RESUMO
One of the main factors affecting cattle fertility is pre-implantation development of the bovine embryo, which is a complex process regulated by various signal-transduction pathways. The transforming growth factor-ß (TGF-ß) signalling system, which is responsible for many biological processes including cell proliferation, differentiation and apoptosis, also is involved in embryo development. We hypothesized that altered expression of TGF-ß genes in pre-implantation bovine embryos is associated with morphological abnormalities of these embryos. To test this hypothesis, we produced embryos in vitro and classified them at the blastocyst stage as either normally developed blastocysts or degenerates (growth-arrested embryos). The expression patterns of 25 genes from the TGF-ß pathway were assessed using quantitative real time PCR. Ten genes showed differential expression between the two embryo groups, four genes displayed similar expressional profiles, and 11 genes had no detectable expression. An altered expression profile was statistically significant for 10 of the 14 expressed genes, and all were up-regulated in degenerate embryos vs. blastocysts. Furthermore, genomic association analysis of the cows from which embryos were produced revealed a significant association of ID3 and BMP4 polymorphisms--two of the most significant differentially expressed genes--with fertilization rate and blastocyst rate, respectively. Taken together, we conclude that TGF-ß pathway genes, especially BMP4 and ID3 play a vital function in the regulation of pre-implantation embryo development at both embryo and maternal levels. Hence, these genes may be suitable as genetic markers for embryo development and fertility in cattle.
Assuntos
Blastocisto/fisiologia , Bovinos/embriologia , Desenvolvimento Embrionário/genética , Transdução de Sinais/genética , Fator de Crescimento Transformador beta/genética , Animais , Feminino , Fertilidade/genética , Regulação da Expressão Gênica no Desenvolvimento , Marcadores Genéticos , Gravidez , Reação em Cadeia da Polimerase em Tempo RealRESUMO
OBJECTIVE: Identifying neural activity biomarkers of brain disease is essential to provide objective estimates of disease burden, obtain reliable feedback regarding therapeutic efficacy, and potentially to serve as a source of control for closed-loop neuromodulation. In Parkinson's disease (PD), microelectrode recordings (MER) are routinely performed in the basal ganglia to guide electrode implantation for deep brain stimulation (DBS). While pathologically-excessive oscillatory activity has been observed and linked to PD motor dysfunction broadly, the extent to which these signals provide quantitative information about disease expression and fluctuations, particularly at short timescales, is unknown. Furthermore, the degree to which informative signal features are similar or different across patients has not been rigorously investigated. We sought to determine the extent to which motor error in PD across patients can be decoded on a rapid timescale using spectral features of neural activity. APPROACH: Here, we recorded neural activity from the subthalamic nucleus (STN) of subjects with PD undergoing awake DBS surgery while they performed an objective, continuous behavioral assessment that synthesized heterogenous PD motor manifestations to generate a scalar measure of motor dysfunction at short timescales. We then leveraged natural motor performance variations as a 'ground truth' to identify corresponding neurophysiological biomarkers. MAIN RESULTS: Support vector machines using multi-spectral decoding of neural signals from the STN succeeded in tracking the degree of motor impairment at short timescales (as short as one second). Spectral power across a wide range of frequencies, beyond the classic 'ß' oscillations, contributed to this decoding, and multi-spectral models consistently outperformed those generated using more isolated frequency bands. While generalized decoding models derived across subjects were able to estimate motor impairment, patient-specific models typically performed better. SIGNIFICANCE: These results demonstrate that quantitative information about short-timescale PD motor dysfunction is available in STN neural activity, distributed across various patient-specific spectral components, such that an individualized approach will be critical to fully harness this information for optimal disease tracking and closed-loop neuromodulation.
Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Gânglios da Base , Biomarcadores , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapiaRESUMO
BACKGROUND: During the deep brain stimulation (DBS) electrode implantation operation with microelectrode recordings (MER) in awake patients, somatotopic testing and test stimulation are performed to improve electrode placement and provide the most beneficial symptom reduction possible, while minimizing side effects. As this procedure is commonly used to alleviate abnormal movements associated with Parkinson's disease (PD) and Essential Tremor (ET), intraoperative assessment of a patient's movements is critical to optimizing surgical benefit. However, despite its importance, movement assessment is typically subjective and qualitative. NEW METHOD: Here, we present a detailed description of a low-cost, open-source system as a solution. RESULTS: The described system measures movements intraoperatively and in synchrony with neurophysiological recordings for both online visualization and offline analysis. COMPARISON WITH EXISTING METHOD(S): Few movement quantification systems are designed to interface with intraoperative neurophysiological recordings; the widespread application of such systems may be limited by their cost and proprietary, closed-source nature. The system presented provides a low-cost, open-source alternative. CONCLUSIONS: The system outlined in this work may improve the DBS procedure by adding valuable objectivity in movement quantification.
Assuntos
Acelerometria/instrumentação , Estimulação Encefálica Profunda/métodos , Monitorização Neurofisiológica Intraoperatória/instrumentação , Movimento/fisiologia , Doença de Parkinson/cirurgia , Tremor/diagnóstico , Acelerometria/métodos , Eletrodos Implantados , Humanos , Monitorização Neurofisiológica Intraoperatória/métodos , Magnetometria/instrumentação , Magnetometria/métodosRESUMO
PURPOSE: As of 2008, the Regulated Health Professions Act in Ontario stipulates that administration of oxygen is a controlled act, which physiotherapists are not authorized to perform but which may be delegated to physiotherapists by another health professional authorized to perform this act. The aims of this study were (1) to survey physiotherapy practice of oxygen administration in Ontario hospitals and (2) to determine the proportion and characteristics of hospitals with delegation policies for physiotherapists to administer oxygen. METHOD: Postal surveys were sent to 208 hospitals. Data were collected on hospital characteristics; the presence of delegation policies; and the practice and training of physiotherapists, physiotherapy assistants, and students in oxygen administration. Data were described by summative statistics. Fisher's exact test and Cramer's V statistic were used to examine associations. Potential prognostic factors were analyzed using logistic regression. RESULTS: Response rate was 82.7%. Physiotherapists administered oxygen in 39% of hospitals, and 28% of hospitals had delegation policies. Larger, urban, or teaching hospitals and those with a matrix structure were most likely to have delegation policies and physiotherapists who administered oxygen. Rehabilitation hospitals were also likely to have such policies. CONCLUSION: Physiotherapists administer oxygen in less than half of Ontario hospitals, very few of which have delegation policies.