Perceptions of pesticides exposure risks by operators, workers, residents and bystanders in Greece, Italy and the UK.

The EU Directive on the sustainable use of pesticides (EU128/2009/EC) requires European Member States to develop training activities targeting occupational exposure to pesticides, and communication material aimed at residents and bystanders. Risk perceptions, knowledge and attitudes associated with passive and occupational exposure to pesticide potentially influence the extent to which different stakeholders adopt self-protective behaviour. A methodology for assessing the link between attitudes, adoption of self-protective behaviours and exposure was developed and tested. A survey was implemented in the Greece, Italy and the UK, and targeted stakeholders associated with pesticide exposure linked to orchards, greenhouse crops and arable crops respectively. The results indicated that the adoption of protective measures is low for residents and bystanders, with the exception of residents in Greece, when compared to operators and workers, who tend to follow recommended safety practices. A regression analysis was used to examine the factors affecting the probability of adopting protective measures as well the as the level of exposure in the case of operators and workers where data are available. The results indicate that the likelihood of engaging in self-protective behaviour is not significantly affected by perceptions of own health being affected by pesticides for residents and bystanders. However, operators who perceive that their heath has been negatively affected by the use of pesticides are found to be more likely to adopt self-protective behaviours. Gender and country differences, in perceptions, attitudes and self-protection are also observed. Recommendations for improved communication, in particular for vulnerable groups, are provided.

Evaluation of cleansing methods for previously worn prostheses.

STATEMENT OF PROBLEM: Although there are many product claims that address the issue of denture sanitization, controlled scientific studies on previously worn dentures have not been performed. PURPOSE: The purpose of this study was to evaluate procedures directed at sanitizing previously worn contaminated dentures from two regions of the United States. MATERIALS AND METHODS: This study examined 51 previously worn dentures from two regions. An established method of denture retrieval, sectioning, and culturing was used, including isolation of anaerobes. Evaluation of microbial contamination posttreatment was used to determine the effects of soaking dentures in Polident (US and European formulations) for varying periods of times/temperatures, microwaving dentures with varying temperatures, sonicating dentures, and immersing the dentures while using a vacuum. A combination of analysis of variance (ANOVA) and general linear model (GLM) of the SPSS was used to analyze the data with P < .05 being considered statistically significant when using a two-tailed test. RESULTS: While all Polident treatments were found to significantly reduce microorganism loads in dentures, extended soaking (8 hours) and 65 degrees C (5 minutes) were the most effective. Microwaving was slightly more effective than either sonication or vacuum. Regardless the treatment, dentures underwent sanitization rather than sterilization. CONCLUSIONS: Denture-borne microorganisms can be significantly reduced by using a Polident solution for 8 hours at room temperature or for 5 minutes at 65 degrees C. Microwaving, sonication, and use of a vacuum were less effective. ClLINICAL IMPLICATIONS The importance of daily use of Polident solution for 8 hours or for 5 minutes at 65 degrees C to sanitize worn prostheses must be stressed.

Minocycline reduces glioma expansion and invasion by attenuating microglial MT1-MMP expression.

Glioma cells release soluble factors, which induce the expression of membrane type 1 matrix metalloprotease (MT1-MMP) in tumor associated microglia and then exploit MT1-MMP mediated matrix degradation for invasion. Here, we show that minocycline blocked the increase in MT1-MMP expression and activity in cultivated microglia stimulated with glioma conditioned medium. Glioma growth within an organotypic brain slice preparation was reduced by minocycline and this reduction depended on the presence of microglia. Glioma growth in an experimental mouse model was strongly reduced by the addition of minocycline to drinking water, compared to untreated controls. Coherently, we observed in our orthotopic glioma implantation model, that MT1-MMP was abundantly expressed in glioma associated microglia in controls, but was strongly attenuated in tumors of minocycline treated animals. Overall, our study indicates that the clinically approved antibiotic minocycline is a promising new candidate for adjuvant therapy against malignant gliomas.

Hospital-based surveillance of rotavirus and other viral agents of diarrhea in children and adults in Russia, 2005-2007.

During a 2-year period in 2005-2007, we conducted surveillance of group A rotaviruses and other enteric agents among patients hospitalized with acute gastroenteritis in 8 different cities of the Russian Federation. Fecal specimens were gathered from 3208 children (including 2848 children aged <5 years) and 1354 adults who were admitted to hospitals in Moscow, St. Petersburg, Chelyabinsk, Nizhnii Novgorod, Tyumen, Khabarovsk, Makhachkala, and Yakutsk. Polymerase chain reaction was performed to detect rotaviruses of groups A and C, noroviruses of genogroups I and II, astrovirus, sapovirus, and enteric adenoviruses (group F). Group A rotavirus was the most common viral pathogen detected among children aged <5 years (43.6%), followed by norovirus (12.5%), whereas norovirus was the pathogen most commonly detected in adults (11.9%). P and G genotypes were determined for 515 rotavirus specimens, and the most prevalent genotypes were G1P[8] (44.9%), G4P[8] (40.0%), G2P[4] (8.5%), and G3P[8] (6.6%). This study is the first multicenter study of rotaviruses in the Russian Federation and documents the important burden of disease caused by this pathogen, which soon may be preventable by vaccination.

Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion.

Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes of patients with malignant gliomas. Invasion of glioma cells into the brain parenchyma is facilitated by metalloprotease-mediated degradation of the extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage by membrane bound metalloproteases. Here, we show that membrane type 1 metalloprotease (MT1-MMP) is up-regulated in glioma-associated microglia, but not in the glioma cells. Overexpression of MT1-MMP is even lethal for glioma cells. Glioma-released factors trigger the expression and activity of MT1-MMP via microglial toll-like receptors and the p38 MAPK pathway, as deletion of the toll-like receptor adapter protein MyD88 or p38 inhibition prevented MT1-MMP expression and activity in cultured microglial cells. Microglial MT1-MMP in turn activates glioma-derived pro-MMP-2 and promotes glioma expansion, as shown in an ex vivo model using MT1-MMP-deficient brain tissue and a microglia depletion paradigm. Finally, MyD88 deficiency or microglia depletion largely attenuated glioma expansion in 2 independent in vivo models.

Transferrin-receptor-mediated iron accumulation controls proliferation and glutamate release in glioma cells.

Transferrin receptors (TfR) are overexpressed in brain tumors, but the pathological relevance has not been fully explored. Here, we show that TfR is an important downstream effector of ets transcription factors that promotes glioma proliferation and increases glioma-evoked neuronal death. TfR mediates iron accumulation and reactive oxygen formation and thereby enhanced proliferation in clonal human glioma lines, as shown by the following experiments: (1) downregulating TfR expression reduced proliferation in vitro and in vivo; (2) forced TfR expression in low-grade glioma accelerated proliferation to the level of high-grade glioma; (3) iron and oxidant chelators attenuated tumor proliferation in vitro and tumor size in vivo. TfR-induced oxidant accumulation modified cellular signaling by inactivating a protein tyrosine phosphatase (low-molecular-weight protein tyrosine phosphatase), activating mitogen-activated protein kinase and Akt and by inactivating p21/cdkn1a and pRB. Inactivation of these cell cycle regulators facilitated S-phase entry. Besides its effect on proliferation, TfR also boosted glutamate release, which caused N-methyl-D-aspartate-receptor-mediated reduction of neuron cell mass. Our results indicate that TfR promotes glioma progression by two mechanisms, an increase in proliferation rate and glutamate production, the latter mechanism providing space for the progressing tumor mass.

Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study.

BACKGROUND: HLA-DRB1 shared epitope (HLA-SE), PTPN22 and CTLA4 alleles are associated with cyclic citrullinated peptide (CCP) and rheumatoid arthritis (RA). OBJECTIVE: We examined associations between HLA-SE, PTPN22, CTLA4 genotypes and RA phenotypes in a large cohort to (a) replicate prior associations with CCP status, and (b) determine associations with radiographic erosions and age of diagnosis. METHODS: A total of 689 RA patients from the Brigham RA Sequential Study (BRASS) were genotyped for HLA-SE, PTPN22 (rs2476601) and CTLA4 (rs3087243). Association between genotypes and CCP, rheumatoid factor (RF) erosive phenotypes and age at diagnosis were assessed with multivariable models adjusting for age, sex and disease duration. Novel causal pathway analysis was used to test the hypothesis that genetic risk factors and CCP are in the causal pathway for predicting erosions. RESULTS: In multivariable analysis, presence of any HLA-SE was strongly associated with CCP+ (odds ratio (OR) 3.05, 95% CI 2.18-4.25), and RF+ (OR 2.53, 95% CI 1.83-3.5) phenotypes; presence of any PTPN22 T allele was associated with CCP+ (OR 1.81, 95% CI 1.24-2.66) and RF+ phenotypes (OR 1.84, 95% CI 1.27-2.66). CTLA4 was not associated with CCP or RF phenotypes. While HLA-SE was associated with erosive RA phenotype (OR 1.52, 95% CI 1.01-2.17), this was no longer significant after conditioning on CCP. PTPN22 and CTLA4 were not associated with erosive phenotype. Presence of any HLA-SE was associated with an average 3.6 years earlier diagnosis compared with absence of HLA-SE (41.3 vs 44.9 years, p = 0.002) and PTPN22 was associated with a 4.2 years earlier age of diagnosis (39.5 vs 43.6 years, p = 0.002). CTLA4 genotypes were not associated with age at diagnosis of RA. CONCLUSIONS: In this large clinical cohort, we replicated the association between HLA-SE and PTPN22, but not CTLA4 with CCP+ and RF+ phenotypes. We also found evidence for associations between HLA-SE, and PTPN22 and earlier age at diagnosis. Since HLA-SE is associated with erosive phenotype in unconditional analysis, but is not significant after conditioning on CCP, this suggests that CCP is in the causal pathway for predicting erosive phenotype.

Cytokines as mediators for or effectors against rotavirus disease in children.

Rotavirus is the most common cause of severe gastroenteritis in young children, but the pathogenesis and immunity of this disease are not completely understood. To examine the host response to acute infection, we collected paired serum specimens from 30 children with rotavirus diarrhea and measured the levels of nine cytokines (interleukin-1beta [IL-1beta], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) using a microsphere-based Luminex Flowmetrix system. Patients with acute rotavirus infection had elevated median levels of seven cytokines in serum, and of these, the levels of three (IL-6, IL-10, and IFN-gamma) were significantly (P < 0.05) higher than those in serum from control children without diarrhea. Patients with fever had significantly (P < 0.05) higher levels of IL-6 in serum than control children, and those with fever and more episodes of diarrhea had significantly (P < 0.05) higher levels of TNF-alpha than those without fever and with fewer episodes of diarrhea. We further demonstrated a negative association (P < 0.05) between the levels of IL-2 and the number of stools on the day on which the first blood sample was collected. Finally, patients with vomiting had significantly (P < 0.05) lower levels of IFN-gamma than those without vomiting. Our pilot study provides evidence that the types and magnitudes of cytokine responses to rotavirus infection in children influence or reflect the clinical outcome of disease. These findings suggest that certain cytokines may play an important role in the pathogenesis of and the protection against rotavirus disease in children and, consequently, may provide directions and insights that could prove critical to the prevention or treatment of this important disease.

A statistical comparison of denture sanitation using a commercially available denture cleaner with and without microwaving.

Polymethyl-methacrylate dentures, worn by patients for periods ranging from 12 days to 48 years, were cultured and found to be heavily contaminated with a variety of microorganisms both externally and internally. A commercially available denture sanitizer, used as prescribed by the manufacturer, was ineffective at decontaminating the dentures. This study examined the effectiveness of this denture sanitizer when used in combination with a microwaving procedure. Statistical methods were used to compare the decontamination results of the denture sanitizer applied with and without microwaving. The statistical results indicated that the dentures were decontaminated most effectively when the denture sanitizer was used in conjunction with a two-minute microwave procedure.

Duration of symptoms and spread of colorectal cancer: a short history does not mean early disease.

The 5-year survival rates for colorectal cancer are generally lower in the UK than other European countries. In an attempt to improve prognosis, central government has stipulated that patients with suspicious symptoms ought to be seen within 2 weeks of referral from a primary care physician. In order to evaluate whether symptom duration affects stage at presentation of colorectal cancer, a retrospective analysis of all patients presenting over a 2-year period to a large district general hospital was performed. There was no significant difference (P = 0.885) in Dukes' staging in patients with symptoms lasting less or more than 6 months. Though seeing patients with symptoms suspicious of colorectal cancer in specialist out-patient clinics within 2 weeks of presentation to the primary care physician would probably reduce the number of patients presenting as an emergency, it is unlikely to improve prognosis. Thus funds diverted towards the 2-week wait are probably best utilised for other procedures such as colonoscopy and for improving care once the diagnosis of cancer has been made. Diagnosis of colorectal cancer at an earlier stage is best achieved by screening of the population.

P2 receptors in the murine gastrointestinal tract.

The actions of adenosine, adenosine 5'-triphosphate (ATP), 2-methylthio adenosine diphosphate ADP (2-MeSADP), 2-methylthio ATP (2-MeSATP), alpha,beta-methylene ATP (alpha,beta-meATP) and uridine triphosphate (UTP) on isolated segments of mouse stomach (fundus), duodenum, ileum and colon were investigated. The localization of P2Y(1), P2Y(2), P2Y(4), P2X(1) and P2X(2) receptors and neuronal nitric oxide synthase (NOS) were examined immunohistochemically, and P2Y(1) mRNA was examined with in situ hybridization. The order of potency for relaxation of longitudinal muscle of all regions was: 2-MeSADP>/=2-MeSATP>alpha,beta-meATP>ATP=UTP=adenosine. This is suggestive of P2Y(1)-mediated relaxation and perhaps a further P2Y receptor subtype sensitive to alpha,beta-meATP. As ATP and UTP are equipotent, the presence of a P2Y(2) receptor is indicated. ATP responses were inhibited by the P2Y(1)-selective antagonist MRS 2179, and suramin. P2Y(1) receptors were visualized immunohistochemically in the smooth muscle of the ileum and in a subpopulation for myenteric neurones, which also stained for NOS. P2Y(1) mRNA was localized in neurones in both myenteric and submucosal ganglia in the ileum. Taken together, these results suggest that ATP was acting on non-adrenergic, non-cholinergic inhibitory neurons, which release both nitric oxide (NO) and ATP. Reduced relaxations to 2-MeSADP by tetrodotoxin and N(omega)-nitro-L-arginine methyl ester, are consistent with this possibility. Adenosine acts via P1 receptors to relax smooth muscle of the mouse gut. Segments of mouse colon (in contrast to the stomach and small intestine) were contracted by nucleotides with the potency order: 2-MeSATP>alpha,betameATP>ATP; the contractions showed no desensitization and were antagonized by suramin and PPADS, consistent with responses mediated by P2X(2) receptors. Immunoreactivity to P2X(2) receptors was demonstrated on both longitudinal and circular muscle of the colon, but not in the other regions of the gut, except for a small subpopulation of myenteric neurones. In summary, neuronal P2Y(1) receptors appear to mediate relaxation, largely through NO in all regions of the mouse gut, and to a lesser extent by P2Y(1), P2Y(2) and a novel P2Y receptor subtype responsive to alpha,beta-meATP in smooth muscle, while P2X(2) receptors mediate contraction of colonic smooth muscle.

Gastroenteritis viruses: an overview.

Acute gastroenteritis is among the most common illnesses of humankind, and its associated morbidity and mortality are greatest among those at the extremes of age, children and the elderly. In developing countries, gastroenteritis is a common cause of death in children < 5 years that can be linked to a wide variety of pathogens. In developed countries, while deaths from diarrhoea are less common, much illness leads to hospitalization or doctor visits. Much of the gastroenteritis in children is caused by viruses belonging to four distinct families--rotaviruses, caliciviruses, astroviruses and adenoviruses. Other viruses, such as the toroviruses, picobirnaviruses, picornavirus (the Aichi virus), and enterovirus 22, may play a role as well. Viral gastroenteritis occurs with two epidemiologic patterns, diarrhoea that is endemic in children and outbreaks that affect people of all ages. Viral diarrhoea in children is caused by group A rotaviruses, enteric adenoviruses, astroviruses and the caliciviruses; the illness affects all children worldwide in the first few years of life regardless of their level of hygiene, quality of water, food or sanitation, or type of behaviour. For all but perhaps the caliciviruses, these infections provide immunity from severe disease upon reinfection. Epidemic viral diarrhoea is caused primarily by the Norwalk-like virus genus of the caliciviruses. These viruses affect people of all ages, are often transmitted by faecally contaminated food or water, and are therefore subject to control by public health measures. The tremendous antigenic diversity of caliciviruses and short-lived immunity to infection permit repeated episodes throughout life. In the past decade, the molecular characterization of many of these gastroenteritis viruses has led to advances both in our understanding of the pathogens themselves and in development of a new generation of diagnostics. Application of these more sensitive methods to detect and characterize individual agents is just beginning, but has already opened up new avenues to reassess their disease burden, examine their molecular epidemiology, and consider new directions for their prevention and control through vaccination, improvements in food and water quality and sanitary practices.

Intussusception, rotavirus diarrhea, and rotavirus vaccine use among children in New York state.

OBJECTIVE: To describe epidemiologic features of intussusception and rotavirus diarrhea in New York, to examine the baseline incidence and trends over time, and to ascertain whether an excess of cases occurred in the 9 months of vaccination with the newly licensed rotavirus vaccine. METHODS: Hospital discharge data from 1989 through 1998 were reviewed for children (<1 year old) whose primary or secondary diagnosis was coded as intussusception or rotavirus diarrhea. Characteristics of patients admitted for intussusception and rotavirus diarrhea were compared, and trends over time were examined. For a subset of patients, medical records and vaccine histories for intussusception hospitalizations from October 1998 through June 1999 were analyzed. The number of intussusception cases attributable to rotavirus vaccine was calculated based on the penetration of the vaccine (21%) and a range of excess risks of intussusception among vaccinated children as estimated by the National Immunization Program (NIP). RESULTS: From 1989 through 1998, 1450 intussusception-associated hospitalizations were reported in children <1 year old (average annual incidence 5.4/10 000). Among these children, 47% were treated medically and 53% had surgery, with 9% needing surgical resection. The incidence of intussusception declined over time from 6.1 per 10 000 in 1989 to 3.9 per 10 000 in 1998. Intussusception hospitalizations occurred throughout the year, whereas rotavirus-associated hospitalizations peaked from February to April. Of 20 patients with intussusception whose hospitalization charts were reviewed, 5 had received rotavirus vaccine. All 5 were hospitalized after their first dose of vaccine, were admitted before 7 months of age, were white, and had private insurance. A total of 81 cases of intussusception occurred during the 9-month period of rotavirus vaccination, compared with 78 during the same period in the prevaccination year. The number of excess intussusception cases observed (n = 3) was lower than expected using the NIP estimate of excess risk (1.8) among rotavirus vaccinated children (n = 12) but not significantly different from the risks identified in the NIP cohort studies (1 in 12 000). CONCLUSION: Our data suggest that in New York the rate of intussusception has declined, and approximately 1 child in 2600 develops intussusception before 1 year of age. The different seasonality between intussusception and rotavirus-related hospitalizations suggests that if any causal association exists, it must be small. Unlike other studies, analysis of New York hospitalized discharge data failed to show an appreciable increase in the incidence of intussusception after introduction of the rotavirus vaccine.

A prospective case-control study of the role of astrovirus in acute diarrhea among hospitalized young children.

This study examines the importance of astroviruses as a cause of acute diarrhea in hospitalized children <10 years old during a 5-year period. Stools were screened by electron microscopy and were tested for astrovirus, rotavirus, and enteric adenovirus by EIA. During the study, 14.6% of hospitalized children had diarrhea. Astroviruses were second only to rotaviruses as etiologic agents of both community-acquired and nosocomial diarrhea. Community-acquired astrovirus infection occurred in 6.8% of patients, and nosocomial disease occurred in 16.2%. Most cases occurred from March through June, and astrovirus type 1 was the most common. The symptoms of astrovirus-infected children were similar to those of children with rotavirus infection. However, astrovirus-infected children had a lower median age, less dehydration, and lower symptom severity scores and were less likely to have been admitted for gastroenteritis than were children with rotavirus. Astrovirus, for which only rehydration therapy is required, should be considered as another common diarrheal pathogen in children <2 years old.

Partial spectrum of microorganisms found in dentures and possible disease implications.

While it would appear that denture surfaces alone become colonized by microorganisms, this study showed that the porosity of denture material allows for contamination throughout the entire denture. Further, the numerous opportunistic and pathogenic microorganisms found in this study were unexpected and are known to produce not only substantial oral infections, but also systemic diseases.

The role of magnetic resonance cholangiography in the management of children and young adults after liver transplantation.

We reviewed the results of 50 magnetic resonance (MR) cholangiograms to evaluate their usefulness in directing clinical management in young patients after liver transplantation (LTx). Thirty-two patients underwent 50 MR cholangiograms on a 1.5-T unit. Studies were performed from 1 week to 16 yr after LTx. Indications included biochemical abnormalities with (n = 19) or without (n = 16) biopsy evidence for chronic rejection, sepsis (n = 14), and intractable ascites (n = 1). Original interpretations were compared to laboratory and ultrasound findings, and clinical outcome. Of 19 studies performed on 14 patients with biopsy evidence of chronic rejection, 16 were abnormal on MR (but only one was abnormal on ultrasound), resulting in corrective surgery (n = 1), re-Tx (n = 1), and endoscopic dilatation (n = 1). Of 16 studies on 16 patients with biochemical abnormalities without evidence of chronic rejection on biopsy, 14 were abnormal on MR (but only five of 13 on ultrasound), leading to corrective surgery (n = 3) and re-listing for Tx (n = 3). Thirteen of 14 studies on six patients with sepsis were abnormal on MR (five of nine were abnormal on ultrasound), identifying surgically correctable strictures (n = 2), and leading to re-Tx (n = 1) and percutaneous biliary drainage procedures (n = 2). The one patient with ascites had a normal study. We advocate usage of MR cholangiography for the detection of biliary complications after LTx, particularly in those patients who present with biochemical abnormalities that are not easily explained by acute cellular rejection or viral infection and in those with biliary sepsis.

Molecular characterization of serotype G9 rotavirus strains from a global collection.

Between 1992 and 1998, serotype G9 human rotavirus (RV) strains have been detected in 10 countries, including Thailand, India, Brazil, Bangladesh, Malawi, Italy, France, the United States, the United Kingdom, and Australia, suggesting the possible emergence of the fifth common serotype worldwide. Unlike the previously characterized reference G9 strains (i.e., WI61 and F45), the recent G9 isolates had a variety of gene combinations, raising questions concerning their origin and evolution. To identify the progenitor strain and examine the on-going evolution of the recent G9 strains, we characterized by genetic and antigenic analyses 16 isolates obtained from children with diarrhea in India, Bangladesh, the United States, and Malawi. Specifically, we sequenced their VP7 and NSP4 genes and compared the nucleotide (nt) and deduced amino acid sequences with the reference G9 strains. To identify reassortment, we examined the products of five gene segments; VP4, VP7, and NSP4 genotypes (genes 4, 9, and 10); subgroups (gene 6); electropherotypes (gene 11); and the genogroup profiles of all of the recent G9 isolates. Sequence analysis of the VP7 gene indicated that the recent U.S. P[6],G9 strains were closely related to the Malawian G9 strains (>99% nt identity) but distinct from G9 strains of India ( approximately 97% nt identity), Bangladesh ( approximately 98% nt identity), and the reference strains ( approximately 97% nt identity). Phylogenetic analysis identified a single cluster for the U.S. P[6],G9 strains that may have common progenitors with Malawian P[6],G9 strains whereas separate lineages were defined for the Indian, Bangladeshi, and reference G9 strains. Northern hybridization results indicated that all 11 gene segments of the Malawian P[6],G9 strains hybridized with a probe derived from a U.S. strain of the same genotype and may have the same progenitor, different from the Indian G9 strains, whereas the Bangladesh strains may have evolved from the U.S. G9 progenitors. Overall, our findings suggest that much greater diversity among the newly identified G9 strains has been generated by reassortment between gene segments than through the accumulation of mutations in a single gene.