54 research outputs found

    A Key Role for Neurotensin in Chronic-Stress-Induced Anxiety-Like Behavior in Rats

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    Accepted ManuscriptChronic stress is a major cause of anxiety disorders that can be reliably modeled preclinically, providing insight into alternative therapeutic targets for this mental health illness. Neuropeptides have been targeted in the past to no avail possibly due to our lack of understanding of their role in pathological models. In this study we use a rat model of chronic stress-induced anxiety-like behaviors and hypothesized that neuropeptidergic modulation of synaptic transmission would be altered in the bed nucleus of the stria terminalis (BNST), a brain region suspected to contribute to anxiety disorders. We use brain slice neurophysiology and behavioral pharmacology to compare the role of locally released endogenous neuropeptides on synaptic transmission in the oval (ov) BNST of non-stressed (NS) or chronic unpredictably stressed (CUS) rats. We found that in NS rats, post-synaptic depolarization induced the release of vesicular neurotensin (NT) and corticotropin-releasing factor (CRF) that co-acted to increase ovBNST inhibitory synaptic transmission in 59% of recorded neurons. CUS bolstered this potentiation (100% of recorded neurons) through an enhanced contribution of NT over CRF. In contrast, locally released opioid neuropeptides decreased ovBNST excitatory synaptic transmission in all recorded neurons, regardless of stress. Consistent with CUS-induced enhanced modulatory effects of NT, blockade of ovBNST NT receptors completely abolished stress-induced anxiety-like behaviors in the elevated plus maze paradigm. The role of NT has been largely unexplored in stress and our findings highlight its potential contribution to an important behavioral consequence of chronic stress, that is, exaggerated avoidance of open space in rats.CPN was funded by CIHR Vanier Graduate Scholarship (338319); APVS was funded by Fundação para a Ciência e Tecnologia (SFRH/BPD/52078/2013); ERH was funded by CIHR Postdoctoral Fellowship (MFE-123712); SA was funded by a Queen Elizabeth II Graduate Scholarship in Science and Technology; ÉCD was funded by the Canadian Institute of Health Research (MOP-25953)info:eu-repo/semantics/publishedVersio

    Risk factors for iatrogenic retinal breaks induced by separation of posterior hyaloid face during 23-gauge pars plana vitrectomy

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    Purpose To describe the incidence and features of intraoperative retinal breaks caused by induction of posterior hyaloid face (PHF) separation during 23-gauge pars plana vitrectomy (PPV). Methods A prospective, consecutive, single surgeon, observational study of patients undergoing 23-gauge transconjunctival sutureless vitrectomy for macular pathology or floaters, was carried out between 2009 and 2011 at Calderdale Royal Hospital, UK. PHF separations were categorised as either suction induced or requiring membrane blue (DORC Limited) with suction (adherent). The outcome measure was dichotomised into retinal break or tear and no retinal break or tear. Forced entry and parsimonious multiple logistic regression analyses were conducted, using statistical software, to test for significance of association of the set of recorded factors and covariates with the dichotomised outcome measure. Results Data were collected and analysed from 137 patients. The incidence of iatrogenic retinal breaks associated with PHF separation during 23-gauge PPV was 18.2%. Under both forced entry and parsimonious multiple logistic regression models, the odds of a retinal break or tear reduce by about 3–4% for each increasing year of age. Findings also showed some substantive association in the forced entry model, with the odds of a retinal break or tear for adherent cases being around 3.8 times those for suction-only cases. Conclusions Mechanical detachment of the PHF represents an important risk factor in the formation of retinal breaks. Particular care should be taken to examine intraoperatively for iatrogenic breaks in order to prevent missed breaks and subsequent rhegmatogenous retinal detachments

    Correction: Socio-economic position as a moderator of cardiometabolic outcomes in patients receiving psychotropic treatment associated with weight gain: results from a prospective 12-month inception cohort study and a large population-based cohort.

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    Weight gain and metabolic complications are major adverse effects of many psychotropic drugs. We aimed to understand how socio-economic status (SES), defined as the Swiss socio-economic position (SSEP), is associated with cardiometabolic parameters after initiation of psychotropic medications known to induce weight gain. Cardiometabolic parameters were collected in two Swiss cohorts following the prescription of psychotropic medications. The SSEP integrated neighborhood-based income, education, occupation, and housing condition. The results were then validated in an independent replication sample (UKBiobank), using educational attainment (EA) as a proxy for SES. Adult patients with a low SSEP had a higher risk of developing metabolic syndrome over one year versus patients with a high SSEP (Hazard ratio (95% CI) = 3.1 (1.5–6.5), n = 366). During the first 6 months of follow-up, a significant negative association between SSEP and body mass index (BMI), weight change, and waist circumference change was observed (25 ≤ age < 65, n = 526), which was particularly important in adults receiving medications with the highest risk of weight gain, with a BMI difference of 0.86 kg/m(2) between patients with low versus high SSEP (95% CI: 0.03–1.70, n = 99). Eventually, a causal effect of EA on BMI was revealed using Mendelian randomization in the UKBiobank, which was notably strong in high-risk medication users (beta: −0.47 SD EA per 1 SD BMI; 95% CI: −0.46 to −0.27, n = 11,314). An additional aspect of personalized medicine was highlighted, suggesting the patients’ SES represents a significant risk factor. Particular attention should be paid to patients with low SES when initiating high cardiometabolic risk psychotropic medications
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