Progressive tremor and motor impairment in seizure-prone mutant tremor mice are associated with neurotransmitter dysfunction.

BACKGROUND: The tremor mutant mice present motor impairments comprised of whole-body tremors, ataxia, decreased exploratory behavior, and audiogenic seizures. OBJECTIVES: This study aims to investigate the development of motor dysfunction in this mutant mouse and the relationships with cortical, striatal, and cerebellar levels of GABA, glutamate, glycine, dopamine (DA), serotonin (5-HT), noradrenaline (NOR), and its metabolites. The serum cytokines levels, myelin content, and the astrocytic expression of the glial fibrillary acidic protein (GFAP) investigated the possible influence of inflammation in motor dysfunction. RESULTS: Relative to wild-type (WT) mice, the tremor mice presented: increased tremors and bradykinesia associated with postural instability, decreased range of motion, and difficulty in initiating voluntary movements directly proportional to age; reduced step length for right and left hindlimbs; reduced cortical GABA, glutamate and, aspartate levels, the DOPAC/DA and ratio and increased the NOR levels; in the striatum, the levels of glycine and aspartate were reduced while the HVA levels, the HVA/DA and 5HIAA/5-HT ratios increased; in the cerebellum the glycine, NOR and 5-HIAA levels increased. CONCLUSIONS: We suggest that the motor disturbances resulted mainly from the activation of the indirect striatal inhibitory pathway to the frontal cortex mediated by GABA, glutamate, and aspartate, reducing the dopaminergic activity at the prefrontal cortex, which was associated with the progressive tremor. The reduced striatal and increased cerebellar glycine levels could be partially responsible for the mutant tremor motor disturbances.

Flexible Bayesian modelling in dichotomous item response theory using mixtures of skewed item curves.

Most item response theory (IRT) models for dichotomous responses are based on probit or logit link functions which assume a symmetric relationship between the probability of a correct response and the latent traits of individuals taking a test. This assumption restricts the use of those models to the case in which all items behave symmetrically. On the other hand, asymmetric models proposed in the literature impose that all the items in a test behave asymmetrically. This assumption is inappropriate for great majority of tests which are, in general, composed of both symmetric and asymmetric items. Furthermore, a straightforward extension of the existing models in the literature would require a prior selection of the items' symmetry/asymmetry status. This paper proposes a Bayesian IRT model that accounts for symmetric and asymmetric items in a flexible but parsimonious way. That is achieved by assigning a finite mixture prior to the skewness parameter, with one of the mixture components being a point mass at zero. This allows for analyses under both model selection and model averaging approaches. Asymmetric item curves are designed through the centred skew normal distribution, which has a particularly appealing parametrization in terms of parameter interpretation and computational efficiency. An efficient Markov chain Monte Carlo algorithm is proposed to perform Bayesian inference and its performance is investigated in some simulated examples. Finally, the proposed methodology is applied to a data set from a large-scale educational exam in Brazil.

Progressive tremor and motor impairment in seizure-prone mutant tremor mice are associated with neurotransmitter dysfunction

Background The tremor mutant mice present motor impairments comprised of whole-body tremors, ataxia, decreased exploratory behavior, and audiogenic seizures. Objectives This study aims to investigate the development of motor dysfunction in this mutant mouse and the relationships with cortical, striatal, and cerebellar levels of GABA, glutamate, glycine, dopamine (DA), serotonin (5-HT), noradrenaline (NOR), and its metabolites. The serum cytokines levels, myelin content, and the astrocytic expression of the glial fibrillary acidic protein (GFAP) investigated the possible influence of inflammation in motor dysfunction. Results Relative to wild-type (WT) mice, the tremor mice presented: increased tremors and bradykinesia associated with postural instability, decreased range of motion, and difficulty in initiating voluntary movements directly proportional to age; reduced step length for right and left hindlimbs; reduced cortical GABA, glutamate and, aspartate levels, the DOPAC/DA and ratio and increased the NOR levels; in the striatum, the levels of glycine and aspartate were reduced while the HVA levels, the HVA/DA and 5HIAA/5-HT ratios increased; in the cerebellum the glycine, NOR and 5-HIAA levels increased. Conclusions We suggest that the motor disturbances resulted mainly from the activation of the indirect striatal inhibitory pathway to the frontal cortex mediated by GABA, glutamate, and aspartate, reducing the dopaminergic activity at the prefrontal cortex, which was associated with the progressive tremor. The reduced striatal and increased cerebellar glycine levels could be partially responsible for the mutant tremor motor disturbances.

Exact and computationally efficient Bayesian inference for generalized Markov modulated Poisson processes.

Statistical modeling of temporal point patterns is an important problem in several areas. The Cox process, a Poisson process where the intensity function is stochastic, is a common model for such data. We present a new class of unidimensional Cox process models in which the intensity function assumes parametric functional forms that switch according to a continuous-time Markov chain. A novel methodology is introduced to perform exact (up to Monte Carlo error) Bayesian inference based on MCMC algorithms. The reliability of the algorithms depends on a variety of specifications which are carefully addressed, resulting in a computationally efficient (in terms of computing time) algorithm and enabling its use with large data sets. Simulated and real examples are presented to illustrate the efficiency and applicability of the methodology. A specific model to fit epidemic curves is proposed and used to analyze data from Dengue Fever in Brazil and COVID-19 in some countries.

Measles in bone marrow transplant recipients during an outbreak in São Paulo, Brazil.

In 1997, a measles outbreak was identified in São Paulo. Between February and December, 20 185 cases were confirmed. From April to July 1997, a seroepidemiologic survey was conducted to identify the recipients of bone marrow (BM) transplants who were susceptible to measles and the occurrence of measles in this population. A total of 156 patients were screened by enzyme immunoassay (EIA). Patients with IgG titers more than 100 mIU/mL were considered immune. Measles reimmunization records were also reviewed. Thirty-two vaccinated patients underwent serologic evaluation. Six of 22 patients (27.3%) within 3 years after vaccination lost measles immunity, in contrast to 7 of 10 patients (70%) vaccinated longer than 3 years previously (P =.049). Among the 122 nonvaccinated patients, 41 (33.6%) were susceptible to measles: 4 of 47 patients (8.5%) within the first year after BM transplantation (BMT), and 37 of the 75 patients (49.3%) after the first year after BMT (P <.001). Eight recipients acquired measles, confirmed by serology (EIA). High-avidity IgG antibodies were observed in the acute phase of measles, suggesting a secondary immune response. Measles interstitial pneumonia was observed in one patient. Seven patients had mild symptoms. Exanthema was present in all patients. All but one patient had fever and nonproductive cough. Koplik spots could be observed in 5 patients. Measles can be mild in BM transplant recipients. Exanthema is frequently present but not often typical. Immunity to measles decreases after day +365 after BMT. Additional studies are needed to evaluate the safety of measles vaccine after the first year of BMT, mostly during outbreaks.