Health symptoms among adults living near a coal-burning power plant.

Coal ash is a waste product generated when coal is burned for energy. The purpose of this study was to assess health symptoms in adults living near a coal-burning power plant and compare the symptoms to a non-exposed population. A community-based mixed methods study was conducted with four neighborhoods adjacent to a coal-burning power plant. The comparison population was not exposed to coal ash and did not live near a coal-burning power plant. Adults who lived near the coal-burning power plant were significantly more likely to suffer from respiratory (AOR = 5.27, 95% CI = 2.16-12.0), gingiva (AOR = 2.46, 95% CI = 1.46-4.15), and skin symptoms (AOR = 3.37, 95% CI = 2.09-5.43). Results suggest that health symptoms may develop in people living near coal-burning power plants.

The myeloid immune signature of enterotoxigenic Bacteroides fragilis-induced murine colon tumorigenesis.

Enterotoxigenic Bacteroides fragilis (ETBF), a human commensal and candidate pathogen in colorectal cancer (CRC), is a potent initiator of interleukin-17 (IL-17)-dependent colon tumorigenesis in MinApc+/- mice. We examined the role of IL-17 and ETBF on the differentiation of myeloid cells into myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages, which are known to promote tumorigenesis. The myeloid compartment associated with ETBF-induced colon tumorigenesis in Min mice was defined using flow cytometry and gene expression profiling. Cell-sorted immature myeloid cells were functionally assayed for inhibition of T-cell proliferation and inducible nitric oxide synthase expression to delineate MDSC populations. A comparison of ETBF infection with that of other oncogenic bacteria (Fusobacterium nucleatum or pks+Escherichia coli) revealed a specific, ETBF-associated colonic immune infiltrate. ETBF-triggered colon tumorigenesis is associated with an IL-17-driven myeloid signature characterized by subversion of steady-state myelopoiesis in favor of the generation of protumoral monocytic-MDSCs (MO-MDSCs). Combined action of the B. fragilis enterotoxin BFT and IL-17 on colonic epithelial cells promoted the differentiation of MO-MDSCs, which selectively upregulated Arg1 and Nos2, produced NO, and suppressed T-cell proliferation. Evidence of a pathogenic inflammatory signature in humans colonized with ETBF may allow for the identification of populations at risk for developing colon cancer.

A Dollars and "Sense" Exploration of Vape Shop Spending and E-cigarette Use.

INTRODUCTION: Across the US, vape shops have emerged to provide e-cigarette users access to products not usually available at gas stations or retail stores. As vape shop sales have steadily increased, so have questions about the impact of marketing and price on e-cigarette use behaviors. In this exploratory analysis, we aim to characterize spending on e-cigarettes and evaluate the association with customer perceptions and use behaviors. METHODS: In a cross-sectional survey of vape shop customers (n=78), perceptions and use of e-cigarettes and tobacco products were assessed. Descriptive statistics and multivariate logistic regression were used to evaluate the association between spending and socioeconomic factors, demographics, and use behaviors. RESULTS: Overall, spending amounts ranged from less than $10/month to more than $250/month, with a median around $50-75/month. Males spent more than females (p=0.003), but spending did not significantly differ by age (p=0.13). Customers who spent more than $50/month used lower levels of nicotine (mg/ml) (p=0.003) but a greater quantity of e-liquid (ml/month) (p<0.0001) compared to customers who spent under that amount. Mod use and intention to use e-cigarettes as a cessation device were significantly associated with vape shop spending in the regression model (OR= 17.5; 95% CI= (4.3, 70.2) and OR=0.22; 95% CI= (0.06, 0.75), respectively). CONCLUSIONS: Spending appears to be significantly associated with e-cigarette use behaviors. Making "sense" of the potential relationships between the dollars spent at vape shops and consumer use behaviors is important as regulations for e-cigarette sales are proposed.

Microbiome changes associated with sustained eradication of Clostridium difficile after single faecal microbiota transplantation in children with and without inflammatory bowel disease.

BACKGROUND: Little data are available regarding the effectiveness and associated microbiome changes of faecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI) in children, especially in those with inflammatory bowel disease (IBD) with presumed underlying dysbiosis. AIM: To investigate C. difficile eradication and microbiome changes with FMT in children with and without IBD. METHODS: Children with a history of recurrent CDI (≥3 recurrences) underwent FMT via colonoscopy. Stool samples were collected pre-FMT and post-FMT at 2-10 weeks, 10-20 weeks and 6 months. The v4 hypervariable region of the 16S rRNA gene was sequenced. C. difficile toxin B gene polymerase chain reaction was performed. RESULTS: Eight children underwent FMT for CDI; five had IBD. All had resolution of CDI symptoms. All tested had eradication of C. difficile at 10-20 weeks and 6 months post-FMT. Pre-FMT patient samples had significantly decreased bacterial richness compared with donors (P = 0.01), in those with IBD (P = 0.02) and without IBD (P = 0.01). Post-FMT, bacterial diversity in patients increased. Six months post-FMT, there was no significant difference between bacterial diversity of donors and patients without IBD; however, bacterial diversity in those with IBD returned to pre-FMT baseline. Microbiome composition at 6 months in IBD-negative patients more closely approximated donor composition compared to IBD-positive patients. CONCLUSIONS: FMT gives sustained C. difficile eradication in children with and without IBD. FMT-restored diversity is sustained in children without IBD. In those with IBD, bacterial diversity returns to pre-FMT baseline by 6 months, suggesting IBD host-related mechanisms modify faecal microbiome diversity.

Fecal detection of enterotoxigenic Bacteroides fragilis.

Bacteroides fragilis is a common colonic symbiote of which one subtype, enterotoxigenic Bacteroides fragilis (ETBF), causes inflammatory diarrhea. However, asymptomatic ETBF colonization is common. Through its primary virulence factor, B. fragilis toxin (BFT), ETBF causes asymptomatic, chronic colitis in C57BL/6 mice and increased colon tumorigenesis in multiple intestinal neoplasia mice. Human studies suggest an association between ETBF infection, inflammatory bowel disease, and colon cancer. Additional studies on ETBF epidemiology are, therefore, crucial. The goal of this study is to develop a reliable fecal diagnostic for ETBF. To develop a sensitive assay for ETBF, we tested multiple protocols on mouse stools spiked with serially diluted ETBF. Each assay was based on either touchdown or quantitative polymerase chain reaction (qPCR) and used primers targeted to bft to detect ETBF. Using touchdown PCR or qPCR, the mean ETBF detection limit was 1.55 × 10(6) colony-forming units (CFU)/g stool and 1.33 × 10(4) CFU/g stool, respectively. Augmentation of Bacteroides spp. growth in fecal samples using PYGB (Peptone Yeast Glucose with Bile) broth enhanced ETBF detection to 2.93 × 10(2) CFU/g stool using the touchdown PCR method and 2.63 × 10(2) CFU/g stool using the qPCR method. Fecal testing using combined culture-based amplification and bft touchdown PCR is a sensitive assay for the detection of ETBF colonization and should be useful in studying the role of ETBF colonization in intestinal diseases, such as inflammatory bowel disease and colon cancer. We conclude that touchdown PCR with culture-based amplification may be the optimal ETBF detection strategy, as it performs as well as qPCR with culture-based amplification, but is a less expensive technique.

Few-cycle driven relativistically oscillating plasma mirrors: a source of intense isolated attosecond pulses.

The conditions required for the production of isolated attosecond pulses from relativistically oscillating mirrors (ROM) are investigated numerically and experimentally. In simulations, carrier-envelope-phase-stabilized three-cycle pulses are found to be sufficient to produce isolated attosecond pulses, while two-cycle pulses will predominantly lead to isolated attosecond pulses even in the absence of carrier-envelope stabilization. Using a state-of-the-art laser system delivering three-cycle pulses at multiple-terawatt level, we have generated higher harmonics up to 70 eV photon energy via the ROM mechanism. The observed spectra are in agreement with theoretical expectations and highlight the potential of few-cycle-driven ROM harmonics for intense isolated attosecond pulse generation for performing extreme ultraviolet-pump extreme ultraviolet-probe experiments.

Absolute charge calibration of scintillating screens for relativistic electron detection.

We report on new charge calibrations and linearity tests with high-dynamic range for eight different scintillating screens typically used for the detection of relativistic electrons from laser-plasma based acceleration schemes. The absolute charge calibration was done with picosecond electron bunches at the ELBE linear accelerator in Dresden. The lower detection limit in our setup for the most sensitive scintillating screen (KODAK Biomax MS) was 10 fC/mm(2). The screens showed a linear photon-to-charge dependency over several orders of magnitude. An onset of saturation effects starting around 10-100 pC/mm(2) was found for some of the screens. Additionally, a constant light source was employed as a luminosity reference to simplify the transfer of a one-time absolute calibration to different experimental setups.

Differences in SMN1 allele frequencies among ethnic groups within North America.

BACKGROUND: Spinal muscular atrophy (SMA) is the most common inherited lethal disease of children. Various genetic deletions involving the bi-allelic loss of SMN1 exon 7 are reported to account for 94% of affected individuals. Published literature places the carrier frequency for SMN1 mutations between 1 in 25 and 1 in 50 in the general population. Although SMA is considered to be a pan-ethnic disease, carrier frequencies for many ethnicities, including most ethnic groups in North America, are unknown. OBJECTIVES AND METHODS: To provide an accurate assessment of SMN1 mutation carrier frequencies in African American, Ashkenazi Jewish, Asian, Caucasian, and Hispanic populations, more than 1000 specimens in each ethnic group were tested using a clinically validated, quantitative real-time polymerase chain reaction (PCR) assay that measures exon 7 copy number. RESULTS: The observed one-copy genotype frequency was 1 in 37 (2.7%) in Caucasian, 1 in 46 (2.2%) in Ashkenazi Jew, 1 in 56 (1.8%) in Asian, 1 in 91 (1.1%) in African American, and 1 in 125 (0.8%) in Hispanic specimens. Additionally, an unusually high frequency of alleles with multiple copies of SMN1 was identified in the African American group (27% compared to 3.3-8.1%). This latter finding has clinical implications for providing accurate adjusted genetic risk assessments to the African American population. CONCLUSIONS: Differences in the frequency of SMA carriers were significant among several ethnic groups. This study provides an accurate assessment of allele frequencies and estimates of adjusted genetic risk that were previously unavailable to clinicians and patients considering testing.

Serum mannose-binding lectin deficiency is associated with cryptosporidiosis in young Haitian children.

BACKGROUND: Mannose-binding lectin (MBL) is a component of the innate immune response and binds microbial surfaces through carbohydrate recognition domains. MBL deficiency may contribute to susceptibility to a variety of infectious diseases, particularly in young children. MBL binds to the Cryptosporidium sporozoite and may be important in resistance to cryptosporidiosis. METHODS: We studied the association of serum MBL levels and cryptosporidiosis in a case-control study of young Haitian children with cryptosporidiosis versus children who were control subjects. RESULTS: Ninety-nine children were enrolled, as follows: 49 children with cryptosporidiosis, 41 healthy controls, and 9 children with diarrhea from other causes. Case children were more malnourished than controls, and 49% had persistent or chronic diarrhea. At enrollment, mean serum MBL levels were markedly lower in children with cryptosporidiosis (P = .002), as was the number of children with an MBL deficiency of < or = 70 ng/mL (P = .005). In multivariate analysis, the association of cryptosporidiosis and MBL deficiency persisted (P = .002; adjusted odds ratio, 22.4), as did the association of cryptosporidiosis with general malnutrition. The subset of children with cryptosporidiosis and MBL deficiency were more likely to be male (P = .025). CONCLUSIONS: MBL may be an important component of innate immune protection against Cryptosporidium infection in young children. Additional studies are necessary to determine whether MBL intestinal losses, deficient epithelial expression, and/or genetic polymorphisms in the MBL gene contribute to MBL deficiency in cryptosporidiosis and other enteric infections in young children.

Visible-laser acceleration of relativistic electrons in a semi-infinite vacuum.

We demonstrate a new particle acceleration mechanism using 800 nm laser radiation to accelerate relativistic electrons in a semi-infinite vacuum. The experimental demonstration is the first of its kind and is a proof of principle for the concept of laser-driven particle acceleration in a structure loaded vacuum. We observed up to 30 keV energy modulation over a distance of 1000 lambda, corresponding to a 40 MeV/m peak gradient. The energy modulation was observed to scale linearly with the laser electric field and showed the expected laser-polarization dependence. Furthermore, as expected, laser acceleration occurred only in the presence of a boundary that limited the laser-electron interaction to a finite distance.

Disruption of inhibitory G-proteins mediates a reduction in atrial beta-adrenergic signaling by enhancing eNOS expression.

OBJECTIVE: Cardiac parasympathetic nerve activity is reduced in most cardiovascular disease states, and this may contribute to enhanced cardiac sympathetic responsiveness. Disruption of inhibitory G-proteins (Gi) ablates the cholinergic pathway and increases cardiac endothelial nitric oxide (NO) synthase (eNOS) expression, suggesting that NO may offset the impaired attenuation of beta-adrenergic regulation of supraventricular excitability. To test this, we investigated the role of endogenous NO production on beta-adrenergic regulation of rate (HR), contraction (CR) and calcium (Ca2+) handling in atria following blockade of Gi-coupled muscarinic receptors. METHODS: Mice were administered pertussis toxin (PTx, n=105) or saline (C, n=100) intraperitoneally. After 3 days, we measured CR, HR, and NOS protein levels in isolated atria. Intracellular calcium (Ca2+) transients and Ca2+ current density (I(Ca)) were also measured in atrial myocytes. RESULTS: PTx treatment increased atrial myocyte eNOS protein levels compared to C (P<0.05). This did not affect basal atrial function but was associated with a significant reduction in the CR and HR response to isoprenaline (ISO) compared with C. NOS inhibition normalized responses in PTx atria with respect to responses in C atria (P<0.05), which were unaffected. Furthermore, PTx did not affect ISO-stimulated HR and CR in eNOS gene knockout mice (n=40). In agreement with these findings, the ISO-mediated increase in Ca2+ transient was suppressed in PTx-treated myocytes (P<0.05), whereas I(Ca) did not differ between groups. CONCLUSION: eNOS-derived NO inhibits beta-adrenergic responses following disruption of Gi signaling. This suggests that increased eNOS expression may be a compensatory mechanism which reduces beta-adrenergic regulation of heart rate when cardiac parasympathetic control is impaired.

Multi-level assessment protocol (MAP) for adoption in multi-site clinical trials.

The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multi-site clinical trials, and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked: How might the technology of multi-site clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing 8 organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. In analysis of interview data we identified four conceptual themes which are likely to affect adoption and may be informative in future multi-site clinical trials. We offer the conclusion that planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice.

An adenosine A2a agonist increases sleep and induces Fos in ventrolateral preoptic neurons.

Considerable evidence indicates that adenosine may be an endogenous somnogen, yet the mechanism through which it promotes sleep is unknown. Adenosine may act via A1 receptors to promote sleep, but an A2a receptor antagonist can block the sleep induced by prostaglandin D(2). We previously reported that prostaglandin D(2) activates sleep-promoting neurons of the ventrolateral preoptic area, and we hypothesized that an A2a receptor agonist also should activate these neurons. Rats were instrumented for sleep recordings, and an injection cannula was placed in the subarachnoid space just anterior to the ventrolateral preoptic area. After an 8-10-day recovery period, the A2a receptor agonist CGS21680 (20 pmol/min) or saline was infused through the injection cannula, and the animals were killed 2 h later. The brains were stained using Fos immunohistochemistry, and the pattern of Fos expression was studied in the entire brain. CGS21680 increased non-rapid eye movement sleep and markedly increased the expression of Fos in the ventrolateral preoptic area and basal leptomeninges, but it reduced Fos expression in wake-active brain regions such as the tuberomammillary nucleus. CGS21680 also induced Fos in the shell and core of the nucleus accumbens and in the lateral subdivision of the central nucleus of the amygdala. To determine whether these effects may have been mediated through A1 receptors, an additional group of rats received subarachnoid infusion of the A1 receptor agonist N(6)-cyclopentyladenosine (2 pmol/min). In contrast to CGS21680, infusion of N(6)-cyclopentyladenosine into the subarachnoid space produced only a small decrease in rapid eye movement sleep, and the pattern of Fos expression induced by N(6)-cyclopentyladenosine was notable only for decreased Fos in regions near the infusion site. These findings suggest that an adenosine A2a receptor agonist may activate cells of the leptomeninges or nucleus accumbens that increase the activity of ventrolateral preoptic area neurons. These ventrolateral preoptic area neurons may then coordinate the inhibition of multiple wake-promoting regions, resulting in sleep.

The toxins of Bacteroides fragilis.

Bacteroides fragilis are both key commensals and important human pathogens. Particular strains of B. fragilis, termed enterotoxigenic B. fragilis (ETBF), are recently identified enteric pathogens of children and adults. These strains are distinguished by secretion of a 20kDa metalloprotease toxin (B. fragilis toxin or BFT), the first recognized and only established toxin to date for B. fragilis. Three isotypes of BFT are encoded by distinct bft loci contained within a 6kb chromosomal region unique to ETBF strains termed the B. fragilis pathogenicity island (BfPAI). Experimental studies have suggested that the cellular target for BFT is E-cadherin, the primary protein of the zonula adherens. It is postulated that BFT cleavage of E-cadherin is critical in precipitating the intracellular events culminating in the two established activities for BFT; namely, stimulation of secretion in ligated intestinal segments in several animal species and alteration of cellular morphology only in epithelial cells that retain the ability to polarize and form a tight junctional complex. Future studies will be directed to characterizing in greater detail both the molecular genetics of the BFT toxin and the precise steps in its cellular mechanism of action.

A longitudinal study of Giardia lamblia infection in north-east Brazilian children.

OBJECTIVE: To evaluate the epidemiology of Giardia lamblia infection, investigate factors which might be associated with clinical manifestations and recurrence, and examine the role of copathogens in disease course. METHODS: Prospective 4-year cohort study of children born in an urban slum in north-eastern Brazil. RESULTS: Of 157 children followed for > or = 3 months, 43 (27.4%) were infected with Giardia. The organism was identified in 8.8% of all stool specimens, and although found with similar frequency in non-diarrhoeal (7.4%) and diarrhoeal stools (9.7%), was more common in children with persistent (20.6%) than acute diarrhoea (7.6%, P=0.002). Recurrent or relapsing infections were common (46%). Children with symptomatic infections had significantly lower weight-for-age and height-for-age than asymptomatic children. Copathogens were not associated with disease course. CONCLUSION With its protean clinical manifestations, Giardia may be associated with substantial morbidity amongst children in Brazil.

Nitric oxide does not modulate the hyperpolarization-activated current, I(f), in ventricular myocytes from spontaneously hypertensive rats.

OBJECTIVE: : In sinoatrial (SA) node cells, nitric oxide (NO) exerts a dual effect on the hyperpolarization-activated current, I(f), i.e. in basal conditions NO enhances I(f) whereas in the presence of beta-adrenergic stimulation it decreases it. Recent studies have shown that I(f) is present in ventricular myocytes from hypertrophied or failing hearts where it may promote abnormal automaticity. Since these pathological conditions are associated with increased sympathetic tone and upregulation of myocardial NO production, we set out to investigate whether I(f) is similarly modulated by NO in hypertrophied ventricular myocytes. METHODS: Left ventricular myocytes were isolated from 18-20-month-old spontaneously hypertensive rats (SHRs). Membrane current was measured under whole-cell or amphotericin-perforated patch-clamp conditions, at 35 degrees C. RESULTS: Application of diethylamine-NO (DEA-NO, 1-100 microM) did not alter the amplitude or voltage dependence of activation of I(f) under basal conditions (half-activation voltage, V(h): control -82.9+/-2.6, DEA-NO -84.0+/-2.6 mV). Similarly, I(f) was not affected by the inhibition of endogenous NO production (L-NMMA, 500 microM) or guanylate cyclase (ODQ, 10 microM). Forskolin (10 microM) or isoprenaline (100 nM) elicited a positive shift in V(h) but subsequent application of DEA-NO did not further affect the properties of I(f). CONCLUSIONS: Our results show that, unlike in SA node cells, in SHR ventricular myocytes basal and adrenergically stimulated I(f) is not modulated by exogenous NO or by constitutive NO or cGMP production.

Investigation of a secondary syringe exchange program for homeless young adult injection drug users in San Francisco, California, U.S.A.

This study investigated an HIV prevention program for homeless young adult injection drug users (IDUs) that combined a secondary syringe exchange program (SEP) with community-level activities. Homeless young IDUs were recruited from street-based settings in San Francisco, and a structured questionnaire was administered. The secondary SEP operated in a circumscribed geographic area, and for analytic purposes respondents were assigned to the intervention site group if they primarily spent time in this area (n = 67), or the comparison site group if they primarily spent time elsewhere (n = 55). Almost all (96%) intervention site youth had used the secondary SEP in the past 30 days and were significantly more likely to regularly use SEP. In bivariate analysis, comparison site IDUs were more likely to share syringes, reuse syringes, share the cotton used to filter drugs, and use condoms with casual sex partners only inconsistently. In multivariate analysis, comparison site remained positively associated with sharing syringes (adjusted odds ratio [AOR], 3.748; 95% confidence interval [CI], 1.406-9.988), reusing syringes (AOR, 2.769; 95% CI,1.120-6.847), and inconsistent condom use with casual sex partners (AOR, 4.825; 95% CI, 1.392- 16.721). This suggests that the intervention was effective in delivering SEP services to homeless young adult IDUs, and that IDUs who frequented the intervention site had a lower HIV risk than comparison group IDUs.