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Forward solutions with different levels of complexity are employed for localization of current generators, which are responsible for the electric and magnetic fields measured from the human brain. The influence of brain anisotropy on the forward solution is poorly understood. The goal of this study is to validate an anisotropic model for the intracranial electric forward solution by comparing with the directly measured 'gold standard'. Dipolar sources are created at known locations in the brain and intracranial electroencephalogram (EEG) is recorded simultaneously. Isotropic models with increasing level of complexity are generated along with anisotropic models based on Diffusion tensor imaging (DTI). A Finite Element Method based forward solution is calculated and validated using the measured data. Major findings are (1) An anisotropic model with a linear scaling between the eigenvalues of the electrical conductivity tensor and water self-diffusion tensor in brain tissue is validated. The greatest improvement was obtained when the stimulation site is close to a region of high anisotropy. The model with a global anisotropic ratio of 10:1 between the eigenvalues (parallel: tangential to the fiber direction) has the worst performance of all the anisotropic models. (2) Inclusion of cerebrospinal fluid as well as brain anisotropy in the forward model is necessary for an accurate description of the electric field inside the skull. The results indicate that an anisotropic model based on the DTI can be constructed non-invasively and shows an improved performance when compared to the isotropic models for the calculation of the intracranial EEG forward solution. © The Author(s) 2009.

Summary: Background: Vitamin D may modulate adipogenesis. However, limited studies have investigated the effect of maternal vitamin D during pregnancy on offspring adiposity or cardiometabolic parameters with inconclusive results. Objectives: The objective of this study is to examine the association of maternal 25(OH)‐vitamin D [25(OH)D] status with offspring obesity and cardiometabolic characteristics in 532 mother–child pairs from the prospective pregnancy cohort Rhea in Crete, Greece. Methods: Maternal 25(OH)D concentrations were measured at the first prenatal visit (mean: 14 weeks, SD: 4). Child outcomes included body mass index standard deviation score, waist circumference, skin‐fold thickness, blood pressure and serum lipids at ages 4 and 6 years. Body fat percentage was also measured at 6 years. Body mass index growth trajectories from birth to 6 years were estimated by mixed effects models with fractional polynomials of age. Adjusted associations were obtained via multivariable linear regression analyses. Results: About two‐thirds of participating mothers had 25(OH)D concentrations <50 nmol L−1. Offspring of women in the low 25(OH)D tertile (<37.7 nmol L−1) had higher body mass index standard deviation score (β 0.20, 95% CI: 0.03, 0.37), and waist circumference (β 0.87 95% CI: 0.12, 1.63) at preschool age, compared with the offspring of women with higher 25(OH)D measurements (≥37.7 nmol L−1), on covariate‐adjusted analyses. The observed relationships persisted at age 6 years. We found no association between maternal 25(OH)D concentrations and offspring blood pressure or serum lipids at both time points. Conclusions: Exposure to very low 25(OH)D concentrations in utero may increase childhood adiposity indices. Given that vitamin D is a modifiable risk factor, our findings may have important public health implications. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus is a common disease in developed countries, but in Greece national figures on its prevalence are lacking.Objectives: The aim of this study was to identify the burden of known diabetes mellitus through its estimation in the area of responsibility of the Spili Health Centre, based on the health information system that had been established in Primary Health Care in rural Crete.Method: The diagnosis of diabetes was retrospectively documented by reviewing all medical records (n = 47151) at the Spili Health Centre and its five regional outposts during the period 1/6/1988-1/7/1993. The diagnostic criteria of WHO were used to establish the diagnosis.Results: After excluding the patients who had died, we found 210 patients with diabetes mellitus. Thirty cases were evaluated with OGTT because of mild but not diagnostic elevations of fasting plasma glucose, on more than one occasion. The prevalence of diabetes after age and sex standardization of that for the European population was estimated at 1.52% (1.31% in males and 1.68 in females).Conclusions: Our study shows that: 1) the role of the GPs and one appropriate information system in measuring the prevalence of known diabetes mellitus are now considered important within the Greek context; 2) diabetes mellitus seems not to be a rare disease in rural Crete. The estimated prevalence appears to be similar to the prevalence rates reported in other areas of rural Greece. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis is a disease endemic in Greece. Cases collected between the years 1975 and 1979 are analyzed form a clinico-epidemiologic point of view. Prevalence is highest in the Ionian islands and Crete. The disease most commonly affects individuals 10 to 20 years of age. The exposed parts of the body are most commonly involved, particularly the face. The period of highest incidence is mid-winter. [ABSTRACT FROM AUTHOR]

Animal studies suggest that prenatal vitamin D status may affect fetal brain growth. However, human studies are scarce with conflicting results. We aimed to investigate the association of maternal 25-hydroxyvitamin D [25(OH) D] levels with multiple neurodevelopmental outcomes at 4 years of age. We included 487 mother-child pairs from the prospective pregnancy cohort, "Rhea" in Crete, Greece. Maternal serum 25(OH) D concentrations were measured at the first prenatal visit (13 ± 2.4 weeks). Cognitive functions at 4 years were assessed by means of the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by means of Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Children of women in the high 25(OH) D tertile (>50.7 nmol/l) had 37% decreased number of hyperactivity-impulsivity symptoms (IRR 0.63, 95% CI 0.39, 0.99, p trend  = 0.05) and 40% decreased number of total ADHD-like symptoms (IRR 0.60, 95% CI 0.37, 0.95, p trend  = 0.03) at 4 years of age, compared to children of women in the low 25(OH) D tertile (<38.4 nmol/l), after adjustment for several confounders. Similar associations were found with the hyperactivity/inattention score of the SDQ questionnaire. Children of mothers with high 25(OH) D levels had also fewer total behavioral difficulties (beta-coeff: -1.25, 95% CI -2.32, -0.19) and externalizing symptoms (beta-coeff: -0.87, 95% CI -1.58, -0.15) at preschool age. The observed associations were stronger in girls than in boys (p for interaction  < 0.1). No association was observed between maternal 25(OH) D concentrations and cognitive function in preschoolers. Our results suggest that high maternal vitamin D levels in early pregnancy may protect against behavioral difficulties, especially ADHD-like symptoms at preschool age.

Studies have suggested an association between maternal obesity pre-pregnancy and gestational diabetes (GDM) with impaired offspring neurodevelopment, but it is not clear if these associations are explained by shared familiar characteristics. We aimed to assess the associations of maternal and paternal obesity, maternal glucose intolerance in early pregnancy and GDM, with offspring neurodevelopment at 4 years of age. We included 772 mother-child pairs from the "Rhea" Mother-Child cohort in Crete, Greece. Data on maternal/paternal body mass index (BMI) and maternal fasting serum samples for glucose and insulin measurements were collected at 12 weeks of gestation. GDM screening was performed at 24-28 weeks. Neurodevelopment at 4 years was assessed using the McCarthy Scales of Children's Abilities. Behavioral difficulties were assessed by Strengths and Difficulties Questionnaire and Attention Deficit Hyperactivity Disorder Test. Multivariate linear regression analyses showed that maternal obesity was associated with a significant score reduction in general cognitive ability (β-coeff -4.03, 95% CI: -7.08, -0.97), perceptual performance (β-coeff -4.60, 95% CI: -7.74, -1.47), quantitative ability (β-coeff -4.43, 95% CI: -7.68, -1.18), and executive functions (β-coeff -4.92, 95% CI: -8.06, -1.78) at 4 years of age, after adjustment for several confounders and paternal BMI. Maternal obesity was also associated with increased behavioral difficulties (β-coeff 1.22, 95% CI: 0.09, 2.34) and ADHD symptoms (β-coeff 4.28, 95% CI: 1.20, 7.36) at preschool age. Paternal obesity maternal glucose intolerance in early pregnancy and GDM was not associated with child neurodevelopment. These findings suggest that maternal obesity may impair optimal child neurodevelopment at preschool age independently of family shared characteristics.

The number of Australians aged 85 years and over is projected to double by 2032 with an additional 82,000 residential care places required by 2025 (Sudholz 2016).

Context: Maternal pre-pregnancy obesity may increase the risk of childhood obesity but it is unknown whether other metabolic factors in early pregnancy such as lipid profile and hypertension are associated with offspring cardiometabolic traits., Objective: Our objective was to investigate whether fasting lipid, glucose, and insulin levels during early pregnancy and maternal pre-pregnancy weight status, are associated with offspring adiposity measures, lipid levels and blood pressure at preschool age., Design and Methods: The study included 618 mother-child pairs of the pregnancy cohort "Rhea" study in Crete, Greece. Pregnant women were recruited at the first prenatal visit (mean: 12 weeks, SD: 0.7). A subset of 348 women provided fasting serum samples for glucose and lipid measurements. Outcomes measures were body mass index, abdominal circumference, sum of skinfold thickness, and blood pressure measurements at 4 years of age. A subsample of 525 children provided non-fasting blood samples for lipid measurements., Results: Pre-pregnancy overweight/obesity was associated with greater risk of offspring overweight/obesity (RR: 1.83, 95%CI: 1.19, 2.81), central adiposity (RR: 1.97, 95%CI: 1.11, 3.49), and greater fat mass by 5.10 mm (95%CI: 2.49, 7.71) at 4 years of age. These associations were more pronounced in girls. An increase of 40 mg/dl in fasting serum cholesterol levels in early pregnancy was associated with greater skinfold thickness by 3.30 mm (95%CI: 1.41, 5.20) at 4 years of age after adjusting for pre-pregnancy BMI and several other confounders. An increase of 10 mmHg in diastolic blood pressure in early pregnancy was associated with increased risk of offspring overweight/obesity (RR: 1.22, 95%CI: 1.03, 1.45), and greater skinfold thickness by 1.71 mm (95% CI: 0.57, 2.86) at 4 years of age., Conclusions: Metabolic dysregulation in early pregnancy may increase the risk of obesity at preschool age.

The AKT-mTOR pathway is activated in diabetic nephropathy. Renin-angiotensin system modulators exert beneficial effects on the diabetic kidney. We explored the action of losartan on AKT-mTOR phosphorylation in glomeruli and podocytes. Diabetes mellitus was induced to Sprague-Dawley rats by streptozotocin. Five months later, the rats were commenced on losartan and euthanized 2 months later. Kidneys were processed for immunofluorescence studies. Glomeruli were isolated for Western blot analysis. Diabetes increased activated forms of AKT and mTOR both in glomeruli and podocytes. In diabetic rats, losartan decreased phosphorylated/activated forms of AKT (Thr308) and mTOR (Ser2448) in glomeruli but decreased only activated mTOR in podocytes. However, in both glomeruli and podocytes of healthy animals, an inverse pattern was evident. In conclusion, a new body of evidence indicates the differential activation of AKT-mTOR in glomeruli and podocytes of healthy and diabetic animals in response to losartan.

Objective: To describe our 3-year experience in the long-term efficacy and safety of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery for the management of patients with primary hyperparathyroidism (p-HPT)., Design: Prospective study with a mean follow-up of 19.6 +/- 10.6 months., Patients: Our study population included 19 consecutive high risk patients with p-HPT, who met the criteria for surgery., Measurements: Under ultrasonic guidance, ethanol (95%) was injected into parathyroid glands with a volume of >or= 0.15 cm(3). With the aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections were carried out, in an interval of 2 weeks, until normalization of iPTH was reached or until no residual blood supply was detected by ultrasound in the gland. Biochemical parameters were monitored throughout the study., Results: At 6-month follow-up, normalization of iPTH levels (10-65 ng/l) was achieved in 11 (58%) patients (responders). Of the eight remaining patients (nonresponders), six patients had reduced (but not normalized) iPTH levels and two patients required parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19 patients (89.5%) became normocalcaemic (serum Ca 200 ng/l. The only complication was a transient dysphonia noticed in three patients., Conclusions: PEIT is a safe and effective nonsurgical treatment for patients with p-HPT, who are unsuitable for surgical intervention.

Prolactin (PRL) circadian profiles were analyzed using methods of nonlinear dynamics, directly from the experimental data, by combining in a single time-series (432 measurements), six individual 24-hour PRL profiles (72 measurements per profile, sampling interval = 20 min), obtained from young healthy human volunteers (4 males, 2 females), under basal conditions. Significant autocorrelation exists between any given point of the time series and a limited number of its successors. Fourier analysis showed a dominant frequency of 1 cycle/24 h, without sub-24-hour harmonics. Poincaré section indicated the presence of a fractal attractor and a sketch of the attractor revealed a highly convoluted geometric structure with a conical contour. The box-counting dimension (D0), information dimension (D1) and correlation dimension (D2) of the attractor had low, fractal values, did not differ significantly from each other, and exhibited saturation at an embedding dimension of 2. The evidence taken together suggests that, under basal conditions, the daily changes in the peripheral blood levels of PRL are governed by nonlinear deterministic dynamics, with a dominant rhythm of 1 cycle/day mixed with a higher-frequency, low-amplitude signal.

The aim of this study was to define factor(s) influencing fetal erythropoiesis following bone marrow transplantation. Thirty-one transplanted patients (14 males, 17 females) were studied. The underlying diseases were chronic myelogenous leukaemia (CML, 18 patients), acute myeloblastic leukaemia (AML, 7 patients) and acute lymphoblastic leukaemia (ALL, 6 patients). Reticulocyte and peripheral F cell estimation was carried out in donors and patients before transplantation and repeatedly during recovery. For F cell estimation, an indirect immunofluorescence assay was utilized. A significant increase above pre-BMT values in the percentage of F cells was observed in all patients from days 11 to 40 after transplantation. The increase of F cells on days 15, 18, 25, 32, 40 and 50 after transplantation was statistically significant in 14 patients who had shown an increase of F cells following chemotherapy (high responders) compared with the remaining 17 patients who did not respond so significantly. This finding supports the influence of the host bone marrow micro environment. The nature of the mechanisms operating remains to determined.

Gonadotropin secretion is diminished in the presence of hyperprolactinemia, and previous studies have shown that PRL can reduce GnRH secretion and impair LH responses to GnRH. To investigate the mechanisms of the inhibitory effects of PRL on the pituitary, we administered intraarterial pulse injections of GnRH (25 ng/pulse every 30 min) to castrate testosterone-implanted male rats placed in restraint cages. Serum PRL, GnRH receptor (GnRH-R), and LH responses to GnRH were measured at intervals over 72 h. In control animals which received saline pulses, serum PRL was transiently elevated to the range of 100-150 ng/ml during the first 24 h, GnRH-R remained stable (approximately 300 fmol/mg protein) and serum LH was low (less than 10 ng/ml) throughout the 72 h. GnRH pulses in castrate testosterone-implanted animals increased GnRH-R to values (approximately 600 fmol/mg) similar to those in castrate controls (no testosterone implant, saline pulses) through 48 h, but GnRH-R declined to baseline values by 72 h in both groups. Serum LH responses to GnRH pulses were only present at 24 h. Administration of bromocriptine throughout the 72 h to immobilized castrate rats or to castrate testosterone-replaced animals treated with GnRH pulses suppressed serum PRL, and GnRH-R concentrations remained elevated through 72 h. Serum LH responses to GnRH pulses were 5- to 20-fold higher in bromocriptine-treated rats, and responses were present throughout the 72 h of the experiment. Delaying the start of bromocriptine treatment until 36 h (after the spontaneous PRL peak) resulted in reduced GnRH-R and LH responses at 72 h. Similarly, administration of ovine PRL (during the first 48 h) to bromocriptine-treated rats produced low GnRH-R concentrations at 72 h. Thus, the transient elevation of PRL seen in immobilized rats can inhibit the GnRH-stimulated increase in GnRH-R and is associated with reduced LH responses to GnRH. These results indicate that PRL has a direct inhibitory effect on the gonadotrope and suggest that impaired GnRH-R responses to GnRH are one of the mechanisms involved in the diminished gonadotropin secretion seen in hyperprolactinemia.

l-Thyroxine is converted to 3,5,3'-l-triiodothyronine (T(3)) as well as to 3,3',5'-l-triiodothyronine (reverse T(3)). One product of further deiodination is 3,3'-diiodothyronine (3,3'T(2)). The serum levels of reverse T(3) and 3,3'T(2) change considerably in various physiological and disease states. We previously found that reverse T(3) and 3,3'T(2) bind to the solubilized hepatic nuclear "receptors" for thyroid hormones. This led us to study binding and actions of these metabolites in cultured rat pituitary cells in which glucose consumption and growth hormone production are regulated by T(3) and l-thyroxine. Reverse T(3) and 3,3'T(2) stimulated growth hormone production and glucose consumption and inhibited nuclear binding of radioactive T(3). Either metabolite produced maximal effects that equaled those of T(3), and neither inhibited the T(3) response. Further, additive effects were observed when reverse T(3) was combined with submaximal concentrations of T(3). In serum-free and serum-containing media, concentrations of 3,3'T(2) 50- to 70- and 10- to 100-fold greater, respectively, than those of T(3) were required for equivalent stimulations and for inhibition of nuclear binding by T(3). The relative activity differences under the two conditions can be attributed to weaker serum protein binding of 3,3'T(2) than T(3). With cells in serum-free media, reverse T(3) was a less avid competitor than 3,3'T(2) for T(3) binding by the nuclear receptors, and was less potent than 3,3'T(2) (0.001 the potency of T(3)) in inducing growth hormone production or glucose oxidation. In incubations with serum-containing media, reverse T(3) was an ineffective competitor for T(3) binding, and had only 0.1 the inducing potency of 3,3'T(2) (0.001 the potency of T(3)). The weaker activity of reverse T(3) relative to 3,3'T(2) in serum-containing media could be explained by stronger serum binding of reverse T(3) than 3,3'T(2). In addition, after long-term incubation of cells with radioactive reverse T(3), much of the cell-associated radioactivity was recovered as 3,3'T(2). These studies suggest that reverse T(3) and 3,3'T(2) can stimulate thyroid hormone-regulated functions as weak agonists by acting via the same receptors that mediate T(3) actions. Moreover, some of the effects of reverse T(3) may be due to 3,3'T(2) produced by deiodination of reverse T(3).

In this study we examined the changes in alpha and LH beta mRNAs in anterior pituitaries of male and female rats after castration. mRNA concentrations were measured by an optimized RNA dot blot hybridization assay. Rat alpha and LH beta cDNAs were nick-translated to specific activities of 2-5 X 10(8) cpm/micrograms and were used as hybridization probes. The total RNA per assay, RNA per dot, and saturating amounts of probe were optimized. The intra- and interassay coefficients of variation were 5% and 28%, respectively. Both alpha and LH beta mRNA concentrations increased after castration, but marked differences were observed in the kinetics of responses in male and female rats. In males, alpha and LH beta mRNAs were increased by 24 h postcastration (by 25% and 38%, respectively), and 4- to 5-fold increases over intact controls were evident by 18 days. Alpha mRNA rose rapidly and had doubled by 2 days, whereas LH beta mRNA concentrations showed a similar increase by 6-7 days postcastration. The slower rise in LH beta mRNA was associated with a transient decline in serum and pituitary LH concentrations between 2 and 6 days after castration. In female rats, alpha mRNA increased more slowly. Alpha concentrations had doubled by 10 days, while a similar increase in LH beta mRNA occurred 7 days after castration. Thereafter, both subunit mRNAs continued to rise, and by day 20 alpha mRNA was increased 5-fold and LH beta mRNA 16-fold over values in intact females. Serum and pituitary LH concentrations rose gradually, and both were increased by 7-10 days after castration. The increase in serum and pituitary LH followed a time course similar to that of the progressive rise in LH beta mRNA concentrations. These data show that an increase in steady state LH subunit mRNA concentrations is one of the mechanisms involved in increased gonadotropin biosynthesis and secretion after castration. The kinetics of LH subunit mRNA and LH secretory responses are different in male and female rats and suggest that the concentration of LH beta mRNA may be a limiting factor in LH secretion.

Alpha and LH beta subunit mRNAs were measured in pituitaries of 4-day cycling rats during the estrous cycle. A two-fold increase in alpha mRNA occurred between 0800-2000 h on diestrus, but alpha mRNA concentrations were stable during other days of the cycle. LH beta mRNA concentrations were low during estrus and metestrus (11-16 pg cDNA bound/100 micrograms pituitary DNA), but were elevated (27-30 pg) between 0800-2000 h on diestrus. A second increase in LH beta mRNA was observed on the afternoon of proestrus, prior to the onset of the LH surge with maximum values (45 pg) coincident with peak LH secretion. LH beta mRNA concentrations declined rapidly and had fallen to basal values by midnight on proestrus. These data show that alpha and LH beta mRNAs change in a similar manner during metestrus, diestrus and estrus, suggesting coordinate regulation of alpha and LH beta gene expression at these times. During the LH surge, however, LH beta mRNA alone is increased, suggesting that the LH beta gene can be differentially expressed at times when maximum LH secretion is occurring.

In this paper, we describe a case of lichen planus of the mouth with intense melanosis, in a middle-aged white male. Due to its unusual clinical characteristics, we believe that this case represents a rare variant of lichen planus of the oral mucosa. The histopathologic findings, differential diagnosis and its possible connection with lichen planus pigmentosus of the skin are discussed.

Pemphigus is a bullous autoimmune disease of the skin and mucosae. Recently pemphigus has been associated with malignant disorders originating from several tissues. Two cases of oral pemphigus associated with chronic lymphocytic leukemia are reported. Direct immunofluorescence studies of oral biopsy material showed a pattern consistent with pemphigus in both cases. The nature of the anti-ICS antibodies was IgG. However, in one case anti-ICS antibodies were detected in the serum while in the other anti-striated-muscle autoantibodies were present. The clinical course and interrelationship of the two disorders are discussed.

An acute transient fall in the number of pituitary GnRH receptors (GnRH-R) is observed before the preovulatory gonadotropin surge in cycling rats and before the afternoon daily gonadotropin surge in ovariectomized estradiol-treated rats. In the latter model, this fall can be reproduced by administration of the opioid antagonist naloxone, whereas the opioid agonist morphine acutely increases GnRH-R. In this study we investigated the mechanisms of this opioid effect and examined the effects of other neurotransmitter substances on modulation of pituitary GnRH-R. Administration of the dopaminergic agonists bromocriptine and L-dopa or the alpha-adrenergic receptor blocker phenoxybenzamine elevated GnRH-R acutely from average basal values of 240 +/- 22 and 254 +/- 21 fmol/mg protein to maximal values of 374 +/- 49, 441 +/- 67 and 461 +/- 75 fmol/mg, respectively, whereas the alpha-adrenergic agonist clonidine transiently decreased GnRH-R to 186 +/- 19 fmol/mg. Placement of radiofrequency lesions in the mediobasal hypothalamus or pretreatment with anti-GnRH serum completely abolished the ability of both morphine and naloxone to modulate the number of GnRH-R. These data indicate that the opioid-induced modulation of pituitary GnRH-R requires an intact hypothalamus and that both dopaminergic and alpha-adrenergic neurotransmitter systems may be involved. The final step of this action probably involves acute modulation of GnRH secretion (altered frequency and/or amplitude), which results in acute transient changes in the number of pituitary GnRH-R.

The influence of GnRH pulse frequency on LH subunit mRNA concentrations was examined in castrate, testosterone-replaced male rats. GnRH pulses (25 ng/pulse) or saline to controls, were given via a carotid cannula at intervals of 7.5-240 min for 48 h. alpha and LH beta mRNA concentrations were 109 +/- 23 and 30 +/- 5 pg cDNA bound/100 micrograms pituitary DNA, respectively, in saline controls. GnRH pulse intervals of 15, 30, and 60 min resulted in elevated alpha and LH beta mRNAs (P less than 0.01) and maximum responses (4-fold, alpha; 3-fold, LH beta) were seen after the 30-min pulses. Acute LH release to the last GnRH pulse was seen after the 15-, 30-, and 60-min pulse intervals. In contrast, LH subunit mRNAs were not increased and acute LH release was markedly impaired after the rapid (7.5 min) or slower (120 and 240 min) pulse intervals. Equalization of total GnRH dose/48 h using the 7.5- and 240-min intervals did not increase LH subunit mRNAs to levels produced by the optimal 30-min interval. These data indicate that the frequency of the pulsatile GnRH stimulus regulates expression of alpha and LH beta mRNAs in male rats. Further, GnRH pulse frequencies that increase subunit mRNA concentrations are associated with continuing LH responsiveness to GnRH.