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    2494 research outputs found

    Serum microRNA miR-501-3p as a potential biomarker related to the progression of Alzheimer\u2019s disease

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    Abstract MicroRNAs (miRNAs) are attractive molecules to utilize as one of the blood-based biomarkers for neurodegenerative disorders such as Alzheimer\u2019s disease (AD) because miRNAs are relatively stable in biofluid, including serum or plasma. To determine blood miRNA biomarkers for AD with next-generation sequencing genome-wide, we first surveyed 45 serum samples. These came from 27 AD patients and 18 controls (discovery set) that underwent autopsy within two weeks after their serum sampling and were neuropathologically diagnosed. We found that three miRNAs, hsa-miR-501-3p, hsa-let-7f-5p, and hsa-miR-26b-5p, were significantly deregulated between the AD samples and the controls. The deregulation for hsa-miR-501-3p was further confirmed by quantitative reverse transcription polymerase chain reaction (PCR) in a validation set composed of 36 clinically diagnosed AD patients and 22 age-matched cognitively normal controls with a sensitivity and specificity of 53% and 100%, respectively (area under the curve\u2009=\u20090.82). Serum hsa-miR-501-3p levels were downregulated in AD patients, and its lower levels significantly correlated with lower Mini-Mental State Examination scores. Contrary to its serum levels, we found that hsa-miR-501-3p was remarkably upregulated in the same donors\u2019 AD brains obtained at autopsy from the discovery set. The hsa-miR-501-3p overexpression in cultured cells, which mimicked the hsa-miR-501-3p upregulation in the AD brains, induced significant downregulation of 128 genes that overrepresented the Gene Ontology terms, DNA replication, and the mitotic cell cycle. Our results suggest that hsa-miR-501-3p is a novel serum biomarker that presumably corresponds to pathological events occurring in AD brains

    Mental illness and violent behavior: the role of dissociation

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    Abstract Background The role of mental illness in violent crime is elusive, and there are harmful stereotypes that mentally ill people are frequently violent criminals. Studies find greater psychopathology among violent offenders, especially convicted homicide offenders, and higher rates of violence perpetration and victimization among those with mental illness. Emotion dysregulation may be one way in which mental illness contributes to violent and/or criminal behavior. Although there are many stereotyped portrayals of individuals with dissociative disorders (DDs) being violent, the link between DDs and crime is rarely researched. Methods We reviewed the extant literature on DDs and violence and found it is limited to case study reviews. The present study addresses this gap through assessing 6-month criminal justice involvement among 173 individuals with DDs currently in treatment. We investigated whether their criminal behavior is predicted by patient self-reported dissociative, posttraumatic stress disorder and emotion dysregulation symptoms, as well as clinician-reprted depressive disorders and substance use disorder. Results Past 6\ua0month criminal justice involvement was notably low: 13% of the patients reported general police contact and 5% reported involvement in a court case, although either of these could have involved the DD individual as a witness, victim or criminal. Only 3.6% were recent criminal witnesses, 3% reported having been charged with an offense, 1.8% were fined, and 0.6% were incarcerated in the past 6\ua0months. No convictions or probations in the prior 6\ua0months were reported. None of the symptoms reliably predicted recent criminal behavior. Conclusions In a representative sample of individuals with DDs, recent criminal justice involvement was low, and symptomatology did not predict criminality. We discuss the implications of these findings and future directions for research

    Development and characterization of novel microsatellite markers for the Common Pheasant (Phasianus colchicus) using RAD-seq

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    Abstract Background The Common Pheasant ( Phasianus colchicus ) Linnaeus, 1758 is the most widespread pheasant in the world and widely introduced as a game bird. Increasing needs for conservation genetics and management of both wild and captive populations require permanent genetic resources, such as polymorphic microsatellites in order to genotype individuals and populations. Methods In this study, 7598 novel polymorphic microsatellites for the Common Pheasant were isolated using a RAD-seq approach at an Illumina high-throughput sequencing platform. A panel of ten novel microsatellites and three existing ones from the chicken genome were multiplexed and genotyped on a set of 90 individuals of Common Pheasants (representing nine subspecies and ten individuals each) and 10 individuals of the Green Pheasant ( P. versicolor ). Results These 13 microsatellites exhibited moderate to high levels of polymorphism, with the number of alleles per locus ranging from 2 to 8 and expected heterozygosities from 0.049 to 0.905. The first analysis of the genetic structure of subspecies/populations using a Bayesian clustering approach, implemented in STRUCTURE, showed two genetic clusters, corresponding to both the Green and the Common Pheasant, with further evidence of subpopulation structuring within the Common Pheasants. Conclusion These markers are useful genetic tools for sustainable uses and evolutionary studies in these two Phasianus pheasants and probably other closely related game birds

    Longitudinal studies in ECEC: challenges of translating research into policy action

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    Biomaterials and tissue engineering for scar management in wound care

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    Abstract Scars are a natural and unavoidable result from most wound repair procedures and the body\u2019s physiological healing response. However, they scars can cause considerable functional impairment and emotional and social distress. There are different forms of treatments that have been adopted to manage or eliminate scar formation. This review covers the latest\ua0research in the past decade on using either natural agents or synthetic biomaterials in treatments for scar reduction

    Simulation and mental health outcomes: a scoping review

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    Abstract Background A scoping review was conducted in order to map and determine the gaps in literature on the impact of simulation as an educational approach to improve mental health care outcomes. As it became apparent that no literature existed on this topic, the study aimed to examine the educational impact of simulation on mental health education. Methods An established five-stage scoping methodology was used: (1) identification of the research question, (2) identification of relevant studies, (3) study selection, (4) charting the data and (5) collation, summarising and reporting of results. CINAHL, ProQuest, PubMed, MEDLINE, EMBASE and PsychINFO databases were searched. These databases were deemed to represent a majority of the literature while accommodating for the particular search strategy used for this review. Websites that provide grey literature were also searched for articles of relevance. Results A total of 48 articles were included in this review, with a considerable portion of studies conducted in the USA and UK. Others were conducted in an array of locations including Australia, Canada, Iran and Taiwan. Of the included articles, seven groups of simulation methods (including standardised patients, virtual reality and manikins as patients) were evident, with standardised patients being most prominent. Conclusions Literature is lacking to evidence the benefit of simulation on mental health patient outcomes. However, the available literature suggests a variety of simulation-based education, and training methods are currently being used within mental healthcare education. The findings do suggest some methods of simulation, such as the use of standardised patients, are more commonly used in education and have been deemed as effective to assist in mental health education. As no article specifically examining the mental health outcomes of patients treated by health professionals taught by simulation was identified, the educational outcomes outlined in this paper may be used to inform further research, incorporating mental health patient outcomes

    Incidence of hepatitis C among people who inject drugs in Ireland

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    Abstract Background Comprehensive information on the incidence and duration of hepatitis C virus (HCV) infection for people who inject drugs (PWID) in Ireland is not available. We created an incidence curve of injecting drug use in Ireland and subsequently estimated incidence of hepatitis C virus (HCV) infection. Methods Anonymised data from the National Drug Treatment Reporting System (NDTRS) were used to identify all people who inject drugs (PWIDs) and who entered drug treatment for the first time between 1991 and 2014. A curve, estimating the incidence of injecting, was created to plot PWIDs by year of commencing injecting. The curve was adjusted for missing data on PWIDs in treatment and for PWIDs who were never treated. An adjustment was made to account for injectors who had never shared injecting equipment. The incidence of HCV infection and chronic infection in PWIDs was estimated by applying published rates. Results Between 1991 and 2014, 14,320 injectors were registered on NDTRS. The majority were young (median age 25\ua0years), male (74%), lived in Dublin (73%) and injected an opiate (e.g. heroin) (94%). The estimated total number of injectors up to the end of 2014 was 16,382. An estimated 12,423 (95% CI 10,799-13,161) were infected with HCV, and 9,317 (95% CI 8,022-9,996) became chronically infected. The estimated annual number of new HCV infections among PWIDs increased steeply from the late 1970s and peaked in 1998. By 2014, almost 30% of injectors were estimated to have been infected for over 20\ua0years. Conclusions This is the first comprehensive national estimate of the incidence of HCV in PWIDs in Ireland and will inform planning and developing appropriate health care services

    Genotype- and sex-dependent effects of altered Cntnap2 expression on the function of visual cortical areas

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    Abstract Background Autism spectrum disorder (ASD) is a heritable, heterogeneous neurodevelopmental disorder that is four times more likely to affect males than females. Despite this overt sex bias, it is unclear how genetic mutations associated with ASD alter cortical circuitry to produce the behavioral phenotypes by which ASD is diagnosed. Contactin-associated protein-like 2 ( CNTNAP2 ) is an ASD-associated gene, and while Cntnap2 knockout (KO) mice recapitulate many of the features of ASD, the effect on cortical circuitry is poorly understood. Moreover, although heterozygous (Het) mice are the more relevant genotype for ASD-linked CNTNAP2 mutations in humans, to our knowledge, no effects in Het mice have been previously reported. Methods Intrinsic signal optical imaging was used to measure functional visual responses in primary and higher visual cortical areas in male and female Cntnap2 KO, Het, and wild-type (WT) mice. Main effect of genotype was assessed with one-way ANOVA. Visual responses were also measured in P17\u201318 and P30\u201332 KO and WT mice. Main effects of age and genotype were assessed using two-way ANOVA. Results Visually evoked activity in dorsal stream associated higher visual areas in both KO and Het adult males was decreased relative to WT adult males. This decrease was not observed in adult females. Additionally, no significant difference was observed between WT and KO males at P17\u201318 with differences beginning to emerge at P30\u201332. Conclusions The functional responses of cortical circuitry in male mice are more strongly affected by Cntnap2 mutations than females, an effect present even in Hets. The observed differences in males emerge with development beginning at P30\u201332. These results reveal genotype- and sex-dependent effects of altered Cntnap2 expression and can shed light on the sex-dependent incidence of ASD

    Genetic and economic benefits of selection based on performance recording and genotyping in lower tiers of multi-tiered sheep breeding schemes

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    Abstract Background Performance recording and genotyping in the multiplier tier of multi-tiered sheep breeding schemes could potentially reduce the difference in the average genetic merit between nucleus and commercial flocks, and create additional economic benefits for the breeding structure. Methods The genetic change in a multiple-trait breeding objective was predicted for various selection strategies that included performance recording, parentage testing and genomic selection. A deterministic simulation model was used to predict selection differentials and the flow of genetic superiority through the different tiers. Cumulative discounted economic benefits were calculated based on trait gains achieved in each of the tiers and considering the extra revenue and associated costs of applying recording, genotyping and selection practices in the multiplier tier of the breeding scheme. Results Performance recording combined with genomic or parentage information in the multiplier tier reduced the genetic lag between the nucleus and commercial flock by 2\ua0to\ua03\ua0years. The overall economic benefits of improved performance in the commercial tier offset the costs of recording the multiplier. However, it took more than 18\ua0years before the cumulative net present value of benefits offset the costs at current test prices. Strategies in which recorded multiplier ewes were selected as replacements for the nucleus flock did modestly increase profitability when compared to a closed nucleus structure. Applying genomic selection is the most beneficial strategy if testing costs can be reduced or by genotyping only a proportion of the selection candidates. When the cost of genotyping was reduced, scenarios that combine performance recording with genomic selection were more profitable and reached breakeven point about 10\ua0years earlier. Conclusions Economic benefits can be generated in multiplier flocks by implementing performance recording in conjunction with either DNA pedigree recording or genomic technology. These recording practices reduce the long genetic lag between the nucleus and commercial flocks in multi-tiered breeding programs. Under current genotyping costs, the time to breakeven was found to be generally very long, although this varied between strategies. Strategies using either genomic selection or DNA pedigree verification were found to be economically viable provided the price paid for the tests is lower than current prices, in the long-term

    Genome-wide standing variation facilitates long-term response to bidirectional selection for antibody response in chickens

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    Abstract Background Long-term selection experiments provide a powerful approach to gain empirical insights into adaptation, allowing researchers to uncover the targets of selection and infer their contributions to the mode and tempo of adaptation. Here we implement a pooled genome re-sequencing approach to investigate the consequences of 39 generations of bidirectional selection in White Leghorn chickens on a humoral immune trait: antibody response to sheep red blood cells. Results We observed wide genome involvement in response to this selection regime. Many genomic regions were highly differentiated resulting from this experimental selection regime, an involvement of up to 20% of the chicken genome (208.8\ua0Mb). While genetic drift has certainly contributed to this, we implement gene ontology, association analysis and population simulations to increase our confidence in candidate selective sweeps. Three strong candidate genes, MHC , SEMA5A and TGFBR2 , are also presented. Conclusions The extensive genomic changes highlight the polygenic genetic architecture of antibody response in these chicken populations, which are derived from a common founder population, demonstrating the extent of standing immunogenetic variation available at the onset of selection

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