Randomized controlled trial of propranolol on social communication and anxiety in children and young adults with autism spectrum disorder.

RATIONALE: Autism spectrum disorder (ASD) is characterized by impaired social communication and is also frequently characterized by co-occurring anxiety. Propranolol is widely utilized to treat performance and public speaking anxiety. Single-dose psychopharmacological challenge studies suggested benefits using propranolol for verbal tasks and social interaction. OBJECTIVE: We conducted a double-blinded, placebo-controlled trial of the ß-adrenergic antagonist propranolol in ASD for social interaction, anxiety, and language. METHODS: Seventy-four participants with ASD, age 7-24 years, were enrolled and randomized to a 12-week course of propranolol or placebo, with blinded assessments at baseline, 6 weeks, and 12 weeks. The primary outcome was the General Social Outcome Measure-2 (GSOM-2) for social interaction, and secondary outcomes were the Clinician Global Clinical Impression-Improvement (CGI-I) ratings independently conducted for social interaction, anxiety, and language at 6 weeks and 12 weeks. RESULTS: Sixty-nine participants completed the 12-week visit. No significant effect of drug was found for the GSOM-2 or the CGI-I for social interaction or language. CGI-I for anxiety showed greater improvement with propranolol at the 12-week time point (p = 0.045, odds ratio = 2.58 (95% CI = 1.02-6.52). Expected decreases in heart rate and blood pressure were observed with propranolol, and side effects were uncommon. CONCLUSIONS: Propranolol did not impact social interaction measures or language, but there were indications of a beneficial effect for anxiety. This will need confirmation in a larger multicenter trial, monitoring markers or characteristics to identify those participants most likely to respond to propranolol for anxiety, and determine whether there is a subset of participants that are responsive for other previously reported outcomes.

Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?

The human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The risk of being infected at least once in a lifetime among both men and women is estimated to be 50%. Although the majority of HPV infections are asymptomatic and improve within 2 years, approximately 10% of individuals develop a persistent infection and have an increased risk of developing carcinomas. The association of HPV and genital cancer is well established. However, there is evidence that HPV may also be associated with other cancers, including those of the gastrointestinal system. The aim of this review is to organize the current evidence of associations between HPV infections and oropharyngeal and gastrointestinal cancers, including the following: oropharyngeal, esophageal, gastric, colorectal, and anal cancers. A comprehensive review of the most up-to-date medical literature concluded that an HPV infection might have a role in the oncogenesis of gastrointestinal tract cancers. HPV may have a causal relationship with oropharyngeal and esophageal squamous cell cancers. However, the association between HPV and gastric and colorectal cancers is weaker. The development of cancer in the oropharyngeal and gastrointestinal tract is usually multifactorial, with HPV having a role in at least a subset of these cancers. HPV infections pose a big challenge due to their burden of infection and their oncogenic potential.

Spatial and temporal trends of poly- and perfluoroalkyl substances in fish fillets and water collected from pool 2 of the Upper Mississippi River.

In 2011, poly- and perfluoroalkyl substances (PFASs) were analyzed in surface water and fish fillet samples taken from Pool 2 of the Upper Mississippi River, a 33-mile stretch inclusive of the Minneapolis/St. Paul, Minnesota (USA) metropolitan area. Approximately 100 each of bluegill, freshwater drum, smallmouth bass, and white bass were sampled within the study area. Surface water samples were also collected from each of the 10 sampling reaches established for the study. Water and fillet samples were analyzed for perfluorinated carboxylic acids (C4-C12), perfluorinated sulfonic acids (C4, C6, and C8), and perfluorooctane sulfonamide. Perfluorooctane sulfonate (PFOS) was observed with the greatest frequency in fish fillets and ranged from 3.0 to 760 ng/g wet weight. Mean (geometric) PFOS concentrations in bluegill, freshwater drum, smallmouth bass, and white bass were 20, 28, 29, and 58 ng/g wet weight, respectively. When compared with fish data collected in 2009, a significant reduction (p < 0.05) in PFOS concentrations was noted. This finding was confirmed based on data from studies conducted in 2012 and 2013. Overall, between 2009 and 2013, PFOS concentrations decreased by 65, 76, and 50% for bluegill, freshwater drum, and white bass, respectively (44% decrease for smallmouth bass from 2009 to 2012). These declines in fish PFOS concentrations are consistent with ongoing efforts to effectively control sources of PFASs to the Mississippi River. Environ Toxicol Chem 2017;36:3138-3147. © 2017 SETAC.

Bioaccumulation of polychlorinated dibenzo-p-dioxins, dibenzofurans, and dioxin-like polychlorinated biphenyls in fishes from the Tittabawassee and Saginaw Rivers, Michigan, USA.

Characterizing biological factors associated with species-specific accumulation of contaminants is one of the major focuses in ecotoxicology and environmental chemistry studies. In this study, polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and non- and mono-ortho-substituted polychlorinated biphenyl (PCB) congeners were analyzed in various fish species from the Tittabawassee and Saginaw Rivers (12 fish species; n=314 individuals), Michigan, USA. Due to their migratory habits, greater delta(13)C stable isotope values were found in walleye and white sucker among 12 fish species. Meanwhile, the delta(15)N values indicated that the trophic status was least in carp and greatest in largemouth bass. The greatest total concentrations of dioxins were found in fishes with the lowest trophic status (carp (n=50) followed by channel catfish (n=49)), and concentrations of SigmaPCDD/Fs (20-440pg/g ww (wet weight)), SigmaPCBs (16-690ng/g ww), and TEQs (6.8-350pg/g ww) in carp were also greater than the least mean concentrations in other fishes. Contributions of various biological factors to the species accumulation were assessed. Body weight and lipid content were found to be the most significant factors influencing accumulation of SigmaPCDD/Fs. Lipid content and trophic level seemed to be dominant factors determining accumulation of SigmaPCB and TEQs, but negative correlations between trophic status and concentrations of SigmaPCBs and TEQs were observed possibly due to the great concentrations in benthivorous fishes such as carp occupying lower trophic levels. These factors can be used to predict the contaminant levels of dioxins and health risks of the fishes in the river ecosystem.

Chronic effects of polychlorinated dibenzofurans on mink in laboratory and field environments.

Mink are often used as a sentinel species in ecological risk assessments of chemicals such as polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), and dibenzofurans (PCDFs) that cause toxicity mediated through the aromatic hydrocarbon receptor. Considerable toxicological information is available on the effects of PCBs and PCDDs on mink, but limited toxicological information is available for PCDFs. Thus, exposure concentrations at which adverse effects occur could not be determined reliably for complex mixtures in which PCDFs dominate the total calculated concentration of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ). Two studies were conducted to evaluate the potential toxicity of PCDFs to mink. The first was a chronic exposure, conducted under controlled laboratory conditions, in which mink were exposed to 2,3,7,8-tetrachlorodibenzofuran (2,3,7,8-TCDF) concentrations as great as 2.4 x 10(3) ng 2,3,7,8-TCDF/kg wet-weight (ww) diet or 2.4 x 10(2) ng TEQ(2006-WHO-mammal)/kg ww diet. In that study, transient decreases in body masses of kits relative to the controls was the only statistically significant effect observed. The second study was a 3-y field study during which indicators of individual health, including hematological and morphological parameters, were determined for mink exposed chronically to a mixture of PCDDs and PCDFs under field conditions. In the field study, there were no statistically significant differences in any of the measured parameters between mink exposed to a median estimated dietary dose of 31 ng TEQ(2006-WHO-mammal)/kg ww and mink from an upstream reference area where they had a median dietary exposure of 0.68 ng TEQ(2006-WHO-mammal)/kg ww. In both studies, concentrations of TEQ(2006-WHO-mammal) to which the mink were exposed exceeded those at which adverse effects, based on studies with PCDD and PCB congeners, would have been expected. Yet in both instances where PCDF congeners were the sole or predominant source of the TEQ(2006-WHO-mammal), predicted adverse effects were not observed. Taken together, the results of these studies suggest that the values of the mammalian-specific toxicity equivalency factors suggested by the World Health Organization overestimate the toxic potency of PCDFs to mink. Therefore, hazard cannot be accurately predicted by making comparisons to toxicity reference values derived from exposure studies conducted with PCBs or PCDDs in situations where mink are exposed to TEQ mixtures dominated by PCDFs.

Effects of repeated exposure to malathion on growth, food consumption, and locomotor performance of the western fence lizard (Sceloporus occidentalis).

Effects of repeated pollutant exposure on growth, locomotor performance, and behavior have rarely been evaluated in reptiles. We administered three doses of malathion (2.0, 20, or 100mg/kg body weight) to western fence lizards (Sceloporus occidentalis) over an 81day period. Eight and 23% mortality occurred at 20 and 100mg/kg (p=0.079) and 85% of lizards in the 100mg/kg group exhibited clinical symptoms of poisoning. Growth, food consumption, body condition index, and terrestrial locomotor performance were not significantly influenced by malathion. However, arboreal sprint velocity was significantly reduced in lizards receiving 100mg/kg. Fifty percent of lizards in the 100mg/kg group also refused to sprint in the arboreal setting (p=0.085). Based on these results, arboreal locomotor performance was the most sensitive metric of exposure we evaluated. Further study of compounds such as malathion is warranted due to highly variable application rates and exposure scenarios.

Accumulation of polychlorinated biphenyls from floodplain soils by passerine birds.

Eggs, nestlings, and adults of the eastern bluebird (Sialia sialis) and house wren (Troglodytes aedon) were collected at a polychlorinated biphenyl (PCB)-contaminated site and a reference location on the Kalamazoo River (MI, USA). Eggs and nestlings of eastern bluebirds at the more contaminated location contained concentrations of 8.3 and 1.3 mg/kg, respectively, of total PCBs and 77 and 6.3 ng/kg, respectively, of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs). Eggs, nestlings, and adults of house wrens from the contaminated location contained 6.3, 0.77, and 3.2 mg/kg, respectively, of PCBs and 400, 63, and 110 ng/kg, respectively, of TEQs. Concentrations of total PCBs and TEQs in tissues at the more contaminated location were significantly greater than concentrations in tissues at the reference site for all tissue types of both species. Exposures of the two species studied were different, which suggests that terrestrial-based insectivorous passerine species, foraging in the same area, may have differential exposure to PCBs depending on specific foraging techniques and the insect orders that are targeted. Despite the greater accumulation of PCBs at the more contaminated location, the risk of exposure to PCBs did not exceed the threshold for adverse effects at either location.