Publications

We present correlation coefficient estimates between a number of ground motion intensity measures ( IMs), as measured from the NGA-West2 database, with focus on the correlation of vertical–vertical and vertical–horizontal ground motion components. The IMs considered include spectral accelerations with periods from 0.01 to 10 s, peak ground acceleration, peak ground velocity, and significant duration (for 5%–75% and 5%–95% definitions). To facilitate their use, parametric equations are also fitted to the correlation models. Finally, the dependence of the obtained correlation coefficients to magnitude, distance, and Vs 30 is evaluated.

Background: Glucocorticoid resistance is often a result of mutations in the human glucocorticoid receptor α (hGRα) gene, which impair one or more of hGRα's functions. We investigated the molecular mechanisms through which two previously described mutant receptors, hGRαR477H and hGRαG679S, with amino acid substitutions in the DNA- and ligand-binding domains, respectively, affect glucocorticoid signal transduction. Methods and Results: In transient transfection assays, hGRαR477H displayed no transcriptional activity, whereas hGRαG679S showed a 55% reduction in its ability to stimulate the transcription of the glucocorticoid-responsive mouse mammary tumor virus promoter in response to dexamethasone compared with the wild-type hGRα. Neither hGRαR477H nor hGRαG679S exerted a dominant negative effect upon the wild-type receptor. Dexamethasone binding assays showed that hGRαR477H preserved normal affinity for the ligand, whereas hGRαG679S displayed a 2-fold reduction compared with hGRα. Nuclear translocation studies confirmed predominantly cytoplasmic localization of the mutant receptors in the absence of ligand. Exposure to dexamethasone resulted in slower translocation of hGRαR477H (25 min) and hGRαG679S (30 min) into the nucleus than the wild-type hGRα (12 min). In chromatin immunoprecipitation assays in cells stably transfected with the mouse mammary tumor virus promoter, hGRαR477H did not bind to glucocorticoid-response elements, whereas hGRαG679S preserved its ability to bind to glucocorticoid-response elements. Finally, in glutathione-S-transferase pull-down assays, hGRαG679S interacted with the glucocorticoid receptor-interacting protein 1 coactivator in vitro only through its activation function (AF)-1, unlike the hGRαR477H and hGRα, which interacted with the glucocorticoid receptor-interacting protein 1 through both their AF-1 and AF-2. Conclusions: The natural mutants hGRαR477H and hGRαG679S cause generalized glucocorticoid resistance by affecting different functions of the glucocorticoid receptor, which span the cascade of the hGR signaling system.

Abstract As the rate of obesity and the incidence of diabetes mellitus have been increasing, diabetic neuropathy has become the most common cause of peripheral neuropathy in developed countries. In addition, a variety of pathogenetically heterogeneous disorders can lead to impairment of the peripheral nervous system including amyloidosis, vitamin deficiencies, uremia and lipid disorders, alcohol abuse, autoimmune and infectious diseases as well as exposure to environmental toxins. We have noted that a combination of these disorders may aggravate the manifestations of peripheral diabetic neuropathy, an effect, which is most pronounced when metabolic and non-metabolic pathologies lead to cumulative damage. Current treatment options are limited and generally have unsatisfactory results in most patients. Therapeutic apheresis (INUSpherese®) allows the removal of metabolic, inflammatory, immunologic and environmental contributors to the disease process and may be an effective treatment option. We reviewed the developments in therapeutic apheresis for metabolic and non-metabolic peripheral neuropathy, including the current literature as well as data from our university diabetes center.

The objective of the study was to evaluate the long-term effect of GnRH analog (GnRHa) treatment on final height (FH), body mass index (BMI), body composition, bone mineral density (BMD), and ovarian function.Ninety-two females, evaluated in adulthood, were categorized as follows: group A, 47 girls with idiopathic central precocious puberty (33 GnRHa treated and 14 nontreated); group B, 24 girls with isolated GH deficiency (15 GnRHa and GH treated and nine GH treated); group C, 21 girls with idiopathic short stature (seven GnRHa and GH treated, seven GnRHa treated, and seven nontreated).FH, BMD, and percent fat mass of GnRHa-treated patients in all three groups were comparable with those of the respective nontreated subjects. BMI values of GnRHa-treated and nontreated subjects in groups A and C were comparable, whereas in group B, a higher BMI was found in subjects treated only with GH. Nontreated patients with ICPP had greater maximal ovarian volumes, higher LH and LH to FSH ratio, and more severe hirsutism than GnRHa-treated ones. Menstrual cycle characteristics were not different between treated and nontreated subjects. The prevalence of polycystic ovary syndrome in treated and untreated girls with ICPP was comparable, whereas in the entire cohort, it was 11.1% in GnRHa treated and 32.1% in the untreated (P = 0.02).Girls treated in childhood with GnRHa have normal BMI, BMD, body composition, and ovarian function in early adulthood. FH is not increased in girls with ICPP in whom GnRHa was initiated at about 8 yr. There is no evidence that GnRHa treatment predisposes to polycystic ovary syndrome or menstrual irregularities.

Nerve Growth Factor (NGF) is crucial for the functional accuracy of the cholinergic neurons in the central nervous system and for the growth and phenotypic maintenance of neurons in the peripheral nervous system. PURPOSE: We investigated the acute and chronic effects of a swimming training season of young athletes on serum NGF, both at rest and after a maximal exercise bout. METHODS: Eleven well-trained male swimmers (14.08 ± 1.0 yrs) participated in the study. Measurements were carried out at the beginning of the training season (T1) as well as pre- and post- taper of each of the two competitive periods (i.e., T2, T3 for the first macrocycle, and T4, T5 for the second macrocycle, respectively). Blood samples were drawn at pre- and 1 hour post a maximal, 400 m swimming testing. Serum NGF levels were measured by ELISA. Adjustment for exercise-induced plasma volume changes was performed before data analysis. Two-way ANOVA with repeated measures was used for statistics. RESULTS: Rest NGF values were not significantly different throughout the experimental period, although there was a tendency for them to increase from T1 to T5 (56%: T1 15.56 ± 1.4 vs T5 24.23 ± 5.6; p > 0.05). No significant differences were found among the post 400 m testing timepoints or between pre-post testing (p > 0.05) (T1: 15.56 ± 1.4 vs 19.31 ± 5.0; p > 0.05, T2: 15.16 ± 1.9 vs 14.35 ± 1.7; p > 0.05, T3: 16.34 ± 1.3 vs 13.99 ± 1.8; p > 0.05, T4: 16.81 ± 1.7 vs 17.18 ± 2.3; p > 0.05, T5: 24.23 ± 5.6 vs 18.27 ± 2.8; p > 0.05). CONCLUSIONS: This data suggest that long-term swimming training may affect the resting concentrations of circulating NGF in young swimmers. More studies are needed to further examine the NGF responses at different timepoints during the recovery period after acute bout(s) of swimming exercise.

To critically assess the effectiveness of complementary/alternative medicine modalities, comprising body/mind stress-releasing techniques, on the breastfeeding (BF) success of mothers of full-term newborns.Literature review in Medline and other available database sources until December 2015, and critical analysis of pooled data. The study selection included randomized-controlled trials, case-control studies, and case series.The total number of analyzed studies was 9. Among them, three represented level-I, two level-II, one level-III, and three level-IV evidence. The pooled maternal population was 2135. Interventions that could influence cognition management seem effective in improving BF initiation and duration (strength of recommendation B), manual relaxation techniques in promoting BF initiation (strength of recommendation B), and auditory-mediated mind guidance in promoting BF duration (strength of recommendation C). The implementation of environmental sensory stimulations improves maternal perception about breastfeeding practice (strength of recommendation C).Certain methods of complementary and alternative medicine show positive effect on breastfeeding. Further studies with good quality evidence, dedicated follow-up of the families after discharge, and strict definitions of breastfeeding and weaning are necessary to confirm the effectiveness of the identified interventions.

Pediatric thrombosis (PT) represents a rare condition that can manifest from neonatal life to adolescence, encompassing life-threatening complications. Its pathogenesis is attributed to immature hemostasis in conjunction with environmental and genetic factors, predominantly including those resulting in increased levels of plasminogen activator inhibitor 1 (PAI-1), the principal inhibitor of fibrinolysis, which is subject to upstream regulation by angiotensin-converting enzyme (ACE). Although the implication of microRNAs (miRNAs), epigenetic modulators of gene expression, has been demonstrated in adult thrombosis, evidence is lacking in the pediatric setting. Here, we investigated the involvement of two miRNA regulators of PAI-1 (<i>SERPINE1</i> gene) in PT, in relation to clinical and genetic parameters that induce PAI-1 fluctuations. Following bioinformatic target-prediction, miRNA expression was assessed by quantitative real-time PCR in serum-samples of 19 pediatric patients with thrombosis (1-18 months post-incident), and 19 healthy controls. Patients were genotyped for the <i>SERPINE1</i>-4G/5G and <i>ACE</i>-I/D polymorphisms by PCR-based assays. Genotypic and thrombosis-related clinical data were analyzed in relation to miRNA-expression. Two miRNAs (miR-145-5p, miR-34a-5p) were identified to target <i>SERPINE1</i> mRNA, with miR-34a additionally targeting the mRNA of <i>ACE</i>. The expression of miR-34a was significantly decreased in patients compared to controls (<i>p</i> = 0.029), while no difference was observed in miR-145 expression. Within patients, miR-34a expression demonstrated a peak 1-3 months post-thrombosis and was diminished upon treatment completion (<i>p</i> = 0.031), followed by a slight long-term increase. MiR-34a levels differed significantly by thrombosis site (<i>p</i> = 0.019), while a significant synergistic interaction between site and onset type (provoked/unprovoked) was detected (<i>p</i> = 0.016). Finally, an epistatic modification was observed in cerebral cases, since double homozygosity (4G/4G + D/D) led to a miR-34 decrease, with D/D carriership reversing the 4G/4G-induced upregulation of miR-34a (<i>p</i> = 0.006). Our findings suggest that in pediatric thrombosis, downregulation of miR-34a is indicative of impaired fibrinolytic capacity, attributed to deficient regulation of the inhibitory ACE/PAI-1 axis.

Prolonged elevations of glucocorticoids have been linked to the effective disturbances experienced by patients with Cushing's syndrome. Major depression has been most commonly reported in patients with endogenous Cushing's syndrome. The purpose of this study was to determine whether these patients experience melancholic or 'atypical' subtype depression and to determine relations between current psychological functioning and factors such as duration and severity of Cushing's syndrome.We examined 33 adult patients with documented Cushing's syndrome and 17 hospitalized, matched controls, using standardized structured interviews and tests.During the active phase of Cushing's syndrome (prior to and/or on admission), 66.7% of all patients reported histories meeting criteria for a psychiatric diagnosis. Of those with a diagnosis during Cushing's syndrome, 50% reported major depression. Upon presentation to this institution, atypical depression was the most common diagnosis involving 51.5% (n =17) of all enrolled patients. Of the 17 with atypical depression, 8 reported a co-morbid psychiatric disorder. The duration of Cushing's syndrome was an important factor in predicting whether patients sought psychological intervention or met criteria for psychiatric diagnosis.Patients with active endogenous Cushing's syndrome exhibit significant psychopathology expressed primarily by atypical depression. Longer duration of Cushing's syndrome may place them at increased risk of such psychopathology.

A bstract : Glucocorticoids regulate diverse functions important for the maintenance of central nervous system, cardiovascular, metabolic, and immune homeostasis. The actions of these hormones are mediated by the specific intracellular glucocorticoid receptors (GRs). Pathologic conditions associated with changes of tissue sensitivity to these hormones have been described. The syndrome of familial/sporadic glucocorticoid resistance is characterized by hypercortisolism without Cushing syndrome stigmata. Many of the patients present with hypertension, with or without hypokalemic alkalosis, as a result of elevated concentrations of cortisol and other salt‐retaining steroids. The molecular defects of 4 kindreds and one sporadic case have been elucidated as inactivating mutations in the ligand‐binding domain of the GR. In two patients in whom the GR was mutated at amino acid isoleucine 559 to aspartic acid (GRαI559N) and isoleucine 747 to methionine (GRαI747M), respectively, glucocorticoid resistance developed at the heterozygous state, with transdominant negative activity of each of the mutant receptors upon the wild‐type protein. Retention of the wild‐type receptor in the cytoplasm by the mutant receptor was found in the former, while inappropriate accumulation of p160‐type coactivators on the promoter region of glucocorticoid‐responsive genes, because of a defective interaction between the AF2 region of the mutant receptor and the LXXLL motif of the coactivators, was determined in the latter. These results suggest that the pathologic mechanisms of glucocorticoid resistance is quite broad, and this is reflected in the wide variability of the clinical picture in patients with the syndrome.