Pharmacological characterization of psychosis-like behavior in the MPTP-lesioned nonhuman primate model of Parkinson's disease.

Investigation of the pathophysiology of psychosis in Parkinson's disease (PD), as well as the assessment of potential novel therapeutics, has been limited by the lack of a well-validated animal model. MPTP-lesioned primates exhibit abnormal behaviors that are distinct from dyskinesia and parkinsonism and may represent behavioral correlates of neural processes related to psychosis in PD. Here we assess four types of behavior--agitation, hallucinatory-like responses to nonapparent stimuli, obsessive grooming, and stereotypies that are termed "psychosis-like"--and define their pharmacology using a psychosis-like behavior rating scale. By assessing the actions of drugs known to enhance or attenuate psychosis in PD patients, we find that the pharmacology of these behaviors recapitulates, in several respects, the pharmacology of psychosis in PD. Thus, levodopa and apomorphine elicited psychosis-like behaviors. Amantadine significantly decreased levodopa-induced dyskinesia but exacerbated psychosis-like behaviors. Haloperidol reduced psychosis-like behaviors but at the expense of increased parkinsonian disability while the atypical neuroleptics clozapine and quetiapine reduced psychosis-like behaviors without significant effect on parkinsonian disability. The response of different components of the psychotomimetic behavior suggested the involvement of both dopaminergic and nondopaminergic mechanisms in their expression.     

Brain-derived neurotrophic factor facilitates in vivo internalization of tetanus neurotoxin C-terminal fragment fusion proteins in mature mouse motor nerve terminals

In a previous study it was reported that fusion proteins composed of the atoxic C-terminal fragment of tetanus toxin (TTC) and green fluorescent protein or beta-galactosidase (GFP-TTC and beta-gal-TTC, respectively) rapidly cluster at motor nerve terminals of the mouse neuromuscular junction (NMJ). Because this traffic involves presynaptic activity, probably via the secretion of active molecules, we examined whether it is affected by brain-derived neurotrophic factor (BDNF). Quantitative confocal microscopy and a fluorimetric assay for beta-gal activity revealed that co-injecting BDNF and the fusion proteins significantly increased the kinetics and amount of the proteins' localization at the NMJ and their internalization by motor nerve terminals. The observed increases were independent of synaptic vesicle recycling because BDNF did not affect spontaneous quantal acetylcholine release. In addition, injecting anti-BDNF antibody shortly before injecting GFP-TTC, and before co-injecting GFP-TTC and BDNF, significantly reduced the fusion protein's localization at the NMJ. Co-injecting GFP-TTC with neurotrophin-4 (NT-4) or glial-derived neurotrophic factor (GDNF), but not with nerve growth factor, neurotrophin-3 or ciliary neurotrophic factor, also significantly increased the fusion protein's localization at the NMJ. Thus, TTC probes may use for their neuronal internalization endocytic pathways normally stimulated by BDNF, NT-4 and GDNF binding. Different tyrosine kinase receptors with similar signalling pathways are activated by BDNF/NT-4 and GDNF binding. Thus, activated components of these signalling pathways may be involved in the TTC probes' internalization, perhaps by facilitating localization of receptors of TTC in specific membrane microdomains or by recruiting various factors needed for internalization of TTC.     

Comparison of the impact of atrial fibrillation on the risk of early death after stroke in women versus men

BACKGROUND: Atrial fibrillation (AF) is considered a predictive factor of poor clinical outcome in patients with an ischemic stroke (IS). This study addressed whether the impact of AF on the in-hospital mortality after first ever IS is different according to the patient's gender. METHODS: We prospectively studied 1678 patients with first ever IS consecutively admitted to two University Hospitals. We recorded demographic data, vascular risk factors, and the stroke severity (NIHSS) at admission analyzing their impact on the in-hospital mortality and on the combined mortality-dependency at discharge using a Cox proportional hazards model. Two variable interactions between those factors independently related to in-hospital mortality and combined mortality-dependency at discharge were tested. RESULTS: Overall in-hospital mortality was 11.3%. Cox proportional hazards model showed that NIHSS at admission (HR: 1.178 [95% CI 1.149-1.207]), age (HR: 1.044 [95% CI 1.026-1.061]), AF (HR: 1.416 [95% CI 1.048-1.913]), male gender (HR: 1.853 [95% CI 1.323-2.192) and ischemic heart disease (HR: 1.527 [95% CI 1.063-2.192]) were independent predictors of in-hospital mortality. A significant interaction between gender and AF was found (p = 0.017). Data were stratified by gender, showing that AF was an independent predictor of poor outcome just for woman (HR: 2.183 [95% CI 1.403-3.396]; p < 0.001). The independent predictors of combined mortality-disability at discharge were NIHSS at admission (HR: 1.052 [95% CI 1.041-1.063]), age (HR: 1.011 [95% CI 1.004-1.018]), AF (HR: 1.197 [95% CI 1.031-1.390]), ischemic heart disease (HR: 1.222 [95% CI 1.004-1.488]), and smoking (HR: 1.262 [95% CI 1.033-1.541]). CONCLUSIONS: The impact of AF is different in the two genders and appears as a specific ischemic stroke predictor of in-hospital mortality just for women.     

Glial cell line-derived neurotrophic factor promotes the arborization of cultured striatal neurons through the p42/p44 mitogen-activated protein kinase pathway

Glial cell line-derived neurotrophic factor (GDNF) promotes the survival or differentiation of several types of neurons. This study examines GDNF-induced signal transduction and biological effects in cultured striatal neurons. Results show that GDNF addition to striatal cultures transiently increased the protein levels of phosphorylated p42/p44, but did not change the levels of phosphorylated Akt. GDNF effects on phosphorylated p42/p44 levels were blocked by the mitogen-activated protein kinase (MAPK) pathway specific inhibitors (PD98059 and U0126). Activation of the p42/p44 MAPK pathway by GDNF led to an increase in the degree of dendritic arborization and axon length of both GABA- and calbindin-positive neurons but had no effect on their survival and maturation. These GDNF-mediated effects were suppressed in the presence of the inhibitor of the MAPK pathway (PD98059). Furthermore, the addition of the phosphatidylinositol 3-kinase pathway specific inhibitor (LY294002) blocked GDNF-mediated striatal cell differentiation suggesting that the basal activity of this pathway is needed for the effects of GDNF. Our results indicate that treatment of cultured striatal cells with GDNF specifically activates the p42/p44 MAPK pathway, leading to an increase in the arborization of GABA- and calbindin-positive neurons.     

Linfadenitis cervical debida a granuloma de silicona tras implantes mamarios

IntroductionA foreign body reaction due to silicone where it is infiltrated or at the places to which it can migrate is known as siliconoma. The use of silicone in breast augmentation procedures can provoke this reaction at the neck level in cases of leakage from mammary implants.MethodsWe reviewed the cases of patients with increased size neck lymph nodes who had previously undergone plastic surgery of the breast with highly cohesive silicone gel implants.ResultsIn a 10-year period, we identified 12 cases with silicone-infiltrated neck lymphadenopathies, histologically confirmed by fine needle aspiration. They represented 3.5% of patients attended for neck lymph node study. We removed those detected by physical examination and CT in 5 cases, due to pathological characteristics of the node or a previous malignant history. In 2 of these nodes recurred, and node size also increased in 2 of the other 7 non-operated cases. After implant removal, silicone leakage was observed in only 7 cases.ConclusionsCohesive gel silicone used for mammary implants can generate increased neck lymphadenopathies as a secondary effect due to systemic reactions against the silicone when it migrates in cases of implant failure. Surgical options for involved nodes usually do not offer good long-term results.     

Incidental finding of migrated pacing lead fragment into pulmonary artery detected with CT

This case shows a rare complication of a migrated atrial lead into the pulmonary artery incidentally detected during a comprehensive evaluation of coronary CT angiography.     

Early-Life Exposure to Outdoor Air Pollution and Respiratory Health,Ear Infections,and Eczema in Infants from the INMA Study

Background: Prenatal and early-life periods may be critical windows for harmful effects of air pollution on infant health.Objectives: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12–18 months of age in a Spanish birth cohort of 2,199 infants.Methods: We obtained parentally reported information on doctor-diagnosed lower respiratory tract infections (LRTI) and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO₂) and benzene with temporally adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations.Results: A 10-µg/m³ increase in average NO₂ during pregnancy was associated with LRTI [relative risk (RR) = 1.05; 95% CI: 0.98, 1.12] and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO₂ were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared with NO₂, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, so we were unable to discern the relative importance of each exposure period.Conclusions: Our findings support the hypothesis that early-life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.     

Adaptation into Spanish of the Warwick–Edinburgh Mental Well-being Scale (WEMWBS) and preliminary validation in a student sample

Purpose

There is growing interest in the assessment of positive mental health as a global indicator of societal wealth. We aimed to adapt the Warwick–Edinburgh Mental Well-being scale (WEMWBS) into Spanish and to perform a preliminary evaluation of its metric properties.

Methods

Forward and back-translations and cognitive debriefing were carried out. University students (n = 148) were recruited to evaluate the final Spanish version, following the UK original study. Distribution of WEMWBS responses, internal consistency, test–retest reliability, construct validity, and factor structure were assessed.

Results

Only 4 (out of 14) items of the initial Spanish version were not rated as conceptually and linguistically equivalent to the original and were modified. The final version was clear and comprehensible. Global score’s Cronbach’s alpha (0.90), item-total score correlations (0.44–0.76), and test–retest ICC (0.84) were all satisfactory. Moderate to high correlations (r = 0.45–0.70) were observed between the WEMWBS and validity scales. Preliminary confirmatory factor analyses did not support the hypothesis of a single factor.

Conclusions

A conceptually equivalent Spanish version of the WEMWBS was obtained with high internal consistency, good test–retest reliability, and similar construct validity as the original instrument. Further validity and factorial studies are necessary in larger and more heterogeneous samples.