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This project used a retrospective case series design to investigate factors associated with stroke in a rural area in Appalachian Kentucky. The south-eastern region of the U.S. is often referred to as the ‘stroke belt,’ and includes the Appalachian region of the state of Kentucky. Data were collected from medical records of patients from a neurology practice and regional hospital with a diagnosis of stroke from March 2012 through November 2015. Data were collected without personal identifiers and included demographic characteristics, stroke type, treatments received, and referrals for additional care including rehabilitation. Data from a total of 84 stroke cases diagnosed between March 2012 and November 2015 were included. Of the 84 cases, 46 (54.8%) were female and all but one was Caucasian. The distribution by race is consistent with the population of the region. The stroke cases ranged in age from 41 to 92 (M=66.3) and the age at stroke diagnosis ranged from 40 to 90 (M=65.7). Fourteen (16.7%) had evidence of a previous stroke at diagnosis. For smokers, the mean age at diagnosis was 62.7 for smokers while for non-smokers it was 67.5. The study reported smoking rates that were nearly three-times the national average, and the smokers in this study were found to have stroke onset approximately five-years earlier than non-smokers. The results from this case series support the need for further investigation on stroke prevalence and factors contributing to continued risk for stroke in Appalachia.

Purpose Familial exudative vitreoretinopathy (FEVR) is caused by mutations in the genes encoding low-density lipoprotein receptor-related protein (LRP5) or its interacting partners, namely frizzled class receptor 4 (FZD4) and norrin cystine knot growth factor (NDP). Mouse models for Lrp5, Fzd4, and Ndp have proven to be important for understanding the retinal pathophysiology underlying FEVR and systemic abnormalities related to defective Wnt signaling. Here, we report a new mouse mutant, tvrm111B, which was identified by electroretinogram (ERG) screening of mice generated in the Jackson Laboratory Translational Vision Research Models (TVRM) mutagenesis program. Methods ERGs were used to examine outer retinal physiology. The retinal vasculature was examined by in vivo retinal imaging, as well as by histology and immunohistochemistry. The tvrm111B locus was identified by genetic mapping of mice generated in a cross to DBA/2J, and subsequent sequencing analysis. Gene expression was examined by real-time PCR of retinal RNA. Bone mineral density (BMD) was examined by peripheral dual-energy X-ray absorptiometry. Results The tvrm111B allele is inherited as an autosomal recessive trait. Genetic mapping of the decreased ERG b-wave phenotype of tvrm111B mice localized the mutation to a region on chromosome 19 that included Lrp5. Sequencing of Lrp5 identified the insertion of a cytosine (c.4724_4725insC), which is predicted to cause a frameshift that disrupts the last three of five conserved PPPSPxS motifs in the cytoplasmic domain of LRP5, culminating in a premature termination. In addition to a reduced ERG b-wave, Lrp5tvrm111B homozygotes have low BMD and abnormal features of the retinal vasculature that have been reported previously in Lrp5 mutant mice, including persistent hyaloid vessels, leakage on fluorescein angiography, and an absence of the deep retinal capillary bed. Conclusions The phenotype of the Lrp5tvrm111B mutant includes abnormalities of the retinal vasculature and of BMD. This model may be a useful resource to further our understanding of the biological role of LRP5 and to evaluate experimental therapies for FEVR or other conditions associated with LRP5 dysfunction.

PurposeFetal mice require light exposure in utero during early gestation for normal vascular development in the eye. Because angiogenic abnormalities in retinopathy of prematurity (ROP) are manifested in preterm infants, we investigated whether day length during early gestation was associated with severe ROP (SROP).DesignSingle-center, retrospective cohort study.ParticipantsWe included a total of 343 premature infants (401-1250 g birth weight [BW], from 1998-2002): 684 eyes (1 eye each of 2 patients excluded) with 76 eyes developing SROP, defined as (1) classic threshold ROP in zone I or II, (2) type 1 ROP in zone I, or (3) in a few eyes, type 1 ROP in posterior zone II that was treated.MethodsFor each infant, average day length (ADL) was calculated during different cumulative time periods and time windows after the estimated date of conception (EDC). Multiple logistic regression analysis (with generalized estimating equations to account for inter-eye correlation) was performed.Main outcome measuresAssociation of ADL during early gestation with SROP.ResultsIn a model evaluating all 684 eyes with 76 eyes developing SROP, BW, gestational age, multiple births, race, per capita income in the mother's residence ZIP code, and ADL during the first 90 days after the EDC were factors associated with the development of SROP. Each additional hour of ADL (90 days) decreased the likelihood of SROP by 28% (P = 0.015; odds ratio [OR], 0.72; 95% confidence interval [CI], 0.55-0.94). In a model evaluating the subset of 146 prethreshold ROP eyes with 76 eyes developing SROP, each additional hour of ADL during the first 105 days after the EDC decreased the likelihood of SROP by 46% (P = 0.001; OR, 0.54; 95% CI, 0.37-0.78). Time windows when ADL was most closely associated with SROP were 31 to 60 days and 61 to 90 days after the EDC for the all eyes and the prethreshold ROP eyes models, respectively.ConclusionsHigher ADL during early gestation was associated with a lower risk for SROP and may imply a role for prophylactic light treatment during early gestation to decrease the risk of SROP.

This paper describes a refresher training and continuing education programme in clinical and community ophthalmology for para-medical ophthalmic assistants (PMOAs) conducted by the Lions Aravind Institute of Community Ophthalmology. The course participants included 60 PMOAs working either in district hospitals, primary health centres or mobile units from the districts in Maharashtra. Each training programme was spread over 43 hours in 4 days and included lectures, practical demonstrations, and hands-on training in the outpatient, inpatient, and operation theatre of the training institution. Participants were given exposure to outreach activities in an eye camp and a satellite eye centre resembling a district hospital. The PMOAs found the training to be useful and it was seen that areas like patient counselling, instrument and equipment maintenance, and assistance in the operation theatre for newer surgical procedures which were lacking in the basic training were fulfilled in this training programme. Regional Institutes of Ophthalmology, upgraded medical colleges, and other eye-care institutions which have facilities and manpower could organise similar refresher and continuing education programmes for PMOAs so that they could be utilised more efficiently in the blindness-control activities in the country.

Macrophages have been suggested to stimulate neo-lymphangiogenesis in settings of inflammation via two potential mechanisms: (1) acting as a source of lymphatic endothelial progenitor cells via the ability to transdifferentiate into lymphatic endothelial cells and be incorporated into growing lymphatic vessels; and (2) providing a crucial source of pro-lymphangiogenic growth factors and proteases. We set out to establish whether cells of the myeloid lineage are important for development of the lymphatic vasculature through either of these mechanisms. Here, we provide lineage tracing evidence to demonstrate that lymphatic endothelial cells arise independently of the myeloid lineage during both embryogenesis and tumour-stimulated lymphangiogenesis in the mouse, thus excluding macrophages as a source of lymphatic endothelial progenitor cells in these settings. In addition, we demonstrate that the dermal lymphatic vasculature of PU.1-/- and Csf1r-/- macrophage-deficient mouse embryos is hyperplastic owing to elevated lymphatic endothelial cell proliferation, suggesting that cells of the myeloid lineage provide signals that act to restrain lymphatic vessel calibre in the skin during development. In contrast to what has been demonstrated in settings of inflammation, macrophages do not comprise the principal source of pro-lymphangiogenic growth factors, including VEGFC and VEGFD, in the embryonic dermal microenvironment, illustrating that the sources of patterning and proliferative signals driving embryonic and disease-stimulated lymphangiogenesis are likely to be distinct. Refereed/Peer-reviewed