We report the chromosomal localization, mutant gene identification, ophthalmic appearance, histology, and functional analysis of two new hereditary mouse models of retinal degeneration not having the Pde6brd1("r", "rd", or "rodless") mutation. One strain harbors an autosomal recessive mutation that maps to mouse chromosome 5. Sequence analysis showed that the retinal degeneration is caused by a missense point mutation in exon 13 of the beta-subunit of the rod cGMP phosphodiesterase (beta-PDE) gene (Pde6b). The gene symbol for this strain was set as Pde6brd10, abbreviated rd10 hereafter. Mice homozygous for the rd10 mutation showed histological changes at postnatal day 16 (P16) of age and sclerotic retinal vessels at four weeks of age, consistent with retinal degeneration. Retinal sections were highly positive for TUNEL and activated caspase-3 immunoreactivity, specifically in the outer nuclear layer (ONL). ERGs were never normal, but rod and cone ERG a- and b-waves were easily measured at P18 and steadily declined over 90% by two months of age. Protein extracts from rd10 retinas were positive for beta-PDE immunoreactivity starting at about the same time as wild-type (P10), though signal averaged less than 40% of wild-type. Interestingly, rearing rd10 mice in total darkness delayed degeneration for at least a week, after which morphological and functional loss progressed irregularly. With the second strain, a complementation test with rd1 mice revealed that the retinal degeneration phenotype observed represents a possible new allele of Pde6b. Sequencing demonstrated a missense point mutation in exon 16 of the beta-subunit of rod phosphodiesterase gene, different from the point mutations in rd1 and rd10. The gene symbol for this strain was set as Pde6bnmf137, abbreviated nmf137 hereafter. Mice homozygous for this mutation showed retinal degeneration with a mottled retina and white retinal vessels at three weeks of age. The exon 13 missense mutation (rd10) is the first known occurrence of a second mutant allele spontaneously arising in the Pde6b gene in mice and may provide a model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in humans. It may also provide a better model for experimental pharmaceutical-based therapy for RP because of its later onset and milder retinal degeneration than rd1 and nmf137.

Exposure to higher personal-level PM₂.₅ during routine daily activity measured with low-bias and minimally-confounded personal monitors was associated with modest increases in systolic blood pressure and trends towards arterial vasoconstriction. Comparable elevations in community PM₂.₅ levels were not related to these outcomes, suggesting that specific components within personal and background ambient PM₂.₅ may elicit differing cardiovascular responses.

These results suggest that subretinal electrical stimulation provides temporary preservation of retinal function in the RCS rat. In addition, implantation of an active or inactive device into the subretinal space causes morphologic preservation of photoreceptors in the RCS rat until 8 weeks after surgery. Further studies are needed to determine whether the correlation of neuropreservation with subretinal implantation is due to electrical stimulation and/or a mechanical presence of the implant in the subretinal space.

The US Environmental Protection Agency recently conducted the Detroit Exposure and Aerosol Research Study (DEARS). The study began in 2004 and involved community, residential, and personal-based measurements of air pollutants targeting 120 participants and their residences. The primary goal of the study was to evaluate and describe the relationship between air toxics, particulate matter (PM), PM constituents, and PM from specific sources measured at a central site monitor with those from the residential and personal locations. The impact of regional, local (point and mobile), and personal sources on pollutant concentrations and the role of physical and human factors that might influence these concentrations were investigated. A combination of active and passive sampling methodologies were employed in the collection of PM mass, criteria gases, semivolatile organics, and volatile organic compound air pollutants among others. Monitoring was conducted in six selected neighborhoods along with one community site using a repeated measure design. Households from each of the selected communities were monitored for 5 consecutive days in the winter and again in the summer. Household, participant and a variety of other surveys were utilized to better understand human and household factors that might affect the impact of ambient-based pollution sources upon personal and residential locations. A randomized recruitment strategy was successful in enrolling nearly 140 participants over the course of the study. Over 36,000 daily-based environmental data points or records were ultimately collected. This paper fully describes the design of the DEARS and the approach used to implement this field monitoring study and reports select preliminary findings.

TUDCA is efficacious and safe in preserving vision in the rd10 mouse model of RP when treated between P6 and P30. At P30, a developmental stage at which nearly all rods are absent in the rd10 mouse model of RP, TUDCA treatment preserved rod and cone function and greatly preserved overall photoreceptor numbers.

No abstract

Solid fuel burning cookstoves are a major source of household air pollution (HAP) and a significant environmental health risk in Sri Lanka. We report results of the first field study in Sri Lanka to include direct measurements of both real-time indoor concentrations and personal exposures of fine particulate matter (PM ) in households using the two most common stove types in Sri Lanka. A purposive sample of 53 households was selected in the rural community of Kopiwatta in central Sri Lanka, roughly balanced for stove type (traditional or improved 'Anagi') and ventilation (chimney present or absent). At each household, 48-h continuous real-time measurements of indoor kitchen PM and personal (primary cook) PM concentrations were measured using the RTI MicroPEM personal exposure monitor. Questionnaires were used to collect data related to household demographics, characteristics, and self-reported health symptoms. All primary cooks were female and of an average age of 47 years, with 66% having completed primary education. Median income was slightly over half the national median monthly income. Use of Anagi stoves was positively associated with a higher education level of the primary cook (P = 0.026), although not associated with household income (P = 0.18). The MicroPEM monitors were well-received by participants, and this study's valid data capture rate exceeded 97%. Participant wearing compliance during waking hours was on average 87.2% on Day 1 and 83.3% on Day 2. Periods of non-compliance occurred solely during non-cooking times. The measured median 48-h average indoor PM concentration for households with Anagi stoves was 64 μg/m if a chimney was present and 181 μg/m if not. For households using traditional stoves, these values were 70 μg/m if a chimney was present and 371 μg/m if not. Overall, measured indoor PM concentrations ranged from a minimum of 33 μg/m to a maximum of 940 μg/m , while personal exposure concentrations ranged from 34 to 522 μg/m . Linear mixed effects modeling of the dependence of indoor concentrations on stove type and presence or absence of chimney showed a significant chimney effect (65% reduction; P < 0.001) and an almost significant stove effect (24% reduction; P = 0.054). Primary cooks in households without chimneys were exposed to substantially higher levels of HAP than those in households with chimneys, while exposures in households with traditional stoves were moderately higher than those with improved Anagi stoves. As expected, simultaneously measuring both indoor concentrations and personal exposure levels indicate significant exposure misclassification bias will likely result from the use of a stationary monitor as a proxy for personal exposure. While personal exposure monitoring is more complex and expensive than deploying simple stationary devices, the value an active personal PM monitor like the MicroPEM adds to an exposure study should be considered in future study designs.

A review of 14,667 necropsy reports for every year from 1965 to 1990 and 6,436 diagnostic venograms performed from 1976 to 1990 was undertaken at a single teaching hospital. A progressive reduction in the percentage of necropsies reporting fatal pulmonary embolism from 6.1 to 2.1 %, occurred over the 25-year period (χ² tests for linear trend with time p < 0.00001). Over the last decade, there has been a significant reduction in the rate of venographically diagnosed postoperative deep vein thrombosis (DVT) from 49.9 to 24.7 per 100,000 population (p < 0.0001) which was in marked contrast to the constant rate of non-postoperative DVT. Our findings suggest that the introduction of thromboprophylactic measures, in addition to changes in hospital practice, may have had a highly significant effect on the pattern of this serious, but potentially avoidable disease.