Zhaovance9833

among populations and subphenotypes of PD.Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.The quantitative genetic contribution to antisocial behavior is well established, but few, if any, genetic variants are established as risk factors. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may modulate interpersonal aggression. We here investigated whether single-nucleotide polymorphisms (SNPs) in the OXT receptor gene (OXTR) are associated with the expression of antisocial behavior. A discovery sample, including both sexes, was drawn from the Child and Adolescent Twin Study in Sweden (CATSS; n=2372), and a sample from the Twin Study of Child and Adolescent Development (TCHAD; n=1232) was used for replication. Eight SNPs in OXTR, selected on previous associations with social and antisocial behavior, were genotyped in the participants of CATSS. Significant polymorphisms were subsequently genotyped in TCHAD for replication. Participants completed self-assessment questionnaires-Life History of Aggression (LHA; available only in CATSS), and Self-Reported Delinquency (SRD; available in bothbehavior.Schizophrenia (SZ) is a devastating psychiatric condition affecting numerous brain systems. Recent studies have identified genetic factors that confer an increased risk of SZ and participate in the disease etiopathogenesis. In parallel to such bottom-up approaches, other studies have extensively reported biological changes in patients by brain imaging, neurochemical and pharmacological approaches. This review highlights the molecular substrates identified through studies with SZ patients, namely those using top-down approaches, while also referring to the fruitful outcomes of recent genetic studies. We have subclassified the molecular substrates by system, focusing on elements of neurotransmission, targets in white matter-associated connectivity, immune/inflammatory and oxidative stress-related substrates, and molecules in endocrine and metabolic cascades. selleck chemicals We further touch on cross-talk among these systems and comment on the utility of animal models in charting the developmental progression and interaction of these substrates. Based on this comprehensive information, we propose a framework for SZ research based on the hypothesis of an imbalance in homeostatic signaling from immune/inflammatory, oxidative stress, endocrine and metabolic cascades that, at least in part, underlies deficits in neural connectivity relevant to SZ. Thus, this review aims to provide information that is translationally useful and complementary to pathogenic hypotheses that have emerged from genetic studies. Based on such advances in SZ research, it is highly expected that we will discover biomarkers that may help in the early intervention, diagnosis or treatment of SZ.The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10(-17)) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely.A boy at 12 days of age developed neonatal herpes simplex virus (HSV) type 2 infection with central nervous system (CNS) disease. After a 21-day course of high-dose intravenous acyclovir, the patient recovered with negative results for HSV DNA in serum and cerebrospinal fluid. Two weeks after a 6-month course of oral valacyclovir suppressive therapy with negative virological assessment, the disease recurred. Another 21-day course of intravenous acyclovir and subsequent 1-year course of oral suppressive therapy were completed. He showed mild developmental delay in language-social skills at 18 months of age. Although recurrences of neonatal HSV infection with CNS disease after suppressive therapy are uncommon, both clinical and virological assessments at the end of the suppressive therapy may be required. Administration of extended long-term suppressive ACV therapy should be considered to reduce the rate of recurrence.Whipple's disease, a systemic, chronic infectious disease caused by Tropheryma whipplei, is extremely rare in Asian populations. A correct diagnosis is necessary due to its high mortality rate. Unfortunately, patients are apt to be misdiagnosed with connective tissue diseases since they typically present with arthritis or arthralgia. There are three diagnostic tools for Whipple's disease using intestinal tissues 1) periodic acid-Schiff (PAS)-positive macrophages; 2) electron microscopic observation; and 3) polymerase chain reaction (PCR). It is challenging to diagnose this disease in the absence of histological findings, especially in Japan, where the clinical protocol currently used to make the diagnosis needs improvement, although symptomology and PCR results may be sufficient. Herein, we investigated a 24-year-old Japanese woman who had suffered from intermittent fever, migratory arthralgia, and watery diarrhea for several months. Her biopsied intestinal tissue was negative for foamy macrophages and PAS-positive cells, and electron microscopy did not provide diagnostic insight. PCR amplification of the specimens, however, successfully revealed T. whipplei. Whipple's disease was diagnosed based on a positive PCR result and strong clinical suspicion. The patient was treated parenterally with ceftriaxone (2 g daily) for two weeks, followed by oral treatment with 160 mg trimethoprim and 800 mg sulfamethoxazole twice per day. After one month of treatment, her symptoms disappeared and inflammatory markers returned to normal levels. This case illustrates the practicality and effectiveness of a PCR-based diagnostic test in combination with clinical suspicion to correctly diagnose Whipple's disease, especially in cases when a histological examination does not provide insight.

Cognitive impairment increases fall risk in older adults. Dual-task testing is an accepted way to assess the interaction between cognition and mobility; however, there is a lack of evidence-based recommendations for dual-task testing to evaluate fall risk in clinical practice.

To evaluate the association between dual-task testing protocols and future fall risk, and to identify the specific dual-task test protocols associated with elevated risk.

MEDLINE, Pubmed and EMBASE electronic databases were searched from January 1988 to September 2013.

Two independent raters identified prospective cohort studies (duration of at least 1 year) of dual-task assessment in community-dwelling participants aged ≥60 years, with 'falls' as the primary outcome.

Methodological quality was scored independently by two raters using a published checklist of criteria for evaluating threats to the validity of observational studies.

Deterioration in gait during dual-task testing compared with single-task performance was associated with increased fall risk. Shortcomings within the literature significantly limit knowledge translation of dual-task gait protocols into clinical practice.

There is a paucity of prospective studies on the association of dual-task gait assessment with fall risk.

Changes in gait under dual-task testing are associated with future fall risk, and this association is stronger than that for single-task conditions. Limitations in the available literature preclude development of detailed recommendations for dual-task gait testing procedures in clinical practice to identify and stratify fall risk in older adults.

Changes in gait under dual-task testing are associated with future fall risk, and this association is stronger than that for single-task conditions. Limitations in the available literature preclude development of detailed recommendations for dual-task gait testing procedures in clinical practice to identify and stratify fall risk in older adults.

Farmers constitute an occupation group at a heightened suicide risk compared to the general population. To date, research has tried to explain this peculiarity by identifying suicide risk factors that are common to the whole of the farming population. There are, however, indications that risk factors may be different for different sub-populations of farmers, such as younger/older farmers or farm managers/farm labourers. This study compared the characteristics of suicides by farm managers and farm labourers, while controlling for the effect of age.

A review of two datasets, the Queensland Suicide Register and the National Coroners Information System, was conducted in which a total of 78 cases of farm managers and 69 cases of farm labourers were identified as a suicide during 2000-2009, Queensland, Australia. The main outcome measures included various demographic characteristics, circumstances related to death, health and mental health variables, and history of stressful life events.

The two groups differed in marital status, living arrangements, ethnicity, physical and mental illness, alcohol and drug abuse, contact with a health professional prior to death, and specific life events such as relationship breakdown and recent/pending unemployment.