286 research outputs found

    Postnatal development of the neural retina in a South American opossum: Monodelphis domestica

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    Postnatal retinal development was studied in a marsupial opossum, Monodelphis domestica using light microscopy and 3H-thymidine autoradiography. For the light microscopic study, opossum neonates at 1, 3, 7, 14, 21, 25 and 28 days of age were euthanized, fixed and processed into paraffin sections for hematoxylin and eosin staining. The distinct ganglion cell layer, first observed on postnatal day (P) 7, was separated from the outer neuroblasts by the inner plexiform layer. The neuroblast layer was divided into inner and outer nuclear layers on P25 by the presumptive outer plexiform layer, indicated by discrete intercellular spaces located between the nuclear laminae. Prior to P28, mitoses occurred along the ventricular margin of the neuroblast retina bordering on the intraretinal space. The retina achieved an adult-like appearance at the fourth postnatal week, with mitoses restricted to the extreme retinal periphery in the outer nuclear layer. The 3H-thymidine autoradiographic study traced the differentiation of neuroblasts into their respective retinal lamina during postnatal development. Neonatal opossums at 1, 3, 7, 14, 21 and 28 days of age received a single dose intraperitoneal injection of 3H-thymidine and survived for 1, 7, 14, 21 or 28 days post-injection. The opossums were euthanized and processed for paraffin sectioning and for autoradiography. The NTB-2 emulsion-dipped slides underwent 8 weeks of exposure before development into autoradiograms, followed by H/E counterstaining. This study showed constituent cells of each nuclear lamina differentiate concurrently in two phases. 3H-thymidine labeled cells differentiated in the first phase were ganglion cells, horizontal cells and cone photoreceptors from Pl to P3, with 3H-thymidine labeled bipolar cells, amacrine cells and rod photoreceptors differentiated in the second phase starting at P3 and extending to the fourth postnatal week. A central to peripheral gradient of cell differentiation was exhibited, with 3H-thymidine labeled cells first observed in the central retina and cells differentiated at later ages observed in increasingly peripheral positions within the retina. The pattern of cellular differentiation in Monodelphis domestica was similar to that found in placental mammals and other marsupial mammals. Monodelphis domestica is an ideal animal model for mammalian retinogenesis due to its extreme embryonic appearance at birth and to its rapid postnatal retinal development

    Synthesis of calculational methods for the design and analysis of radiation shields for nuclear rocket systems. Volume 2 - Analysis of radiation measurements in a nuclear rocket propellant tank mockup using simulated liquid hydrogen

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    Calculational methods for nuclear rocket radiation shield design - analysis of radiation measurements in nuclear rocket propellant tank mockup using simulated liquid hydroge

    Nuclear rocket shielding methods, modification, updating, and input data preparation. Volume 5 - Two-dimensional, discrete ordinates transport technique Final progress report

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    Two dimensional, discrete ordinates transport technique for use with nuclear rocket shielding methods, modification, updating, and data input preparation - Vol.

    Nuclear rocket shielding methods, modification, updating, and input data preparation. Volume 1 - Synopsis of methods and results of analysis Final progress report

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    Analysis of data systems and computer programs for nuclear rocket shielding methods, modification, updating, and data input preparation - Vol.

    Nuclear rocket shielding methods, modification, updating, and input data preparation. Volume 3 - Cross section generation and data processing techniques Final progress report

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    Cross section generation and data processing techniques for nuclear rocket shielding methods, modification, updating, and input data preparation - Vol.

    Involvement of fast-spiking cells in ictal sequences during spontaneous seizures in rats with chronic temporal lobe epilepsy

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    Epileptic seizures represent altered neuronal network dynamics, but the temporal evolution and cellular substrates of the neuronal activity patterns associated with spontaneous seizures are not fully understood. We used simultaneous recordings from multiple neurons in the hippocampus and neocortex of rats with chronic temporal lobe epilepsy to demonstrate that subsets of cells discharge in a highly stereotypical sequential pattern during ictal events, and that these stereotypical patterns were reproducible across consecutive seizures. In contrast to the canonical view that principal cell discharges dominate ictal events, the ictal sequences were predominantly composed of fast-spiking, putative inhibitory neurons, which displayed unusually strong coupling to local field potential even before seizures. The temporal evolution of activity was characterized by unique dynamics where the most correlated neuronal pairs before seizure onset displayed the largest increases in correlation strength during the seizures. These results demonstrate the selective involvement of fast spiking interneurons in structured temporal sequences during spontaneous ictal events in hippocampal and neocortical circuits in experimental models of chronic temporal lobe epilepsy

    Design and clinical evaluation of robust PID control of propofol anesthesia in children

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    This paper describes the design of a robust PID controller for propofol infusion in children and presents the results of clinical evaluation of this closed-loop system during endoscopic investigations in children age 6y-17y. The controller design is based on a set of models that describes the inter- patient variability in the response to propofol infusion in the study population. The PID controller is tuned to achieve sufficient robustness margins for the identified uncertainty. 108 children were enrolled in the study, anesthesia was closed-loop controlled in 102 of these cases. Clinical evaluation of the system shows that closed-loop control of both induction and maintenance of anesthesia in children based on the WAVCNS index as a measure of clinical effect is feasible. A robustly tuned PID controller can accommodate the inter-patient variability in children and spontaneous breathing can be maintained in most subjects

    Clostridium difficile infection after cardiac surgery: Prevalence, morbidity, mortality, and resource utilization

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    ObjectiveDespite increasing efforts to prevent infection, the prevalence of hospital-associated Clostridium difficile infections (CDI) is increasing. Heightened awareness prompted this study of the prevalence and morbidity associated with CDI after cardiac surgery.MethodsA total of 22,952 patients underwent cardiac surgery at Cleveland Clinic from January 2005 to January 2011. CDI was diagnosed by enzyme immunoassay for toxins and, more recently, polymerase chain reaction (PCR) testing. Hospital outcomes and long-term survival were compared with those of the remaining population in propensity-matched groups.ResultsOne hundred forty-five patients (0.63%) tested positive for CDI at a median of 9 days postoperatively, 135 by enzyme immunoassay and 11 by PCR. Its prevalence more than doubled over the study period. Seventy-seven patients (48%) were transfers from outside hospitals. Seventy-three patients (50%) were exposed preoperatively to antibiotics and 79 (56%) to proton-pump inhibitors. Patients with CDI had more baseline comorbidities, more reoperations, and received more blood products than patients who did not have CDI. Presenting symptoms included diarrhea (107; 75%), distended abdomen (48; 34%), and abdominal pain (27; 19%). All were treated with metronidazole or vancomycin. Sixteen patients (11%) died in hospital, including 5 of 10 who developed toxic colitis; 3 of 4 undergoing total colectomy survived. Among matched patients, those with CDI had more septicemia (P < .0001), renal failure (P = .0002), reoperations (P < .0001), prolonged postoperative ventilation (P < .0001), longer hospital stay (P < .0001), and lower 3-year survival, 52% versus 64% (P = .03), than patients who did not have CDI.ConclusionsAlthough rare, the prevalence of CDI is increasing, contributing importantly to morbidity and mortality after cardiac surgery. If toxic colitis develops, mortality is high, but colectomy may be lifesaving

    A novel epilepsy mutation in the sodium channel SCN1A identifies a cytoplasmic domain for {beta} subunit interaction

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    A mutation in the sodium channel SCN1A was identified in a small Italian family with dominantly inherited generalized epilepsy with febrile seizures plus (GEFS+). The mutation, D1866Y, alters an evolutionarily conserved aspartate residue in the C-terminal cytoplasmic domain of the sodium channel {alpha} subunit. The mutation decreased modulation of the {alpha} subunit by {beta}1, which normally causes a negative shift in the voltage dependence of inactivation in oocytes. There was less of a shift with the mutant channel, resulting in a 10 mV difference between the wild-type and mutant channels in the presence of {beta}1. This shift increased the magnitude of the window current, which resulted in more persistent current during a voltage ramp. Computational analysis suggests that neurons expressing the mutant channels will fire an action potential with a shorter onset delay in response to a threshold current injection, and that they will fire multiple action potentials with a shorter interspike interval at a higher input stimulus. These results suggest a causal relationship between a positive shift in the voltage dependence of sodium channel inactivation and spontaneous seizure activity. Direct interaction between the cytoplasmic C-terminal domain of the wild-type{alpha} subunit with the {beta}1or {beta}3 subunit was first demonstrated by yeast two-hybrid analysis. The SCN1A peptide K1846-R1886 is sufficient for {beta} subunit interaction. Coimmunoprecipitation from transfected mammalian cells confirmed the interaction between the C-terminal domains of the {alpha} and {beta}1 subunits. The D1866Y mutation weakens this interaction, demonstrating a novel molecular mechanism leading to seizure susceptibility
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