Modern molecular study of weight gain related to antidepressant treatment: clinical implications of the pharmacogenetic testing.

Antidepressant medication influences cellular lipogenesis, being associated with metabolic side effects including weight gain. Due to the increasing use of antidepressants in children and adolescents, their metabolic and endocrine adverse effects are of particular concern, especially within this pediatric population that appears to be at greater risk. Genetic factors with a possible influence on antidepressant's adverse effects include CYP [cytochrome P450 (CYP450)] polymorphisms. We target to evaluate the efficacy of the pharmacogenetic testing, when prescribing antidepressants, in correlation with the occurrence of adverse events and weight gain. Our research was performed between the years 2010 and 2016, in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania. We recruited 80 patients, children and adolescents with depressive disorders. Our study sample was divided in two groups: G1 - 40 patients took treatment after pharmacogenetic testing, and G2 - 40 patients without pharmacogenetic testing before the treatment election. Our results show statistically significant differences concerning the weight gain for groups G1 (with pharmacogenetic testing) and G2 (without pharmacogenetic testing). The CYP genotype and the pharmacogenetic testing, for choosing the personalized antidepressant therapy in children and adolescents with depressive disorders, proved to be good predictors for the response to antidepressants and the side effects registered, especially for weight gain. The significant correlations between the CYP polymorphisms for group G2 (without pharmacogenetic testing) and the weight gain/body mass index (BMI) increase, as major side effects induced by antidepressants, proved the fact that the pharmacogenetic screening is needed in the future clinical practice, allowing for individualized, tailored treatment, especially for at-risk pediatric categories.

Expression and significance of Ki-67 in lung cancer.

Ki-67 parameter is a proliferation marker in malignant tumors. The increased proliferation activity and the decreased prognosis in lung cancer determined us to investigate different parameters connected to the tumor's aggression, such as cellularity, Ki-67 positivity rate, and proliferating cell nuclear antigen (PCNA). We evaluated the proliferative activity in 62 primary lung tumors by determining the cell's percentage of Ki-67 and immunoreactive PCNA (using MIB-1 and PCNA monoclonal antibodies), classifying Ki-67 and PCNA immunoreactivity into three score groups. The results obtained emphasized a linkage between Ki-67 score with the histological tumor subtype, tumor cellularity and degree of differentiation and with other proliferation immunohistochemistry (IHC) markers, such as p53 cellular tumor antigen. The tumor's cellularity, the Ki-67 positivity rate and PCNA, together with the clinical stage and the histological differentiation bring extra pieces of useful information in order to anticipate the evolution and the prognosis of lung cancer.

Integrative clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological correlations in depressive and anxiety disorders.

We approach the theme of modern treatment strategies, based on clinico-biological, pharmacogenetic, neuroimagistic, neuroendocrinological and psychological integrative correlations in the management of depressive and comorbid anxiety disorders. We target to evaluate the efficacy of the pharmacogenetic testing and the evolution, functioning of patients in correlation with specific neurobiological, neuroimagistic and neuroendocrinological markers. Our research was conducted between 2010-2016 on 80 children and adolescents with depressive and comorbid anxiety disorders - 40 children (G1 group), who benefited in choosing the pharmacotherapy from pharmacogenetic testing and 40 children without testing (G2 group). Also, the patients were evaluated through magnetic resonance (MR) spectroscopy at baseline and after pharmacotherapy. The efficacy of the chosen therapy in correlation with the pharmacogenetic testing was evaluated through the mean change in the CDRS (Children's Depression Rating Scale) total scores, in the CGI-S÷I (Clinical Global Impression - Severity÷Improvement), CGAS (Children's Global Assessment Scale) and through the change of the relevant neurobiological markers and MR spectroscopy metabolites. We evaluated the side effects through the PAERS (Pediatric Adverse Events Rating Scale)-Clinician. Our results show statistically significant differences of the clinical scores between the studied groups: for those subjects who benefited of pharmacogenetic testing, the CDRS, the global functioning scores prove a higher clinical improvement, a better compliance and lower PAERS side effects scores and also improvement concerning the MR spectroscopy dosed metabolites values. Our research was a proof sustaining the use of the pharmacogenetic testing in clinical practice and the value of investigating relevant neurobiological, neuroimagistic and neuroendocrinological markers for a personalized therapy in depressive disorders.

Health-related quality of life in patients with hallux valgus.

BACKGROUND AND AIMS: No deformity of the forefoot occurs more frequently than hallux valgus (HV), which is considered to be medial deviation of the first metatarsal and lateral deviation and rotation of the hallux, either with or without medial soft tissue enlargement of the metatarsal head. The HV deformity can lead to painful motion of the joint or difficulty in daily joint activity that often requires surgical correction. The aims of this study were to investigate the levels of foot pain and quality of life of patients with HV before and after surgery. Our study is focusing on imagistic investigations in HV, clinical aspects, specific treatment, foot pain levels, quality of life and general health before and after surgery. PATIENTS, MATERIALS AND METHODS: Our research was conducted in the period 2010-2015. We recruited 56 patients, 35 women and 21 men, age range 20 to 76 years, mean age 44.4 years, with HV (radiographic HV angle 25-40 and >40). We applied Visual Analogue Scales (VAS) for the foot pain and the Euro Quality of Life - five dimensions health questionnaire (EQ-5D). RESULTS: The results show statistically significant differences concerning the foot pain levels in VAS and also pain/discomfort, mobility and anxiety÷depression in the EQ-5D subscale in HV before and after surgery. The results prove high improvement of the scores of foot pain, discomfort, mobility and anxiety÷depression after surgery. Concerning the participation in usual activities and the self-care, the obtained results were not statistically significant. CONCLUSIONS: Our research was a proof that the surgery in HV represents a fruitful pathway of intervention and care and shows a high rate of success, favorable outcomes and improvement in quality of life of the patients.

Expression of E-cadherin in lung carcinoma, other than those with small cells (NSCLC).

It was suggested that the decrease and/or loss of E-cadherin expression in non-small cell lung cancer (NSCLC) is responsible for the development of the malignant phenotype. Moreover, clinical studies showed that the reduced expression of E-cadherin is associated with tumoral differentiation, with the presence of lymph node metastasis and with unfavorable diagnosis of patients with NSCLC. In order to evaluate if E-cadherin expression is involved in the NSCLC pathogenesis and significantly associated with clinicopathological parameters, we investigated the immunohistochemical (IHC) expression of E-cadherin in 47 lung carcinomas with tumoral resection pieces in the control peritumoral lung tissue, looking for possible correlations between the expression of this molecule and the clinicomorphological features and the evolutive prognosis of the patients. E-cadherin expression was preserved in 10 (21.28%) of the 47 NSCLCs immunostained with anti-E-cadherin antibody and reduced÷absent in 37 of the 47 (78.72%) NSCLCs studied. E-cadherin plays a major role in the intercellular adhesion. The reduced expression of E-cadherin indicates an unfavorable prognosis and can be a useful prognosis factor in NSCLC - for patients with reduced expression of the E-cadherin÷α-catenin complex, needing chemotherapy or radiotherapy.

The effect of neurobiological changes in the brain of children with schizophrenia, ultra high-risk for psychosis and epilepsy: clinical correlations with EEG and neuroimagistic abnormalities.

Relatively little research has been conducted on quantitative electroencephalography (QEEG) activity in patients with psychosis÷schizophrenia, especially in populations at-risk for the illness. Further studies are needed, in order to offer a possible endophenotypic marker of the cerebral functioning, associated with psychosis÷schizophrenia, in correlation with the neuroimaging, the neurocognitive, biochemical, molecular genetic tests, clinical aspects and the EEG activity from the same subjects. The aim was to investigate the role the QEEG abnormalities play in the etiology of psychosis÷schizophrenia, whether it can provide an endophenotype for psychosis and to make some correlations with the results obtained through magnetic resonance (MR) spectroscopy, for proper early detection and intervention. The prospective research was performed in the University Clinic of Child and Adolescent Psychiatry, Timisoara, Romania, involving 55 children with schizophrenia or ultra high-risk (UHR) for psychosis (groups 1, 2, 3 and 4) and 55 children as healthy controls (group 5). Groups 1 and 2 (28 children) are diagnosed with schizophrenia, groups 3 and 4 are UHR for psychosis (27 children), and group 5 represents healthy controls. Groups 1 and 3 had convulsive seizures in their personal history. We noticed: through the QEEG, numerous patterns of theta and delta activity, the diminished amplitude of the alpha band waves and the diminished alpha activity; also, the onset of psychosis was earlier at those presenting convulsive seizures in their personal history (groups 1 and 3); also, specific neuroimagistic abnormalities and modifications. The cerebral lesions, appearing during the development, raise the liability for schizophrenia. The high-risk for schizophrenia is correlated with the personal history of epilepsy, as well as with the family risk for psychosis.

Reversible arterial redistribution in a fetus with true umbilical cord knot: case report and review of literature.

Umbilical cord knot (UCK) affects around 1% of pregnancies and tightening of UCK is a very rare and highly unpredictable complication of pregnancy that can lead to fetal demise or neonatal death. The majority of authors agree that very little could be done to prevent fetal deaths in pregnancies with undiagnosed tight UCK. We herein report the case of a 39-year-old, gravidity five, parity three, pregnant woman at 40 weeks and five days age of pregnancy, whose pregnancy evolved without complications and who was admitted to hospital for the management of the birth. Although the last ultrasound examination before birth showed a reversible arterial redistribution in the fetus dependent on the postural status of the pregnant women and other factors associated with umbilical cord knot were present, the diagnosis was missed because of the factors' non-specificity. After a spontaneous labor without complications a dead male fetus, weight 3300 g, without heartbeat, Apgar score 0 was delivered. Macroscopic and microscopic findings confirmed that the cause of neonatal death was asphyxia caused by a tight UCK. The aim of our paper is to present the dramatic outcome of a pregnancy with a fetus with a tight umbilical cord knot (UCK), to bring to attention the signs that suggested the diagnosis, and to review the literature on this subject.