Inconsistent Effects of Iron-Folic Acid and/or Zinc Supplementation on the Cognitive Development of Infants

Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 µg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (≥85% correct; A-not-B), deteriorated performance (<75% correct and >1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio=0.67; 95% confidence interval 0.46-0.97; p<0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p>0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors

The Role of Zinc and Iron-Folic Acid Supplementation on Early Child Temperament and Eating Behaviors in Rural Nepal: A Randomized Controlled Trial

Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4–17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (β = −0.03, 95% CI −0.3, 0.2) or iron-folic acid and non-iron-folic acid (β = 0.08, 95% CI −0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (β = −0.14, 95% CI −0.3, 0.04) or between iron and non-iron eating behavior scores (β = −0.11, 95% CI −0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (β = −0.3, 95% CI −0.6, −0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation

Ocular syphilis resurgence in an urban underserved community in the United States

AIM: To evaluate the clinical characteristics, demographics, and visual outcomes of patients with ocular syphilis at an urban hospital to increase awareness and assist in earlier diagnosis and treatment of the resurgent disease. METHODS: A retrospective chart review was performed on patients with ICD-9 and ICD-10 diagnosis codes correlating with syphilis or syphilis-related ocular diseases between 2010 and 2019. Variables evaluated included age, gender, race, vision, ocular findings, human immunodeficiency virus (HIV) status and men who have sex with men status, recreational drug and alcohol use. RESULTS: Ocular syphilis was diagnosed in 40 patients (53 eyes) of a total of 229 patients who tested positive for syphilis via serum and/or cerebrospinal fluid treponemal testing from 2010-2019. Among patients with ocular syphilis, most patients were males, aged 45 or above and Black, and had no diagnosed HIV infection. Approximately 50% patients had 20/40 vision or better. Nearly 50% had non-granulomatous anterior uveitis as their initial presentation, and 49% of patients had involvement of the posterior segment. Neovascular glaucoma (5.7%), papillitis (7.5%), vasculitis (5.7%), and retinal detachment (5.7%) were rarer presentations of the disease and were associated with a poorer visual prognosis. CONCLUSION: Given the increased prevalence and protean manifestations of syphilis, early diagnosis and treatment are paramount. More studies on ocular syphilis are warranted to understand this resurging disease

Inconsistent Effects of Iron-Folic Acid and/or Zinc Supplementation on the Cognitive Development of Infants

Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 \ub5g of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance ( 6585% correct; A-not-B), deteriorated performance (&lt;75% correct and &gt;1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio=0.67; 95% confidence interval 0.46-0.97; p&lt;0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p&gt;0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors

Short-term Succinic Acid Treatment Mitigates Cerebellar Mitochondrial OXPHOS Dysfunction, Neurodegeneration and Ataxia in a Purkinje-specific Spinocerebellar Ataxia Type 1 (SCA1) Mouse Model

Mitochondrial dysfunction plays a significant role in neurodegenerative disease including ataxias and other movement disorders, particularly those marked by progressive degeneration in the cerebellum. In this study, we investigate the role of mitochondrial oxidative phosphorylation (OXPHOS) deficits in cerebellar tissue of a Purkinje cell-driven spinocerebellar ataxia type 1 (SCA1) mouse. Using RNA sequencing transcriptomics, OXPHOS complex assembly analysis and oxygen consumption assays, we report that in the presence of mutant polyglutamine-expanded ataxin-1, SCA1 mice display deficits in cerebellar OXPHOS complex I (NADH-coenzyme Q oxidoreductase). Complex I genes are upregulated at the time of symptom onset and upregulation persists into late stage disease; yet, functional assembly of complex I macromolecules are diminished and oxygen respiration through complex I is reduced. Acute treatment of postsymptomatic SCA1 mice with succinic acid, a complex II (succinate dehydrogenase) electron donor to bypass complex I dysfunction, ameliorated cerebellar OXPHOS dysfunction, reduced cerebellar pathology and improved motor behavior. Thus, exploration of mitochondrial dysfunction and its role in neurodegenerative ataxias, and warrants further investigation

The impact of food assistance on food insecure populations during conflict: Evidence from a quasi-experiment in Mali

Mali, a vast landlocked country at the heart of West Africa in the Sahel region, is one of the least developed and most food insecure countries in the world. Mali suffered from a series of political, constitutional and military crises since January 2012, including the loss of government control of northern territories from April 2012 until January 2013. A range of humanitarian aid interventions were scaled up in response to these complex crises. In this study, we exploit data from a unique pre-crisis baseline to evaluate the impact of humanitarian aid on the food security of rural populations. We design a quasi-experimental study based on two survey rounds, five years apart, in the Mopti region in Northern Mali. Data was collected from 66 communities randomly selected from within food-insecure districts. Study outcomes include household expenditures and food consumption and a proxy for child nutritional status (height measurements). We estimate program impact by combining propensity score matching and difference-in-difference. Food assistance was found to increase household non-food and food expenditures and micro-nutrient availability. Disaggregating by degree of conflict exposure showed that the effects on children's height and caloric and micro-nutrient consumption were mostly concentrated in areas not in the immediate vicinity of the conflict, unlike the increase in food expenditures that were driven by households located in close proximity to armed groups. The effects were also concentrated on households receiving at least two forms of food assistance. In villages where armed groups were present, food assistance improved household zinc consumption and also appeared to support food expenditures. Food transfers are thus found to exert a protective effect among food insecure population in conflict context

Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening

Intestinal Epithelial-Derived TAK1 Signaling Is Essential for Cytoprotection against Chemical-Induced Colitis

We have previously reported that intestinal epithelium-specific TAK1 deleted mice exhibit severe inflammation and mortality at postnatal day 1 due to TNF-induced epithelial cell death. Although deletion of TNF receptor 1 (TNFR1) can largely rescue those neonatal phenotypes, mice harboring double deletion of TNF receptor 1 (TNFR1) and intestinal epithelium-specific deletion of TAK1 (TNFR1KO/TAK1(IE)KO) still occasionally show increased inflammation. This indicates that TAK1 is important for TNF-independent regulation of intestinal integrity.In this study, we investigated the TNF-independent role of TAK1 in the intestinal epithelium. Because the inflammatory conditions were sporadically developed in the double mutant TNFR1KO/TAK1(IE)KO mice, we hypothesize that epithelial TAK1 signaling is important for preventing stress-induced barrier dysfunction. To test this hypothesis, the TNFR1KO/TAK1(IE)KO mice were subjected to acute colitis by administration of dextran sulfate sodium (DSS). We found that loss of TAK1 significantly augments DSS-induced experimental colitis. DSS induced weight loss, intestinal damages and inflammatory markers in TNFR1KO/TAK1(IE)KO mice at higher levels compared to the TNFR1KO control mice. Apoptosis was strongly induced and epithelial cell proliferation was decreased in the TAK1-deficient intestinal epithelium upon DSS exposure. These suggest that epithelial-derived TAK1 signaling is important for cytoprotection and repair against injury. Finally, we showed that TAK1 is essential for interleukin 1- and bacterial components-induced expression of cytoprotective factors such as interleukin 6 and cycloxygenase 2.Homeostatic cytokines and microbes-induced intestinal epithelial TAK1 signaling regulates cytoprotective factors and cell proliferation, which is pivotal for protecting the intestinal epithelium against injury

The First Post-Kepler Brightness Dips of KIC 8462852

We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process

Genome-Wide Diet-Gene Interaction Analyses for Risk of Colorectal Cancer

Dietary factors, including meat, fruits, vegetables and fiber, are associated with colorectal cancer; however, there is limited information as to whether these dietary factors interact with genetic variants to modify risk of colorectal cancer. We tested interactions between these dietary factors and approximately 2.7 million genetic variants for colorectal cancer risk among 9,287 cases and 9,117 controls from ten studies. We used logistic regression to investigate multiplicative gene-diet interactions, as well as our recently developed Cocktail method that involves a screening step based on marginal associations and gene-diet correlations and a testing step for multiplicative interactions, while correcting for multiple testing using weighted hypothesis testing. Per quartile increment in the intake of red and processed meat were associated with statistically significant increased risks of colorectal cancer and vegetable, fruit and fiber intake with lower risks. From the case-control analysis, we detected a significant interaction between rs4143094 (10p14/near GATA3) and processed meat consumption (OR = 1.17; p = 8.7E-09), which was consistently observed across studies (p heterogeneity = 0.78). The risk of colorectal cancer associated with processed meat was increased among individuals with the rs4143094-TG and -TT genotypes (OR = 1.20 and OR = 1.39, respectively) and null among those with the GG genotype (OR = 1.03). Our results identify a novel gene-diet interaction with processed meat for colorectal cancer, highlighting that diet may modify the effect of genetic variants on disease risk, which may have important implications for prevention. © 2014