Optogenetics and its application in neural degeneration and regeneration

Neural degeneration and regeneration are important topics in neurological diseases. There are limited options for therapeutic interventions in neurological diseases that provide simultaneous spatial and tem-poral control of neurons. This drawback increases side effects due to non-specific targeting. Optogenetics is a technology that allows precise spatial and temporal control of cells. Therefore, this technique has high potential as a therapeutic strategy for neurological diseases. Even though the application of optogenetics in understanding brain functional organization and complex behaviour states have been elaborated, reviews of its therapeutic potential especially in neurodegeneration and regeneration are still limited. This short review presents representative work in optogenetics in disease models such as spinal cord injury, multiple sclerosis, epilepsy, Alzheimer's disease and Parkinson's disease. It is aimed to provide a broader perspective on opto-genetic therapeutic potential in neurodegeneration and neural regeneration.     

The utilization of dental care services according to health insurance coverage in Catalonia (Spain)

Abstract –  The aim of this study was to assess the relationship of dental care service use with health insurance and its evolution. The Catalan Health Interview Survey is a cross-sectional study conducted in 1994 ( n  = 15 000) and 2001–2 ( n  = 8400) by interviews at home to a representative sample of Catalonia (Spain). All the estimates were obtained by applying weights to restore the representativeness of the Catalonia general population. In the bivariate analysis, age, gender, social class and health insurance coverage were statistically associated with a dental visit in the previous year ( P  < 0.001). Analysis with logistic regression showed that health insurance status has a statistically significant association with utilization ( P  < 0.001), which was independent of the other socio-economic factors (age, gender, country of birth, and social class). However, the falling trend of differences by health insurance coverage is of note (adjusted OR = 2.2 and 1.5 at 1994 and 2002, respectively); as well as the positive evolution of the overall rate of dental service care use in the previous year, from 26.7% in 1994 to 34.3% in 2002. Future studies will be needed to monitor this tendency.     

Postmortem intracranial neuropathology in children following cardiac transplantation

At Loma Linda University Children's Hospital, the medical information of 405 pediatric patients who received orthotopic cardiac transplantation were reviewed. Of those who died (n=136), 86% (n=117) underwent postmortem examinations, and the brain was examined in 61% (n=82, male=39). The number and type of intracranial lesions present were compiled, and these were matched to underlying functional cardiac disease categories. Intracranial abnormalities were present in 87%. Infarct was the most common primary central nervous system pathology in hypoplastic left heart syndrome (41%) but was also observed frequently in children with obstructive lesions (37%), cyanotic disease (31%), or cardiac shunting (29%). Secondary findings included extraparenchymal hemorrhage in obstructive lesions (31%); hypoxic changes occurred in 15% of patients with cyanotic disease and in 14% of those with cardiac shunting. Thirty-three percent of children with restrictive lesions had no neuropathology reported. Postmortem examination brain weights were matched against age and sex norms, with 29% of females and 36% of males below two standard deviations. These findings revealed that intracranial pathology was present in the majority of transplanted children who underwent postmortem examination, and that infarctive changes constituted the most common neuropathologic abnormality. Additionally, a number of children had significantly reduced brain weight.     

Role of p38 mitogen activated protein kinase in a model of osteosarcoma-induced pain

The focus of this work was to examine the potential role of p38 mitogen activated protein kinase (p38) in a mouse model of bone cancer (osteosarcoma) pain. To generate osteosarcoma and sham animals, osteosarcoma cells or medium were injected into the medullary canal of the femur. Initially, ipsilateral tactile allodynia was observed in both groups, but by 12 days post-surgery, thresholds in the sham group returned towards baseline while hypersensitivity in the osteosarcoma group lasted throughout the study. An increase in phosphorylated p38 was detected by western blotting in dorsal root ganglia (DRG) and spinal cord day 14 after surgery. Immunohistochemistry showed that p38 was phosphorylated in DRG and spinal dorsal horn neurons at this time point. Two doses of a selective p38 inhibitor, SCIO-469, were administered in the chow starting 5 days post-surgery and continued throughout the study. Treatment with SCIO-469 led to a decrease in osteosarcoma-induced clinical score but had no effect on the allodynia. Bone erosion and tumor growth were also examined but no significant reduction of bone erosion or tumor growth was observed in the SCIO-469 treated mice. These data suggest that the p38 signaling pathway does not play a major role in bone cancer-mediated pain.     

Do trauma patients with a Glasgow Coma Scale score of 3 and bilateral fixed and dilated pupils have any chance of survival?

BACKGROUND: Low Glasgow Coma Scale score (GCS) and pupillary status predict poor outcomes in head injury (HI) patients. We compared the mortality of GCS 3 patients having bilateral fixed and dilated pupils (BFDP) with GCS 3 patients having reactive pupils (RP). We then determined if trauma system or patient factors were responsible for the difference in mortality. METHODS: We reviewed all adult, blunt HI patients with GCS=3, admitted to our institution from January 1, 2001 to December 31, 2003. Demographics, injury data, prehospital times, procedures, and outcomes were recorded. RESULTS: During this period, 245 patients were admitted with GCS of 3, and met inclusion criteria. In all, 173 patients were analyzed, after excluding 23 patients who were dead-on-arrival, and 45 others, who were intoxicated with alcohol, or received paralytic agents in the trauma room. All BFDP patients died, whereas 42.0% of reactive pupil (RP) patients died (p < 0.0001). With regards to patient factors, BFDP patients were more likely to be unstable, have extra-axial bleeding, and evidence of midline shift and/or herniation. Trauma system factors, however, may also have had an impact on outcome. Despite having more extra-axial bleeding, BFDP patients were less likely to have a neurosurgical operation than RP patients. CONCLUSION: Patients with GCS of 3 and BFDP have a dismal prognosis. These patients have suffered devastating brain injuries and tend to be hemodynamically unstable. Clinicians, however, are less likely to aggressively treat BFDP patients than RP patients. Further prospective studies are required to determine which patients with GCS of 3 and BFDP are likely to benefit from aggressive treatment.     

Quantification of regional ventilation from treatment planning CT

PURPOSE: We describe a method of quantifying regional ventilation from the radiotherapy treatment planning computed tomography (CT) images, with the goal of developing functional images for treatment planning and optimization. METHODS AND MATERIALS: A series of exhalation breath-hold (eBH-CT) and inhalation breath-hold (iBH-CT) CT images obtained using a feedback-guided breath-hold technique for radiotherapy treatment planning was selected. The eBH-CT was mapped on a voxel-by-voxel basis to the iBH-CT using a deformable image registration algorithm. By using the average CT number over a 3 mm(3) region surrounding each pair of mapped voxels, the change in fraction of air per voxel (i.e., regional ventilation) was calculated. This methodology was applied to a series of 22 patients. The calculated total ventilation was compared to the change in contoured lung volumes between the exhalation and inhalation CTs (measured tidal volume). RESULTS: A significant correlation was found between the calculated and measured tidal volumes for the left (R = 0.982) and right (R = 0.985), and for both lungs combined (R = 0.985). In the resulting images, the regional ventilation was highly variable and corresponded with the spatial distribution of differences in the CT values (Hounsfield units) between the eBH-CT and the iBH-CT images. CONCLUSIONS: A method of quantifying regional ventilation from radiotherapy treatment planning CT data sets was demonstrated. The ventilation images can be used in plan optimization to minimize injury to functioning lung.     

Do T90 and SaO2 nadir identify a different phenotype in obstructive sleep apnea?

Sleep and Breathing - Severity of obstructive sleep apnea (OSA) is commonly based upon the apnea-hypopnea index (AHI). However, patients with similar AHIs may demonstrate widely varying...     

Human immunodeficiency virus enhances hepatitis C virus replication by differential regulation of IFN and TGF family genes

HIV co‐infection significantly impacts the natural history of hepatitis C virus (HCV) by increasing plasma HCV viral load, accelerating liver disease progression, and reducing rates of HCV clearance. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the impact of HIV on cytokine expression is unknown. In this study, an HCV continuous infection cell culture system was modified to permit co‐infection with HIV to test the hypothesis that virus‐induced disregulation of immune‐response genes, particularly interferons and TGF‐β, may create a permissive environment for the initial establishment of HIV/HCV co‐infection in the host. CCR5‐expressing Huh‐7.5 hepatoma cells were transduced with human CD4 antigen to allow HIV infection in vitro. Co‐infection of CD4⁺ Huh‐7.5 cells with HIV and HCV or co‐culture of HIV‐infected CD4⁺ Huh‐7.5 cells and HCV‐infected Huh‐7.5 cells increased the level of HCV RNA compared to HCV mono‐infection. Quantitative gene expression analysis revealed HIV‐induced up regulation of most tested IFN family genes when compared to HCV or co‐infection. HCV infection induced up regulation of many TGF family genes that were subsequently down‐regulated in the presence of HIV or HIV/HCV. Interestingly, co‐infection resulted in down regulation of several IFN genes and significant up regulation of TGF‐β genes leading to an overall enhancement of HCV replication. These data suggest that HIV infection may influence HCV replication in vitro by increasing levels of HCV RNA, possibly through the differential regulation of endogenous IFN and TGF family genes. J. Med. Virol. 84:1344–1352, 2012. © 2012 Wiley Periodicals, Inc.