Neuronal Programmed Cell Death-1 Ligand Expression Regulates Retinal Ganglion Cell Number in Neonatal and Adult Mice

OBJECTIVES:: During mouse retina maturation, the final number of retinal ganglion cells (RGCs) is determined by highly regulated programmed cell death. Previous studies demonstrated that the immunoregulatory receptor programmed cell death-1 (PD-1) promotes developmental RGC death. To identify the functional signaling partner(s) for PD-1, we identified retinal expression of PD-1 ligands and examined the effect of PD-1 ligand expression on RGC number. We also explored the hypothesis that PD-1 signaling promotes the development of functional visual circuitry. METHODS:: Characterization of retinal and brain programmed cell death-1 ligand 1 (PD-L1) expression were examined by immunofluorescence on tissue sections. The contribution of PD-ligands, PD-L1, and programmed cell death-1 ligand 2 (PD-L2) to RGC number was examined in PD-ligand knockout mice lacking 1 or both ligands. Retinal architecture was assessed by spectral-domain optical coherence tomography, and retinal function was analyzed by electroretinography in wild-type and PD-L1/L2 double-deficient mice. RESULTS:: PD-L1 expression is found throughout the neonatal retina and persists in adult RGCs, bipolar interneurons, and Müller glia. In the absence of both PD-ligands, there is a significant numerical increase in RGCs (34% at postnatal day 2 [P2] and 18% in adult), as compared to wild type, and PD-ligands have redundant function in this process. Despite the increased RGC number, adult PD-L1/L2 double-knockout mice have normal retinal architecture and outer retina function. CONCLUSION:: This study demonstrates that PD-L1 and PD-L2 together impact the final number of RGCs in adult mice and supports a novel role for active promotion of neuronal cell death through PD-1 receptor-ligand engagement.     

Medication adherence in schizophrenia

Non-adherence is a major problem in the treatment of schizophrenia. Its high prevalence, potentially severe consequences and associated costs make the study of this phenomenon a priority issue. In this article, basic non-adherence concepts of prevalence, consequences, evaluation methods, methodological restrictions of available studies, risk factors and intervention strategies, are reviewed. Studying non-adherence risk factors is a necessary step toward designing adequately oriented intervention strategies. An operative definition of adherence and good knowledge of its evaluation methods are essential to study this phenomenon. Unfortunately, most available studies contain methodological restrictions, especially concerning the evaluation methods, and an agreed operative definition of adherence has only very recently been reached. Knowing non-adherence risk factors, intervention strategies and available evidence on their effectiveness is essential in making treatment decisions in daily clinical practice.     

Pregnancy in patients with Sydenham's Chorea

BackgroundSydenham’s Chorea is a frequent cause of chorea during pregnancy, chorea gravidarum. The aim of this article is to describe the effect of pregnancy in a consecutive series of patients with diagnosis of Sydenham’s Chorea.MethodsA chart review was performed of all patients with the diagnosis of Sydenham’s Chorea followed up at our institution from 07/1993 through 08/2010 and who became pregnant.ResultsFrom 66 patients, 20 became pregnant. Of these 20 patients, 15 (75%) developed chorea gravidarum. Generalized chorea was found in 67% of these 15 patients, focal or multifocal chorea was identified in 20% and 13.4% developed hemichorea. In 80% of cases chorea began in the first 6 months of gestation. Three women with previous persistent chorea experienced worsening of the movement disorder during pregnancy. Remission occurred after delivery in 11 patients whereas the other four remained with non-disabling chorea during the first 12 months after delivery. Abortion occurred in two patients (13%). All patients with chorea gravidarum subsequently treated with oral contraceptives developed recurrence of chorea.ConclusionsChorea gravidarum is a frequent complication of pregnancy in patients with previous history of Sydenham’s Chorea and an increased risk of miscarriage should be considered. Our findings confirm the notion that chorea gravidarum results from hormonal changes acting on previously dysfunctional basal ganglia.     

Factorial validity and measurement equivalence of the Client Assessment of Treatment Scale for psychiatric inpatient care - a study in three European countries

Patients' views of inpatient care need to be assessed for research and routine evaluation. For this a valid instrument is required. The Client Assessment of Treatment Scale (CAT) has been used in large scale international studies, but its psychometric properties have not been well established. The structural validity of the CAT was tested among involuntary inpatients with psychosis. Data from locations in three separate European countries (England, Spain and Bulgaria) were collected. The factorial validity was initially tested using single sample confirmatory factor analyses in each country. Subsequent multi-sample analyses were used to test for invariance of the factor loadings, and factor variances across the countries. Results provide good initial support for the factorial validity and invariance of the CAT scores. Future research is needed to cross-validate these findings and to generalise them to other countries, treatment settings, and patient populations.     

Malnutrition in infancy as a susceptibility factor for temporal lobe epilepsy in adulthood induced by the pilocarpine experimental model

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.     

Granulomatous slack skin‐like clinical findings in Sézary syndrome

Granulomatous slack skin (GSS) is a very rare condition that has been described as a variant of mycosis fungoides. It is characterized by the development of bulky and pendulous skin folds in flexural areas that are histologically formed by atypical T lymphocytes, histiocytes and giant cells. We report the case of a 37‐year‐old African‐American female with history of Sézary syndrome (SS) that while on treatment for the disease and in a space of 1 month developed exorbitant slack folds in the axillae and cervical area mimicking GSS. The absence of giant cells and epithelioid granulomas in the biopsy ruled out this diagnosis. We report this peculiar SS presentation that clinically resembles GSS, but with histopathology that does not show the typical features of this condition. We also review the literature in regard to SS, GSS and granulomatous mycosis fungoides (GMF), particularly the existing criteria to differentiate these various entities.     

Changes in the sympathetic innervation of the gut in rotenone treated mice as possible early biomarker for Parkinson’s disease

Introduction

Involvement of the peripheral nervous system (PNS) is relatively common in Parkinson’s disease (PD) patients. PNS alterations appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients. In previous studies, we have shown that environmental toxins can trigger the disease by acting on the enteric nervous system.

Material and methods

Here, we analyzed the effect of mitochondrial Complex I inhibition on sympathetic neuritis in vivo and sympathetic neurons in vitro. Combining in vivo imaging and protein expression profiling.

Results

we found that rotenone, a widely used mitochondrial Complex I inhibitor decreases the density of sympathetic neurites innervating the gut in vivo, while in vitro, it induces the redistribution of intracellular alpha-synuclein and neurite degeneration. Interestingly, sympathetic neurons are much more resistant to rotenone exposure than mesencephalic dopaminergic neurons.

Conclusion

Altogether, these results suggest that enteric sympathetic denervation could be an initial pre-motor alteration in PD progression that could be used as an early biomarker of the disease.

     

Canine Leishmaniasis in Southeastern Spain

To examine prevalence changes and risk factors for canine leishmaniasis, we conducted a cross-sectional seroprevalence study and a survey during April–June 2006. Seroprevalence had increased at the meso-Mediterranean bioclimatic level over 22 years. Risk was highest for dogs that were older, large, lived outside, and lived at the meso-Mediterranean level.