period is not well characterized. The objective of this study was to report the perioperative trends of changing sexual interest and desire in a cohort of women undergoing surgery for suspected gynecologic malignancies. This is an ancillary analysis of a cohort study analyzing health-related outcomes in women who underwent primary surgical management of a suspected gynecologic malignancy between 10/2013 and 10/2014. Subjects completed the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Questionnaire (PROMIS-SFQ) preoperatively and questions on sexual interest and desire at one, three, and six months postoperatively. Bivariate tests and multiple linear regression were used to analyze data. Of 231 women who completed a baseline PROMIS-SFQ, 187 (81%) completed one-month, 170 (74%) three-month, and 174 (75%) six-month follow-up interviews. Following surgery, 71% of enrolled subjects were diagnosed with a malignancy. Women age women age >55 (-5.5±1.0 vs -2.3±0.9, p=0.02). In a multivariable analysis, age women of all ages (-5.6, 95% CI: -9.6, -1.5). This study provides new data regarding the timing and magnitude of changes in sexual interest following gynecologic oncology procedures. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. MRI diagnosis of suspected atlanto-occipital dissociation in childhood

    Energy Technology Data Exchange (ETDEWEB)

    Grabb, B.C.; Frye, T.A.; Hedlund, G.L.; Vaid, Y.N.; Royal, S.A. [Department of Radiology, The Children`s Hospital of Alabama, Birmingham (United States); Grabb, P.A. [Department of Neurosurgery, University of Alabama at Birmingham (United States)

    1999-04-01

    Objective. To demonstrate the utility of magnetic resonance (MR) imaging in the diagnosis of complete and partial ligamentous injuries in patients with suspected atlanto-occipital dissociation (AOD). Materials and methods. Five patients with suspected AOD had MR imaging performed within an average of 4 days after injury. MR scans were reviewed with specific analysis of craniocervical ligamentous structures. Charts were reviewed to obtain clinical information regarding presentation, treatment, hospital course, and outcome. Results. Two patients demonstrated MR evidence of complete AOD. One had disruption of all visualized major ligamentous structures at the craniocervical junction with anterolisthesis and evidence of cord damage. The second had injuries to the tectorial membrane, superior band of the cruciform ligament, apical ligament, and interspinous ligament at C 1-2. The remaining three patients sustained incomplete severance of the ligamentous structures at the craniocervical junction. All patients demonstrated subtle radiographic findings suggestive of AOD, including soft tissue swelling at the craniocervical junction without fracture. The two patients with complete AOD died. The three patients with partial AOD were treated with stabilization. On follow-up, these three children were asymptomatic following their craniocervical injury. Conclusion. MR imaging of acute AOD provides accurate identification of the craniocervical ligaments injured, classification of full versus partial ligamentous disruption, and analysis of accompanying spinal cord injury. This information is important for early appropriate neurosurgical management and preservation of neurologic function in survivors. (orig.) With 7 figs., 1 tab., 14 refs.

  8. MRI diagnosis of suspected atlanto-occipital dissociation in childhood.

    Science.gov (United States)

    Grabb, B C; Frye, T A; Hedlund, G L; Vaid, Y N; Grabb, P A; Royal, S A

    1999-04-01

    To demonstrate the utility of magnetic resonance (MR) imaging in the diagnosis of complete and partial ligamentous injuries in patients with suspected atlanto-occipital dissociation (AOD). Five patients with suspected AOD had MR imaging performed within an average of 4 days after injury. MR scans were reviewed with specific analysis of craniocervical ligamentous structures. Charts were reviewed to obtain clinical information regarding presentation, treatment, hospital course, and outcome. Two patients demonstrated MR evidence of complete AOD. One had disruption of all visualized major ligamentous structures at the craniocervical junction with anterolisthesis and evidence of cord damage. The second had injuries to the tectorial membrane, superior band of the cruciform ligament, apical ligament, and interspinous ligament at C 1-2. The remaining three patients sustained incomplete severance of the ligamentous structures at the craniocervical junction. All patients demonstrated subtle radiographic findings suggestive of AOD, including soft tissue swelling at the craniocervical junction without fracture. The two patients with complete AOD died. The three patients with partial AOD were treated with stabilization. On follow-up, these three children were asymptomatic following their craniocervical injury. MR imaging of acute AOD provides accurate identification of the craniocervical ligaments injured, classification of full versus partial ligamentous disruption, and analysis of accompanying spinal cord injury. This information is important for early appropriate neurosurgical management and preservation of neurologic function in survivors.

  9. CT Pulmonary Angiography and Suspected Acute Pulmonary Embolism

    Energy Technology Data Exchange (ETDEWEB)

    Enden, T.; Kloew, N.E. [Ullevaal Univ. Hospital, Oslo (Norway). Dept. of Cardiovascular Radiology

    2003-05-01

    Purpose: To evaluate the use and quality of CT pulmonary angiography in our department, and to relate the findings to clinical parameters and diagnoses. Material and Methods: A retrospective study of 324 consecutive patients referred to CT pulmonary angiography with clinically suspected pulmonary embolism (PE). From the medical records we registered clinical parameters, blood gases, D-dimer, risk factors and the results of other relevant imaging studies. Results: 55 patients (17%) had PE detected on CT. 39 had bilateral PE, and 8 patients had isolated peripheral PE. 87% of the examinations showing PE had satisfactory filling of contrast material including the segmental pulmonary arteries, and 60% of the subsegmental arteries. D-dimer test was performed in 209 patients, 85% were positive. A negative D-dimer ruled out PE detected at CT. Dyspnea and concurrent symptoms or detection of deep vein thrombosis (DVT), contraceptive pills and former venous thromboembolism (VTE) were associated with PE. The presence of only one clinical parameter indicated a negative PE diagnosis (p < 0.017), whereas two or more suggested a positive PE diagnosis (p < 0.002). CT also detected various ancillary findings such as consolidation, pleural effusion, nodule or tumor in nearly half of the patients; however, there was no association with the PE diagnosis. Conclusion: The quality of CT pulmonary angiography was satisfactory as a first-line imaging of PE. CT also showed additional pathology of importance in the chest. Our study confirmed that a negative D-dimer ruled out clinically suspected VTE.

  10. Ocular lesions following suspected lightning injury in a horse.

    Science.gov (United States)

    Evans, Paige M; Armour, Micki D; Dubielzig, Richard R

    2012-07-01

      To describe the gross and histopathological ocular findings in a horse following suspected lightning injury.   The eyes of a 2-year-old thoroughbred gelding were clinically and histopathologically evaluated following a severe lightning storm following euthanasia because of visual impairment.   Severe corneal edema and hydrops were noted clinically oculus dexter. Indirect ophthalmoscopy revealed bilateral symmetrical raised hyporeflective peripapillary geographic lesions. Histopathologic evaluation revealed corneal edema in the right eye with normal corneal endothelium. Posterior segment evaluation revealed localized, pericentral choroidal lesions characterized by the presence of hemorrhage, early fibrosis, and minimal lymphoplasmacytic, neutrophilic, and histiocytic inflammation with spindle cell proliferation. The retinas overlying the choroidal lesions were necrotic and mostly absent. Peripheral to the focal lesion, the retina abruptly returned to normal architecture peripheral to a zone of apoptotic photoreceptors. Centrally, swollen axons extended into the optic disc.   There have been few descriptions of ocular lesions in animals following suspected lightning injury. We believe these findings to be unique because of the type of thermal injury that may be characteristic of lightening injury. We do not know whether these lesions would have progressed over time. © 2011 American College of Veterinary Ophthalmologists.

  11. Suspected side effects to the quadrivalent human papilloma vaccine.

    Science.gov (United States)

    Brinth, Louise; Theibel, Ann Cathrine; Pors, Kirsten; Mehlsen, Jesper

    2015-04-01

    The quadrivalent vaccine that protects against human papilloma virus types 6, 11, 16 and 18 (Q-HPV vaccine, Gardasil) was included into the Danish childhood vaccination programme in 2009. During the past years, a collection of symptoms primarily consistent with sympathetic nervous system dysfunction have been described as suspected side effects to the Q-HPV vaccine. We present a description of suspected side effects to the Q-HPV vaccine in 53 patients referred to our Syncope Unit for tilt table test and evaluation of autonomic nervous system function. All patients had symptoms consistent with pronounced autonomic dysfunction including different degrees of orthostatic intolerance, severe non-migraine-like headache, excessive fatigue, cognitive dysfunction, gastrointestinal discomfort and widespread pain of a neuropathic character. We found consistency in the reported symptoms as well as between our findings and those described by others. Our findings neither confirm nor dismiss a causal link to the Q-HPV vaccine, but they suggest that further research is urgently warranted to clarify the pathophysiology behind the symptoms experienced in these patients and to evaluate the possibility and the nature of any causal link and hopefully establish targeted treatment options. not relevant. not relevant.

  12. Patch Testing in Suspected Allergic Contact Dermatitis to Cosmetics

    Science.gov (United States)

    Paulose, Rekha

    2014-01-01

    Background. Increasing use of cosmetics has contributed to a rise in the incidence of allergic contact dermatitis (ACD) to cosmetics. It is estimated that 1–5.4% of the population is sensitized to a cosmetic ingredient. Patch testing helps to confirm the presence of an allergy and to identify the actual allergens which are chemical mixtures of various ingredients. Objectives. The aims of this study are to perform patch testing in suspected ACD to cosmetics and to identify the most common allergen and cosmetic product causing dermatitis. Methods. Fifty patients with suspected ACD to cosmetics were patch-tested with 38 antigens of the Indian Cosmetic Series and 12 antigens of the Indian Standard Series. Results. The majority (58%) of patients belonged to the 21–40 years age group. The presence of ACD to cosmetics was confirmed in 38 (76%) patients. Face creams (20%), hair dyes (14%), and soaps (12%) were the most commonly implicated. The most common allergens identified were gallate mix (40%), cetrimide (28%), and thiomersal (20%). Out of a total of 2531 patches applied, positive reactions were obtained in 3.75%. Conclusion. Incidence of ACD to cosmetics was greater in females. Face creams and hair dyes were the most common cosmetic products implicated. The principal allergens were gallate mix, cetrimide, and thiomersal. PMID:25295057

  13. Feline toxicological emergencies: when to suspect and what to do.

    Science.gov (United States)

    Grave, Tobias W; Boag, Amanda K

    2010-11-01

    Confirmed or suspected intoxications with a wide variety of agents represent a small but important group of feline emergency cases. Generally it is thought that toxicities are less common in cats compared with dogs, with a higher proportion relating to dermal as opposed to oral exposure. Once toxicity is suspected or diagnosed, it must be recognised that treatment regimes may need modification compared with those established for dogs. Different drugs or different dosages may be warranted and the choice of available drugs may be reduced. This review draws on published studies, case reports and clinical experience to summarise key features of the general management of the intoxicated feline patient before describing some of the more serious and common intoxications in more detail. The focus throughout the review is on the peculiarities of feline metabolism and how they may impact on presentation and treatment. The aim is to assist companion animal and feline practitioners, who are in the frontline when it comes to managing these emergency cases. Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

  14. The Genetics of Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Eberhart, Johann K; Parnell, Scott E

    2016-06-01

    The term "fetal alcohol spectrum disorders" (FASD) defines the full range of ethanol (EtOH)-induced birth defects. Numerous variables influence the phenotypic outcomes of embryonic EtOH exposure. Among these variables, genetics appears to play an important role, yet our understanding of the genetic predisposition to FASD is still in its infancy. We review the current literature that relates to the genetics of FASD susceptibility and gene-EtOH interactions. Where possible, we comment on potential mechanisms of reported gene-EtOH interactions. Early indications of genetic sensitivity to FASD came from human and animal studies using twins or inbred strains, respectively. These analyses prompted searches for susceptibility loci involved in EtOH metabolism and analyses of candidate loci, based on phenotypes observed in FASD. More recently, genetic screens in animal models have provided an additional insight into the genetics of FASD. Understanding FASD requires that we understand the many factors influencing phenotypic outcome following embryonic EtOH exposure. We are gaining ground on understanding some of the genetics behind FASD, yet much work remains to be carried out. Coordinated analyses using human patients and animal models are likely to be highly fruitful in uncovering the genetics behind FASD. Copyright © 2016 by the Research Society on Alcoholism.

  15. Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

    Directory of Open Access Journals (Sweden)

    Rafael Chacon

    Full Text Available We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

  16. Influenza Illness among Case-Patients Hospitalized for Suspected Dengue, El Salvador, 2012.

    Science.gov (United States)

    Chacon, Rafael; Clara, Alexey Wilfrido; Jara, Jorge; Armero, Julio; Lozano, Celina; El Omeiri, Nathalie; Widdowson, Marc-Alain; Azziz-Baumgartner, Eduardo

    2015-01-01

    We estimate the proportion of patients hospitalized for suspected dengue that tested positive for influenza virus in El Salvador during the 2012 influenza season. We tested specimens from 321 hospitalized patients: 198 patients with SARI and 123 patients with suspected dengue. Among 121 hospitalized suspected dengue (two co-infected excluded) patients, 28% tested positive for dengue and 19% positive for influenza; among 35 with suspected dengue and respiratory symptoms, 14% were positive for dengue and 39% positive for influenza. One percent presented co-infection between influenza and dengue. Clinicians should consider the diagnosis of influenza among patients with suspected dengue during the influenza season.

  17. Surveillance Recommendations for Children with Overgrowth Syndromes and Predisposition to Wilms Tumors and Hepatoblastoma

    NARCIS (Netherlands)

    Kalish, J.M.; Doros, L.; Helman, L.J.; Hennekam, R.C.; Kuiper, R.P.; Maas, S.M.; Maher, E.R.; Nichols, K.E.; Plon, S.E.; Porter, C.C.; Rednam, S.; Schultz, K.A.P.; States, L.J.; Tomlinson, G.E.; Zelley, K.; Druley, T.E.

    2017-01-01

    A number of genetic syndromes have been linked to increased risk for Wilms tumor (WT), hepatoblastoma (HB), and other embryonal tumors. Here, we outline these rare syndromes with at least a 1% risk to develop these tumors and recommend uniform tumor screening recommendations for North America.

  18. The role of latent internalizing and externalizing predispositions in accounting for the development of comorbidity among common mental disorders.

    Science.gov (United States)

    Kessler, Ronald C; Petukhova, Maria; Zaslavsky, Alan M

    2011-07-01

    Although numerous studies have examined the latent structure of internalizing and externalizing mental disorders, the effects of this structure in predicting the development of comorbidity have remained unexamined until recently. A novel approach to study the effects of latent internalizing and externalizing predispositions to the development of comorbidity was used to analyze data from 14 countries in the WHO World Mental Health Survey Initiative. Pervasive significant positive associations were found between temporally primary and secondary internalizing and externalizing disorders in survival analyses, with time-lagged associations consistently stronger within domains than between domains. The vast majority of these associations were explained by latent internalizing and externalizing variables. Specific phobia and obsessive compulsive disorder were the most important internalizing components and hyperactivity disorder and oppositional-defiant disorder the most important externalizing components. Several intriguing residual time-lagged associations remained significant, though, even after controlling latent predispositions. The latent variable model suggests that common causal pathways account for most comorbidity among internalizing-externalizing disorders. These pathways should be the focus of future research on the development of comorbidity, although isolation of consistent residual time-lagged associations between certain pairs of primary-secondary disorders is also important in pointing the way to subsequent focused study.

  19. Nonsteroidal Anti-Inflammatory Drugs Quickly Resolve Symptoms Associated with EBV-Induced Infectious Mononucleosis in Patients with Atopic Predispositions.

    Science.gov (United States)

    Kazama, Itsuro; Miura, Chieko; Nakajima, Toshiyuki

    2016-02-14

    Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus (EBV) infection. In adults, the symptoms can often be severe and prolonged, sometimes causing serious complications. Analgesic or antipyretic drugs are normally used to relieve the symptoms. However, there is no causal treatment for the disease. Two cases of adult patients with atopic predispositions developed nocturnal fever, general fatigue, pharyngitis and lymphadenopathy after an exacerbation of atopic symptoms or those of allergic rhinitis. Due to the positive results for EBV viral-capsid antigen (VCA) IgM and negative results for EBV nuclear antigen (EBNA) IgG, diagnoses of infectious mononucleosis induced by EBV were made in both cases. Although oral antibiotics or acetaminophen alone did not improve the deteriorating symptoms, including fever, headache and general fatigue, nonsteroidal anti-inflammatory drugs (NSAIDs), such as tiaramide or loxoprofen, completely improved the symptoms quickly after the initiation. In these cases, given the atopic predispositions of the patients, an enhanced immunological response was likely to be mainly responsible for the pathogenesis of the symptoms. In such cases, NSAIDs, that are known to reduce the activity of EBV, may dramatically improve the deteriorating symptoms quickly after the initiation. In the present cases, the immunosuppressive property of these drugs was considered to suppress the activity of lymphocytes and thus provide the rapid and persistent remission of the disease.

  20. International Veterinary Epilepsy Task Force's current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs

    DEFF Research Database (Denmark)

    Hülsmeyer, Velia-Isabel; Fischer, Andrea; Mandigers, Paul J. J.

    2015-01-01

    , and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management...

  1. Using Internet Artifacts to Profile a Child Pornography Suspect

    Directory of Open Access Journals (Sweden)

    Marcus K. Rogers

    2014-03-01

    Full Text Available Digital evidence plays a crucial role in child pornography investigations. However, in the following case study, the authors argue that the behavioral analysis or “profiling” of digital evidence can also play a vital role in child pornography investigations. The following case study assessed the Internet Browsing History (Internet Explorer Bookmarks, Mozilla Bookmarks, and Mozilla History from a suspected child pornography user’s computer. The suspect in this case claimed to be conducting an ad hoc law enforcement investigation. After the URLs were classified (Neutral; Adult Porn; Child Porn; Adult Dating sites; Pictures from Social Networking Profiles; Chat Sessions; Bestiality; Data Cleaning; Gay Porn, the Internet history files were statistically analyzed to determine prevalence and trends in Internet browsing. First, a frequency analysis was used to determine a baseline of online behavior. Results showed 54% (n = 3205 of the URLs were classified as “neutral” and 38.8% (n = 2265 of the URLs were classified as a porn website. Only 10.8% of the URLs were classified as child pornography websites. However when the IE history file was analyzed by visit, or “hit,” count, the Pictures/Profiles (31.5% category had the highest visit count followed by Neutral (19.3%, Gay Porn (17%, and Child Porn (16.6%. When comparing the frequency of URLs to the Hit Count for each pornography type, it was noted that the accused was accessing gay porn, child porn, chat rooms, and picture profiles (i.e., from Facebook more often than adult porn and neutral websites. The authors concluded that the suspect in this case was in fact a child pornography user and not an ad hoc investigator, and the findings from the behavioral analysis were admitted as evidence in the sentencing hearing for this case. The authors believe this case study illustrates the ability to conduct a behavioral analysis of digital evidence. More work is required to further validate the

  2. Teicoplanin versus vancomycin for proven or suspected infection.

    Science.gov (United States)

    Cavalcanti, Alexandre B; Goncalves, Anderson R; Almeida, Claudia S; Bugano, Diogo Dg; Silva, Eliezer

    2010-06-16

    Vancomycin and teicoplanin are commonly used to treat gram-positive infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). There is uncertainty regarding the effects of teicoplanin compared to vancomycin on kidney function with some previous studies suggesting teicoplanin is less nephrotoxic than vancomycin. To investigate the efficacy and safety of vancomycin versus teicoplanin in patients with proven or suspected infection. We searched the Cochrane Renal Group's Specialised Register, CENTRAL, MEDLINE, EMBASE, reference lists of nephrology textbooks, review articles with relevant studies and sent letters seeking information about unpublished or incomplete studies to investigators involved in previous studies. We searched for randomised controlled trials (RCTs) in any language comparing teicoplanin to vancomycin for patients with proven or suspected infection. Two authors independently evaluated methodological quality and extracted data using standardised data extraction forms. Study investigators were contacted for information not available in the original manuscripts. Random effects model was used to estimate the pooled risk ratio (RR) with 95% confidence interval (CI). We included 24 studies (2,610 patients) in this review. Teicoplanin reduced the risk of nephrotoxicity compared to vancomycin (RR 0.66, 95% CI 0.48 to 0.90).The effects of teicoplanin or vancomycin were similar for clinical cure (RR 1.03, 95% CI 0.98 to 1.08), microbiological cure (RR 0.98, 95% CI 0.93 to 1.03) and mortality (RR 1.02, 95% CI 0.79 to1.30). Six studies reported no cases of acute kidney injury (AKI) needing dialysis. Adverse events were less frequent with teicoplanin including cutaneous rash (RR 0.57, 95% CI 0.35 to 0.92), red man syndrome (RR 0.21, 95% CI 0.08 to 0.59) and total adverse events (RR 0.73, 95% CI 0.53 to 1.00). A lower risk of nephrotoxicity with teicoplanin was observed in patients either with (RR 0.51, 95% CI 0.30 to 0.88) or

  3. Genetics underlying an individualized approach to adult spinal disorders

    Directory of Open Access Journals (Sweden)

    Corey Walker

    2016-11-01

    Full Text Available Adult spinal disorders are a significant cause of morbidity across the world and carry significant health and economic burdens. Genetic predispositions are increasingly considered for these conditions and are becoming understood. Advances in molecular technologies since the mid-1990s have made possible genetic characterizations of these diseases in many populations, and recent findings have provided insight into the underlying pathophysiologic mechanisms. These studies have made clear the genetic heterogeneity producing clinical phenotypes and suggest that individualized treatments are possible in the future. We review the genetics of cervical spondylotic myelopathy, ossification of the posterior longitudinal ligament, and adult lumbar scoliotic deformity, highlighting recent genetic discoveries and the potential for personalized future therapeutics for these patients.

  4. [Basic aspects of medical genetics].

    Science.gov (United States)

    Pajarola, Sandra; Bachmann, Ruxandra; Niedrist, Dunja; Rauch, Anita

    2013-11-27

    The human genome consists of 23 pairs of chromosomes that contain 20 000-25 000 genes. Genetic disorders can be caused by different mechanisms, and therefore the confirmation of a suspected diagnosis requires knowledge of the underlying defect, so that the correct test can be applied. Monogenic diseases are caused by disturbances in a single gene, and currently only targeted diagnostic testing is available following a specific clinical suspicion. Chromosomal disorders usually involve multiple genes, so that the symptoms are often less specific. Specialists in Medical Genetics FMH are trained in creating a clinical genetic differential diagnosis, requesting the according laboratory test, interpretating the results and providing expert genetic counseling in presymptomatic and prenatal diagnosis. In Switzerland, specific legal principles and ethical guidelines must be taken into account.

  5. [Difficulties of genetic counselling in rare, mainly neurogenetic disorders].

    Science.gov (United States)

    Horváth, Emese; Nagy, Nikoletta; Széll, Márta

    2014-08-03

    In recent decades methods used for the investigation of the genetic background of rare diseases showed a great improvement. The aim of the authors was to demonstrate difficulties of genetic counselling and investigations in case of five rare, mainly neurogenetic diseases. During pre-test genetic counselling, the disease suspected from the clinical symptoms and the available genetic tests were considered. During post-test genetic counselling, the results of the genetic tests were discussed. In three of the five cases genetic tests identified the disease-causing genetic abnormalities, while in two cases the causative abnormalities were not identified. Despite a great improvement of the available genetic methods, the causative genetic abnormalities cannot be identified in some cases. The genetic counsellor has a key role in the assessment and interpretation of the results and in helping the family planning.

  6. Familial Myelodysplastic/Acute Leukemia Syndromes—Myeloid Neoplasms with Germline Predisposition

    Science.gov (United States)

    Baptista, Renata Lyrio Rafael; dos Santos, Anna Cláudia Evangelista; Gutiyama, Luciana Mayumi; Solza, Cristiana; Zalcberg, Ilana Renault

    2017-01-01

    Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text. PMID:28955657

  7. Impact of selected family socio-economic factors on coordinational predispositions of children

    OpenAIRE

    Jarosław Domaradzki

    2011-01-01

    Introduction: Biological growth of children is genetically determined but there are a lot of factors modifying trends of growth. Among them the most important seems to be parents’ education and number of children in family – socio-economical factors. Factors don’t affect organism individually. Interactions between them can increase or decrease. So the aim of the work was to estimate the influence of socio-economic factors like parents’ education and number of children in ...

  8. Familial Myelodysplastic/Acute Leukemia Syndromes—Myeloid Neoplasms with Germline Predisposition

    Directory of Open Access Journals (Sweden)

    Renata Lyrio Rafael Baptista

    2017-09-01

    Full Text Available Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.

  9. Familial Myelodysplastic/Acute Leukemia Syndromes—Myeloid Neoplasms with Germline Predisposition

    OpenAIRE

    Baptista, Renata Lyrio Rafael; dos Santos, Anna Cláudia Evangelista; Gutiyama, Luciana Mayumi; Solza, Cristiana; Zalcberg, Ilana Renault

    2017-01-01

    Although most cases of myeloid neoplasms are sporadic, a small subset has been associated with germline mutations. The 2016 revision of the World Health Organization classification included these cases in a myeloid neoplasm group with a predisposing germline mutational background. These patients must have a different management and their families should get genetic counseling. Cases identification and outline of the major known syndromes characteristics will be discussed in this text.

  10. Uncoding the genetic heterogeneity of myelodysplastic syndrome.

    Science.gov (United States)

    Lindsley, R Coleman

    2017-12-08

    Myelodysplastic syndrome (MDS) is a clinically heterogeneous disease characterized by functional impairment of hematopoiesis and abnormal bone marrow morphology. The type and severity of hematopoietic dysfunction in MDS are highly variable, and the kinetics of disease progression are difficult to predict. Genomic studies have shown that MDS is typically driven by a multistep somatic genetic process affecting a core set of genes. By definition, recurrent MDS driver mutations all drive clonal dominance, although they can have stereotyped positions in the clonal hierarchy or patterns of comutation association and exclusivity. Furthermore, environmental context, such as exposures to cytotoxic chemotherapy or the presence of germ-line predisposition, can influence disease pathogenesis and clinical outcomes. This review will address how an enhanced understanding of MDS genetics may enable refinement of current diagnostic schema, improve understanding of the pathogenesis of therapy-related MDS, and identify germ-line predispositions to development of MDS that are more common than recognized by standard clinical evaluation. © 2016 by The American Society of Hematology. All rights reserved.

  11. Pararenal splenosis encountered during the evaluation of a suspected pheochromocytoma.

    Science.gov (United States)

    Brown, Joel D; Kwee, Sandi

    2010-11-01

    The authors describe a patient in whom pararenal splenosis nodules were initially interpreted as probable pheochromocytoma. A 22-year-old man with chronic glomerulonephritis, hypertension and a childhood history of splenectomy was hospitalized for a hypertensive emergency. He did not improve with aggressive antihypertensive therapy. A pheochromocytoma was suspected, and a renal ultrasound and a magnetic resonance imaging showed 2 left pararenal masses. Laboratory evaluation for pheochromocytoma and aldosteronoma were negative. Biopsies of the masses were planned, but the masses were subsequently shown to be splenic tissue by a (99m)technnetium heat-damaged red blood cell scan. Ectopic splenic masses, eg, splenosis or accessory spleens, should be considered in patients with undiagnosed abdominal or kidney masses and a history of splenectomy.

  12. Seroprevalance of brucellosis among suspected cases in Malaysia.

    Science.gov (United States)

    Jama'ayah, M Z; Heu, J Y; Norazah, A

    2011-06-01

    Brucellosis is a zoonotic disease which can be transmitted by direct or indirect contact with infected animal or their products. It is an important public health problem but little is known on brucellosis in the Malaysian population. The aim of this study was to determine the presence of Brucella antibodies using commercial Brucella IgG and IgM ELISA kits (Vircell, SL, Barcelona Spain). A total of 184 sera from suspected patients were received from 16 hospitals in Malaysia over the years 2004 to 2009. Only 10 serum samples (5.4%) were positive for Brucella antibodies in which 5 showed the presence of both IgM and IgG. Most of the positive patients were occupationally involved with animals. This study suggests the seroprevalance of brucellosis among individuals who have contact with infected animals in Malaysia is low.

  13. Unenhanced MR Imaging in adults with clinically suspected acute appendicitis

    DEFF Research Database (Denmark)

    Chabanova, Elizaveta; Balslev, Ingegerd; Achiam, Michael

    2011-01-01

    PURPOSE: The purpose of the study was to evaluate unenhanced Magnetic Resonance Imaging (MRI) for the diagnosis of appendicitis or another surgery-requiring condition in an adult population scheduled for emergency appendectomy based on a clinical diagnosis of suspected acute appendicitis. MATERIALS...... radiologists and one surgeon independent of each other and compared with surgical and pathological records. RESULTS: According to the surgical and histopathological findings 30 of 48 patients (63%) had acute appendicitis. Of the remaining 18 patients, 4 patients had no reasons for the clinical symptoms and 14...... patients had other pathology. For the three reviewers the performance of MRI in the diagnosis of acute appendicitis showed the following sensitivity, specificity and accuracy ranges: 83-93%, 50-83% and 77-83%. Moderate (kappa=0.51) and fair (kappa=0.31) interobserver agreements in the MR diagnosis of acute...

  14. CT diagnosis of suspected acute appendicitis in adult patients

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    Yamase, Hiroshi; Sahashi, Kiyomi; Kawai, Masayuki; Kishida, Yoshihiko; Sumida, Kei; Kawamura, Ken-ichi [Gifu Syakaihoken Hospital (Japan)

    1998-06-01

    In order to assess the CT diagnosis of suspected acute appendicitis, we performed abdominal contrasted CT measurements in 77 patients from 20 to 86 years old, and of 50 men and 27 women from June 1993 to June 1996. The surgical findings were compared with the preoperative CT findings. By the preoperative CT imaging, we can know the degree and the position of inflammation in appendix vermiformis and the degree and the spread of periappendicular inflammation in the case of appendicitis, and can make a differential diagnosis of diverticulitis or gynecological diseases from appendicitis. It is important to make a preoperative diagnosis by the objectively excellent abdominal CT imaging and to avoid unnecessary surgery. (K.H.)

  15. Cost-effectiveness of routine imaging of suspected appendicitis.

    Science.gov (United States)

    D'Souza, N; Marsden, M; Bottomley, S; Nagarajah, N; Scutt, F; Toh, S

    2018-01-01

    Introduction The misdiagnosis of appendicitis and consequent removal of a normal appendix occurs in one in five patients in the UK. On the contrary, in healthcare systems with routine cross-sectional imaging of suspected appendicitis, the negative appendicectomy rate is around 5%. If we could reduce the rate in the UK to similar numbers, would this be cost effective? This study aimed to calculate the financial impact of negative appendicectomy at the Queen Alexandra Hospital and to explore whether a policy of routine imaging of such patients could reduce hospital costs. Materials and methods We performed a retrospective analysis of all appendicectomies over a 1-year period at our institution. Data were extracted on outcomes including appendix histology, operative time and length of stay to calculate the negative appendicectomy rate and to analyse costs. Results A total of 531 patients over 5 years of age had an appendicectomy. The negative appendicectomy rate was 22% (115/531). The additional financial costs of negative appendicectomy to the hospital during this period were £270,861. Universal imaging of all patients with right iliac fossa pain that could result in a 5% negative appendicectomy rate would cost between £67,200 and £165,600 per year but could save £33,896 (magnetic resonance imaging), £105,896 (computed tomography) or £132,296 (ultrasound) depending on imaging modality used. Conclusions Negative appendicectomy is still too frequent and results in additional financial burden to the health service. Routine imaging of patients with suspected appendicitis would not only reduce the negative appendicectomy rate but could lead to cost savings and a better service for our patients.

  16. Reliability of Examination Findings in Suspected Community-Acquired Pneumonia.

    Science.gov (United States)

    Florin, Todd A; Ambroggio, Lilliam; Brokamp, Cole; Rattan, Mantosh S; Crotty, Eric J; Kachelmeyer, Andrea; Ruddy, Richard M; Shah, Samir S

    2017-09-01

    The authors of national guidelines emphasize the use of history and examination findings to diagnose community-acquired pneumonia (CAP) in outpatient children. Little is known about the interrater reliability of the physical examination in children with suspected CAP. This was a prospective cohort study of children with suspected CAP presenting to a pediatric emergency department from July 2013 to May 2016. Children aged 3 months to 18 years with lower respiratory signs or symptoms who received a chest radiograph were included. We excluded children hospitalized ≤14 days before the study visit and those with a chronic medical condition or aspiration. Two clinicians performed independent examinations and completed identical forms reporting examination findings. Interrater reliability for each finding was reported by using Fleiss' kappa (κ) for categorical variables and intraclass correlation coefficient (ICC) for continuous variables. No examination finding had substantial agreement (κ/ICC > 0.8). Two findings (retractions, wheezing) had moderate to substantial agreement (κ/ICC = 0.6-0.8). Nine findings (abdominal pain, pleuritic pain, nasal flaring, skin color, overall impression, cool extremities, tachypnea, respiratory rate, and crackles/rales) had fair to moderate agreement (κ/ICC = 0.4-0.6). Eight findings (capillary refill time, cough, rhonchi, head bobbing, behavior, grunting, general appearance, and decreased breath sounds) had poor to fair reliability (κ/ICC = 0-0.4). Only 3 examination findings had acceptable agreement, with the lower 95% confidence limit >0.4: wheezing, retractions, and respiratory rate. In this study, we found fair to moderate reliability of many findings used to diagnose CAP. Only 3 findings had acceptable levels of reliability. These findings must be considered in the clinical management and research of pediatric CAP. Copyright © 2017 by the American Academy of Pediatrics.

  17. Investigating suspected acute pulmonary embolism - what are hospital clinicians thinking?

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    McQueen, A.S. [Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne (United Kingdom)], E-mail: andrewmcqueen7@hotmail.com; Worthy, S. [Department of Radiology, Royal Victoria Infirmary, Newcastle upon Tyne (United Kingdom); Keir, M.J. [Department of Medical Physics, Royal Victoria Infirmary, Newcastle upon Tyne (United Kingdom)

    2008-06-15

    Aims: To assess local clinical knowledge of the appropriate investigation of suspected acute pulmonary embolism (PE) and this compare with the 2003 British Thoracic Society (BTS) guidelines as a national reference standard. Methods: A clinical questionnaire was produced based on the BTS guidelines. One hundred and eight-six participants completed the questionnaires at educational sessions for clinicians of all grades, within a single NHS Trust. The level of experience amongst participants ranged from final year medical students to consultant physicians. Results: The clinicians were divided into four groups based on seniority: Pre-registration, Junior, Middle, and Senior. Forty-six point eight percent of all the clinicians correctly identified three major risk factors for PE and 25.8% recognized the definition of the recommended clinical probability score from two alternatives. Statements regarding the sensitivity of isotope lung imaging and computed tomography pulmonary angiography (CTPA) received correct responses from 41.4 and 43% of participants, respectively, whilst 81.2% recognized that an indeterminate ventilation-perfusion scintigraphy (V/Q) study requires further imaging. The majority of clinicians correctly answered three clinical scenario questions regarding use of D-dimers and imaging (78, 85, and 57.5%). There was no statistically significant difference between the four groups for any of the eight questions. Conclusions: The recommended clinical probability score was unfamiliar to all four groups of clinicians in the present study, and the majority of doctors did not agree that a negative CTPA or isotope lung scintigraphy reliably excluded PE. However, questions based on clinical scenarios received considerably higher rates of correct responses. The results indicate that various aspects of the national guidelines on suspected acute pulmonary embolism are unfamiliar to many UK hospital clinicians. Further research is needed to identify methods to improve

  18. Role of DR-70 immunoassay in suspected malignant pleural effusion

    Science.gov (United States)

    Sengupta, Amitabha; Saha, Kaushik; Jash, Debraj; Banerjee, Sourindra Nath; Biswas, Nirendra Mohan; Dey, Atin

    2013-01-01

    Context: A good proportion of patients with undiagnosed pleural effusion (PE) turn into malignancy over a period of time. Identification of positive biomarker may help in selecting the individuals who require close follow-up. Aims: The aims of this study were to evaluate the role of DR-70 immunoassay in suspected malignant PE. Settings and Design: We conducted a cross-sectional study among 89 patients of suspected malignant PE and 50 normal subjects (NS) were taken as control. Materials and Methods: Patients with exudative PE; who had pleural fluid lymphocyte count greater than 50% and adenosine deaminase less than 30 U/L were taken as cases. We had selected NSs among relatives of patients having normal blood chemistry and radiological investigations. Sensitivity and specificity of the test to differentiate malignant and non-malignant PE and also to identify PE with underlying malignancy was analyzed. Results: Mean value of DR-70 in NS was found to be 0.83 ± 0.273 mg/L without any significant difference between males (0.82 mg/L) and females (0.85 mg/L). Mean value of DR-70 in PE with underlying cancer was 5.03 ± 3.79 mg/L. Sensitivity (80%) and specificity (77.78%) of the test was maximum in PE with underlying cancer using cut-off value of 2 mg/L. Mean value DR-70 in malignant PE was 5.18 ± 3.75 mg/L and in non-malignant PE was 3.73 ± 3.74 mg/L without any statistically significant difference (P = 0.08). Conclusions: DR-70 assay has high sensitivity in detecting underlying lung cancer, but has no role in differentiating malignant PE from non-malignant PE. PMID:24339491

  19. Stroke genetics: prospects for personalized medicine

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    Markus Hugh S

    2012-09-01

    Full Text Available Abstract Epidemiologic evidence supports a genetic predisposition to stroke. Recent advances, primarily using the genome-wide association study approach, are transforming what we know about the genetics of multifactorial stroke, and are identifying novel stroke genes. The current findings are consistent with different stroke subtypes having different genetic architecture. These discoveries may identify novel pathways involved in stroke pathogenesis, and suggest new treatment approaches. However, the already identified genetic variants explain only a small proportion of overall stroke risk, and therefore are not currently useful in predicting risk for the individual patient. Such risk prediction may become a reality as identification of a greater number of stroke risk variants that explain the majority of genetic risk proceeds, and perhaps when information on rare variants, identified by whole-genome sequencing, is also incorporated into risk algorithms. Pharmacogenomics may offer the potential for earlier implementation of 'personalized genetic' medicine. Genetic variants affecting clopidogrel and warfarin metabolism may identify non-responders and reduce side-effects, but these approaches have not yet been widely adopted in clinical practice.

  20. Interactions between Genetics and Sugar-Sweetened Beverage Consumption on Health Outcomes: A Review of Gene–Diet Interaction Studies

    Directory of Open Access Journals (Sweden)

    Danielle E. Haslam

    2018-01-01

    Full Text Available The consumption of sugar-sweetened beverages (SSB, which includes soft drinks, fruit drinks, and other energy drinks, is associated with excess energy intake and increased risk for chronic metabolic disease among children and adults. Thus, reducing SSB consumption is an important strategy to prevent the onset of chronic diseases, and achieve and maintain a healthy body weight. The mechanisms by which excessive SSB consumption may contribute to complex chronic diseases may partially depend on an individual’s genetic predisposition. Gene–SSB interaction investigations, either limited to single genetic loci or including multiple genetic variants, aim to use genomic information to define mechanistic pathways linking added sugar consumption from SSBs to those complex diseases. The purpose of this review is to summarize the available gene-SSB interaction studies investigating the relationships between genetics, SSB consumption, and various health outcomes. Current evidence suggests there are genetic predispositions for an association between SSB intake and adiposity; evidence for a genetic predisposition between SSB and type 2 diabetes or cardiovascular disease is limited.