Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.

EFEMP1 R345W is a dominant mutation causing Doyne honeycomb retinal dystrophy/malattia leventinese (DHRD/ML), a rare blinding disease with clinical pathology similar to age-related macular degeneration (AMD). Aged Efemp1  R345W/R345W knock-in mice (Efemp1ki/ki) develop microscopic deposits on the basal side of retinal pigment epithelial cells (RPE), an early feature in DHRD/ML and AMD. Here, we assessed the role of alternative complement pathway component factor B (FB) in the formation of these deposits. RNA-seq analysis of the posterior eyecups revealed increased unfolded protein response, decreased mitochondrial function in the neural retina (by 3 months of age) and increased inflammatory pathways in both neural retina and posterior eyecups (at 17 months of age) of Efemp1ki/ki mice compared with wild-type littermate controls. Proteomics analysis of eye lysates confirmed similar dysregulated pathways as detected by RNA-seq. Complement activation was increased in aged Efemp1ki/ki eyes with an approximately 2-fold elevation of complement breakdown products iC3b and Ba (P < 0.05). Deletion of the Cfb gene in female Efemp1ki/ki mice partially normalized the above dysregulated biological pathway changes and oral dosing of a small molecule FB inhibitor from 10 to 12 months of age reduced sub-RPE deposits by 65% (P = 0.029). In contrast, male Efemp1ki/ki mice had fewer sub-RPE deposits than age-matched females, no elevation of ocular complement activation and no effect of FB inhibition on sub-RPE deposits. The effects of FB deletion or inhibition on Efemp1ki/ki mice supports systemic inhibition of the alternative complement pathway as a potential treatment of dry AMD and DHRD/ML.

Screening Medications for Association with Progression to Wet Age-Related Macular Degeneration.

PURPOSE: There is an urgent need for treatments that prevent or delay development to advanced age-related macular degeneration (AMD). Drugs already on the market for other conditions could affect progression to neovascular AMD (nAMD). If identified, these drugs could provide insights for drug development targets. The objective of this study was to use a novel data mining method that can simultaneously evaluate thousands of correlated hypotheses, while adjusting for multiple testing, to screen for associations between drugs and delayed progression to nAMD. DESIGN: We applied a nested case-control study to administrative insurance claims data to identify cases with nAMD and risk-set sampled controls that were 1:4 variable ratio matched on age, gender, and recent healthcare use. PARTICIPANTS: The study population included cases with nAMD and risk set matched controls. METHODS: We used a tree-based scanning method to evaluate associations between hierarchical classifications of drugs that patients were exposed to within 6 months, 7 to 24 months, or ever before their index date. The index date was the date of first nAMD diagnosis in cases. Risk-set sampled controls were assigned the same index date as the case to which they were matched. The study was implemented using Medicare data from New Jersey and Pennsylvania, and national data from IBM MarketScan Research Database. We set an a priori threshold for statistical alerting at P ≤ 0.01 and focused on associations with large magnitude (relative risks ≥ 2.0). MAIN OUTCOME MEASURES: Progression to nAMD. RESULTS: Of approximately 4000 generic drugs and drug classes evaluated, the method detected 19 distinct drug exposures with statistically significant, large relative risks indicating that cases were less frequently exposed than controls. These included (1) drugs with prior evidence for a causal relationship (e.g., megestrol); (2) drugs without prior evidence for a causal relationship, but potentially worth further exploration (e.g., donepezil, epoetin alfa); (3) drugs with alternative biologic explanations for the association (e.g., sevelamer); and (4) drugs that may have resulted in statistical alerts due to their correlation with drugs that alerted for other reasons. CONCLUSIONS: This exploratory drug-screening study identified several potential targets for follow-up studies to further evaluate and determine if they may prevent or delay progression to advanced AMD.

CULTURE OF OPPRESSION IN AFRICAN-AMERICANS WITH HEART FAILURE.

African-Americans are disproportionately affected and have a greater incidence of heart failure compared to other populations. Current literature identifies many contributory factors, among which is the role of culture. Culture, defined to include socioeconomic status and the historical and sociological experience of African-Americans, may play a pivotal role in how clients manage their symptoms of heart failure. This study attempts to explain how culture contributes to the lack of successful management of heart failure among African-Americans using the framework of Hofstede's cultural dimensions of power distance and individualism.

Fulbrighter's journey.

This article provides a synopsis of a Fulbright scholar's journey to Jordan, filled with challenges, opportunities, and life-changing experiences. The author received a Fulbright lecturing award for 2011-2012 for the Jordan University of Science and Technology School of Nursing. This manuscript discusses the experience of teaching graduate students in nursing in the Middle East, collaborating with Muslim professors on research projects, and organizing a fundraiser that provided financial support for refugees and disadvantaged students at the university.

Differential Proteins Expression Distinguished Between Patients With Infectious and Noninfectious Uveitis.

PURPOSE: We investigated the aqueous humor proteome and associated plasma proteome in patients with infectious or noninfectious uveitis. METHODS: AH and plasma were obtained from 28 patients with infectious uveitis (IU), 29 patients with noninfectious uveitis (NIU) and 35 healthy controls undergoing cataract surgery. The proteins profile was analyzed by SomaScan technology. RESULTS: We found 1844 and 2484 proteins up-regulated and 124 and 161 proteins down-regulated in the AH from IU and NIU groups, respectively. In the plasma, three proteins were up-regulated in NIU patients, and one and five proteins were down-regulated in the IU and NIU patients, respectively. The results of pathway enrichment analysis for both IU and NIU groups were related mostly to inflammatory and regulatory processes. CONCLUSION: SomaScan was able to detect novel AH and plasma protein biomarkers in IU and NIU patients. Also, the unique proteins found in both AH and plasma suggest a protein signature that could distinguish between infectious and noninfectious uveitis.

Zinc transport from the endoplasmic reticulum to the cytoplasm via Zip7 is necessary for barrier dysfunction mediated by inflammatory signaling in RPE cells.

Inflammatory signaling induces barrier dysfunction in retinal-pigmented epithelium (RPE) cells and plays a role in the pathology of age-related macular degeneration (AMD). We studied the role of Zn flux from the endoplasmic reticulum (ER) to the cytoplasm via Zip7 during inflammatory signaling in RPE cells. In ARPE-19 cells, Zip7 inhibition reduced impedance loss, FITC-dextran permeability and cytokine induction caused by challenge with IL-1ß/TNF-α. Zip7 inhibition in iPS-derived RPE cells challenged with TNF- α reduced barrier loss in TER assays. In ARPE-19 cells, a Zn ionophore restored cytokine induction and barrier loss in cells challenged with IL-1 ß /TNF- α despite Zip7 inhibition. A cell permeable Zn chelator demonstrated that Zn is essential for IL-1 ß /TNF- α signaling. ER stress caused by Zip7 inhibition in ARPE-19 cells was found to partially contribute to reducing barrier dysfunction caused by IL-1 ß /TNF- α. Overall, it was shown that Zn flux through Zip7 from the ER to the cytoplasm plays a critical role in driving barrier dysfunction caused by inflammatory cytokines in RPE cells.

Sugar-Sweetened Beverages Contribute Significantly to College Students' Daily Caloric Intake in Jordan: Soft Drinks Are Not the Major Contributor.

Sugar sweetened beverages (SSBs) are caloric-dense and associated with poor diet quality which may result in weight gain and obesity. Obesity is an independent risk factor for several chronic diseases. This study aimed to (1) assess the consumption level of SSBs among college students in Jordan and (2) examine the relationship of consumption level to body weight. The current study is a cross-sectional study conducted on 967 college students (55.3% males and 44.7% females). Consumption of SSBs was assessed using validated questionnaires. SSBs were classified into four major categories (hot drinks, fruit drinks, energy drinks, and soft drinks). Anthropometric measurements of the participants including body weight, height, and waist circumferences were recorded. Male students consumed more calories from SSBs compared to female students (p = 0.016). The mean contribution of SSBs to daily energy intake among college students was 480 kcal with the highest contribution from sugar sweetened hot drinks and fruit drinks. A significant positive relationship was found in BMI (p = 0.006) and waist circumference (p = 0.030) for participants consuming calories from SSBs. In conclusion, beverages with added sugar contribute substantially to the daily energy intake of college students in Jordan.

ADIPOR1 is essential for vision and its RPE expression is lost in the Mfrprd6 mouse.

The knockout (KO) of the adiponectin receptor 1 (AdipoR1) gene causes retinal degeneration. Here we report that ADIPOR1 protein is primarily found in the eye and brain with little expression in other tissues. Further analysis of AdipoR1 KO mice revealed that these animals exhibit early visual system abnormalities and are depleted of RHODOPSIN prior to pronounced photoreceptor death. A KO of AdipoR1 post-development either in photoreceptors or the retinal pigment epithelium (RPE) resulted in decreased expression of retinal proteins, establishing a role for ADIPOR1 in supporting vision in adulthood. Subsequent analysis of the Mfrprd6 mouse retina demonstrated that these mice are lacking ADIPOR1 in their RPE layer alone, suggesting that loss of ADIPOR1 drives retinal degeneration in this model. Moreover, we found elevated levels of IRBP in both the AdipoR1 KO and the Mfrprd6 models. The spatial distribution of IRBP was also abnormal. This dysregulation of IRBP hypothesizes a role for ADIPOR1 in retinoid metabolism.

Are there gender differences in the reasons why African Americans delay in seeking medical help for symptoms of an acute myocardial infarction?

OBJECTIVES: To identify gender differences in delay time and the reasons why African Americans delay in seeking medical care for symptoms of acute myocardial infarction (AMI). DESIGN: Cross-sectional. SETTING: Five hospitals in the San Francisco and East Bay areas. PATIENTS: Sixty-one African American men and women diagnosed with an AMI. MAIN OUTCOME MEASURES: Prehospital delay time. RESULTS: Median delay time was longer for women compared to men (4.4 hours vs 3.5 hours), although the difference was not significant. Single women delayed longer than single men (P = .03), and women who were alone when symptoms began delayed longer than women with someone (P = .03). Women who received advice to seek help or call 911 upon symptom onset had shorter delays compared to women who were not advised to call 911 (P = .01). Men at home delayed longer than men who experienced their symptoms outside the home (P = .01). Men with emergency room insurance delayed longer than men without emergency room insurance (P = .03), and men who took an ambulance to the hospital had shorter delay times than men who took other means of transportation (P = .04). CONCLUSION: Women compared to men often delay seeking treatment for an AMI, which further increases their risks. Our findings suggest specific characteristics that can serve as a profile to those African Americans most likely to delay seeking treatment for AMI.

Innovations in postoperative pain management: continuous infusion of local anesthetics.

Patients and health care providers alike struggle with alleviating postoperative pain. Patients with unrelieved pain are less likely to cough, breathe deeply, or move easily after surgery, which adversely affects their recovery. Innovations in technology, such as continuous infusion of local anesthetics, have revolutionized postoperative pain management. Technological improvements in needles, catheter insertion techniques, and effortless drug delivery systems are facilitating prolonged analgesia with few adverse effects, increasing patient satisfaction, and expediting postoperative recovery.

Factors associated with prolonged prehospital delay of African Americans with acute myocardial infarction.

BACKGROUND: Delays in seeking treatment for signs and symptoms of acute myocardial infarction are longer for African Americans than for whites. OBJECTIVE: To determine factors associated with prolonged delay and the extent to which perceived racism influences prehospital delay in African Americans with acute myocardial infarction. METHODS: Sixty-one African Americans with acute myocardial infarction were interviewed within 1 month of hospital admission. Delay times were calculated on the basis of the interviews. Independent t tests and chi(2) tests were used to determine factors associated with prolonged delays. RESULTS: Median delay was 4.25 hours and did not differ significantly between women and men (4.42 vs 3.50 hours). Most patients (69%) experienced their initial signs and symptoms at home, often witnessed by family members or friends (70%). Delay was longer for insured patients than for uninsured patients (4.45 vs 0.50 hours). Single, widowed, or divorced patients had longer delay times than did married patients (5.33 vs 2.50 hours), and patients with diabetes delayed longer than did those without diabetes (7.29 vs 3.50 hours). Perceived racism did not differ significantly between patients who delayed seeking treatment and those who did not. CONCLUSIONS: Median delay times were substantially longer than the recommended time of less than 1 hour, reducing the benefit from reperfusion therapies. Education and counseling of patients and their families should be a major strategy in optimizing patients' outcomes and decreasing the time to definitive treatment.

Accustomed to enduring: experiences of African-American women seeking care for cardiac symptoms.

OBJECTIVE: Understand the meaning of delayed treatment seeking in African-American women with unstable angina and myocardial infarction. METHODS: Phenomenologic analysis of in-depth interview data and field notes on 12 African-American women hospitalized with unstable angina or myocardial infarction. RESULTS: Women's interpretation of and response to symptoms were informed by experiences of marginalization and their self-understanding as people who were strong and who had endured life's hardships. When hospitalized, some women experienced trivialization of their complaints by clinicians and a focus on technological procedures over respectfully attending to their concerns, which provided further disincentives to seeking care. Three major themes emerged: misrecognition and discounting of symptoms, enduring, and influence of faith. CONCLUSIONS: Experiences of marginalization shape responses to symptoms, care-seeking behavior, and interpretation of subsequent care experiences for African-American women with cardiac disease, who may experience different symptoms as well as interpret them differently than members of other groups.

The contents of the resuscitation trolley.

This article describes the contents of a standard hospital resuscitation trolley for cardiopulmonary resuscitation. Each item is discussed in terms of its function and the rationale for its inclusion.

Stage of change of 6 health-related behaviors among patients with type 2 diabetes.

AIMS: Assessing patients' current stage of change toward 6 healthy behaviors related to diabetes control. Behaviors studied were smoking cessation (2) regular exercise; (3) consuming 5 servings or more of fruits and vegetables; (4) decreasing intake of refined sugar; (5) reducing saturated fat; and (6) self monitoring of blood glucose (SMBG). METHODS: Stage of change (SOC) for several diabetes control-related behaviors was assessed for 737 patients with type 2 diabetes using a staging algorithm. Socio-demographic data were collected by a structured interview-based questionnaire. RESULTS: There was high degree of readiness toward consuming diets with less saturated fat and simple sugar. Very low degree of readiness was reported for self-monitoring of blood glucose on a regular bases and for practicing physical exercise. Half of the participants (50.9%) were in the precontemplation stage for consuming ≥5 servings of fruits and vegetables every day. Significant correlations were obtained between the degree of readiness for several behaviors (p<0.01). Age, gender, income and education were all related to the stage of change of the studied behaviors (p<0.01). CONCLUSIONS: Patients with diabetes in Jordan are still in the pre-action stages for practicing exercise, consuming 5 servings or more of fruit and vegetable, and self-monitoring of blood glucose. The current finding suggests a need for nutritional education and interventions to raise awareness of lifestyle factors influencing glycemic control among diabetics.

Women and heart disease: missed opportunities.

One woman dies of cardiovascular disease (CVD) every minute in the United States. CVD is the primary cause of mortality in US women, substantially affecting the lives of African American women compared to other ethnic groups. In a national survey conducted by the American Heart Association, 87% of women surveyed failed to cite heart disease as a major threat to their health. These misperceptions may lead women to underestimate their risk for CVD, resulting in a delay in seeking medical care, thus increasing their morbidity and mortality rates. Professional association guidelines and Internet resources for women and their health care providers are available to address the risk factors of smoking, diabetes mellitus, obesity, hypertension, hyperlipidemia, and physical inactivity. Unless women are informed and educated about these risk factors, they are unable to modify their lifestyles, be proactive in their health care, or reduce their cardiovascular risks.