5,312 research outputs found

    Desistance from Sexual Offending: A Policy and Research Agenda Whose Time Has Come

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    For the past three decades or so, criminal justice policies have been enacted under the assumption that individuals who have been convicted of a sex offense are life course persistent sex offenders. In that context, research has been heavily focused on the assessment of risk and the prediction of sexual recidivism. Simultaneously, little to no attention has been given to the majority of individuals convicted of sex offenses who are not arrested or convicted again.Researchers have witnessed a growing gap between scientific knowledge and the sociolegal response to sexual violence and abuse. The current legal landscape carries important social implications and significant life course impact for a growing number of individuals. More recently, theoretical and research breakthroughs in the study of desistance from crime and delinquency have been made that can help shed some light on desistance from sex offending. Desistance research, in the context of sex offending, however, represents serious theoretical, ethical, legal, and methodological challenges. To that end, this article introduces a special issue exploring current themes in desistance research by examining the life course of individuals convicted of a sexual offense while contextualizing their experiences of desistance.No Full Tex

    Integration Is Correlated With Mental Health Help-Seeking From the General Practitioner: Syrian Refugees' Preferences and Perceived Barriers

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    Despite a seemingly higher need, refugees in Europe tend to underuse mental health (MH) services. To better understand this underuse, it is important to understand refugees' willingness and ability to seek help from their general practitioner (GP) when experiencing MH problems. We employed a combined vignette and survey design to explore how the GP fits into the larger context of help-seeking preferences among a sample of Syrian refugees in Norway (n = 92), and what barriers they perceive in accessing help from the GP. We also examined how indicators of integration relate to seeking help from the GP. We take an exploratory approach. Participants were presented a vignette of an individual with symptoms in line with ICD-10 and DSM-5 criteria for depression. Participants were somewhat likely to seek help from the GP; however, seeking help from one's relationship with Allah/God and one's partner was preferred. Furthermore, while the GP was rated a somewhat likely help-seeking source, most participants indicated an average of two barriers to seeking help from the GP. Finally, social ties to the majority population in the form of social integration and feelings of connectedness with the host country (psychological integration) were positively correlated with likelihood of seeking help from the GP. Taken together, these findings suggest that the GP is considered a viable source of help among Syrians with a refugee background in the current sample, but that this may be influenced by perceived barriers and social as well as psychological integration. Addressing these barriers and promoting psychosocial integration with the host country are key to facilitating access and usage amongst refugees in need of MH services.publishedVersio

    Quantitative in situ hybridization with enhanced sensitivity in soft, bone and tooth tissue using digoxigenin tagged RNA probes

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    Uvod: Kvantitativna neradioaktivna in situ hibridizacija je moćna tehnika za lokalizaciju ekspresije transkripata mRNA. Ove metode omogućavaju otkrivanje mRNA uz visoku rezoluciju na razini jedne jedine stanice. Dosad najšire opisani neradioaktivni protokoli rabili su deblje kriostatske rezove mekog tkiva i lokalizirali visoko zastupljene gene bez kvantificiranja. Materijali i metode: Mi smo razvili metodu neradioaktivne in situ hibridi-zacije pomoću tankih rezova demineraliziranog koštanog tkiva uklopljenog u parafin, uz otkrivanje nisko zastupljenih gena i kvantifikaciju in situ signala. Naš protokol zasniva se na optimalnoj sintezi digoksigeninom obilježenih DNA probi za vizualiziranje vrlo nisko zastupljenih gena u mekom, koštanom i zubnom tkivu uklopljenom u parafin. Naša nova tehnika prikazuje in situ signal uz umnožavanje i pojačanje boje kroz reakciju alkalnefosfataze. Rezultati: Osjetljivost je na razini radioaktivnih protokola, a rezolucija je na razini pojedine stanice, štoje bolje nego kod radioaktivnih protokola. Kvantificiranje in situ hibridizacijskog signala, što se ranije radilo pomoću radioaktivnog ili fluorescentnog obilježavanja, sad je moguće s alkalnom fosfatazom pomoću naše tehnike i programa ImageJ. Zaključak: Prikazani primjeri pokazuju kako slijedeća metoda ima bolju dokazanu rezoluciju i jednaku osjetljivost kao radioaktivno obilježene metode u različitim tkivima s mogućom kvantifikacijom;to pak pokazuje da se ova metoda općenito može rabiti u istraživačkim kao i u kliničkim laboratorijima.Introduction: Quantitative non-radioactive in situ hybridization is a powerful technique for localizing the expression of mRNA transcripts. These methods enable mRNAs to be detected with great resolution on a single cell level. Up to date the most published non-radioactive protocols used thick cryostat sections in soft tissue localizing high abundant genes without quantification. Material and methods: We developed a non-radioactive in situ hybridization method using thin sections of demineralized bone paraffin embedded tissue with low abundant gene detection and in situ signal quantification. Our protocol is based on the optimal synthesis of digoxigenin labeled RNA probes to visualize very low abundant genes in soft, bone and tooth paraffin embedded tissues. Our new technique visualizes an in situ signal with amplification and enhanced color by developing alkaline phosphatase reaction. Results: The sensitivity is at the level of radioactivity and the resolution is at the level of a single cell, which is better than with radioactivity. Quantification of in situ hybridization signal, previously used with radioactive or fluorescent labeling, is now possible with alkaline phosphatase using our technique and ImageJ program. Conclusion: The presented examples show that the following method has better proven resolution and equivalent sensitivity to radioactive labeled methods in different tissues with quantification ability, thus indicating that this method can generally be used in research and clinical laboratories

    Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA).

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    BackgroundEpigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health.ObjectiveWe sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes.MethodsWe estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [[Formula: see text]]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y ([Formula: see text]). We ran the same analyses in the Generation R Study for replication ([Formula: see text]). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression.ResultsLiving closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study.ConclusionsOur discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034

    A eta-alpha and A eta-beta peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

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    Background: Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods: With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results: We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions: These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD

    Heightened immune response to autocitrullinated porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis

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    Background: Rheumatoid arthritis (RA) is characterised by autoimmunity to citrullinated proteins, and there is increasing epidemiologic evidence linking Porphyromonas gingivalis to RA. P gingivalis is apparently unique among periodontal pathogens in possessing a citrullinating enzyme, peptidylarginine deiminase (PPAD) with the potential to generate antigens driving the autoimmune response. Objectives: To examine the immune response to PPAD in patients with RA, individuals with periodontitis (PD) and controls (without arthritis), confirm PPAD autocitrullination and identify the modified arginine residues. Methods: PPAD and an inactivated mutant (C351A) were cloned and expressed and autocitrullination of both examined by immunoblotting and mass spectrometry. ELISAs using PPAD, C351A and another P gingivalis protein arginine gingipain (RgpB) were developed and antibody reactivities examined in patients with RA (n=80), individuals with PD (n=44) and controls (n=82). Results: Recombinant PPAD was a potent citrullinating enzyme. Antibodies to PPAD, but not to Rgp, were elevated in the RA sera (median 122 U/ml) compared with controls (median 70 U/ml; p<0.05) and PD (median 60 U/ml; p<0.01). Specificity of the anti-peptidyl citrullinated PPAD response was confirmed by the reaction of RA sera with multiple epitopes tested with synthetic citrullinated peptides spanning the PPAD molecule. The elevated antibody response to PPAD was abolished in RA sera if the C351A mutant was used on ELISA. Conclusions: The peptidyl citrulline-specific immune response to PPAD supports the hypothesis that, as a bacterial protein, it might break tolerance in RA, and could be a target for therapy

    Prevalence and incidence of carpal tunnel syndrome in US working populations: pooled analysis of six prospective studies

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    OBJECTIVES: Most studies of carpal tunnel syndrome (CTS) incidence and prevalence among workers have been limited by small sample sizes or restricted to a small subset of jobs. We established a common CTS case definition and then pooled CTS prevalence and incidence data across six prospective studies of musculoskeletal outcomes to measure CTS frequency and allow better studies of etiology. METHODS: Six research groups collected prospective data at >50 workplaces including symptoms characteristic of CTS and electrodiagnostic studies (EDS) of the median and ulnar nerves across the dominant wrist. While study designs and the timing of data collection varied across groups, we were able to create a common CTS case definition incorporating both symptoms and EDS results from data that were collected in all studies. RESULTS: At the time of enrollment, 7.8% of 4321 subjects met our case definition and were considered prevalent cases of CTS. During 8833 person-years of follow-up, an additional 204 subjects met the CTS case definition for an overall incidence rate of 2.3 CTS cases per 100 person-years. CONCLUSIONS: Both prevalent and incident CTS were common in data pooled across multiple studies and sites. The large number of incident cases in this prospective study provides adequate power for future exposure– response analyses to identify work- and non-work-related risk factors for CTS. The prospective nature allows determination of the temporal relations necessary for causal inference

    Cx43 Overexpression in Osteocytes Prevents Osteocyte Apoptosis and Preserves Cortical Bone Quality in Aging Mice

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    Young, skeletally mature mice lacking Cx43 in osteocytes exhibit increased osteocyte apoptosis and decreased bone strength, resembling the phenotype of old mice. Further, the expression of Cx43 in bone decreases with age, suggesting a contribution of reduced Cx43 levels to the age-related changes in the skeleton. We report herein that Cx43 overexpression in osteocytes achieved by using the DMP1-8kb promoter (Cx43OT mice) attenuates the skeletal cortical but not trabecular bone phenotype of aged, 14-month-old mice. The percentage of Cx43-expressing osteocytes was higher in Cx43OT mice, whereas the percentage of Cx43-positive osteoblasts remained similar to wild-type (WT) littermate control mice. The percentage of apoptotic osteocytes and osteoblasts was increased in aged WT mice compared with skeletally mature, 6-month-old WT mice, and the percentage of apoptotic osteocytes, but not osteoblasts, was decreased in age-matched Cx43OT mice. Aged WT mice exhibited decreased bone formation and increased bone resorption as quantified by histomorphometric analysis and circulating markers compared with skeletally mature mice. Further, aged WT mice exhibited the expected decrease in bone biomechanical structural and material properties compared with young mice. Cx43 overexpression prevented the increase in osteoclasts and decrease in bone formation on the endocortical surfaces and the changes in circulating markers in the aged mice. Moreover, the ability of bone to resist damage was preserved in aged Cx43OT mice both at the structural and material level. All together, these findings suggest that increased Cx43 expression in osteocytes ameliorates age-induced cortical bone changes by preserving osteocyte viability and maintaining bone formation, leading to improved bone strength. © 2018 American Society for Bone and Mineral Research
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