DNA damage and health effects in juvenile haddock (Melanogrammus aeglefinus) exposed to PAHs associated with oil-polluted sediment or produced water.

The research objective was to study the presence of DNA damages in haddock exposed to petrogenic or pyrogenic polyaromatic hydrocarbons (PAHs) from different sources: 1) extracts of oil produced water (PW), dominated by 2-ring PAHs; 2) distillation fractions of crude oil (representing oil-based drilling mud), dominated by 3-ring PAHs; 3) heavy pyrogenic PAHs, mixture of 4/5/6-ring PAHs. The biological effect of the different PAH sources was studied by feeding juvenile haddock with low doses of PAHs (0.3-0.7 mg PAH/kg fish/day) for two months, followed by a two-months recovery. In addition to the oral exposure, a group of fish was exposed to 12 single compounds of PAHs (4/5/6-ring) via intraperitoneal injection. The main endpoint was the analysis of hepatic and intestinal DNA adducts. In addition, PAH burden in liver, bile metabolites, gene and protein expression of CYP1A, GST activity, lipid peroxidation, skeletal deformities and histopathology of livers were evaluated. Juvenile haddock responded quickly to both intraperitoneal injection and oral exposure of 4/5/6-ring PAHs. High levels of DNA adducts were detected in livers three days after the dose of the single compound exposure. Fish had also high levels of DNA adducts in liver after being fed with extracts dominated by 2-ring PAHs (a PW exposure scenario) and 3-ring PAHs (simulating an oil exposure scenario). Elevated levels of DNA adducts were observed in the liver of all exposed groups after the 2 months of recovery. High levels of DNA adduct were found also in the intestines of individuals exposed to oil or heavy PAHs, but not in the PW or control groups. This suggests that the intestinal barrier is very important for detoxification of orally exposures of PAHs.

Frontal cortex selectively overrides auditory processing to bias perception for looming sonic motion.

Rising intensity sounds signal approaching objects traveling toward an observer. A variety of species preferentially respond to looming over receding auditory motion, reflecting an evolutionary perceptual bias for recognizing approaching threats. We probed the neural origins of this stark perceptual anisotropy to reveal how the brain creates privilege for auditory looming events. While recording neural activity via electroencephalography (EEG), human listeners rapidly judged whether dynamic (intensity varying) tones were looming or receding in percept. Behaviorally, listeners responded faster to auditory looms confirming a perceptual bias for approaching signals. EEG source analysis revealed sensory activation localized to primary auditory cortex (PAC) and decision-related activity in prefrontal cortex (PFC) within 200 ms after sound onset followed by additional expansive PFC activation by 500 ms. Notably, early PFC (but not PAC) activity rapidly differentiated looming and receding stimuli and this effect roughly co-occurred with sound arrival in auditory cortex. Brain-behavior correlations revealed an association between PFC neural latencies and listeners' speed of sonic motion judgments. Directed functional connectivity revealed stronger information flow from PFC → PAC during looming vs. receding sounds. Our electrophysiological data reveal a critical, previously undocumented role of prefrontal cortex in judging dynamic sonic motion. Both faster neural bias and a functional override of obligatory sensory processing via selective, directional PFC signaling toward auditory system establish the perceptual privilege for approaching looming sounds.

A pilot investigation of audiovisual processing and multisensory integration in patients with inherited retinal dystrophies.

BACKGROUND: In this study, we examined audiovisual (AV) processing in normal and visually impaired individuals who exhibit partial loss of vision due to inherited retinal dystrophies (IRDs). METHODS: Two groups were analyzed for this pilot study: Group 1 was composed of IRD participants: two with autosomal dominant retinitis pigmentosa (RP), two with autosomal recessive cone-rod dystrophy (CORD), and two with the related complex disorder, Bardet-Biedl syndrome (BBS); Group 2 was composed of 15 non-IRD participants (controls). Audiovisual looming and receding stimuli (conveying perceptual motion) were used to assess the cortical processing and integration of unimodal (A or V) and multimodal (AV) sensory cues. Electroencephalography (EEG) was used to simultaneously resolve the temporal and spatial characteristics of AV processing and assess differences in neural responses between groups. Measurement of AV integration was accomplished via quantification of the EEG's spectral power and event-related brain potentials (ERPs). RESULTS: Results show that IRD individuals exhibit reduced AV integration for concurrent audio and visual (AV) stimuli but increased brain activity during the unimodal A (but not V) presentation. This was corroborated in behavioral responses, where IRD patients showed slower and less accurate judgments of AV and V stimuli but more accurate responses in the A-alone condition. CONCLUSIONS: Collectively, our findings imply a neural compensation from auditory sensory brain areas due to visual deprivation.

Very low embryonic crude oil exposures cause lasting cardiac defects in salmon and herring.

The 1989 Exxon Valdez disaster exposed embryos of pink salmon and Pacific herring to crude oil in shoreline spawning habitats throughout Prince William Sound, Alaska. The herring fishery collapsed four years later. The role of the spill, if any, in this decline remains one of the most controversial unanswered questions in modern natural resource injury assessment. Crude oil disrupts excitation-contraction coupling in fish heart muscle cells, and we show here that salmon and herring exposed as embryos to trace levels of crude oil grow into juveniles with abnormal hearts and reduced cardiorespiratory function, the latter a key determinant of individual survival and population recruitment. Oil exposure during cardiogenesis led to specific defects in the outflow tract and compact myocardium, and a hypertrophic response in spongy myocardium, evident in juveniles 7 to 9 months after exposure. The thresholds for developmental cardiotoxicity were remarkably low, suggesting the scale of the Exxon Valdez impact in shoreline spawning habitats was much greater than previously appreciated. Moreover, an irreversible loss of cardiac fitness and consequent increases in delayed mortality in oil-exposed cohorts may have been important contributors to the delayed decline of pink salmon and herring stocks in Prince William Sound.

Potent phototoxicity of marine bunker oil to translucent herring embryos after prolonged weathering.

Pacific herring embryos (Clupea pallasi) spawned three months following the Cosco Busan bunker oil spill in San Francisco Bay showed high rates of late embryonic mortality in the intertidal zone at oiled sites. Dead embryos developed to the hatching stage (e.g. fully pigmented eyes) before suffering extensive tissue deterioration. In contrast, embryos incubated subtidally at oiled sites showed evidence of sublethal oil exposure (petroleum-induced cardiac toxicity) with very low rates of mortality. These field findings suggested an enhancement of oil toxicity through an interaction between oil and another environmental stressor in the intertidal zone, such as higher levels of sunlight-derived ultraviolet (UV) radiation. We tested this hypothesis by exposing herring embryos to both trace levels of weathered Cosco Busan bunker oil and sunlight, with and without protection from UV radiation. Cosco Busan oil and UV co-exposure were both necessary and sufficient to induce an acutely lethal necrotic syndrome in hatching stage embryos that closely mimicked the condition of dead embryos sampled from oiled sites. Tissue levels of known phototoxic polycyclic aromatic compounds were too low to explain the observed degree of phototoxicity, indicating the presence of other unidentified or unmeasured phototoxic compounds derived from bunker oil. These findings provide a parsimonious explanation for the unexpectedly high losses of intertidal herring spawn following the Cosco Busan spill. The chemical composition and associated toxicity of bunker oils should be more thoroughly evaluated to better understand and anticipate the ecological impacts of vessel-derived spills associated with an expanding global transportation network.

Sublethal exposure to crude oil during embryonic development alters cardiac morphology and reduces aerobic capacity in adult fish.

Exposure to high concentrations of crude oil produces a lethal syndrome of heart failure in fish embryos. Mortality is caused by cardiotoxic polycyclic aromatic hydrocarbons (PAHs), ubiquitous components of petroleum. Here, we show that transient embryonic exposure to very low concentrations of oil causes toxicity that is sublethal, delayed, and not counteracted by the protective effects of cytochrome P450 induction. Nearly a year after embryonic oil exposure, adult zebrafish showed subtle changes in heart shape and a significant reduction in swimming performance, indicative of reduced cardiac output. These delayed physiological impacts on cardiovascular performance at later life stages provide a potential mechanism linking reduced individual survival to population-level ecosystem responses of fish species to chronic, low-level oil pollution.

Changes in tobacco use among adolescent smokers in substance abuse treatment.

Adolescents with substance use disorders (SUDs) smoke cigarettes more than youth in the general population. Little is known about changes in smoking patterns during and after outpatient SUD treatment. We examined whether receiving SUD treatment had a differential impact on cigarette smoking behaviors of mild (<10 cigarettes per day [CPD]), moderate (10-19 CPD), and heavy (>or=20 CPD) smokers (smoked on >or=60 days in the past 90). Our sample included 378 adolescents from the Cannabis Youth Treatment study, who were assessed at intake, and after 3, 6, 9, and 12 months. Results indicate that after controlling for the effect of changes in cannabis use, mild smokers decreased days of smoking during treatment and follow-up, whereas moderate and heavy smokers demonstrated a small decrease over treatment, and no change over follow-up. Heavy smokers demonstrated a slight decrease in CPD during the treatment phase. These results suggest that, whereas cigarette smoking may decrease for mild smokers while in SUD treatment, the addition of specialized smoking interventions may be necessary to effect change in cigarette smoking for moderate and heavy smokers.

Dietary toxins, endoplasmic reticulum (ER) stress and diabetes.

The incidence of Type 1 diabetes has been increasing at a rate too rapid to be due to changes in genetic risk. Instead changes in environmental factors are the likely culprit. The endoplasmic reticulum (ER) plays an important role in the production of newly synthesized proteins and interference with these processes leads to ER stress. The insulin-producing beta cells are particularly prone to ER stress as a result of their heavy engagement in insulin production. Increasing evidence suggests ER stress is central to initiation and progression of Type 1 diabetes. An early environmental exposure, such as toxins and viral infections, can impart a significant physiological load on beta cells to initiate abnormal processing of proinsulin, ER stress and insulin secretory defects. Release of altered proinsulin from the beta cells early in life may trigger autoimmunity in those with genetic susceptibility leading to cytokine-induced nitric oxide production and so exacerbating ER stress in beta cells, ultimately leading to apoptosis of beta cells and diabetes. Here we suggest that ER stress is an inherent cause of beta cell dysfunction and environmental factors, in particular dietary toxins derived from Streptomyces in infected root vegetables, can impart additional stress that aggravates beta cell death and progression to diabetes. Furthermore, we propose that the increasing incidence of Type 1 diabetes may be accounted for by increased dietary exposure to ER-stress-inducing Streptomyces toxins.

Maternal diet during pregnancy and islet autoimmunity in offspring.

BACKGROUND: Recent studies on the etiology of type 1 diabetes mellitus (T1DM) suggest that the components of the infant diet are associated with islet autoimmunity (IA), a precursor of T1DM. The role of prenatal nutritional exposures has not been thoroughly investigated. METHODS: The Diabetes Autoimmunity Study in the Young has enrolled newborns from 1993 to 2004 at increased risk for T1DM based on human leukocyte antigen (HLA) genotype and family history of T1DM. The child is tested for islet autoantibodies at 9 and 15 months, 2 yr, and annually thereafter. We conducted a cohort study of 642 subjects for whom a Willett food frequency questionnaire for the mother's third trimester diet was completed. A case is defined as a subject who tests positive for islet autoantibodies at two consecutive blood draws and is still positive (or diabetic) at last follow-up (n = 27). Maternal consumption frequencies of potatoes, other root vegetables, gluten-containing foods, non-gluten cereal grains, cow's milk and cow's milk products, fruits, vegetables, meat and poultry, and fish were analyzed in a survival analysis. RESULTS: Adjusting for breast-feeding duration, age at first cereal introduction, ethnicity, HLA genotype, family history of T1DM, and total caloric intake, higher maternal intake of potatoes (hazard ratio for one standard deviation difference: 0.49, 95% confidence interval: 0.28-0.86) was associated with a delayed time to IA onset. No other food groups ingested during pregnancy were associated with IA in the child. CONCLUSIONS: The composition of the maternal diet during pregnancy may play a role in the offspring's risk of development of IA and potentially T1DM.

Motivational enhancement and coping skills training for cocaine abusers: effects on substance use outcomes.

AIMS: This clinical trial investigated effects of motivational enhancement treatment (MET) and group coping-skills training (CST) tailored for cocaine dependence. Effects of MET were hypothesized to be greater with CST and for less motivated patients. DESIGN AND INTERVENTIONS: A 2 x 2 design investigated two individual sessions of MET compared to meditation-relaxation (MRT), followed by four group sessions of CST versus drug education (ED), as daily adjuncts to intensive treatment. SETTING: The substance abuse program provided full-day treatment with a learning-theory and 12-Step orientation. PARTICIPANTS: Cocaine-dependent patients were recruited. MEASUREMENTS: Assessment included treatment retention; change in cocaine-related urge, self-efficacy, pros and cons, and motivation; substance use and problems during 12-month follow-up. Findings Of 165 patients, follow-up status is known for 90% (n = 149). Patients in MET with low initial motivation to change reported less cocaine and alcohol relapse and use days and fewer alcohol problems than MET patients with higher initial motivation. MET produced more employment improvement than MRT, with no other significant benefit for MET. Patients with higher motivation had more cocaine use and alcohol problems after MET than MRT. Group CST reduced cocaine and alcohol use during follow-up for women only and reduced alcohol relapse for men and women. CONCLUSIONS: MET is more beneficial for patients with lower initial motivation than for patients with high initial motivation. CST reduced cocaine and alcohol use for women only and reduced alcohol relapses, in contrast to results with lengthier individual CST.