Association Between Dietary Intake and Function in Amyotrophic Lateral Sclerosis.

Importance: There is growing interest in the role of nutrition in the pathogenesis and progression of amyotrophic lateral sclerosis (ALS). Objective: To evaluate the associations between nutrients, individually and in groups, and ALS function and respiratory function at diagnosis. Design, setting, and participants: A cross-sectional baseline analysis of the Amyotrophic Lateral Sclerosis Multicenter Cohort Study of Oxidative Stress study was conducted from March 14, 2008, to February 27, 2013, at 16 ALS clinics throughout the United States among 302 patients with ALS symptom duration of 18 months or less. Exposures: Nutrient intake, measured using a modified Block Food Frequency Questionnaire (FFQ). Main outcomes and measures: Amyotrophic lateral sclerosis function, measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), and respiratory function, measured using percentage of predicted forced vital capacity (FVC). Results: Baseline data were available on 302 patients with ALS (median age, 63.2 years [interquartile range, 55.5-68.0 years]; 178 men and 124 women). Regression analysis of nutrients found that higher intakes of antioxidants and carotenes from vegetables were associated with higher ALSFRS-R scores or percentage FVC. Empirically weighted indices using the weighted quantile sum regression method of "good" micronutrients and "good" food groups were positively associated with ALSFRS-R scores (β [SE], 2.7 [0.69] and 2.9 [0.9], respectively) and percentage FVC (β [SE], 12.1 [2.8] and 11.5 [3.4], respectively) (all P < .001). Positive and significant associations with ALSFRS-R scores (β [SE], 1.5 [0.61]; P = .02) and percentage FVC (β [SE], 5.2 [2.2]; P = .02) for selected vitamins were found in exploratory analyses. Conclusions and relevance: Antioxidants, carotenes, fruits, and vegetables were associated with higher ALS function at baseline by regression of nutrient indices and weighted quantile sum regression analysis. We also demonstrated the usefulness of the weighted quantile sum regression method in the evaluation of diet. Those responsible for nutritional care of the patient with ALS should consider promoting fruit and vegetable intake since they are high in antioxidants and carotenes

A Cohort study evaluation of maternal PCB exposure related to time to pregnancy in daughters

Background: Polychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants. Developmental exposures are suspected to impact reproduction. Analysis of mixtures of PCBs may be problematic as components have a complex correlation structure, and along with limited sample sizes, standard regression strategies are problematic. We compared the results of a novel, empirical method to those based on categorization of PCB compounds by (1) hypothesized biological activity previously proposed and widely applied, and (2) degree of ortho- substitution (mono, di, tri), in a study of the relation of maternal serum PCBs and daughter’s time to pregnancy. Methods: We measured PCBs in maternal serum samples collected in the early postpartum in 289 daughters in the Child Health and Development Studies birth cohort. We queried time to pregnancy in these daughters 28–31 years later. We applied a novel weighted quantile sum approach to find the bad-actor compounds in the PCB mixture found in maternal serum. The approach includes empirical estimation of the weights through a bootstrap step which accounts for the variation in the estimated weights. Results: Bootstrap analyses indicated the dominant functionality groups associated with longer TTP were the dioxin-like, anti-estrogenic group (average weight, 22%) and PCBs not previously classified by biological activity (54%). In contrast, the unclassified PCBs were not important in the association with shorter TTP, where the anti-estrogenic groups and the PB-inducers group played a more important role (60% and 23%, respectively). The highly chlorinated PCBs (average weight, 89%) were mostly associated with longer TTP; in contrast, the degree of chlorination was less discriminating for shorter TTP. Finally, PCB 56 was associated with the strongest relationship with TTP with a weight of 47%. Conclusions: Our empirical approach found some associations previously identified by two classification schemes, but also identified other bad actors. This empirical method can generate hypotheses about mixture effects and mechanisms and overcomes some of the limitations of standard regression techniques

Higher blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations correlate with lower olfactory scores in essential tremor

Harmane (1-methyl-9H-pyrido[3,4-b]indole), a neurotoxin, may be an environmental risk factor for essential tremor (ET). Harmane and related chemicals are toxic to the cerebellum. Whether it is through this mechanism (cerebellar toxicity) that harmane leads to ET is unknown. Impaired olfaction may be a feature of cerebellar disease

What are the determinants of childhood infections in India’s peri-urban slums? A case study of eight cities

BACKGROUND: Respiratory Tract Infections (RTIs) and Gastro-Intestinal (GI) infections are the leading causes of child mortality and morbidity. This study investigates the associations between the individual, household and slum-level determinants of children’s health and vulnerability to RTIs and GI infections in peri-urban slums in India; an area of research interest at the Childhood Infections and Pollution Consortium. METHODS: The 2015–16 Indian National Family Health Survey was used for data analysis on children aged 0–5 years. NFHS-4 includes data on slums in eight Indian cities, including Delhi, Meerut, Kolkata, Indore, Mumbai, Nagpur, Hyderabad, Chennai. The outcome variables, having fever and cough (FeCo) and diarrhoea in the last two weeks, were used to define the phenotype of infections; for this analysis fever and cough were measures of RTIs and diarrhoea was used to measure GI infections. Exposures considered in this study include variables at the individual, household and slum level and were all informed by existing literature. Multilevel models were used to estimate the association between exposures and outcomes variables; a prior of Cauchy distribution with a scale of 2.5 was selected when building the multilevel logistic models. RESULTS: The total sample size of the number of children included in the analysis was n = 1,424. Data was imputed to account for missingness, and the original and imputed sample showing similar distributions. Results showed that diarrhoea and FeCo were both found to be more present in younger children than older children by a few months. In fixed effects, the odds of developing FeCo were higher if the mother perceives the child was born smaller than average (AOR 4.41, 1.13–17.17, P<0.05) at individual level. On the other hand, the odds of the diarrhoea outcome were lower if the child was older (AOR 0.97, 0.96–0.98, P<0.05) at individual level, and household’s water source was public tap or standpipe (AOR 0.54, 0.31–0.96, P<0.05) at household level. CONCLUSION: The determinants of health, both social and related to health care, at all levels demonstrated linkages to child morbidity in RTIs and GI infections. The empirical evidence highlights the need for contextualised ideas at each level, including one health approach when designing interventions to improve child health

Dietary epidemiology of essential tremor: meat consumption and meat cooking pactices

Background/Aim: Harmane [1-methyl-9H-pyrido(3,4-b)indole] is a tremor-producing neurotoxin. Blood harmane concentrations are elevated in essential tremor (ET) patients for unclear reasons. Potential mechanisms include increased dietary harmane intake (especially through well-cooked meat) or genetic-metabolic factors. We tested the hypothesis that meat consumption and level of meat doneness are higher in ET cases than in controls. Methods: Detailed data were collected using the Lawrence Livermore National Laboratory Meat Questionnaire. Results: Total current meat consumption was greater in men with than without ET (135.3 ± 71.1 vs. 110.6 ± 80.4 g/day, p = 0.03) but not in women with versus without ET (80.6 ± 50.0 vs. 79.3 ± 51.0 g/day, p = 0.76). In an adjusted logistic regression analysis in males, higher total current meat consumption was associated with ET (OR = 1.006, p = 0.04, i.e., with 10 additional g/day of meat, odds of ET increased by 6%). Male cases had higher odds of being in the highest than lowest quartile of total current meat consumption (adjusted OR = 21.36, p = 0.001). Meat doneness level was similar in cases and controls. Conclusion: This study provides evidence of a dietary difference between male ET cases and male controls. The etiological ramifications of these results warrant additional investigation

Cancer and blood concentrations of the comutagen harmane in essential tremor

Blood concentrations of harmane, a tremor-producing neurotoxin, are elevated in essential tremor (ET). Harmane is also a comutagen. Using a case-control design, we compared the prevalence of cancer in ET cases vs. controls, and determined whether blood harmane concentrations are elevated among ET cases with cancer. 66/267 (24.7%) ET cases vs. 55/331 (16.6%) controls had cancer (adjusted OR 1.52, 95% CI 1.01 — 2.30, P = 0.04). Among specific cancer types, colon cancer was more prevalent in ET cases than controls (2.6% vs. 0.6%, P = 0.04). Log blood harmane concentration was higher in ET cases vs. controls (P = 0.02) and in participants with vs. without cancer (P = 0.02). Log blood harmane concentration was highest in ET cases with cancer when compared with other groups (P = 0.009). These links between cancer and ET and between high blood harmane and cancer in ET deserve further study

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors likely play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. In 2002, we demonstrated elevated blood harmane concentrations in an initial sample of 100 ET cases compared to 100 controls. Between 2002 and 2007, we assembled a new and larger sample of ET cases and controls. We now attempt to replicate our previous findings. Cases and controls were frequency-matched on age, gender, and race. Blood harmane concentrations were quantified by high-performance liquid chromatography. Subjects comprised 150 ET cases and 135 controls (mean age 65.3 ± 15.5 vs. 65.5 ± 14.2 years, p = 0.94). Mean log blood harmane concentration was ∼50% higher in cases than controls (0.50 ± 0.54 g−10/ml vs. 0.35 ± 0.62 g−10/ml, p = 0.038). In a logistic regression analysis, log blood harmane concentration was associated with ET (ORadjusted 1.56, 95% CI 1.01–2.42, p = 0.04), and odds of ET was 1.90 (95% CI 1.07–3.39, p = 0.029) in the highest versus lowest log blood harmane tertile. Log blood harmane was highest in ET cases with familial ET (0.53 ± 0.57 g−10/ml), intermediate in cases with sporadic ET (0.43 ± 0.45 g−10/ml) and lowest in controls (0.35 ± 0.62 g−10/ml) (test for trend, p = 0.026). Blood harmane appears to be elevated in ET. The higher concentrations in familial ET suggests that the mechanism may involve genetic factors