Publications

Stress has deleterious effects on brain health and yet, the prognostic value of psychosocial stress regarding the most common types of dementias, including Alzheimer disease, is still unclear. The primary aim of this systematic review was to explore the association between psychosocial stress and late onset dementia. We classified 24articles from Medline, PsycINFO, CINAHL, and Web of Science, as pertaining toxic categories of psychosocial and trauma-related stress (low socio-economic status [SES] related inequalities, marital status, posttraumatic stress disorder, work stress, “vital exhaustion” [VE], and, combined stressors). Using the Quality of Prognosis Studies in Systematic Reviews tool, we judged the quality of evidence to be low. This systematic review provided some non-robust, yet suggestive evidence that the above psychosocial types of stress are associated with increased risk of dementia in later life. Future robust, longitudinal studies with repeated validated measures of psychosocial stress and dementiaare required to strengthen or refute these findings.

ABSTRACT Vpr and selected mutants were used in a Saccharomyces cerevisiae two-hybrid screen to identify cellular interactors. We found Vpr interacted with 14-3-3 proteins, a family regulating a multitude of proteins in the cell. Vpr mutant R80A, which is inactive in cell cycle arrest, did not interact with 14-3-3. 14-3-3 proteins regulate the G 2 /M transition by inactivating Cdc25C phosphatase via binding to the phosphorylated serine residue at position 216 of Cdc25C. 14-3-3 overexpression in human cells synergized with Vpr in the arrest of cell cycle. Vpr did not arrest efficiently cells not expressing 14-3-3σ. This indicated that a full complement of 14-3-3 proteins is necessary for optimal Vpr function on the cell cycle. Mutational analysis showed that the C-terminal portion of Vpr, known to harbor its cell cycle-arresting activity, bound directly to the C-terminal part of 14-3-3, outside of its phosphopeptide-binding pocket. Vpr expression shifted localization of the mutant Cdc25C S216A to the cytoplasm, indicating that Vpr promotes the association of 14-3-3 and Cdc25C, independently of the presence of serine 216. Immunoprecipitations of cell extracts indicated the presence of triple complexes (Vpr/14-3-3/Cdc25C). These results indicate that Vpr promotes cell cycle arrest at the G 2 /M phase by facilitating association of 14-3-3 and Cdc25C independently of the latter's phosphorylation status.

Extracellular vesicles (EVs) are a heterogeneous group of lipid-bound vesicles released by cells into the extracellular space. EVs are an important mediator of intercellular communications and carry a wide variety of molecules that exert a biological function, such as lipids, nucleic acids, proteins, ions, and adenosine triphosphate (ATP). Extracellular vesicles are classified into microvesicles, exosomes, and apoptotic bodies depending on their biogenesis and size. Exosomes are spherical lipid-bilayer vesicles with a diameter of about 40 to 100 nm. Exosomes originate from intracellular endosomal compartments, while microvesicles originated directly from a cell’s plasma membrane and apoptotic bodies originate from cells undergoing apoptosis and are released via outward blebbing and fragmentation of the plasma membrane. Specifically, exosomes have garnered great attention since they display great potential as both biomarkers and carriers of therapeutic molecules.

The glucocorticoid receptor antagonist RU 486 has been used to treat the hypercortisolism of patients with nonpituitary Cushing's syndrome. Since endogenous cortisol production fluctuates in many patients with either the ectopic ACTH syndrome or adrenocortical tumors, treatment of these patients with a fixed dose of RU 486 introduces the risk of adrenal insufficiency. While RU 486 possesses some glucocorticoid agonist activity in addition to its potent antagonist effects, it is not known whether this intrinsic agonist activity is of sufficient magnitude to prevent adrenal insufficiency and sustain life. To answer this question three groups of bilaterally adrenalectomized cynomolgus monkeys (n = 5/group) were randomized to receive a daily injection of RU 486 (5 mg/kg.day), cortisol (1.25 mg/kg.day), or saline (placebo). All adrenalectomized monkeys received weekly im injections of deoxycorticosterone pivalate (1 mg) to prevent mineralocorticoid deficiency. Five sham-adrenalectomized monkeys served as controls and received im injections of saline (placebo). Blood was collected before adrenalectomy or sham operation and every 3 days postoperatively for measurement of serum electrolytes, blood urea nitrogen, and creatinine; plasma ACTH concentrations; and complete blood and differential cell counts. All sham-operated and cortisol-replaced adrenalectomized monkeys survived, and none developed overt biochemical evidence of adrenal insufficiency. All placebo and RU 486-replaced adrenalectomized monkeys expired within 33 days after adrenalectomy, presumably from adrenal insufficiency. These findings suggest that while RU 486 is a partial glucocorticoid agonist, its degree of glucocorticoid agonism is inadequate to prevent adrenal insufficiency and support life in adrenalectomized primates.

Given the heterogeneity of Attention-Deficit Hyperactivity Disorder (ADHD), there is a constant need for proper diagnosis, employing more accurate, efficient, patient-friendly, and clinician-friendly tools. We developed a Greek version of the National Institute for Children's Health Quality (NICHQ) Vanderbilt ADHD Diagnostic Parent Rating Scale (VADPRS) for follow-up assessment and examined its reliability and validity. A total of 100 schoolchildren (65 girls and 35 boys) between 7 and 12 years old with ADHD were included in the study. The internal consistency and test–retest reliability were examined via principal component analysis. Three-component structure in our study accounts for 74.63% of the tool's variance. The questions' loadings onto the factors and the internal reliability of the three factors were satisfactory. Finally, the reliability of all factors presented was found adequately high, confirming the high internal consistency of the items. Our results suggest that the Greek version of the VADPRS-follow-up may be used as an accurate psychometric instrument for the purposes of diagnosing ADHD. Furthermore, the combined use of the VADPRS-follow-up with other widely accepted tools, such as the ADHD Rating Scale-IV, may present clinical utility in collating parent information concerning the behavioural phenotype of their children.

No abstract is provided for this article.

There is a well described temporal relation between hormonal secretion and sleep phase, with hormones of the hypothalamic-pituitary-adrenal (HPA) axis possibly playing a role in determining entry into and duration of different sleep stages. In this study sleep features were studied in primary Addison’s patients with undetectable levels of cortisol treated in a double blind, randomized, cross-over fashion with either hydrocortisone or placebo supplementation. We found that REM latency was significantly decreased in Addison’s patients when receiving hydrocortisone at bedtime, whereas REM sleep time was increased. There was a trend toward an increase in the percentage of time in REM sleep and the number of REM sleep episodes. Waking time after sleep onset was increased, whereas no differences were observed between the two conditions when total sleep time or specific non-REM sleep parameters were evaluated. Our results suggest that in Addison’s patients, cortisol plays a positive, permissive role in REM sleep regulation and may help to consolidate sleep. These effects may be mediated either directly by the central effects of glucocorticoids and/or indirectly through CRH and/or ACTH.

<b>Background/Objectives</b>: Childhood cancer survivors (CCS) experience chronic health problems and significant metabolic burden. Timely identification of CCS at higher metabolic risk requires novel biomarkers. Irisin, a novel myokine/adipokine has been associated with metabolic, bone and reproductive diseases, but its role in the health of CCS is unknown. The aim of this study was to examine irisin concentrations in children and adolescent CCS (vs. controls) and their association with metabolic, bone and hormonal parameters. <b>Methods</b>: Children and adolescent CCS, aged 8-18 years, as well as healthy controls, underwent a detailed physical, body composition, biochemical, hormonal and serum irisin assessment at least 6 months post-treatment. <b>Results</b>: A total of 59 children and adolescents (36 CCS, 23 controls; mean age ± SD 12.8 ± 2.9 years; 10 prepubertal, 49 pubertal) participated in the study. Serum irisin concentrations (ng/mL) were significantly lower in CCS than controls [median (IQR) 6.54 (4.12) vs. 11.70 (8.75) ng/mL, respectively, <i>p</i> < 0.001]. In the total study sample, serum irisin was correlated negatively with LH (r_s = -0.314, <i>p</i> < 0.05), CRP (r_s = -0.366, <i>p</i> < 0.005), age (r_s = -0.323, <i>p</i> < 0.05) and positively with ALP (r_s = 0.328, <i>p</i> < 0.05). Serum irisin was also positively correlated with ApoB and Lpa (r_s = 0.410 and 0.421, respectively, <i>p</i> < 0.05) in CCS, and with PTH (r = 0.542, <i>p</i> < 0.005) in controls. Multivariate linear regression analysis indicated parathyroid hormone (PTH) as the only independent variable affecting irisin concentrations. <b>Conclusions</b>: Study results reinforce the irisin-PTH interplay hypothesis. Future studies are needed to clarify the potential role of irisin as a bone biomarker of CCS in childhood and adolescence.