INFECTIOUS KERATITIS-ASSOCIATED ENDOPHTHALMITIS: A 14-Year Study.

PURPOSE: To describe the demographics, characteristics, management, and outcomes of eyes with endophthalmitis related to infectious keratitis. METHODS: Retrospective chart review of all patients treated for infectious keratitis-associated infectious endophthalmitis between 2001 and 2014 at University Hospital, Rutgers New Jersey Medical School. RESULTS: Thirty-eight cases with infectious keratitis-associated infectious endophthalmitis were identified (21 men [55%], mean age: 66.2 ± 20.7 years), with average time from the beginning of ulcer symptoms to endophthalmitis of 11.0 days. Associated systemic conditions (diabetes, HIV, immunosuppressive therapy, cirrhosis, or dementia) were present in 57.9%; 60.5% had previous intraocular surgery. Etiology showed gram-positive bacteria in 14 cases (36.9%), gram-negative bacteria in 7 (18.4%), fungi in 4 (10.5%), and no growth/unknown in 12 (31.6%). Nineteen cases (50%) presented with no light perception and were primarily enucleated. The remaining 19 eyes each received intravitreal antibiotics (mean: 1.5 injections); 8 (42.0%) underwent pars plans vitrectomy with vitreous biopsy, whereas 5 (26.3%) received emergency corneal transplantation. Final visual acuity was no light perception in 6 eyes (3 secondarily enucleated), light perception in 2, hand motion in 7, counting fingers in 2, and ≥20/50 in 2. CONCLUSION: Our study of 38 eyes with infectious keratitis-associated infectious endophthalmitis revealed generally poor visual outcomes and a high rate of systemic conditions and previous intraocular surgery.

Structural requirements for interaction of peroxisomal targeting signal 2 and its receptor PEX7.

The import of a subset of peroxisomal matrix proteins is mediated by the peroxisomal targeting signal 2 (PTS2). The results of our sequence and physical property analysis of known PTS2 signals and of a mutational study of the least characterized amino acids of a canonical PTS2 motif indicate that PTS2 forms an amphipathic helix accumulating all conserved residues on one side. Three-dimensional structural modeling of the PTS2 receptor PEX7 reveals a groove with an evolutionarily conserved charge distribution complementary to PTS2 signals. Mammalian two-hybrid assays and cross-complementation of a mutation in PTS2 by a compensatory mutation in PEX7 confirm the interaction site. An unstructured linker region separates the PTS2 signal from the core protein. This additional information on PTS2 signals was used to generate a PTS2 prediction algorithm that enabled us to identify novel PTS2 signals within human proteins and to describe KChIP4 as a novel peroxisomal protein.

Ocular telehealth screenings in an urban community.

The current U.S. economic recession has resulted in a loss of income, housing, and healthcare coverage. Our major goal in this socioeconomic setting was to provide ophthalmic remote health screenings for urban soup kitchen and homeless populations in order to identify and refer undetected vision-threatening disease (VTD). We assessed visual acuity, blood pressure, pulse/oxygen saturation, body mass index, and intraocular pressure for 341 participants at soup kitchens as part of the homeless outreach program in Newark, NJ. History of diabetes, hypertension, and smoking, last ocular examination, and ocular history were noted. Imaging was performed with an 8.2 megapixel non-mydriatic retinal camera with high-speed Internet ready for off-site second opinion image evaluation. Positive VTD findings were identified in 105 participants (31%) (mean age, 53.6 years), of whom 78% were African American, 73% males, and 62% smokers. We detected glaucoma in 34 participants (32%), significant cataract in 22 (21%), diabetic retinopathy in 5 (5%), optic atrophy in 1 (1%), age-related macular degeneration in 1 (1%), and other retinal findings in 43 (41%). The incidence of VTDs was higher among this cohort than among study groups in previous screenings (31% vs. 12%). This finding shows an increase in ocular morbidity in a younger, at-risk population with elevated rates of hypertension, diabetes, and smoking. Functional visual impairment was 2.5 times higher than the national average (16% vs. 6.4%). Comprehensive, community-based screenings can provide more sensitive detection of VTDs in high-risk groups with low access to ophthalmic care and can be an integral part of recession solutions for improving healthcare.

Investigation of factors controlling PM2.5 variability across the South Korean Peninsula during KORUS-AQ.

The Korea - United States Air Quality Study (May - June 2016) deployed instrumented aircraft and ground-based measurements to elucidate causes of poor air quality related to high ozone and aerosol concentrations in South Korea. This work synthesizes data pertaining to aerosols (specifically, particulate matter with aerodynamic diameters <2.5 micrometers, PM2.5) and conditions leading to violations of South Korean air quality standards (24-hr mean PM2.5 < 35 µg m-3). PM2.5 variability from AirKorea monitors across South Korea is evaluated. Detailed data from the Seoul vicinity are used to interpret factors that contribute to elevated PM2.5. The interplay between meteorology and surface aerosols, contrasting synoptic-scale behavior vs. local influences, is presented. Transboundary transport from upwind sources, vertical mixing and containment of aerosols, and local production of secondary aerosols are discussed. Two meteorological periods are probed for drivers of elevated PM2.5. Clear, dry conditions, with limited transport (Stagnant period), promoted photochemical production of secondary organic aerosol from locally emitted precursors. Cloudy humid conditions fostered rapid heterogeneous secondary inorganic aerosol production from local and transported emissions (Transport/Haze period), likely driven by a positive feedback mechanism where water uptake by aerosols increased gas-to-particle partitioning that increased water uptake. Further, clouds reduced solar insolation, suppressing mixing, exacerbating PM2.5 accumulation in a shallow boundary layer. The combination of factors contributing to enhanced PM2.5 is challenging to model, complicating quantification of contributions to PM2.5 from local versus upwind precursors and production. We recommend co-locating additional continuous measurements at a few AirKorea sites across South Korea to help resolve this and other outstanding questions: carbon monoxide/carbon dioxide (transboundary transport tracer), boundary layer height (surface PM2.5 mixing depth), and aerosol composition with aerosol liquid water (meteorologically-dependent secondary production). These data would aid future research to refine emissions targets to further improve South Korean PM2.5 air quality.

Reduction of spermatogenesis but not fertility in Creb3l4-deficient mice.

Creb3l4 belongs to the CREB/ATF family of transcription factors that are involved in mediating transcription in response to intracellular signaling. This study shows that Creb3l4 is expressed at low levels in all organs and in different stages of embryogenesis but is present at very high levels in the testis, particularly in postmeiotic male germ cells. In contrast to CREB3L4 in the human prostate, of which specific expression was detected, Creb3l4 transcripts in the mouse prostate could be detected only by RT-PCR. To identify the physiological function of Creb3l4, the murine gene was inactivated by replacement with the gene encoding green fluorescent protein. Surprisingly, Creb3l4-deficient mice were born at expected ratios, were healthy, and displayed normal long-term survival rates. Despite a significant reduction in the number of spermatozoa in the epididymis of Creb3l4(-)(/)(-) mice, the breeding of mutant males with wild-type females was productive and the average litter size was not significantly altered in comparison to wild-type littermates. Further analyses revealed that the seminiferous tubules of Creb3l4(-)(/)(-) mice contained all of the developmental stages, though there was evidence for increased apoptosis of meiotic/postmeiotic germ cells. These results suggest that Creb3l4 plays a role in male germ cell development, but its loss is insufficient to completely compromise the production of spermatozoa.

A systematic review of as needed versus treat and extend ranibizumab or bevacizumab treatment regimens for neovascular age-related macular degeneration.

PURPOSE: To evaluate the relative efficacy of as needed versus treat and extend regimen for the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a systematic review of studies that evaluated the efficacy of as needed or treat and extend regimen for neovascular AMD by searching multiple databases up to December 2013. Included studies were selected based on study duration of no less than 12 months, availability of outcome data, treatment protocol for as needed groups or pro re nata (PRN) receiving bevacizumab or ranibizumab, and all studies with treat extend protocols following the 'inject and extend' regimen. The outcome data were pooled and analysed. RESULTS: 1046 peer reviewed articles meeting our initial search criteria were returned. After further review by two independent reviewers, 8 studies meeting treat and extend protocol and 62 studies meeting PRN protocol were included. The mean improvement in visual acuity in the PRN group was 5.4 ETDRS letters compared with 10.4 ETDRS letters in the treat and extend group. The PRN group received an average of 5.60 injections at 1 year compared with 8.09 in the treat and extend group. Central retinal thickness improved on average by 100.32 µ in the PRN group compared with 87.7 µ in the treat and extend group. CONCLUSIONS: Though our study suggests superiority of the treat and extend regimen to PRN treatment in a 12-month period, this review demonstrates the need for randomised clinical trials to confirm our findings and to evaluate long-term efficacy outcomes with these regimens compared with monthly therapy.

Corneoscleral Laceration and Ocular Burns Caused by Electronic Cigarette Explosions.

PURPOSE: To report cases of acute globe rupture and bilateral corneal burns from electronic cigarette (EC) explosions. METHODS: Case series. RESULTS: We describe a series of patients with corneal injury caused by EC explosions. Both patients suffered bilateral corneal burns and decreased visual acuity, and one patient sustained a unilateral corneoscleral laceration with prolapsed iris tissue and hyphema. A review of the scientific literature revealed no prior reported cases of ocular injury secondary to EC explosions; however, multiple media and government agency articles describe fires and explosions involving ECs, including at least 4 with ocular injuries. CONCLUSIONS: Given these cases and the number of recent media reports, ECs pose a significant public health risk. Users should be warned regarding the possibility of severe injury, including sight-threatening ocular injuries ranging from corneal burns to full-thickness corneoscleral laceration.

Impacts of brown carbon from biomass burning on surface UV and ozone photochemistry in the Amazon Basin.

The spectral dependence of light absorption by atmospheric particulate matter has major implications for air quality and climate forcing, but remains uncertain especially in tropical areas with extensive biomass burning. In the September-October 2007 biomass-burning season in Santa Cruz, Bolivia, we studied light absorbing (chromophoric) organic or "brown" carbon (BrC) with surface and space-based remote sensing. We found that BrC has negligible absorption at visible wavelengths, but significant absorption and strong spectral dependence at UV wavelengths. Using the ground-based inversion of column effective imaginary refractive index in the range 305-368 nm, we quantified a strong spectral dependence of absorption by BrC in the UV and diminished ultraviolet B (UV-B) radiation reaching the surface. Reduced UV-B means less erythema, plant damage, and slower photolysis rates. We use a photochemical box model to show that relative to black carbon (BC) alone, the combined optical properties of BrC and BC slow the net rate of production of ozone by up to 18% and lead to reduced concentrations of radicals OH, HO2, and RO2 by up to 17%, 15%, and 14%, respectively. The optical properties of BrC aerosol change in subtle ways the generally adverse effects of smoke from biomass burning.

Systemic inflammatory response depends on initial stroke severity but is attenuated by successful thrombolysis.

BACKGROUND AND PURPOSE: To determine whether body temperature, c-reactive protein (CRP), and white blood cell (WBC) count within the first days after stroke onset correlate with infarct size and stroke severity, and to examine whether successful thrombolysis reduces poststroke inflammation. METHODS: Out of 1500 consecutive acute ischemic stroke patients, 346 cases (43 patients with thrombolysis) were selected according to the following criteria: admission to hospital < or =24 hours after event, absence of prestroke and poststroke infectious disease, no intracerebral hemorrhage or brain stem stroke, and data availability. Body temperature, WBC within 3 days, and CRP within 5 days of event were determined daily. Lesion volume was measured by planimetry on computed tomography or MRI scans. Successful thrombolysis was defined as improvement on the National Institutes of Health Stroke Scale of > or =4 points within 24 hours. RESULTS: Increase of inflammatory parameters correlated significantly with lesion volume and stroke severity. This was shown for body temperature on days 2 and 3 (P<0.001), CRP on days 1 to 5 (P<0.05), and WBC on days 1 to 3 (P<0.01). Patients with successful thrombolysis had reduced body temperature on day 3, WBC on days 2 and 3, and CRP on days 3 to 5 (P<0.05). CONCLUSIONS: Patients with a larger stroke volume and more severe stroke deficits have higher body temperature, CRP, and WBC count in the acute phase after stroke. Successful thrombolysis is related to a significantly attenuated inflammatory response.

STAC: A method for testing the significance of DNA copy number aberrations across multiple array-CGH experiments.

Regions of gain and loss of genomic DNA occur in many cancers and can drive the genesis and progression of disease. These copy number aberrations (CNAs) can be detected at high resolution by using microarray-based techniques. However, robust statistical approaches are needed to identify nonrandom gains and losses across multiple experiments/samples. We have developed a method called Significance Testing for Aberrant Copy number (STAC) to address this need. STAC utilizes two complementary statistics in combination with a novel search strategy. The significance of both statistics is assessed, and P-values are assigned to each location on the genome by using a multiple testing corrected permutation approach. We validate our method by using two published cancer data sets. STAC identifies genomic alterations known to be of clinical and biological significance and provides statistical support for 85% of previously reported regions. Moreover, STAC identifies numerous additional regions of significant gain/loss in these data that warrant further investigation. The P-values provided by STAC can be used to prioritize regions for follow-up study in an unbiased fashion. We conclude that STAC is a powerful tool for identifying nonrandom genomic amplifications and deletions across multiple experiments. A Java version of STAC is freely available for download at http://cbil.upenn.edu/STAC.

Dystonia and parkinsonism in GM1 type 3 gangliosidosis.

GM1 gangliosidosis is due to beta-galactosidase deficiency. Only patients with type 3 disease survive into adulthood and develop movement disorders. Clinical descriptions of this form are rare, particularly in non-Japanese patients. We describe four new patients and systematically analyze all previous reports found by a literature search and contacts with the authors for additional information. Generalized dystonia remained the predominant feature throughout the disease course and was often associated with akinetic-rigid parkinsonism. GM1 gangliosidosis must be considered as a cause of early-onset generalized dystonia, particularly in patients with short stature and skeletal dysplasia.