High-caloric diets may slow the progression of amyotrophic lateral sclerosis; however, key macronutrients have not been identified. We examined whether dietary macronutrients are associated with the ...rate of progression and length of survival among the prospective cohort study participants.
Participants with a confirmed diagnosis of sporadic amyotrophic lateral sclerosis enrolled in the Multicenter Cohort Study of Oxidative Stress were included (n = 304). We evaluated baseline macronutrient intake assessed by food frequency questionnaire in relation to change in revised amyotrophic lateral sclerosis functional rating scale total-score, and tracheostomy-free survival using linear regression and Cox proportional hazard models. Baseline age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised amyotrophic lateral sclerosis functional rating scale total-score, and forced vital capacity were included as covariates.
Baseline higher glycemic index and load were associated with less decline of revised amyotrophic lateral sclerosis functional rating scale total score at 3-month follow-up (β = -0.13, 95% CI -0.2, -0.01, p = 0.03) and (β = -0.01, 95% CI -0.03, -0.0007, p = 0.04), respectively. Glycemic index second-quartile, third-quartile, and fourth-quartile groups were associated with less decline at 3 months by 1.9 (95% CI -3.3, -0.5, p = 0.008), 2.0 (95% CI -3.3, -0.6, p = 0.006), and 1.6 (95% CI -3.0, -0.2, p = 0.03) points compared with the first-quartile group; the glycemic load fourth-quartile group had 1.4 points less decline compared with the first-quartile group (95% CI -2.8, 0.1, p = 0.07). Higher glycemic index was associated with a trend toward longer tracheostomy-free survival (HR 0.97, 95% CI 0.93, 1.00, p = 0.07).
Higher dietary glycemic index and load are associated with slower disease progression in amyotrophic lateral sclerosis. ANN NEUROL 2024;95:217-229.
Background
Prenatal exposure to opioids (PEO) is a worldwide public health issue. Opioids cross the placental barrier and may affect the developing foetus and the birth outcomes.
Objectives
This ...review aimed to explore newborns’ weight, length and head circumference, preterm birth, and perinatal death as primary outcomes in relation to PEO. The secondary outcomes were gestational age at birth, Apgar scores and length of hospitalisation after delivery.
Data sources
PubMed, Embase, PsycInfo and the Web of Science.
Study selection and data extraction
Inclusion criteria were (i) cohort, case‐control or cross‐sectional peer‐reviewed studies published in English through 1 March 2021; (ii) comparing outcomes between prenatal exposed and unexposed groups to opioids (prescribed or obtained illegally). Exclusion criteria were foetal alcohol syndrome and non‐opioid primary exposure.
Synthesis
Data were extracted by two authors. The Newcastle‐Ottawa Quality Assessment Scale was used for study quality assessment. Due to heterogeneity across studies, we used random effects models to obtain pooled standardised mean difference (SMD), pooled risk ratio (RR) and 95% confidence interval (CI).
Results
Data from 80 studies were extracted. In meta‐analyses, opioid‐exposed neonates had lower birthweight (SMD −0.77, 95% CI −0.90, −0.64, I2 = 82%), smaller head circumference (SMD −0.67, 95% CI −0.86, −0.48, I2 = 84%), shorter birth length (SMD −0.97, 95% CI −1.24, −0.70, I2 = 91%) and gestational age (SMD −0.45, 95% CI −0.60, −0.30, I2 = 80%) than unexposed neonates. Pooled risks of neonatal death and preterm birth were higher among opioid‐exposed compared to unexposed neonates (RR 4.05, 95% CI 2.12, 7.72, I2 = 73%; and RR 1.92, 95% CI 1.57, 2.35, I2 = 99%).
Conclusions
We found increased risks of adverse birth outcomes in relation to PEO. Caution should be used in interpreting the findings, as many studies were rated as poor quality, and with substantial inter‐study heterogeneity. Future studies should ensure comparability of opioid‐exposed and ‐unexposed group to strengthen internal validity.
In risk evaluation, the effect of mixtures of environmental chemicals on a common adverse outcome is of interest. However, due to the high dimensionality and inherent correlations among chemicals ...that occur together, the traditional methods (e.g. ordinary or logistic regression) suffer from collinearity and variance inflation, and shrinkage methods have limitations in selecting among correlated components. We propose a weighted quantile sum (WQS) approach to estimating a body burden index, which identifies "bad actors" in a set of highly correlated environmental chemicals. We evaluate and characterize the accuracy of WQS regression in variable selection through extensive simulation studies through sensitivity and specificity (i.e., ability of the WQS method to select the bad actors correctly and not incorrect ones). We demonstrate the improvement in accuracy this method provides over traditional ordinary regression and shrinkage methods (lasso, adaptive lasso, and elastic net). Results from simulations demonstrate that WQS regression is accurate under some environmentally relevant conditions, but its accuracy decreases for a fixed correlation pattern as the association with a response variable diminishes. Nonzero weights (i.e., weights exceeding a selection threshold parameter) may be used to identify bad actors; however, components within a cluster of highly correlated active components tend to have lower weights, with the sum of their weights representative of the set. Supplementary materials accompanying this paper appear on-line.
Telomere length (TL) limits somatic cell replication. However, the shortest among the telomeres in each nucleus, not mean TL, is thought to induce replicative senescence. Researchers have relied on ...Southern blotting (SB), and techniques calibrated by SB, for precise measurements of TL in epidemiological studies. However, SB provides little information on the shortest telomeres among the 92 telomeres in the nucleus of human somatic cells. Therefore, little is known about the accumulation of short telomeres with age, or whether it limits the human lifespan. To fill this knowledge void, we used the Telomere‐Shortest‐Length‐Assay (TeSLA), a method that tallies and measures single telomeres of all chromosomes. We charted the age‐dependent buildup of short telomeres (<3 kb) in human hematopoietic cells from 334 individuals (birth‐89 years) from the general population, and 18 patients with dyskeratosis congenita‐telomere biology disorders (DC/TBDs), whose hematopoietic cells have presumably reached or are close to their replicative limit. For comparison, we also measured TL with SB. We found that in hematopoietic cells, the buildup of short telomeres occurs in parallel with the shortening with age of mean TL. However, the proportion of short telomeres was lower in octogenarians from the general population than in patients with DC/TBDs. At any age, mean TL was longer and the proportion of short telomeres lower in females than in males. We conclude that though converging to the TL‐mediated replicative limit, hematopoietic cell telomeres are unlikely to reach this limit during the lifespan of most contemporary humans.
Population studies have principally focused on the role of mean telomere length in human health and longevity. The availability of new telomere length measurement techniques enables examining the relations between the shortest telomeres and human diseases.
Background
The prenatal period is a period of vulnerability during which neurotoxic exposures exert persistent changes in brain development and behavior. Polybrominated diphenyl ethers (PBDEs), used ...as flame retardants in commercial products, are known to be developmental neurotoxicants. PBDEs were phased out of use in the United States a decade ago, but exposure remains widespread due to their release from existing products and biopersistence. Despite consistent animal and epidemiological evidence of developmental neurotoxicity, the neural substrates linking prenatal PBDE serum concentrations to impaired neurodevelopment are poorly understood.
Methods
In the present study, we used resting state functional magnetic resonance imaging (fMRI) to examine associations between prenatal PBDE concentrations measured in maternal serum and intrinsic functional network organization (i.e., global and local efficiency; estimated using a graph‐theoretical approach) in 5‐year‐old children (n = 34). We explored whether PBDE serum concentrations were associated with executive functioning (EF) assessed using a parent‐report questionnaire (BRIEF‐P) (n = 106) and whether changes in intrinsic functional network organization linked the association between prenatal PBDE serum concentrations and EF problems.
Results
Children with higher prenatal PBDE serum concentrations showed: (a) increased global efficiency of brain areas involved in visual attention (e.g., inferior occipital gyrus) (β's = .01, FDR‐corrected p's ≤ .05); (b) more reported EF problems (β's = .001, FDR‐corrected p's ≤ .05). Higher global efficiency of brain areas involved in visual attention was associated with more EF problems (β's = .01, FDR‐corrected p's < .05).
Conclusions
Intrinsic functional network organization of visual attention brain areas linked prenatal PBDE concentrations to EF problems in childhood. Visual attention may contribute to the development of higher‐order cognitive functions, such as EF, which could be explored in future studies.
To evaluate associations between work-related stress, stressful life events, and perceived stress and semen quality.
Cross-sectional analysis.
Northern California.
193 men from the Child Health and ...Development Studies evaluated between 2005-2008.
None.
Measures of stress including job strain, perceived stress, and stressful life events; outcome measures of sperm concentration, percentage of motile sperm, and percentage of morphologically normal sperm.
We found an inverse association between perceived stress score and sperm concentration (estimated coefficient b=-0.09×10(3)/mL; 95% confidence interval CI=-0.18, -0.01), motility (b=-0.39; 95% CI=-0.79, 0.01), and morphology (b=-0.14; 95% CI, -0.25, -0.04) in covariate-adjusted linear regression analyses. Men who experienced two or more stressful life events in the past year compared with no stressful events had a lower percentage of motile sperm (b=-8.22; 95% CI, -14.31, -2.13) and a lower percentage of morphologically normal sperm (b=-1.66; 95% CI, -3.35, 0.03) but a similar sperm concentration. Job strain was not associated with semen parameters.
In this first study to examine all three domains of stress, perceived stress and stressful life events but not work-related stress were associated with semen quality.
Sporadic amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the ...pro-oxidative/antioxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting that multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly supports the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis.
Exposure to manganese via inhalation has long been known to elicit neurotoxicity in adults, but little is known about possible consequences of exposure via drinking water. In this study, we report ...results of a cross-sectional investigation of intellectual function in 142 10-year-old children in Araihazar, Bangladesh, who had been consuming tube-well water with an average concentration of 793 μg Mn/L and 3 μg arsenic/L. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children's intellectual function was assessed on tests drawn from the Wechsler Intelligence Scale for Children, version III, by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead, As, Mn, and hemoglobin concentrations. After adjustment for sociodemographic covariates, water Mn was associated with reduced Full-Scale, Performance, and Verbal raw scores, in a dose-response fashion; the low level of As in water had no effect. In the United States, roughly 6% of domestic household wells have Mn concentrations that exceed 300 μg Mn/L, the current U.S. Environmental Protection Agency lifetime health advisory level. We conclude that in both Bangladesh and the United States, some children are at risk for Mn-induced neurotoxicity.
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