The etiology of major depressive disorder (MDD) remains poorly understood. Our previous studies suggest a role for the aryl hydrocarbon receptor (AhR) in depression. ...2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic environmental contaminant, with a high AhR binding affinity, and an established benchmark for assessing AhR activity. Therefore, this study examined the effect of TCDD on depression-like behaviors. Female mice were fed standard chow or a high-fat diet (HFD) for 11 weeks, and their weight was recorded. Subsequently, they were tested for baseline sucrose preference and splash test grooming. Then, TCDD (0.1 µg/kg/day) or vehicle was administered orally for 28 days, and mice were examined for their sucrose preference and performances in the splash test, forced swim test (FST), and Morris water maze (MWM) task. TCDD significantly decreased sucrose preference, increased FST immobility time, and decreased groom time in chow-fed mice. HFD itself significantly reduced sucrose preference. However, TCDD significantly increased FST immobility time and decreased groom time in HFD-fed mice. A small decrease in bodyweight was observed only at the fourth week of daily TCDD administration in chow-fed mice, and no significant effects of TCDD on bodyweights were observed in HFD-fed mice. TCDD did not have a significant effect on spatial learning in the MWM. Thus, this study demonstrated that TCDD induces a depression-like state, and the effects were not due to gross lethal toxicity. This study further suggests that more studies should examine a possible role for AhR and AhR-active environmental pollutants in precipitating or worsening MDD.
•TCDD induces a depression-like state in a rodent model.•The depression-like state induced by TCDD was not ameliorated by a rich diet.•TCDD's effects on mood were not attributed to gross lethal toxicity.•This study further suggests the role of AhR in mood regulation.•AhR-active environmental pollutants might be involved in causing or exacerbating MDD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Methylation in CpG sites of the PPARGC1A gene (encoding PGC1-α) has been associated with adiposity, insulin secretion/sensitivity indexes and type 2 diabetes. We assessed the association between the ...methylation profile of the PPARGC1A gene promoter gene in leukocytes with insulin secretion/sensitivity indexes in normoglycemic women. A standard oral glucose tolerance test (OGTT) and an abbreviated version of the intravenous glucose tolerance test (IVGTT) were carried out in
= 57 Chilean nondiabetic women with measurements of plasma glucose, insulin, and C-peptide. Bisulfite-treated DNA from leukocytes was evaluated for methylation levels in six CpG sites of the proximal promoter of the PPARGC1A gene by pyrosequencing (positions -816, -783, -652, -617, -521 and -515). A strong correlation between the DNA methylation percentage of different CpG sites of the PPARGC1A promoter in leukocytes was found, suggesting an integrated epigenetic control of this region. We found a positive association between the methylation levels of the CpG site -783 with the insulin sensitivity Matsuda composite index (rho = 0.31;
= 0.02) derived from the OGTT. The CpG hypomethylation in the promoter position -783 of the PPARGC1A gene in leukocytes may represent a biomarker of reduced insulin sensitivity after the ingestion of glucose.
Despite newer type 2 diabetes (T2D) medications, patients do not always achieve metabolic targets, remaining at risk for cardiorenal complications. Therapeutic decisions are generally made by the ...healthcare team without considering patients' preferences. We aimed to evaluate patients' T2D treatment preference in two Latin-American countries between two different oral medication profiles, one resembling dipeptidyl peptidase-4 inhibitors (DPP4i) and another resembling sodium-glucose cotransporter-2 inhibitors (SGLT2i).
In this cross-sectional, multicenter study from June to September 2020, patients with T2D from Argentina and Mexico (n = 390) completed a discrete choice experiment questionnaire to identify preferences between DPP4i (medication profile A) and SGLT2i (medication profile B). The reason behind patients' choice, and the association between their baseline characteristics and their preference were evaluated using logistic regression methods.
Most participants (88.2%) preferred SGLT2i's profile. Participants with older age (p = 0.0346), overweight or obesity (p < 0.0001), high blood pressure (BP; p < 0.0001), high total cholesterol (p = 0.0360), and glycosylated hemoglobin (HbA1c) <7% (p = 0.0001) were more likely to choose SGLT2i compared with DPP4i's profile. The most and least important reasons to choose either drug profile were HbA1c reduction and genital infection risk, respectively. The likelihood of selecting the SGLT2i's profile significantly increased in participants with increased body mass index (BMI; odds ratio OR = 8.9, 95% confidence interval CI: 3.5-22.5, p < 0.05), high BP (OR = 4.9, 95% CI: 1.9-12.4, p < 0.05), and lower education level (OR = 3.6, 95% CI: 1.0-12.6, p < 0.05).
Latin-American patients with T2D preferred medication with a profile resembling SGLT2i over one resembling DPP4i as a treatment option. A patient-centered approach may aid the healthcare team in decision-making for improved outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Organophosphorus (OP) insecticides were among the first pesticides that EPA reevaluated as part of the Food Quality Protection Act of 1996. Our goal was to assess exposure to OP insecticides in the ...U.S. general population over a six-year period. We analyzed 7,456 urine samples collected as part of three two-year cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999-2004. We measured six dialkylphosphate metabolites of OP pesticides to assess OP pesticide exposure. In NHANES 2003-2004, dimethylthiophosphate was detected most frequently with median and 95th percentile concentrations of 2.03 and 35.3 μg/L, respectively. Adolescents were two to three times more likely to have diethylphosphate concentrations above the 95th percentile estimate of 15.5 μg/L than adults and senior adults. Conversely, for dimethyldithiophosphate, senior adults were 3.8 times and 1.8 times more likely to be above the 95th percentile than adults and adolescents, respectively, while adults were 2.1 times more likely to be above the 95th percentile than the adolescents. Our data indicate that the most vulnerable segments of our population-children and older adults-have higher exposures to OP pesticides than other population segments. However, according to DAP urinary metabolite data, exposures to OP pesticides have declined during the last six years at both the median and 95th percentile levels.
The aim of this study was to examine various psychosocial, behavioral, and socio-environmental factors in a multiethnic sample of healthy-weight, overweight, and obese youths in the United States ...(US) and Mexico and determine differences by sex. We conducted a cross-sectional analysis of 633 youths aged 11-18 years who completed a self-reported questionnaire. Height and weight were measured to determine body mass index (BMI). Overweight and obese youth in both countries were significantly more likely to report a higher body image dissatisfaction (Odds Ratio (OR) = 1.67 and OR= 2.95, respectively), depressive symptoms (OR = 1.08 and OR = 1.12, respectively), perceive themselves as overweight (OR = 2.57) or obese (OR = 5.30), and a lower weight-specific quality of life (OR = 0.97 and OR = 0.95, respectively) than healthy-weight youth. Obese youth have lower healthy lifestyle priorities (OR = 0.75) and are less likely to be physically active (OR = 0.79) and eat breakfast (OR = 0.47) than healthy-weight youth. Additionally, overweight and obese youth are more likely to engage in weight control behaviors (OR = 5.19 and OR = 8.88, respectively) and restrained eating than healthy-weight youth. All the aforementioned results had a p-value of <0.05, which was considered statistically significant. The association between these factors and overweight or obesity remained significant after controlling for age, sex, race/ethnicity, and country. In conclusion, obesity was associated with a range of psychosocial, behavioral, and socio-environmental risk factors in both countries. Our findings support the need for multifactorial approaches when developing interventions to address the growing problem of obesity among youth in the US and Mexico.
We have developed a method to measure 12 urinary phenolic metabolites of pesticides or related chemicals. The target chemicals for our method are 2-isopropoxyphenol; 2,4-dichlorophenol; ...2,5-dichlorophenol; carbofuranphenol; 2,4,5-trichlorophenol; 2,4,6-trichlorophenol; 3,5,6-trichloro-2-pyridinol; para-nitrophenol, ortho-phenylphenol, pentachlorophenol, 1-naphthol and 2-naphthol. The sample preparation involves enzyme hydrolysis, isolation of the target chemicals using solid phase extraction cartridges, a phase-transfer catalyzed derivatization, cleanup using sorbent-immobilized liquid/liquid extraction cartridges, and concentration of the sample. Derivatized samples are analyzed by capillary gas chromatography-tandem mass spectroscopy using isotope dilution calibration for quantification. The limits of detection are in the mid ng/L range and the average coefficient of variation was below 15% for most of the analytes. Using our method, we measured concentrations of the target chemicals in urine samples from the general population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed a once weekly application, resulting in ...an increased sustained viral response rate. The analysis of serum HCV dynamics has been shown to be useful in predicting clinical effects and optimizing the treatment regimen.
The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b plus ribavirin.
Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once-weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once-weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy.
Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2. Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively. A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy. Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients.
Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.
Organophosphorus (OP) insecticides were among the first pesticides that EPA reevaluated as part of the Food Quality Protection Act of 1996. Our goal was to assess exposure to OP insecticides in the ...U.S. general population over a six-year period. We analyzed 7,456 urine samples collected as part of three two-year cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999–2004. We measured six dialkylphosphate metabolites of OP pesticides to assess OP pesticide exposure. In NHANES 2003–2004, dimethylthiophosphate was detected most frequently with median and 95th percentile concentrations of 2.03 and 35.3 µg/L, respectively. Adolescents were two to three times more likely to have diethylphosphate concentrations above the 95th percentile estimate of 15.5 µg/L than adults and senior adults. Conversely, for dimethyldithiophosphate, senior adults were 3.8 times and 1.8 times more likely to be above the 95th percentile than adults and adolescents, respectively, while adults were 2.1 times more likely to be above the 95th percentile than the adolescents. Our data indicate that the most vulnerable segments of our population—children and older adults—have higher exposures to OP pesticides than other population segments. However, according to DAP urinary metabolite data, exposures to OP pesticides have declined during the last six years at both the median and 95th percentile levels.
Organophosphorus (OP) insecticides were among the first pesticides that EPA reevaluated as part of the Food Quality Protection Act of 1996. Our goal was to assess exposure to OP insecticides in the ...U.S. general population over a six-year period. We analyzed 7,456 urine samples collected as part of three two-year cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999–2004. We measured six dialkylphosphate metabolites of OP pesticides to assess OP pesticide exposure. In NHANES 2003–2004, dimethylthiophosphate was detected most frequently with median and 95th percentile concentrations of 2.03 and 35.3 µg/L, respectively. Adolescents were two to three times more likely to have diethylphosphate concentrations above the 95th percentile estimate of 15.5 µg/L than adults and senior adults. Conversely, for dimethyldithiophosphate, senior adults were 3.8 times and 1.8 times more likely to be above the 95th percentile than adults and adolescents, respectively, while adults were 2.1 times more likely to be above the 95th percentile than the adolescents. Our data indicate that the most vulnerable segments of our population—children and older adults—have higher exposures to OP pesticides than other population segments. However, according to DAP urinary metabolite data, exposures to OP pesticides have declined during the last six years at both the median and 95th percentile levels.
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