2,226 research outputs found
Candidate Gene-Based Association Study of Antipsychotic-Induced Movement Disorders in Long-Stay Psychiatric Patients: A Prospective Study
OBJECTIVE: Four types of antipsychotic-induced movement disorders: tardive dyskinesia (TD), parkinsonism, akathisia and tardive dystonia, subtypes of TD (orofacial and limb truncal dyskinesia), subtypes of parkinsonism (rest tremor, rigidity, and bradykinesia), as well as a principal-factor of the movement disorders and their subtypes, were examined for association with variation in 10 candidate genes (PPP1R1B, BDNF, DRD3, DRD2, HTR2A, HTR2C, COMT, MnSOD, CYP1A2, and RGS2). METHODS: Naturalistic study of 168 white long-stay patients with chronic mental illness requiring long-term antipsychotic treatment, examined by the same rater at least two times over a 4-year period, with a mean follow-up time of 1.1 years, with validated scales for TD, parkinsonism, akathisia, and tardive dystonia. The authors genotyped 31 SNPs, associated with movement disorders or schizophrenia in previous studies. Genotype and allele frequency comparisons were performed with multiple regression methods for continuous movement disorders. RESULTS: VARIOUS SNPS REACHED NOMINAL SIGNIFICANCE: TD and orofacial dyskinesia with rs6265 and rs988748, limb truncal dyskinesia with rs6314, rest tremor with rs6275, rigidity with rs6265 and rs4680, bradykinesia with rs4795390, akathisia with rs4680, tardive dystonia with rs1799732, rs4880 and rs1152746. After controlling for multiple testing, no significant results remained. CONCLUSIONS: The findings suggest that selected SNPs are not associated with a susceptibility to movement disorders. However, as the sample size was small and previous studies show inconsistent results, definite conclusions cannot be made. Replication is needed in larger study samples, preferably in longitudinal studies which take the fluctuating course of movement disorders and gene-environment interactions into account
Global implications of the European Food System : A food systems approach
The EU is a major player in the world market for agricultural products, both dependent on commodity imports from many countries, and exporting high-value agricultural products. There is a need to better understand the impact - on people, planet and profit - of the EU trade on food systems outside the EU, with a focus on Low- and Middle-Income Countries (LMIC). This will help the EU to steer its actions and policies in other directions where this is deemed necessary to achieve the Sustainable Development Goals (SDGs)
Proportioning whole-genome single-nucleotide-polymorphism diversity for the identification of geographic population structure and genetic ancestry
The identification of geographic population structure and genetic ancestry
on the basis of a minimal set of genetic markers is desirable for a wide
range of applications in medical and forensic sciences. However, the
absence of sharp discontinuities in the neutral genetic diversity among
human populations implies that, in practice, a large number of neutral
markers will be required to identify the genetic ancestry of one
individual. We showed that it is possible to reduce the amount of markers
required for detecting continental population structure to only 10
single-nucleotide polymorphisms (SNPs), by applying a newly developed
ascertainment algorithm to Affymetrix GeneChip Mapping 10K SNP array data
that we obtained from samples of globally dispersed human individuals (the
Y Chromosome Consortium panel). Furthermore, this set of SNPs was able to
recover the genetic ancestry of individuals from all four continents
represented in the original data set when applied to an independent, much
larger, worldwide population data set (Centre d'Etude du Polymorphisme
Humain-Human Genome Diversity Project Cell Line Panel). Finally, we
provide evidence that the unusual patterns of genetic variation we
observed at the respective genomic regions surrounding the five most
informative SNPs is in agreement with local positive selection being the
explanation for the striking SNP allele-frequency differences we found
between continental groups of human populations
EFFECTS OF FIXATION AND SUBSTRATE PROTECTION ON THE ISOENZYMES OF ASPARTATE AMINOTRANSFERASE STUDIED IN A QUANTITATIVE CYTOCHEMICAL MODEL SYSTEM
N-acetyltransferase 2 polymorphism in Parkinson's disease. The Rotterdam study
The N-acetyltransferase-2 gene (NAT-2) has been associated with Parkinson's disease. The genotype associated with slow acetylation has been reported to be increased in patients with Parkinson's disease. Three mutant alleles M1, M2, and M3 of NAT-2 were investigated in 80 patients with idiopathic Parkinson's disease and 161 age matched randomly selected controls from a prospective population based cohort study. The allelic frequencies and genotypic distributions in patients were very similar to those found in controls. In controls the frequency of the wild type allele increased significantly with age suggesting that the mutant alleles are associated with an increased risk of mortality. These findings suggest that NAT-2 polymorphism is not a major genetic determinant of idiopathic Parkinson's disease, but may be a determinant of mortality in the general population
Presenile Alzheimer dementia characterized by amyloid angiopathy and large amyloid core type senile plaques in the APP 692Ala-Gly mutation
Geometrical quadrupolar frustration in DyB
Physical properties of DyB have been studied by magnetization, specific
heat, and ultrasonic measurements. The magnetic entropy change and the
ultrasonic properties in the intermediate phase II indicate that the degeneracy
of internal degrees of freedom is not fully lifted in spite of the formation of
magnetic order. The ultrasonic attenuation and the huge softening of
in phase II suggests existence of electric-quadrupolar (orbital) fluctuations
of the 4-electron. These unusual properties originate from the geometrical
quadrupolar frustration.Comment: 4 pages, 4 figures, accepted for publication in Journal of the
Physical Society of Japa
Observation of an Estuarine Turbidity Maximum in the Highly Impacted Capibaribe Estuary, Brazil
Background: Alterations in insulin-like growth factor I (IGF-I) signaling have been associated with dementia and Alzheimer's disease (AD). Studies on the association between IGF-I levels and dementia risk have been inconclusive. We reported earlier that higher levels of IGF-I receptor stimulating activity are associated with a higher prevalence and incidence of dementia. Objective: In the present study, we test the robustness of the association between IGF-I receptor stimulating activity and dementia by extending the follow-up period to 16 years and investigate possible effect modification by apolipoprotein E (ApoE). Methods: At baseline, circulating IGF-I receptor stimulating activity was determined by the IGF-I kinase receptor activation (KIRA) assay in 1,014 elderly from the Rotterdam Study. Dementia was assessed from baseline (1997-1999) to follow-up in January 2015. Associations of IGF-I receptor stimulating activity and incident dementia were assessed with Cox proportional hazards models. Results: During 10,752 person-years of follow-up, 174 people developed dementia. In the extended follow-up we no longer observed a dose-response relationship between IGF-I receptor stimulating activity and risk of dementia [adjusted odds ratio 1.11; 95% confidence interval (CI) 0.97-1.28]. Interestingly, we found evidence of an interaction between ApoE-ε4 and tertiles of IGF-I receptor stimulating activity. IGF-I receptor stimulating activity in the median and top tertiles was related to increased dementia incidence in hetero- and homozygotes of the ApoE-ε4 allele, but did not show any association with dementia risk in people without the ApoE-ε4 allele (adjusted odds ratio medium vs. low IGF-I receptor stimulating activity in ApoE-ε4 carriers: 1.45; 95% CI 1.00-2.12). These findings suggest a threshold effect in ApoE-ε4 carriers. In line with the hypothesis that downregulation of IGF-I signaling is associated with increased dementia risk, ApoE-ε4 homozygotes without prevalent dementia displayed lower levels of IGF-I receptor stimulating activity than heterozygotes and non-carriers. Conclusion: The findings shed new light on the association between IGF-I signaling and the neuropathology of dementia and ask for replication in other cohorts, using measures of IGF-I receptor stimulating activity rather than total serum levels as putative markers of dementia risk
The effect of an e-learning supported Train-the-Trainer program on implementation of suicide guidelines in mental health care.
AbstractBackgroundRandomized studies examining the effect of training of mental health professionals in suicide prevention guidelines are scarce. We assessed whether professionals benefited from an e-learning supported Train-the-Trainer programme aimed at the application of the Dutch multidisciplinary suicide prevention guideline.Methods45 psychiatric departments from all over the Netherlands were clustered in pairs and randomized. In the experimental condition, all of the staff of psychiatric departments was trained by peers with an e-learning supported Train-the-Trainer programme. Guideline adherence of individual professionals was measured by means of the response to on-line video fragments. Multilevel analyses were used to establish whether variation between conditions was due to differences between individual professionals or departments.ResultsMultilevel analysis showed that the intervention resulted in an improvement of individual professionals. At the 3 month follow-up, professionals who received the intervention showed greater guideline adherence, improved self-perceived knowledge and improved confidence as providers of care than professionals who were only exposed to traditional guideline dissemination. Subgroup analyses showed that improved guideline adherence was found among nurses but not among psychiatrists and psychologists. No significant effect of the intervention on team performance was found.LimitationsThe ICT environment in departments was often technically inadequate when displaying the video clips clip of the survey. This may have caused considerable drop-out and possibly introduced selection bias, as professionals who were strongly affiliated to the theme of the study might have been more likely to finish the study.ConclusionsOur results support the idea that an e-learning supported Train-the-Trainer programme is an effective strategy for implementing clinical guidelines and improving care for suicidal patients.Trial registrationNetherlands Trial Register (NTR3092 www.trialregister.nl)
Rare Genetic Variant in SORL1 May Increase Penetrance of Alzheimer's Disease in a Family with Several Generations of APOE-ɛ4 Homozygosity
BACKGROUND: The major genetic risk factor for late onset Alzheimer's disease (AD) is the APOE-ɛ4 allele. However, APOE-ɛ4 homozygosity is not fully penetrant, suggesting co-occurrence of additional genetic variants. OBJECTIVE: To identify genetic factors that, next to APOE-ɛ4 homozygosity, contribute to the development of AD. METHODS: We identified a family with nine AD patients spanning four generations, with an inheritance pattern suggestive of autosomal dominant AD, with no variants in PSEN1, PSEN2, or APP. We collected DNA from four affected and seven unaffected family members and performed exome sequencing on DNA from three affected and one unaffected family members. RESULTS: All affected family members were homozygous for the APOE-ɛ4 allele. Statistical analysis revealed that AD onset in this family was significantly earlier than could be expected based on APOE genotype and gender. Next to APOE-ɛ4 homozygosity, we found that all four affected family members carried a rare variant in the VPS10 domain of the SORL1 gene, associated with AβPP processing and AD risk. Furthermore, three of four affected family members carried a rare variant in the TSHZ3 gene, also associated with AβPP processing. Affected family members presented between 61 and 74 years, with variable presence of microbleeds/cerebral amyloid angiopathy and electroencephalographic abnormalities. CONCLUSION: We hypothesize that next to APOE-ɛ4 homozygosity, impaired SORL1 protein function, and possibly impaired TSHZ3 function, further disturbed Aβ processing. The convergence of these genetic factors over several generations might clarify the increased AD penetrance and the autosomal dominant-like inheritance pattern of AD as observed in this family
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