Intermittent theta-burst stimulation rescues dopamine-dependent corticostriatal synaptic plasticity and motor behavior in experimental parkinsonism. Possible role of glial activity.

Background: Recent studies support the therapeutic utility of repetitive transcranial magnetic stimulation in Parkinson's disease (PD), whose progression is correlated with loss of corticostriatal long-term potentiation and long-term depression. Glial cell activation is also a feature of PD that is gaining increasing attention in the field because astrocytes play a role in chronic neuroinflammatory responses but are also able to manage dopamine (DA) levels. Methods: Intermittent theta-burst stimulation protocol was applied to study the effect of therapeutic neuromodulation on striatal DA levels measured by means of in vivo microdialysis in 6-hydroxydopamine-hemilesioned rats. Effects on corticostriatal synaptic plasticity were studied through in vitro intracellular and whole-cell patch clamp recordings while stepping test and CatWalk were used to test motor behavior. Immunohistochemical analyses were performed to analyze morphological changes in neurons and glial cells. Results: Acute theta-burst stimulation induced an increase in striatal DA levels in hemiparkinsonian rats, 80 minutes post-treatment, correlated with full recovery of plasticity and amelioration of motor performances. With the same timing, immediate early gene activation was restricted to striatal spiny neurons. Intense astrocytic and microglial responses were also significantly reduced 80 minutes following theta-burst stimulation. Conclusion: Taken together, these results provide a first glimpse on physiological adaptations that occur in the parkinsonian striatum following intermittent theta-burst stimulation and may help to disclose the real potential of this technique in treating PD and preventing DA replacement therapy-associated disturbances

Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment

Overweight and obesity in youth is a worldwide public health problem. Overweight and obesity in childhood and adolescents have a substantial effect upon many systems, resulting in clinical conditions such as metabolic syndrome, early atherosclerosis, dyslipidemia, hypertension and type 2 diabetes (T2D). Obesity and the type of body fat distribution are still the core aspects of insulin resistance and seem to be the physiopathologic links common to metabolic syndrome, cardiovascular disease and T2D. The earlier the appearance of the clustering of risk factors and the higher the time of exposure, the greater will be the chance of developing coronary disease with a more severe endpoint. The age when the event may occur seems to be related to the presence and aggregation of risk factors throughout life

Correctors of mutant CFTR enhance subcortical cAMP-PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization

The most common mutation of the cystic fibrosis transmembrane regulator (CFTR) gene, F508del, produces a misfolded protein resulting in its defective trafficking to the cell surface and an impaired chloride secretion. Pharmacological treatments partially rescue F508del CFTR activity either directly by interacting with the mutant protein and/or indirectly by altering the cellular protein homeostasis. Here, we show that the phosphorylation of ezrin together with its binding to phosphatidylinositol-4,5-bisphosphate (PIP2) tethers the F508del CFTR to the actin cytoskeleton, stabilizing it on the apical membrane and rescuing the sub-membrane compartmentalization of cAMP and activated PKA. Both the small molecules trimethylangelicin (TMA) and VX-809, which act as 'correctors' for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. Latrunculin B treatment or expression of the inactive ezrin mutant T567A reverse the TMA and VX-809-induced effects highlighting the role of corrector-dependent ezrin activation and actin re-organization in creating the conditions to generate a sub-cortical cAMP pool of adequate amplitude to activate the F508del-CFTR-dependent chloride secretion

Conhecimento de mulheres sobre alguns aspectos do papiloma vírus humano

Study design: cross-sectional Objective: the current study aimed to assess the knowledge of women seen in two outpatient clinic of gynecology and obstetrics about the Human Papilloma Virus (HPV). Methodology: using secondary data from an electronic database that information was collected through a questionnaire during the period from 2007 to 2012. Results: were included 1470 women with average age of 30.7 years. Among women, 51.0% had heard about HPV, but only 41.6% knew of its sexual transmission and 33.3% knew about the relation of the pathogen with cervical cancer. Conclusion: data allowed to conclude that knowledge about HPV is poor, requiring improvement of educational interventions for the prevention of HPV infection and its worsening.Modelo do estudo: transversal. Objetivo do estudo: verificar o conhecimento de mulheres atendidas em dois ambulatórios de Ginecologia e Obstetrícia sobre o Papiloma Vírus Humano (HPV). Metodologia: foram utilizados dados secundários de um banco de dados eletrônico em que as informações foram coletadas por meio de um questionário no período de 2007 a 2012. Resultados: foram incluídas 1.470 mulheres com média de idade de 30,7 anos. Dentre as mulheres, 51,0% já haviam ouvido falar de HPV, porém, apenas 41,6% sabiam da transmissão sexual e 33,3% da relação do patógeno com o câncer de colo uterino. Conclusão: os dados permitiram concluir que o conhecimento sobre HPV é deficiente, necessitando desenvolvimento de ações educativas voltadas para a prevenção da infecção pelo HPV e seu agravamento

A population-based study on myelodysplastic syndromes in the Lazio Region (Italy), medical miscoding and 11-year mortality follow-up. The Gruppo Romano-Laziale Mielodisplasie experience of retrospective multicentric registry

Data on Myelodysplastic Syndromes (MDS) are difficult to collect by cancer registries because of the lack of reporting and the use of different classifications of the disease. In the Lazio Region, data from patients with a confirmed diagnosis of MDS, treated by a hematology center, have been collected since 2002 by the Gruppo Romano-Laziale Mielodisplasie (GROM-L) registry, the second MDS registry existing in Italy. This study aimed at evaluating MDS medical miscoding during hospitalizations, and patients' survival. For these purposes, we selected 644 MDS patients enrolled in the GROM-L registry. This cohort was linked with two regional health information systems: the Hospital Information System (HIS) and the Mortality Information System (MIS) in the 2002-2012 period. Of the 442 patients who were hospitalized at least once during the study period, 92% had up to 12 hospitalizations. 28.5% of patients had no hospitalization episodes scored like MDS, code 238.7 of the International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM). The rate of death during a median follow-up of 46 months (range 0.9-130) was 45.5%. Acute myeloid leukemia (AML) was the first cause of mortality, interestingly a relevant portion of deaths is due to cerebro-cardiovascular events and second tumors. This study highlights that MDS diagnosis and treatment, which require considerable healthcare resources, tend to be under-documented in the HIS archive. Thus we need to improve the HIS to better identify information on MDS hospitalizations and outcome. Moreover, we underline the importance of comorbidity in MDS patients' survival

A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT)

No abstract availabl

Diagnóstico inmunológico de la Equinococcosis Ovina

El inmunodiagnóstico en el ovino presenta problemas de sensibilidad y especificidad que limitan su aplicación en sistemas de vigilancia de la enfermedad. El Objetivo del trabajo fue desarrollar una técnica sensible, específica y económica para el diagnóstico de la echinococcosis quística en ovinos naturalmente infectados y evaluar la validez de la necropsia como prueba de referencia. 247 ovinos fueron estudiados en sala de faena confirmándose los diagnósticos parasitológicos mediante histología. Los sueros obtenidos fueron procesados mediante enzimo inmuno ensayo con tres preparaciones antigénicas: LHT (líquido hidatídico total), S2B (fracción purificada de LHT) y B y confirmados mediante western blot. EIE con las tres preparaciones antigénicas fue eficaz para discriminar E. granulosus de Cisticercos tenuícolis y Taenia spp. Sueros de ovinos negativos macroscópicamente resultaron reactivos a EIE y positivos a WB. La sensibilidad fue de 89.2% para LHT, 80.0% para S2B y 86.4% para B. La especificidad fue del 89.5% para LHT, 93.9% para S2B y 92.8% para B en el total de la majada. La sensibilidad en corderos resultó de 78.6 con LHT, 75.0 con S2B y 64.3 con B. El diagnóstico macroscópico en sala de faena demostró tener limitaciones como prueba de referencia para el inmunodiagnóstico de la equinococcosis quística en el ovino, resultando necesario incluir histología y WB como pruebas de referencia. EIE resultó una técnica con sensibilidad y especificidad adecuadas para su uso en sistemas de vigilancia y evaluación de programas de control, resultando LHT la preparación antigénica de mayor valor

Lice, rodents, and many hopes: a rare disease in a young refugee

Borrelia recurrentis infection is a louse-borne disease and Leptospirosis is a rat-borne zoonosis, both endemic in areas characterized by a low hygiene condition. This is the first case of life-threatening Borrelia recurrentis and Leptospira species co-infectio