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Background: Robotic pancreatectomy is gaining momentum; however, limited data exist on the long-term survival of this approach for pancreatic ductal adenocarcinoma (PDAC). The objective of this study is to compare the long-term oncologic outcomes of robotic pancreaticoduodenectomy (RPD) and robotic distal pancreatectomy (RDP) to open surgery in patients with PDAC., Study Design: Robotic and open pancreatectomy for stages I-III PDAC were obtained from the 2010 to 2016 National Cancer Database., Results: We identified 17 831 pancreaticoduodenectomies and 2718 distal pancreatectomies of which 626 (4%) and 332 (12%) were robotic, respectively. There was no difference in median overall survival between RPD (22.0 months) and open pancreatoduodenectomy (21.8 months; logrank P = .755). The adjusted hazard ratio [HR] was 1.014 (95% confidence interval [CI]: 0.903-1.139). The median overall survival for RDP (35.3 months) was higher than open distal pancreatectomy (ODP) (24.9 months; logrank P = .001). The adjusted HR suggests a benefit to RDP compared to ODP (HR, 0.744; 95% CI: 0.632-0.868) CONCLUSION: In a national cohort of resected pancreatic adenocarcinoma, the robotic platform was associated with similar long-term survival for pancreaticoduodenectomy, but improved survival for distal pancreatectomy., (© 2020 Wiley Periodicals, Inc.)

Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio = 4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P = 0.004) and surgical intervention in advanced disease (P = 3.6 × 10 - 6 ). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.

Introduction: The postpartum period can be a challenging experience for many women as they adjust to the physical and social changes after childbirth. Mindfulness-based interventions have been developed for stress reduction in a variety of health contexts, including pregnancy. These interventions provide strategies that may help new mothers handle the physical, emotional, and relationship challenges of the postpartum period and increase acceptance of postpartum physical changes and body image. Limited research has explored whether women use skills learned in prenatal mindfulness classes for the postpartum experience and parenting. The purpose of this study was to explore women's experience with mindfulness in the year after childbirth., Methods: Twelve women who participated in a Mindfulness for Childbirth and Parenting course during pregnancy were interviewed between 2 and 16 months postpartum. The semistructured interview guide included questions on how participants may have used mindfulness to approach a variety of positive and negative postpartum experiences. Qualitative description methodology guided the research team to code the transcripts independently. The team met to review and achieve consensus in the development of codes, categories, and themes from the data., Results: Four themes were identified in women's postpartum experiences: 1) developing a new relationship with postpartum challenges, 2) formal practices of mindfulness to address postpartum challenges, 3) informal practices to address postpartum challenges, and 4) life-changing and transformative experiences. These themes showed a pathway by which participants used mindfulness skills to address postpartum challenges and to transform these challenges with a positive perspective., Discussion: Mindfulness skills helped class participants cope with physical and emotional challenges postpartum and fostered positive meaningful relationships with partners and newborns. Findings have implications for future research on mindfulness-based interventions and the postpartum experience., (© 2018 by the American College of Nurse-Midwives.)

Background: It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB)., Design: In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations., Results: A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB., Conclusion: An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB., (© 2017 Wiley Periodicals, Inc.)

Purpose: Worldwide, the most frequent cause of visual impairment is uncorrected refractive error. This analysis focused on the distribution and associations of refractive, corneal and ocular residual astigmatism., Methods: As part of the Gutenberg Health study, a population-based cross-sectional study was conducted in the general population of Germany. A comprehensive ophthalmological examination including refraction, tonometry, and Scheimpflug imaging of the anterior cornea (Pachycam) was performed. In addition to the magnitude and type (with-the-rule, against-the-rule, oblique) of the refractive or corneal astigmatism, we calculated the vector components (J 0 , J 45 ) of both astigmatisms and calculated the ocular residual astigmatism. We performed multiple quantile regression analysis to evaluate the factors associated with refractive, corneal and ocular residual astigmatisms., Results: A total of 13,558 subjects (49% female) with a mean age of 54.0 years (range 35-74 years) were included in this study. The prevalence of refractive astigmatism (>1.0D) was 13.0% in right eyes and 12.0% in left eyes, and 85% of these subjects wore spectacles. The distribution of refractive astigmatism showed a two-peak distribution with high astigmatism for with-the-rule and against-the-rule astigmatism. The associated factors were corneal curvature, age and sex for the different astigmatisms (p < 0.001)., Conclusions: We analyzed the prevalence of different astigmatisms within a European population. We confirmed a shift with aging from with-the-rule to against-the-rule astigmatism to refractive and corneal astigmatism. Astigmatism has a large impact on visual perception; more than 85% of people with astigmatism over one diopter wore glasses for distance vision.

Since the advent of anticoagulation and component storage of human blood products, allogeneic red blood cell transfusion has been one of the most common practices in modern medicine. Efforts to reduce the biochemical effects of storage, collectively known as the red blood cell storage lesion, and prolong the storage duration have led to numerous advancements in erythrocyte storage solutions. Cryopreservation and frozen storage of red blood cells in glycerol have been successfully utilised by many civilian and military institutions worldwide. Through progressive improvements in liquid storage of erythrocytes in novel storage solutions, the logistical need for cryopreserved red blood cells in the civilian setting has diminished. A growing body of current literature is focused on the clinical consequences of packed red blood cell age. Modern cryopreservation techniques show promise as a cost-effective method to ameliorate the negative effect of the red blood cell storage lesion, while meeting the technical and logistical needs of both civilian and military medicine. This review outlines the history of red blood cell cryopreservation, the clinical impact of red cell storage, and highlights the current literature on frozen blood and its impact on modern transfusion.

Percutaneous pulmonary valve implantation (PPVI) has become a widely practiced treatment option for patients with right ventricular outflow tract (RVOT) dysfunction. For this procedure, the Melody transcatheter pulmonary valve has become the most widely used system. On-label indications are limited to the treatment of failing circumferential conduits. However, there is growing but still limited experience with the off-label treatment of native or patched RVOTs. Here, the case is reported of a 57-year-old patient in whom redo-surgery for a dysfunctional pulmonary valve could be avoided by PPVI into the patched RVOT at 51 years after tetralogy of Fallot repair.

Background/aims: Major depressive disorder is one of the most common diseases in western countries. The disease is mainly defined by its psychiatric symptoms. However, the disease has also many symptoms outside the central nervous system, in particular cardiovascular symptoms. Recent studies demonstrated that the acid sphingomyelinase/ceramide system plays an important role in the development of major depressive disorder and functions as a target of antidepressants., Methods: Here, we investigated (i) whether ceramide accumulates in endothelial cells in the neurogenetic zone of the hippocampus after glucocorticosterone-mediated stress, (ii) whether ceramide is released into the extracellular space of the hippocampus and (iii) whether extracellular ceramide inhibits neuronal proliferation. Ceramide was determined in endothelial cell culture supernatants or extracellular hippocampus extracts by a kinase assay. Endothelial ceramide in the hippocampus was analyzed by confocal microscopy of brain sections stained with Cy3-labelled anti-ceramide antibodies and FITC-Isolectin B4. Neuronal proliferation was measured by incubation of pheochromocytoma neuronal cells with culture supernatants and extracellular hippocampus extracts., Results: Treatment of cultured endothelial cells with glucocorticosterone induces a release of ceramide into the supernatant. Likewise, treatment of mice with glucocorticosterone triggers a release of ceramide into the extracellular space of the hippocampus. The release of ceramide is inhibited by concomitant treatment with the antidepressant amitriptyline, which also inhibits the activity of the acid sphingomyelinase. Studies employing confocal microscopy revealed that ceramide is formed and accumulates exclusively in endothelial cells in the hippocampus of stressed mice, a process that was again prevented by co-application of amitriptyline. Ceramide released in the culture supernatant or into the extracellular space of the hippocampus reduced proliferation of neurons in vitro., Conclusion: The data suggest a novel model for the pathogenesis of major depressive disorder, i.e. the release of ceramide-enriched microvesicles from endothelial cells that negatively affect neuronal proliferation in the hippocampus, but may also induce cardiovascular disease and other systemic symptoms of patients with major depressive disorder., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background/aims: Major depressive disorder is a severe, common and often chronic disease with a significant mortality due to suicide. The pathogenesis of major depression is still unknown. It is assumed that a reduction of neurogenesis in the hippocampus plays an important role in the development of major depressive disorder. However, the mechanisms that control proliferation of neuronal stem cells in the hippocampus require definition. Here, we investigated the role of Janus-Kinase 3 (Jak-3) for stress-induced inhibition of neurogenesis and the induction of major depression symptoms in mice., Methods: Stress was induced by the application of glucocorticosterone. Brain sections were stained with phospho-specific antibodies and analysed by confocal microscopy to measure phosphorylation of Jak-3 specifically in the hippocampus. Jak-3 inhibitors and the antidepressant amitriptyline were applied to counteract stress. The effects of the inhibitors were determined by a set of behavioural tests and analysis of Jak-3 phosphorylation in brain sections. Acid sphingomyelinase-deficient mice were employed to test whether Jak3 is downstream of ceramide., Results: The data show that stress reduces neurogenesis, which is restored by simultaneous application of Jak-3 inhibitors. Inhibition of neurogenesis correlated with an anxious-depressive behaviour that was also normalized upon application of a Jak-3-inhibitor. Confocal microscopy data revealed that stress triggers a phosphorylation and thereby activation of Jak-3 in the hippocampus. Amitriptyline, a commonly used antidepressant that blocks the acid sphingomyelinase, or acid sphingomyelinase-deficiency reduced stress-induced phosphorylation of Jak-3., Conclusion: Our data show that Jak-3 is activated by stress at least partially via the acid sphingomyelinase and is involved in the mediation of stress-induced major depression., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Background: Melatonin has been shown to have antidepressive effects. We tested whether melatonin inhibits the acid sphingomyelinase/ceramide system and mediates its antidepressive effects via inhibition of the acid sphingomyelinase and a reduction of ceramide in the hippocampus. Antidepressants such as amitriptyline and fluoxetine were previously shown to inhibit the acid sphingomyelinase/ceramide system, which mediates neurogenesis and behavioral changes induced by these drugs., Methods: The effect of melatonin on the activity of the acid sphingomyelinase prior to and after treatment with melatonin was determined in cultured neurons and in vivo in the hippocampus of mice by measuring the consumption of [14C] sphingomyelin. Ceramide was measured by DAG kinase assay and fluorescence microscopy of the hippocampus and of cultured neurons. Neurogenesis in the hippocampus was analyzed by in vivo labeling with bromodeoxyuridine. Behavior was assessed in standardized tests., Results: Melatonin treatment inhibited acid sphingomyelinase in vitro in cultured pheochromocytoma cells and in vivo in the hippocampus, which resulted in a reduction of ceramide in vitro and in vivo. The inhibition of the acid sphingomyelinase/ceramide system translated into increased neurogenesis in glucocorticosterone-stressed mice after treatment with melatonin, an effect that is abrogated in acid sphingomyelinase-deficient mice. Likewise, melatonin improved the depressive behavior of stressed mice, a therapeutic effect that was again absent in acid sphingomyelinase-deficient animals., Conclusion: These data indicate that the antidepressive effects of melatonin as well as the induction of neurogenesis triggered by this drug are mediated by an inhibition of the acid sphingomyelinase/ceramide system. This is the first study to identify melatonin as an inhibitor of the acid sphingomyelinase., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Objective: Diabetic retinopathy (DR) is the leading cause of blindness in people of working age. The purpose of this paper is to report the prevalence and cardiovascular associations of diabetic retinopathy and maculopathy (DMac) in Germany., Research Design and Methods: The Gutenberg Health Study (GHS) is a population-based study with 15,010 participants aged between 35 at 74 years from the city of Mainz and the district of Mainz-Bingen. We determined the weighted prevalence of DR and DMac by assessing fundus photographs of persons with diabetes from the GHS data base. Diabetes was defined as HbA1c ≥ 6.5%, known diagnosis diabetes mellitus or known diabetes medication. Furthermore, we analysed the association between DR and cardiovascular risk factors and diseases., Results: Overall, 7.5% (1,124/15,010) of the GHS cohort had diabetes. Of these, 27.7% were unaware of their disease and thus were newly diagnosed by their participation in the GHS. The prevalence of DR and DMac was 21.7% and 2.3%, respectively among patients with diabetes. Vision-threatening disease was present in 5% of the diabetic cohort. In the multivariable analysis DR (all types) was associated with age (Odds Ratio [95% confidence interval]: 0.97 [0.955-0.992]; p = 0.006) arterial hypertension (1.90 [1.190-3.044]; p = 0.0072) and vision-threatening DR with obesity (3.29 [1.504-7.206]; p = 0.0029). DR (all stages) and vision-threatening DR were associated with duration of diabetes (1.09 [1.068-1.114]; p<0.0001 and 1.18 [1.137-1.222]; p<0.0001, respectively)., Conclusions: Our calculations suggest that approximately 142 000 persons aged between 35 and 74 years have vision threatening diabetic retinal disease in Germany [corrected].Prevalence of DR was lower in the GHS compared to East-Asian studies. Associations were found with age, arterial hypertension, obesity, and duration of diabetes mellitus.

Purpose: To analyze the association between myopia and educational level in an adult European cohort., Design: Population-based cross-sectional study., Participants: A cohort of the Gutenberg Health Study, including 4658 eligible enrollees between 35 and 74 years of age., Methods: We applied a standardized protocol entailing a comprehensive questionnaire; thorough ophthalmic, general, cardiovascular, and psychological examinations; and laboratory tests, including genetic analyses. We documented achievement levels in school education and post-school professional education. The spherical equivalent (SE) was determined by noncycloplegic autorefractometry. We fitted mixed linear models including age, gender, and 45 myopia-associated single nucleotide polymorphisms (SNP) as covariates., Main Outcome Measures: Prevalence and magnitude of myopia in association with years spent in school and level of post-school professional education., Results: Individuals who graduated from school after 13 years were more myopic (median, -0.5 diopters [D]; first quartile [Q1]/third quartile [Q3], -2.1/0.3 D) than those who graduated after 10 years (median, -0.2 D; Q1/Q3, -1.3/0.8 D), than those who graduated after 9 years (median, 0.3 D; Q1/Q3, -0.6/1.4 D), and than those who never finished secondary school (median, 0.2 D; Q1/Q3, -0.5/1.8 D; P<0.001, respectively). The same holds true for persons with a university degree (median, -0.6 D; Q1/Q3, -2.3/0.3 D) versus those who finished secondary vocational school (median, 0 D; Q1/Q3, -1.1/0.8 D) or primary vocational school (median, 0 D; Q1/Q3, -0.9/1.1 D) versus persons without any post-school professional qualification (median, 0.6 D; Q1/Q3, -0.4/1.7 D; P<0.001, respectively). Of persons who graduated from school after 13 years, 50.9% were myopic (SE, ≤-0.5 D) versus 41.6%, 27.1%, and 26.9% after 10 years, in those who graduated after 9 years, and in those who never graduated from secondary school, respectively (P<0.001). In university graduates, the proportion of myopic persons was higher (53%) than that of those who graduated from secondary (34.8%) or primary (34.7%) vocational schools and than in those without any professional training (23.9%; P<0.001, respectively). In multivariate analyses: higher school and professional levels of education were associated with a more myopic SE independent of gender. There was a small effect of age and SNPs., Conclusions: Higher levels of school and post-school professional education are associated with a more myopic refraction. Participants with higher educational achievements more often were myopic than individuals with less education., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to describe the sex- and age-specific prevalence of age-related macular degeneration (AMD) and its correlation with urban or rural residence in a large and relatively young European cohort., Methods: We evaluated fundus photographs from participants in the Gutenberg Health Study (GHS), a population-based, prospective, observational, single-centre study in the Rhineland-Palatine region in midwestern Germany. The participants were 35-74 years of age at enrolment. The fundus images were classified as described in the Rotterdam Study and were graded independently by two experienced ophthalmologists (CK and UBK) based on the presence of hard and soft drusen, retinal pigmentary abnormalities, and signs of atrophic or neovascular age-related macular generation (AMD)., Results: Photographs from 4,340 participants were available for grading. Small, hard drusen (<63 μm, stages 0b and 0c) were present in 37.4% of participants (95% confidence interval [CI], stage 0b, 31.6% [30.3-33.7]; stage 0c, 5.8% [5.1-6.5]). Early AMD (soft drusen, pigmentary abnormalities, stages 1-3) was present in 3.8% of individuals in the youngest age group (35-44 years) (95% CI, stage 1a, 0.4% [0.3-0.5%]; stage 1b, 3.2% [2.9-3.5%]; stage 2a, 0.1% [0.1-0.2%]; stage 2b, 0% [0-0.0%]; stage 3, 0.1% [0.1-0.2%]), whereas late AMD (stages 4a and 4b) did not appear in the youngest age group. In all age groups, signs of early AMD were detected in 11.9% of individuals (stage 1a, 2.1% [1.7-2.6]; stage 1b, 8.0% [7.2-8.8]; stage 2a, 1.0% [0.7-1.3]; stage 2b, 0.5% [0.3-0.7]; stage 3, 0.3% [0.2-0.6]). Late AMD (geographic atrophy or neovascular AMD) was found in 0.2% of individuals (stage 4a, 0.1 % [0.0-0.2]; stage 4b, 0.1% [0.0-0.2]). AMD increased significantly with age (odds ratio [OR], 1.09; 95% CI, 1.08-1.10). Sex, iris colour, and residence (rural vs. urban) were not associated with different rates of AMD., Conclusions: In this study, the prevalence of AMD increased dramatically with age; however, although AMD is usually thought to occur after age 50, signs of early AMD were found in 3.8% of individuals in the youngest age group (younger than 45 years). This population-based sample is the first to provide substantial epidemiologic data from a large German cohort, including data on macular degeneration in younger age groups and incidence data after recall.

Purpose: The aim of this study was to evaluate the correlations between general anthropometric features and cardiovascular parameters and central corneal thickness (CCT) in an adult European cohort., Methods: Analysis was based on a Gutenberg Health Study cohort that included 5000 subjects (2540 male, 2460 female), aged 35 to 74 years at enrollment. The participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination (slit-lamp biomicroscopy; autorefractometry; noncontact tonometry; fundus photography; CCT measurements (optical pachymetry); visual field testing; and a thorough general examination focused on cardiovascular parameters, psychosomatic evaluation, and laboratory tests including genetic analysis., Results: Reliable CCT measurements were available for 4708 right eyes (OD, 94.2%), 4721 left eyes (OS, 94.4%), and both eyes (OU) in 4698 subjects (94.0%). The mean CCT was 555 ± 35 μm in men and 549 ± 35 μm in women. In multiple linear regression analysis, the CCT was associated with gender [P < 0.001 for OU], body height [in men, P = 0.007 for OD, P = 0.04 for OS; in women P < 0.001 for OU], and body mass index (P < 0.001 for OD, P = 0.001 for OS). In men only, the CCT correlated with the body weight [P = 0.024 (OD), P = 0.048 (OS)] and smoking [P = 0.006 (OD), P < 0.001 (OS)]. No correlations were found between the CCT and dyslipidemia, diabetes, or hypertension., Conclusions: The CCT was associated with male gender, body height, and body mass index in an adult white cohort. It correlated with body weight and nicotine abuse in men only. No associations were found between the CCT and dyslipidemia, diabetes, or hypertension.

Main Objective: To evaluate the distribution of central corneal thickness (CCT) in a large German cohort and to analyse its relationship with intraocular pressure and further ocular factors., Design: Population-based, prospective, cohort study., Methods: The Gutenberg Health Study (GHS) cohort included 4,698 eligible enrollees of 5,000 subjects (age range 35-74 years) who participated in the survey from 2007 to 2008. All participants underwent an ophthalmological examination including slitlamp biomicroscopy, intraocular pressure measurement, central corneal thickness measurement, fundus examination, and were given a questionnaire regarding glaucoma history. Furthermore, all subjects underwent fundus photography and visual field testing using frequency doubling perimetry., Results: Mean CCT was 557.3 ± 34.3 µm (male) and 551.6±35.2 µm in female subjects (Mean CCT from right and left eyes). Younger male participants (35-44 years) presented slightly thicker CCT than those older. We noted a significant CCT difference of 4 µm between right and left eyes, but a high correlation between eyes (Wilcoxon test for related samples: p<0.0001). Univariable linear regression stratified by gender showed that IOP was correlated with CCT (p<0.0001). A 10 µm increase in CCT led to an increase in IOP between 0.35-0.38 mm Hg, depending on the eye and gender. Multivariable linear regression analysis revealed correlations between gender, spherical equivalent (right eyes), and CCT (p<.0001 and p=0.03, respectively)., Conclusions: We observed positive correlations between CCT and IOP and gender. CCT was not correlated with age, contact lens wear, positive family history for glaucoma, lens status, or iris colour.

Urban particulate air pollution is a serious health issue. Trees within cities can remove fine particles from the atmosphere and consequently improve air quality and human health. Tree effects on PM2.5 concentrations and human health are modeled for 10 U.S. cities. The total amount of PM2.5 removed annually by trees varied from 4.7 tonnes in Syracuse to 64.5 tonnes in Atlanta, with annual values varying from $1.1 million in Syracuse to $60.1 million in New York City. Most of these values were from the effects of reducing human mortality. Mortality reductions were typically around 1 person yr(-1) per city, but were as high as 7.6 people yr(-1) in New York City. Average annual percent air quality improvement ranged between 0.05% in San Francisco and 0.24% in Atlanta. Understanding the impact of urban trees on air quality can lead to improved urban forest management strategies to sustain human health in cities., (Published by Elsevier Ltd.)

Purpose: To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort., Design: Population-based, cross-sectional study., Participants: This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment., Methods: Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visual field testing; and a thorough general examination focused on cardiovascular parameters, psychological evaluation, and laboratory tests, including genetic analysis., Main Outcome Measures: Mean and reference interval of IOP stratified by age, gender, and eye., Results: Mean ± standard deviation (SD) IOP was 14.0 ± 2.6 mmHg in both eyes, 13.9 ± 2.7 mmHg in right eyes, and 14.0 ± 2.7 mmHg in left eyes. Mean ± SD IOP in men (n = 2216) and in women (n = 2119) was 14.1 ± 2.7 mmHg and 13.9 ± 2.5 mmHg with an intersex difference (P = 0.009). Positive univariate associations with higher IOP were detected for brown iris color, central corneal thickness, hypertension, diabetes, smoking, obesity, dyslipidemia, body mass index, weight, hip size (women only), waist circumference, and waist-to-hip ratio. Multivariate testing revealed male gender, central corneal thickness, brown iris color, hypertension, smoking, and waist-to-hip ratio to be correlated with higher IOP. In women, age correlated negatively with IOP in the multivariate analysis., Conclusions: Intraocular pressure distribution in this cohort yielded a lower mean IOP than in similar white study populations. Increasing age in women correlated with lower IOP. Association analyses with several systemic characteristics revealed that cardiovascular risk factors correlated with higher IOP., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Central corneal thickness (CCT) has become an endophenotype of major interest for the genetically complex disorder glaucoma. CCT has a high heritability, and thin CCT is an independent risk factor for the diagnosis and progression of open-angle glaucoma. Genome-wide association studies thus provide genetic loci associated with CCT and potentially related to open-angle glaucoma. The distribution of CCT and prevalence of glaucoma in population-based studies have demonstrated ethnic differences suggesting ethnic-dependent variations in the genetic determinants of CCT. We conducted a genome-wide association study in Caucasians (n = 3,931) from the Gutenberg Health Study (Germany) followed by replication of 30 genome-wide significant SNPs or SNPs of interest (P < 10(-5)) in the Rotterdam Study (The Netherlands, n = 1,418). In a combined analysis, we confirmed quantitative trait loci on chromosomes 9q34 and 16q24 for association with CCT. On chromosome 16q24, the locus is located in an intergenic region near the ZNF469 gene (top SNP: rs9938149, P = 1.45 × 10(-12)). ZNF469 missense mutation is involved in a syndrome with very thin cornea (brittle cornea syndrome). The second locus on chromosome 9q34 represents the intergenic region between the RXRA and COL5A1 gene (top SNP: rs3132306, P = 2.71 × 10(-10)). Collagen type 5 determines the diameter of the corneal collagen fibrils. In our Caucasian population-based GWA study, we reinforce the involvement of collagen-related genes influencing CCT in Caucasians. We could not confirm the collagen type 8 locus on chromosome 1 as reported in Asian studies.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to have a role in the pathogenesis of inflammatory, edematous, neovascular and neurodegenerative disorders. Several TNF-blocking drugs have been developed and approved, and are in clinical use for inflammatory diseases such as rheumatoid arthritis, psoriasis and ankylosing spondylitis. TNF-α blockers are widely used in ophthalmology as an off-label alternative to "traditional" immunosuppressive and immune-modulatory treatments in noninfectious uveitis. Preliminary studies suggest a positive effect of intravenously administered TNF-α blockers, mainly infliximab, for treating refractory diabetic macular edema and neovascular age-related macular degeneration. Unfortunately, much of the current data raises considerable safety concerns for intravitreal use of TNF-α inhibitors, in particular, intraocular inflammatory responses have been reported after intravitreal injection of infliximab. Results of dose-finding studies and humanized antibody or antibody fragments (e.g. adalimumab) are anticipated in the coming years; these will shed light on potential benefits and risks of local and systemic TNF-α blockers used for treatment of diseases of the retina and choroid.

Recently, corrodible magnesium-based alloys have been introduced for use as cardiovascular stents and orthopedic implants. However, rapid corrosion rates have raised questions about their biocompatibility. Therefore, we developed a binary fluoride-coated magnesium-calcium alloy with improved degradation kinetics. Biocompatibility of the alloys was evaluated with metabolic assays (colorimetric WST-1 test). Furthermore, five different probes of magnesium-calcium alloys (MgCa 0.4, 0.6, 0.8, 1.2, and 2.0 wt %) were cocultivated with human smooth muscle cells and endothelial cells. To investigate the decomposition kinetics in a physiological environment the alloys were used untreated and fluoride coated (MgF(2)). Mg and Ca decreased the metabolic activity in vascular cells dose-dependently, with cytotoxic effects only at unphysiological concentrations. Uncoated magnesium alloys showed signs of decomposition after a short incubation time of 24 h in contrast to MgF(2) coated alloys. After 10 days smooth muscle and endothelial cells around the alloys were still alive, whereas colonization of the surfaces was only observed for smooth muscle cells. The fluoride-coated MgCa alloys exhibited good results concerning mechanical properties, degradation kinetics, and biocompatibility in vitro. We conclude that a binary fluoride magnesium-calcium alloy is a promising candidate for the production of cardiovascular stents., (Copyright 2009 Wiley Periodicals, Inc.)

Iron is the major alloy component for a large variety of cardiovascular devices such as stents. In recent studies it has been shown that biodegradable iron or iron based stents exhibit good mechanical features with no pronounced neointimal proliferation. Whole genome gene profiling using DNA chip technology revealed that genes involved in cholesterol and fatty acid metabolism (low-density lipoprotein receptor, LDL-R; 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 (HMGCS1) and fatty acid desaturase 1 (FADS1) are up-regulated after exposure of vascular smooth muscle cells with soluble ferrous iron. To analyze the effects of iron on these genes in detail we co-incubated human vascular smooth muscle cells for 12 and 24 h with different concentrations of ferrous (soluble iron(II)-gluconate) and ferric iron (soluble iron(III)-chloride), Ferrlecit, a commercially available drug (ferric iron-gluconate complex) and solid iron coils. The expression of LDL-R, HMGCS1 and FADS1 was analyzed using TaqMan Real-time PCR. After 24 h, all forms of iron led to a significant up-regulation of the examined genes. At high concentrations the expression rates declined, probably as a result of reduced metabolic activity. The most prominent effects were observed after co-incubation with Ferrlecit, probably caused by an increased bioavailability of the iron gluconate complex. We postulate that both, bi- and trivalent forms of iron induce the expression of LDL-R, HMGCS1 and FADS1 by generation of highly reactive oxygen species. Further animal experiments using tissues from iron-stented vessels may lead to a more profound insight into iron induced expression of cholesterol- and fatty acid metabolism related genes.

Background: Interventional closure of atrial septal defects (ASD) and surgical tunnel fenestrations in Fontan patients has become the procedure of choice for many years. Recently, the BioSTAR Occluder, a modification of the Starflex device with a resorbable matrix has become available., Patients: Ten Biostar devices were implanted in nine children with interatrial septal defects, one within a fontan baffle, eight with secundum atrial septal defects. The age of the patients ranged from 11 months to 17 years, the body weight ranged from 12.9-78 kg., Results: 10 BioSTAR devices were implanted in nine patients. In one patient, two BioSTAR devices were used to occlude multiple defects within the oval fossa. All defects were successfully and uneventfully occluded. Mean procedure time was 56 (range 28-125). Mean fluoroscopy time was 4.8 (range 1.1 to 13.0) min. None of the nine patients showed residual shunts after device implantation. After 30 days no shunt was seen in the control transthoracic echocardiography. No adverse effects like allergic reactions, tachyarrhythmia or thrombembolic events occurred in any of the patients., Conclusion: The BioSTAR closure device is a safe and effective device for the closure of a variety of interatrial shunts in children including multifenestrated interatrial defects and fontan fenestrations, however, possible long term consequences (e.g., fractures, recurrent shunts after scaffold degradation) remain to be studied., (Copyright 2009 Wiley-Liss, Inc.)

The detailed molecular processes associated with postnatal remodelling of blood vessels are presently not understood. To characterize the response of the patients undergoing stenting of the patent arterial duct, we harvested samples of vascular tissue during surgical repair. Histological analysis of explanted ducts confirmed the patency of the ducts immediately after birth. As expected, a previously unstented duct that was examined 7 months after birth had become closed and ligamentous. Whole genome expression profiling of these samples showed that a large fraction, over 10%, of the gene sequences examined were expressed differentially between the samples taken from patients with open as opposed to the ligamentous duct. Interestingly, in 2 patients in whom closure was prevented by insertion of stents, one showed an expression profile that was similar to that of the patient initially having an unstented open duct, whereas the other was more closely related to the profile of the patient with a duct that had become ligamentous. Moreover, in 2 specimens obtained from patients with stented pulmonary arteries, a large fraction of the genes that were differentially expressed were identical to the pattern seen in the samples from the patients with open ducts. The gene regulation appeared to be independent of the nature of the respective malformations, and the site of implantation of the stents. These findings suggest that a set of differentially expressed genes are indicative for a transcriptional programme in neonatal remodelling of the arterial duct, which may also take place in patients in whom ductal closure is prevented by stents, or in those with stented pulmonary arteries. The differentially expressed genes included a significant number of extracellular matrix synthetic genes, and could therefore be predictive for vascular remodelling and neointimal formation.

The aim of this study was to determine the additional important information obtained on prebypass epicardial 3-dimensional imaging (E-3D) compared with transesophageal 2-dimensional echocardiography (TEE-2D) in young patients who undergoing aortic valve repair. From January 2004 to May 2007, all patients who underwent reconstructive surgery of the native aortic valve and intraoperative TEE-2D and E-3D were retrospectively reviewed. Thirteen structural anatomic variables of the aortic valve for TEE-2D and E-3D were evaluated, scored, and compared (by a blinded observer) with intraoperative surgical findings. Nineteen patients underwent valve repair. The median age at surgery was 10 years (range 1 day to 24 years). The primary aortic valve disease was regurgitation (n = 19), and 2 patients had additional valvar stenosis. TEE-2D and E-3D were able to detect 82% (n = 204) and 91% (n = 225), respectively, of the intraoperative findings (n = 247) (p = 0.006). Individual evaluation scores were higher for E-3D (median 12, interquartile range 11 to 13) than for TEE-2D (median 11, interquartile range 10 to 12) (p = 0.01) compared with surgical findings (score 13). Differences in detection sensitivity occurred for commissural fusion (n = 7), leaflet perforation or deficiency (n = 5), and leaflet prolapse (n = 2). TEE-2D was more likely to have false-negative findings than E-3D (36 vs 16 findings, p = 0.001). In conclusion, intraoperative E-3D provides additional important information over TEE-2D for aortic valve repair in young patients. Such 3-dimensional echocardiographic imaging has become an important intraoperative modality for valve repair at the investigators' institution.

The present case report assesses the individual performance-related workload in three male children with left ventricular outflow tract (LVOT) obstruction during alpine skiing. Spirometric data (VO(2)) and heart rate (HR) were monitored during alpine skiing in various terrains according to the subject's performance level. A portable spirometric device was used for on-slope data sampling. Relative workload was calculated in relation to peak cardiorespiratory values, obtained during an incremental laboratory cycle test. On the slope the subjects reached 78% to 103% of their peak ergometric HR and a VO(2peak) of 65% to 100%. Young beginners and intermediates with LVOT obstruction seem to face a high cardiorespiratory stress during alpine skiing. For the beginner, an additional load is seen during uphill sidestepping with skis. In children suffering from congenital heart disease, physiological aspects of sports activities such as skiing should not be viewed separately from the possibilities of sports participation and social interactions.

We present a patient who had benign symmetrical lipomatosis. He was treated surgically (6 operations), and the results were satisfactory. we discuss various factors in this disease and suggest the possibility of a nonsurgical treatment being developed in the future.

A patient who had facial lacerations and then developed Kaposi's varicelliform eruption is reported. Presently, there is no specific therapy for this disease.

This paper discusses the rationale leading to the purchase of a medium resolution computergraphics system and modification of existing computer software for the production of scientific publication graphs and presentation color slides. Capabilities of the system and components are reported.

A case is presented in which intraoperative visual evoked response (VER) monitoring was employed during correction of orbital hypertelorism. This procedure is noninvasive and does not interfere with the execution of the operation. The operative time is prolonged only a few minutes to record the VER. This technique is a simple and safe method for detecting intraoperative damage to the optic nerve and chiasm, and may prove useful in avoiding damage to these critical structures during craniofacial surgical procedures.

An unusual and severe injury to the soft tissues of the shoulder with exposure of the humeral head and glenohumeral joint is presented. The principles of muscle transposition were applied to rotation of the deltoid muscle in achievement of wound closure. Healing was rapid and satisfactory, and a useful upper extremity was salvaged.