Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium.

Bipolar disorder (BD) is a progressive psychiatric disorder with more than 3% prevalence worldwide. Affected individuals experience recurrent episodes of depression and mania, disrupting normal life and increasing the risk of suicide greatly. The complexity and genetic heterogeneity of psychiatric disorders have challenged the development of animal and cellular models. We recently reported that hippocampal dentate gyrus (DG) neurons differentiated from induced pluripotent stem cell (iPSC)-derived fibroblasts of BD patients are electrophysiologically hyperexcitable. Here we used iPSCs derived from Epstein-Barr virus-immortalized B-lymphocytes to verify that the hyperexcitability of DG-like neurons is reproduced in this different cohort of patients and cells. Lymphocytes are readily available for research with a large number of banked lines with associated patient clinical description. We used whole-cell patch-clamp recordings of over 460 neurons to characterize neurons derived from control individuals and BD patients. Extensive functional analysis showed that intrinsic cell parameters are very different between the two groups of BD neurons, those derived from lithium (Li)-responsive (LR) patients and those derived from Li-non-responsive (NR) patients, which led us to partition our BD neurons into two sub-populations of cells and suggested two different subdisorders. Training a Naïve Bayes classifier with the electrophysiological features of patients whose responses to Li are known allows for accurate classification with more than 92% success rate for a new patient whose response to Li is unknown. Despite their very different functional profiles, both populations of neurons share a large, fast after-hyperpolarization (AHP). We therefore suggest that the large, fast AHP is a key feature of BD and a main contributor to the fast, sustained spiking abilities of BD neurons. Confirming our previous report with fibroblast-derived DG neurons, chronic Li treatment reduced the hyperexcitability in the lymphoblast-derived LR group but not in the NR group, strengthening the validity and utility of this new human cellular model of BD.

Standardization of a phonetic-phonological test for European-Portuguese children.

OBJECTIVE: To develop and standardize a phonetic-phonological test (Teste Fonético-Fonológico-Avaliação da Linguagem Pré-Escolar, TFF-ALPE) for the assessment of European-Portuguese (EP) children's articulation and phonological abilities. PATIENTS AND METHODS: In order to standardize TFF-ALPE, 768 children aged 3;0-6;11 participated in this study. The standardization, validity and reliability of TFF-ALPE were analyzed. RESULTS: TFF-ALPE presents strong cohesion and has strong inter- and intrajudge reliability. There was also a strong correlation between the TFF-ALPE data and those obtained in other studies. The content validity was demonstrated by the description of the test domain and the items that comprise TFF-ALPE. CONCLUSION: TFF-ALPE is a valid and reliable phonetic-phonological assessment instrument that speech-language pathologists can use with EP-speaking children.

Trypanosoma cruzi: chemotherapy with benznidazole in mice inoculated with strains from Paraná state and from different endemic areas of Brazil.

Strains of Trypanosoma cruzi from different geographical areas have shown different levels of susceptibility to trypanosomicidal drugs. The susceptibility in vivo to benznidazole was investigated in eighteen strains of T. cruzi. Twelve were isolated from chronic chagasic patients from different Chagas' disease endemic areas. The other six strains were isolated from the northwestern region of Paraná state; two of them from patients, three from triatomines (Triatoma sordida) and one from wild reservoir (Didelphis sp.). To test drug the infected mice were divided into two groups of twenty. One group was treated with benznidazole for twenty consecutive days and the other group was used as untreated control. The treatment began after detection of the infection by direct blood examination or haemoculture. The control of cure was done through haemoculture and indirect immunofluorescence test. The drug eliminated the inflammatory lesions of the skeletal muscle of mice considered cured and from the heart of most of them. Moreover, the inflammatory lesions were reduced in treated but not cured animals. The T. cruzi strains studied showed a gradient of drug susceptibility that varied from 0% to 100%. Ten strains were considered sensitive to the treatment (61 to 100% of cure), one strain was partially sensitive (50% of cure) and seven strains were considered resistant to the treatment (0 to 40% of cure). This variation was observed both in strains of T. cruzi isolated from domestic and sylvatic cycles.

[Vasculitis associated with ANCA]. / Vasculites associadas ao ANCA.

The authors present a case report of a 62-year old woman, with hypertension for many years. She suffered from weakness, anorexia and weight loss in the last 6 months. On admission, anemia, elevated ESR, haematuria, proteinuria and renal failure were present. Renal biopsy was compatible with chronic glomerulonephritis. The clinical picture and positivity for P-ANCA suggested systemic vasculitis. Later evidence of maxillary sinusitis and nasal mucosae ulcers as well as pneumonitis, although biopsy did not reveal granulomas, suggested the diagnosis of Wegener Vasculitis. Medicated with Cyclophosphamide and Prednisolone, for a year, with improvement. The authors make a brief discussion of the clinical criteria for classification of ANCA-associated systemic vasculitis.