The Risk of West Nile Virus Infection Is Associated with Combined Sewer Overflow Streams in Urban Atlanta, Georgia, USA

BACKGROUND: At present, the factors favoring transmission and amplification of West Nile Virus (WNV) within urban environments are poorly understood. In urban Atlanta, Georgia, the highly polluted waters of streams affected by combined sewer overflow (CSO) represent significant habitats for the WNV mosquito vector Culex quinquefasciatus. However, their contribution to the risk of WNV infection in humans and birds remains unclear.\ud \ud OBJECTIVES: Our goals were to describe and quantify the spatial distribution of WNV infection in mosquitoes, humans, and corvids, such as blue jays and American crows that are particularly susceptible to WNV infection, and to assess the relationship between WNV infection and proximity to CSO-affected streams in the city of Atlanta, Georgia.\ud \ud MATERIALS AND METHODS: We applied spatial statistics to human, corvid, and mosquito WNV surveillance data from 2001 through 2007. Multimodel analysis was used to estimate associations of WNV infection in Cx. quinquefasciatus, humans, and dead corvids with selected risk factors including distance to CSO streams and catch basins, land cover, median household income, and housing characteristics.\ud \ud RESULTS: We found that WNV infection in mosquitoes, corvids, and humans was spatially clustered and statistically associated with CSO-affected streams. WNV infection in Cx. quinquefasciatus was significantly higher in CSO compared with non-CSO streams, and WNV infection rates among humans and corvids were significantly associated with proximity to CSO-affected streams, the extent of tree cover, and median household income.\ud \ud CONCLUSIONS: Our study strongly suggests that CSO-affected streams are significant sources of Cx. quinquefasciatus mosquitoes that may facilitate WNV transmission to humans within urban environments. Our findings may have direct implications for the surveillance and control of WNV in other urban centers that continue to use CSO systems as a waste management practice

Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas

Although high-dose methotrexate (HD-MTX) is the most effective drug against primary CNS lymphomas (PCNSL), outcome-determining variables related to its administration schedule have not been defined. The impact on toxicity and outcome of the area under the curve (AUC(MTX)), dose intensity (DI(MTX)) and infusion rate (IR(MTX)) of MTX and plasmatic creatinine clearance (CL(crea)) was investigated in a retrospective series of 45 PCNSL patients treated with three different HD-MTX-based combinations. Anticonvulsants were administered in 31 pts (69%). Age >60 years, anticonvulsant therapy, slow IR(MTX) (1100 micromol hl(-1) were independently associated with a better survival. Slow CL(crea) and high AUC(MTX) are favourable outcome-determining factors in PCNSL, while slow CL(crea) is significantly related to higher toxicity. AUC(MTX) significantly correlates with age, anticonvulsant therapy, IR(MTX), and DI(MTX). These findings, which seem to support the choice of an MTX dose >/=3 gm(-2) in a 4-6-h infusion, every 3-4 weeks, deserve to be assessed prospectively in future trials. MTX dose adjustments in patients with fast CL(crea) should be investigated

Investigating the global genomic diversity of Escherichia coli using a multi-genome DNA microarray platform with novel gene prediction strategies

<p>Abstract</p> <p>Background</p> <p>The gene content of a diverse group of 183 unique <it>Escherichia coli </it>and <it>Shigella </it>isolates was determined using the Affymetrix GeneChip^®<it>E. coli </it>Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping tool. The probe set design utilized by this array provided the opportunity to determine the gene content of each strain very accurately and reliably. This array constitutes 10,112 independent genes representing four individual <it>E. coli </it>genomes, therefore providing the ability to survey genes of several different pathogen types. The entire ECOR collection, 80 EHEC-like isolates, and a diverse set of isolates from our FDA strain repository were included in our analysis.</p> <p>Results</p> <p>From this study we were able to define sets of genes that correspond to, and therefore define, the EHEC pathogen type. Furthermore, our sampling of 63 unique strains of O157:H7 showed the ability of this array to discriminate between closely related strains. We found that individual strains of O157:H7 differed, on average, by 197 probe sets. Finally, we describe an analysis method that utilizes the power of the probe sets to determine accurately the presence/absence of each gene represented on this array.</p> <p>Conclusions</p> <p>These elements provide insights into understanding the microbial diversity that exists within extant <it>E. coli </it>populations. Moreover, these data demonstrate that this novel microarray-based analysis is a powerful tool in the field of molecular epidemiology and the newly emerging field of microbial forensics.</p

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

<p>Abstract</p> <p>Background</p> <p>Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.</p> <p>Methods</p> <p>This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.</p> <p>Results</p> <p>No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).</p> <p>Conclusion</p> <p>Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.</p> <p>Trial registration</p> <p>Nederlands Trial Register NTR1395</p

Epithelial p38α Controls Immune Cell Recruitment in the Colonic Mucosa

Intestinal epithelial cells (IECs) compose the first barrier against microorganisms in the gastrointestinal tract. Although the NF-κB pathway in IECs was recently shown to be essential for epithelial integrity and intestinal immune homeostasis, the roles of other inflammatory signaling pathways in immune responses in IECs are still largely unknown. Here we show that p38α in IECs is critical for chemokine expression, subsequent immune cell recruitment into the intestinal mucosa, and clearance of the infected pathogen. Mice with p38α deletion in IECs suffer from a sustained bacterial burden after inoculation with Citrobacter rodentium. These animals are normal in epithelial integrity and immune cell function, but fail to recruit CD4+ T cells into colonic mucosal lesions. The expression of chemokines in IECs is impaired, which appears to be responsible for the impaired T cell recruitment. Thus, p38α in IECs contributes to the host immune responses against enteric bacteria by the recruitment of immune cells

Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.</p> <p>This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers.</p> <p>Methods</p> <p>Four focus group discussions (two women and two men groups) were conducted among 27 purposively selected patients (13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied.</p> <p>Results</p> <p>The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified.</p> <p>Conclusion</p> <p>The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.</p

Early B-cell Factor gene association with multiple sclerosis in the Spanish population

BACKGROUND: The etiology of multiple sclerosis (MS) is at present not fully elucidated, although it is considered to result from the interaction of environmental and genetic susceptibility factors. In this work we aimed at testing the Early B-cell Factor (EBF1) gene as a functional and positional candidate risk factor for this neurological disease. Axonal damage is a hallmark for multiple sclerosis clinical disability and EBF plays an evolutionarily conserved role in the expression of proteins essential for axonal pathfinding. Failure of B-cell differentiation was found in EBF-deficient mice and involvement of B-lymphocytes in MS has been suggested from their presence in cerebrospinal fluid and lesions of patients. METHODS: The role of the EBF1 gene in multiple sclerosis susceptibility was analyzed by performing a case-control study with 356 multiple sclerosis patients and 540 ethnically matched controls comparing the EBF1 polymorphism rs1368297 and the microsatellite D5S2038. RESULTS: Significant association of an EBF1-intronic polymorphism (rs1368297, A vs. T: p = 0.02; OR = 1.26 and AA vs. [TA+TT]: p = 0.02; OR = 1.39) was discovered. This association was even stronger after stratification for the well-established risk factor of multiple sclerosis in the Major Histocompatibility Complex, DRB1*1501 (AA vs. [TA+TT]: p = 0.005; OR = 1.78). A trend for association in the case-control study of another EBF1 marker, the allele 5 of the very informative microsatellite D5S2038, was corroborated by Transmission Disequilibrium Test of 53 trios (p = 0.03). CONCLUSION: Our data support EBF1 gene association with MS pathogenesis in the Spanish white population. Two genetic markers within the EBF1 gene have been found associated with this neurological disease, indicative either of their causative role or that of some other polymorphism in linkage disequilibrium with them

Probing the Role of Protein Surface Charge in the Activation of PrfA, the Central Regulator of Listeria monocytogenes Pathogenesis

Listeria monocytogenes is a food-borne intracellular bacterial pathogen capable of causing serious human disease. L. monocytogenes survival within mammalian cells depends upon the synthesis of a number of secreted virulence factors whose expression is regulated by the transcriptional activator PrfA. PrfA becomes activated following bacterial entry into host cells where it induces the expression of gene products required for bacterial spread to adjacent cells. Activation of PrfA appears to occur via the binding of a small molecule cofactor whose identity remains unknown. Electrostatic modeling of the predicted PrfA cofactor binding pocket revealed a highly positively charged region with two lysine residues, K64 and K122, located at the edge of the pocket and another (K130) located deep within the interior. Mutational analysis of these residues indicated that K64 and K122 contribute to intracellular activation of PrfA, whereas a K130 substitution abolished protein activity. The requirement of K64 and K122 for intracellular PrfA activation could be bypassed via the introduction of the prfA G145S mutation that constitutively activates PrfA in the absence of cofactor binding. Our data indicate that the positive charge of the PrfA binding pocket contributes to intracellular activation of PrfA, presumably by facilitating binding of an anionic cofactor

Rightward hemispheric asymmetries in auditory language cortex in children with autistic disorder: an MRI investigation

Purpose: determine if language disorder in children with autistic disorder (AD) corresponds to abnormalities in hemispheric asymmetries in auditory language cortex. Methods: MRI morphometric study in children with AD (n = 50) to assess hemispheric asymmetries in auditory language cortex. A key region of interest was the planum temporale (PT), which is larger in the left hemisphere in most healthy individuals. Results: (i) Heschl’s gyrus and planum polare showed typical hemisphere asymmetry patterns; (ii) posterior Superior Temporal Gyrus (pSTG) showed significant rightward asymmetry; and (iii) PT showed a trend for rightward asymmetry that was significant when constrained to right-handed boys (n = 30). For right-handed boys, symmetry indices for pSTG were significantly positively correlated with those for PT. PT asymmetry was age dependent, with greater rightward asymmetry with age. Conclusions: results provide evidence for rightward asymmetry in auditory association areas (pSTG and PT) known to subserve language processing. Cumulatively, our data provide evidence for a differing maturational path for PT for lower functioning children with AD, with both pre- and post-natal experience likely playing a role in PT asymmetry

VLDL Hydrolysis by Hepatic Lipase Regulates PPARδ Transcriptional Responses

PPARs (α,γ,δ) are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL), an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown.Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL) to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP), angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro.These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight into specific lipid mediators and pathways of lipid metabolism that regulate transcription