ABSTRACT
Chemicals in food are widely used leading to significant human exposure. Allura Red AC (AR) is a highly common synthetic colorant; however, little is known about its impact on colitis. Here, we show chronic exposure of AR at a dose found in commonly consumed dietary products exacerbates experimental models of colitis in mice. While intermittent exposure is more akin to a typical human exposure, intermittent exposure to AR in mice for 12 weeks, does not influence susceptibility to colitis. However, exposure to AR during early life primes mice to heightened susceptibility to colitis. In addition, chronic exposure to AR induces mild colitis, which is associated with elevated colonic serotonin (5-hydroxytryptamine; 5-HT) levels and impairment of the epithelial barrier function via myosin light chain kinase (MLCK). Importantly, chronic exposure to AR does not influence colitis susceptibility in mice lacking tryptophan hydroxylase 1 (TPH1), the rate limiting enzyme for 5-HT biosynthesis. Cecal transfer of the perturbed gut microbiota by AR exposure worsens colitis severity in the recipient germ-free (GF) mice. Furthermore, chronic AR exposure elevates colonic 5-HT levels in naïve GF mice. Though it remains unknown whether AR has similar effects in humans, our study reveals that chronic long-term exposure to a common synthetic colorant promotes experimental colitis via colonic 5-HT in gut microbiota-dependent and -independent pathway in mice.

ABSTRACT
Processed foods, accounting for most consumable food categories today, contain considerable amounts of food additives. Food additives are substances added to food products to improve taste, consistency, appearance, or shelf life. Various food additives, such as phthalates, bisphenol A, tartrazine, erythrosine, artificial sweeteners, and parabens, have been identified as potential sources of endocrine-disrupting chemicals (EDCs) in processed foods. EDCs are substances that frequently interfere with the regular functioning of the endocrine system, creating an unusual environment in the biological system, which leads to adverse health effects such as the disruption of hormone synthesis, receptor binding, and signal transduction pathways, as well as energy metabolic homeostatic disorders which potentially increasing the risk of obesity, type-2 diabetes, cardiometabolic diseases and may also trigger allergic reactions. Consequently, they can also impact mammary gland development, and reproductive function, further leading to developmental abnormalities. This review aims to insights into the various food additives that act as potential endocrine-disrupting chemicals (EDCs) and to describe their applications in the food industry, as well as the failure of hormonal homeostatic mechanisms, which eventually result in hazardous health effects. It also outlines strategies to reduce the use of food additives and suggests alternative additives with minimal or no endocrine-disrupting properties, highlighting their importance for maintaining human health.

ABSTRACT
The incidence of colorectal cancer (CRC) among young people has been on the rise for the past four decades and its underlying causes are only just starting to be uncovered. Recent studies suggest that consuming ultra-processed foods and pro-inflammatory diets may be contributing factors. The increase in the use of synthetic food colors in such foods over the past 40 years, including the common synthetic food dye Allura Red AC (Red 40), coincides with the rise of early-onset colorectal cancer (EOCRC). As these ultra-processed foods are particularly appealing to children, there is a growing concern about the impact of synthetic food dyes on the development of CRC. Our study aimed to investigate the effects of Red 40 on DNA damage, the microbiome, and colonic inflammation. Despite a lack of prior research, high levels of human exposure to pro-inflammatory foods containing Red 40 highlight the urgency of exploring this issue. Our results show that Red 40 damages DNA both in vitro and in vivo and that consumption of Red 40 in the presence of a high-fat diet for 10 months leads to dysbiosis and low-grade colonic inflammation in mice. This evidence supports the hypothesis that Red 40 is a dangerous compound that dysregulates key players involved in the development of EOCRC.

In conclusion, our study, distinguished by meticulous dietary control and selected CRC-related outcome measurements, underscores Red 40's adverse effects. The combination of in vitro and in vivo models facilitates nuanced exploration of CRC-relevant mechanisms. Nonetheless, our study does possess limitations, including the need for more detailed mechanistic insights into observed changes. As we continue to examine how Red 40 triggers low-grade inflammation, with emphasis on relevant microbial species, we acknowledge the challenges in extrapolating results from animal models to human contexts. To this, the current study advances our understanding of Red 40's detrimental effects on health, highlighting the potential of chronic exposure to elevate CRC risk. We demonstrate that Red 40 inflicts DNA damage, particularly in the presence of a HFD, which leads to altered gut microbiota and subsequent inflammation in the distal colon. These findings contribute to the growing body of evidence illustrating Red 40's adverse impact on colorectal carcinogenesis. Future endeavors should incorporate human studies to deepen insights into Red 40's role in EOCRC's natural history, alongside further laboratory investigations to elucidate underlying mechanisms.

ABSTRACT
Attention Deficit Hyperactivity Disorder, also known as ADHD, is a neurodevelopmental disorder diagnosed in children. The exact cause of ADHD is not known, but, along with genetic factors, it is possible that environmental factors including toxins and diet may affect symptom severity. Of these dietary components, artificial food coloring (AFC), while approved by the Food and Drug Administration (FDA), has been suspected to be associated with ADHD symptoms. Of the nine FDA-certified food colors, two are used for artificial blue coloring: Blue No. 1 and Blue No. 2. There is limited literature describing the possible role of blue AFC in causing symptoms of ADHD in children. This paper provides a review of the literature surrounding artificial food coloring and its ability to affect the neurodevelopment of children in a way that could increase the behavioral indicators of ADHD. To do this, search criteria were established using a combination of MeSH terms about blue AFCs and ADHD and were entered into PubMed, along with limits on article types and publication dates from January 2000 to June 2022. There was a total of 20 articles that met this search criterion. These articles were reviewed by authors, and the ones not relevant to the topic were excluded. In total, four studies were chosen to be included in this article. After reviewing the literature, it was found that restriction diets, specifically those excluding AFCs, may affect symptom severity. The source of these changes is not known, but possible mechanisms include AFCs causing nutritional deficiencies and allergic reactions or altering neurotransmitter levels. More research is necessary to describe the neurotoxicity of artificial blue dyes in humans.

CONCLUSION
The studies that were reviewed in this article show that diet, especially consumption of artificial food coloring, produces statistically significant increases in ADHD symptoms in children. The mechanism for how AFCs cause such neurological and behavioral changes is not definitively known, but there are a few possible explanations. These include some well-studied hypotheses for the mechanism of ADHD that AFCs could contribute to, such as the dopamine hypothesis, but some less-studied causes like nutritional deficiencies and histamine release may also be possible. While several studies examine the effect of a combination of AFCs on ADHD symptoms in children, there is very little research done on just Blue No. 1 or Blue No. 2 in children. This is illustrated by the low number of studies reviewed in the article after the PubMed search on blue AFC and ADHD, limiting the strength of the conclusions that can be made from the results. In mice and rats, Blue No. 1 specifically has been found to affect neurodevelopment and hyperactive behavior, while Blue No. 2 has not been shown to have any definitive toxicity. There is a need for more research to determine how these individual compounds affect humans, especially because of the ability for Blue #1 to cross the blood-brain barrier. Understanding how artificial blue food dyes affect the brain and behavior of humans through increased research on the topic could provide alternative treatment options for children with ADHD.

ABSTRACT
Titanium dioxide nanoparticles (TiO2 NPs) have been extensively used in industry, medicine, and daily life, and have shown potential toxic effects for animals or humans. We noted that the effects of TiO2 NPs on the immune system and its mechanism of action in animals or humans have not been elucidated. Thus, mice were exposed to the TiO2 NPs (0, 1.25, 2.5, or 5 mg kg-1 body weight) for 9 consecutive months. Exposure to TiO2 NPs was accumulated in the thymus, leading to a decrease in body weight and increases in the weight of the thymus or thymus indices. In the blood, exposure to TiO2 NPs significantly decreased white blood cell, red blood cell, reticulocyte, haemoglobin, and mean corpuscular haemoglobin concentration; and increased mean corpuscular volume, mean corpuscular haemoglobin, platelets, and mean platelet volume. The reductions of lymphocyte subsets, including CD3+, CD4+, CD8+, B cell, and natural killer cell, were observed in the TiO2 NP-treated mouse thymus. Appearance of starry-sky aspect of the cortex that is given by the body of macrophages, bleeding, severe hemolysis or congestion, fatty degeneration, and cell apoptosis or necrosis were observed in the thymus following TiO2 NPs exposure. Importantly, TiO2 NPs increased expression of nucleic factor-κB(NF-κB), IκB kinase1/2, interleukin-1β, interleukin -4, regulated upon activation normal T-cell expressed and secreted, cyclooxygenase 2, neutrophil gelatinase-associated lipocalin, purinergic receptors-7, interferon-inducible protein 10, hypoxia inducible factor 1-α, p-c-Jun N-terminal kinase, p-p38, and p-extracellular signal-regulated kinase 1/2 protein, respectively; whereas suppressed expression of IκB, peroxisome proliferater-activated receptor-γ, trefoil factor 1, peroxisome proliferator activated receptor gamma coactivator-1α, and prostaglandin E2 proteins in the thymus, respectively. Taken together, these results suggest that TiO2 NPs exerts toxic effects on lymphoid organs and T cell and innate immune cell homeostasis in mice and that these immunotoxic potential effects may result from the activation of NF-κB-mediated mitogen-activated protein kinases (MAPKs) pathway.

ABSTRACT
Objectives: Removing artificial food coloring (AFC) is a common dietary intervention for children with Attention-Deficit/Hyperactivity Disorder (ADHD), but has not been tested in young adults. This pilot study examined the effects of AFC on ADHD symptoms and electroencephalography (EEG) in college students with and without ADHD.

Methods: At baseline, control and ADHD participants completed the Adult ADHD Self-Report Scale (ASRS), simple and complex attention measures, and resting-state EEG recordings. ADHD participants (n = 18) and a subset of controls (extended control group or EC, n = 11) avoided AFC in their diet for 2 weeks and then were randomized to a double-blind, placebo-controlled crossover challenge. Subjects received either 225 mg AFC disguised in chocolate cookies or placebo chocolate cookies for 3 days each week, with testing on the third day each week. Baseline comparisons were made using Student's t-test or Wilcoxon rank sum tests and challenge period analyses were run using General Linear Modeling.

Results: The ADHD group had significantly greater scores on the ASRS (p < 0.001), confirming a symptom differential between groups; however, there were no differences in attentional measures or EEG at baseline. The AFC challenge resulted in an increase in posterior mean gamma power (p = 0.05), a decrease in posterior relative alpha power (p = 0.04), and a marginal increase in inattentive symptoms (p = 0.08) in the ADHD group. There were no effects of AFC in the EC group.

Discussion: This study indicates that AFC exposure may affect brainwave activity and ADHD symptoms in college students with ADHD. Larger studies are needed to confirm these findings.

Read the full article of the Consumer Reports study for recommendations and specific brands with the highest levels of infant formula contaminants. This can be seen at -

https://www.consumerreports.org/babies-kids/baby-formula/baby-formula-contaminants-test-results-a7140095293

ABSTRACT
Requirements for iron and docosahexaenoic acid (DHA) content of infant formula varies by country. Powdered full-term infant formula purchase data from all major physical stores in the US between 2017-2019 were obtained from CIRCANA, Inc. Iron and DHA composition and scoop sizes for each formula were obtained from manufacturers. The equivalent liquid ounces of prepared formula were calculated. Average iron and DHA content were compared between formula types and to both US and European formula composition requirements. These data represent 55.8 billion ounces of formula. The average iron content of all formula purchased was: 1.80 mg/100 kcal. This iron concentration is within the FDA regulations. However, it exceeds the maximum allowable iron concentration of infant formula (Stage 1) set by the European Commission of 1.3 mg/100 kcal. A total of 96% of formula purchased had an iron concentration of >1.3 mg/100 kcal. DHA is not a required ingredient in US formulas. The average DHA content of all formula purchased was: 12.6 mg/100 kcal. This DHA concentration is far below the minimum required DHA concentrations of infant formula (Stage 1) and follow-on formula (Stage 2) set by the European Commission of 20 mg/100 kcal. These are novel insights into the iron and DHA intake of formula-fed infants in the US. As international infant formulas have entered the US market due to the formula shortage, parents and providers need to be aware of regulatory differences in formula nutrient composition.

ABSTRACT
Fatty acid esters of 3-monochloropropanediol (3-MCPD), 2-monochlorpropanediol (2-MCPD), and glycidol are process-induced chemical contaminants found in refined vegetable oils. Due to their toxicological properties, there is potential concern regarding exposure to these compounds, particularly for formula-fed infants where refined edible oils are the primary fat source in commercial infant formulas.

In order to assess exposure, 55 commercial oil samples, specifically intended for use in infant formula, were collected in 2015 from various infant formula manufacturers in the United States and analysed using a LC-MS/MS direct detection method. At the time of collection, there were no validated methods for the analysis of MCPD and glycidyl esters in infant formula.

Therefore, analysis of these commercial oil samples served as an alternative for confirming the presence of these ester contaminants in infant formula. Bound 3-MCPD and glycidol concentrations in these oils ranged from below the limit of quantitation (< LOQ) to 5.13 µg g-1 and < LOQ to 6.14 µg g-1, respectively. Highest ester concentrations were observed in palm olein samples. Concentrations of bound 3-MCPD and glycidol in the commercial oils were consistent with previously published occurrence studies at the time, suggesting that oils used in the manufacture of infant formula were similar (or processed in a similar manner) as refined oils marketed directly to consumers in 2015.

In order to determine if conditions during infant formula production impact the presence of 3-MCPD and glycidyl esters in the finished products, concentrations in oils were compared to concentrations in finished infant formula collected at approximately the same time. The comparison revealed that conditions used in the manufacture of infant formula likely initiate the destruction or conversion of glycidyl esters to other compounds, resulting in lower amounts of bound glycidol in the final product relative to the concentrations originally present in the refined oils.

..................
ABSTRACT
Fluoride mediated disruption of sex steroid hormones has been demonstrated in animals. However, evidence from humans was limited and contradictory, especially for children and adolescents. Based on data of the National Health and Nutrition Survey (NHANES) 2013–2016, a total of 3392 subjects aged 6–19 years were analyzed in this cross-sectional study. Both plasma and water fluoride levels were quantified electrometrically using the ion-specific electrode. Sex steroid hormones of total testosterone, estradiol and sex hormone-binding globulin (SHBG) were tested in serum. Percent changes and 95% confidence intervals (CIs) in sex steroid hormones associated with tertiles of fluoride levels (setting the first as reference) were estimated using adjusted linear regression models by stratification of gender and age. Compared with subjects at the first tertile of plasma fluoride, percent changes (95% CIs) in testosterone were −8.08% (−17.36%, 2.25%) and −21.65% (−30.44%, −11.75%) for the second and third tertiles, respectively (P trend <0.001). Male adolescents at the third tertile of plasma fluoride had decreased levels of testosterone (percent change = −21.09%, 95% CIs = −36.61% to −1.77%). Similar inverse associations were also found when investigating the relationships between plasma fluoride and estradiol. Besides, the data indicated decreased levels of SHBG associated with water and plasma fluoride among the male adolescents (percent change of the third tertile = −9.39%, 95% CIs = −17.25% to −0.78%) and female children (percent change of the second tertile = −10.78%, 95% CIs = −17.55% to −3.45%), respectively. The data indicated gender- and age-specific inverse associations of fluoride in plasma and water with sex steroid hormones of total testosterone, estradiol and SHBG in U.S. children and adolescents. Prospective cohort studies are warranted to confirm the causality.

In their concluding remarks, researches stated, "This study adds to the growing evidence that even low-level fluoride exposure early in life may adversely impact child cognition. Prenatal exposure was associated with lower cognitive abilities with no indication of a threshold..... Both perceptual reasoning and verbal ability appeared to be affected. Because even minor changes in cognition at a population level have important implications for public health, the overall results raise concerns about the existing guidelines and standards for fluoride in drinking water."

ABSTRACT
Background:
There are indications that fluoride exposure considered to be beneficial for dental health may not be safe from a neurodevelopmental perspective.

Objective:
We assessed the impact of prenatal and childhood fluoride exposure on cognitive abilities at 5 and 10 years of age.

Methods:
We studied 500 mother–child pairs from the MINIMat (Maternal and Infant Nutrition Interventions in Matlab) birth cohort in rural Bangladesh. Urinary fluoride concentrations were measured in the pregnant women at gestational week 8 and in their children at 5 and 10 years of age using an ion-selective electrode and adjusting for specific gravity. Cognitive abilities were assessed using the Wechsler Preschool and Primary Scale for Intelligence, Third Edition, and the Wechsler Intelligence Scale, Fourth Edition, at 5 and 10 years of age, respectively. Associations of urinary fluoride concentrations (log2-transformed) with cognitive abilities (raw scores) were assessed with multivariable-adjusted linear or spline regression models. Water fluoride concentrations at the time of the follow-up of the children at 10 years of age were also measured.

Results:
Maternal urinary fluoride concentrations (median: 0.63mg/L, 5th–95th percentiles: 0.26–1.41mg/L) were inversely associated with full-scale raw scores at 5 and 10 years [B (95% confidence interval): −2.8 (−5.1, −0.6) and −4.9 (−8.0, −1.8), respectively, by exposure doubling]. In cross-sectional analysis at 10 years, child urinary fluoride (overall median: 0.66mg/L, 5th–95th percentiles: 0.34–1.26mg/L) above −0.47 on the log2-scale (corresponding to 0.72mg/L) was inversely associated with full-scale raw scores [B (95% confidence interval): −12.1 (−21.2, −3.0)]. The association at 5 years of age was also negative but nonsignificant. For both prenatal and childhood exposure, associations were most noticeable with perceptual reasoning, but also verbal scores. The estimate for the association between urinary fluoride at 10 years of age and perceptual reasoning became 18% lower after adjustment for prenatal exposure. Inconsistent sex-specific differences were observed.

Conclusion:
Urinary fluoride concentrations measured prenatally and during childhood (child urinary fluoride concentrations above −0.47 on the log2 scale, corresponding to 0.72mg/L) were associated with lower cognitive abilities, especially perceptual reasoning and verbal abilities, in Bangladeshi children

Introduction: Dental fluorosis has been assessed only 3 times in nationally representative oral health surveys in the United States. The first survey was conducted by the National Institute of Dental Research from 1986 to 1987. Subsequently, the National Health and Nutrition Examination Survey (NHANES) conducted fluorosis assessments from 1999 to 2004 and more recently from 2011 to 2012. A large increase in prevalence and severity of fluorosis occurred between the 1986-1987 and 1999-2004 surveys.

Objectives: To determine whether the trend of increasing fluorosis continued in the 2011-2012 survey.

Methods: We analyzed publicly available data from the 2011-2012 NHANES, calculating fluorosis prevalence and severity using 3 measures: person-level Dean's Index score, total prevalence of those with Dean's Index of very mild degree and greater, and Dean's Community Fluorosis Index. We examined these fluorosis measures by several sociodemographic factors and compared results with the 2 previous surveys. Analyses accounted for the complex design of the surveys to provide nationally representative estimates.

Results: Large increases in severity and prevalence were found in the 2011-2012 NHANES as compared with the previous surveys, for all sociodemographic categories. For ages 12 to 15 y-an age range displaying fluorosis most clearly-total prevalence increased from 22% to 41% to 65% in the 1986-1987, 1999-2004, and 2011-2012 surveys, respectively. The rate of combined moderate and severe degrees increased the most, from 1.2% to 3.7% to 30.4%. The Community Fluorosis Index increased from 0.44 to 0.67 to 1.47. No clear differences were found in fluorosis rates among categories for most of the sociodemographic variables in the 2011-2012 survey.

Conclusion: Large increases in fluorosis prevalence and severity occurred. We considered several possible spurious explanations for these increases but largely ruled them out based on counterevidence. We suggest several possible real explanations for the increases.

Knowledge transfer statement: The results of this study greatly increase the evidence base indicating that objectionable dental fluorosis has increased in the United States. Dental fluorosis is an undesirable side effect of too much fluoride ingestion during the early years of life. Policy makers and professionals can use the presented evidence to weigh the risks and benefits of water fluoridation and early exposure to fluoridated toothpaste.

Objective: To explore the association between fluoride in drinking water and the prevalence and severity of fluorosis and dental caries in children living in communities receiving fluoridated salt.

Material and methods: Participants were schoolchildren (n = 457) living in two rural areas of the State of Morelos, Mexico, where the water fluoride concentration was 0.70 or 1.50 ppm. Dental caries status was assessed using Pitts' criteria. Lesions that were classified as D3 (decayed) were identified to determine the decayed, missing, and filled teeth index (D3MFT). Fluorosis was assessed using the Thylstrup-Fejerskov Index (TFI). Information regarding drinking water source and oral hygiene practices (tooth brushing frequency, dentifrice use, and oral hygiene index) was obtained.

Results: The prevalence of fluorosis (TFI ≥1) in communities with 0.70 and 1.50 ppm water fluoride was 39.4 and 60.5% (p = 0.014), respectively, while the prevalence of more severe forms (TFI ≥4) was 7.9 and 25.5% (p < 0.001), respectively. The mean D3MFT was 0.49 (±1.01) in the 0.70 ppm community and 0.61 (±1.47) in the 1.50 ppm community (p = 0.349). A logistic regression model for caries (D3 >1) showed that higher fluorosis categories (TFI 5-6 OR = 6.81, p = 0.001) were associated with higher caries experience, adjusted by age, number of teeth present, tooth brushing frequency, bottled water use, and natural water fluoride concentration.

Conclusions: The prevalence of fluorosis was associated with the water fluoride concentration. Fluorosis at moderate and severe levels was associated with a higher prevalence of dental caries, compared with lesser degrees of fluorosis. The impact of dental fluorosis should be considered in dental public health programs.

Known as jowar, this corn neighbor contained nearly 17-times more fluoride when grown using treated water than when grown using non-fluoridated water (8.8 ppm vs 0.52 ppm). This means 4 ounces of corn (a half cup) contains the same amount of fluoride as 2 liters of water and should be of great concern. Fluoride is known to accumulate in soil over time which could explain the apparent rising levels of fluoride in food crops.

ABSTRACT:
Background and aim: A staple food crops have varied role in diet of people living in particular regions of world; hence, it is critical to recognize their productivity. Therefore, the purpose of this study was to estimate fluoride concentration in staple food crops grown in highly fluoridated and non-fluoridated regions and its correlation with soil.

Method: Total 36 samples were collected of which 18 samples consisting of each three samples of rice, redgram and jowar were selected. Likewise 18 corresponding soil samples from both areas were collected. All samples were ashed for 4-6 hours at 550°C in muffle furnace. The samples were allowed to cool, after which 10 ml distilled water was added to each sample and fluoride concentration was determined using ion selective electrode method, before each sample analysis the instrument was standardized using fluoride containing TISAB (III) buffer solution. The data was tabulated and subjected to cross-sectional observational statistical analysis using SPSS software applying unpaired t-test and Pearson's test.

Result: The mean fluoride concentration in crops and soils were rice (0.79 ppm), redgram (4.26 ppm), jowar (8.8 ppm) and in soil of rice (1.23 ppm), redgram (1.23 ppm) and jowar (1.21 ppm) respectively in fluoridated area. Where as in non-fluoridated area rice (0.07 ppm), redgram (0.81 ppm), jowar (0.81 ppm) and in soil of rice (0.61 ppm), redgram (0.07 ppm) and jowar (0.52 ppm) respectively. The resultant correlation between staple food crops with their corresponding soils were found highly significant in both regions with P value <0.005; hence, crops in fluoridated region exhibited increased fluoride retention, whereas crops in non-fluoridated region had optimal fluoride levels.

Conclusion: Fluoride concentration in food crops has strong correlation with their respective soils and water irrigation properties.

ABSTRACT:
Objective: Environmental toxins are known to be one of the important factors in the development of Parkinson's disease (PD). This study was designed to investigate the possible contribution of fluoride (F) exposure to oxidative stress and neurodegeneration in rats with PD induced by rotenone (ROT).

Materials and methods: A total of 72 Wistar albino male rats were used in the experiment and 9 groups were formed with 8 animals in each group. ROT (2 mg/kg) was administered subcutaneously (sc) for 28 days. Different doses of sodium fluoride (NaF) (25, 50 and 100 ug/mL) were given orally (po) for 4 weeks. Malondialdehyde (MDA), glutathione (GSH), nitric oxide (NO), oxidative DNA damage (8-OHdG) and cholinesterase (AChE/BChE) enzyme activities were evaluated in serum and brain tissue homogenates.

Results: Rats treated with ROT and NaF had significant increases in serum and brain MDA, NO content, and decreases in GSH. In addition, the combination of ROT and NaF triggered oxidative DNA damage and resulted in increased AChE/BChE activity.

Conclusions: Findings suggest that NaF and ROT may interact synergistically leading to oxidative damage and neuronal cell loss. As a result, we believe that exposure to pesticides in combination with NaF is one of the environmental factors that should not be ignored in the etiology of neurological diseases such as PD in populations in areas with endemic fluorosis.

Background:
Hepato and nephrotoxicity of fluoride have been demonstrated in animals, but few studies have examined potential effects in humans. This population-based study examines the relationship between chronic low-level fluoride exposure and kidney and liver function among United States (U.S.) adolescents. This study aimed to evaluate whether greater fluoride exposure is associated with altered kidney and liver parameters among U.S. youth.

Methods:
This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (2013-2016). We analyzed data from 1,983 and 1,742 adolescents who had plasma and water fluoride measures respectively and did not have kidney disease. Fluoride was measured in plasma and household tap water. Kidney parameters included estimated glomerular filtration rate (calculated by the original Schwartz formula), serum uric acid, and the urinary albumin creatinine ratio. Liver parameters were assessed in serum and included alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, gamma glutamate transferase, and albumin. Survey-weighted linear regression examined relationships between fluoride exposure and kidney and liver parameters after covariate adjustment. A Holm-Bonferroni correction accounted for multiple comparisons.

Results:
The average age of adolescents was 15.4 years. Median water and plasma fluoride concentrations were 0.48 mg/L and 0.33 μmol/L respectively. A 1 umol/L increase in plasma fluoride was associated with a 10.36 mL/min/1.73 m2 lower estimated glomerular filtration rate - a 0.29 mg/dL higher serum uric acid concentration and a 1.29 mg/dL lower blood urea nitrogen concentration. A 1.0 mg/L increase in water fluoride was associated with a 0.93 mg/dL lower blood urea nitrogen concentration.

Conclusions:
Fluoride exposure may contribute to complex changes in kidney and liver related parameters among U.S. adolescents. As the study is cross-sectional, reverse causality cannot be ruled out; therefore, altered kidney and/or liver function may impact bodily fluoride absorption and metabolic processes.

As the full study are behind a "pay-wall," I am not able to get detailed results of specific fluoride levels and biological effects. However, considering that fluoride can have any effect on this critical defenses. for these changes.

ABSTRACT
Colon microenvironment and microbiota dysbiosis are closely related to various human metabolic diseases. In this study, a total of 72 healthy female mice were exposed to fluoride (F) (0, 25, 50 and 100 mg/L F−) in drinking water for 70 days. The effect of F on intestinal barrier and the diversity and composition in colon microbiota have been evaluated. Meanwhile, the relationship among F-induced colon microbiota alterations and antimicrobial peptides (AMPs) expression and short-chain fatty acids (SCFAs) level also been assessed. The results suggested that F decreased the goblet cells number and glycoprotein expression in colon. And further high-throughput 16S rRNA gene sequencing result demonstrated that F exposure induced the diversity and community composition of colonic microbiota significantly changes. Linear Discriminant Analysis Effect Size (LEfSe) analysis identified 11 predominantly characteristic taxa which may be the biomarker in response to F exposure. F-induced intestinal microbiota perturbations lead to the significantly decreased SCFAs levels in colon. Immunofluorescence results showed that F increased the protein expression of interleukin-17A (IL-17A) and IL-22 (P < 0.01) and disturbed the expression of interleukin-17 receptor A (IL-17RA) and IL-22R (P < 0.05 or P < 0.01). In addition, the increased expression of IL-17A and IL-22 cooperatively enhanced the mRNA expression of AMPs which response to F-induced microbiota perturbations. Collectively, destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure. Colonic homoeostasis imbalance would be helpful for finding the source of F-induced chronic systemic diseases.

Snippets from the orginal article

Animals and treatment
A total of 72 healthy female 21-day-old Kunming mice were purchased from the Experimental Animal Centre of Zhengzhou University, which were fed with a standard diet and housed under a 12 h light/dark cycle at a temperature of 22 °C ± 2 °C room for one week. After 7 days of acclimation, the mice were randomly divided into 4 groups of 18. The experimental design is as follows: mice in control group were given distilled water and standard diet, whereas the mice in the F groups were fed with...

Effect of F on the morphology, goblet cells number and glycoprotein expression in colon
Fig. 1 showed that, compared with the control group (Fig. 1A1), F exposure induce histopathological lesions in colonic tissues consisting of shortening and atrophy of colonic gland, mild to moderate necrosis of enterocytes, and a decrease in the number of goblet cells (Fig. 1B1, C1 and D1). With increasing F dose intake, the damage of colon tissue was more serious.
AB-PAS and PAS staining showed the distribution of goblet cells and glycoproteins. Obviously, the numbers of AB-PAS positive cells
Discussion
The intestinal barrier plays a pivotal role in maintaining the intestinal homoeostasis. Mucin glycoproteins secreted by goblet cells assemble into mucus layer is the front line of host defense against endogenous and exogenous irritants which play an important role in intestinal infections (Kim and Ho, 2010). Mucin glycoproteins secreted by goblet cells assemble into mucus layer is the front line of host defense against endogenous and exogenous irritants which play an important role in
Conclusion
Our results revealed that F destroy colonic microenvironment, lead to decrease the goblet cells number and glycoprotein secretion. Meanwhile, F disturbed AMPs expression by increased the level of IL-17A and IL-22. Destroyed microenvironment and disturbed AMPs are the primary reason of microbiota dysbiosis in colon after F exposure (Fig. 7). These results would be helpful for understanding the mechanism of F-induced colonic homeostasis imbalance. Colonic homoeostasis imbalance may be the source

ABSTRACT
The aim of this study was to examine the association between fluoride exposure and bone mineral density (BMD) in children and adolescents. We used data from the National Health and Nutrition Examination Survey (NHANES) 2015–2016. The fluoride concentrations in the water samples, plasma samples, and urine samples were measured electrometrically using an ion-specific electrode. Total body less head BMD (TBLH BMD) was measured using dual-energy X-ray absorptiometry (DXA). Weighted generalized linear regression models and restricted cubic splines (RCS) regression models were used to analyze the relationships between the three types of fluoride exposure and TBLH BMD. We performed subgroup analyses stratified by sex. A total of 1413 US children and adolescents were included in our study. In our linear regression models, we found inverse associations between fluoride concentrations in water and plasma and TBLH BMD. Additionally, we discovered a non-linear association between fluoride concentrations in water and plasma and TBLH BMD. No significant association or non-linear relationship was found between urine fluoride levels and TBLH BMD. This nationally representative sample study provides valuable insight into the intricate connection between fluoride exposure and skeletal health in children and adolescents.

Although this reduction in immune system quality typically (but not always) occurs at higher doses as seen in animal studies, the fact that fluoride constantly accumulates in the human body over time would suggest older Americans (with a higher body burden of fluoride) would be particularly vulnderable to the immune weakening effects of fluoride.

ABSTRACT
Excessive fluoride intake from residential environments may affect multiple tissues and organs; however, the specific pathogenic mechanisms are unclear. Researchers have recently focused on the damaging effects of fluoride on the immune system. Damage to immune function seriously affects the quality of life of fluoride-exposed populations and increases the incidence of infections and malignant tumors. Probing the mechanism of damage to immune function caused by fluoride helps identify effective drugs and methods to prevent and treat fluorosis and improve people’s living standards in fluorosis-affected areas. Here, the recent literature on the effects of fluoride on the immune system is reviewed, and research on fluoride damage to the immune system is summarized in terms of three perspectives: immune organs, immune cells, and immune-active substances. We reviewed that excessive fluoride can damage immune organs, lead to immune cells dysfunction and interfere with the expression of immune-active substances. This review aimed to provide a potential direction for future fluorosis research from the perspective of fluoride-induced immune function impairment. In order to seek the key regulatory indicators of fluoride on immune homeostasis in the future.

ABSTRACT
This study provides diverse lines of evidence demonstrating that fluoride (F) exposure contributes to degenerative eye diseases by stimulating or inhibiting biological pathways associated with the pathogenesis of cataract, age-related macular degeneration and glaucoma. As elucidated in this study, F exerts this effect by inhibiting enolase, τ-crystallin, Hsp40, Na+, K+-ATPase, Nrf2, γ -GCS, HO-1 Bcl-2, FoxO1, SOD, PON-1 and glutathione activity, and upregulating NF-κB, IL-6, AGEs, HsP27 and Hsp70 expression. Moreover, F exposure leads to enhanced oxidative stress and impaired antioxidant activity. Based on the evidence presented in this study, it can be concluded that F exposure may be added to the list of identifiable risk factors associated with pathogenesis of degenerative eye diseases. The broader impact of these findings suggests that reducing F intake may lead to an overall reduction in the modifiable risk factors associated with degenerative eye diseases. Further studies are required to examine this association and determine differences in prevalence rates amongst fluoridated and non-fluoridated communities, taking into consideration other dietary sources of F such as tea. Finally, the findings of this study elucidate molecular pathways associated with F exposure that may suggest a possible association between F exposure and other inflammatory diseases. Further studies are also warranted to examine these associations.

ABSTRACT
Fluorine is an essential trace element to which humans and animals are exposed through water, food, air and products used for dental health. Numerous studies have reported the detrimental effects of fluoride on testicular function and fertility; however, the underlying mechanisms of testosterone biosynthesis remain unclear. In this study, Leydig cells, the primary cells responsible for the production and regulation of steroid hormones in the testis, were used to elicit effects of sodium fluoride on the steroidogenic pathway. Leydig cells were treated with 0, 0.1, 1, 10 and 100 mg/L sodium fluoride for 24 h, respectively. The result of the study showed that sodium fluoride significantly decreased cell viability and cell proliferation, increased cell cytotoxicity and decreased the amounts of testosterone and 3′,5′-cyclic adenosine monophosphate levels in a concentration-dependent manner. Also, these results indicated that NaF suppressed the expression of steroidogenic genes (steroidogenic acute regulatory protein, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase type I and 17β-hydroxy dehydrogenase type III) and proteins (luteinizing hormone receptor, cholesterol side-chain cleavage enzyme, 3β-hydroxy dehydrogenase), by changing the mRNA expression levels of the transcription factors (steroidogenic factor-1, GATA binding protein-4, nerve growth factor IB and nuclear receptor subfamily 0 group B member 1).

Higher blood fluoride levels in some children could be explained by the fact that kidneys are the main organ for blood fluoride removal. As some children have significantly less kidney filtration and efficiency than others, this could be a plausible explanation for the discrepancy. Scientists also stated blood levels showed higher levels of fluoride in children than adolescents. In fact, the authors stated that because of this discrepancy, and more detrimental fluoride effects in younger children, they should be given alternative sources of drinking water.

This study suggests that scarring of teeth into adulthood from the addition of fluoride to water systems is to be expected in homes where fluoride is added to water supplies and could psychologically and financially impact many individuals.

ABSTRACT
Drinking water fluoridation was a mid-twentieth century innovation based on the medical hypothesis that consuming low doses of fluoride at the teeth forming years provided protection against dental decays. Numerous studies showed that high level exposure to fluoride could cause dental and skeleton fluorosis. However, there was limited study focusing on the fluorosis effect of low levels of exposure to fluoride. Therefore, our study aimed to examine whether the low level of fluoride exposure (measured in blood plasma and household tap water) was associated with the risk of dental fluorosis based on data of the National Health and Nutrition Examination Survey (NHANES) 2015–2016. We analyzed data in 2098 children and adolescents who had Dean's Index scores, and water and plasma fluoride measures. The Dean's Index score was measured by calibrated dental examiners using the modified Dean's fluorosis classification system. Fluoride was measured in plasma and household tap water. In this study, we found that the rate of fluoride concentration in water above the recommended level of 0.7 mg/L was 25%, but the prevalence of dental fluorosis was 70%. Binary logistic regression adjusted for covariates showed that higher water fluoride concentrations (0.31–0.50, 0.51–0.70, > 0.70 compared 0.00–0.30) were associated with higher odds of dental fluorosis (OR = 1.48, 95% CI: 1.13–1.96, p = 0.005; OR = 1.92, 95% CI: 1.44–2.58, p < 0.001, and OR = 2.30, 95% CI: 1.75–3.07, p < 0.001, respectively). The pattern of regression between plasma fluoride and dental fluorosis was similar. Inclusion, our study showed that even low level of water or plasma fluoride exposure was associated with increased the risk of dental fluorosis. The safety of public health approach of drinking water fluoridation for global dental caries reduction are urgently needed further research.

In conclusion, the researchers stated, "In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period."

ABSTRACT
Importance: Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.

Objective: To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.

Design, setting, and participants: This prospective cohort study utilized urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks' gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.

Exposure: Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.

Main outcomes and measures: Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.

Results: A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = .008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).

Conclusions and relevance: In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.

ABSTRACT
Background: Epidemiologic and animal-based studies have raised concern over the potential impact of fluoride exposure on neurobehavioral development as manifested by lower IQ and deficits in attention. To date, no prospective epidemiologic studies have examined the effects of prenatal fluoride exposure on behavioral outcomes using fluoride biomarkers and sensitive measures of attention.

Objective: We aimed to examine the association between prenatal fluoride exposure and symptoms associated with attention-deficit/hyperactivity disorder (ADHD).

Method: 213 Mexican mother-children pairs of the Early Life Exposures to Environmental Toxicants (ELEMENT) birth cohort study had available maternal urinary samples during pregnancy and child assessments of ADHD-like behaviors at age 6-12. We measured urinary fluoride levels adjusted for creatinine (MUFcr) in spot urine samples collected during pregnancy. The Conners' Rating Scales-Revised (CRS-R) was completed by mothers, and the Conners' Continuous Performance Test (CPT-II) was administered to the children.

Results: Mean MUFcr was 0.85 mg/L (SD = 0.33) and the Interquartile Range (IQR) was 0.46 mg/L. In multivariable adjusted models using gamma regression, a 0.5 mg/L higher MUFcr (approximately one IQR higher) corresponded with significantly higher scores on the CRS-R for DSM-IV Inattention (2.84 points, 95% CI: 0.84, 4.84) and DSM-IV ADHD Total Index (2.38 points, 95% CI: 0.42, 4.34), as well as the following symptom scales: Cognitive Problems and Inattention (2.54 points, 95% CI: 0.44, 4.63) and ADHD Index (2.47 points; 95% CI: 0.43, 4.50). The shape of the associations suggested a possible celling effect of the exposure. No significant associations were found with outcomes on the CPT-II or on symptom scales assessing hyperactivity.

Conclusion: Higher levels of fluoride exposure during pregnancy were associated with global measures of ADHD and more symptoms of inattention as measured by the CRS-R in the offspring.

ABSTRACT
Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain.

Methods:
A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test.

Results:
In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09–1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24–1.85]; 1.57 [95% CI, 1.28–1.92], and 1.72 [95% CI, 1.33–2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64–14.36] and 5.97 [95% CI, 4.54–7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25–19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25–5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91–99] versus 16 [95% CI, 12–18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1–9] versus 8 [95% CI, 6–8]).

Conclusions:
Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

ABSTRACT
The COVID-19 pandemic catalyzed the swift development and distribution of mRNA vaccines, including BNT162b2, to address the disease. Concerns have arisen about the potential neurodevelopmental implications of these vaccines, especially in susceptible groups such as pregnant women and their offspring. This study aimed to investigate the gene expression of WNT, brain-derived neurotrophic factor (BDNF) levels, specific cytokines, m-TOR expression, neuropathology, and autism-related neurobehavioral outcomes in a rat model. Pregnant rats received the COVID-19 mRNA BNT162b2 vaccine during gestation. Subsequent evaluations on male and female offspring included autism-like behaviors, neuronal counts, and motor performance. Molecular techniques were applied to quantify WNT and m-TOR gene expressions, BDNF levels, and specific cytokines in brain tissue samples. The findings were then contextualized within the extant literature to identify potential mechanisms. Our findings reveal that the mRNA BNT162b2 vaccine significantly alters WNT gene expression and BDNF levels in both male and female rats, suggesting a profound impact on key neurodevelopmental pathways. Notably, male rats exhibited pronounced autism-like behaviors, characterized by a marked reduction in social interaction and repetitive patterns of behavior. Furthermore, there was a substantial decrease in neuronal counts in critical brain regions, indicating potential neurodegeneration or altered neurodevelopment. Male rats also demonstrated impaired motor performance, evidenced by reduced coordination and agility. Our research provides insights into the effects of the COVID-19 mRNA BNT162b2 vaccine on WNT gene expression, BDNF levels, and certain neurodevelopmental markers in a rat model. More extensive studies are needed to confirm these observations in humans and to explore the exact mechanisms. A comprehensive understanding of the risks and rewards of COVID-19 vaccination, especially during pregnancy, remains essential.

ABSTRACT
With the worldwide goal of ending the pandemic, mRNA vaccines have been introduced as a valuable tool to help achieve both herd immunity and protect the most vulnerable. Neurological side effects from such vaccines have been increasingly documented, but to date, they are still deemed rare with no caution advised per the Centers for Disease Control and Prevention (CDC). As more of the younger population (under 40) are getting vaccinated according to recent approval and CDC recommendations, the real-world safety reporting data on adverse events have yet had time to catch up. We present three distinct neurological events that occurred after the Pfizer mRNA vaccine (BioNTech, Mainz, Germany), without identifiable alternate etiologies, in patients with an average age of 36 years presenting to an urban Florida clinic, all within eight weeks of one another. The presented cases occurred within hours of the second dose and, in one case, after the third booster dose of the Pfizer mRNA vaccine. These cases illustrate rising concerns of risks in widely recognized very low-risk age categories. A clearly delineated risk-benefit strategy likely needs to be implemented.

Boys with at least one comorbidity (obesity, diabetes etc), do appear to have a reduced risk of hospitalization. It was also stated that if the child at any point did have a natural infection (which can be quantified by natural antibodies), there was no benefit seen from vaccination, thereby suggesting no medical reason to vaccinate a child who has previously had a natural COVID-19 infection.

ABSTRACT
Male patients ages 12–17 years have an elevated risk of mRNA vaccination-associated myo/pericarditis. A risk-benefit analysis of first and second doses of mRNA vaccination in adolescent boys by health status and history of SARS-CoV-2 infection has not been performed.

Methods
Using the Vaccine Adverse Event Reporting System (VAERS), we identified BNT162b2 (Pfizer-BioNTech) myo/pericarditis occurrence according to CDC criteria. Main outcomes were as follows: 1) post-vaccination myo/pericarditis crude incidence in adolescents aged 12–15 and 16–17; and 2) two risk-benefit analyses by age, sex, comorbidity, variant and history of infection.

Results
Cases of myo/pericarditis (n = 253) included 129 after dose 1 and 124 after dose 2, 86.9% were hospitalized. Incidence per million after dose two in male patients aged 12–15 and 16–17 was 162.2 and 93.0, respectively. Weighing post-vaccination myo/pericarditis against COVID-19 hospitalization during delta, our risk-benefit analysis suggests that among 12–17-year-olds, two-dose vaccination was uniformly favourable only in nonimmune girls with a comorbidity. In boys with prior infection and no comorbidities, even one dose carried more risk than benefit according to international estimates. In the setting of omicron, one dose may be protective in nonimmune children, but dose two does not appear to confer additional benefit at a population level.

Conclusions
Our findings strongly support individualized paediatric COVID-19 vaccination strategies which weigh protection against severe disease vs. risks of vaccine-associated myo/pericarditis. Research is needed into the nature and implications of this adverse effect as well as immunization strategies which reduce harms in this overall low-risk cohort.

Below are five classes of EDCs (endocrine disrupting chemicals) Harvard scientists identified which they believe could be weaken immune function and worsen viral infections.

CHEMICAL #1 - PCB'S
Found in the coloring of common housepaint and sometimes very high in homes built in the 60s and 70s, because of its use in caulking, paint and wood varnish. It's also emitted from coal-fired power plants which then rain down in our waterways, soil and pastures where it concentrates in fish and even reaches high levels in meat of pasture raised cattle.

CHEMICAL #2 - DIOXIN
Found in bleached paper, car exhaust, and emitted at high levels in backyard trash burning and municipal incinerators. Also forms in some pesticides and emitted from coal-fired power plants.

CHEMICAL #3 - PESTICIDES
Cytokine immune disruption potential was also found from a number of common pesticides used in food and homes. This included the pesticides chlordane (found in homes before 1990), chlorpyrifos (in food and newer homes), atrazine (weed killer), cypermethrin, DDT and DDE (which we ingest from foods grown imported from South America that allow DDT).

Since several of these pesticides are found at high levels in foods produced using conventional-based agriculture, it would suggest eating organic could have a protective effect from Covid-19. Some studies have shown high Covid outbreaks near agricutural communities which would seem plausible as well.

CHEMICAL #4 - PLASTICS
When looking through Harvard's cytokine damaging list - there is also mention of a plastic chemical BPA which is used in water bottles, food packaging and even dental fillings. There is also concern for BPA replacements including bisphenol F (BPF) and bisphenol-S (BPS). This is telling us that even BPA-Free is meaningless as replacement plastics are typically BPS.

CHEMICAL #5 - DISINFECTANTS
Evidence now suggests some of the disinfectant and antibacterial chemicals we previously believed would prevent infection are now showing the potential to increase the risk of infection.

One of these disinfectant chemicals that can mimic immune system cytokines is "triclosan," and while banned in some products, it's still used in a number of U.S. antbacterial lotions, liquid hand soaps, foaming hand anitizers, mouthwash, deodorants, paints and even wooden pencils.

CHEMICAL #6 - COSMETICS
Cosmetics such as facial makeup and lipstick need to be thickened - and the plastic chemical known as phthalates is used for this purpose. Unfortunately, it is also on Harvard's list of immune system influencing chemicals. Cosmetics also need preservatives and contain chemicals called parabens, also on the list of EDCs linked to COVID-19.

INTRODUCTION
PFAS chemicals are added to consumer products to make them resistant to water and oil. They are added to pizza boxes, microwave popcorn bags, frozen microwave meals, paint and are very common in cosmetics, lipstick and sunscreens.

Recent studies have shown PFAS chemicals decrease numbers of natural killer cells (our main Covid defense) as well as decrease antibody production.

BELOW IS A SUMMARY OF THIS STUDY PUBLISHED IN THE HARVARD SCHOOL OF PUBLIC HEALTH NEWSLETTER

People who had elevated blood levels of a toxic chemical called perfluorobutanoic acid (PFBA) had an increased risk of a more severe course of COVID-19 than those who did not have elevated levels, according to a new study led by Harvard T.H. Chan School of Public Health.

PFBA is part of a class of man-made chemicals known as perfluorinated alkylate substances (PFASs), which have previously been shown to suppress immune function.

The study, published December 31, 2020 in PLOS ONE, was led by Philippe Grandjean, adjunct professor of environmental health.

PFASs have water- and grease-resistant properties and are used in a wide variety of products, including nonstick cookware, waterproof clothing, food packaging, and firefighting foams. PFBA, more than other PFASs, is known to accumulate in the lungs, according to the study.

Researchers looked at PFAS levels in blood samples from 323 Danish individuals infected with the coronavirus. They found that those with higher PFBA levels had higher odds of being hospitalized, winding up in intensive care, and dying than those with lower levels.

The findings suggest that further study is needed to determine whether elevated exposures to other environmental immunotoxicants may worsen COVID-19 outcomes, the authors wrote.

When a CoronaVirus is on the verge of starting a major infection in the human body, an immune cell called a natural killer cell is attacking the virus with intensity and desperately trying to sway the see-saw so the virus loses and the body wins. Unfortunately, the common food pesticide chlorpyrifos, appears to have the ability to sway things in favor of the virus winning.

In a study out of Nippon Medical School in Tokyo, Japan, researchers exposed natural killer cells to low levels of chlorpyrifos from 0 to 100 parts per million for 1 to 72 hours. The effect was so great that the cells didn't just become "weak" - the exposures resulted in the death of natural killer cells by a process called apoptosis.

When the SARS coronavirus enters cells, it results in formation of large amounts of free-radicals. This can potentially lead to damage and death to cells in blood vessels and organs.

Normally, cells in the human body have a defense against these free radicals, including production of antioxidants (such as glutathione) which neutralize excessive free-radicals.

However, those with moderate to severe COVID-19 have been found to have far lower levels of these antioxidant defenses, thereby allowing free-radicals to cause more harm, and providing an explanation for their more severe reaction to the virus.

To compensate for this lack of antioxidant protection from COVID-19 free-radical formation, scientists are suggesting the administration of the over-the-counter supplement called Pycnogenol, which is made from French Maritime Pine Bark.

The logic here is that pynogenol will function to reduce the excessive formation of free-radicals causing oxidative stress, inflammation and damage to cells in the body.

ABSTRACT
Corona virus disease 2019 (COVID-19) is triggered by the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV2) and has rapidly developed into a worldwide pandemic. Unlike other SARS viruses, SARS-CoV2 does not solely impact the respiratory system, but additionally leads to inflammation of endothelial cells, microvascular injuries and coagulopathies, thereby affecting multiple organs. Recent reports of patients who were infected with SARS-CoV2 suggest persistent health problems even months after the initial infection. The French maritime pine bark extract PycnogenolⓇ has demonstrated anti-inflammatory, vascular and endothelium-protective effects in over 90 human clinical studies. It is proposed that PycnogenolⓇ may be beneficial in supporting recovery and mitigating symptoms and long-term consequences resulting from a SARS-CoV2 infection in COVID-19 patients.

ABSTRACT
When facing an acute viral infection, our immune systems need to function with finite precision to enable the elimination of the pathogen, whilst protecting our bodies from immune-related damage. In many instances however this “perfect balance” is not achieved, factors such as ageing, cancer, autoimmunity and cardiovascular disease all skew the immune response which is then further distorted by viral infection. In SARS-CoV-2, although the vast majority of COVID-19 cases are mild, as of 24 August 2020, over 800,000 people have died, many from the severe inflammatory cytokine release resulting in extreme clinical manifestations such as acute respiratory distress syndrome (ARDS) and hemophagocytic lymphohistiocytosis (HLH). Severe complications are more common in elderly patients and patients with cardiovascular diseases. Natural killer (NK) cells play a critical role in modulating the immune response and in both of these patient groups, NK cell effector functions are blunted. Preliminary studies in COVID-19 patients with severe disease suggests a reduction in NK cell number and function, resulting in decreased clearance of infected and activated cells, and unchecked elevation of tissue-damaging inflammation markers. SARS-CoV-2 infection skews the immune response towards an overwhelmingly inflammatory phenotype. Restoration of NK cell effector functions has the potential to correct the delicate immune balance required to effectively overcome SARS-CoV-2 infection.

Researchers then go on to suggest factors that can improve natural killer function - including exercise.

ABSTRACT
Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States.

........................

DISCUSSION
esticides are important tools for malaria control but may have unanticipated effects on human health. We found that bendiocarb, a carbamate pesticide in common use worldwide, is absorbed in pregnant women, transferred to the fetus, and remains detectable in infancy. Exposure to bendiocarb in utero had clear biological effects on the fetal immune system, independent of its impact on malaria vector control. These included dose-dependent alterations in immune cell homeostasis and function, encompassing both lymphoid and myeloid-derived lineages, including decreased FoxP3+ regulatory CD4 cells, increased cord plasma cytokines and chemokines, increased T cell production of inflammatory cytokines, and decreased T cell proliferation. Together, these changes suggest a shift in fetal T cell homeostasis toward an inflammatory response, and away from regulatory differentiation that is believed to be critical for the maintenance of maternofetal tolerance19,20.

ABSTRACT
The use of pesticides to reduce mosquito vector populations is a cornerstone of global malaria control efforts, but the biological impact of most pesticides on human populations, including pregnant women and infants, is not known. Some pesticides, including carbamates, have been shown to perturb the human immune system. We measure the systemic absorption and immunologic effects of bendiocarb, a commonly used carbamate pesticide, following household spraying in a cohort of pregnant Ugandan women and their infants. We find that bendiocarb is present at high levels in maternal, umbilical cord, and infant plasma of individuals exposed during pregnancy, indicating that it is systemically absorbed and trans-placentally transferred to the fetus. Moreover, bendiocarb exposure is associated with numerous changes in fetal immune cell homeostasis and function, including a dose-dependent decrease in regulatory CD4 T cells, increased cytokine production, and inhibition of antigen-driven proliferation. Additionally, prenatal bendiocarb exposure is associated with higher post-vaccination measles titers at one year of age, suggesting that its impact on functional immunity may persist for many months after birth. These data indicate that in utero bendiocarb exposure has multiple previously unrecognized biological effects on the fetal immune system.

ABSTRACT
Studies from Africa suggest that vitamin A supplementation may reduce morbidity and mortality rates associated with measles among poorly nourished children. We studied 20 children with measles in Long Beach, Calif., and found that 50% (95% confidence interval; 28% to 72%) were vitamin A deficient. This frequency among presumably well nourished American children supports evaluation of vitamin A status as a part of acute management of measles in the United States.

ABSTRACT
Recent studies show that vitamin A levels decrease during measles and that vitamin A therapy can improve measles outcome in children in the developing world. Vitamin A levels of children with measles have not been studied in developed countries. We therefore measured vitamin A levels in 89 children with measles younger than 2 years and in a reference group in New York City, NY. Vitamin A levels in children with measles ranged from 0.42 to 3.0 mumol/L; 20 (22%) were low. Children with low levels were more likely to have fever at a temperature of 40 degrees C or higher (68% vs 44%), to have fever for 7 days or more (54% vs 23%), and to be hospitalized (55% vs 30%). Children with low vitamin A levels had lower measles-specific antibody levels. No child in the reference group had a low vitamin A level. Our data show that many children younger than 2 years in New York City have low vitamin A levels when ill with measles, and that such children seem to have lower measles-specific antibody levels and increased morbidity. Clinicians may wish to consider vitamin A therapy for children younger than 2 years with severe measles. Additional studies of vitamin A in measles and other infectious diseases, and in vaccine efficacy trials, should be done.

ABSTRACT
The objective of the present study was to determine whether vitamin A prevents pneumonia, diarrhoea and other infections in children with measles. A meta-analysis was carried out of randomized controlled trials identified through a systematic search of the medical literature for studies that used vitamin A to treat measles. A total of 492 children, aged from 6 months to 13 years, were supplemented with vitamin A, and 536 children were given placebo in six trials, five of which were conducted in hospitals and one in a community setting. The main outcome measures were: incidence of pneumonia, diarrhoea, croup, and otitis media; and duration of pneumonia, diarrhoea, fever and hospitalization. There was no significant reduction in the incidence of pneumonia or diarrhoea but there was a 47 per cent reduction in the incidence of croup (RR = 0.53; 95 per cent CI = 0.29-0.89) in children who were treated with 200 000 IU of vitamin A on 2 consecutive days. Only one study reported a 74 per cent reduction in the incidence of otitis media (RR = 0.26 95 per cent CI = 0.05-0.92). There was a statistically significant decrease in the duration of diarrhoea, pneumonia, hospital stay and fever in individual studies. It was concluded that vitamin A does have a beneficial effect on morbidity associated with measles and should be used as a treatment for hospitalized measles cases.

ABSTRACT
The development and wide-spread use of mumps vaccine resulted in a dramatic and sustained decrease in the incidence of mumps disease; however, since 2000, an increase in the size and number of mumps outbreaks in the United States and other countries has sparked renewed interest in the durability of mumps-specific immunity elicited by mumps vaccination. The most likely explanation for mumps cases in previously immunized persons may be secondary vaccine failure, or waning immunity. In the current study, we examined changes in markers of measles and mumps immunity at two timepoints, approximately 7 and 17 years after two-dose MMR-II® vaccination, in a cohort of 98 healthy adults.

Our results indicate that mumps IgG titers exhibited a large and significant decline during this time period, while mumps neutralizing Ab titers were relatively stable. There was a similar discrepancy with measles-specific immune responses. For both pathogens, neutralizing antibody titers were fairly low and, given the length of time since vaccination, may have already declined. These data suggest that specific immune outcomes may wane at different rates and highlight our currently incomplete understanding of protective immune responses to mumps and measles.

Background
Previous studies suggest that per- and polyfluoroalkyl substances (PFAS) may act as immune suppressants. However, research about the impact of PFAS exposure on antibody responses to the measles, mumps, rubella (MMR) vaccine is limited and inconsistent.

Methods
This report includes 748 mother–child pairs from the Boston Birth Cohort, with 8 PFAS compounds measured in maternal plasma shortly after delivery. IgG reactivities to measles and rubella were profiled in cord blood and venous blood plasma during early childhood, using Phage ImmunoPrecipitation Sequencing. Linear regression models were applied to assess the relationships between log2-transformed PFAS and IgG reactivities as measured by Viral Aggregate Reactivity score (VARscore, with inverse normal transformation) for measles and rubella. Quantile g-computation was applied to evaluate the PFAS mixture – VARscore associations.

Results
The detection rate for 8 PFAS compounds ranged from 90 % to 100 % in maternal plasma. Maternal PFAS burden score (P = 0.01), but not individual PFAS compounds, was associated with lower VARscore for measles in cord blood. In 348 children after receiving the MMR vaccine, three maternal PFAS compounds (Me-PFOSA-AcOH, PFHpS and PFHxS) were significantly associated with lower measles VARscore (P < 0.05). Me-PFOSA-AcOH and PFHxS were significantly associated with higher risk of having low reactivity to measles defined as VARscore < 25th percentile. PFAS mixture analysis revealed a significant inverse association between quantile of the PFAS mixture and measles VARscore (P = 0.025) in children after vaccination, with PFHxS as an important contributor to this association. These inverse associations were more pronounced in Black children (compared to non-Black children) and in preterm children (compared to term children). In comparison, no associations were found for rubella VARscore.

Conclusions
This prospective birth cohort study provides suggestive evidence that maternal PFAS exposure is associated with a reduced immune response to the measles vaccine, especially, among Black or preterm children.

ABSTRACT
Background: Breast-feeding protects against many infectious diseases and may also influence immunization outcomes.

Aim: This study investigated if breast-feeding protects against clinical measles and if it modified the effect of immunization.

Methods: We used logistic regression with data for 10 207 individuals from the 1970 British Cohort study (BCS70). Breast-feeding data were collected at five years of age, and information on clinical measles infection, as well as socio-economic measures was collected at the age of ten years. Breast feeding was categorized as: breast-fed <1 month (n = 1611), breast-fed for 1-3 months (n = 1016), breast-fed for more than three months (n = 1108), breast-feeding of uncertain duration (n = 21) and never breast-fed (n = 6451).

Results: Breast-feeding for more than three months was negatively associated with a diagnosis of clinical measles infection after adjustment for crowding, social class, measles vaccination, parity and sex with an odds ratio (95% confidence interval) of 0.69 (0.60-0.81) compared with those who never breast-fed. Measles vaccination was highly associated with low risk for measles with: 0.14 (0.13-0.16). Age at acute measles infection was not associated with breastfeeding. Breast-feeding did not notably alter measles immunization efficacy.

Conclusion: Immunization against measles provides effective protection against the disease. A more modest reduction in the risk of a measles diagnosis is associated with breast-feeding. The associations with a diagnosis of measles for breast-feeding and measles immunization are independent of each other.

ABSTRACT
Receiving the measles vaccination is crucial for controlling the disease and preventing severe complications. However, adverse reactions can occur in individuals with inborn errors of immunity. This case report details a severe reaction to the measles vaccine in a ten-month-old female with a homozygous mutation in the IFNAR2 gene, leading to immunodeficiency-45. Following vaccination, she developed viremia, meningoencephalitis, and multi-organ failure. Genetic analysis identified a Variant of Uncertain Significance (VUS) in the IFNAR2 gene, which is essential for type I interferon (IFN-I) signaling. This case highlights the importance of incorporating genetic screening into vaccination programs for individuals at risk. It demonstrates the complex relationship between genetic mutations and the immune responses to the vaccines.

ABSTRACT
Background.
We investigated a measles outbreak among healthcare workers (HCWs) by assessing laboratory characteristics, measles vaccine effectiveness, and serological correlates for protection.

Methods.
Cases were laboratory-confirmed measles in HCWs from hospital X during weeks 12–20 of 2014. We assessed cases’
severity and infectiousness by using a questionnaire. We tested cases’ sera for measles immunoglobulin M, immunoglobulin G, avidity, and plaque reduction neutralization (PRN). Throat swabs and oral fluid samples were tested by quantitative polymerase chain reaction. We calculated attack rates (ARs) by vaccination status and estimated measles vaccine effectiveness as 1 − [ARvaccinated/ARunvaccinated].

Results.
Eight HCWs were notified as measles cases; 6 were vaccinated with measles vaccine twice, 1 was vaccinated once, and 1 was unvaccinated. All 6 twice-vaccinated cases had high avidity and PRN titers. None reported severe measles or onward transmission. Two of 4 investigated twice-vaccinated cases had pre-illness PRN titers of >120 mIU/mL. Among 106 potentially exposed HCWs, the estimated effectiveness of 2 doses of measles vaccine was 52% (95% confidence interval [CI], −207%–93%).

Conclusions.
Measles occurred in 6 twice-vaccinated HCWs, despite 2 having adequate pre-exposure neutralizing antibodies. None of the twice-vaccinated cases had severe measles, and none had onward transmission, consistent with laboratory findings suggesting a secondary immune response. Improving 2-dose MMR coverage among HCWs would have likely reduced the size of this
outbreak.

ABSTRACT
Background: Studies in developing countries have shown that children with measles have low serum retinol concentrations and that lower retinol levels are associated with measles-related mortality. Vitamin A therapy has been shown to reduce mortality among African children with acute measles.

Objectives: To determine whether serum retinol concentration is low among children with measles in the United States and to determine whether retinol concentration is associated with illness severity.

Setting: Pediatric referral hospital and clinic in Milwaukee, WI, during the measles outbreak of 1989-1990.

Patients: One hundred fourteen patients < or = 5 years of age evaluated for serologically confirmed measles with serum obtained within 5 days following rash onset.

Methods: Serum retinol concentration was determined by high-performance liquid chromatography. Clinical data were collected by hospital record review. A modified Pediatric Risk of Mortality (PRISM) score was used to assess physiologic instability as a measure of illness severity.

Results: Retinol concentrations ranged from 0.25 to 1.18 mumol/L (median 0.58 mumol/L); 82 (72%) patients had low retinol concentration (< or = 0.70 mumol/L). Median retinol concentrations were lower among hospitalized patients (0.56 vs 0.70, P = .006) and patients with pneumonia (0.52 vs 0.64, P = .02) but higher among children with otitis media (0.63 vs 0.54, P = .01). Higher modified PRISM scores, reflecting greater physiologic instability, were associated with lower retinol concentration (beta coefficient -.0147, P = .025). In multivariate analysis, higher modified PRISM scores were associated with lower retinol concentration (beta coefficient -.0144, P = .025) even after controlling for hospitalization, presence of complications, race, age, receipt of Aid to Families With Dependent Children, gender, and interval from rash onset until serum was collected.

Conclusions: Among these children with measles in an urban United States community, retinol concentrations were depressed, and the degree of depression was associated with illness severity. Vitamin A therapy should be considered for children with measles in the United States who require hospitalization.

ABSTRACT
How intestinal microbes regulate metabolic syndrome is incompletely understood. We show that intestinal microbiota protects against development of obesity, metabolic syndrome and pre-diabetic phenotypes by inducing commensal-specific Th17 cells. High-fat, high-sugar diet promoted metabolic disease by depleting Th17-inducing microbes, and recovery of commensal Th17 cells restored protection. Microbiota-induced Th17 cells afforded protection by regulating lipid absorption across intestinal epithelium in an IL-17-dependent manner. Diet-induced loss of protective Th17 cells was mediated by the presence of sugar. Eliminating sugar from high-fat diet protected mice from obesity and metabolic syndrome in a manner dependent on commensal-specific Th17 cells. Sugar and ILC3 promoted outgrowth of Faecalibaculum rodentium that displaced Th17-inducing microbiota. These results define dietary and microbiota factors posing risk for metabolic syndrome. They also define a microbiota-dependent mechanism for immuno-pathogenicity of dietary sugar and highlight an elaborate interaction between diet, microbiota, and intestinal immunity in regulation of metabolic disorders.

Sugar in mouse diets promotes metabolic disease by upsetting the gut microbial balance and driving loss of the Th17 cells that regulate lipid absorption by the intestinal epithelium.

ABSTRACT
Objectives
To examine the prospective associations between consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice with type 2 diabetes before and after adjustment for adiposity, and to estimate the population attributable fraction for type 2 diabetes from consumption of sugar sweetened beverages in the United States and United Kingdom.

Design
Systematic review and meta-analysis.

Data sources and eligibility
PubMed, Embase, Ovid, and Web of Knowledge for prospective studies of adults without diabetes, published until February 2014. The population attributable fraction was estimated in national surveys in the USA, 2009–10 (n=4729 representing 189.1 million adults without diabetes) and the UK, 2008–12 (n=1932 representing 44.7 million).

Synthesis methods
Random effects meta-analysis and survey analysis for population attributable fraction associated with consumption of sugar sweetened beverages.

Results
Prespecified information was extracted from 17 cohorts (38 253 cases/10 126 754 person years). Higher consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, by 18% per one serving/day (95% confidence interval 9% to 28%, I2 for heterogeneity=89%) and 13% (6% to 21%, I2=79%) before and after adjustment for adiposity; for artificially sweetened beverages, 25% (18% to 33%, I2=70%) and 8% (2% to 15%, I2=64%); and for fruit juice, 5% (−1% to 11%, I2=58%) and 7% (1% to 14%, I2=51%). Potential sources of heterogeneity or bias were not evident for sugar sweetened beverages. For artificially sweetened beverages, publication bias and residual confounding were indicated. For fruit juice the finding was non-significant in studies ascertaining type 2 diabetes objectively (P for heterogeneity=0.008). Under specified assumptions for population attributable fraction, of 20.9 million events of type 2 diabetes predicted to occur over 10 years in the USA (absolute event rate 11.0%), 1.8 million would be attributable to consumption of sugar sweetened beverages (population attributable fraction 8.7%, 95% confidence interval 3.9% to 12.9%); and of 2.6 million events in the UK (absolute event rate 5.8%), 79 000 would be attributable to consumption of sugar sweetened beverages (population attributable fraction 3.6%, 1.7% to 5.6%).

Conclusions
Habitual consumption of sugar sweetened beverages was associated with a greater incidence of type 2 diabetes, independently of adiposity. Although artificially sweetened beverages and fruit juice also showd positive associations with incidence of type 2 diabetes, the findings were likely to involve bias. None the less, both artificially sweetened beverages and fruit juice were unlikely to be healthy alternatives to sugar sweetened beverages for the prevention of type 2 diabetes. Under assumption of causality, consumption of sugar sweetened beverages over years may be related to a substantial number of cases of new onset diabetes.

CONCLUSIONS
Observational cohort studies support that consumption of sugar sweetened beverages is associated with incident type 2 diabetes, and independently of adiposity. This finding was stable in sensitivity analyses assessing influence of population characteristics, potential residual confounding, and publication bias. By contrast, although artificially sweetened beverages and fruit juice showed a positive association with incident type 2 diabetes, the quality of evidence is limited by potential bias and heterogeneity by study design. Although causality has not been established and precision needs to be improved, this study informs the potential efficacy of reducing the consumption of sugar sweetened beverages in a contemporary population. Moreover, findings support that neither artificially sweetened beverages nor fruit juice are suitable alternatives to sugar sweetened beverages for the prevention of type 2 diabetes.

ABSTRACT
Question
Is greater intake of sugar-sweetened beverages associated with greater risk of liver cancer or chronic liver disease mortality?

Findings
In 98 786 postmenopausal women followed up for a median of 20.9 years, compared with consuming 3 servings or less of sugar-sweetened beverages per month, women consuming 1 or more servings per day had significantly higher rates of liver cancer (18.0 vs 10.3 per 100 000 person-years; adjusted hazard ratio [HR], 1.85) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years; adjusted HR, 1.68).

Meaning
Compared with 3 or fewer sugar-sweetened beverages per month, consuming 1 or more sugar-sweetened beverages per day was associated with a significantly higher incidence of liver cancer and death from chronic liver diseases.

Abstract
Importance
Approximately 65% of adults in the US consume sugar-sweetened beverages daily.

Objective
To study the associations between intake of sugar-sweetened beverages, artificially sweetened beverages, and incidence of liver cancer and chronic liver disease mortality.

Design, Setting, and Participants
A prospective cohort with 98 786 postmenopausal women aged 50 to 79 years enrolled in the Women’s Health Initiative from 1993 to 1998 at 40 clinical centers in the US and were followed up to March 1, 2020.

Exposures
Sugar-sweetened beverage intake was assessed based on a food frequency questionnaire administered at baseline and defined as the sum of regular soft drinks and fruit drinks (not including fruit juice); artificially sweetened beverage intake was measured at 3-year follow-up.

Main Outcomes and Measures
The primary outcomes were (1) liver cancer incidence, and (2) mortality due to chronic liver disease, defined as death from nonalcoholic fatty liver disease, liver fibrosis, cirrhosis, alcoholic liver diseases, and chronic hepatitis. Cox proportional hazards regression models were used to estimate multivariable hazard ratios (HRs) and 95% CIs for liver cancer incidence and for chronic liver disease mortality, adjusting for potential confounders including demographics and lifestyle factors.

Results
During a median follow-up of 20.9 years, 207 women developed liver cancer and 148 died from chronic liver disease. At baseline, 6.8% of women consumed 1 or more sugar-sweetened beverage servings per day, and 13.1% consumed 1 or more artificially sweetened beverage servings per day at 3-year follow-up. Compared with intake of 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more servings per day had a significantly higher risk of liver cancer (18.0 vs 10.3 per 100 000 person-years [P value for trend = .02]; adjusted HR, 1.85 [95% CI, 1.16-2.96]; P = .01) and chronic liver disease mortality (17.7 vs 7.1 per 100 000 person-years [P value for trend <.001]; adjusted HR, 1.68 [95% CI, 1.03-2.75]; P = .04). Compared with intake of 3 or fewer artificially sweetened beverages per month, individuals who consumed 1 or more artificially sweetened beverages per day did not have significantly increased incidence of liver cancer (11.8 vs 10.2 per 100 000 person-years [P value for trend = .70]; adjusted HR, 1.17 [95% CI, 0.70-1.94]; P = .55) or chronic liver disease mortality (7.1 vs 5.3 per 100 000 person-years [P value for trend = .32]; adjusted HR, 0.95 [95% CI, 0.49-1.84]; P = .88).

Conclusions and Relevance
In postmenopausal women, compared with consuming 3 or fewer servings of sugar-sweetened beverages per month, those who consumed 1 or more sugar-sweetened beverages per day had a higher incidence of liver cancer and death from chronic liver disease. Future studies should confirm these findings and identify the biological pathways of these associations.

This observational study evaluated incidence of liver cancer and death from chronic liver disease among postmenopausal women by comparing intake of 3 or fewer servings of sugar-sweetened beverages per month vs intake of 1 or more sugar-sweetened beverages per day.

.............................
ABSTRACT
Background: An association between sweetened beverages and several cardiometabolic diseases has been reported, but their association with atrial fibrillation (AF) is unclear. We aimed to investigate the associations between consumption of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) and risk of consumption with AF risk and further evaluate whether genetic susceptibility modifies these associations.

Methods: A total of 201 856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire were included. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: During a median follow-up of 9.9 years, 9362 incident AF cases were documented. Compared with nonconsumers, individuals who consumed >2 L/wk of SSB or ASB had an increased risk of AF (HR, 1.10 [95% CI, 1.01-1.20] and HR, 1.20 [95% CI, 1.10-1.31]) in the multivariable-adjusted model. A negative association was observed between the consumption of ≤1 L/wk of PJ and the risk of AF (HR, 0.92 [95% CI, 0.87-0.97]). The highest HRs (95% CIs) of AF were observed for participants at high genetic risk who consumed >2 L/wk of ASB (HR, 3.51 [95% CI, 2.94-4.19]), and the lowest HR were observed for those at low genetic risk who consumed ≤1 L/wk of PJ (HR, 0.77 [95% CI, 0.65-0.92]). No significant interactions were observed between the consumption of SSB, ASB, or PJ and genetic predisposition to AF.

Conclusions: Consumption of SSB and ASB at >2 L/wk was associated with an increased risk for AF. PJ consumption ≤1 L/wk was associated with a modestly lower risk for AF. The association between sweetened beverages and AF risk persisted after adjustment for genetic susceptibility to AF. This study does not demonstrate that consumption of SSB and ASB alters AF risk but rather that the consumption of SSB and ASB may predict AF risk beyond traditional risk factors.

ABSTRACT
Background: Despite some reports of cardiometabolic disorders associated with the risk of Alzheimer's disease (AD), limited studies have been conducted to examine the association between excessive sugar intake (a risk factor for cardiometabolic disorders) and AD risk.

Aim: The purpose of our study was to evaluate if excessive sugar intake has a significant long-term effect on the risk of AD.

Methods: A population sample of 37,689 participants, who enrolled in the United States (US) Women's Health Initiative - Dietary Modification Trial (WHI-DM) in 1993-2005 and its extended observational follow-up study through 1 March 2019, were analyzed. Dietary sugar intake was measured using food frequency questionnaires. AD was classified by reports using a standard questionnaire. A dietary pattern that explained the maxima variations in sugar intake was constructed using reduced rank regression (RRR) technique. Associations of RRR dietary pattern scores and sugar intake (g/day) by quartiles (Q1 through Q4) with AD risk were examined using Cox proportional hazards regression analysis with adjusting for key covariates.

Results: During a mean follow-up of 18.7 years, 4586 participants reported having incident AD. The total incidence rate (95% confidence interval [CI]) of AD was 6.5 (6.3-6.7) per 1000 person-years (PYs). The incidence rates (95% CI) of AD by total sugar intake were 6.2 (5.8-6.6), 6.4 (6.0-6.8), 6.6 (6.3-7.0), and 6.9 (6.5-7.3) per 1000 PYs among those in quartiles (Q) 1 to Q4 (toward higher sugar consumption) of total sugar intake, respectively (test for trend of AD incident rates, p < 0.001). Individuals in Q4 of total sugar intake had a 1.19 higher risk of incident AD than those in Q1 (hazard ratio [HR] = 1.19, 95% CI: 1.05-1.34, p = 0.01). An estimated increase of 10 g/day in total sugar intake (about 2.4 teaspoons) was associated with an increased AD risk by 1.3-1.4%. Of six subtypes of sugar intake, lactose was significantly associated with AD risk.

Conclusions: Our study indicates that excessive total sugar intake was significantly associated with AD risk in women. Of six subtypes of sugar intake, lactose had a stronger impact on AD risk.

Abstract
Background and purpose: Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort.

Methods: We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food-frequency questionnaire at cohort examinations 5 (1991-1995), 6 (1995-1998), and 7 (1998-2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10 years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer's disease).

Results: After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer's disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26-6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18-7.07) for Alzheimer's disease. Sugar-sweetened beverages were not associated with stroke or dementia.

Conclusions: Artificially sweetened soft drink consumption was associated with a higher risk of stroke and dementia.

ABSTRACT
The associations between sugar-sweetened beverage (SSB) consumption and the risk of stroke, depression, cancer, and cause-specific mortality have not been determined, and the quantitative aspects of this link remain unclear. This meta-analysis therefore conducted a systematic review and dose-response analysis to determine their causal links. The database searches were conducted in PubMed, Cochrane library, Embase, Web of Science up to 10 November 2021. The intervention effects were evaluated by relative risk (RR) with 95% confidences (CI). Thirty-two articles met the inclusion criteria. Higher levels of SSB consumption significantly increased the risk of stroke (RR 1.12, 95% CI 1.03-1.23), depression (1.25, 1.11-1.41), cancer (1.10, 1.03-1.17), and all-cause mortality (1.08, 1.05-1.11) compared with none or lower SSB intake. The associations were dose-dependent, with per 250 mL increment of SSB intake daily increasing the risk of stroke, depression, cancer, and all-cause mortality by RR 1.09 (1.03-1.15), 1.08 (1.06-1.10), 1.17 (1.04-1.32), and 1.07 (1.03-1.11), respectively. The link was curved for depression and cancer risk (pnon-linear < 0.05). Subgroup analysis suggested that higher SSB intake increased ischemic stroke by 10%, CVD-caused mortality by 13%, and cancer-caused mortality by 6.0% than none or lower SSB consumption. It is suggested that SSB accounts for a leading risk factor of stroke, depression, cancer, and mortality, and that the risk rises in parallel with the increment of SSB intake (and is affected by participant characteristics).

CONCLUSIONS
Our study demonstrated that the risk of stroke, depression, cancer, and mortality increased in parallel to the increment of SSB consumption. The findings have clinical significance since the risk factors are modifiable, and reduction of SSB consumption helps to prevent some chronic diseases and disease-related mortality. However, well-designed prospective studies are still needed to confirm the findings of our reports and to determine the correlation between SSB consumption and the occurrence of some important chronic diseases, such as dementia and Parkinson’s disease.

ABSTRACTOver the last few years, several reports on the safety of antidepressants use in pregnancy have been published. Studies concerning the adverse effects of exposure to selective serotonin reuptake inhibitors (SSRI) during pregnancy on the developing foetus have indicated an increased risk of various congenital malformations and untoward effects such as poor neonatal adaptation syndrome or persistent pulmonary hypertension, but there still remain inconsistencies between various study results. This paper aims at reviewing the literature on the risks of exposure to antidepressants during pregnancy. SSRIs are generally considered as first-line antidepressant treatment in pregnancy, as they are generally safe and effective. To minimize the teratogenic risks, pregnant women should receive the minimal effective dose of the medication. Depression during pregnancy must not be left untreated, and it should also be remembered that the condition may extend into the postpartum period.D

Objective: Antidepressant use during gestation has been associated with risk of major congenital malformations but estimates can lack statistical power or be confounded by maternal depression. We aimed to determine the association between first-trimester exposure to antidepressants and the risk of major congenital malformations in a cohort of depressed/anxious women.

Setting and participants: Data were obtained from the Quebec Pregnancy Cohort (QPC). All pregnancies with a diagnosis of depression or anxiety, or exposed to antidepressants in the 12 months before pregnancy, and ending with a live-born singleton were included.

Outcome measures: Antidepressant classes (selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA) and other antidepressants) and types were individually compared with non-exposure during the first trimester (depressed untreated). Major congenital malformations overall and organ-specific malformations in the first year of life were identified.

Results: 18 487 pregnant women were included. When looking at the specific types of antidepressant used during the first trimester, only citalopram was increasing the risk of major congenital malformations (adjusted OR, (aOR) 1.36, 95% CI 1.08 to 1.73; 88 exposed cases), although there was a trend towards increased risk for the most frequently used antidepressants. Antidepressants with serotonin reuptake inhibition effect (SSRI, SNRI, amitriptyline (the most used TCA)) increased the risk of certain organ-specific defects: paroxetine increased the risk of cardiac defects (aOR 1.45, 95% CI 1.12 to 1.88), and ventricular/atrial septal defects (aOR 1.39, 95% CI 1.00 to 1.93); citalopram increased the risk of musculoskeletal defects (aOR 1.92, 95% CI 1.40 to 2.62), and craniosynostosis (aOR 3.95, 95% CI 2.08 to 7.52); TCA was associated with eye, ear, face and neck defects (aOR 2.45, 95% CI 1.05 to 5.72), and digestive defects (aOR 2.55, 95% CI 1.40 to 4.66); and venlafaxine was associated with respiratory defects (aOR 2.17, 95% CI 1.07 to 4.38).

Conclusions: Antidepressants with effects on serotonin reuptake during embryogenesis increased the risk of some organ-specific malformations in a cohort of pregnant women with depression.

RESULTS
Between 1999–2002 and 2007–2010, the age-adjusted prevalence of obesity among adults aged ≥18 years increased from 26.5% to 33.0% among men and from 32.4% to 34.9% among women (Table 1). Controlling for age and race/ethnicity in regression models indicated that the increase in the prevalence of obesity over the study period was statistically significant among men but not among women.

The prevalence of obesity differed substantially across categories of various demographic characteristics (Table 1). Among men, there was little difference in the prevalence of obesity by race/ethnicity, but among women, the overall (1999–2010) prevalence among non-Hispanic blacks (51%) was 10 percentage points higher than that among Mexican-Americans and 20 percentage points higher than that among non-Hispanic white women.

Inverse associations were identified between the prevalence of obesity and educational attainment that were statistically significant among both men and women; differences were much greater among women (Table 1). These associations appeared to be nonlinear. For example, among men, the prevalence was lowest (25%) among college graduates but highest (35%) among those who had completed some college. Among women, the overall prevalence of obesity among those who had completed college was 13–16 percentage points lower than in other groups, but there was little difference in obesity prevalence between those who had not finished high school and those who had completed some college. The analysis of disability status of adults aged ≥60 years indicated that the overall prevalence of obesity among those who reported having difficulties with four or more activities was substantially higher than obesity prevalence among those without a disability (men: 16 percentage points higher; women: 27 percentage points higher).

In contrast to these differences, which were larger among women, the association of obesity with country of birth and language spoken at home was stronger among men (Table 1). Mexican-American men who were born in the United States had 13 percentage points higher overall prevalence of obesity than men born in Mexico (39% versus. 26%), but the equivalent difference among Mexican-American women was only 3 percentage points. Similarly, Mexican-American men who spoke mostly English at home had a 12 percentage points higher overall prevalence of obesity compared with those who spoke mostly Spanish at home (38% versus 26%), while there was no significant difference among Mexican-American women. As assessed by an interaction term (each characteristic x study period) in sex-specific regression models, there was no indication that disparities in obesity prevalence varied across the 12-year study period among either men or women.

Between 1999–2002 and 2007–2010, the prevalence of obesity among children and adolescents aged 2–17 years increased from 15.4% to 18.6% among boys and from 13.8% to 15.1% among girls (Table 2). After adjustment for age and race/ethnicity in regression models, the increase over the six 2-year study cycles was statistically significant among boys but not among girls.

Differences in the prevalence of obesity among children and adolescents over the 12-year study period across categories of the various characteristics were somewhat similar to those among adults (Tables 1 and 2). Substantial differences existed in the prevalence of obesity by race/ethnicity; among boys, prevalence was highest among Mexican-Americans (24%), whereas among girls, prevalence was highest among non-Hispanic blacks (22%). Educational attainment of the adult head of household was associated inversely with obesity among both boys and girls. Overall, the prevalence of obesity among children and adolescents whose adult head of household had completed college was approximately half that of prevalence among children whose adult head of household did not complete high school. In contrast to the differences among adults, the prevalence of obesity among Mexican-American children did not differ significantly according to either country of birth or language spoken at home.

The aim of this study was to investigate levels of polychlorinated biphenyls (marker and dioxin-like congeners), polycyclic aromatic hydrocarbons (EPA 15 + 1), polybrominated diphenyl ethers (14 predominant congeners) and pesticides (74 compounds) in various cold-pressed vegetable oils. Poppy seed oil, rapeseed oil, sesame seed oil, pumpkinseed oil, hempseed oil, linaire oil, borage oil and evening star oil were investigated. Results of this study revealed that concentrations of PCBs, PBDEs and PAHs were low in majority of the investigated samples. However, high concentrations of organophosphorus insecticides were found. Chlorpyrifos methyl and pirimiphos methyl were the pesticide residues most commonly found in the studied oils. Concentration of 15 + 1 EPA PAHs was within the 17.85 - 37.16 ug kg-1 range, concentration of (marker) PCBs varied from 127 to 24,882 pg g-1, dioxin-like TEQ values were below 0.1 pg TEQ g-1. Concentration of PBDEs was below LOQ in most cases.

ABSTRACT
Background: Pesticide contamination in oil crops and processed products is an important food safety concern. The study was aimed to investigate the pesticide residue changes in press processing of peanut oil and frying of chips.

Results: Five pesticides - chlorpyrifos, deltamethrin, methoxyfenozide, azoxystrobin and propargite - which are often applied during growth period in peanut plants, were selected to investigate their residue changes in cold press processing of peanut oil and frying of potato chips. Results showed that the residues of the five pesticides were decreased by 3.1-42.6% during air-drying before oil pressing. The residues of chlorpyrifos, deltamethrin, methoxyfenozide and propargite in peanut oil were 2.05-3.63 times higher than that in peanut meal after cold pressing of the oil, except for azoxystrobin having a slightly lower residue in peanut oil, with 0.92 times that in peanut meal. The processing factors of the five pesticides in peanut oil ranged from 1.17 to 2.73 and were highly related to the log Kow of the pesticides. The higher the log Kow , the more easily was the pesticide partitioned in the peanut oil. Besides, as frying time increase during preparation of chips, the concentration of pesticides in peanut oil decreased gradually by 6.7-22.1% compared to the first frying. In addition, 0.47-11.06% of the pesticides were transferred to the chips through frying with contaminated oil.

Conclusion: This is first report showing that pesticides can transfer from contaminated oil to chips. There exists a potential dietary health risk by using pesticide-contaminated oil for frying chips. This work could provide basic data for accurate dietary risk assessment of pesticide residues in peanut oil and its frying products. © 2021 Society of Chemical Industry.

ABSTRACT
Fatty acid esters of 3-monochloropropanediol (3-MCPD) and glycidol are processing contaminants found in a wide range of edible oils. While both 3-MCPD and glycidol have toxicological properties that at present has concerns for food safety, the published occurrence data are limited. Occurrence information is presented for the concentrations of 3-MCPD and glycidyl esters in 116 retail and/or industrial edible oils and fats using LC-MS/MS analysis of intact esters. The concentrations for bound 3-MCPD ranged from below the limit of quantitation (< LOQ) to 0.09 mg kg-1 (ppm) in 22 unrefined oils and from 0.005 to 7.2 mg kg-1 (ppm) in 94 refined oils. The concentrations for bound glycidol ranged from < LOQ to 0.03 mg kg-1 (ppm) in unrefined oil samples and from < LOQ to 10.5 mg kg-1 (ppm) in processed oil samples. The highest concentrations for both 3-MCPD and glycidol were seen in refined palm oil and palm olein samples. Palm olein samples also contained a higher percentage of 3-MCPD in mono-ester form than any other type of oil.

ABSTRACT
Between 1973 and 1989, the incidence of non-Hodgkin's lymphoma (NHL) increased by nearly 60% in the United States, one of the largest increases of any cancer. In 1993, approximately 43,000 new cases of NHL will be diagnosed and over 20,000 deaths due to NHL will occur. The annual incidence rate of NHL per 100,000 persons in the US has risen from 5.9 in 1950 to 13.7 in 1989. This increase has occurred in both males and females, blacks and whites, and in all age groups except the very young. The largest increase has occurred in the elderly, and rates have increased more rapidly in rural areas. Most of the increase cannot be attributed to acquired immunodeficiency syndrome. Similar findings have been reported from other developed countries. Epidemiologic studies indicate that environmental factors may play an important role in the etiology of NHL. In this paper, current knowledge concerning the epidemiology of NHL is summarized, with special emphasis on environmental factors of possible etiologic importance, such as drugs, pesticides, solvents and other chemicals, dusts and particles, hair dyes, smoking, Helicobacter pylori infection, and diet. Many different environmental factors of low risk acting on large segments of the population could account for much of the increase in NHL.

PARAGRAPH 3
The resurgence of pertussis has been noticeable over the past several years. In the United States, there were 48277 cases of pertussis in 2012, more than any year in the previous 50 years. Approximately 10% of the cases were infants and 50% were adolescents or adults [3]. Mirroring the United States, there has been a global increase in the number of cases among adolescents and adults, mainly because of poor vaccine coverage and waning immunity [2, 4, 5]. Despite its dramatic symptoms, pertussis is still likely underdiagnosed due to poor awareness of the disease, misdiagnosis, and lack of diagnostic techniques. This is especially obvious in China, where there were only 2183 reported cases of pertussis in 2012, which is especially significant given the huge population and relatively poor healthcare system [6]. The criteria for diagnosis of pertussis issued by China's Center for Disease Control and Prevention have not been updated for more than a decade and do not include PCR. This may partially account for the low reporting rate [7]. Adolescents and adults with waning immunity and unrecognized pertussis are the most important sources of infection for children. This is why a booster tetanus toxoid, reduced diphtheria toxoid, and acelluar pertussis vaccine (Tdap) (a combination vaccine similar to diphtheria, tetanus toxoid, and acelluar pertussis vaccine [DTaP] with a lower dose of B. pertussis acellular components) is recommended for persons aged less than or equal to 11 years [8]. In this case, the mother was the most likely source of infection.