Monoamine related functional gene variants and relationships to monoamine metabolite concentrations in CSF of healthy volunteers

BACKGROUND: Concentrations of monoamine metabolites in human cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. CSF monoamine metabolite concentrations are partly determined by genetic influences. METHODS: We investigated possible relationships between DNA polymorphisms in the serotonin 2C receptor (HTR2C), the serotonin 3A receptor (HTR3A), the dopamine D(4 )receptor (DRD4), and the dopamine β-hydroxylase (DBH) genes and CSF concentrations of 5-hydroxyindolacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (n = 90). RESULTS: The HTR3A 178 C/T variant was associated with 5-HIAA levels (p = 0.02). The DBH-1021 heterozygote genotype was associated with 5-HIAA (p = 0.0005) and HVA (p = 0.009) concentrations. Neither the HTR2C Cys23Ser variant, nor the DRD4 -521 C/T variant were significantly associated with any of the monoamine metabolites. CONCLUSIONS: The present results suggest that the HTR3A and DBH genes may participate in the regulation of dopamine and serotonin turnover rates in the central nervous system

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Environmental assessment model for pharmaceutical products - Environmental risks related to Active Pharmaceutical Ingredients (API) and carbon footprint in a life cycle perspective

To be able to assess the environmental consequences of pharmaceutical products, reliable, comparable and relevant information is needed about the environmental impacts along the life cycle of the product. This project has developed and proposed a model for environmental assessment of pharmaceutical products, in regard to environmental risks related to emissions of Active Pharmaceutical Ingredient (API) from production processes and product carbon footprint in a life cycle perspective. The two parts is intended to supplement and expand the current environmental classification at Fass.se, which covers environmental risks from release of API from patient excretion in Swedish water recipients. The model is aimed to facilitate comparability of performed assessments of products with the same API and allow for third party review and validation, to ensure credibility and quality of reported results. The environmental risk part of the proposed model includes production stages where API can be/is released to the environment and builds on the current environmental classification at Fass.se. The carbon footprint part of the model covers greenhouse gas emissions in a life cycle perspective. We propose to use the framework described in ISO 14025 for environmental product declarations and initiate the development of Product Category Rules (PCR) for pharmaceutical products. Different potential options for such development are outlined in the report. The proposed model is aimed to deliver product specific environmental assessment results that may be used in a wide variety of different applications to control, manage and reduce impacts along the pharmaceutical value chain and drive improvements in different parts of the chain. The report includes an overview of potential use of the information, such as pharmaceutical benefits subsidy systems, procurement, process and product improvement, guidance in product choice as well as assessments in conjunction with product approval. The actual intended application of results, however, needs to be better understood in order to prioritise and guide further development and implementation of the model.This report proposes a model for environmental assessment of pharmaceutical products, in regard to environmental risks related to emissions of Active Pharmaceutical Ingredient (API) from production processes and product carbon footprint in a life cycle perspective. The proposed model is aimed to deliver results that may be used in different applications. The project has been performed in cooperation with The Research-Based Pharmaceutical Industry (LIF)

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The Babytwins Study Sweden (BATSS) : A Multi-Method Infant Twin Study of Genetic and Environmental Factors Influencing Infant Brain and Behavioral Development

Twin studies can help us understand the relative contributions of genes and environment to phenotypic trait variation, including attentional and brain activation measures. In terms of applying methodologies such as electroencephalography (EEG) and eye tracking, which are key methods in developmental neuroscience, infant twin studies are almost nonexistent. Here, we describe the Babytwins Study Sweden (BATSS), a multi-method longitudinal twin study of 177 MZ and 134 DZ twin pairs (i.e., 622 individual infants) covering the 5−36 month time period. The study includes EEG, eye tracking and genetics, together with more traditional measures based on in-person testing, direct observation and questionnaires. The results show that interest in participation in research among twin parents is high, despite the comprehensive protocol. DNA analysis from saliva samples was possible in virtually all participants, allowing for both zygosity confirmation and polygenic score analyses. Combining a longitudinal twin design with advanced technologies in developmental cognitive neuroscience and genomics, BATSS represents a new approach in infancy research, which we hope to have impact across multiple disciplines in the coming years

Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women.

Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women