Linking Early Life Hypothalamic-Pituitary-Adrenal Axis Functioning, Brain Asymmetries, and Personality Traits in Dyslexia: An Informative Case Study.

Developmental dyslexia (DD) is a multi-system disorder, combining influences of susceptibility genes and environmental factors. The causative interaction between specific genetic factors, brain regions, and personality/mental disorders, as well as specific learning disabilities, has been thoroughly investigated with regard to the approach of developing a multifaceted diagnostic procedure with an intervention strategy potential. In an attempt to add new translational evidence to the interconnection of the above factors in the occurrence of DD, we performed a combinatorial analysis of brain asymmetries, personality traits, cognitive and learning skills, and expression profiles of selected genes in an adult, early diagnosed with DD, and in his son of typical development. We focused on the expression of genes, based on the assumption that the regulation of transcription may be affected by genetic and epigenetic factors. The results highlighted a potential chain link between neuroplasticity-related as well as stress-related genes, such as BDNF, Sox4, mineralocorticoid receptor (MR), and GILZ, leftward asymmetries in the amygdala and selective cerebellum lobules, and tendencies for personality disorders and dyslexia. This correlation may reflect the presence of a specific neuro-epigenetic component of DD, ensuing from the continuous, multifaceted difficulties in the acquisition of cognitive and learning skills, which in turn may act as a fostering mechanism for the onset of long-term disorders. This is in line with recent findings demonstrating a dysfunction in processes supported by rapid neural adaptation in children and adults with dyslexia. Accordingly, the co-evaluation of all the above parameters may indicate a stress-related dyslexia endophenotype that should be carefully considered for a more integrated diagnosis and effective intervention.

Measuring the stress of the surgeons in training and use of a novel interventional program to combat it.

PURPOSE: Stress poses a serious risk for training surgeons since their performance and well-being in reflected in patients' health. This study focuses on measuring the stress of training surgeons and at the same time evaluates prospectively the results of an innovative program that uses alternative techniques to combat the effects of stress. METHODS: The study was a pilot randomized controlled trial, with a duration of 6 months. Participants were allocated to a control and an intervention group. Trainees then completed three questionnaires, quality of life, perceived stress scale (PSS) and job content questionnaire serving as a baseline measurement. Only the intervention group used diaphragmatic breathing and progressive muscular relaxation techniques, twice a day, for 20 minutes each, and for a total period of eight weeks. At the end of the study, the same questionnaires were completed again by both groups. RESULTS: The sample of the study included 28 and 32 trainees in the control and the intervention group, respectively. The Cronbach's α value for the PSS stress-measuring questionnaire was 0.772. The intervention group presented statistically significant lower values of stress (30.50, P < 0.05) in comparison to the control group (27.54). CONCLUSION: The medical community, and especially surgeons, have been reluctant up to now to embrace interventional programs that go beyond the traditional use of medication in order to address stress related issues. The positive results and feedback from small studies, such as ours, can provide the driving force for further research that will give us solid, evidence-based, answers.

Thiopurine methyltransferase genotype and thiopurine S-methyltransferase activity in Greek children with inflammatory bowel disease.

BACKGROUND: Azathioprine (AZA) and 6-mercaptopurine (6MP) are used in the treatment of pediatric inflammatory bowel disease (IBD). Genetic variations in thiopurine S-methyltranfarase (TPMT) gene have been correlated with enzyme activity and with the occurrence of adverse events to AZA and 6MP. The aim of the present study was to examine the sensitivity and specificity of TPMT genotyping for TPMT enzymatic activity, reducing harm from thiopurine by pretesting, and the association of thiopurine toxicity with TPMT status in children with IBD. METHODS: TPMT red blood cell (RBC) activity was measured by using a radiochemical method and genotype was determined for the TPMT alleles *2, *3A, *3B and *3C in 108 thiopurinetreated pediatric IBD patients with a mean age of 11.3 years (range 3-16). RESULTS: Significant TPMT activity differences between wild-type and heterozygous and homozygous mutated subjects were observed. We divided TPMT activity into three categories according to frequency distribution: low (16.67%), intermediate (25.92%) and high (57.41%). The whole population included a total of 77.78% of homozygous wild-type subjects, 15.74% heterozygous variants, 1.85% homozygous variants and five (4.63%) compound heterozygous variant TPMT*3B/*3C. The overall concordance rate between TPMT genotypes and phenotypes was 88.2%. Seven carriers of at least one variant allele and low or intermediate TPMT activity developed adverse effects. CONCLUSIONS: Our findings suggest that carriers of at least one variant allele and both intermediate and absent TPMT activity have an increased risk of developing thiopurine-induced myelotoxicity compared with individuals with normal genotype and TPMT activity.