Role of the KCNJ Gene Variants in the Clinical Outcome of Type 1 Diabetes.

Diabetes is considered as a disease with a wide and continuous clinical spectrum, ranging from Type 1 (T1D) and Type 2 Diabetes (T2D) with complex multifactorial causes. In the last years, particular attention has been focused on the predictive value and therapeutic potential of single nucleotide polymorphisms (SNPs). SNPs can alter the seed-sequence in miRNA's loci and miRNA target sites causing changes in the structure and influencing the binding function. Only few studies have investigated the clinical influence of SNPs, in particular potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ) gene variants in T1D population. The aim of the study is to investigate the occurrence and the possible metabolic significance of KCNJ polymorphism in a group of pediatric patients with T1D. The study was performed in a cohort of 90 Caucasian children and adolescents with T1D and 93 healthy subjects. Rs5210 polymorphism has been analyzed with a prevalence of the GG genotype in the patient group suggesting its association with T1D. Therefore, a relationship was found between GG genotype and body mass index (BMI) at diagnosis and insulin requirement (IR) after 6 months. The study suggested an action for rs5210 in determining the metabolic features of T1D pediatric patients, by showing some clues of insulin resistance in patients carrying that polymorphism.

Comparison between CaGene 5.1 and 6.0 for BRCA1/2 mutation prediction: a retrospective study of 150 BRCA1/2 genetic tests in 517 families with breast/ovarian cancer.

During the past years, several empirical and statistical models have been developed to discriminate between carriers and non-carriers of germline BRCA1/BRCA2 (breast cancer 1, early onset/breast cancer 2, early onset) mutations in families with hereditary breast or ovarian cancer. Among these, the BRCAPRO or CaGene model is commonly used during genetic counseling, and plays a central role in the identification of potential carriers of BRCA1/2 mutations. We compared performance and clinical applicability of BRCAPRO version 5.1 vs version 6.0 in order to assess diagnostic accuracy of updated version. The study was carried out on 517 pedigrees of patients with familial history of breast or ovarian cancer, 150 of which were submitted to BRCA1/2 mutation screening, according to BRCAPRO evaluation or to criteria based on familial history. In our study, CaGene 5.1 was more sensitive than CaGene 6.0, although the latter showed a higher specificity. Both BRCAPRO versions better discriminate BRCA1 than BRCA2 mutations. This study evidenced similar performances in the two BRCAPRO versions even if the CaGene 6.0 has underestimated the genetic risk prediction in some BRCA mutation-positive families. Genetic counselors should recognize this limitation and during genetic counseling would be advisable to use a set of criteria in order to improve mutation carrier prediction.

Amniotic Fluid Stem Cells: A Novel Source for Modeling of Human Genetic Diseases.

In recent years, great interest has been devoted to the use of Induced Pluripotent Stem cells (iPS) for modeling of human genetic diseases, due to the possibility of reprogramming somatic cells of affected patients into pluripotent cells, enabling differentiation into several cell types, and allowing investigations into the molecular mechanisms of the disease. However, the protocol of iPS generation still suffers from technical limitations, showing low efficiency, being expensive and time consuming. Amniotic Fluid Stem cells (AFS) represent a potential alternative novel source of stem cells for modeling of human genetic diseases. In fact, by means of prenatal diagnosis, a number of fetuses affected by chromosomal or Mendelian diseases can be identified, and the amniotic fluid collected for genetic testing can be used, after diagnosis, for the isolation, culture and differentiation of AFS cells. This can provide a useful stem cell model for the investigation of the molecular basis of the diagnosed disease without the necessity of producing iPS, since AFS cells show some features of pluripotency and are able to differentiate in cells derived from all three germ layers "in vitro". In this article, we describe the potential benefits provided by using AFS cells in the modeling of human genetic diseases.

A new case of "de novo" BRCA1 mutation in a patient with early-onset breast cancer.

Most of the de novo BRCA1/2 mutations have been identified in patients with early-onset breast cancer and without family history of the disease. The identification of these alterations could play a prominent role in the prevention and treatment strategies and may influence clinical management of patients.

Understanding the pathology and treatment of traumatic brain injury and posttraumatic stress disorder: a therapeutic role for hyperbaric oxygen therapy.

Traumatic brain injury (TBI) is an intracranial injury caused by external trauma leading to different degrees of brain damage. TBI can cause a wide array of symptoms and range in severity from concussion to coma and death. The link between TBI and posttraumatic stress disorder (PTSD) has received increasing attention due to the high incidence of these conditions in soldiers returning from recent conflicts. TBI has been associated with an increased risk of PTSD. Additionally, TBI and PTSD often demonstrate overlapping symptoms. In this article, we discuss the different forms of TBI and their links to PTSD. We also discuss current therapies for TBI and PTSD, in particular detailing the therapeutic potential of hyperbaric oxygen therapy in the management of these conditions.