Publications by authors named "Rachel Silver"

38 Publications

Randomized trial of a novel lifestyle intervention compared with the Diabetes Prevention Program for weight loss in adult dependents of military service members.

Am J Clin Nutr 2021 10;114(4):1546-1559

Energy Metabolism, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

Background: Lifestyle interventions are the first-line treatment for obesity, but participant weight loss is typically low.

Objectives: We evaluated the efficacy of an alternative lifestyle intervention [Healthy Weight for Living (HWL)] compared with a modified Diabetes Prevention Program (m-DPP). HWL was based on a revised health behavior change model emphasizing hunger management and the development of healthy food preferences. m-DPP was a standard Diabetes Prevention Program implemented with counselor time matched to HWL. Participants were adult dependents of military personnel and had overweight or obesity.

Methods: Participants were randomly assigned to HWL (n = 121) or m-DPP (n = 117), delivered primarily by group videoconference with additional midweek emails. The primary outcome was 12-mo weight change. Secondary outcomes included 6-mo changes in cardiometabolic risk factors and diet. Intention-to-treat (ITT) and complete case (CC) analyses were performed using linear mixed models.

Results: Retention did not differ between groups (72% and 66% for HWL and m-DPP at 12 mo, respectively; P = 0.30). Mean ± SE adjusted 12-mo weight loss in the ITT cohort was 7.46 ± 0.85 kg for HWL and 7.32 ± 0.87 kg for m-DPP (P = 0.91); in the CC cohort, it was 7.83 ± 0.82 kg for HWL and 6.86 ± 0.88 kg for m-DPP (P = 0.43). Thirty-eight percent of HWL and 30% of m-DPP completers achieved ≥10% weight loss (P = 0.32). Improvements in systolic blood pressure, LDL cholesterol, triglycerides, fasting glucose, general health, sleep, and mood were similar across groups; improvements in diastolic blood pressure were greater in m-DPP. Adjusted group mean reductions in energy intake were not significantly different between groups, but HWL participants were more adherent to their dietary prescription for lower glycemic index and high fiber and protein (P = 0.05 to <0.001 for ITT).

Conclusions: HWL and m-DPP showed equivalent and clinically impactful mean weight loss with cardiometabolic benefits. These results identify an alternative approach for behavioral treatment of overweight and obesity.This trial was registered at clinicaltrials.gov as NCT02348853.
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http://dx.doi.org/10.1093/ajcn/nqab259DOI Listing
October 2021

Healthy Aging-Nutrition Matters: Start Early and Screen Often.

Adv Nutr 2021 07;12(4):1438-1448

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.

The amount of time spent in poor health at the end of life is increasing. This narrative review summarizes consistent evidence indicating that healthy dietary patterns and maintenance of a healthy weight in the years leading to old age are associated with broad prevention of all the archetypal diseases and impairments associated with aging including: noncommunicable diseases, sarcopenia, cognitive decline and dementia, osteoporosis, age-related macular degeneration, diabetic retinopathy, hearing loss, obstructive sleep apnea, urinary incontinence, and constipation. In addition, randomized clinical trials show that disease-specific nutrition interventions can attenuate progression-and in some cases effectively treat-many established aging-associated conditions. However, middle-aged and older adults are vulnerable to unhealthy dietary patterns, and typically consume diets with inadequate servings of healthy food groups and essential nutrients, along with an abundance of energy-dense but nutrient-weak foods that contribute to obesity. However, based on menu examples, diets that are nutrient-dense, plant-based, and with a moderately low glycemic load are better equipped to meet the nutritional needs of many older adults than current recommendations in US Dietary Guidelines. These summary findings indicate that healthy nutrition is more important for healthy aging than generally recognized. Improved public health messaging about nutrition and aging, combined with routine screening and medical referrals for age-related conditions that can be treated with a nutrition prescription, should form core components of a national nutrition roadmap to reduce the epidemic of unhealthy aging.
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http://dx.doi.org/10.1093/advances/nmab032DOI Listing
July 2021

Differences in rapid increases in county-level COVID-19 incidence by implementation of statewide closures and mask mandates - United States, June 1-September 30, 2020.

Ann Epidemiol 2021 05 14;57:46-53. Epub 2021 Feb 14.

Public Health Law Program, Centers for Disease Control and Prevention, Atlanta, GA.

Background And Objective: Community mitigation strategies could help reduce COVID-19 incidence, but there are few studies that explore associations nationally and by urbanicity. In a national county-level analysis, we examined the probability of being identified as a county with rapidly increasing COVID-19 incidence (rapid riser identification) during the summer of 2020 by implementation of mitigation policies prior to the summer, overall and by urbanicity.

Methods: We analyzed county-level data on rapid riser identification during June 1-September 30, 2020 and statewide closures and statewide mask mandates starting March 19 (obtained from state government websites). Poisson regression models with robust standard error estimation were used to examine differences in the probability of rapid riser identification by implementation of mitigation policies (P-value< .05); associations were adjusted for county population size.

Results: Counties in states that closed for 0-59 days were more likely to become a rapid riser county than those that closed for >59 days, particularly in nonmetropolitan areas. The probability of becoming a rapid riser county was 43% lower among counties that had statewide mask mandates at reopening (adjusted prevalence ratio = 0.57; 95% confidence intervals = 0.51-0.63); when stratified by urbanicity, associations were more pronounced in nonmetropolitan areas.

Conclusions: These results underscore the potential value of community mitigation strategies in limiting the COVID-19 spread, especially in nonmetropolitan areas.
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http://dx.doi.org/10.1016/j.annepidem.2021.02.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882220PMC
May 2021

Opening of Large Institutions of Higher Education and County-Level COVID-19 Incidence - United States, July 6-September 17, 2020.

MMWR Morb Mortal Wkly Rep 2021 Jan 8;70(1):14-19. Epub 2021 Jan 8.

During early August 2020, county-level incidence of coronavirus disease 2019 (COVID-19) generally decreased across the United States, compared with incidence earlier in the summer (1); however, among young adults aged 18-22 years, incidence increased (2). Increases in incidence among adults aged ≥60 years, who might be more susceptible to severe COVID-19-related illness, have followed increases in younger adults (aged 20-39 years) by an average of 8.7 days (3). Institutions of higher education (colleges and universities) have been identified as settings where incidence among young adults increased during August (4,5). Understanding the extent to which these settings have affected county-level COVID-19 incidence can inform ongoing college and university operations and future planning. To evaluate the effect of large colleges or universities and school instructional format* (remote or in-person) on COVID-19 incidence, start dates and instructional formats for the fall 2020 semester were identified for all not-for-profit large U.S. colleges and universities (≥20,000 total enrolled students). Among counties with large colleges and universities (university counties) included in the analysis, remote-instruction university counties (22) experienced a 17.9% decline in mean COVID-19 incidence during the 21 days before through 21 days after the start of classes (from 17.9 to 14.7 cases per 100,000), and in-person instruction university counties (79) experienced a 56.2% increase in COVID-19 incidence, from 15.3 to 23.9 cases per 100,000. Counties without large colleges and universities (nonuniversity counties) (3,009) experienced a 5.9% decline in COVID-19 incidence, from 15.3 to 14.4 cases per 100,000. Similar findings were observed for percentage of positive test results and hotspot status (i.e., increasing among in-person-instruction university counties). In-person instruction at colleges and universities was associated with increased county-level COVID-19 incidence and percentage test positivity. Implementation of increased mitigation efforts at colleges and universities could minimize on-campus COVID-19 transmission.
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http://dx.doi.org/10.15585/mmwr.mm7001a4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790156PMC
January 2021

Rapid Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Detention Facility, Louisiana, USA, May-June, 2020.

Emerg Infect Dis 2021 Feb 4;27(2):421-429. Epub 2021 Jan 4.

To assess transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a detention facility experiencing a coronavirus disease outbreak and evaluate testing strategies, we conducted a prospective cohort investigation in a facility in Louisiana, USA. We conducted SARS-CoV-2 testing for detained persons in 6 quarantined dormitories at various time points. Of 143 persons, 53 were positive at the initial test, and an additional 58 persons were positive at later time points (cumulative incidence 78%). In 1 dormitory, all 45 detained persons initially were negative; 18 days later, 40 (89%) were positive. Among persons who were SARS-CoV-2 positive, 47% (52/111) were asymptomatic at the time of specimen collection; 14 had replication-competent virus isolated. Serial SARS-CoV-2 testing might help interrupt transmission through medical isolation and quarantine. Testing in correctional and detention facilities will be most effective when initiated early in an outbreak, inclusive of all exposed persons, and paired with infection prevention and control.
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http://dx.doi.org/10.3201/eid2702.204158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853536PMC
February 2021

Association of counselor weight status and demographics with participant weight loss in a structured lifestyle intervention.

Obes Res Clin Pract 2021 Jan-Feb;15(1):69-72. Epub 2020 Dec 5.

Energy Metabolism Laboratory, USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington St., Boston, MA 02111, United States.

Objective: There is substantial variability in the effectiveness of group lifestyle interventions for weight loss. We examined associations between intervention weight loss counselors and participant weight loss and program engagement in a structured lifestyle intervention.

Methods: Data were from 575 adults (87% female, 51 (12) years, baseline BMI: 32.4 (7.2) kg/m) in an 11-week structured group lifestyle program. Participants self-enrolled in groups led by 11 weight loss counselors based on meeting times. All weight loss counselors received the same training. Linear mixed models were used to evaluate counselor predictors of participant percent (%) weight loss and program engagement (weight reporting throughout 11 weeks).

Results: Of the 575 participants, 415 (72%) defined as complete reporters, i.e. reported weight weekly, lost a mean 7.3% weight (range: +3.1% to 16.2%). Participant weight loss differed between weight loss counselors (p = 0.003), and adjusted mean participant weight loss by weight loss counselor ranged from 6% to 9%. Weight loss was greater for weight loss counselors with a graduate degree in nutrition than weight loss counselors with another graduate degree (8.3% versus 6.4%, p = 0.05), but was not different between weight loss counselors with and without graduate degrees. Higher counselor BMI was associated with higher participant weight loss (p = 0.005).

Conclusions: These results demonstrate the potential for quantitatively important effects of weight loss counselor characteristics on participant success and engagement in structured lifestyle interventions, indicating a need for research in this area.
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http://dx.doi.org/10.1016/j.orcp.2020.11.005DOI Listing
September 2021

Identification of Presymptomatic and Asymptomatic Cases Using Cohort-Based Testing Approaches at a Large Correctional Facility-Chicago, Illinois, USA, May 2020.

Clin Infect Dis 2021 03;72(5):e128-e135

Cermak Health Services, Chicago, Illinois, USA.

Background: Coronavirus disease 2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. Correctional and detention facilities are at high risk of experiencing outbreaks. We aimed to evaluate cohort-based testing among detained persons exposed to laboratory-confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to identify presymptomatic and asymptomatic cases.

Methods: During 1-19 May 2020, 2 testing strategies were implemented in 12 tiers or housing units of the Cook County Jail, Chicago, Illinois. Detained persons were approached to participate in serial testing (n = 137) and offered tests at 3 time points over 14 days (day 1, days 3-5, and days 13-14). The second group was offered a single test and interview at the end of a 14-day quarantine period (day 14 group) (n = 87).

Results: 224 detained persons were approached for participation and, of these, 194 (87%) participated in ≥1 interview and 172 (77%) had ≥1 test. Of the 172 tested, 19 were positive for SARS-CoV-2. In the serial testing group, 17 (89%) new cases were detected, 16 (84%) on day 1, 1 (5%) on days 3-5, and none on days 13-14; in the day 14 group, 2 (11%) cases were identified. More than half (12/19; 63%) of the newly identified cases were presymptomatic or asymptomatic.

Conclusions: Our findings highlight the utility of cohort-based testing promptly after initiating quarantine within a housing tier. Cohort-based testing efforts identified new SARS-CoV-2 asymptomatic and presymptomatic infections that may have been missed by symptom screening alone.
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http://dx.doi.org/10.1093/cid/ciaa1802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799274PMC
March 2021

Comparison of Molecular Subtyping and Antimicrobial Resistance Detection Methods Used in a Large Multistate Outbreak of Extensively Drug-Resistant Campylobacter jejuni Infections Linked to Pet Store Puppies.

J Clin Microbiol 2020 09 22;58(10). Epub 2020 Sep 22.

Division of Foodborne, Waterborne, and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

is a leading cause of enteric bacterial illness in the United States. Traditional molecular subtyping methods, such as pulsed-field gel electrophoresis (PFGE) and 7-gene multilocus sequence typing (MLST), provided limited resolution to adequately identify outbreaks and separate out sporadic isolates during outbreak investigations. Whole-genome sequencing (WGS) has emerged as a powerful tool for outbreak detection. In this investigation, 45 human and 11 puppy isolates obtained during a 2016-2018 outbreak linked to pet store puppies were sequenced. Core genome multilocus sequence typing (cgMLST) and high-quality single nucleotide polymorphism (hqSNP) analysis of the sequence data separated the isolates into the same two clades containing minor within-clade differences; however, cgMLST analysis does not require selection of an appropriate reference genome, making the method preferable to hqSNP analysis for surveillance and cluster detection. The isolates were classified as sequence type 2109 (ST2109)-a rarely seen MLST sequence type. PFGE was performed on 38 human and 10 puppy isolates; PFGE patterns did not reliably predict clustering by cgMLST analysis. Genetic detection of antimicrobial resistance determinants predicted that all outbreak-associated isolates would be resistant to six drug classes. Traditional antimicrobial susceptibility testing (AST) confirmed a high correlation between genotypic and phenotypic antimicrobial resistance determinations. WGS analysis linked isolates in humans and pet store puppies even when canine exposure information was unknown, aiding the epidemiological investigation during the outbreak. WGS data were also used to quickly identify the highly drug-resistant profile of these outbreak-associated isolates.
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http://dx.doi.org/10.1128/JCM.00771-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7512158PMC
September 2020

Effects of food supplementation on cognitive function, cerebral blood flow, and nutritional status in young children at risk of undernutrition: randomized controlled trial.

BMJ 2020 07 22;370:m2397. Epub 2020 Jul 22.

Department of Psychology, Tufts University, Medford, MA, USA.

Objective: To assess the effects of food supplementation on improving working memory and additional measures including cerebral blood flow in children at risk of undernutrition.

Design: Randomized controlled trial.

Setting: 10 villages in Guinea-Bissau.

Participants: 1059 children aged 15 months to 7 years; children younger than 4 were the primary population.

Interventions: Supervised isocaloric servings (≈1300 kJ, five mornings each week, 23 weeks) of a new food supplement (NEWSUP, high in plant polyphenols and omega 3 fatty acids, within a wide variety and high fortification of micronutrients, and a high protein content), or a fortified blended food (FBF) used in nutrition programs, or a control meal (traditional rice breakfast).

Main Outcome Measurements: The primary outcome was working memory, a core executive function predicting long term academic achievement. Additional outcomes were hemoglobin concentration, growth, body composition, and index of cerebral blood flow (CBF). In addition to an intention-to-treat analysis, a predefined per protocol analysis was conducted in children who consumed at least 75% of the supplement (820/925, 89%). The primary outcome was assessed by a multivariable Poisson model; other outcomes were assessed by multivariable linear mixed models.

Results: Among children younger than 4, randomization to NEWSUP increased working memory compared with the control meal (rate ratio 1.20, 95% confidence interval 1.02 to 1.41, P=0.03), with a larger effect in the per protocol population (1.25, 1.06 to 1.47, P=0.009). NEWSUP also increased hemoglobin concentration among children with anemia (adjusted mean difference 0.65 g/dL, 95% confidence interval 0.23 to 1.07, P=0.003) compared with the control meal, decreased body mass index z score gain (-0.23, -0.43 to -0.02, P=0.03), and increased lean tissue accretion (2.98 cm, 0.04 to 5.92, P=0.046) with less fat (-5.82 cm, -11.28 to -0.36, P=0.04) compared with FBF. Additionally, NEWSUP increased CBF compared with the control meal and FBF in both age groups combined (1.14 mm/s×10, 0.10 to 2.23, P=0.04 for both comparisons). Among children aged 4 and older, NEWSUP had no significant effect on working memory or anemia, but increased lean tissue compared with FBF (4.31 cm, 0.34 to 8.28, P=0.03).

Conclusions: Childhood undernutrition is associated with long term impairment in cognition. Contrary to current understanding, supplementary feeding for 23 weeks could improve executive function, brain health, and nutritional status in vulnerable young children living in low income countries. Further research is needed to optimize nutritional prescriptions for regenerative improvements in cognitive function, and to test effectiveness in other vulnerable groups.

Trial Registration: ClinicalTrials.gov NCT03017209.
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http://dx.doi.org/10.1136/bmj.m2397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374799PMC
July 2020

Bi-allelic Pathogenic Variants in TUBGCP2 Cause Microcephaly and Lissencephaly Spectrum Disorders.

Am J Hum Genet 2019 11 17;105(5):1005-1015. Epub 2019 Oct 17.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.

Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies are highly enriched for genes encoding microtubules and microtubule-associated proteins, and this enrichment highlights the critical role for these genes in cortical growth and gyrification. Using exome sequencing and family based rare variant analyses, we identified a homozygous variant (c.997C>T [p.Arg333Cys]) in TUBGCP2, encoding gamma-tubulin complex protein 2 (GCP2), in two individuals from a consanguineous family; both individuals presented with microcephaly and developmental delay. GCP2 forms the multiprotein γ-tubulin ring complex (γ-TuRC) together with γ-tubulin and other GCPs to regulate the assembly of microtubules. By querying clinical exome sequencing cases and through GeneMatcher-facilitated collaborations, we found three additional families with bi-allelic variation and similarly affected phenotypes including a homozygous variant (c.1843G>C [p.Ala615Pro]) in two families and compound heterozygous variants consisting of one missense variant (c.889C>T [p.Arg297Cys]) and one splice variant (c.2025-2A>G) in another family. Brain imaging from all five affected individuals revealed varying degrees of cortical malformations including pachygyria and subcortical band heterotopia, presumably caused by disruption of neuronal migration. Our data demonstrate that pathogenic variants in TUBGCP2 cause an autosomal recessive neurodevelopmental trait consisting of a neuronal migration disorder, and our data implicate GCP2 as a core component of γ-TuRC in neuronal migrating cells.
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http://dx.doi.org/10.1016/j.ajhg.2019.09.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848995PMC
November 2019

Cryptosporidiosis Outbreaks - United States, 2009-2017.

MMWR Morb Mortal Wkly Rep 2019 Jun 28;68(25):568-572. Epub 2019 Jun 28.

Cryptosporidium is a parasite that causes cryptosporidiosis, a profuse, watery diarrhea that can last up to 3 weeks in immunocompetent patients and can lead to life-threatening malnutrition and wasting in immunocompromised patients.* Fecal-oral transmission can occur by ingestion of contaminated recreational water, drinking water, or food, or through contact with infected persons or animals. For the period 2009-2017, public health officials from 40 states and Puerto Rico voluntarily reported 444 cryptosporidiosis outbreaks resulting in 7,465 cases. Exposure to treated recreational water (e.g., in pools and water playgrounds) was associated with 156 (35.1%) outbreaks resulting in 4,232 (56.7%) cases. Other predominant outbreak exposures included contact with cattle (65 outbreaks; 14.6%) and contact with infected persons in child care settings (57; 12.8%). The annual number of reported cryptosporidiosis outbreaks overall increased an average of approximately 13% per year over time. Reversing this trend will require dissemination of prevention messages to discourage swimming or attending child care while ill with diarrhea and encourage hand washing after contact with animals. Prevention and control measures can be optimized by improving understanding of Cryptosporidium transmission through regular analysis of systematically collected epidemiologic and molecular characterization data.
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http://dx.doi.org/10.15585/mmwr.mm6825a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6597118PMC
June 2019

Development of a Videoconference-Adapted Version of the Community Diabetes Prevention Program, and Comparison of Weight Loss With In-Person Program Delivery.

Mil Med 2019 12;184(11-12):647-652

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington St Boston, MA 02111.

Introduction: Effective, standardized, and easily accessible weight management programs are urgently needed for military beneficiaries. Videoconference interventions have the potential for widespread scaling, and can provide both real time interaction and flexibility in delivery times regardless of location, but there is little information on their effectiveness and acceptability.

Materials And Methods: This study as part of a larger weight loss trial describes the videoconference adaption of Group Lifestyle Balance (GLB) program, a community group-based Diabetes Prevention Program intervention, and provides a comparison of weight loss and meeting attendance between in-person and videoconference delivery modes over 12 weeks in adult family members of military service members. Forty-three participants were enrolled from two military installations and received either the videoconference-adapted or an in-person GLB program in a non-randomized trial design. Differences in program attendance and percent weight lost at 12 weeks were compared by independent samples t-tests and nonparametric methods. Group differences in the percentage of weight lost over the 12-week period were analyzed using a linear mixed model.

Results: All GLB intervention components were successfully delivered by videoconference with minor adaptations for the different delivery mechanism. Participant retention was 70% and 96% in the in-person and videoconference groups, respectively (p = 0.04). Completing participants in both groups lost a significant percent body weight over the 12 week intervention (p < 0.001) and there was no difference in percent body weight after 12 weeks of intervention (6.2 ± 3.2% and 5.3 ± 3.4% for in-person and videoconference at 12 weeks, respectively; p = 0.60).

Conclusion: This study describes the first videoconference adaption of the GLB program for use in military families. Attrition was lower in the videoconference group, and there were a similar levels of weight loss in both groups regardless of delivery modality. Videoconference weight loss interventions are effective and feasible for scaling to support healthy weight management in military as well as civilian populations.
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http://dx.doi.org/10.1093/milmed/usz069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910883PMC
December 2019

Corneal incision architecture: VICTUS femtosecond laser vs manual keratome.

Clin Ophthalmol 2019 10;13:147-152. Epub 2019 Jan 10.

Department of Ophthalmology, Federal University of Sao Paulo, Sao Paulo, Brazil,

Purpose: To evaluate anatomical differences between laser (VICTUS) and manual constructed phacoemulsification incisions.

Setting: Study was conducted at the Hospital de Olhos Paulista, Sao Paulo, Brazil.

Design: This is a prospective, observational, consecutive nonrandomized cohort.

Patients And Methods: Sixteen patients (18 eyes) had phacoemulsification surgery, nine eyes had manual incisions and nine eyes had femtosecond incisions. All incisions were performed by the same surgeon. All incisions were evaluated at the 1st and 30th postoperative day with anterior segment optical coherence tomography to evaluate anatomical features. Inclusion criterion was presence of low visual acuity due to cataract. Exclusion criteria were other ocular pathologies, previous trauma, or corneal wound healing disease, as any intra or postoperative complication. Three different corneal specialists analyzed wound architecture features (epithelial or endothelial gap, incision edema, number of planes, Descemet's detachment, and loss of wound sealing) at both visits. ImageJ (National Institutes of Health) software was also used to analyze anatomical features of incisions.

Results: Almost all incisions had edema at the first postoperative day. All femto incisions were triplanar, as intended, unlike manual incisions, which showed two uniplanar incisions (=0.009). All laser incisions presented partial loss of wound sealing, while five keratome incisions had no loss of wound sealing at the first postoperative day (=0.03).

Conclusion: These findings support the hypothesis that laser constructed incisions are more precisely constructed than manual, although corneal wound healing was similar between the two groups at the 30th postoperative day, with a tendency to a faster anatomical improvement in the keratome group.
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http://dx.doi.org/10.2147/OPTH.S181144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6330980PMC
January 2019

Measured energy content of frequently purchased restaurant meals: multi-country cross sectional study.

BMJ 2018 12 12;363:k4864. Epub 2018 Dec 12.

State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, PRC

Objective: To measure the energy content of frequently ordered meals from full service and fast food restaurants in five countries and compare values with US data.

Design: Cross sectional survey.

Setting: 223 meals from 111 randomly selected full service and fast food restaurants serving popular cuisines in Brazil, China, Finland, Ghana, and India were the primary sampling unit; 10 meals from five worksite canteens were also studied in Finland. The observational unit was frequently ordered meals in selected restaurants.

Main Outcome Measure: Meal energy content, measured by bomb calorimetry.

Results: Compared with the US, weighted mean energy of restaurant meals was lower only in China (719 (95% confidence interval 646 to 799) kcal versus 1088 (1002 to 1181) kcal; P<0.001). In analysis of variance models, fast food contained 33% less energy than full service meals (P<0.001). In Finland, worksite canteens provided 25% less energy than full service and fast food restaurants (mean 880 (SD 156) versus 1166 (298); P=0.009). Country, restaurant type, number of meal components, and meal weight predicted meal energy in a factorial analysis of variance (R=0.62, P<0.001). Ninety four per cent of full service meals and 72% of fast food meals contained at least 600 kcal. Modeling indicated that, except in China, consuming current servings of a full service and a fast food meal daily would supply between 70% and 120% of the daily energy requirements for a sedentary woman, without additional meals, drinks, snacks, appetizers, or desserts.

Conclusion: Very high dietary energy content of both full service and fast food restaurant meals is a widespread phenomenon that is probably supporting global obesity and provides a valid intervention target.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6290458PMC
http://dx.doi.org/10.1136/bmj.k4864DOI Listing
December 2018

Are Gluten-Free Diets More Nutritious? An Evaluation of Self-Selected and Recommended Gluten-Free and Gluten-Containing Dietary Patterns.

Nutrients 2018 Dec 3;10(12). Epub 2018 Dec 3.

Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111, USA.

Gluten-free (GF) eating patterns are frequently perceived to be healthier than gluten-containing (GC) ones, but there has been very little research to evaluate this viewpoint. The effect of GF eating patterns on dietary composition was assessed using two independent approaches. One approach compared macronutrients and typical shortfall nutrients between MyPlate example menus developed with either GC or equivalent GF foods. In this analysis, the GF menus were significantly lower in protein, magnesium, potassium, vitamin E, folate, and sodium ( = 0.002⁻0.03), with suggestive trends towards lower calcium and higher fat ( = 0.06⁻0.08). The second approach was a meta-analysis of seven studies comparing information on the nutrient intakes of adults with celiac disease following a GF diet with control subjects eating a GC diet, and differences were evaluated using paired -tests or Wilcoxon Signed rank tests. In this analysis, consuming a GF diet was associated with higher energy and fat intakes, and lower fiber and folate intakes compared to controls ( < 0.001 to = 0.03). After adjusting for heterogeneity and accounting for the large mean effect size (-0.88 ± 0.09), the lower fiber remained significant ( < 0.001). These combined analyses indicate that GF diets are not nutritionally superior except for sodium, and in several respects are actually worse.
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http://dx.doi.org/10.3390/nu10121881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317051PMC
December 2018

Multidrug-Resistant Campylobacter jejuni Outbreak Linked to Puppy Exposure - United States, 2016-2018.

MMWR Morb Mortal Wkly Rep 2018 Sep 21;67(37):1032-1035. Epub 2018 Sep 21.

Campylobacter causes an estimated 1.3 million diarrheal illnesses in the United States annually (1). In August 2017, the Florida Department of Health notified CDC of six Campylobacter jejuni infections linked to company A, a national pet store chain based in Ohio. CDC examined whole-genome sequencing (WGS) data and identified six isolates from company A puppies in Florida that were highly related to an isolate from a company A customer in Ohio. This information prompted a multistate investigation by local and state health and agriculture departments and CDC to identify the outbreak source and prevent additional illness. Health officials from six states visited pet stores to collect puppy fecal samples, antibiotic records, and traceback information. Nationally, 118 persons, including 29 pet store employees, in 18 states were identified with illness onset during January 5, 2016-February 4, 2018. In total, six pet store companies were linked to the outbreak. Outbreak isolates were resistant by antibiotic susceptibility testing to all antibiotics commonly used to treat Campylobacter infections, including macrolides and quinolones. Store record reviews revealed that among 149 investigated puppies, 142 (95%) received one or more courses of antibiotics, raising concern that antibiotic use might have led to development of resistance. Public health authorities issued infection prevention recommendations to affected pet stores and recommendations for testing puppies to veterinarians. This outbreak demonstrates that puppies can be a source of multidrug-resistant Campylobacter infections in humans, warranting a closer look at antimicrobial use in the commercial dog industry.
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http://dx.doi.org/10.15585/mmwr.mm6737a3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6147421PMC
September 2018

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Am J Obstet Gynecol 2019 01 29;220(1):120. Epub 2018 Aug 29.

Friedman School of Nutrition Science and Policy, Maternal Infant Research Institute, Tufts University, 800 Washington Street, Box 394, Boston, MA 02111.

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http://dx.doi.org/10.1016/j.ajog.2018.08.038DOI Listing
January 2019

Observational Study on a Mindfulness Training for Smokers within a Smoking Cessation Program.

Mindfulness (N Y) 2017 Dec 20;8(6):1698. Epub 2017 Jun 20.

Duke Cancer Institute, Duke University, Durham, NC, USA.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863924PMC
December 2017

Informed Decision-Making in the Context of Prenatal Chromosomal Microarray.

J Genet Couns 2018 09 7;27(5):1130-1147. Epub 2018 Mar 7.

Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.
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http://dx.doi.org/10.1007/s10897-018-0231-yDOI Listing
September 2018

Prioritizing Zoonoses for Global Health Capacity Building-Themes from One Health Zoonotic Disease Workshops in 7 Countries, 2014-2016.

Emerg Infect Dis 2017 12;23(13)

Zoonotic diseases represent critical threats to global health security. Effective mitigation of the impact of endemic and emerging zoonotic diseases of public health importance requires multisectoral collaboration and interdisciplinary partnerships. The US Centers for Disease Control and Prevention created the One Health Zoonotic Disease Prioritization Tool to help countries identify zoonotic diseases of greatest national concern using input from representatives of human health, agriculture, environment, and wildlife sectors. We review 7 One Health Zoonotic Disease Prioritization Tool workshops conducted during 2014-2016, highlighting workshop outcomes, lessons learned, and shared themes from countries implementing this process. We also describe the tool's ability to help countries focus One Health capacity-building efforts to appropriately prevent, detect, and respond to zoonotic disease threats.
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http://dx.doi.org/10.3201/eid2313.170418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711306PMC
December 2017

Associations Between Vitamin D Intake and Progression to Incident Advanced Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2017 09;58(11):4569-4578

Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States.

Purpose: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but no prospective studies have explored the impact of vitamin D. We evaluated the association between vitamin D intake and progression to advanced AMD.

Methods: Among 2146 participants (3965 eyes), 541 (777 eyes) progressed from early or intermediate AMD to advanced disease (mean follow-up: 9.4 years) based on ocular imaging. Nutrients were log transformed and calorie adjusted. Survival analysis was used to assess associations between incident advanced disease and vitamin D intake. Neovascular disease (NV) and geographic atrophy (GA) were evaluated separately. Combined effects of dietary vitamin D and calcium were assessed based on high or low consumption of each nutrient.

Results: There was a lower risk of progression to advanced AMD in the highest versus lowest quintile of dietary vitamin D intake after adjustment for demographic, behavioral, ocular, and nutritional factors (hazard ratio [HR]: 0.60; 95% confidence interval [CI]: 0.43-0.83; P trend = 0.0007). Similar results were observed for NV (HR: 0.59; 95% CI: 0.39-0.89; P trend = 0.005) but not GA (HR: 0.83; 95% CI: 0.53-1.30; P trend = 0.35). A protective effect was observed for advanced AMD among participants with high vitamin D and low calcium compared to the group with low levels for each nutrient (HR: 0.67; 95% CI: 0.50-0.88; P = 0.005). When supplement use was considered, the effect was in the protective direction but was not significant.

Conclusions: A diet rich in vitamin D may prevent or delay progression to advanced AMD, especially NV. Additional exploration is needed to elucidate the potential protective role of vitamin D and its contribution to reducing visual loss.
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http://dx.doi.org/10.1167/iovs.17-21673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5595226PMC
September 2017

Optical Coherence Tomography Features Preceding the Onset of Advanced Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2017 07;58(9):3519-3529

Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, United States 2Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States 5Sackler School of Graduate Biomedical Sciences and Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, United States.

Purpose: Age-related macular degeneration (AMD) is a progressive disease with multifactorial etiology. There is a need to identify clinical features that are harbingers of advanced disease. We evaluated morphologic features of the retina and choroid on optical coherence tomography (OCT) to determine if they predict progression to advanced disease.

Methods: Progressors transitioned from early or intermediate AMD to advanced disease (n = 40 eyes), and were matched on baseline AMD grade and follow-up interval to nonprogressors who did not develop advanced AMD (n = 40 eyes). Features of the neurosensory retina, photoreceptors, retinal pigment epithelium (RPE), and choroid were evaluated. Logistic regression was used to evaluate univariate associations between features and progression to overall advanced AMD, geographic atrophy (GA), and neovascular disease (NV). Multivariate associations based on stepwise regression models were also assessed.

Results: Ellipsoid zone disruption was associated with progression to overall advanced AMD and NV (odds ratios [ORs]: 17.9 and 30.6; P < 0.001), with a similar trend observed for GA. Drusenoid RPE detachment, RPE thickening, and retinal pigmentary hyperreflective material were significantly associated with higher risk of progression to advanced AMD (ORs: 5.0-8.5) and NV (ORs: 10.8-17.2). Pigmentary hyperreflective material was associated with progression to GA (OR: 7.5, P = 0.009). Total retinal thickness, pigmentary hyperreflective material, nascent GA features, and choroidal vessel abnormalities were independently associated with progression to advanced AMD in a multivariate stepwise model.

Conclusions: Abnormalities in the photoreceptors, retinal thickness, RPE, and choroid were associated with higher risk of developing advanced AMD. These findings provide insights into disease progression, and may be helpful to identify earlier endpoints for clinical studies.
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http://dx.doi.org/10.1167/iovs.17-21696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512971PMC
July 2017

Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration.

Invest Ophthalmol Vis Sci 2016 Nov;57(14):5843-5855

Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland.

Purpose: Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD.

Methods: Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR-positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis.

Results: In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls.

Conclusions: The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease.
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http://dx.doi.org/10.1167/iovs.16-20049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098452PMC
November 2016

Periodontal Ehlers-Danlos Syndrome Is Caused by Mutations in C1R and C1S, which Encode Subcomponents C1r and C1s of Complement.

Am J Hum Genet 2016 Nov 13;99(5):1005-1014. Epub 2016 Oct 13.

Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Innsbruck 6020, Austria.

Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder characterized by early-onset periodontitis leading to premature loss of teeth, joint hypermobility, and mild skin findings. A locus was mapped to an approximately 5.8 Mb region at 12p13.1 but no candidate gene was identified. In an international consortium we recruited 19 independent families comprising 107 individuals with pEDS to identify the locus, characterize the clinical details in those with defined genetic causes, and try to understand the physiological basis of the condition. In 17 of these families, we identified heterozygous missense or in-frame insertion/deletion mutations in C1R (15 families) or C1S (2 families), contiguous genes in the mapped locus that encode subunits C1r and C1s of the first component of the classical complement pathway. These two proteins form a heterotetramer that then combines with six C1q subunits. Pathogenic variants involve the subunit interfaces or inter-domain hinges of C1r and C1s and are associated with intracellular retention and mild endoplasmic reticulum enlargement. Clinical features of affected individuals in these families include rapidly progressing periodontitis with onset in the teens or childhood, a previously unrecognized lack of attached gingiva, pretibial hyperpigmentation, skin and vascular fragility, easy bruising, and variable musculoskeletal symptoms. Our findings open a connection between the inflammatory classical complement pathway and connective tissue homeostasis.
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http://dx.doi.org/10.1016/j.ajhg.2016.08.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5097948PMC
November 2016

Histopathological Insights Into Choroidal Vascular Loss in Clinically Documented Cases of Age-Related Macular Degeneration.

JAMA Ophthalmol 2016 Nov;134(11):1272-1280

Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland.

Importance: Age-related macular degeneration (AMD) is a multifactorial disease with genetic and environmental factors contributing to risk. Histopathologic changes underlying AMD are not fully understood, particularly the relationship between choriocapillaris (CC) dysfunction and phenotypic variability of this disease.

Objective: To examine histopathologic changes in the CC of eyes with clinically documented AMD.

Design, Setting, And Participants: The study was designed in 2011. Tissues were collected post mortem (2012-2016), and histopathological images were obtained from participants enrolled in AMD studies since 1988. Clinical records and images were collected from participants as standard protocol. Eyes without AMD (n = 4) and eyes with early (n = 9), intermediate (n = 5), and advanced stages of AMD (geographic atrophy, n = 5; neovascular disease, n = 13) were evaluated. Choroidal vasculature was labeled using Ulex europaeus agglutinin lectin and examined using confocal microscopy.

Main Outcomes And Measures: A standardized classification system was applied to determine AMD stage. Ocular records and images were reviewed and histopathologic analyses performed. Viability of the choroidal vasculature was analyzed for each AMD stage.

Results: All participants were white. Fourteen were male, and 16 were female. The mean age was 90.5 years among AMD patients and 88.5 years among control participants. Submacular CC dropout without retinal pigment eipthelial (RPE) loss was observed in all cases with early stages of AMD. Higher vascular area loss for each AMD stage was observed compared with control participants: 20.5% in early AMD (95% CI, 11.2%-40.2%; P < .001), 12.5% in intermediate AMD (95% CI, 2.9%-21.4%; P = .01), 39.0% loss in GA (95% CI, 32.1%-45.4%; P < .001), and 38.2% loss in neovascular disease where RPE remained intact (95% CI, 27.7%-47.9%; P < .001). Hypercellular, apparent neovascular buds were adjacent to areas of CC loss in 22.2% of eyes with early AMD and 40% of eyes with intermediate AMD.

Conclusions And Relevance: Retinal pigment epithelial atrophy preceded CC loss in geographic atrophy, but CC loss occurred in the absence of RPE atrophy in 2 of 9 eyes with early-stage AMD. Given the cross-sectional nature of this study and the small number of eyes evaluated, definitive conclusions regarding this progression cannot be determined with certainty. We speculate that neovascular buds may be a precursor to neovascular disease. Hypoxic RPE resulting from reduced blood supply might upregulate production of vascular endothelial growth factor, providing the stimulus for neovascular disease.
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http://dx.doi.org/10.1001/jamaophthalmol.2016.3519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6014730PMC
November 2016

Response to AREDS supplements according to genetic factors: survival analysis approach using the eye as the unit of analysis.

Br J Ophthalmol 2016 Dec 28;100(12):1731-1737. Epub 2016 Jul 28.

Channing Division of Network Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts, USA.

Background/aims: The Age-Related Eye Disease Study (AREDS) reported the beneficial impact of antioxidant and zinc supplements on the risk of progression to advanced stages of age-related macular degeneration (AMD). We evaluated the role of genetic variants in modifying the relationship between supplementation and progression to advanced AMD.

Methods: Among 4124 eyes (2317 subjects with a genetic specimen), 882 progressed from no AMD, early or intermediate AMD to overall advanced disease, including geographic atrophy (GA) and neovascular disease (NV) over the course of the clinical trial. Survival analysis using individual eyes as the unit of analysis was used to assess the effect of supplementation on AMD outcomes, with adjustment for demographic, environmental, ocular and genetic covariates. Interaction effects between supplement groups and individual complement factor H (CFH) Y402H and age-related maculopathy susceptibility 2 (ARMS2) genotypes, and composite genetic risk groups combining the number of risk alleles for both loci, were evaluated for their association with progression.

Results: Among antioxidant and zinc supplement users compared with the placebo group, subjects with a non-risk genotype for CFH (TT) had a lower risk of progression to advanced AMD (HR: 0.55, 95% CI 0.32 to 0.95, p=0.033). No significant treatment effect was apparent among subjects who were homozygous for the CFH risk allele (CC). A protective effect was observed among high-risk ARMS2 (TT) carriers (HR: 0.52, 95% CI 0.33 to 0.82, p=0.005). Similar results were seen for the NV subtype but not GA.

Conclusions: The effectiveness of antioxidant and zinc supplementation appears to differ by genotype. Further study is needed to determine the biological basis for this interaction.

Trial Registration Number: NCT00594672, pre-results.
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http://dx.doi.org/10.1136/bjophthalmol-2016-308624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570490PMC
December 2016

Dietary folate, B vitamins, genetic susceptibility and progression to advanced nonexudative age-related macular degeneration with geographic atrophy: a prospective cohort study.

Am J Clin Nutr 2016 Apr;103(4):1135-44

Background: There is growing evidence of the importance of nutrition in age-related macular degeneration (AMD), but few studies have explored associations with folate and B vitamins. No effective therapeutic strategy for geographic atrophy (GA) is available, and prevention could be of great value.

Objective: We investigated associations between dietary folate, B vitamins, and progression to GA and whether these associations might be modified by genetic susceptibility.

Design: Among 2525 subjects (4663 eyes) in the Age-Related Eye Disease Study, 405 subjects (528 eyes) progressed to GA over 13 y. Folate and B vitamins were log transformed and calorie adjusted separately for men and women. Ten loci in 7 AMD genes [complement factor H, age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1, complement component 2, complement component 3, complement factor B, collagen type VIII α 1, and RAD51 paralog B] were examined. Survival analysis was used to assess associations between incident GA and dietary intake of folate and B vitamins. Interaction effects between these nutrients and genetic variation on AMD risk were also evaluated. Subjects with at least one eye free of advanced AMD at baseline were included in these analyses.

Results: There was a reduced risk of progression to GA with increasing intake of thiamin, riboflavin, and folate after adjusting for age, sex, and total energy intake (P-trend = 0.01, 0.03, and 0.001, respectively). After adjustment for demographic, behavioral, ocular, and genetic covariates, trends remained statistically significant for folate (P-trend = 0.007) and were borderline for thiamin (P-trend = 0.05). Riboflavin did not retain statistical significance (P-trend = 0.20). Folate was significantly associated with lower risk of incident GA among subjects homozygous for the complement component 3 (C3) R102G rs2230199 nonrisk genotype (CC) (HR = 0.43; 95% CI: 0.27, 0.70; P = 0.0005) but not subjects carrying the risk allele (G) (P = 0.76). Neither folate nor any B vitamin was significantly associated with neovascular AMD.

Conclusions: High folate intake was associated with a reduced risk of progression to GA. This relation could be modified by genetic susceptibility, particularly related to the C3 genotype. This trial was registered at clinicaltrials.gov as NCT00594672.
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http://dx.doi.org/10.3945/ajcn.115.117606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807698PMC
April 2016

On the use of differential solubility in aqueous ethanol solutions to narrow the DP range of food-grade starch hydrolysis products.

Food Chem 2016 Apr 10;197(Pt A):872-80. Epub 2015 Nov 10.

Department of Food Science and Technology, Oregon State University, Corvallis, OR, USA. Electronic address:

Considerable research is focused on understanding the functionality of starch hydrolysis products (SHP) consisting of glucose, maltose, maltooligosaccharides (MOS), and maltopolysaccharides (MPS). A confounding factor in this research is the high molecular dispersity of commercially available SHP. The study presented herein characterizes a flexible fractionation approach for lowering the dispersity of such products. This was accomplished by fractionating a corn syrup solids (CSS) preparation based on the differential solubility of its component saccharides in aqueous-ethanol solutions. Products obtained from selected fractionations were characterized with respect to degree of polymerization (DP; liquid chromatography), dextrose equivalency (reducing sugar assays), and prevalence of branching (NMR). Glucose and maltose were preferentially removed from CSS using high (⩾90%) ethanol extractants. Preparations with relatively narrow ranges of MOS, lower DP MPS, and higher DP MPS were obtained through repetitive 70%-ethanol extractions. Linear, as opposed to branched, MOS and MPS were preferentially extracted under all conditions tested.
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http://dx.doi.org/10.1016/j.foodchem.2015.10.120DOI Listing
April 2016

Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study.

Am J Clin Nutr 2015 Nov 21;102(5):1196-206. Epub 2015 Oct 21.

Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center, Boston, MA;

Background: Adherence to a Mediterranean-type diet is linked to a lower risk of mortality and chronic disease, but the association with the progression of age-related macular degeneration (AMD) and genetic susceptibility is unknown.

Objective: We examined the association of adherence to the Mediterranean diet and genetic susceptibility with progression to advanced AMD.

Design: Among 2525 subjects in the AREDS (Age-Related Eye Disease Study), 1028 eyes progressed to advanced AMD over 13 y. Baseline data for demographic and behavioral covariates were collected by using questionnaires. Dietary data were collected from food-frequency questionnaires. The alternate Mediterranean diet (aMeDi) score (range: 0-9) was constructed from individual intakes of vegetables, fruit, legumes, whole grains, nuts, fish, red and processed meats, alcohol, and the ratio of monounsaturated to saturated fats. Ten genetic loci in 7 genes [complement factor H (CFH), age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 (ARMS2/HTRA1), complement component 2 (C2), complement factor B (CFB), complement component 3 (C3), collagen type VIII α 1 (COL8A1), and RAD51 paralog B (RAD51B)] were examined. Survival analysis was used to assess individual eyes for associations between incident AMD and aMeDi score, as well as interaction effects between aMeDi score and genetic variation on risk of AMD.

Results: A high aMeDi score (score of 6-9) was significantly associated with a reduced risk of progression to advanced AMD after adjustment for demographic, behavioral, ocular, and genetic covariates (HR: 0.74; 95% CI: 0.61, 0.91; P-trend = 0.007). The aMeDi score was significantly associated with a lower risk of incident advanced AMD among subjects carrying the CFH Y402H nonrisk (T) allele (P-trend = 0.0004, P-interaction = 0.04). The aMeDi score was not associated with AMD among subjects who were homozygous for the risk (C) allele.

Conclusion: Higher adherence to a Mediterranean diet was associated with reduced risk of progression to advanced AMD, which may be modified by genetic susceptibility. This trial was registered at clinicaltrials.gov as NCT00594672.
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http://dx.doi.org/10.3945/ajcn.115.111047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4625588PMC
November 2015

Risk Prediction for Progression of Macular Degeneration: 10 Common and Rare Genetic Variants, Demographic, Environmental, and Macular Covariates.

Invest Ophthalmol Vis Sci 2015 Apr;56(4):2192-202

Channing Division of Network Medicine, Harvard Medical School, Harvard University, Boston, Massachusetts, United States.

Purpose: To determine the association between genetic variants and transition to advanced age-related macular degeneration (AMD), and to develop a predictive model and online application to assist in clinical decision making.

Methods: Among 2951 subjects in the Age-Related Eye Disease Study, 834 progressed from no AMD, early AMD, or intermediate AMD to advanced disease. Survival analysis was used to assess which genetic, demographic, environmental, and macular covariates were independently associated with progression. Attributable risk, area under the curve statistics (AUCs), and reclassification odds ratios (ORs) were calculated. Split-sample validation was performed. An online risk calculator was developed and is available in the public domain at www.seddonamdriskscore.org.

Results: Ten genetic loci were independently associated with progression, including newly identified rare variant C3 K155Q (hazard ratio: 1.7, 95% confidence interval: 1.2-2.5, P = 0.002), three variants in CFH, and six variants in ARMS2/HTRA1, CFB, C3, C2, COL8A1, and RAD51B. Attributable risk calculations revealed that 80% of incident AMD is attributable to genetic factors, adjusting for demographic covariates and baseline macular phenotypes. In a model including 10 genetic loci, age, sex, education, body mass index, smoking, and baseline AMD status, the AUC for progression to advanced AMD over 10 years was 0.911. Split-sample validation showed a similar AUC (0.907). Reclassification analyses indicated that subjects were categorized into a more accurate risk category if genetic information was included (OR 3.2, P < 0.0001).

Conclusions: Rare variant C3 K155Q was independently associated with AMD progression. The comprehensive model may be useful for identifying and monitoring high-risk patients, selecting appropriate therapies, and designing clinical trials.
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http://dx.doi.org/10.1167/iovs.14-15841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405097PMC
April 2015
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