Implanted Peroneal Nerve Stimulator Treatment for Drop Foot Caused by Central Nervous System Lesion:A Twelve-Month Follow-up of 21 Patients

OBJECTIVE: Drop foot is a common impairment following stroke or other causes of central pathology. We report data on patient self-perceived performance, satisfaction with performance, walking ability, and adverse effects after surgical implantation of the ActiGait(®) drop foot stimulator. DESIGN: Prospective case study with a 12-month follow-up. SUBJECTS: Twenty-one participants with drop foot caused by central nervous system lesion. METHODS: The patients’ self-perceived performance and satisfaction with performance were evaluated using the Canadian Occupational Performance Measure (COPM). Walking ability was assessed using a 10-m walk test and a 6-min walk. Nerve conduction of the peroneal nerve was examined in 10 patients. RESULTS: At follow-up, COPM self-percieved performance from 3.2 to 6.7 points, the median increase being 2.8 (interquartile range (IQR) 2.2–5.0), p < 0.001. Likewise, the COPM satisfaction with performance increased from 2.6 to 6.9 points, the median increase being 4.2 (IQR 2.8–5.8), p < 0.001. Walking velocity increased 0.1 m/s from a baseline measurement of 0.73 m/s (95% confidence interval (95% CI) 0.03–0.2), n = 21, p < 0.01, and walking distance increased by 33 m, from a baseline measurement of 236 m (95% CI 15–51), n = 21, p < 0.001. CONCLUSION: Stimulation of the peroneal nerve by an implantable stimulator increases self-perceived performance, satisfaction with performance, and ambulation in patients with long-lasting drop foot caused by a central nervous system lesion

Estudio para Determinar la Calidad del Agua de Pozo, Mediante los Parámetros Físicos, Químicos y Microbiológicos en la Comunidad de Miramar, Provincia de Colón

El objetivo principal de esta investigación es determinar la calidad de agua del Pozo de Miramar y el Río de Miramar. Se realizaron 3 idas a Miramar una visita exploratoria para aplicar una encuesta y 2 viajes para recolectar muestras de diferentes puntos estratégicos para el análisis del agua de la comunidad; Se realizaron 12 pruebas a las muestras del agua las cuales son: pH, Temperatura, Fosfato, Nitrato, Turbiedad, Conductividad, Salinidad, Oxígeno Disuelto, DBO, Coliformes Totales, Coliformes Fecales, Enterococos Fecales.Con los valores obtenidos en el laboratorio de las muestras tomadas en los diferentes puntos de la comunidad se pudo determinar un Índice de calidad de Agua para los puntos como los del río y el pozo. Dando como resultado la calidad de agua del río en mala y el pozo en regular. El agua muestreada en las casas y escuela se comparó con la legislación vigente para agua potable dando un resultado desfavorable ya que hay evidencia que está contaminada por la bacteria E. Coli.Incluso se desarrolló un prototipo de aplicación tipo Android para que calculara el Índice de calidad del agua por el método sumativo de Brown, este prototipo tiene como objetivo asistir a los investigadores para llevar un registro de los resultados y un orden cronológico de manera más accesible. Se llegó a la conclusión de que el agua que es transportada a la comunidad desde el pozo está contaminada y por lo tanto puede causar enfermedades tras su consumo a los habitantes

Intravital FRAP imaging using an E-cadherin-GFP mouse reveals disease- and drug-dependent dynamic regulation of cell-cell junctions in live tissue

E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse that enables intravital photobleaching and quantification of E-cadherin mobility in live tissue without affecting normal biology. We demonstrate the broad applications of this mouse by examining E-cadherin regulation in multiple tissues, including mammary, brain, liver, and kidney tissue, while specifically monitoring E-cadherin mobility during disease progression in the pancreas. We assess E-cadherin stability in native pancreatic tissue upon genetic manipulation involving Kras and p53 or in response to anti-invasive drug treatment and gain insights into the dynamic remodeling of E-cadherin during in situ cancer progression. FRAP in the E-cadherin-GFP mouse, therefore, promises to be a valuable tool to fundamentally expand our understanding of E-cadherin-mediated events in native microenvironments

Cytomegaloviral determinants of CD8+ T cell programming and RhCMV/SIV vaccine efficacy

Simian immunodeficiency virus (SIV) insert-expressing, 68–1 Rhesus Cytomegalovirus (RhCMV/SIV) vectors elicit major histocompatibility complex (MHC)-E- and -II-restricted, SIV-specific CD8(+) T cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against SIV challenge in the rhesus monkeys (RMs) has not been characterized. We show that these unconventional responses resulted from a chance genetic rearrangement in 68–1 RhCMV that abrogated the function of eight distinct immunomodulatory gene products encoded in two RhCMV genomic regions (Rh157.5/Rh157.4 and Rh158–161), revealing three patterns of unconventional response inhibition. Differential repair of these genes with either RhCMV-derived or orthologous human CMV (HCMV)-derived sequences (UL128/UL130; UL146/UL147) leads to either of two distinct CD8(+) T cell response types – MHC-Ia-restricted-only, or a mix of MHC-II- and MHC-Ia-restricted CD8(+) T cells. Response magnitude and functional differentiation are similar to RhCMV 68–1, but neither alternative response type mediated protection against SIV challenge. These findings implicate MHC-E-restricted CD8(+) T cell responses as mediators of anti-SIV efficacy and indicate that translation of RhCMV/SIV vector efficacy to humans will likely require deletion of all genes that inhibit these responses from the HCMV/HIV vector

Transient tissue priming via ROCK inhibition uncouples pancreatic cancer progression, sensitivity to chemotherapy, and metastasis

The emerging standard of care for patients with inoperable pancreatic cancer is a combination of cytotoxic drugs gemcitabine and Abraxane, but patient response remains moderate. Pancreatic cancer development and metastasis occur in complex settings, with reciprocal feedback from microenvironmental cues influencing both disease progression and drug response. Little is known about how sequential dual targeting of tumor tissue tension and vasculature before chemotherapy can affect tumor response. We used intravital imaging to assess how transient manipulation of the tumor tissue, or "priming," using the pharmaceutical Rho kinase inhibitor Fasudil affects response to chemotherapy. Intravital Förster resonance energy transfer imaging of a cyclin-dependent kinase 1 biosensor to monitor the efficacy of cytotoxic drugs revealed that priming improves pancreatic cancer response to gemcitabine/Abraxane at both primary and secondary sites. Transient priming also sensitized cells to shear stress and impaired colonization efficiency and fibrotic niche remodeling within the liver, three important features of cancer spread. Last, we demonstrate a graded response to priming in stratified patient-derived tumors, indicating that fine-tuned tissue manipulation before chemotherapy may offer opportunities in both primary and metastatic targeting of pancreatic cancer

A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts.

The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a RhoA-fluorescence resonance energy transfer (FRET) biosensor mouse and its utility for monitoring real-time activity of RhoA in a variety of native tissues in vivo. We assess changes in RhoA activity during mechanosensing of osteocytes within the bone and during neutrophil migration. We also demonstrate spatiotemporal order of RhoA activity within crypt cells of the small intestine and during different stages of mammary gestation. Subsequently, we reveal co-option of RhoA activity in both invasive breast and pancreatic cancers, and we assess drug targeting in these disease settings, illustrating the potential for utilizing this mouse to study RhoA activity in vivo in real time