Ansiedad ante exámenes en universitarios: papel de engagement, inteligencia emocional y factores asociados con pruebas académicas / Test Anxiety university students: role of engagement, emotional intelligence and factors associated to academic test solving

Resumen Introducción: La ansiedad ante los exámenes (AE) es común entre universitarios e implica manifestaciones cognitivas, motoras y fisiológicas de tensión y preocupación permanente ante la evaluación que puede afectar su desempeño académico. Objetivo: Evaluar si el engagement, la inteligencia emocional y los factores asociados con la realización de pruebas académicas predicen las manifestaciones de AE en una muestra de 400 estudiantes universitarios. Método: Mediante un diseño predictivo transversal se evaluó el engagement (Vigor, Dedicación, Absorción), la inteligencia emocional (Atención, Claridad, Reparación) y diversos factores relacionados con pruebas académicas, analizando su relación con las manifestaciones de AE, y se construyeron modelos de regresión categórica para definir el nivel predictivo de las variables. Resultados: Se descartó la relación entre engagement y AE (p>0,05) mientras que Claridad y Reparación se asociaron inversamente con las manifestaciones de AE, excepto las fisiológicas. Diferentes factores asociados con la realización de exámenes como control docente, temor a la evaluación y tipo de preguntas predicen las respuestas de ansiedad fisiológica (R2=0,10, p<0,01), motora (R2=0,09, p<0,01) y cognitiva (R2=0,12, p<0,01). La Claridad predice negativamente la ansiedad motora (β=-0,131, p<0,01). Conclusiones: Engagement académico y AE se registran como variables independientes una de la otra, entre tanto, la Claridad emocional regula débilmente la ansiedad motora. Factores cognitivos y situacionales al momento de realizar exámenes son relevantes en el desencadenamiento de la respuesta ansiosa.

Abstract Introduction: Test Anxiety (TA) is common among university students and involves cognitive, motor, and physiological manifestations of tension and permanent concern about exams that may affect their academic performance. Objective: Assess whether engagement, emotional intelligence and factors associated with academic test solving predict the manifestations of TA in a sample of 400 university students. Method: Using a cross-sectional predictive design, engagement (Vigor, Dedication, Absorption), emotional intelligence (Attention, Clarity, Repair) and several factors related to academic test solving were evaluated, analyzing their relationship with the manifestations of TA, and categorical regression models were constructed to define the predictive level of the variables. Results: The relationship between engagement and TA was discarded (p>0,05) while Clarity and Repair were inversely associated with TA manifestations, except the physiological ones. Different factors associated with exams such as professor control, fear of exams and the question type predict physiological (R2=0,10, p<0,01), motor (R2=0,09, p<0,01) and cognitive (R2=0,12, p<0,01) anxiety responses. Clarity predicts motor anxiety (β=-0,131, p<0,01) negatively. Conclusions: Academic engagement and TA are registered as independent variables of each other; meanwhile, emotional Clarity regulates motor anxiety weakly. Cognitive and situational factors at the time of exams are relevant in the triggering of the anxious response.

Predictores de la ansiedad ante la estadística: Ansiedad ante los exámenes y baja depuración cognitiva / Statistics anxiety is predicted by test anxiety and lack of cognitive depuration

Las competencias en estadística responden al desarrollo de habilidades esenciales para la comprensión de la realidad y la toma de decisiones personales y profesionales. Un gran número de profesiones emplea la estadística como elemento esencial en investigación y análisis de información, pero también es común la respuesta de ansiedad ante estos contenidos. El objetivo de este estudio fue analizar las estrategias metacognitivas implicadas en procesos de ansiedad ante la estadística, así como el papel de la ansiedad ante los exámenes en este fenómeno. Se analizó una muestra de universitarios habituados al tratamiento de información cuantitativa, en ellos se observaron bajos niveles de estrategias metacognitivas para el aprendizaje y niveles moderados de ansiedad. En un modelo de regresión se identificó que la ansiedad estadística se predice débilmente por la falta de depuración y fuertemente por la ansiedad ante los exámenes

Statistics competencies respond to the development of essential skills for understanding reality and making personal and professional decisions. A lot of professions use statistics as an essential element in research and information analysis, but anxiety about statistical content is also common. The objective of this study was to analyze the metacognitive strategies involved in processes of statistics anxiety, as well as the role of test anxiety in this phenomenon. We analyzed a sample of university students accustomed to the treatment of quantitative information, in which low levels of metacognitive strategies for learning and moderate levels of anxiety were observed. In a regression model, it was identified that statistics anxiety is weakly predicted due to the lack of depuration and strongly by test anxiety

New Insights into the Genetics of Fetal Megacystis: ACTG2 Mutations, Encoding γ-2 Smooth Muscle Actin in Megacystis Microcolon Intestinal Hypoperistalsis Syndrome (Berdon Syndrome).

OBJECTIVE: To identify the molecular basis for prenatally suspected cases of megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) (MIM 249210) in 3 independent families with clinical and radiographic evidence of MMIHS. METHODS: Whole-exome sequencing (WES) and Sanger sequencing of the ACTG2 gene. RESULTS: We identified a novel heterozygous de novo missense variant in ACTG2 c.770G>A (p.Arg257His) encoding x03B3;-2 smooth muscle actin (ACTG2) in 2 siblings with MMIHS, suggesting gonadal mosaicism of one of the parents. Two additional de novo missense variants (p.Arg257Cys and p.Arg178His) in ACTG2 were identified in 2 additional MMHIS patients. All of our patients had evidence of fetal megacystis and a normal or slightly increased amniotic fluid volume. Additional findings included bilateral renal hydronephrosis, an enlarged fetal stomach, and transient dilated bowel loops. ACTG2 immunostaining of the intestinal tissue showed an altered muscularis propria, a markedly thinned longitudinal muscle layer, and a reduced amount and abnormal distribution of ACTG2. CONCLUSION: Our study demonstrates that de novo mutations in ACTG2 are a cause of fetal megacystis in MMIHS and that gonadal mosaicism may be present in a subset of cases. These findings have implications for the counseling of families with a diagnosis of fetal megacystis with a preserved amniotic fluid volume and associated gastrointestinal findings.

Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR and LMBRD1 Genes.

Disorders of cobalamin deficiency are a heterogeneous group of disorders with at least 19 autosomal recessive-associated genes. Familial samples of an infant who died due to presumed cobalamin deficiency were referred for clinical exome sequencing. The patient died before obtaining a blood sample or skin biopsy, autopsy was declined, and DNA yielded from the newborn screening blood spot was insufficient for diagnostic testing. Whole-exome sequencing of the mother, father, and unaffected sister and tailored bioinformatics analysis was applied to search for mutations in underlying disorders with recessive inheritance. This approach identified alterations within two genes, each of which was carried by one parent. The mother carried a missense alteration in the MTR gene (c.3518C>T; p.P1173L) which was absent in the father and the sister. The father carried a translational frameshift alteration in the LMBRD1 gene (c.1056delG; p.L352Lfs*18) which was absent in the mother and present in the heterozygous state in the sister. These mutations in the MTR (MIM# 156570) and LMBRD1 (MIM# 612625) genes have been described in patients with disorders of cobalamin metabolism complementation groups cblG and cblF, respectively. The child's clinical presentation and biochemical results demonstrated overlap with both cblG and cblF. Sanger sequencing using DNA from the infant's blood spot confirmed the inheritance of the two alterations in compound heterozygous form. We present the first example of exome sequencing leading to a diagnosis in the absence of the affected patient. Furthermore, the data support the possibility for potential digenic inheritance associated with cobalamin deficiency.

Expanding the clinical and mutational spectrum of Kaufman oculocerebrofacial syndrome with biallelic UBE3B mutations.

Biallelic mutations of UBE3B have recently been shown to cause Kaufman oculocerebrofacial syndrome (also reported as blepharophimosis-ptosis-intellectual disability syndrome), an autosomal recessive condition characterized by hypotonia, developmental delay, intellectual disability, congenital anomalies, characteristic facial dysmorphic features, and low cholesterol levels. To date, six patients with either missense mutations affecting the UBE3B HECT domain or truncating mutations have been described. Here, we report on the identification of homozygous or compound heterozygous UBE3B mutations in six additional patients from five unrelated families using either targeted UBE3B sequencing in individuals with suggestive facial dysmorphic features, or exome sequencing. Our results expand the clinical and mutational spectrum of the UBE3B-related disorder in several ways. First, we have identified UBE3B mutations in individuals who previously received distinct clinical diagnoses: two sibs with Toriello-Carey syndrome as well as the patient reported to have a "new" syndrome by Buntinx and Majewski in 1990. Second, we describe the adult phenotype and clinical variability of the syndrome. Third, we report on the first instance of homozygous missense alterations outside the HECT domain of UBE3B, observed in a patient with mildly dysmorphic facial features. We conclude that UBE3B mutations cause a clinically recognizable and possibly underdiagnosed syndrome characterized by distinct craniofacial features, hypotonia, failure to thrive, eye abnormalities, other congenital malformations, low cholesterol levels, and severe intellectual disability. We review the UBE3B-associated phenotypes, including forms that can mimick Toriello-Carey syndrome, and suggest the single designation "Kaufman oculocerebrofacial syndrome".

Congenital lethal motor neuron disease with a novel defect in ribosome biogenesis.

OBJECTIVE: We describe a novel congenital motor neuron disease with early demise due to respiratory insufficiency with clinical overlap with spinal muscular atrophy with respiratory distress (SMARD) type 1 but lacking a mutation in the IGHMBP2 gene. METHODS: Exome sequencing was used to identify a de novo mutation in the LAS1L gene in the proband. Pathogenicity of the mutation was validated using a zebrafish model by morpholino-mediated knockdown of las1l. RESULTS: We identified a de novo mutation in the X-linked LAS1L gene in the proband (p.S477N). The mutation is in a highly conserved region of the LAS1L gene predicted to be deleterious by bioinformatic analysis. Morpholino-based knockdown of las1l, the orthologous gene in zebrafish, results in early lethality and disruption of muscle and peripheral nerve architecture. Coinjection of wild-type but not mutant human RNA results in partial rescue of the phenotype. CONCLUSION: We report a patient with a SMARD phenotype due to a mutation in LAS1L, a gene important in coordinating processing of the 45S pre-rRNA and maturation of the large 60S ribosomal subunit. Similarly, the IGHMB2 gene associated with SMARD type 1 has been suggested to have an important role in ribosomal biogenesis from its role in processing the 45S pre-rRNA. We propose that disruption of ribosomal maturation may be a common pathogenic mechanism linking SMARD phenotypes caused by both IGHMBP2 and LAS1L.

Patient decisions for disclosure of secondary findings among the first 200 individuals undergoing clinical diagnostic exome sequencing.

PURPOSE: Exome sequencing of a single individual for a clinical indication may result in the identification of incidental deleterious variants unrelated to the indication for testing (secondary findings). Given the recent availability of clinical exome testing, there is a limited knowledge regarding the disclosure preferences and impact of secondary findings in a clinical diagnostic setting. In this article, we provide preliminary data regarding the preferences for secondary findings results disclosure based on the first 200 families referred to Ambry Genetics for diagnostic exome sequencing. METHODS: Secondary findings were categorized into four groups in the diagnostic exome sequencing consent: carrier status of recessive disorders, predisposition to later-onset disease, predisposition to increased cancer risk, and early-onset disease. In this study, we performed a retrospective analysis of patient responses regarding the preferences for secondary findings disclosure. RESULTS: The majority of patients (187/200; 93.5%) chose to receive secondary results for one or more available categories. Adult probands were more likely than children to opt for blinding of secondary data (16 vs. 4%, respectively). Among responses for blinding, preferences were evenly scattered among categories. CONCLUSION: These data represent the unprecedented results of a large reference laboratory providing clinical exome sequencing. We report, for the first time, the preferences of patients and families for the receipt of secondary findings based on clinical genome sequencing. Overwhelmingly, families undergoing exome sequencing opt for the disclosure of secondary findings. The data may have implications regarding the development of guidelines for secondary findings reporting among patients with severe and/or life-threatening disease undergoing clinical genomic sequencing.

A human de novo mutation in MYH10 phenocopies the loss of function mutation in mice.

We used whole exome sequence analysis to investigate a possible genetic etiology for a patient with the phenotype of intrauterine growth restriction, microcephaly, developmental delay, failure to thrive, congenital bilateral hip dysplasia, cerebral and cerebellar atrophy, hydrocephalus, and congenital diaphragmatic hernia (CDH). Whole exome sequencing identified a novel de novo c.2722G > T (p.E908X) mutation in the Myosin Heavy Chain 10 gene (MYH10) which encodes for non-muscle heavy chain II B (NMHC IIB). Mutations in MYH10 have not been previously described in association with human disease. The E908X mutation is located in the coiled-coil region of the protein and is expected to delete the tail domain and disrupt filament assembly. Nonmuscle myosin IIs (NM IIs) are a group of ubiquitously expressed proteins, and NM II B is specifically enriched in neuronal tissue and is thought to be important in neuronal migration. It is also expressed in cardiac myocytes along with NM IIC. Homozygous NMHC II B-/B- mouse knockouts die by embryonic day (E)14.5 with severe cardiac defects (membranous ventricular septal defect and cardiac outflow tract abnormalities) and neurodevelopmental disorders (progressive hydrocephalus and neuronal migrational abnormalities). A heterozygous MYH10 loss of function mutation produces a severe neurologic phenotype and CDH but no apparent cardiac phenotype and suggests that MYH10 may represent a novel gene for brain malformations and/or CDH.

Mutation in SNAP25 as a novel genetic cause of epilepsy and intellectual disability.

Whole exome sequencing using a parent-child trio design to identify de novo mutations provides an efficient method to identify novel genes for rare diseases with low reproductive fitness that are difficult to study by more classical genetic methods of linkage analysis. We describe a 15 y old female with severe static encephalopathy, intellectual disability, and generalized epilepsy. After extensive metabolic and genetic testing, whole exome sequencing identified a novel de novo variant in Synaptosomal-associated protein-25 (SNAP25), c.142G > T p.Phe48Val alteration. This variant is predicted to be damaging by all prediction algorithms. SNAP25 is part of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein complex which is involved in exocytotic release of neurotransmitters. Genetic alterations in Snap25 in animal models can cause anxiety-related behavior, ataxia and seizures. We suggest that SNAP25 mutations in humans are a novel genetic cause of intellectual disability and epilepsy.

[A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams]. / Estudo retrospectivo dos níveis de ácido hipúrico urinário em exames de toxicologia ocupacional.

Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams). Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant difference was found in individuals grouped according to their status in each of the established intervals, their reference numbers, and maximum biological levels allowed. Hippuric acid levels detected indicate low risk of toluene exposure for the population under evaluation, probably due to a growing concern with the deployment of measures regarding occupational hygiene.

Estudo retrospectivo dos níveis de ácido hipúrico urinário em exames de toxicologia ocupacional / A retrospective study analysis of urinary hippuric acid levels in occupational toxicology exams

O ácido hipúrico é o principal metabólito do tolueno, solvente amplamente utilizado em processos industriais e com importantes efeitos tóxicos, fato que justifica a preocupação em monitorar regularmente sujeitos com risco de exposição ocupacional a este solvente. O objetivo deste trabalho foi avaliar os níveis de ácido hipúrico encontrados em trabalhadores submetidos à monitorização biológica. Foi realizado um estudo retrospectivo com dados dos anos de 2002 a 2005, no qual foram analisados os resultados e a situação do empregado na oportunidade do exame (periódico, demissional e admissional). Os resultados indicam uma redução significativa nos níveis de ácido hipúrico em 2005. Exames periódicos obtiveram resultados superiores aos exames admissionais e demissionais, e não foi verificada diferença significativa nas proporções dos sujeitos agrupados de acordo com a situação funcional em cada um dos intervalos estabelecidos segundo o valor de referência e o índice biológico máximo permitido. Os níveis de ácido hipúrico detectados indicam um baixo de risco de exposição ao tolueno na população avaliada, provavelmente em decorrência da preocupação crescente com a implantação de medidas de higiene ocupacional.

Hippuric acid is the primary metabolite of toluene, a solvent widely used in industrial processes with considerable toxic effects, a fact which justifies regularly monitoring individuals with occupational exposure to this solvent. This work aims at evaluating urinary hippuric acid levels found in workers subject to biological monitoring. A retrospective study was carried out with data referring from 2002 to 2005, in which exams results and employment status were analyzed (periodic, post-employment, and pre-employment exams). Results indicate a significant reduction in hippuric acid levels for 2005. Periodic exams presented higher results than pre-employment and post-employment exams. No significant difference was found in individuals grouped according to their status in each of the established intervals, their reference numbers, and maximum biological levels allowed. Hippuric acid levels detected indicate low risk of toluene exposure for the population under evaluation, probably due to a growing concern with the deployment of measures regarding occupational hygiene.

Beyond Li Fraumeni Syndrome: clinical characteristics of families with p53 germline mutations.

PURPOSE: A clinical testing cohort was used to gain a broader understanding of the spectrum of tumors associated with germline p53 mutations to aid clinicians in identifying high-risk families. PATIENTS AND METHODS: Full sequencing of the coding exons (2 to 11) and associated splice junctions of the p53 gene was performed on 525 consecutive patients whose blood samples were submitted for diagnostic testing. Clinical features of p53 germline carriers in this cohort were characterized, clinical referral schemes based on reported p53-associated family phenotypes were evaluated, and practical mutation prevalence tables were generated. RESULTS: Mutations were identified in 91 (17%) of 525 patients submitted for testing. All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC). Every individual with a choroid plexus tumor (eight of eight) and 14 of 21 individuals with a childhood ACC had a mutation regardless of family history. Based on reported personal and family history, 95% of patients (71 of 75) with a mutation met either classic Li Fraumeni syndrome (LFS) or Chompret criteria. A simplified prevalence table provides a concise summary of individual and family characteristics associated with p53 mutations. CONCLUSION: This is, to our knowledge, the largest single report of diagnostic testing for germline p53 mutations, yielding practical mutation prevalence tables and suggesting clinical utility of classic LFS and Chompret criteria for identifying a subset of cancer-prone families with p53 germline mutations, with important implications for diagnosis and management.

Somatic microindels in human cancer: the insertions are highly error-prone and derive from nearby but not adjacent sense and antisense templates.

Somatic microindels (microdeletions with microinsertions) have been studied in normal mouse tissues using the Big Blue lacI transgenic mutation detection system. Here we analyze microindels in human cancers using an endogenous and transcribed gene, the TP53 gene. Microindel frequency, the enhancement of 1-2 microindels and other features are generally similar to that observed in the non-transcribed lacI gene in normal mouse tissues. The current larger sample of somatic microindels reveals recurroids: mutations in which deletions are identical and the co-localized insertion is similar. The data reveal that the inserted sequences derive from nearby but not adjacent sequences in contrast to the slippage that characterizes the great majority of pure microinsertions. The microindel inserted sequences derive from a template on the sense or antisense strand with similar frequency. The estimated error rate of the insertion process of 13% per bp is by far the largest reported in vivo, with the possible exception of somatic hypermutation in the immunoglobulin gene. The data constrain possible mechanisms of microindels and raise the question of whether microindels are 'scars' from the bypass of large DNA adducts by a translesional polymerase, e.g. the 'Tarzan model' presented herein.

p53 Testing for Li-Fraumeni and Li-Fraumeni-like syndromes.

Li-Fraumeni Syndrome (LFS; OMIM #151623) is an autosomal dominant cancer predisposition syndrome characterized by early onset tumors including sarcomas, breast cancer, leukemia, brain tumors, and adrenocortical carcinoma. Li-Fraumeni syndrome is primarily attributed to germline mutations in the p53 tumor suppressor gene, which encodes tumor protein 53. In addition to germline p53 mutations, the p53 gene is the most commonly mutated gene in human cancers, with as much as 50% of tumors containing somatic p53 mutations. This unit provides a protocol to perform germline mutation analysis of the p53 gene. The protocol includes steps for amplification and sequencing of the entire coding region of the p53 gene (exons 2 to 11). The protocol was designed for detecting germline alterations from DNA extracted from blood; however, with some additional optimization, it could also be used to detect somatic mutations in DNA extracted from tumors.

Evidence for mutation showers.

Mutants in the Big Blue transgenic mouse system show spontaneous clustered multiple mutations with unexpectedly high frequency, consistent with chronocoordinate events. We tested the prediction that the multiple mutations seen within the lacI mutation target sometimes occur in the context of chronocoordinate multiple mutations spanning multiple kilobases (mutation showers). Additional sequencing of mutants was performed in regions immediately flanking the lacI region (total of 10.7 kb). Nineteen additional mutations were found outside the lacI region ("ectomutations") from 10 mutants containing two or more lacI mutations, whereas only one ectomutation was found in 130 mutants with a single mutation (P < 0.0001). The mutation showers had an average of approximately one mutation per 3 kb. Four mutants showed closely spaced double mutations in the new sequence, and analysis of the spacing between these mutations revealed significant clustering (P = 0.0098). To determine the extent of the mutation showers, regions (8.5 kb total) remote from the lacI region (approximately 16-17 kb away) were sequenced. Only two additional ectomutations were found in these remote regions, consistent with mutation showers that generally do not extend more than approximately 30 kb. We conclude that mutation showers exist and that they constitute at least 0.2% and possibly 1% or more of mutational events observed in this system. The existence of mutation showers has implications for oncogenesis and evolution, raising the possibilities of "cancer in an instant" and "introns as sponges to reduce the deleterious impact of mutation showers."