An Accidental Nutritionist.

My career as an accidental nutritionist began with my immersion in cholera control, a cyclone disaster, a smallpox epidemic, and formal training in ophthalmology and epidemiology. Interest in blindness prevention inexplicably led me to (re)pioneer the effects, treatment, and prevention of vitamin A deficiency, while faced with intense criticism by many leading scientists in the nutrition community. The resulting efforts by the World Health Organization and UNICEF in support of programs for the global control of vitamin A deficiency still face vocal opposition by some senior scientists, despite having been estimated to have saved tens of millions of children from unnecessary death and blindness. This entire journey was largely an accident!

The 2016 American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) Database: Characteristics and Methods.

PURPOSE: To describe the characteristics of the patient population included in the 2016 IRIS® Registry (Intelligent Research in Sight) database for analytic aims. DESIGN: Description of a clinical data registry. PARTICIPANTS: The 2016 IRIS Registry database consists of 17 363 018 unique patients from 7200 United States-based ophthalmologists in the United States. METHODS: Electronic health record (EHR) data were extracted from the participating practices and placed into a clinical database. The approach can be used across dozens of EHR systems. MAIN OUTCOME MEASURES: Demographic characteristics. RESULTS: The 2016 IRIS Registry database includes data about patient demographics, top-coded disease conditions, and visit rates. CONCLUSIONS: The IRIS Registry is a unique, large, real-world data set that is available for analytics to provide perspectives and to learn about current ophthalmic care and treatment outcomes. The IRIS Registry can be used to answer questions about practice patterns, use, disease prevalence, clinical outcomes, and the comparative effectiveness of different treatments. Limitations of the data are the same limitations associated with EHR data in terms of documentation errors or missing data and the lack of images. Currently, open access to the database is not available, but there are opportunities for researchers to submit proposals for analyses, for example through a Research to Prevent Blindness and American Academy of Ophthalmology Award for IRIS Registry Research.

The Johns Hopkins Bloomberg School of Public Health: A Brief History of a Century of Epidemiologic Discovery.

During its first century, the Johns Hopkins University Bloomberg School of Public Health has been home to several faculty members who have played leading roles in defining and expanding the field and science of epidemiology. They have done so by training leaders in the field, creating new methods and applications, and making relevant discoveries in the worlds of infectious and chronic diseases. These methodologic innovations and discoveries underlie many of today's major health policies and practices.

Burning Fossil Fuels: Impact of Climate Change on Health.

A recent, sophisticated granular analysis of climate change in the United States related to burning fossil fuels indicates a high likelihood of dramatic increases in temperature, wet-bulb temperature, and precipitation, which will dramatically impact the health and well-being of many Americans, particularly the young, the elderly, and the poor and marginalized. Other areas of the world, where they lack the resources to remediate these weather impacts, will be even more greatly affected. Too little attention is being paid to the impending health impact of accumulating greenhouse gases.

A novel device for assessing dark adaptation in field settings.

BACKGROUND: Aberrant dark adaptation is common to many ocular diseases and pathophysiological conditions, including vitamin A deficiency, cardiopulmonary diseases, and hypoxia. Scotopic vision and pupillary responsiveness have typically been measured using subjective, time-consuming methods. Existing techniques are particularly challenging for use in developing country settings, where vitamin A deficiency remains a major public health problem. Our aim was design a compact, low cost, and easily operated device to assess dark adaptation in the field. METHODS: The Portable Field Dark Adaptometer (PFDA) incorporates a digital camera, a retinal bleaching flash, and a Ganzfeld light source inside a pair of light-obscuring goggles. After a ~10 min period of dark adaption, the infrared camera digitally records afferent pupillary responses to graded light stimuli (-2.9 to 0.1 log cd/m(2)). We tested this device in a variety of field settings to assess: a) ease of use and b) whether test data could clearly and accurately depict the well-known dose-response relationship between light intensity and pupil contraction. A total of 822 videos were collected. We used an open source video analysis software to measure pupil size in pixel units. Pupillary responsiveness was expressed as the percent change in pupil size from pre- to post-light exposure. Box plots, t test, and multi-level mixed effects linear regression modeling were used to characterize the relationship between light intensity and pupillary response. RESULTS: The PFDA was employed with only minor technical challenges in Bangladesh, Kenya, Zambia, and Peru. Our data show a clear linear increase in pupillary constriction with increasing log light intensity. Light intensity was a strong predictor of pupillary response, regardless of baseline pupil size. CONCLUSIONS: The consistent physiological response demonstrated here supports the use of the PFDA as a reliable tool to measure dark adaptation. As a next step, PFDA measurements will be validated against biochemical indicators of vitamin A status and hypoxemia. Ultimately, this new technology may provide a novel approach for nutritional assessment, with potential clinical applications.

Maternal vitamin A supplementation and lung function in offspring.

BACKGROUND: Vitamin A is important in regulating early lung development and alveolar formation. Maternal vitamin A status may be an important determinant of embryonic alveolar formation, and vitamin A deficiency in a mother during pregnancy could have lasting adverse effects on the lung health of her offspring. We tested this hypothesis by examining the long-term effects of supplementation with vitamin A or beta carotene in women before, during, and after pregnancy on the lung function of their offspring, in a population with chronic vitamin A deficiency. METHODS: We examined a cohort of rural Nepali children 9 to 13 years of age whose mothers had participated in a placebo-controlled, double-blind, cluster-randomized trial of vitamin A or beta-carotene supplementation between 1994 and 1997. RESULTS: Of 1894 children who were alive at the end of the original trial, 1658 (88%) were eligible to participate in the follow-up trial. We performed spirometry in 1371 of the children (83% of those eligible) between October 2006 and March 2008. Children whose mothers had received vitamin A had a forced expiratory volume in 1 second (FEV(1)) and a forced vital capacity (FVC) that were significantly higher than those of children whose mothers had received placebo (FEV(1), 46 ml higher with vitamin A; 95% confidence interval [CI], 6 to 86; FVC, 46 ml higher with vitamin A; 95% CI, 8 to 84), after adjustment for height, age, sex, body-mass index, calendar month, caste, and individual spirometer used. Children whose mothers had received beta carotene had adjusted FEV(1) and FVC values that were similar to those of children whose mothers had received placebo (FEV(1), 14 ml higher with beta carotene; 95% CI, -24 to 54; FVC, 17 ml higher with beta carotene, 95% CI, -21 to 55). CONCLUSIONS: In a chronically undernourished population, maternal repletion with vitamin A at recommended dietary levels before, during, and after pregnancy improved lung function in offspring. This public health benefit was apparent in the preadolescent years.

The Impact of Social Determinants of Health on Vision Loss From Cataracts and Cataract Surgery Utilization in the United States-A National Health Interview Survey Analysis.

PURPOSE: To investigate the association of social determinants of health (SDOH) factors and cataract-related outcomes disparities. DESIGN: Cross-sectional, with a nationally representative sample. METHODS: We used publicly available data from the 2008, 2016, and 2017 National Health Interview Survey data sets. Outcome measures included self-reported prevalence for ever been diagnosed with cataract, vision loss secondary to cataracts, and the likelihood of undergoing cataract surgery. Survey-weighted, multivariable logistic regression models, adjusted for age, race and ethnicity, and other relevant covariates, were used to examine the association between SDOH factors and cataract-related outcomes. RESULTS: A total of 81,551 participants were included, who were predominantly between 18 and 44 years of age (49.6%), female (51.7%), and White (74.8%). Multivariable regression models with age as a covariate showed that individuals who were not working were more likely to report having cataracts than those who were working (P < .001). Those who needed but could not afford medical care in the past year were more likely to report vision loss secondary to cataracts than their counterparts (P < .001). Uninsured participants were less likely to report undergoing cataract surgery than those with private insurance (P = .03). Individuals with higher income (poverty-income ratio: 1.00-2.99 vs <1.00) were more likely to report undergoing cataract surgery (P = .04). CONCLUSIONS: Several SDOH factors were associated with disparities in rates of cataract-related outcomes. These findings highlight the importance of ophthalmologists screening for social risks in patients with cataract, as these social factors are important barriers for access to care.

Effects of vitamin A or beta carotene supplementation on pregnancy-related mortality and infant mortality in rural Bangladesh: a cluster randomized trial.

CONTEXT: Maternal vitamin A deficiency is a public health concern in the developing world. Its prevention may improve maternal and infant survival. OBJECTIVE: To assess efficacy of maternal vitamin A or beta carotene supplementation in reducing pregnancy-related and infant mortality. DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked, placebo-controlled trial among pregnant women 13 to 45 years of age and their live-born infants to 12 weeks (84 days) postpartum in rural northern Bangladesh between 2001 and 2007. Interventions Five hundred ninety-six community clusters (study sectors) were randomized for pregnant women to receive weekly, from the first trimester through 12 weeks postpartum, 7000 µg of retinol equivalents as retinyl palmitate, 42 mg of all-trans beta carotene, or placebo. Married women (n = 125,257) underwent 5-week surveillance for pregnancy, ascertained by a history of amenorrhea and confirmed by urine test. Blood samples were obtained from participants in 32 sectors (5%) for biochemical studies. MAIN OUTCOME MEASURES: All-cause mortality of women related to pregnancy, stillbirth, and infant mortality to 12 weeks (84 days) following pregnancy outcome. RESULTS: Groups were comparable across risk factors. For the mortality outcomes, neither of the supplement group outcomes was significantly different from the placebo group outcomes. The numbers of deaths and all-cause, pregnancy-related mortality rates (per 100,000 pregnancies) were 41 and 206 (95% confidence interval [CI], 140-273) in the placebo group, 47 and 237 (95% CI, 166-309) in the vitamin A group, and 50 and 250 (95% CI, 177-323) in the beta carotene group. Relative risks for mortality in the vitamin A and beta carotene groups were 1.15 (95% CI, 0.75-1.76) and 1.21 (95% CI, 0.81-1.81), respectively. In the placebo, vitamin A, and beta carotene groups the rates of stillbirth and infant mortality were 47.9 (95% CI, 44.3-51.5), 45.6 (95% CI, 42.1-49.2), and 51.8 (95% CI, 48.0-55.6) per 1000 births and 68.1 (95% CI, 63.7-72.5), 65.0 (95% CI, 60.7-69.4), and 69.8 (95% CI, 65.4-72.3) per 1000 live births, respectively. Vitamin A compared with either placebo or beta carotene supplementation increased plasma retinol concentrations by end of study (1.46 [95% CI, 1.42-1.50] µmol/L vs 1.13 [95% CI, 1.09-1.17] µmol/L and 1.18 [95% CI, 1.14-1.22] µmol/L, respectively; P < .001) and reduced, but did not eliminate, gestational night blindness (7.1% for vitamin A vs 9.2% for placebo and 8.9% for beta carotene [P < .001 for both]). CONCLUSION: Use of weekly vitamin A or beta carotene in pregnant women in Bangladesh, compared with placebo, did not reduce all-cause maternal, fetal, or infant mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00198822.

Magrabi ICO Cameroon Eye Institute, Yaoundé, Cameroon: Ophthalmology Subspecialty Patient Care and Training Center in Central Africa.

PURPOSE: To report establishment of the Magrabi ICO Cameroon Eye Institute at Yaoundé, Cameroon, as an ophthalmology subspecialty patient care and training center in Central Africa. DESIGN: Perspective. METHODS: Assessment of unpublished and published material. RESULTS: To improve, preserve and restore eye health and vision in a region with world-high prevalence of functional vision impairment and blindness, the Africa Eye Foundation established the Magrabi ICO Cameroon Eye Institute as an ophthalmology subspecialty patient care center for all in need and a training center for ophthalmologists, ophthalmology subspecialists, and allied personnel. In 2017, the year of its inauguration and the first year of operation, the Magrabi ICO Cameroon Eye Institute provided ophthalmology subspecialty care to more than 25 000 patients and surgery for pediatric and adult cataract, glaucoma, retinal disease, oculoplastic disorders, and other vision-threatening conditions. Outreach programs extended care to an additional 2500 individuals in rural communities and 7 training courses were conducted for ophthalmologists and allied personnel. CONCLUSION: Through ophthalmology subspecialty patient care and the training of ophthalmologists and allied personnel, Magrabi ICO Cameroon Eye Institute is acting to enhance vision and the quality of life for individuals and families in all segments of society.

Vitamin a deficiency and clinical disease: an historical overview.

Vitamin A deficiency has a plethora of clinical manifestations, ranging from xerophthalmia (practically pathognomonic) to disturbances in growth and susceptibility to severe infection (far more protean). Like other classical vitamin deficiency states (scurvy, rickets), some of the signs and symptoms of xerophthalmia were recognized long ago. Reports related to vitamin A and/or manifestations of deficiency might conveniently be divided into "ancient" accounts; eighteenth to nineteenth century clinical descriptions (and their purported etiologic associations); early twentieth century laboratory animal experiments and clinical and epidemiologic observations that identified the existence of this unique nutrient and manifestations of its deficiency; and, most recently, a flowering of carefully conducted clinical studies and field-based randomized trials that documented the full extent and impact of deficiency among the poor of low- and middle-income countries, which in turn changed global health policy.

The human immunodeficiency virus (HIV)-1 protease inhibitor saquinavir inhibits proteasome function and causes apoptosis and radiosensitization in non-HIV-associated human cancer cells.

Cancer cells frequently show high constitutive activity of the antiapoptotic transcription factor nuclear factor kappaB (NF-kappaB), which results in their enhanced survival. Activation of NF-kappaB classically depends on degradation of its inhibitor IkappaBalpha by the 26s proteasome. Specific proteasome inhibitors induce apoptosis in cancer cells and, at nonlethal concentrations, sensitize cells to the cytotoxic effects of ionizing radiation and chemotherapeutic drugs. Recently, the protease coded by the HIV-I virus has been shown to share cleavage activities with the proteasome. For this reason, we investigated whether the HIV-I protease inhibitor saquinavir can inhibit NF-kappaB activation, block 26s proteasome activity in prostate cancer cells, and promote their apoptosis. The effect of saquinavir on LPS/IFN-gamma-induced activation of NF-kappaB was assessed by gel-shift assays and by Western analysis of corresponding IkappaBalpha-levels. Its effect on 20s and 26s proteasome activity was analyzed with a fluorogenic peptide assay using whole cell lysates from LnCaP, DU-145, and PC-3 prostate cancer cells pretreated with saquinavir for 9 h. Proteasome inhibition in living cells was assessed using ECV 304 cells stably transfected with an expression plasmid for an ubiquitin/green fluorescence protein fusion protein (ECV 304/10). Apoptosis was monitored morphologically and by flow cytometry. Saquinavir treatment prevented LPS/IFN-gamma-induced activation of NF-kappaB in RAW cells and stabilized expression of IkappaBalpha. It inhibited 20s and 26s proteasome activity in lysates from LnCaP, DU-145, and PC-3 prostate cancer cells with an IC(50) of 10 micro M and caused the accumulation of an ubiquitin/green fluorescence protein fusion protein in living ECV 304/10 cells. Incubation of PC-3 and DU-145 prostate cancer, U373 glioblastoma, and K562 and Jurkat leukemia cells with saquinavir caused a concentration-dependent induction of apoptosis. In the case of PC-3 and DU-145, saquinavir sensitized the surviving cells to ionizing radiation. We conclude that saquinavir inhibits proteasome activity in mammalian cells as well as acting on the HIV-I protease. Because saquinavir induced apoptosis in human cancer cells, HIV-I protease inhibitors might become a new class of cytotoxic drugs, alone or in combination with radiation or chemotherapy.

The erythropoietin-receptor pathway modulates survival of cancer cells.

Anemia in cancer patients is associated with reduced quality of life and local failure after radiation treatment. However, the use of erythropoietin to correct cancer anemia and to improve radiation efficacy was disappointing. Erythropoietin-receptor signaling mainly acts via activation of STAT 5, but also crossactivates the antiapoptotic transcription factor NF-kappaB. This causes neuroprotection against oxidative stress and implies radioprotection. In order to investigate possible radioprotective effects of erythropoietin-receptor signaling, we used an in vitro model system employing HeLa TetOff cells, stably transfected with an expression vector for the erythropoietin-receptor gene. Using electrophoretic mobility shift assays, we could demonstrate strong activation of NF-kappaB by erythropoietin-receptor signaling in HeLa cells. Activation of NF-kappaB did not require degradation of IkappaBalpha and was not prevented by proteasome inhibition. Furthermore, stimulation with erythropoietin resulted in a 50% increased clonogenicity of erythropoietin-receptor-expressing cells but did not alter radiation sensitivity itself. As most human tumors express erythropoietin receptor, we advocate a restricted use erythropoietin to patients suffering from erythropoietin-receptor-expressing cancers.