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Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited disorders affecting one or multiple components of the innate and/or adaptive immune system. Currently, over 300 underlying genetic defects have been discovered. The most common clinical findings in patients with PIDs are infections, autoimmunity, and malignancies. Despite international efforts, the cancer risk associated with PIDs, given the heterogeneous character of this group of diseases, is difficult to estimate. The diverse underlying mechanisms of cancer in PID add another layer of complexity. Treatment of cancer within a context of PID is complicated by serious toxicities and long-term effects, including second malignancies. This review will focus on the little-known crossroad between PID and cancer genes and the value thereof for directing future research on our understanding of cancer in PID and for the identification of early cancer biomarkers in PID patients.

Objectives: To investigate the lead exposure levels, and the effect of blood lead level (BLL) on recurrent respiratory infections in children aged 3–7 years in Shenyang. Methods: A case-control study including 78 children with recurrent respiratory infections and 141 controls was performed. Venous blood was obtained for BLL, and a questionnaire was completed. Results: The BLL was significantly higher in children with recurrent respiratory infections than that in the control group [Median (IQR): 2.56 (1.29–6.19) vs 1.99 (0.90–5.92) µg/dL, P=0.029]. Children with BLL ≥1.95 µg/dL were more likely to be suffering from recurrent respiratory infections (OR=2.328, 95%CI=1.228–4.413) than those with BLL <1.95 µg/dL. Conclusions: High lead level can increase the risk of respiratory infections in preschool children. [ABSTRACT FROM AUTHOR]

Panel sequencing is a practical option in genetic diagnosis. Enrichment and library preparation steps are critical in the diagnostic setting. In order to test the value of HaloPlex technology in diagnosis, we designed a custom oncogenetic panel including 62 genes. The procedure was tested on a training set of 71 controls and then blindly validated on 48 consecutive hereditary breast/ovarian cancer (HBOC) patients tested negative for BRCA1/2 mutation. Libraries were sequenced on HiSeq2500 and data were analysed with our academic bioinformatics pipeline. Point mutations were detected using Varscan2, median size indels were detected using Pindel and large genomic rearrangements (LGR) were detected by DESeq. Proper coverage was obtained. However, highly variable read depth was observed within genes. Excluding pseudogene analysis, all point mutations were detected on the training set. All indels were also detected using Pindel. On the other hand, DESeq allowed LGR detection but with poor specificity, preventing its use in diagnostics. Mutations were detected in 8% of BRCA1/2-negative HBOC cases. HaloPlex technology appears to be an efficient and promising solution for gene panel diagnostics. Data analysis remains a major challenge and geneticists should enhance their bioinformatics knowledge in order to ensure good quality diagnostic results.

At the time of the release of this publication in 2013 its author Lisa Karger was a private undergraduate student of Sarah Lawrence College (New York, United States) and specialized in "human genetics". The publication highlighted the empirical part of the thesis, namely, an experiment carried out within the framework of the Human Genetics Program, supported by the Grant Special Interest Group (SIG)-Prenatal SIG + SIG-Psychiatric from the national professional society in the field of genetic psychiatry NCGC (National Society of Genetic Counselors). Referring to the professionals of this community, the author explains: ".. I study the possibility of clinical genetic testing of patients with schizophrenia in finding the drivers for such testing ... I've prepared a 20-minute questionnaire to discuss your current work and your point of view on this issue, ... in order to assess the selected positions from the point of view of clinical perspectives". Description of the experiment and its results is accompanied by in-depth analysis of various aspects of the problem of genetic testing and the treatment (psychotherapeutic support) of persons with diagnosed schizophrenia and persons at risk of the disease.

This study investigates the effects of information and predisposition on individual responses to hypothetical questions. By employing the empirical implications of theoretical models (EITM) framework, I confirm that information and predisposition have positive effects on individual substantive responses to the hypothetical questions about the independence-unification issue in Taiwan. Respondents with higher levels of information and predisposition are more likely to provide substantive responses. More importantly, information and predisposition exert a negative interaction effect on individual responses to hypothetical questions, which implies that when an individual counts more on information to respond to hypothetical questions, her predisposition plays a less important role in her responses and vice versa. Finally, this study suggests that hypothetical questions are effective to probe individual opinion on specific issues under hypothetical conditions.

The World Health Organization warns of alarmingly high levels of sedentary behavior in our current society. In terms of the adolescent population, a substantial percentage of them do not meet the global recommendations for weekly physical activity. Therefore, this qualitative study aimed to analyze the predisposition and future preferences for physical activity and sports (PAS) and leisure practices of 142 adolescents, as well as identifying the challenges and proposed improvements, while considering gender differences. The participants' reflections were gathered through semistructured interviews and focus groups and subjected to an inductive analysis. The main findings indicate a high intention to engage in future PAS and leisure activity. Individual sports were predominantly mentioned by girls, while team sports were mainly favored by boys. Additionally, boys expressed a preference for technology-related leisure activities, whereas girls leaned towards artistic activities. The participants emphasized the necessity to renew sports and recreational facilities and to adapt to the range of activities offered. At the same time, they acknowledged that reallocating economic resources would improve the quality of sports and health-care services. Consequently, institutions should tailor their programs of PAS and leisure activities to align with the preferences, ages, and genders of the youth population.

Juvenile myelomonocytic leukemia (JMML) and myelodysplastic syndromes (MDS) of children are rare and aggressive diseases. They both have the particularity of being very frequently associated with an underlying predisposition syndrome, which must be systematically investigated by meticulous clinical exam completed by molecular analysis on fibroblasts, in order to guarantee the best therapeutic management. New generation sequencing techniques have made it possible to better define the landscape of constitutional predisposing pathologies, to understand the clonal evolution that leads to the development of hematological malignancies and to identify new prognostic markers. In these two diseases, the only curative treatment is allogeneic hematopoietic stem cell transplantation, for which the appropriate timeframe, the type of donor and the conditioning must be decided in consultation with the expert teams in each entity., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Sepsis is a complex condition defined by the systemic response to infection. Severity assessment scoring systems are used to aid the physician in deciding whether aggressive treatment is needed or not. In this study, various severity assessment scoring systems, namely Acute Physiology and Chronic Health Evaluation II (APACHE II), Rapid Emergency Medicine Score (REMS), Sequential Organ Failure Assessment (SOFA), Multiple Organ Dysfunction Score (MODS), Predisposition, Infection, Response, and Organ Dysfunction (PIRO), and Mortality in Emergency Department Sepsis (MEDS), were compared to assess their sensitivity and specificity. Materials and Methods: A prospective cohort study was conducted over 6 months. The study was conducted in the intensive care unit (ICU) of a tertiary care teaching hospital. All patients above 18 years of age with confirmed sepsis diagnosis and a well-defined outcome were included in the study. Results: A total of 193 patients were included in the study. The mean age was 57.2 ± 15.3 (mean ± standard deviation) years. Majority of the patients were male, 125 (64.76%). Overall mortality was 108 (55.9%). The calculated area under the receiver operating characteristic curve was 0.86 (95% confidence interval [CI]: 0.80–0.90) for APACHE II, 0.81 (95% CI: 0.75–0.87) for REMS, 0.80 (95% CI: 0.74–0.86) for SOFA, 0.74 (95% CI: 0.67–0.80) for MODS, 0.78 (95% CI: 0.71–0.84) for PIRO, and 0.77 (95% CI: 0.71–0.83) for MEDS. Sensitivity and specificity for APACHE II were 81.5 and 75.3, respectively. Conclusions: In our study, APACHE II score was found to be the most sensitive and specific in predicting the severity of sepsis compared to other scores. [ABSTRACT FROM AUTHOR]

Abstract Germline syndromes in myeloid leukemias are being discovered increasingly in patients, and their identification is essential for proper medical management to yield positive health outcomes for patients and their families. There needs to be a greater appreciation of germline predisposition driving the development of hematologic malignancies within the field of myeloid malignancies. Characterization of the influence of germline mutations on the development of myeloid malignancies is ongoing by utilization of next generation sequencing data and prognostic panels. Here, we propose modifications to the utilization and analysis of genetic results, specifically to have a high index of clinical suspicion for germline predisposition, to use assays that are comprehensive for detection of these variants, and a few caveats to interpreting sequencing data. Presented are the benefits and shortcomings of prognostic panels and clinical examples of the utilization of the prognostic panel used within the Department of Pathology at The University of Chicago. The examples demonstrate that panels performed for prognostication on DNA derived from malignant cells are able to identify patients with germline syndromes, but they can lack coverage for genes that confer inherited susceptibility. Furthermore, the panels are often not designed to find duplication and deletion mutations, which calls for a need to improve assay design and bioinformatic approaches to interpret such variants using these data. [ABSTRACT FROM AUTHOR]

Background: The vulnerability hypothesis suggests that impairments after remission of depressive episodes reflect a pre-existing vulnerability, while the scar hypothesis proposes that depression leaves residual impairments that confer risk of subsequent episodes. We prospectively examined vulnerability and scar effects in mental and physical functioning in a representative Dutch population sample. Methods: Three waves were used from the Netherlands Mental Health Survey and Incidence Study-2, a population-based study with a 6-years follow-up. Mental and physical functioning were assessed with the Medical Outcomes Study Short Form (SF-36). Major depressive disorder (MDD) was assessed with the Composite International Diagnostic Interview 3.0. Vulnerability effects were examined by comparing healthy controls (n = 2826) with individuals who developed a first-onset depressive episode during first follow-up but did not have a lifetime diagnosis of MDD at baseline (n = 181). Scarring effects were examined by comparing pre- and post-morbid functioning in individuals who developed a depressive episode after baseline that was remitted at the third wave (n = 108). Results: Both mental (B = −5.4, s.e. = 0.9, p < 0.001) and physical functioning (B = −8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who developed a first depressive episode after baseline compared with healthy controls. This effect was most pronounced in people who developed a severe episode. No firm evidence of scarring in mental or physical functioning was found. In unadjusted analyses, physical functioning was still lowered post-morbidly (B = −5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in adjusted analyses. Conclusions: Functional impairments after remission of depression seem to reflect a pre-existing vulnerability rather than a scar. [ABSTRACT FROM AUTHOR]

Problem statement: Although the study of students' attitudes toward physical education (PE) is of particular importance, there are only a few tools that study a variety of factors. Developing a tool that evaluates various factors helps to a better understanding of students' attitudes. Purposes: The purposes of this research were: (a) the development, and investigation of reliable and valid instruments that evaluate students' attitudes and predispositions toward PE, the assessment in PE, and how attitudes related to factors 'enjoyment' and 'effort,' (b) the examination of the statistically significant differences in grade, age, gender, and teacher's gender, (c) the analysis of the correlations between the factors of the questionnaires. Method: A total of 638 students (327 boys, 311 girls) participated from fifth, sixth, seventh and tenth grade. Attitudes towards Physical Education were measured through Phillips and Silverman (2012) questionnaire, while Predispositions towards Physical Education were assessed through Hilland, Stratton, Vinson, and Fairclough Physical Education Predisposition Scale (2009). Furthermore, a scale of 8 items was developed to assess Attitudes toward assessment in Physical Education. In addition, effort and enjoyment were measured. Results: All factors demonstrated acceptable internal consistency (α > .70) and confirmatory factor analysis confirmed structural validity of the scales. A one-way analysis of variance and post hoc test revealed that attitudes toward PE and toward assessment in PE were significantly higher in fifth, sixth and seventh grade compared with tenth grade students. Strong positive correlation was revealed between cognitive and affective factor. A total of 58% of enjoyment, and 44% effort were explained by the independent variables. Conclusions: The high validity and reliability of these instruments along with the variety of factors investigated, provide a strong base to conduct future research on students' attitudes. [ABSTRACT FROM AUTHOR]

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Black dot caused by Colletotrichum coccodes was initially considered a mild disease of potato, mainly infecting weakened plants. In the past two decades the fungus has been reported to infect roots and stems relatively early in the growing season, be prevalent on potato and in field soil in major potato production regions of the world, cause early death of foliage by itself and in association with other pathogens, reduce plant and root growth, and to reduce potato yields. Furthermore, the tuber phase of the disease is recognized as a major problem in that unsightly blemishes reduce value of fresh market potatoes. C. coccodes has been dubbed an elusive pathogen because infections are latent, disease symptoms on foliage are often non-descript and can be confused with other potential causes, disease effects on potato yield have not been consistent, and the disease is not satisfactorily managed. Sources of variation on yield likely arise from genetic variation within the pathogen population; the host population such as potato cultivar, maturity class, and plant organs infected; environmental variables; cultural and management practices such as timing of fungicide application; crop duration; post-harvest conditions; and interactions of C. coccodes with other microbes and with potato cultivars. Considerable research has been done on potato black dot during the last two decades, the scope of this paper is to define our current understanding on the disease and summarize disease management strategies. [ABSTRACT FROM AUTHOR]

The article offers information about the application of a tree-ring isotope based conceptual model to examine mechanisms and predispositions in relation to drought induced tree mortality, which is likely to increase in future as climate models forecast increased frequency of drought conditions. Other information about a strategy for dealing with drought as well as a tree’s predisposition to carbon starvation or to hydraulic failure is presented.

Résumé L’exploration d’une thrombopénie prolongée est une situation classique en pédiatrie. La cause la plus fréquente reste le purpura thrombopénique immunologique. Cependant, il est important de savoir remettre en cause ce diagnostic en cas d’atypie, d’association syndromique, d’antécédents familiaux de thrombopénie ou d’hémopathie myéloïde maligne, ou d’évolution inhabituelle, et d’évoquer l’hypothèse d’une thrombopénie constitutionnelle. Il s’agit d’un vaste groupe de pathologies qui a bénéficié ces dernières années des avancées de la génétique et de la biologie moléculaire. Ceci a permis la description d’un grand nombre d’entités clinicobiologiques formant un large spectre de pathologies aux pronostics et aux profils évolutifs diverses. Améliorer les connaissances sur ces pathologies, pour certaines de description récente, a pour but d’adapter au mieux la prise en charge et la surveillance des patients. Devant le nombre croissant d’anomalies génétiques décrites, nous proposons une classification des thrombopénies constitutionnelles basées sur deux données simples : le caractère isolé ou syndromique de la thrombopénie et la taille des plaquettes ou le volume plaquettaire moyen, avec une revue de la littérature récente. Notre but est de faciliter une démarche diagnostique rationnelle et ciblée au sein d’un groupe de pathologies en évolution constante. Malgré les progrès spectaculaires des connaissances, la moitié des patients atteints d’une thrombopénie constitutionnelle n’ont pas à ce jour de diagnostic génétique étiologique. Cette proportion sera probablement réduite dans les prochaines années, ce qui permettra d’améliorer la qualité de la prise en charge des patients. Summary Investigating a chronic thrombocytopenia is an usual matter for a pediatrician. The most frequent diagnosis is autoimmune thrombocytopenia. However, in case of unusual presentation or evolution, syndromic association, familial history of thrombocytopenia or myeloid malignancy, the hypothesis of a constitutional thrombocytopenia has to be considered. This is a large spectrum of diseases with different prognosis and evolution. It has benefited from the inputs of genetics and molecular biology over the past few years. Recent genetic knowledge enabled the description of several diseases. Being aware of these new entities is crucial for a better characterization of the diseases, in order to adapt the management strategy to each specific feature. Considering the growing number of new genes and new mutations described, we propose a classification of genetics thrombocytopenia relaying on two simple parameters: the isolated or syndromic pattern of the thrombocytopenia and on the mean platelet size and volume, based on a recent literature review. We aimed at demonstrating the diagnosis algorythm with simple clinicobiological data among a moving spectrum of diseases. However, nowadays half constitutional thrombocytopenias stay genetically undiagnosed. This proportion should be decreased in the next years, which will lead to a better management of the patients. [ABSTRACT FROM AUTHOR]

Facing purchase choice involving ambiguity in product quality, consumers behave in a boundedly rational manner. Consumers also exhibit varying degrees of predisposition toward a product. We present a simple model of boundedly rational choice under ambiguity. The model's key feature is that it captures the interaction between predisposition and ambiguity. We build on the choice model to derive demand curves and the unique equilibrium market outcomes (regarding prices, profits, and market shares) under duopolistic competition. In equilibrium, market shares are proportional to prices. In symmetric competition, higher equilibrium prices obtain when the ambiguity in product quality is high or when the customer base is partisan. For vertically differentiated products, the strategy of a higher-quality firm to marginally reduce ambiguity depends on the ambiguity level inherent in the product-market environment. The presence of informed customers may increase the equilibrium prices and profits of both firms. An understanding of the predisposition-ambiguity interaction may improve the firm's information and brand management strategy. [ABSTRACT FROM AUTHOR]

Background: Four explanations for the concurrent and prospective associations between temperament and psychopathology in children have been suggested: predisposition, complication/scar, common cause/continuity, and pathoplasty/exacerbation. Because the confounding effects of common causes have not been ruled out in prior work, the support for the various explanations is uncertain. Methods: Screen‐stratified community samples of 4‐year olds in Trondheim, Norway (n = 1,042), and 3‐year olds in Barcelona, Spain (n = 622), were assessed biennially for symptoms of attention‐deficit/hyperactivity (ADHD), oppositional defiant (ODD), conduct (CD), anxiety, and depressive disorders through interviewer‐based psychiatric interviews across four waves of data collection. The parents completed child temperament ratings. The data were analyzed with random and fixed effects regression adjusted for all time‐invariant unmeasured confounders (e.g., genetics, common methods bias, item overlap). Results: In both Norway and Spain and across ages, negative affect predisposed children to symptoms of all disorders except CD, low effortful control predisposed children to ADHD and ODD‐symptoms, and surgency predisposed children to increased ADHD‐symptoms. Complication effects were observed in the Spanish children for ADHD‐symptoms, which increased surgency and diminished effortful control, and for ODD‐symptoms, which decreased surgency. The common cause and pathoplasty/exacerbation explanations were not supported. Conclusions: The present results are consistent with the view that temperament plays a causal role in the development of symptoms of psychiatric disorders in children. Because temperament is malleable, interventions targeting the affective, attentional, and behavioral regulatory components of temperament may reduce psychopathology in children. [ABSTRACT FROM AUTHOR]

Background: The human helminth infections include ascariasis, trichuriasis, hookworm infections, schistosomiasis, lymphatic filariasis (LF) and onchocerciasis. It is estimated that almost 2 billion people worldwide are infected with helminths. Whilst the WHO treatment guidelines for helminth infections are mostly aimed at controlling morbidity, there has been a recent shift with some countries moving towards goals of disease elimination through mass drug administration, especially for LF and onchocerciasis. However, as prevalence is driven lower, treating entire populations may no longer be the most efficient or cost-effective strategy. Instead, it may be beneficial to identify individuals or demographic groups who are persistently infected, often termed as being "predisposed" to infection, and target treatment at them. Methods: The authors searched Embase, MEDLINE, Global Health, and Web of Science for all English language, human-based papers investigating predisposition to helminth infections published up to October 31st, 2017. The varying definitions used to describe predisposition, and the statistical tests used to determine its presence, are summarised. Evidence for predisposition is presented, stratified by helminth species, and risk factors for predisposition to infection are identified and discussed. Results: In total, 43 papers were identified, summarising results from 34 different studies in 23 countries. Consistent evidence of predisposition to infection with certain species of human helminth was identified. Children were regularly found to experience greater predisposition to Ascaris lumbricoides, Schistosoma mansoni and S. haematobium than adults. Females were found to be more predisposed to A. lumbricoides infection than were males. Household clustering of infection was identified for A. lumbricoides, T. trichiura and S. japonicum. Ascaris lumbricoides and T. trichiura also showed evidence of familial predisposition. Whilst strong evidence for predisposition to hookworm infection was identified, findings with regards to which groups were affected were considerably more varied than for other helminth species. Conclusion: This review has found consistent evidence of predisposition to heavy (and light) infection for certain human helminth species. However, further research is needed to identify reasons for the reported differences between demographic groups. Molecular epidemiological methods associated with whole genome sequencing to determine 'who infects whom' may shed more light on the factors generating predisposition. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

To measure the attitudes of physician candidates concerning phytotherapy practices and determine the variables affecting their attitudes. The study data were collected from 524 physician candidates, who were medical faculty students, using a Scale on Attitudes toward Phytotherapy Practices developed by the researchers. Since there is no scale in the literature that reliably and validly reveals the attitudes of physician candidates toward phytotherapy practices, researchers have developed a new scale. Exploratory and confirmatory factor analyses were used in the process of scale development. Univariate and multiple statistical methods were used for descriptive data analysis. The developed scale consisted of three factors, 'trust in phytotherapy', 'phytotherapy use', and 'predisposition', and 23 items based on the five-point Likert type. It was found that physicians' attitudes toward 'phytotherapy use' were closer to the positive side, while they were undecided concerning the subscales of 'trust in phytotherapy' and 'predisposition'. The attitudes of first-grade physician candidates toward phytotherapy practices were positive, but more negative attitudes were observed in later grades. These findings show that this newly developed scale is reliable and valid and can be used to measure the attitudes of physician candidates towards phytotherapy. In addition, it is thought that the use of phytotherapy can be extended with more scientific studies using different media channels, raising awareness among individuals about phytotherapy, and adding courses that include phytotherapy and its applications to the medical education curriculum. [ABSTRACT FROM AUTHOR]

Intensive development of DNA analysis technologies and large-scale genome-wide association studies have led to accumulation of a large array of data on the relationship between genetic factors and various phenotypic manifestations, including monogenic and polygenic hereditary diseases. This has greatly extended the capabilities of clinical diagnostics and predictive medicine in the field of socially significant diseases. For example, the role of a genetic component of the risk for such multifactorial and polyetiologic disease as stroke is now actively explored. Large-scale studies have revealed both general and specific genetic markers associated only with a certain type and subtype of stroke. This review analyzes the current state of the problem of using genetic markers for diagnosis of predisposition to stroke, complex issues associated with multiplicity of risk factors for stroke, and potential development in this area. [ABSTRACT FROM AUTHOR]

Introduction The PI3K-AKT-mTOR pathway may be involved in the development of central nervous system (CNS) metastasis from breast cancer. Accordingly, herein we explored whether single nucleotide polymorphisms (SNPs) of this pathway are associated with altered risk of CNS metastasis formation in metastatic breast cancer patients. Methods The GENEOM study ( NCT00959556 ) included blood sample collection from breast cancer patients treated in the neoadjuvant, adjuvant or metastatic setting. We identified patients with CNS metastases for comparison with patients without CNS metastasis, defined as either absence of neurological symptoms or normal brain magnetic resonance imaging (MRI) before death or during 5-year follow-up. Eighty-eight SNPs of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian (or mechanistic) target of rapamycin (mTOR) pathway genes were selected for analysis: AKT1 (17 SNPs), AKT2 (4), FGFR1 (2), mTOR (7), PDK1 (4), PI3KR1 (11), PI3KCA (20), PTEN (17), RPS6KB1 (6). Results Of 342 patients with metastases, 207 fulfilled the inclusion criteria: One-hundred-and-seven patients remained free of CNS metastases at last follow-up or date of death whereas 100 patients developed CNS metastases. Among clinical parameters, hormonal and human epidermal growth factor receptor-2 (HER2) status as well as vascular tumour emboli was associated with risk of CNS metastasis. Only PI3KR1-rs706716 was associated with CNS metastasis in univariate analysis after Bonferroni correction (p < 0.00085). Multivariate analysis showed associations between AKT1-rs3803304, AKT2-rs3730050, PDK1-rs11686903 and PI3KR1-rs706716 and CNS metastasis . Conclusion PI3KR1-rs706716 may be associated with CNS metastasis in metastatic breast cancer patients and could be included in a predictive composite score to detect early CNS metastasis irrespective of breast cancer subtype. [ABSTRACT FROM AUTHOR]

Background: Thyroid cancer is a common malignant disease of the endocrine system with increasing incidence rates over the last few decades. In this study, we sought to analyze the possible association of 45 single nucleotide polymorphisms (SNPs) with thyroid cancer in a population from Rio Grande do Norte, Brazil. Methods: Based on histological analysis by a pathologist, 80 normal thyroid specimens of tissue adjacent to thyroid tumors were obtained from the biobank at the Laboratory of Pathology of Liga Norte Riograndense Contra o Câncer, Natal, RN. Patient samples were then genotyped using the MassARRAY platform (Sequenon, Inc) followed by statistical analysis employing the SNPassoc package in R program. The genotypic frequencies of all 45 SNPs obtained from the International HapMap Project database and based on data from the ancestral populations of European and African origin were used to compose the control study group. Results: In our study, the following 9 SNPs showed significant differences in their frequency when comparing the study and control groups: rs3744962, rs258107, rs1461855, rs4075022, rs9943744, rs4075570, rs2356508, rs17485896 and rs2651339. Furthermore, the SNPs rs374492 C/T and rs258107 C/T were associated with a relative risk for thyroid carcinoma of 3.78 (p = 6.27 x 10e-5) and 2.91 (p=8.27x10e-5), respectively, after Bonferroni's correction for multiple comparisons. Conclusions: These nine polymorphisms could be potential biomarkers of predisposition to thyroid carcinoma in the population from Rio Grande do Norte. However, complementary studies including a control group with samples obtained from healthy subjects in Rio Grande do Norte state, should be conducted to confirm these results. [ABSTRACT FROM AUTHOR]

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 secondary education students, aged 15-17 (Mage = 15.35, SD = 0.49), divided into two groups: control (n = 15) and experimental (n = 20). The intervention programme was applied in the experimental group to 12 acrosport unit lessons based on motivational strategies by means of TARGET areas (i.e. Task, authority, recognition, grouping, evaluation and time). Firstly, the experimental group obtained significantly higher values in perceived support of the basic psychological needs and in the perceived task-oriented motivational climate in the acrosport unit. Secondly, this intervention was effective in generating a significant increase in predisposition towards physical education in the experimental group. Noteworthy is the need to generate interventions in different content areas that may improve students' predisposition towards physical education, which could contribute to them adopting a more active lifestyle. [ABSTRACT FROM AUTHOR]

Congenital anomalies that are diagnosed in at least 120,000 US infants every year are the leading cause of infant death and contribute to disability and pediatric hospitalizations. Several large-scale epidemiologic studies have provided substantial evidence of an association between congenital anomalies and cancer risk in children, suggesting potential underlying cancer-predisposing conditions and the involvement of developmental genetic pathways. Electronic medical records from 1,107 pediatric, adolescent, and young adult oncology patients were reviewed. The observed number (O) of congenital anomalies among children with a specific pediatric cancer subtype was compared to the expected number (E) of anomalies based on the frequency of congenital anomalies in the entire study population. The O/E ratios were tested for significance using Fisher's exact test. The Kaplan-Meier method was used to compare overall and neurological malignancy survival rates following tumor diagnosis. Thirteen percent of patients had a congenital anomaly diagnosis prior to their cancer diagnosis. When stratified by congenital anomaly subtype, there was an excess of neurological anomalies among children with central nervous system tumors (O/E = 1.56, 95%CI 1.13-2.09). Male pediatric cancer patients were more likely than females to have a congenital anomaly, particularly those <5 years of age (O/E 1.35, 95%CI 0.97-1.82). Our study provides additional insight into the association between specific congenital anomaly types and pediatric cancer development. Moreover, it may help to inform the development of new screening policies and support hypothesis-driven research investigating mechanisms underlying tumor predisposition in children with congenital anomalies. [ABSTRACT FROM AUTHOR]

Objective To describe the epidemiology and the types of eye disorders that are presumed to be inherited ( PIED) in three large Italian dog breeds. Animals Three large Italian dog breeds: Neapolitan Mastiff ( FCI code: 197), Maremma Sheepdog ( FCI code: 201), and Italian Corso dog ( FCI code: 343). Procedures All dogs that underwent a complete ophthalmic examination between 1992 and 2012 were included in this prospective observational study. The prevalence of eye disorders with 95% confidence intervals was reported for presumed healthy dogs and for dogs referred to a veterinary center for an ophthalmic consultation. Univariate and multivariate logistic regression techniques were used to generate odds ratios. Results Of 605 dogs examined during the study period, 351 dogs were affected by at least one PIED (58%; 95% CI: 54-62%). The prevalence of PIED was significantly lower in dogs presented for ophthalmic examination (53.8%) as compared to presumed healthy dogs (62.2%)( OR: 1.4; 95% CI: 1.02-1.9; P = 0.037). Also after multivariate adjustment for the period of observation, the odds of Neapolitan Mastiff (92.1%; OR: 21.4; 95% CI: 11.1-41.4) and of Cane Corso (57.7%; OR: 2.5; 95% CI: 1.7-3.6) suffering a PIED were greater than the Maremma Sheepdog (35.4%). The most common PIED in each breed were entropion (24.3% of all the PIED) in the Neapolitan Mastiff, ectropion (36.6%) in the Corso dog, and cataract (27.9%) in the Maremma Sheepdog. Conclusions Clinicians should be aware that three large Italian dog breeds frequently suffer PIED. Breed standards should be reconsidered, and breeding programs should be directed at limiting such disorders. [ABSTRACT FROM AUTHOR]

Intuitive thinking would argue that political or ideological orientation does not correlate with nonpolitical decisions, and certainly not with nonideological cognitive tasks. However, that is what happens in some cases. Previous neuropolitics studies have found that liberals are more adept at dealing with novel information than conservatives. This finding suggests that conservatives and liberals possess different cognitive skills. For the purposes of this article, two studies were executed to test whether this difference remained in alternative environmental settings. To this end, two novel cognitive tasks were designed in which one type of ideology or another was privileged according to the cognitive environment created by the tasks. Experimental findings indicate that liberals committed fewer errors than conservatives in one kind of cognitive environment, while conservatives scored higher in another. [ABSTRACT FROM AUTHOR]

Objective To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design. Methods The transcriptome and methylome of peripheral monocytes were compared between monozygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples. Results >100 differentially expressed genes and ∼1800 differentially methylated CpGs were detected in peripheral monocytes between MG patients and controls. Several transcripts associated with immune homeostasis and inflammation resolution were reduced in MG patients. Only a relatively few genes differed between the discordant healthy and MG co-twins, and both their expression and methylation profiles demonstrated very high similarity. Interpretation This is the first study to characterize the DNA methylation profile in MG, and the expression profile of immune cells in MZ twins with MG. Results suggest that numerous small changes in gene expression or methylation might together contribute to disease. Impaired monocyte function in MG and decreased expression of genes associated with inflammation resolution could contribute to the chronicity of the disease. Findings may serve as potential new predictive biomarkers for disease and disease activity, as well as potential future targets for therapy development. The high similarity between the healthy and the MG discordant twins, suggests that a molecular signature might precede a clinical phenotype, and that genetic predisposition may have a stronger contribution to disease than previously assumed. [ABSTRACT FROM AUTHOR]