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Subchronic toxicities of C1O2, NaCIO2, NaCIO3 and NH2CI were studied in the African Green monkeys (Cercopithecus aethiops). The chemicals were administered in drinking water during 30-60 days subchronic rising dose protocols. The only unexpected and significant toxic effect was elicited by C102; this chemical inhibited thyroid metabolism in the animals at a dose of ca. 9.0 mg/kg/day. A statistically significant decrease of serum thyroxine occurred after the fourth week of exposure to 100 mg/l.concentration. The extent of thyroid suppression was dose dependent in each individual monkey, and was reversible after cessation of exposure. NaCIO2 and NaCIO3 failed to elicit similar effects in doses up to ca. 60 mg/kg/day. Also, NaCIO4 or NH2CI did not cause TA suppression in doses of 10 mg/kg/day. The selective thyroid effect of C102 was unexplained and it appeared to be paradoxical since C102 was rapidly reduced by the oral and gastric secretions to nonoxidizing species (presumably Cl-). No evidence of thyroid effects were detected in the serum of human volunteers who ingested -1 mg/I. of C102 in drinking water as a result of routine use in the community water treatment process.Sodium chlorite induced dose-dependent oxidative stress on hematopoesis, causing decreased hemoglobin and red cell count and increased methemoglobin content. At the same time, serum transaminase (SGPT) levels showed significant subclinical elevation. The hematologic effects of NaCl02 rebounded during exposure indicating compensatory hemopoietic activity taking effect during oxidative stress. Sodium chlorate and chloramine did not induce detectable hematologic changes in the animals.

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Toxicological studies dealing with recent findings of health effects of drinking water disinfectants are reviewed. Experiments with monkeys and rodents indicate that the biological activity of ingested disinfectants is expressed via their chemical interaction with the mucosal epithelia, secretory products, and nutritional contents of the alimentary tract. Evidence exists that a principal partner of this redox interaction is the iodide of nutritional origin that is ubiquitous in the gastrointestinal tract. Thus the observation that subchronic exposure to chlorine dioxide (ClO2) in drinking water decreases serum thyroxine levels in mammalian species can be best explained with changes produced in the chemical form of the bioavailable iodide. Ongoing and previously reported mechanistic studies indicate that oxidizing agents such as chlorine-based disinfectants oxidize the basal iodide content of the gastrointestinal tract. The resulting reactive iodine species readily attaches to organic matter by covalent bonding. Evidence suggests that the extent to which such iodinated organics are formed is proportional to the magnitude of the electromotive force and stoichiometry of the redox couple between iodide and the disinfectant. Because the extent of thyroid uptake of the bioavailable iodide does not decrease during ClO2 ingestion, it seems that ClO2 does not cause iodide deficiency of sufficient magnitude to account for the decrease in hormonogenesis. Absorption of one or more of iodinated molecules, e.g., nutrients, hormones, or cellular constituents of the alimentary tract having thyromimetic or thyroid inhibitory properties, is a better hypothesis for the effects seen.ImagesFIGURE 1. aFIGURE 1. bFIGURE 1. c

This chapter glances into the experience of leading diversity, equity, and inclusion (DEI) work while living in Minneapolis before, during, and after the murder of George Floyd, the subsequent uprisings, and racial reckoning of 2020. Ironically, the progressive state of Minnesota has been the site of multiple state-involved murders while also consistently voting Democrats into the White House and U.S. congress. This Minnesota paradox creates a unique place for DEI work. The author explores theories of white guilt and white saviorism, provides context about the racial and social environment of Minnesota, and provides recommendations for Black women DEI practitioners and those that employ them.

The University of Minnesota (UMN) School of Public Health (SPH) asked graduates about their experiences as students and as alumni. Of 1186 respondents indicating gender, 140 were women who self-identified as members of a marginalized group. Fifty-one percent of these respondents were White women. Compared with White women, Black, Indigenous, and people of color (BIPOC) women were more likely to report that they felt they did not belong, were uncomfortable, or experienced bias and/or discrimination in their program, although the results were not statistically significantly different at P < .05. Survey results show a clear difference in experience between White and BIPOC alumni. The results indicate a need to improve cultural competence/humility, along with a need to move away from what may be construed as White-centered events, pedagogy, and leadership. With this evidence, the UMN SPH has an opportunity to improve our outreach strategies and initiatives.

Ketogenic therapy is a treatment for intractable epilepsy involving a high fat, adequate protein, and low carbohydrate diet. A prospective study was conducted to examine serum beta‐hydroxybutyrate (BHB) and glucose (Glu) response at fasting, 30 min, 1 hr, and 2 hr after the ingestion of a ketogenic meal. Patients were stratified by age and route of feeding and comparisons were made for BHB/Glu and percent change from fasting. Data were available for 23 patients with mean age of 10.2±5 years and time on diet of 51.4±38 months. Mean percent changes at 30 min, 1 hr, and 2 hr for both BHB and Glu were less than 10%. Regression analyses were performed for BHB/Glu and percent changes and ratio, Cal/kg/day, fat, carbohydrate, and protein % of calories, fat and carbohydrate in g/kg/day and all correlations (r) were found to be less than 0.5 and r2 less than 0.3. Time on diet correlated to percent change of BHB at 30 min (r=0.5, r2=0.3, p=0.01). Fasting BHB/Glu was negatively correlated with age (r= ‐0.5, r2=0.2, p=0.03). Overall, BHB and Glu levels are maintained relatively constant. Stabilization of energy metabolism may be a factor in the mechanism of action against seizures.Effect of time after meal and age on BHB/Glu*p<0.05, #p=0.09 comparing <10yr and >10yrGrant Funding SourceNIH ‐ General Clinical Research Center

Metabolomics is the global analysis of metabolites within various tissues and biological fluids. The metabolome more closely represents the phenotype than the genome or proteome as metabolite fluxes are a product of both genetic and environmental influences. Thus, metabolomics may provide insight into the nutritional, metabolic, and general health status during different stages of the life cycle and during pathological conditions. The workflow is as follows: formulate hypothesis ‐ design study ‐ collect samples ‐ prepare and analyze samples to identify compounds ‐ analyze data ‐ evaluate hypothesis and generate hypotheses ‐ apply to patient care. Although experts in each area of the workflow are needed, at least one team member must provide continuity from formulation of hypotheses to patient care. We are testing the hypotheses that the plasma carnitinome will change in piglets between days 2 through 8 of life, in young healthy adults before and after being placed on a trial ketogenic diet, and in patients with epilepsy when treated with ketogenic therapy. The long term goal is to more effectively and efficiently translate research concerning changes in the carnitinome and metabolome into practical solutions for patients with various pathological conditions. This continuity and integration of knowledge from basic science to the clinic will accelerate research from discovery to improved patient care.