A whole genome association study of mother-to-child transmission of HIV in Malawi.

Background: More than 300,000 children are newly infected with HIV each year, predominantly through mother-to-child transmission (HIV MTCT). Identification of host genetic traits associated with transmission may more clearly explain the mechanisms of HIV MTCT and further the development of a vaccine to protect infants from infection. Associations between transmission and a selection of genes or single nucleotide polymorphisms (SNP)s may give an incomplete picture of HIV MTCT etiology.

Comparison of genome-wide variation between Malawians and African ancestry HapMap populations.

Understanding genetic variation between populations is important because it affects the portability of human genome-wide analytical methods. We compared genetic variation and substructure between Malawians and other African and non-African HapMap populations. Allele frequencies and adjacent linkage disequilibrium (LD) were measured for 617 715 single nucleotide polymorphisms (SNPs) across subject genomes.

The transcription factor 7-like 2 (TCF7L2) polymorphism may be associated with focal arteriolar narrowing in Caucasians with hypertension or without diabetes: the ARIC Study.

Background: Transcription factor 7-like 2 (TCF7L2) has emerged as a consistently replicated susceptibility gene for type 2 diabetes, however, whether the TCF7L2 gene also has similar effects on the retinal microvasculature is less clear. We therefore aimed to investigate the association between the transcription factor 7-like 2 (TCF7L2) rs7903146 polymorphism and retinal microvascular phenotypes in the Atherosclerosis Risk in Communities (ARIC) Study (1993-1995).

Methods: This was a population-based, cross-sectional study of 10,320 middle-aged African American (n = 2,199) and Caucasian (n = 8,121) men and women selected from four United States communities to examine the association between TCF7L2 rs7903146 polymorphism and retinal microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous nicking, arteriolar and venular calibers).

Pulmonary kinematics from tagged hyperpolarized helium-3 MRI.

Purpose: To propose and test the feasibility of a novel method for quantifying 3D regional pulmonary kinematics from hyperpolarized helium-3 tagged MRI in human subjects using a tailored image processing pipeline and a recently developed nonrigid registration framework.

Materials And Methods: Following image acquisition, inspiratory and expiratory tagged (3)He magnetic resonance (MR) images were preprocessed using various image filtering techniques to enhance the tag surfaces. Segmentation of the three orthogonal sets of tag planes in each lung produced distinct point-set representations of the tag surfaces.

Dynamics of specific antibody responses induced in mallards after infection by or immunization with low pathogenicity avian influenza viruses.

Natural infections with different subtypes of low pathogenicity avian influenza viruses (LPAIVs) are very common in wild duck populations. Recent outbreaks of high pathogenicity avian influenza virus (HPAIV) H5N1 in Eurasian and African countries stimulated monitoring activities in aquatic wild bird populations. Surveillance mainly focused on virus detection.

Alternans resonance and propagation block during supernormal conduction in cardiac tissue with decreased [K(+)](o).

Cardiac restitution is an important factor in arrhythmogenesis. Steep positive action potential duration and conduction velocity (CV) restitution slopes promote alternans and reentrant arrhythmias. We examined the consequences of supernormal conduction (characterized by a negative CV restitution slope) on patterns of conduction and alternans in strands of Luo-Rudy model cells and in cultured cardiac cell strands.

Limited susceptibility of chickens, turkeys, and mice to pandemic (H1N1) 2009 virus.

To determine susceptibility of chickens, turkeys, and mice to pandemic (H1N1) 2009 virus, we conducted contact exposure and inoculation experiments. We demonstrated that chickens were refractory to infection. However, oculo-oronasally inoculated turkeys and intranasally inoculated mice seroconverted without clinical signs of infection.

Genome-wide linkage analysis of 1,233 prostate cancer pedigrees from the International Consortium for Prostate Cancer Genetics using novel sumLINK and sumLOD analyses.

Background: Prostate cancer (PC) is generally believed to have a strong inherited component, but the search for susceptibility genes has been hindered by the effects of genetic heterogeneity. The recently developed sumLINK and sumLOD statistics are powerful tools for linkage analysis in the presence of heterogeneity.

Methods: We performed a secondary analysis of 1,233 PC pedigrees from the International Consortium for Prostate Cancer Genetics (ICPCG) using two novel statistics, the sumLINK and sumLOD.

Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples.

Remoxipride is a selective dopamine D(2) receptor antagonist, and useful as a model compound in mechanism-based pharmacological investigations. To that end, studies in small animals with serial sampling over time are needed. For these small volume samples currently no suitable analytical methods are available.

Effects of combined oral contraceptive ethinylestradiol (30 microg) and dienogest (2 mg) on carbohydrate metabolism during 1 year of conventional or extended-cycle use.

The effects of extended regimens of combined oral contraceptives (COCs) on carbohydrate metabolism are largely unknown. The present study compared the effects of a COC containing 30 microg ethinylestradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year. Parameters of carbohydrate metabolism were measured in 59 women treated with EE/DNG either conventionally (13 cycles of 21+7 days) or in extended-cycle regimen (4 cycles of 84+7 days).

The use of screening instruments for detecting alcohol and other drug use disorders in first-episode psychosis.

The high rate of drug abuse among patients with psychosis represents a challenge to clinicians in their treatment of the patients. Powerful screening tools to detect problematic drug use in an early phase of psychotic illness are needed. The aim of the present study was to investigate prevalence of drug use disorders and psychometric properties of the Alcohol Use Disorder Identification Test (AUDIT) and the Drug Use Disorder Identification Test (DUDIT) in 205 first-episode psychosis patients in Oslo, Norway.

Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults.

Plasma homocysteine (Hcy) level is associated with cardiovascular disease and may play an etiologic role in vascular damage, a precursor for atherosclerosis. We performed a genome-wide association study for Hcy in 1786 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey (CLHNS). The most strongly associated single-nucleotide polymorphism (SNP) (rs7422339, P = 4.

Plant health and global change--some implications for landscape management.

Global change (climate change together with other worldwide anthropogenic processes such as increasing trade, air pollution and urbanization) will affect plant health at the genetic, individual, population and landscape level. Direct effects include ecosystem stress due to natural resources shortage or imbalance. Indirect effects include (i) an increased frequency of natural detrimental phenomena, (ii) an increased pressure due to already present pests and diseases, (iii) the introduction of new invasive species either as a result of an improved suitability of the climatic conditions or as a result of increased trade, and (iv) the human response to global change.

Imaging of the distal airways.

Imaging techniques of the lung continue to advance, with improving ability to image the more distal airways. Two imaging techniques are reviewed: computed tomography and magnetic resonance with hyperpolarized helium-3.

Dual representation of item positions in verbal short-term memory: Evidence for two access modes.

Memory sets of = 1~5 digits were exposed sequentially from left-to-right across the screen, followed by recognition probes. Probes had to be compared to memory list items on identity only (Sternberg task) or conditional on list position. Positions were probed randomly or in left-to-right order.

An update on safety studies on the attenuated "RIEMSER Schweinepestoralvakzine" for vaccination of wild boar against classical swine fever.

The RIEMSER Schweinepestoralvakzine is an attenuated vaccine for oral vaccination of wild boar against classical swine fever (CSF). The safety of this licensed bait vaccine which is based on the CSF virus (CSFV) strain "C" was investigated in eight animal species, e.g.

Effect of altered AGP plasma binding on heart rate changes by S(-)-propranolol in rats using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)).

In contrast to the impact of plasma protein binding on pharmacokinetics, no quantitative in vivo information is available on its impact on pharmacodynamics. The pharmacokinetic-pharmacodynamic relationship of the model drug S(-)-propranolol was evaluated using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)), under conditions of altered plasma protein binding resulting from different levels of alpha-1-acid glycoprotein (AGP). Male Wistar Kyoto rats with isoprenaline-induced tachycardia received an intravenous infusion of S(-)-propranolol, on postsurgery day 2 (n = 7) and day 7 (n = 8) with elevated and normal plasma protein binding, respectively.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on lipid metabolism during 1 year of conventional or extended-cycle use.

Background: The effects of extended regimens of combined oral contraceptives (COC) on lipid parameters are largely unknown. The present study compared the effects of a COC containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year.

Study Design: Lipid parameters were measured in 59 women treated with EE/DNG either conventionally (21+7 days) or in extended-cycle regimen (84+7 days).

T lymphocytes impair P-glycoprotein function during neuroinflammation.

The ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp; ABCB1) is highly expressed at the blood-brain barrier (BBB). P-gp actively secretes and keeps the central nervous system (CNS) safe from body-born metabolites, but also from drugs and food components, emphasising the importance of its optimal function to maintain brain homeostasis. Here we demonstrate that vascular P-gp expression and function are strongly decreased during neuroinflammation.

Absence of truncating BRIP1 mutations in chromosome 17q-linked hereditary prostate cancer families.

Background: In a genome-wide scan (GWS) of 175 multiplex prostate cancer (PCa) families from the University of Michigan Prostate Cancer Genetics Project (PCGP), linkage was observed to markers on chromosome 17q21-24, a region that includes two breast cancer susceptibility genes, BRCA1 and BRIP1. BRIP1 is a Fanconi anaemia gene (FANCJ) that interacts with the BRCT domain of BRCA1 and has a role in DNA damage repair. Protein truncating mutations in BRIP1 have been identified in hereditary breast and ovarian cancer families, and a recent report suggested that a recurrent truncating mutation (R798X) may have a role in PCa susceptibility.

A short-breath-hold technique for lung pO2 mapping with 3He MRI.

A pulse-sequence strategy was developed for generating regional maps of alveolar oxygen partial pressure (pO2) in a single 6-sec breath hold, for use in human subjects with impaired lung function. Like previously described methods, pO2 values are obtained by measuring the oxygen-induced T1 relaxation of inhaled hyperpolarized 3He. Unlike other methods, only two 3He images are acquired: one with reverse-centric and the other with centric phase-encoding order.

Characterization of a new chimeric marker vaccine candidate with a mutated antigenic E2-epitope.

A new chimeric pestivirus "CP7_E1E2alf_TLA", based on the infectious cDNA of bovine viral diarrhea virus (BVDV) strain CP7, was constructed. The substitution of BVDV E1 and E2 with the respective proteins of classical swine fever (CSF) strain Alfort 187 allows an optimal heterodimerization of E1 and E2 in the chimeric virus, which is beneficial for efficient and authentic virus assembly and growth. In addition, for implementation of E2-based marker diagnostics, the previously described antigenic CSFV-specific TAVSPTTLR epitope was exchanged with the corresponding E2-epitope of BVDV strain CP7.

Identification of seven new prostate cancer susceptibility loci through a genome-wide association study.

Prostate cancer (PrCa) is the most frequently diagnosed cancer in males in developed countries. To identify common PrCa susceptibility alleles, we previously conducted a genome-wide association study in which 541,129 SNPs were genotyped in 1,854 PrCa cases with clinically detected disease and in 1,894 controls. We have now extended the study to evaluate promising associations in a second stage in which we genotyped 43,671 SNPs in 3,650 PrCa cases and 3,940 controls and in a third stage involving an additional 16,229 cases and 14,821 controls from 21 studies.

Genetic modifiers of liver disease in cystic fibrosis.

Context: A subset (approximately 3%-5%) of patients with cystic fibrosis (CF) develops severe liver disease with portal hypertension.

Objective: To assess whether any of 9 polymorphisms in 5 candidate genes (alpha(1)-antitrypsin or alpha(1)-antiprotease [SERPINA1], angiotensin-converting enzyme [ACE], glutathione S-transferase [GSTP1], mannose-binding lectin 2 [MBL2], and transforming growth factor beta1 [TGFB1]) are associated with severe liver disease in patients with CF.

Design, Setting, And Participants: Two-stage case-control study enrolling patients with CF and severe liver disease with portal hypertension (CFLD) from 63 CF centers in the United States as well as 32 in Canada and 18 outside of North America, with the University of North Carolina at Chapel Hill as the coordinating site.