Ribozyme-mediated reduction of wild-type and mutant cartilage oligomeric matrix protein (COMP) mRNA and protein.

Dominant-negative mutations in the homopentameric extracellular matrix glycoprotein cartilage oligomeric matrix protein (COMP) result in inappropriate intracellular retention of misfolded COMP in the rough endoplasmic reticulum of chondrocytes, causing chondrocyte cell death, which leads to two skeletal dysplasias: pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (EDM1). COMP null mice show no adverse effects on normal bone development and growth, suggesting a possible therapy involving removal of COMP mRNA. The goal of this study was to assess the ability of a hammerhead ribozyme (Ribo56, designed against the D469del mutation) to reduce COMP mRNA expression. In COS7 cells transfected with plasmids that overexpress wild-type or mutant COMP mRNA and Ribo56, the ribozyme reduced overexpressed normal COMP mRNA by 46% and mutant COMP mRNA by 56% in a dose-dependent manner. Surprisingly, the use of recombinant adenoviruses to deliver wild-type or mutant COMP mRNA and Ribo56 simultaneously into COS7 cells proved problematic for the activity of the ribozyme to reduce COMP expression. However, in normal human costochondral cells (hCCCs) infected only with adenoviruses expressing Ribo56, expression of endogenous wild-type COMP mRNA was reduced in a dose-dependent manner by 50%. In chondrocytes that contain heterozygous COMP mutations (D469del, G427E and D511Y) that cause PSACH, Ribo56 was more effective at reducing COMP mRNA (up to 70%). These results indicate that Ribo56 is effective at reducing mutant and wild-type COMP levels in cells and suggests a possible mode of therapy to reduce the mutant protein load.

Access to health care among children in the U.S.: Use of health inequalities measures to evaluate progress in reduction of disparities from 1997 to 2005

Much of the literature on disparities in access to health care among children has focused on measuring absolute and relative differences experienced by race/ethnic groups and, to a lesser extent, socioeconomic groups. However, it is not clear from existing literature how disparities in access to care may have changed over time for children, especially following implementation of the State Children’s Health Insurance Program (SCHIP). The primary objective of this research was to determine if there has been a decrease in disparities in access to care for children across two socioeconomic groups and race/ethnicity groups after SCHIP implementation. Methods commonly used to measure ‘health inequalities’ were used to measure disparities in access to care including population-attributable risk (PAR) and the relative index of inequality (RII). Using these measures there is evidence of a substantial decrease in socioeconomic disparities in health insurance coverage and to a lesser extent in having a usual source of care since the SCHIP program began. There is also evidence of a considerable decrease in non-Hispanic Black disparities in access to care. However, there appears to be a slight increase in disparities in access to care among Hispanic compared to non-Hispanic White children. While there were great improvements in disparities in access to care with the introduction of the SCHIP program, continuing progress in disparities may depend on continuation of the SCHIP program or similar targeted health policy programs. ^

Reduction of setup uncertainties and tumor motion in the radiation therapy of lung tumors

Because the goal of radiation therapy is to deliver a lethal dose to the tumor, accurate information on the location of the tumor needs to be known. Margins are placed around the tumor to account for variations in the daily position of the tumor. If tumor motion and patient setup uncertainties can be reduced, margins that account for such uncertainties in tumor location in can be reduced allowing dose escalation, which in turn could potentially improve survival rates. ^ In the first part of this study, we monitor the location of fiducials implanted in the periphery of lung tumors to determine the extent of non-gated and gated fiducial motion, and to quantify patient setup uncertainties. In the second part we determine where the tumor is when different methods of image-guided patient setup and respiratory gating are employed. In the final part we develop, validate, and implement a technique in which patient setup uncertainties are reduced by aligning patients based upon fiducial locations in projection images. ^ Results from the first part indicate that respiratory gating reduces fiducial motion relative to motion during normal respiration and setup uncertainties when the patients were aligned each day using externally placed skin marks are large. The results from the second part indicate that current margins that account for setup uncertainty and tumor motion result in less than 2% of the tumor outside of the planning target volume (PTV) when the patient is aligned using skin marks. In addition, we found that if respiratory gating is going to be used, it is most effective if used in conjunction with image-guided patient setup. From the third part, we successfully developed, validated, and implemented on a patient a technique for aligning a moving target prior to treatment to reduce the uncertainties in tumor location. ^ In conclusion, setup uncertainties and tumor motion are a significant problem when treating tumors located within the thoracic region. Image-guided patient setup in conjunction with treatment delivery using respiratory gating reduces these uncertainties in tumor locations. In doing so, margins around the tumor used to generate the PTV can be reduced, which may allow for dose escalation to the tumor. ^

Spatial analysis of water body distance and West Nile Virus human cases in Houston, TX

West Nile Virus (WNV) is an arboviral disease that has affected hundreds of residents in Harris County, Texas since its introduction in 2002. Persistent infection, lingering sequelae and other long-term symptoms of patients reaffirm the need for prevention of this important vector-borne disease. This study aimed to determine if living within 400m of a water body increases one’s odds of infection with WNV. Additionally, we wanted to determine if one’s proximity to a particular water type or water body source increased one’s odds of infection with WNV.^ 145 cases’ addresses were abstracted from the initial interview and consent records from a cohort of patients (Epidemiology of Arboviral Encephalitis in Houston study, HSC-SPH-03-039). After applying inclusion criteria, 140 cases were identified for analysis. 140 controls were selected for analysis using a population proportionate to size model and US Census Bureau data. MapMarker USA v14 was used to geocode the cases’ addresses. Both cases’ and controls’ coordinates were uploaded onto a Harris County water shapefile in MapInfo Professional v9.5.1. Distance in meters to the closest water source, closest water source type, and closest water source name were recorded.^ Analysis of Variance (p=0.329, R2 = 0.0034) indicated no association between water body distance and risk of WNV disease. Living near a creek (x2 = 11.79, p < 0.001), or the combined group of creek and gully (x 2 = 14.02, p < 0.001) were found to be strongly associated with infection of WNV. Living near Cypress Creek and its feeders (x2 = 15.2, p < 0.001) was found to be strongly associated with WNV infection. We found that creek and gully habitats, particularly Cypress Creek, were preferential for the local disease transmitting Culex quinquefasciatus and reservoir avian population.^

A comparative review of water disinfection methods appropriate for developing countries and their efficacy, cost-efficiency, and usability

Developing countries are heavily burdened by limited access to safe drinking water and subsequent water-related diseases. Numerous water treatment interventions combat this public health crisis, encompassing both traditional and less-common methods. Of these, water disinfection serves as an important means to provide safe drinking water. Existing literature discusses a wide range of traditional treatment options and encourages the use of multi-barrier approaches including coagulation-flocculation, filtration, and disinfection. Most sources do not delve into approaches specifically appropriate for developing countries, nor do they exclusively examine water disinfection methods.^ The objective of this review is to focus on an extensive range of chemical, physio-chemical, and physical water disinfection techniques to provide a compilation, description and evaluation of options available. Such an objective provides further understanding and knowledge to better inform water treatment interventions and explores alternate means of water disinfection appropriate for developing countries. Appropriateness for developing countries corresponds to the effectiveness of an available, easy to use disinfection technique at providing safe drinking water at a low cost.^ Among chemical disinfectants, SWS sodium hypochlorite solution is preferred over sodium hypochlorite bleach due to consistent concentrations. Tablet forms are highly recommended chemical disinfectants because they are effective and very easy to use, but also because they are stable. Examples include sodium dichloroisocyanurate, calcium hypochlorite, and chlorine dioxide, which vary in cost depending on location and availability. Among physio-chemical disinfection options, electrolysis which produces mixed oxidants (MIOX) provides a highly effective disinfection option with a higher upfront cost but very low cost over the long term. Among physical disinfection options, solar disinfection (SODIS) applications are effective, but they treat only a fixed volume of water at a time. They come with higher initial costs but very low on-going costs. Additional effective disinfection techniques may be suitable depending on the location, availability and cost.^

Implementation of active surveillance cultures and associated infection control practices for the reduction of methicillin resistant Staphylococcus aureus in the healthcare setting: An interrupted time series analysis

OBJECTIVE. To determine the effectiveness of active surveillance cultures and associated infection control practices on the incidence of methicillin resistant Staphylococcus aureus (MRSA) in the acute care setting. DESIGN. A historical analysis of existing clinical data utilizing an interrupted time series design. ^ SETTING AND PARTICIPANTS. Patients admitted to a 260-bed tertiary care facility in Houston, TX between January 2005 through December 2010. ^ INTERVENTION. Infection control practices, including enhanced barrier precautions, compulsive hand hygiene, disinfection and environmental cleaning, and executive ownership and education, were simultaneously introduced during a 5-month intervention implementation period culminating with the implementation of active surveillance screening. Beginning June 2007, all high risk patients were cultured for MRSA nasal carriage within 48 hours of admission. Segmented Poisson regression was used to test the significance of the difference in incidence of healthcare-associated MRSA during the 29-month pre-intervention period compared to the 43-month post-intervention period. ^ RESULTS. A total of 9,957 of 11,095 high-risk patients (89.7%) were screened for MRSA carriage during the intervention period. Active surveillance cultures identified 1,330 MRSA-positive patients (13.4%) contributing to an admission prevalence of 17.5% in high-risk patients. The mean rate of healthcare-associated MRSA infection and colonization decreased from 1.1 per 1,000 patient-days in the pre-intervention period to 0.36 per 1,000 patient-days in the post-intervention period (P<0.001). The effect of the intervention in association with the percentage of S. aureus isolates susceptible to oxicillin were shown to be statistically significantly associated with the incidence of MRSA infection and colonization (IRR = 0.50, 95% CI = 0.31-0.80 and IRR = 0.004, 95% CI = 0.00003-0.40, respectively). ^ CONCLUSIONS. It can be concluded that aggressively targeting patients at high risk for colonization of MRSA with active surveillance cultures and associated infection control practices as part of a multifaceted, hospital-wide intervention is effective in reducing the incidence of healthcare-associated MRSA.^