Effects of soluble copper and copper oxide nanoparticle exposure on the immune system of mussels,Mytilus galloprovincialis

Copper and copper oxide nanomaterials (nCuO) can enter the marine environment negatively impacting mussels, an environmental and commercially relevant organism. We analyzed the effects on the immune system of adult mussels exposed to soluble copper (CuSO₄, 20‐50 μg/L) or nCuO (100‐450 μg/L). CuSO₄ caused significant copper accumulation in gills and cell‐free hemolymph, while nCuO caused cell damage to gills and significant copper accumulation in hemocytes, the most abundant cells in the hemolymph. Both sources of copper caused cellular toxicity in hemocytes by increasing reactive oxygen species production and lysosome abundance, and decreasing multi‐drug resistance transporter activity. Though hemocyte abundance was not affected, their in‐vitro phagocytic activity decreased, explaining the slight (but not statistically significant) increase in bacterial proliferation in mussels exposed to the pathogenic bacteria Vibrio tubiashii following copper exposure. Thus, exposure to non‐lethal concentrations of CuSO₄ or nCuO can potentially increase mussel susceptibility to bacterial infections.     

Fractional Exhaled Nitric Oxide in the Interpretation of Specific Inhalational Challenge Tests for Occupational Asthma

Purpose

Fractional exhaled nitric oxide (FE_NO) measurements are recommended for the assessment of eosinophilic airway inflammation in asthma. Clinically relevant increases in FE_NO have been reported 24 h after positive specific inhalational challenge (SIC) tests in occupational asthma. We aimed to determine whether positive SICs could be discriminated from control tests, on the basis of change in FE_NO.

Methods

We reviewed all positive SICs to a variety of agents performed at our institution 2008–2012 and gathered data on age, sex, asthmatic response (immediate/dual/late), smoking status, inhaled corticosteroid usage, and FE_NO pre- and 24-h postcontrol and positive SIC from each worker. Changes in FE_NO after positive SICs were compared with control SICs from each worker, by using paired Student’s t tests.

Results

In 16 workers, negative control challenges were associated with mean changes in FE_NO of 9 % (95 % CI ?1.14 to 19.01) or 1.1 ppb (95 % CI ?3.59 to 5.84); 2 of 16 (13 %) workers tested showed increases in FE_NO that were clinically relevant based on recent guidelines. Subsequent positive SICs were associated with mean changes in FE_NO of 7 % (95 % CI ?15.73 to 29.6) or 2.1 ppb (95 % CI ?6.07 to 10.19), which were not significantly different to controls; only 2 of 16 (13 %) workers had FE_NO changes that were clinically relevant.

Conclusions

FE_NO changes above the upper confidence limits of ≥20 % or ≥6 ppb may be considered to be outside the range of normality. However, the majority of workers who had clearly positive SICs to common low molecular weight agents also had no statistically or clinically relevant increase in FE_NO. Therefore, change in FE_NO does not predict a positive SIC in this group.     

Interneuron precursor transplants in adult hippocampus reverse psychosis-relevant features in a mouse model of hippocampal disinhibition

GABAergic interneuron hypofunction is hypothesized to underlie hippocampal dysfunction in schizophrenia. Here, we use the cyclin D2 knockout (Ccnd2^−/−) mouse model to test potential links between hippocampal interneuron deficits and psychosis-relevant neurobehavioral phenotypes. Ccnd2^−/− mice show cortical PV⁺ interneuron reductions, prominently in hippocampus, associated with deficits in synaptic inhibition, increased in vivo spike activity of projection neurons, and increased in vivo basal metabolic activity (assessed with fMRI) in hippocampus. Ccnd2^−/− mice show several neurophysiological and behavioral phenotypes that would be predicted to be produced by hippocampal disinhibition, including increased ventral tegmental area dopamine neuron population activity, behavioral hyperresponsiveness to amphetamine, and impairments in hippocampus-dependent cognition. Remarkably, transplantation of cells from the embryonic medial ganglionic eminence (the major origin of cerebral cortical interneurons) into the adult Ccnd2^−/− caudoventral hippocampus reverses these psychosis-relevant phenotypes. Surviving neurons from these transplants are 97% GABAergic and widely distributed within the hippocampus. Up to 6 mo after the transplants, in vivo hippocampal metabolic activity is lowered, context-dependent learning and memory is improved, and dopamine neuron activity and the behavioral response to amphetamine are normalized. These findings establish functional links between hippocampal GABA interneuron deficits and psychosis-relevant dopaminergic and cognitive phenotypes, and support a rationale for targeting limbic cortical interneuron function in the prevention and treatment of schizophrenia.Precursors of most γ-aminobutyric acid (GABA)-releasing interneurons of the cerebral cortex and the hippocampus originate in the embryonic medial ganglionic eminence (MGE) (1–3). A subpopulation of MGE-derived cells differentiates into fast-spiking, parvalbumin-expressing (PV⁺) interneurons that tightly regulate the activity and synchronization of cortical projection neurons (2, 4). Structural and functional deficits in PV⁺ interneurons are hypothesized as a pathophysiological mechanism in schizophrenia and psychotic disorders (4–6).Although psychotic disorders are clearly heterogeneous in etiology, disinhibition within temporolimbic cortical circuits is postulated as a core pathophysiology underlying positive symptoms (e.g., delusions and hallucinations) and a subset of cognitive disturbances that manifest with psychosis (4, 5, 7). Postmortem studies of brains from individuals with psychotic disorders show reduced molecular markers of the number and/or function of PV⁺ interneurons in the hippocampus (6, 8). Consistent with these observations, basal metabolic activity in the hippocampus, as measured with functional magnetic resonance imaging (fMRI), is increased in schizophrenia, a phenotype that predicts psychosis and positive symptom severity (5, 7). This abnormal resting activity is postulated to underlie abnormal recruitment of hippocampal circuits during cognitive performance (5, 9). Striatal dopamine (DA) release capacity is also increased and correlated with positive symptoms in schizophrenia and its risk states (10, 11). Importantly, hippocampal hyperactivity may contribute to DA dysregulation (12), because rodent studies show that caudoventral hippocampal (in the primate, anterior hippocampal) efferents regulate the activity of DA neurons and medial striatal DA release (13, 14).Thus, converging evidence implicates hippocampal disinhibition in the abnormal striatal DA transmission and cognitive impairment in schizophrenia. However, the role of hippocampal inhibitory interneurons in psychosis-relevant circuitry remains to be established. To this end, we used the cyclin D2 (Ccnd2) knockout mouse model (15), which displays a relatively selective deficit in cortical PV⁺ interneurons, and transplantation of interneuron precursors from the MGE to elucidate relationships between reduced hippocampal GABA interneuron function and multiple psychosis-relevant phenotypes, and to explore a novel treatment strategy for psychosis.     

Prostate cancer measurements on serial MRI during active surveillance: it’s time to be PRECISE

Objective:The PRECISE criteria for reporting multiparametric MRI in patients on active surveillance (AS) for prostate cancer (PCa) score the likelihood of clinically significant change over time using a 1–5 scale, where 4 or 5 indicates radiological progression. According to the PRECISE recommendations, the index lesion size can be reported using different definitions of volume (planimetry or ellipsoid formula) or by measuring one or two diameters. We compared different measurements using planimetry as the reference standard and stratified changes according to the PRECISE scores.Methods:We retrospectively analysed 196 patients on AS with PCa confirmed by targeted biopsy who had two MR scans (baseline and follow-up). Lesions were measured on T₂ weighted imaging (T₂WI) according to all definitions. A PRECISE score was assessed for each patient.Results:The ellipsoid formula exhibited the highest correlation with planimetry at baseline (ρ = 0.97) and follow-up (ρ = 0.98) imaging, compared to the biaxial measurement and single maximum diameter. There was a significant difference (p < 0.001) in the yearly percentage volume change between radiological regression/stability (PRECISE 2–3) and progression (PRECISE 4–5) for planimetry (39.64%) and for the ellipsoid formula (46.78%).Conclusion:The ellipsoid formula could be used to monitor tumour growth during AS. Evidence of a significant yearly percentage volume change between radiological regression/stability (PRECISE 2-3) and progression (PRECISE 4-5) has been also observed.Advances in knowledge:The ellipsoid formula is a reasonable surrogate for planimetry in capturing tumour volume changes on T₂WI in patients on imaging-led AS. This is also associated with radiological changes using the PRECISE recommendations.     

Vital Signs: Fruit and Vegetable Intake Among Children — United States, 2003–2010

Background

Eating more fruits and vegetables adds underconsumed nutrients to diets, reduces the risks for leading causes of illness and death, and helps manage body weight. This report describes trends in the contributions of fruits and vegetables to the diets of children aged 2–18 years.

Methods

CDC analyzed 1 day of 24-hour dietary recalls from the National Health and Nutrition Examination Surveys from 2003 to 2010 to estimate trends in children’s fruit and vegetable intake in cup-equivalents per 1,000 calories (CEPC) and trends by sex, age, race/ethnicity, family income to poverty ratio, and obesity status. Total fruit includes whole fruit (all fruit excluding juice) and fruit juice (from 100% juice, foods, and other beverages). Total vegetables include those encouraged in the Dietary Guidelines for Americans, 2010 (i.e., dark green, orange, and red vegetables and legumes), white potatoes, and all other vegetables.

Results

Total fruit intake among children increased from 0.55 CEPC in 2003–2004 to 0.62 in 2009–2010 because of significant increases in whole fruit intake (0.24 to 0.40 CEPC). Over this period, fruit juice intake significantly decreased (0.31 to 0.22 CEPC). Total vegetable intake did not change (0.54 to 0.53 CEPC). No socio-demographic group met the Healthy People 2020 target of 1.1 CEPC vegetables, and only children aged 2–5 years met the target of 0.9 CEPC fruits.

Conclusions

Children’s total fruit intake increased because of increases in whole fruit consumption, but total vegetable intake remained unchanged.

Implications for Public Health Practice

Increased attention to the policies and food environments in multiple settings, including schools, early care and education, and homes might help continue the progress in fruit intake and improve vegetable intake.