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Find video protocols related to scientific articles indexed in Pubmed.
White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging.
J. Neurosci.
PUBLISHED: 11-14-2014
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Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.
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The Norepinephrine Transporter in Attention-Deficit/Hyperactivity Disorder Investigated With Positron Emission Tomography.
JAMA Psychiatry
PUBLISHED: 10-23-2014
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Attention-deficit/hyperactivity disorder (ADHD) research has long focused on the dopaminergic system's contribution to pathogenesis, although the results have been inconclusive. However, a case has been made for the involvement of the noradrenergic system, which modulates cognitive processes, such as arousal, working memory, and response inhibition, all of which are typically affected in ADHD. Furthermore, the norepinephrine transporter (NET) is an important target for frequently prescribed medication in ADHD. Therefore, the NET is suggested to play a critical role in ADHD.
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Syndromes at risk of status epilepticus in children: genetic and pathophysiological issues.
Epileptic Disord
PUBLISHED: 10-18-2014
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Status epilepticus (SE) is a medical emergency with increased risk of morbidity and mortality in all age groups. Recent research has identified a variety of new genes implicated in disorders with severe epilepsies as a prominent feature. Autoimmune mechanisms have also been recently recognised as a cause of epilepsies with SE as a characteristic symptom. Knowledge about the aetiology potentially underlying SE may help to guide diagnostics and eventually influence treatment decisions. This review recapitulates, in brief, the risk of SE in specific clinical settings, provides an overview of paediatric epilepsy syndromes more commonly, or by definition, associated with SE, and summarizes some recent research data on genetic defects and disease mechanisms implicated in the pathogenesis of epilepsies frequently accompanied by SE.
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Structural Connectivity Networks of Transgender People.
Cereb. Cortex
PUBLISHED: 09-14-2014
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Although previous investigations of transsexual people have focused on regional brain alterations, evaluations on a network level, especially those structural in nature, are largely missing. Therefore, we investigated the structural connectome of 23 female-to-male (FtM) and 21 male-to-female (MtF) transgender patients before hormone therapy as compared with 25 female and 25 male healthy controls. Graph theoretical analysis of whole-brain probabilistic tractography networks (adjusted for differences in intracranial volume) showed decreased hemispheric connectivity ratios of subcortical/limbic areas for both transgender groups. Subsequent analysis revealed that this finding was driven by increased interhemispheric lobar connectivity weights (LCWs) in MtF transsexuals and decreased intrahemispheric LCWs in FtM patients. This was further reflected on a regional level, where the MtF group showed mostly increased local efficiencies and FtM patients decreased values. Importantly, these parameters separated each patient group from the remaining subjects for the majority of significant findings. This work complements previously established regional alterations with important findings of structural connectivity. Specifically, our data suggest that network parameters may reflect unique characteristics of transgender patients, whereas local physiological aspects have been shown to represent the transition from the biological sex to the actual gender identity.
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Exploring the impact of BDNF Val66Met genotype on serotonin transporter and serotonin-1A receptor binding.
PLoS ONE
PUBLISHED: 09-04-2014
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The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.
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[Food supplements--possibilities and limitations: Part 6, Safety and possible risks].
Med Monatsschr Pharm
PUBLISHED: 07-29-2014
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Due to the precautionary principle in consumer protection, thresholds for long-term safety of nutrients have to be defined. Three toxical indicators are of interest: lowest observed adverse effect level (LOAEL); no observed adverse effect level (NOAEL) und tolerable level of upper intake (UL). An uptake of a nutrient within the range of UL is without side effects even on the basis of long-term consumption. The UL can be used to derive maximum levels for nutrients in food supplements. In general, vitamins can be regarded as safe nutrients except for vitamin A. Adverse effects only occur at excessive intake far beyond the recommended daily allowances. In contrast, the range of safe intake for minerals, especially trace elements, is much smaller. This can be seen clearly in the case of selenium. In order to prevent severe selenium deficiency a plasma concentration of > 0.25 micromol/l (> 20 microg/l) must be reached. To minimize cancer risk a plasma concentration of 1.5 micromol/l (120 microg/l) is needed. First signs of selenium intoxications occur at plasma levels over 250 microg/l. It is the dose that makes the preventive effect and the poison as well.
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Associations between Omega-3 Index increase and triacylglyceride decrease in subjects with hypertriglyceridemia in response to six month of EPA and DHA supplementation.
Prostaglandins Leukot. Essent. Fatty Acids
PUBLISHED: 07-23-2014
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Ingestion of long-chain n-3 PUFA effectively decreases serum triacylglycerol (TAG) levels and increases the Omega-3 Index, defined as the % of EPA and DHA in erythrocyte fatty acids. However, it remains unclear whether there is a relationship between the Omega-3 Index increase (?O3I increase) and the TAG level decrease (?TAG). We hypothesized that TAG reduction is strongly depended on Omega-3 Index increase.
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Uncertainty during pain anticipation: The adaptive value of preparatory processes.
Hum Brain Mapp
PUBLISHED: 06-30-2014
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Objectives: Anticipatory processes prepare the organism for upcoming experiences. The aim of this study was to investigate neural responses related to anticipation and processing of painful stimuli occurring with different levels of uncertainty. Experimental design: Twenty-five participants (13 females) took part in an electroencephalography and functional magnetic resonance imaging (fMRI) experiment at separate times. A visual cue announced the occurrence of an electrical painful or nonpainful stimulus, delivered with certainty or uncertainty (50% chance), at some point during the following 15 s. Principal observations: During the first 2 s of the anticipation phase, a strong effect of uncertainty was reflected in a pronounced frontal stimulus-preceding negativity (SPN) and increased fMRI activation in higher visual processing areas. In the last 2 s before stimulus delivery, we observed stimulus-specific preparatory processes indicated by a centroparietal SPN and posterior insula activation that was most pronounced for the certain pain condition. Uncertain anticipation was associated with attentional control processes. During stimulation, the results revealed that unexpected painful stimuli produced the strongest activation in the affective pain processing network and a more pronounced offset-P2. Conclusions: Our results reflect that during early anticipation uncertainty is strongly associated with affective mechanisms and seems to be a more salient event compared to certain anticipation. During the last 2 s before stimulation, attentional control mechanisms are initiated related to the increased salience of uncertainty. Furthermore, stimulus-specific preparatory mechanisms during certain anticipation also shaped the response to stimulation, underlining the adaptive value of stimulus-targeted preparatory activity which is less likely when facing an uncertain event. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
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16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.
Hum. Mol. Genet.
PUBLISHED: 06-16-2014
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Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65 046 European population controls (5/393 cases versus 32/65 046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.
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Survival of Norway spruce remains higher in mixed stands under a dryer and warmer climate.
Glob Chang Biol
PUBLISHED: 06-12-2014
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Shifts in tree species distributions caused by climatic change are expected to cause severe losses in the economic value of European forestland. However, this projection disregards potential adaptation options such as tree species conversion, shorter production periods, or establishment of mixed species forests. The effect of tree species mixture has, as yet, not been quantitatively investigated for its potential to mitigate future increases in production risks. For the first time, we use survival time analysis to assess the effects of climate, species mixture and soil condition on survival probabilities for Norway spruce and European beech. Accelerated Failure Time (AFT) models based on an extensive dataset of almost 65 000 trees from the European Forest Damage Survey (FDS) - part of the European-wide Level I monitoring network - predicted a 24% decrease in survival probability for Norway spruce in pure stands at age 120 when unfavorable changes in climate conditions were assumed. Increasing species admixture greatly reduced the negative effects of unfavorable climate conditions, resulting in a decline in survival probabilities of only 7%. We conclude that future studies of forest management under climate change as well as forest policy measures need to take this, as yet unconsidered, strongly advantageous effect of tree species mixture into account.
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Pulmonary arterial hypertension associated with impaired lysosomal endothelin-1 degradation.
Cardiol Young
PUBLISHED: 06-10-2014
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We report on a boy with severe pulmonary arterial hypertension associated with mucolipidosis, a rare lysosomal storage disorder. During diagnostic catheterisation, we found increased endothelin-1 levels, but normal big endothelin-1-levels (the precursor form of endothelin-1), which suggests impaired degradation of endothelin-1 rather than increased synthesis. As endothelin-1 degradation takes place in the lysosome, it appears likely that lysosomal dysfunction caused by the underlying disease contributes to the development of pulmonary arterial hypertension in this patient.
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Analysis of ELP4, SRPX2, and interacting genes in typical and atypical rolandic epilepsy.
Epilepsia
PUBLISHED: 05-30-2014
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Rolandic epilepsy (RE) and its atypical variants (atypical rolandic epilepsy, ARE) along the spectrum of epilepsy-aphasia disorders are characterized by a strong but largely unknown genetic basis. Two genes with a putative (ELP4) or a proven (SRPX2) function in neuronal migration were postulated to confer susceptibility to parts of the disease spectrum: the ELP4 gene to centrotemporal spikes and SRPX2 to ARE. To reexamine these findings, we investigated a cohort of 280 patients of European ancestry with RE/ARE for the etiological contribution of these genes and their close interaction partners. We performed next-generation sequencing and single-nucleotide polymorphism (SNP)-array based genotyping to screen for sequence and structural variants. In comparison to European controls we could not detect an enrichment of rare deleterious variants of ELP4, SRPX2, or their interaction partners in affected individuals. The previously described functional p.N327S variant in the X chromosomal SRPX2 gene was detected in two affected individuals (0.81%) and also in controls (0.26%), with some preponderance of male patients. We did not detect an association of SNPs in the ELP4 gene with centrotemporal spikes as previously reported. In conclusion our data do not support a major role of ELP4 and SRPX2 in the etiology of RE/ARE.
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Geographically weighted regression of land cover determinants of Plasmodium falciparum transmission in the Ashanti Region of Ghana.
Int J Health Geogr
PUBLISHED: 05-23-2014
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Malaria is a mosquito-borne parasitic disease that causes severe mortality and morbidity, particularly in Sub-Saharan Africa. As the vectors predominantly bite between dusk and dawn, risk of infection is determined by the abundance of P. falciparum infected mosquitoes in the surroundings of the households. Remote sensing is commonly employed to detect associations between land use/land cover (LULC) and mosquito-borne diseases. Due to challenges in LULC identification and the fact that LULC merely functions as a proxy for mosquito abundance, assuming spatially homogenous relationships may lead to overgeneralized conclusions.
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Percentile-based assessment of craniosynostosis.
J Craniomaxillofac Surg
PUBLISHED: 04-11-2014
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Perioperative assessment of craniosynostosis is based mostly on subjective scores. In this study, we sought to find an objective method to assess cranial deformation based on normative craniofacial percentiles. Anthropometric datasets from 104 (79 males, 25 females) patients with craniosynostoses were included. Anthropometric data were compared with normative age-dependent percentiles. Deviations above the 90th or below the 10th percentile were defined as significant cranial deformation. The cohort comprised 69 children with sagittal, 22 metopic, nine coronal, two bicoronal, one lambdoid, and one with coronal + lambdoid craniosynostosis. Most children with sagittal synostosis were above the 90th percentile for cranial circumference and length, whereas only 27.9% were below the 10th percentile for cranial width. Most (83%) children with scaphocephaly had cranial indices below the 10th percentile. For trigonocephaly, we found normal cranial circumference values in most patients (10th-90th percentile), 40.9% were above the 90th percentile for cranial length, and 63.1% and 57.9% were above the 90th percentiles for sagittal and transverse circumferences. For unicoronal synostosis transverse circumference was above the 90th percentile in 83.3% of children. Matching of anthropometric data of craniosynostosis patients with craniofacial norms could be useful in grading the clinical picture and potentially adapting the operative procedure.
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P300 amplitude variation is related to ventral striatum BOLD response during gain and loss anticipation: an EEG and fMRI experiment.
Neuroimage
PUBLISHED: 03-14-2014
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The anticipation of favourable or unfavourable events is a key component in our daily life. However, the temporal dynamics of anticipation processes in relation to brain activation are still not fully understood. A modified version of the monetary incentive delay task was administered during separate functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) sessions in the same 25 participants to assess anticipatory processes with a multi-modal neuroimaging set-up. During fMRI, gain and loss anticipation were both associated with heightened activation in ventral striatum and reward-related areas. EEG revealed most pronounced P300 amplitudes for gain anticipation, whereas CNV amplitudes distinguished neutral from gain and loss anticipation. Importantly, P300, but not CNV amplitudes, were correlated to neural activation in the ventral striatum for both gain and loss anticipation. Larger P300 amplitudes indicated higher ventral striatum blood oxygen level dependent (BOLD) response. Early stimulus evaluation processes indexed by EEG seem to be positively related to higher activation levels in the ventral striatum, indexed by fMRI, which are usually associated with reward processing. The current results, however, point towards a more general motivational mechanism processing salient stimuli during anticipation.
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Comparison of the effects of long-chain omega-3 fatty acid supplementation on plasma levels of free and esterified oxylipins.
Prostaglandins Other Lipid Mediat.
PUBLISHED: 03-12-2014
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It is believed that many of the beneficial effects of long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are mediated by their oxidized metabolites, the oxylipins. The formation and biological role of many cytochrome P450 and lipoxygenase derived hydroxy, epoxy and dihydroxy FA, particularly of oxylipins esterified in polar lipids and triglycerides remain unclear. In this study, we compared the impact of twelve weeks of LC n-3 PUFA supplementation on the patterns of free and total (sum of esterified and free) hydroxy, epoxy and dihydroxy FAs.
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Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA.
Prostaglandins Other Lipid Mediat.
PUBLISHED: 02-25-2014
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Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects.
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Schistosoma mansoni in schoolchildren in a Madagascan highland school assessed by PCR and sedimentation microscopy and Bayesian estimation of sensitivities and specificities.
Acta Trop.
PUBLISHED: 02-25-2014
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Madagascar is an endemic area for schistosomiasis, but recent prevalence data are scarce. We investigated stool samples of 410 children aged 4-18 years from a combined primary and secondary school in a Madagascan highland village near Ambositra in order to assess the prevalence of Schistosoma mansoni using microscopy and real-time polymerase chain reaction (PCR). A high prevalence of S. mansoni of 77.1% was detected by PCR, while only 15.2% of microscopic examinations of sedimentation-enriched stools were positive. We estimated the sensitivity and specificity of stool sedimentation microscopy (19.7% and 98.8%) and of PCR (98.9% and 89.3%) using a Bayesian approach for two dependant tests in one population without a reference standard. Our Bayesian posterior estimate of the prevalence is 80.2%. Simple sedimentation technique misses about 4/5 of all PCR-confirmed infections and is insufficient to determine the prevalence of S. mansoni. A survey comparing PCR with a classical standard technique (KatoKatz) is desirable.
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DEPDC5 mutations in genetic focal epilepsies of childhood.
Ann. Neurol.
PUBLISHED: 02-18-2014
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Recent studies reported DEPDC5 loss-of-function mutations in different focal epilepsy syndromes. Here we identified 1 predicted truncation and 2 missense mutations in 3 children with rolandic epilepsy (3 of 207). In addition, we identified 3 families with unclassified focal childhood epilepsies carrying predicted truncating DEPDC5 mutations (3 of 82). The detected variants were all novel, inherited, and present in all tested affected (n=11) and in 7 unaffected family members, indicating low penetrance. Our findings extend the phenotypic spectrum associated with mutations in DEPDC5 and suggest that rolandic epilepsy, albeit rarely, and other nonlesional childhood epilepsies are among the associated syndromes.
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[Food supplements in primary prevention--methodological aspects].
Med Monatsschr Pharm
PUBLISHED: 02-05-2014
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The terms "evidence" or "evidence-based medicine" (EBM) dominate the current biomedical debate. When asked about the usefulness of nutritional supplements, increasingly reliable studies and "evidence-based" recommendations are demanded. However, usually, it remains unclear what is meant by "evidence" and "evidence-based medicine". The aim of the current paper is to clarify and explain why continuous designed evaluation instruments, proofing the efficacy of pharmacological active compounds, cannot be applied without modifications to prove the benefits of nutrients. The focus bases on the following questions: (a) What does evidence-based medicine exactly means and how does it differ from non-evidence-based medicine? (b) What is the meaning of "evidence" and "evidence-based statements"? (c) What types of studies are suitable for securing evidence? (d) How can be drawn summarizing conclusions from various, sometimes divergent, results of single studies? (e) Which specific characteristics must be considered in the nutrition context?
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Relation of progesterone and DHEAS serum levels to 5-HT1A receptor binding potential in pre- and postmenopausal women.
Psychoneuroendocrinology
PUBLISHED: 01-29-2014
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Preclinical research and clinical experience point to a modulation of 5-HT1A receptor expression by gonadal steroid hormones. We examined the effect of estradiol, progesterone and DHEAS on serotonin neurotransmission in 16 premenopausal and 28 postmenopausal women, differentiating by reproductive status. By means of positron emission tomography and the radiotracer [carbonyl-(11)C]WAY-100635, the 5-HT1A receptor binding potential (BP) was quantified in 45 brain regions of interest. Median BP was used as a surrogate marker to estimate the whole brain effect of the steroid hormones on receptor binding. We found a strong negative effect of serum progesterone and DHEAS levels on 5-HT1A receptor binding in postmenopausal women both in the Median BP and on a regional level. Furthermore, there was a non-linear, U-shaped relationship between DHEAS levels and 5-HT1A receptor binding in the pooled sample. Presynaptic 5-HT1A receptor BP in the raphe nuclei was significantly explained in a non-linear way by both progesterone and DHEAS in the pooled sample. Our study confirms in humans a preclinically suggested relation of the steroid hormones progesterone and DHEAS to 5-HT1A receptor binding. We show differential effects of the hormones with regard to reproductive hormonal status. Non-linear, U-shaped relationships between hormone serum concentrations and serotonin neurotransmission might explain paradoxical effects of these hormones on mood.
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Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder.
Hum Brain Mapp
PUBLISHED: 01-22-2014
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Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings.
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Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression.
Hum Brain Mapp
PUBLISHED: 01-17-2014
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Suffering from anhedonia, patients with major depressive disorder (MDD) exhibit alterations in several parts of the serotonergic neurotransmitter system, which are in turn involved in reward processing. However, previous investigations of the serotonin transporter (SERT) focused on regional differences with varying results depending on the clinical syndrome. Here, we aimed to describe the serotonergic system of MDD patients on a network level by evaluating SERT associations across brain regions. Twenty medication free patients with major depression and 20 healthy controls underwent positron emission tomography using the radioligand [(11) C]DASB. SERT binding potentials (BPND ) were quantified voxel-wise with the multilinear reference tissue model 2. In addition, SERT BPND was extracted from the dorsal raphe nucleus (DRN) as an indicator of midbrain serotonergic neurotransmission. Whole-brain linear regression analysis was applied to evaluate the association of DRN SERT bindings to those in projection areas, which was followed by ANCOVA to assess differences in interregional relationships between patients and controls. Although both groups showed widespread positive correlations, group differences were restricted to decreased SERT associations between the DRN and the ventral striatum (right and left respectively: t=5.85, P<0.05 corrected and t=5.07, P<0.1 corrected) when comparing MDD patients (R(2)=0.11 and 0.24) to healthy subjects (R(2)=0.72 and 0.66, P<0.01 and 0.05 corrected). Adjusting for age and sex did not change these findings. This study indicates a disturbed regulation between key regions involved in reward processing via the SERT. Our interregional approach highlights the importance of evaluating pathophysiological alterations on a network level to gain complementary information in addition to regional investigations.
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Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men.
Prostaglandins Leukot. Essent. Fatty Acids
PUBLISHED: 01-14-2014
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Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia.
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Effects of hormone replacement therapy on cerebral serotonin-1A receptor binding in postmenopausal women examined with [carbonyl-¹¹C]WAY-100635.
Psychoneuroendocrinology
PUBLISHED: 01-13-2014
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Preclinical research points to a strong modulatory influence of gonadal hormones on the serotonin system. However, human data corroborating this association remains scarce. The aim of this study was to examine the effects of hormone replacement therapy on 5-HT?A receptor binding in postmenopausal women using positron emission tomography (PET) and the radioligand [carbonyl-(11)C]WAY-100635. In this randomized, double-blind, longitudinal study, 30 postmenopausal women underwent treatment with either a combination of oral 17?-estradiol valerate and micronized progesterone (group 1, n=10), oral 17?-estradiol valerate (group 2, n=10), or placebo (group 3, n=10). Two PET measurements were performed, one the day before treatment start and the second after at least eight weeks of treatment. Plasma levels of estradiol (E?), progesterone (P?), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were collected prior to PET measurements. As expected, hormone replacement therapy led to a significant increase in E? and P4 plasma levels in group 1 and to a significant increase in E? levels in group 2. The 5-HT?A receptor binding did not change significantly after estrogen, combined estrogen/progesterone treatment or placebo in any of the investigated brain regions. There were no significant correlations between changes in E? or P4 values and changes in 5-HT?A receptor binding. Although we were not able to confirm effects of gonadal hormone treatment on 5-HT?A receptor binding, our data do not preclude associations between sex steroid levels and serotonin, the neurotransmitter implicated most strongly in the pathogenesis of affective and anxiety disorders. ClinicalTrials.gov Identifier: NCT00755963.
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Continuous cardiac troponin I release in Fabry disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Fabry disease (FD) is a rare lysosomal storage disorder also affecting the heart. The aims of this study were to determine the frequency of cardiac troponin I (cTNI) elevation, a sensitive parameter reflecting myocardial damage, in a smaller cohort of FD-patients, and to analyze whether persistent cTNI can be a suitable biomarker to assess cardiac dysfunction in FD.
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[Celiac disease--the chameleon among the food intolerances].
Med Monatsschr Pharm
PUBLISHED: 11-26-2013
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Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetically predisposition. Symptoms occur upon exposure to prolamin from wheat, rye, barley and related grain. The pathogenesis of celiac disease has not yet been sufficiently elucidated but is being considered as an autoimmune process. At its core are the deamidation of prolamin fragments, the building of specific antibodies and the activation of cytotoxic T-cells. The immunological inflammatory process is accompanied by structural damages of the enterocytes (villous atrophy, colonization and crypt hyperplasia). The symptoms and their extent depend on the type of the celiac disease; classic and non-classic forms are being distinguished (atypical, oligosymptomatic, latent and silent celiac disease). Characteristics of the classic presentation are malabsorption syndrome and intestinal symptoms such as mushy diarrhea and abdominal distension. The diagnosis of celiac disease is based on four pillars: Anamnesis and clinical presentation, serological evidence of coeliac specific antibodies (IgA-t-TG; IgA-EmA), small intestine biopsy and improvement of symptoms after institution of a gluten-free diet. The basis of the therapy is a lifelong gluten-free diet, i. e. wheat, rye, barley, spelt, green-core, faro-wheat, kamuth and conventional oats as well as food items obtained therefrom. Small amounts of up to 50 mg gluten per day are usually tolerated by most patients; amounts of > or = 100 mg/day lead mostly to symptoms. Gluten-free foods contain < or = 20 ppm or 20 mg/kg (Sign: symbol of the crossed ear or label gluten-free). At the beginning of the therapy the fat and lactose intake may need to be reduced; also the supplementation of single micronutrients (fat-soluble vitamins, folic acid, B12, iron, and calcium) may be required. Alternative therapies are being developed but have not yet been clinically tested.
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[Food supplements--potential and limits: part 3].
Med Monatsschr Pharm
PUBLISHED: 09-28-2013
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Ageing processes are associated with physiological changes, e.g. a reduction of metabolically active body mass and an impaired hunger-satiety regulation, which--combined with chronic diseases and psychosocial problems--significantly increase the risk for malnutrition. However, considering their nutrition and health status elderly people are a very heterogeneous group. The nutrition situation of "young" seniors does generally not differ from the situation of working-age adults while institutionalized elderly people and those in need of care often show signs of a global malnutrition. The critical nutrients in the nutrition of the elderly particularly include vitamin B12 and D. Six percent of all elderly have a manifest and 10 to 30% a functional vitamin B12 deficiency. The main cause is vitamin B12 malabsorption resulting from a type B atrophic gastritis. The functional vitamin B12 deficiency and the associated hyperhomocysteinemia are risk factors for neurodegenerative diseases and accelerate bone loss. With increasing age the vitamin D status is deteriorating. About 50% of the elderly living in private households is deficient in vitamin D; in geriatrics vitamin D deficiency is more the rule than an exception. This is caused by a reduced endogenous biosynthesis, low UVB exposure and a diet low in vitamin D. A vitamin D deficiency increases the risk for falls and fractures as well as the risk for neurodegenerative diseases. Also the overall mortality is increased.
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Benign infantile convulsions (IC) and subsequent paroxysmal kinesigenic dyskinesia (PKD) in a patient with 16p11.2 microdeletion syndrome.
Neurogenetics
PUBLISHED: 09-11-2013
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Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is caused by mutations in the gene PRRT2 located in 16p11.2. A deletion syndrome 16p11.2 is well established and is characterized by intellectual disability, speech delay, and autism. PKD/IC, however, is extremely rare in this syndrome. We describe a case of PKD/IC and 16p11.2 deletion syndrome and discuss modifiers of PRRT2 activity to explain the rare concurrence of both syndromes.
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[Nutrient supplements--possibilities and limitations: part 2].
Med Monatsschr Pharm
PUBLISHED: 08-01-2013
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Pregnant women are at greater risk of an insufficient vitamin and mineral supply. Based on hemodynamic, endocrine and metabolic changes due to pregnancy, the body weight and blood volume increase. These changes result in an increased requirement of most vitamins and minerals while the energy requirement increases by about 10%. Besides iodine (recommended intake as supplement 150 microg/d), iron (recommended intake 30-40 mg/d), vitamin D (recommended intake as supplement 20-50 microg/d), and docosahexaenoic acid (recommended intake 200 mg/d), folic acid is one of the critical micronutrients during pregnancy. Food folate and synthetic folic acid differ in their bioavailability. About 50% of the food folate is absorbed whereas almost 100% of folic acid from supplements is bioavailable. The contents are thus indicated as folate equivalents. In the form ofTHF, folic acid functions as coenzyme for the transfer of C1 units in the metabolism of amino acids, purines and pyrimidines. Folic acid (isolated or in combination with other vitamins and minerals) reduces the total risk for neural tube defects by 72%. For primary prevention it is recommended that all women who are planning to become pregnant take 400-800 microg synthetic folic acid along with a diet rich in folate. The additional intake should be continued at least until the end of the first trimester. For secondary prevention of neural tube defects an intake of 4 mg/d is recommended.
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Mutations in GRIN2A cause idiopathic focal epilepsy with rolandic spikes.
Nat. Genet.
PUBLISHED: 07-18-2013
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Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS). The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10(-18), Fishers exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS (P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fishers exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.
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Long-Chain Omega-3 Fatty Acids Improve Brain Function and Structure in Older Adults.
Cereb. Cortex
PUBLISHED: 06-24-2013
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Higher intake of seafish or oil rich in long-chain omega-3 polyunsaturated fatty acids (LC-n3-FA) may be beneficial for the aging brain. We tested in a prospective interventional design whether high levels of supplementary LC-n3-FA would improve cognition, and addressed potential mechanisms underlying the effects. Sixty-five healthy subjects (50-75 years, 30 females) successfully completed 26 weeks of either fish oil (2.2 g/day LC-n3-FA) or placebo intake. Before and after the intervention period, cognitive performance, structural neuroimaging, vascular markers, and blood parameters were assayed. We found a significant increase in executive functions after LC-n3-FA compared with placebo (P = 0.023). In parallel, LC-n3-FA exerted beneficial effects on white matter microstructural integrity and gray matter volume in frontal, temporal, parietal, and limbic areas primarily of the left hemisphere, and on carotid intima media thickness and diastolic blood pressure. Improvements in executive functions correlated positively with changes in omega-3-index and peripheral brain-derived neurotrophic factor, and negatively with changes in peripheral fasting insulin. This double-blind randomized interventional study provides first-time evidence that LC-n3-FA exert positive effects on brain functions in healthy older adults, and elucidates underlying mechanisms. Our findings suggest novel strategies to maintain cognitive functions into old age.
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[Nutrient supplements - possibilities and limitations].
Med Monatsschr Pharm
PUBLISHED: 06-14-2013
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The consumption of micronutrient-supplements by the general public has become widespread; between 25 and more than 40% of individuals questioned in western developed nations confirm to regularly consume such products. In principle, there are two product categories for micronutrient-supplements - medicinal products (drugs) and foodstuffs. The latter are marketed as food supplements (FS) and dietary foodstuffs for particular nutritional uses including foods for special medical purposes (FSMP). FS serve the general supplementation of any consumer whilst foodstuffs for particular nutritional uses are directed at consumers with special dietary requirements; FSMP are intended for the dietary management of patients. There are clearly defined legal frameworks for those product categories. Independently of their legal product status, six areas of application can be characterised for micronutrient-supplements: general and special supplementation, primary prevention, compensation of disease-related deficits, therapeutic function and containment of diseases or avoidance of subsequent damages (secondary and tertiary function). Gauged with the mean-intake, micro nutrient supply in Germany is sufficient (exception: folic acid and vitamin D; partially also iodine). However, the intake of vitamins E, C, B1 and B2 as well as the minerals calcium, magnesium, zinc and iodine could be improved in 20-50% of the general public. Micro nutrient preparations in physiological dose could contribute to closing this gap in supply.
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Gray matter and intrinsic network changes in the posterior cingulate cortex after selective serotonin reuptake inhibitor intake.
Neuroimage
PUBLISHED: 06-13-2013
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Preclinical studies have demonstrated that serotonin (5-HT) challenge changes neuronal circuitries and microarchitecture. However, evidence in human subjects is missing. Pharmacologic magnetic resonance imaging (phMRI) applying selective 5-HT reuptake inhibitors (SSRIs) and high-resolution structural and functional brain assessment is able to demonstrate the impact of 5-HT challenge on neuronal network morphology and functional activity. To determine how SSRIs induce changes in gray matter and neuronal activity, we conducted a longitudinal study using citalopram and escitalopram. Seventeen healthy subjects completed a structural and functional phMRI study with randomized, cross-over, placebo-controlled, double-blind design. Significant gray matter increases were observed (among other regions) in the posterior cingulate cortex (PCC) and the ventral precuneus after SSRI intake of 10days, while decreases were observed within the pre- and postcentral gyri (all P<0.05, family-wise error [FWE] corrected). Furthermore, enhanced resting functional connectivity (rFC) within the ventral precuneus and PCC was associated with gray matter increases in the PCC (all FWE Pcorr<0.05). Corroborating these results, whole-brain connectivity density, measuring the brains functional network hubs, was significantly increased after SSRI-intake in the ventral precuneus and PCC (all FWE Pcorr<0.05). Short-term administration of SSRIs changes gray matter structures, consistent with previous work reporting enhancement of neuroplasticity by serotonergic neurotransmission. Furthermore, increased gray matter in the PCC is associated with increased functional connectivity in one of the brains metabolically most active regions. Our novel findings provide convergent evidence for dynamic alterations of brain structure and function associated with SSRI pharmacotherapy.
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Recessive TRAPPC11 mutations cause a disease spectrum of limb girdle muscular dystrophy and myopathy with movement disorder and intellectual disability.
Am. J. Hum. Genet.
PUBLISHED: 03-19-2013
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Myopathies are a clinically and etiologically heterogeneous group of disorders that can range from limb girdle muscular dystrophy (LGMD) to syndromic forms with associated features including intellectual disability. Here, we report the identification of mutations in transport protein particle complex 11 (TRAPPC11) in three individuals of a consanguineous Syrian family presenting with LGMD and in five individuals of Hutterite descent presenting with myopathy, infantile hyperkinetic movements, ataxia, and intellectual disability. By using a combination of whole-exome or genome sequencing with homozygosity mapping, we identified the homozygous c.2938G>A (p.Gly980Arg) missense mutation within the gryzun domain of TRAPPC11 in the Syrian LGMD family and the homozygous c.1287+5G>A splice-site mutation resulting in a 58 amino acid in-frame deletion (p.Ala372_Ser429del) in the foie gras domain of TRAPPC11 in the Hutterite families. TRAPPC11 encodes a component of the multiprotein TRAPP complex involved in membrane trafficking. We demonstrate that both mutations impair the binding ability of TRAPPC11 to other TRAPP complex components and disrupt the Golgi apparatus architecture. Marker trafficking experiments for the p.Ala372_Ser429del deletion indicated normal ER-to-Golgi trafficking but dramatically delayed exit from the Golgi to the cell surface. Moreover, we observed alterations of the lysosomal membrane glycoproteins lysosome-associated membrane protein 1 (LAMP1) and LAMP2 as a consequence of TRAPPC11 dysfunction supporting a defect in the transport of secretory proteins as the underlying pathomechanism.
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Bioavailability of long-chain omega-3 fatty acids.
Prostaglandins Leukot. Essent. Fatty Acids
PUBLISHED: 03-04-2013
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Supplements have reached a prominent role in improving the supply of long-chain omega-3 fatty acids, such as Eicosapentaenoic acid (EPA 20:5n-3) and Docosahexaenoic acid (DHA 22:6n-3). Similar to other nutrients, the availability of omega-3 fatty acids is highly variable and determined by numerous factors. However, the question of omega-3 fatty acids bioavailability has long been disregarded, which may have contributed to the neutral or negative results concerning their effects in several studies. This review provides an overview of the influence of chemical binding form (free fatty acids bound in ethylesters, triacylglycerides or phospholipids), matrix effects (capsule ingestion with concomitant intake of food, fat content in food) or galenic form (i.e. microencapsulation, emulsification) on the bioavailability of omega-3 fatty acids. There is a need to systematically investigate the bioavailability of omega-3 fatty acids formulations, which might be a key to designing more effective studies in the future.
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Regional differences in SERT occupancy after acute and prolonged SSRI intake investigated by brain PET.
Neuroimage
PUBLISHED: 02-22-2013
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Blocking of the serotonin transporter (SERT) represents the initial mechanism of action of selective serotonin reuptake inhibitors (SSRIs) which can be visualized due to the technical proceedings of SERT occupancy studies. When compared to the striatum, higher SERT occupancy in the midbrain and lower values in the thalamus were reported. This indicates that occupancy might be differently distributed throughout the brain, which is supported by preclinical findings indicating a regionally varying SERT activity and antidepressant drug concentration. The present study therefore aimed to investigate regional SERT occupancies with positron emission tomography and the radioligand [(11)C]DASB in 19 depressed patients after acute and prolonged intake of oral doses of either 10mg/day escitalopram or 20mg/day citalopram. Compared to the mean occupancy across cortical and subcortical regions, we detected increased SERT occupancies in regions commonly associated with antidepressant response, such as the subgenual cingulate, amygdala and raphe nuclei. When acute and prolonged drug intake was compared, SERT occupancies increased in subcortical areas that are known to be rich in SERT. Moreover, SERT occupancy in subcortical brain areas after prolonged intake of antidepressants was predicted by plasma drug levels. Similarly, baseline SERT binding potential seems to impact SERT occupancy, as regions rich in SERT showed greater binding reduction as well as higher residual binding. These findings suggest a region-specific distribution of SERT blockage by SSRIs and stress the postulated link between treatment response and SERT occupancy to certain brain regions such as the subgenual cingulate cortex.
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Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men.
Prostaglandins Leukot. Essent. Fatty Acids
PUBLISHED: 02-05-2013
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Oxylipins, the oxidation products of unsaturated fatty acids (FA), are potent endogenous mediators being involved in the regulation of various biological processes such as inflammation, pain and blood coagulation. Compared to oxylipins derived from arachidonic acid (AA) by cyclooxygenase action, i.e. prostanoides, only limited information is available about the endogenous levels of hydroxy-, epoxy- and dihydroxy-FA of linoleic acid (LA), AA, ?-linolenic acid (ALA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans. Particularly, it is unknown how metabolic disorders affect endogenous oxylipin levels in humans. Therefore, in the present study we compared the serum concentrations of 44 oxylipins in 20 normolipidemic with 20 hyperlipidemic (total cholesterol >200 mg/dl; LDL-C>130 mg/dl; TG>150 mg/dl) men (age 29-51 y). The serum concentration varied strongly among subjects. For most hydroxy-, epoxy- and dihydroxy-FA the concentrations were comparable to those in plasma reported in earlier studies. Despite the significant change in blood lipid levels the hyperlipidemic group showed only minor differences in oxylipin levels. The hyperlipidemic subjects had a slightly higher serum concentration of 8,9-DiHETrE, 5-HEPE, 10,11-DiHDPE, and a lower concentration of 12,13-DiHOME, 12-HETE, 9,10-DiHODE, and 12,13-DiHODE compared to normolipidemic subjects. Overall the hydroxy-, epoxy- and dihydroxy-FA levels were not changed suggesting that mild combined hyperlipidemia has no apparent effect on the concentration of circulating oxylipins. By contrast, serum levels of several hydroxy-, epoxy-, and dihydroxy-FA are dependent on the individual status of the parent FA. Particularly, a strong correlation between the EPA content in the erythrocyte membrane and the serum concentration of EPA derived oxylipins was observed. Given that the synthesis of EPA from other n-3 FA in humans is low; this suggests that oxylipin levels can be directly influenced by the diet.
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Clinical relevance of different biomarkers in imported plasmodium falciparum malaria in adults: a case control study.
Malar. J.
PUBLISHED: 01-31-2013
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For rapid initiation of anti-malarial treatment and prevention of complications, early diagnosis and risk stratification is important in patients with Plasmodium falciparum malaria. Routine laboratory values do not correlate well with disease severity. The aim of this study was to determine the diagnostic and prognostic value of several biomarkers related to inflammation; endothelial and cardiac dysfunction; coagulation, and haemolysis in imported P. falciparum malaria.
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Application of image-derived and venous input functions in major depression using [carbonyl-(11)C]WAY-100635.
Nucl. Med. Biol.
PUBLISHED: 01-30-2013
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Image-derived input functions (IDIFs) represent a promising non-invasive alternative to arterial blood sampling for quantification in positron emission tomography (PET) studies. However, routine applications in patients and longitudinal designs are largely missing despite widespread attempts in healthy subjects. The aim of this study was to apply a previously validated approach to a clinical sample of patients with major depressive disorder (MDD) before and after electroconvulsive therapy (ECT).
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Impact of COMT genotype on serotonin-1A receptor binding investigated with PET.
Brain Struct Funct
PUBLISHED: 01-17-2013
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Alterations of the inhibitory serotonin-1A receptor (5-HT1A) constitute a solid finding in neuropsychiatric research, particularly in the field of mood and anxiety disorders. Manifold factors influencing the density of this receptor have been identified, e.g., steroid hormones, sunlight exposure and genetic variants of serotonin-related genes. Given the close interactions between serotonergic and dopaminergic neurotransmission, we investigated whether a common single-nucleotide-polymorphism of the catechol-O-methyltransferase (COMT) gene (VAL158MET or rs4680) coding for a key enzyme of the dopamine network that is associated with the pathogenesis of mood disorders and antidepressant treatment response, directly affects 5-HT1A receptor binding potential. Fifty-two healthy individuals (38 female, mean age ± standard deviation = 40.48 ± 14.87) were measured via positron emission tomography using the radioligand [carbonyl-(11)C]WAY-100635. Genotyping for rs4680 was performed using DNA isolated from whole blood with the MassARRAY platform of the software SEQUENOM(®). Whole brain voxel-wise ANOVA resulted in a main effect of genotype on 5-HT1A binding. Compared to A carriers (AA + AG) of rs4680, homozygote G subjects showed higher 5-HT1A binding potential in the posterior cingulate cortex (F (2,49) = 17.7, p = 0.05, FWE corrected), the orbitofrontal cortex, the anterior cingulate cortex, the insula, the amygdala and the hippocampus (voxel-level: p < 0.01 uncorrected, t > 2.4; cluster-level: p < 0.05 FWE corrected). In light of the frequently reported alterations of 5-HT1A binding in anxiety and mood disorders, this study proposes a potential implication of the COMT genotype, more specifically the VAL158MET polymorphism, via modulation of the serotonergic neurotransmission.
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Comparing neural response to painful electrical stimulation with functional MRI at 3 and 7 T.
Neuroimage
PUBLISHED: 01-14-2013
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Progressing from 3T to 7 T functional MRI enables marked improvements of human brain imaging in vivo. Although direct comparisons demonstrated advantages concerning blood oxygen level dependent (BOLD) signal response and spatial specificity, these mostly focused on single brain regions with rather simple tasks. Considering that physiological noise also increases with higher field strength, it is not entirely clear whether the advantages of 7T translate equally to the entire brain during tasks which elicit more complex neuronal processing. Therefore, we investigated the difference between 3T and 7 T in response to transcutaneous electrical painful and non-painful stimulation in 22 healthy subjects. For painful stimuli vs. baseline, stronger activations were observed at 7 T in several brain regions including the insula and supplementary motor area, but not the secondary somatosensory cortex (p<0.05 FWE-corrected). Contrasting painful vs. non-painful stimulation limited the differences between the field strengths to the periaqueductal gray (PAG, p<0.001 uncorrected) due to a similar signal increase at 7 T for both the target and specific control condition in most brain regions. This regional specificity obtained for the PAG at higher field strengths was confirmed by an additional spatial normalization strategy optimized for the brainstem. Here, robust BOLD responses were obtained in the dorsal PAG at 7 T (p<0.05 FWE-corrected), whereas at 3T activation was completely missing for the contrast against non-painful stimuli. To summarize, our findings support previously reported benefits obtained at ultra-high field strengths also for complex activation patterns elicited by painful electrical stimulation. However, this advantage depends on the region and even more on the contrast of interest. The greatest gain at 7 T was observed within the small brainstem region of the PAG, where the increased field strength offered marked improvement for the localization of activation foci with high spatial specificity.
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A prospective randomized trial on preventative methods for positional head deformity: physiotherapy versus a positioning pillow.
J. Pediatr.
PUBLISHED: 01-11-2013
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To evaluate the impact of stretching exercises versus available bedding pillows on positional head deformities.
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RBFOX1 and RBFOX3 mutations in rolandic epilepsy.
PLoS ONE
PUBLISHED: 01-01-2013
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Partial deletions of the gene encoding the neuronal splicing regulator RBFOX1 have been reported in a range of neurodevelopmental diseases, including idiopathic generalized epilepsy. The RBFOX1 protein and its homologues (RBFOX2 and RBFOX3) regulate alternative splicing of many neuronal transcripts involved in the homeostatic control of neuronal excitability. In this study, we explored if structural microdeletions and exonic sequence variations in RBFOX1, RBFOX2, RBFOX3 confer susceptibility to rolandic epilepsy (RE), a common idiopathic focal childhood epilepsy. By high-density SNP array screening of 289 unrelated RE patients, we identified two hemizygous deletions, a 365?kb deletion affecting two untranslated 5-terminal exons of RBFOX1 and a 43 kb deletion spanning exon 3 of RBFOX3. Exome sequencing of 242 RE patients revealed two novel probably deleterious variants in RBFOX1, a frameshift mutation (p.A233Vfs*74) and a hexanucleotide deletion (p.A299_A300del), and a novel nonsense mutation in RBFOX3 (p.Y287*). Although the three variants were inherited from unaffected parents, they were present in all family members exhibiting the RE trait clinically or electroencephalographically with only one exception. In contrast, no deleterious mutations of RBFOX1 and RBFOX3 were found in the exomes of 6503 non-RE subjects deposited in the Exome Variant Server database. The observed RBFOX3 exon 3 deletion and nonsense mutation suggest that RBFOX3 represents a novel risk factor for RE, indicating that exon deletions and truncating mutations of RBFOX1 and RBFOX3 contribute to the genetic variance of partial and generalized idiopathic epilepsy syndromes.
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Light-dependent alteration of serotonin-1A receptor binding in cortical and subcortical limbic regions in the human brain.
World J. Biol. Psychiatry
PUBLISHED: 11-23-2011
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Climate, in particular sunshine, influences mood and energy levels, creating a positive upswing of mood on bright, sunny days and negative downswing in cold, dark winter seasons. Higher serotonin transporter availability in healthy human subjects in times of lesser light exposure and lower serotonin levels have been shown in winter.
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Diet-dependent net endogenous acid load of vegan diets in relation to food groups and bone health-related nutrients: results from the German Vegan Study.
Ann. Nutr. Metab.
PUBLISHED: 08-09-2011
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Dietary composition has been shown to affect acid-base homeostasis and bone health in humans. We investigated the potential renal acid load (PRAL) and the estimated diet-dependent net acid load (net endogenous acid production, NEAP) in adult vegans and evaluated the relationships between NEAP, food groups and intake of bone health-related nutrients.
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Cardiovascular risk in patients with rheumatoid arthritis: assessment of several traditional risk parameters and a German risk score model.
Rheumatol. Int.
PUBLISHED: 07-21-2011
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The present cross-sectional data demonstrate cardiovascular (CV) risk in patients with rheumatoid arthritis (RA). The cross-sectional data were part of an interventional trial that included 100 patients with defined RA. Traditional CV risk parameters and risk score calculation for the German population were used to assess the CV risk profile in the collective given. Proatherogenic lipid profile characterised by increased total cholesterol (? 5.2 mmol/l) and LDL cholesterol (? 3.5 mmol/l) levels was measured in 85 and 66%, respectively, of the study population. Elevated concentrations of homocysteine (? 10 ?mol/l) were reached by 67%. The prevalence of patients at high CV risk was 12% and increased up to 42% after using a multiplication factor of 1.5. No association was seen between the CV risk SCORE and DAS 28 or disease duration. RA patients in this study showed a proatherogenic risk profile with regard to the CV risk factors evaluated. The calculation of a 10-year risk using German risk charts might have led to an overall underestimation of the mean CV risk. Cardiovascular co-morbidity in RA patients must be seen as a major prevention and treatment target and should be monitored adequately.
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Incorporation of EPA and DHA into plasma phospholipids in response to different omega-3 fatty acid formulations--a comparative bioavailability study of fish oil vs. krill oil.
Lipids Health Dis
PUBLISHED: 07-18-2011
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Bioavailability of omega-3 fatty acids (FA) depends on their chemical form. Superior bioavailability has been suggested for phospholipid (PL) bound omega-3 FA in krill oil, but identical doses of different chemical forms have not been compared.
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Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol: part 1, general overview with a focus on ascorbic acid.
Inflamm Allergy Drug Targets
PUBLISHED: 05-10-2011
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As elements of the antioxidant system, cofactors of enzymes, components of transcription factors, and epigenetic modulators, micronutrients, such as vitamins and trace elements, influence various metabolic processes that are directly associated with immune functions. Specifically, the vitamins C and D have been shown to have significance immune function. Therefore, the objective of this review is to elucidate interactions between micronutrients and the immune system. In the initial section of this review, we present a general overview of interactions between the immune system and micronutrients, with a focus on the immunobiologically relevant functions of vitamin C. Immune competent cells accumulate vitamin C against a concentration gradient, with a close relationship between vitamin C supply and immune cell activity, especially phagocytosis activity and T-cell function. Accordingly, one of the consequences of vitamin C deficiency is impaired resistance to various pathogens, while an enhanced supply increases antibody activity and infection resistance.
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Micronutrients at the interface between inflammation and infection--ascorbic acid and calciferol. Part 2: calciferol and the significance of nutrient supplements.
Inflamm Allergy Drug Targets
PUBLISHED: 05-10-2011
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As explained in the first part of the article, vitamins and trace elements influence various metabolic functions that are directly related to immune function. In this context, secosteroid vitamin D has met with growing interest. The discussion has focused on whether and, if so, to what extent, vitamin D might contribute to the prevention and possibly the treatment of infections and autoimmune diseases. We know, for instance, that immune cells are capable of synthesizing calcitriol from its precursor calcidiol, whereby the former enhances the synthesis of antibacterial peptides by macrophages while simultaneously inhibiting the (auto)immune response mediated by T helper cells (Th1). Numerous observational studies support the hypothesis that a vitamin D deficit increases the risk of autoimmune diseases such as type 1 diabetes mellitus, multiple sclerosis, psoriasis and rheumatoid arthritis; however, there are few reliable interventional studies to date. In general, immune status represents a sensitive indicator of micronutrient supply. Conversely, the activity of the immune system has an effect on the status of and requirements for nutrients.
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Diets of modern hunter-gatherers vary substantially in their carbohydrate content depending on ecoenvironments: results from an ethnographic analysis.
Nutr Res
PUBLISHED: 03-18-2011
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In the past, attempts have been made to estimate the carbohydrate contents of preagricultural human diets. Those estimations have primarily been based on interpretations of ethnographic data of modern hunter-gatherers. In this study, it was hypothesized that diets of modern hunter-gatherers vary in their carbohydrate content depending on ecoenvironments. Thus, using data of plant-to-animal subsistence ratios, we calculated the carbohydrate intake (percentage of the total energy) in 229 hunter-gatherer diets throughout the world and determined how differences in ecological environments altered carbohydrate intake. We found a wide range of carbohydrate intake (?3%-50% of the total energy intake; median and mode, 16%-22% of the total energy). Hunter-gatherer diets were characterized by an identical carbohydrate intake (30%-35% of the total energy) over a wide range of latitude intervals (11°-40° north or south of the equator). However, with increasing latitude intervals from 41° to greater than 60°, carbohydrate intake decreased markedly from approximately equal to 20% to 9% or less of the total energy. Hunter-gatherers living in desert and tropical grasslands consumed the most carbohydrates (?29%-34% of the total energy). Diets of hunter-gatherers living in northern areas (tundra and northern coniferous forest) contained a very low carbohydrate content (?15% of the total energy). In conclusion, diets of hunter-gatherers showed substantial variation in their carbohydrate content. Independent of the local environment, however, the range of energy intake from carbohydrates in the diets of most hunter-gatherer societies was markedly different (lower) from the amounts currently recommended for healthy humans.
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Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder.
Neuroimage
PUBLISHED: 02-18-2011
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Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment. Although the amygdala has a central role in perception and processing of threatening cues, little is known about the involved networks and corresponding dysfunctions in social anxiety. Therefore, this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways. Ten patients with anxiety disorders (social and/or panic) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state. Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region. Group comparisons were done by random-effects analysis in SPM. Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional coupling of the left amygdala with the medial orbitofrontal cortex and the posterior cingulate cortex/precuneus. The strength of this functional connectivity showed a negative association with the severity of state anxiety. In addition, an exploratory analysis revealed further reduced functional connectivity and a marked functional separation between the medial orbitofrontal and anterior cingulate cortices in the patient group. Our results suggest alterations within the amygdalar functional connectivity network in social anxiety disorder. Combined with the amygdalar hyperactivation our findings corroborate the proposed dysfunction of the fronto-amygdalar inhibition in anxiety disorders and indicate a modulatory influence of the anterior and posterior cingulate cortices on threat perception and processing.
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Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography - a prospective study.
Dig Liver Dis
PUBLISHED: 01-01-2011
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Outcome of patients with hepatocellular carcinoma is influenced by their histological grade. Invasive biopsy of the lesions is the gold standard in this regard.
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Escitalopram enhances the association of serotonin-1A autoreceptors to heteroreceptors in anxiety disorders.
J. Neurosci.
PUBLISHED: 10-29-2010
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Selective serotonin reuptake inhibitors (SSRIs) represent one of the most common treatment options in major depression and anxiety disorders. By blocking the serotonin transporter, SSRIs modulate serotonergic neurotransmission as well as the function of autoreceptors and heteroreceptors. However, treatment-induced changes on a network level primarily remain unknown. Thus, we evaluated the association between serotonin-1A (5-HT1A) autoreceptors and heteroreceptors before and after SSRIs. Twenty-one patients with anxiety disorders underwent positron emission tomography using [carbonyl-11C]WAY-100635 before and after 12 weeks of escitalopram treatment; 15 of them completed the study protocol. Additionally, 36 drug-naive healthy controls were measured once. The 5-HT1A receptor binding potential (BPND) was quantified for the dorsal raphe nucleus (DRN) using a region-of-interest approach and for the entire brain by calculating parametric maps. Voxel-wise linear regression was applied between DRN autoreceptor and whole-brain heteroreceptor 5-HT1A BPND. Consistent with previous observations, healthy subjects showed widespread positive correlations of 5-HT1A BPND between autoreceptors and heteroreceptors. Comparing patients before versus after escitalopram treatment revealed enhanced associations of autoreceptor-to-heteroreceptor 5-HT1A BPND within the amygdala and hippocampus (R2=0.21-0.28 vs 0.49-0.81; p<0.05-0.001). In contrast, no significant SSRI-induced changes were found for correlations of heteroreceptor-to-heteroreceptor 5-HT1A BPND between several limbic regions. This interregional approach suggests a treatment-induced reinforcement of the association of 5-HT1A binding between autoreceptors and heteroreceptors specifically in areas involved in anxiety disorders. These findings provide complementary information about treatment effects on a network level and confirm the central role of the DRN as a prime regulatory area.
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Evaluation of sound speed for detection of liver fibrosis: prospective comparison with transient dynamic elastography and histology.
J Ultrasound Med
PUBLISHED: 10-23-2010
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The degree of liver fibrosis determines the prognosis and treatment of patients with chronic viral hepatitis. Transient elastography (TE) has been accepted as a noninvasive method for assessment of liver fibrosis. Sound velocity (SV) changes are also dependent on elastic properties of tissue. The aim of this pilot study was to evaluate whether SV estimation of liver tissue allows the determination of fibrosis stages in patients with chronic viral hepatitis.
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Nutrition in oncology: the case of micronutrients (review).
Oncol. Rep.
PUBLISHED: 09-03-2010
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In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patients quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the etiopathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin-multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.
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Latitude, local ecology, and hunter-gatherer dietary acid load: implications from evolutionary ecology.
Am. J. Clin. Nutr.
PUBLISHED: 08-11-2010
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Past estimations of the net base-producing nature of the Paleolithic "Diet of Evolutionary Adaptedness" derived primarily from interpretations of ethnographic data of modern historically studied hunter-gatherers. In our recent ethnographic analyses, we observed large variations in diet-dependent net endogenous acid production (NEAP) among hunter-gatherer diets.
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Cortisol plasma levels in social anxiety disorder patients correlate with serotonin-1A receptor binding in limbic brain regions.
Int. J. Neuropsychopharmacol.
PUBLISHED: 06-02-2010
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Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-11C]WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.
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Respiratory-triggered three-dimensional T2-weighted MR cholangiography after injection of gadoxetate disodium: is it still reliable?
Radiology
PUBLISHED: 04-24-2010
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To test the null hypothesis that there is no quantitative or qualitative difference between respiratory-triggered three-dimensional (3D) T2-weighted magnetic resonance (MR) cholangiography performed before or after administration of gadoxetate disodium.
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Dihydropyrimidinase deficiency: Phenotype, genotype and structural consequences in 17 patients.
Biochim. Biophys. Acta
PUBLISHED: 02-01-2010
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Dihydropyrimidinase (DHP) is the second enzyme of the pyrimidine degradation pathway and catalyses the ring opening of 5,6-dihydrouracil and 5,6-dihydrothymine. To date, only 11 individuals have been reported suffering from a complete DHP deficiency. Here, we report on the clinical, biochemical and molecular findings of 17 newly identified DHP deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological and gastrointestinal abnormalities and markedly elevated levels of 5,6-dihydrouracil and 5,6-dihydrothymine in plasma, cerebrospinal fluid and urine. Analysis of DPYS, encoding DHP, showed nine missense mutations, two nonsense mutations, two deletions and one splice-site mutation. Seventy-one percent of the mutations were located at exons 5-8, representing 41% of the coding sequence. Heterologous expression of 11 mutant enzymes in Escherichia coli showed that all but two missense mutations yielded mutant DHP proteins without significant activity. Only DHP enzymes containing the mutations p.R302Q and p.T343A possessed a residual activity of 3.9% and 49%, respectively. The crystal structure of human DHP indicated that the point mutations p.R490C, p.R302Q and p.V364M affect the oligomerization of the enzyme. In contrast, p.M70T, p.D81G, p.L337P and p.T343A affect regions near the di-zinc centre and the substrate binding site. The p.S379R and p.L7V mutations were likely to cause structural destabilization and protein misfolding. Four mutations were identified in multiple unrelated DHP patients, indicating that DHP deficiency may be more common than anticipated.
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An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study.
Hum. Mutat.
PUBLISHED: 01-07-2010
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L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.
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Estimation of the diet-dependent net acid load in 229 worldwide historically studied hunter-gatherer societies.
Am. J. Clin. Nutr.
PUBLISHED: 12-30-2009
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Nutrition scientists are showing growing interest in the diet patterns of preagricultural (hunter-gatherer) humans. Retrojected preagricultural diets are reportedly predominantly net base producing in contrast to the net acid-producing modern Western diets.
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Social anxiety disorder: epidemiology, biology and treatment.
Psychiatr Danub
PUBLISHED: 11-26-2009
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Social anxiety disorder (SAD) is considered to be one of the most common anxiety disorders. Despite its high prevalence, the disorder is still considerably underdiagnosed and undertreated. SAD shows a typically early onset in childhood or early adolescence and generally becomes chronic. The disease places a massive burden on patients lives, affecting not only their social interactions but also their educational and professional activities, thereby constituting a severe disability. Although substantial progress in the study of the etiology of SAD has been made, no commonly accepted model has emerged yet. Data from genetic and neuroimaging studies point towards a contribution of several neurotransmitter systems (i.e. norepinephrine, dopamine and serotonin) to the pathophysiology of this disorder. Functional magnetic resonance imaging studies have repeatedly emphasized the central role of the amygdalae and insula in the neural circuitry of the disorder. Selective serotonin reuptake inhibitors (SSRI) are commonly accepted as first line therapy, however other substance classes like serotonin norepineprine reuptake inhibitors (SNRI), monoamine oxidase inhibitors (MAOI), benzodiazepines and several other agents have also proved effective. There is still a substantial lack of data on therapeutic options in cases of non-responsive SAD as well as on add-on therapy. A combined treatment-approach including psychotherapy (e.g. cognitive behavioural therapy) may prove useful.
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Prolonged isolated red blood cell transfusion requirement after allogeneic blood stem cell transplantation: identification of patients at risk.
Transfusion
PUBLISHED: 11-19-2009
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Delayed donor red blood cell chimerism (DRCC), pure red blood cell aplasia (PRCA), and autoimmune hemolytic anemia (AIHA) are poorly documented complications after hematopoietic cell transplantation (HCT). The clinical variable "prolonged isolated red blood cell transfusion requirement" (PRTR) was evaluated as a trigger for an extended diagnostic workup.
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Comparative assessment of coagulation changes induced by two different types of heart-lung machine.
Artif Organs
PUBLISHED: 10-16-2009
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The cardiopulmonary bypass (CPB) used in heart surgery has a deleterious effect on hemostasis. The aim of our study was to assess by means of standard laboratory and point-of-care methods changes induced by CPB in coagulation parameters, particularly in platelet function, and to determine whether these changes differ depending on the type of heart-lung machine (HLM) used: minimal extracorporeal circulation system (MECC) and standard HLM. The study enrolled 88 patients scheduled for coronary artery bypass surgery performed on pump. Forty-four interventions were performed with MECC and 44 with standard HLM. Blood was sampled preoperatively, after 30 min on CPB, after weaning from CPB, and 24 h postoperatively. Coagulation and platelet function were assessed using multiple electrode aggregometry (MEA), rotation thromboelastometry, as well as standard laboratory tests. Rotation thromboelastometry and standard laboratory reflected significantly impaired hemostasis after weaning from CPB but no significant differences between the two groups at different time points. Aggregation decreased significantly in both groups as early as 30 min after the institution of CPB (P < 0.05, Mann-Whitney U-test) and recovered within the first 24 h postoperatively, without reaching the preoperative level. Intraoperatively, aggregometry values reflected a significantly more severe reduction of platelet function in standard HLM group than in the MECC group (P < 0.01, ProcMixed test). Our findings suggest that MEA and thromboelastometry reflect impairment of coagulation in cardiac surgery performed on different types of HLM and that platelet function is less affected by MECC than by standard HLM.
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Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects.
Hum Brain Mapp
PUBLISHED: 09-29-2009
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Various studies indicate that serotonin regulates impulsivity and the inhibitory control of aggression. Aggression is also known to be modified by sex hormones, which exert influence on serotonergic neurotransmission. The present study aimed to elucidate potential interactions between human aggression, the inhibitory serotonergic 5-HT(1A) receptor, and sex hormones.
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Intracoronary bone marrow cell transfer after myocardial infarction: 5-year follow-up from the randomized-controlled BOOST trial.
Eur. Heart J.
PUBLISHED: 09-22-2009
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We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27).
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Systemic and vascular markers of inflammation in relation to metabolic syndrome and insulin resistance in adults with elevated atherosclerosis risk.
Atherosclerosis
PUBLISHED: 08-11-2009
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In recent years high sensitive C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) were recognized as risk factors for cardiovascular disease (CVD). The aim of the present study was to investigate the relationship between these vascular and systemic markers of low-grade inflammation and traditional risk factors, the metabolic syndrome (MetS) or insulin resistance (IR).
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Lateralization of the serotonin-1A receptor distribution in language areas revealed by PET.
Neuroimage
PUBLISHED: 05-14-2009
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Lateralization is a well described aspect of the human brain. A plethora of morphological, cytological and functional studies describes hemispheric asymmetry in auditory and language areas. However, no study has reported cortical lateralization in the healthy human brain in vivo on the level of neurotransmitter receptors and in relation to functional organization so far. In this study, we assessed the distribution of the main inhibitory serotonergic receptor (the 5-HT1A receptor) and analyzed its regional binding with regard to hemisphere, sex and plasma levels of sex steroid hormones (testosterone, estradiol, progesterone). We quantified the 5-HT1A receptor binding potential by positron emission tomography (PET) using the highly selective and specific radioligand [carbonyl-11C]WAY-100635 and measured hormone levels in thirty-four (16 females, 18 males) healthy right-handed subjects. The obtained data were analyzed in an automated region of interest (ROI) based approach investigating 14 auditory, language and limbic areas. We found significantly higher 5-HT1A receptor binding in the superior and middle frontal gyri of the right hemisphere, the triangular and orbital parts of the inferior frontal gyrus, the supramarginal gyrus, the superior gyrus of the temporal pole and the middle temporal gyrus. Regions of the primary and secondary auditory cortex (Heschls gyrus and superior temporal gyrus) and the Rolandic operculum displayed significantly higher receptor binding in the left hemisphere. 5-HT1A receptor binding was 1.8-2.9% higher in right frontal ROIs and 2-3.6% higher in left primary and secondary auditory regions. There was no hemispheric difference in 5-HT(1A) receptor binding in the hippocampus, amygdala, and insula. Post-hoc testing suggested that lateralization of 5-HT1A receptor binding differed between the sexes in the triangular part of the inferior frontal gyrus. For the first time, this PET study shows lateralization of the main inhibitory receptor of the serotonergic system in functionally asymmetric organized regions of the healthy human brain in vivo.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.