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Objective To characterize the association between prolonged supine postoperative positioning of patients undergoing Descemet-stripping automated endothelial keratoplasty (DSAEK) and graft dislocation rate. Methods In this retrospective cohort study, medical records of patients who underwent uncomplicated DSAEK surgery at Yitzhak Shamir Medical Center between 2010 and 2019 were reviewed. Nursing documentation of patients’ adherence to supine positioning during the postoperative hospitalization period was collected. A patient was considered compliant if he or she was documented as cooperative with supine positioning throughout the first 24 hours. Results A total of 170 eyes of 138 patients were found eligible. Main indications for surgery were pseudophakic bullous keratopathy (50.6%), previous graft failure (25.9%), and Fuch's endothelial dystrophy (FED; 20.6%). Twelve surgeries were combined with cataract extraction. Postoperative graft detachment occurred in 26 eyes (15.3%) after an average period of 1 day (range, 0–20 days). Compliance with supine positioning was documented in 84.1% (n = 143 patients). Noncompliance rates during the first 24 hours in the detached and nondetached groups were 26.9% (n = 7) and 14.4% (n = 20), respectively; after adjustment for possible confounders, the odds ratio (OR) was 1.44 (p = 0.249). Graft dislocation was observed in 13.3% (19 of 143) and 25.9% (7 of 27) of cooperative and noncooperative patients, respectively (p = 0.17). Subanalysis of 120 eyes with either BPK or FED for which it was the first transplantation demonstrated a protective effect of supine positioning (OR 3.42, confidence interval 1.095–10.700; p = 0.034). Findings for both groups remained unchanged in multivariate analysis. Conclusions We found a statistically significant protective effect of 24 hours of postoperative supine positioning against graft detachment after DSAEK in eyes with no prior transplantations.

Palmoplantar keratodermas (PPKs) form a group of disorders characterized by thickening of palm and sole skin. Over the past 2 decades, many types of inherited PPKs have been found to result from abnormal expression, processing, or function of adhesion proteins.We used exome and direct sequencing to detect causative pathogenic variants. Functional analysis of these variants was conducted using reverse transcription quantitative polymerase chain reaction, immunofluorescence confocal microscopy, immunoblotting, a promoter reporter assay, and chromatin immunoprecipitation.We identified 2 heterozygous variants (c.1226AG and c.633_634dupGT) in KLF4 in 3 individuals from 2 different unrelated families affected by a dominant form of PPK. Immunofluorescence staining for a number of functional markers revealed reduced epidermal DSG1 expression in patients harboring heterozygous KLF4 variants. Accordingly, human keratinocytes either transfected with constructs expressing these variants or downregulated for KLF4 displayed reduced DSG1 expression, which in turn has previously been found to be associated with PPK. A chromatin immunoprecipitation assay confirmed direct binding of KLF4 to the DSG1 promoter region. The ability of mutant KLF4 to transactivate the DSG1 promoter was significantly decreased when compared with wild-type KLF4.Loss-of-function variants in KLF4 cause a novel form of dominant PPK and show its importance in the regulation of epidermal differentiation.

Purpose Immigration studies can shed light on myopia development and reveal high-risk populations. To this end, we investigated the association among immigration, age at immigration, and myopia occurrence during adolescence. Design Population-based, retrospective, cross-sectional study. Participants Six hundred seven thousand eight hundred sixty-two adolescents, Israeli born and immigrants, with origins in the former Union of Soviet Socialist Republics (USSR), Ethiopia, or Israel, assessed for medical fitness for mandatory military service at 17 years of age between 1993 and 2016. Methods Myopia and high myopia were defined based on right eye refractive data. Age at immigration was categorized into 0 to 5 years of age, 6 to 11 years of age, and 12 to 19 years of age. Univariate and multivariate logistic regression models were created. Myopia odds ratios (ORs) were calculated according to immigration status, with Israeli-born natives as controls. Next, myopia ORs were calculated according to age at immigration, with Israeli-born of same origin as controls. Main Outcome Measures Myopia prevalence and ORs. Results Myopia was less prevalent among immigrants than Israeli-born controls. When stratified according to age at immigration, a decrease in myopia prevalence and ORs with increasing age at migration were observed, most prominent in immigrants arriving after 11 years of age, who also showed lower high-myopia ORs. The immigrants from the USSR and Ethiopia arriving after 11 years of age showed a myopia OR of 0.65 (95% confidence interval [CI], 0.63–0.67; P Conclusions Immigrants arriving after 11 years of age showed markedly lower ORs for myopia and high myopia relative to Israeli-born controls or those arriving during early childhood, likely because of environmental and lifestyle changes. Differences between immigrants arriving up to 5 years of age and those arriving between 6 and 11 years of age were relatively smaller, suggesting exposures at elementary school age play a greater role in this population.

An effective epidermal barrier requires structural and functional integration of adherens junctions, tight junctions, gap junctions (GJ), and desmosomes. Desmosomes govern epidermal integrity while GJs facilitate small molecule transfer across cell membranes. Some patients with severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome, caused by biallelic desmoglein 1 (DSG1) mutations, exhibit skin lesions reminiscent of erythrokeratodermia variabilis, caused by mutations in connexin (Cx) genes. We, therefore, examined whether SAM syndrome-causing DSG1 mutations interfere with Cx expression and GJ function. Lesional skin biopsies from SAM syndrome patients (n = 7) revealed decreased Dsg1 and Cx43 plasma membrane localization compared with control and nonlesional skin. Cultured keratinocytes and organotypic skin equivalents depleted of Dsg1 exhibited reduced Cx43 expression, rescued upon re-introduction of wild-type Dsg1, but not Dsg1 constructs modeling SAM syndrome-causing mutations. Ectopic Dsg1 expression increased cell-cell dye transfer, which Cx43 silencing inhibited, suggesting that Dsg1 promotes GJ function through Cx43. As GJA1 gene expression was not decreased upon Dsg1 loss, we hypothesized that Cx43 reduction was due to enhanced protein degradation. Supporting this, PKC-dependent Cx43 S368 phosphorylation, which signals Cx43 turnover, increased after Dsg1 depletion, while lysosomal inhibition restored Cx43 levels. These data reveal a role for Dsg1 in regulating epidermal Cx43 turnover.

The retinoid cycle is the enzymatic pathway that regenerates the vision chromophore, 11-cis retinal, after it is bleached during light absorption. Genetic insults to this cycle result in incurable blinding retinal dystrophies such as retinitis pigmentosa and Leber congenital amaurosis. Previous studies demonstrated that oral treatment with 9-cis-β-carotene rich Dunaliella bardawil powder significantly improved visual and retinal function in patients with fundus albipunctatus night blindness and retinitis pigmentosa. Here we examined the effect of oral treatment with the Dunaliella powder on retinal function and structure in RPE65rd12 mice, a model of a genetic defect in the retinoid cycle. Mice were fed with a control diet, vitamin A deficient diet (VAD) or VAD diet supplemented with Dunaliella powder for 13 months. Mice fed with Dunaliella presented significantly higher dark-adapted (35.7 μV ± 3.1 vs. 6.9 μV ± 2.5, p

Background Atopic dermatitis (AD) is a highly prevalent chronic inflammatory skin disease that is known to be, at least in part, genetically determined. Mutations in caspase recruitment domain-containing protein 14 (CARD14) have been shown to result in various forms of psoriasis and related disorders. Objective We aimed to identify rare DNA variants conferring a significant risk for AD through genetic and functional studies in a cohort of patients affected with severe AD. Methods Whole-exome and direct gene sequencing, immunohistochemistry, real-time PCR, ELISA, and functional assays in human keratinocytes were used. Results In a cohort of patients referred with severe AD, DNA sequencing revealed in 4 patients 2 rare heterozygous missense mutations in the gene encoding CARD14, a major regulator of nuclear factor κB (NF-κB). A dual luciferase reporter assay demonstrated that both mutations exert a dominant loss-of-function effect and result in decreased NF-κB signaling. Accordingly, immunohistochemistry staining showed decreased expression of CARD14 in patients' skin, as well as decreased levels of activated p65, a surrogate marker for NF-κB activity. CARD14-deficient or mutant-expressing keratinocytes displayed abnormal secretion of key mediators of innate immunity. Conclusions Although dominant gain-of-function mutations in CARD14 are associated with psoriasis and related diseases, loss-of-function mutations in the same gene are associated with a severe variant of AD.

Since 2009 governments worldwide have been developing Open Government Data (OGD) programs. Our paper examines the ways in which public agencies in the two leading OGD countries, the US and the UK, have released information assets to promote public sector accountability. Theoretically and empirically, we discuss the vision and execution of the OGD policy in these countries since 2009 and demonstrate that the movement took a different path than the one chartered by the original policy makers. We then propose a new path for the OGD movement to better support the democratic ideal of improved accountability of public sector agencies. Keywords: (Open Data; Accountability; Open Government; Transparency; Disclosure) Copyright : Copyright is held by the authors. 1 Introduction The conceptual origins of the open government data (OGD) movement 1 and freedom of information (FOI) legislation are rooted in a desire to improve public accountability. However, the OGD movement blurred the original intent, combining the goal of accountability with concepts such as participation, collaboration, innovation and improvement of public service. The latter may have no significant impact or even contradict accountability (Peled, 2011; Yu & Robinson, 2012). We therefore ask: Do the designs of US and UK OGD policies demonstrate an understanding of how to harness the potential of OGD to improve public sector accountability? If not, what can be done to fulfill OGD’s promise to improve accountability? We propose that open government programs must be evaluated according to three dimensions: informational, explanatory and enforcement. By empirically examining US and UK OGD datasets, we found a divergence between the OGD vision and its execution since 2009 in these two countries. We explain how the OGD movement grew to its current state of ‘release any data now’ disconnected from the accountability goal. We also propose to provide incentives to agencies to release even less datasets but ones that are more closely aligned with the goal of accountability. Critics may propose that ‘improved accountability’ is but one goal competing against other, no less valuable goals (Robinson et. al. 2009). We propose that the goal of ‘improved accountability’ is so demanding that it sets the ‘OGD bar’ very high. To meet this bar, agencies will be forced to publish information that is better linked to other information, better documented, and embedded in richer context. Such information will therefore also contribute to the attainment of additional OGD.

What role does politics play in the emerging Big Data domain? The paper argues that Big Data political power struggles surface at three distinct levels of analysis: the social sciences, the information state, and bureaucratic politics. At the social sciences level of analysis, Big Data threatens to divide social scientists into antagonistic methodological camps as it does not conform to traditional research techniques. At the information state level of analysis, a handful of powerful agencies and corporations created around data generation are consolidating their competitive advantage and are unlikely to support important data access and privacy protections. The one brighter spot for Big Data is found inside governmental bureaucracy. Here, trends such as “governance by numbers” at the sub-national level and mutually profitable data exchanges at the national level suggest that Big Data may propel agencies to share information better. The article concludes with a proposal to view Dr. John Snow and his work to stop the cholera epidemic in central London in 1854 as an early harbinger of the Big Data movement. Snow’s work displays redeeming features that may mitigate less desirable effects of Big Data projects across the three levels of analysis. These features are a sense of purpose, ingenuity, clever data collection design, collaboration, humility and humanity.