Toxoplasmosis seroprevalence in urban rodents: a survey in Niamey, Niger

A serological survey of Toxoplasma gondii was conducted on 766 domestic and peridomestic rodents from 46 trapping sites throughout the city of Niamey, Niger. A low seroprevalence was found over the whole town with only 1.96% of the rodents found seropositive. However, differences between species were important, ranging from less than 2% in truly commensal Mastomys natalensis, Rattus rattus and Mus musculus, while garden-associated Arvicanthis niloticus displayed 9.1% of seropositive individuals. This is in line with previous studies on tropical rodents - that we reviewed here - which altogether show that Toxoplasma seroprevalence in rodent is highly variable, depending on many factors such as locality and/or species. Moreover, although we were not able to decipher statistically between habitat or species effect, such a contrast between Nile grass rats and the other rodent species points towards a potentially important role of environmental toxoplasmic infection. This would deserve to be further scrutinised since intra-city irrigated cultures are extending in Niamey, thus potentially increasing Toxoplasma circulation in this yet semi-arid region. As far as we are aware of, our study is one of the rare surveys of its kind performed in Sub-Saharan Africa and the first one ever conducted in the Sahel.

Kazal-type serine proteinase inhibitors in the midgut of Phlebotomus papatasi

Sandflies (Diptera: Psychodidae) are important disease vectors of parasites of the genus Leishmania, as well as bacteria and viruses. Following studies of the midgut transcriptome of Phlebotomus papatasi, the principal vector of Leishmania major, two non-classical Kazal-type serine proteinase inhibitors were identified (PpKzl1 and PpKzl2). Analyses of expression profiles indicated that PpKzl1 and PpKzl2 transcripts are both regulated by blood-feeding in the midgut of P. papatasi and are also expressed in males, larva and pupa. We expressed a recombinant PpKzl2 in a mammalian expression system (CHO-S free style cells) that was applied to in vitro studies to assess serine proteinase inhibition. Recombinant PpKzl2 inhibited α-chymotrypsin to 9.4% residual activity and also inhibited α-thrombin and trypsin to 33.5% and 63.9% residual activity, suggesting that native PpKzl2 is an active serine proteinase inhibitor and likely involved in regulating digestive enzymes in the midgut. Early stages of Leishmania are susceptible to killing by digestive proteinases in the sandfly midgut. Thus, characterising serine proteinase inhibitors may provide new targets and strategies to prevent transmission of Leishmania.

Mastoparan, a novel mitogen for Swiss 3T3 cells, stimulates pertussis toxin-sensitive arachidonic acid release without inositol phosphate accumulation

Mastoparan, a basic tetradecapeptide isolated from wasp venom, is a novel mitogen for Swiss 3T3 cells. This peptide induced DNA synthesis in synergy with insulin in a concentration-dependent manner; half-maximum and maximum responses were achieved at 14 and 17 microM, respectively. Mastoparan also stimulated DNA synthesis in the presence of other growth promoting factors including bombesin, insulin-like growth factor-1, and platelet-derived growth factor. The synergistic mitogenic stimulation by mastoparan can be dissociated from activation of phospholipase C. Mastoparan did not stimulate phosphoinositide breakdown, Ca2+ mobilization or protein kinase C-mediated phosphorylation of a major cellular substrate or transmodulation of the epidermal growth factor receptor. In contrast, mastoparan stimulated arachidonic acid release, prostaglandin E2 production, and enhanced cAMP accumulation in the presence of forskolin. These responses were inhibited by prior treatment with pertussis toxin. Hence, mastoparan stimulates arachidonic acid release via a pertussis toxin-sensitive G protein in Swiss 3T3 cells. Arachidonic acid, like mastoparan, stimulated DNA synthesis in the presence of insulin. The ability of mastoparan to stimulate mitogenesis was reduced by pertussis toxin treatment. These results demonstrate, for the first time, that mastoparan stimulates reinitiation of DNA synthesis in Swiss 3T3 cells and indicate that this peptide may be a useful probe to elucidate signal transduction mechanisms in mitogenesis.

Oferta educativa e responsabilização no PDE: o Plano de Ações Articuladas

O artigo analisa perspectivas de responsabilização presentes no Plano de Desenvolvimento da Educação apresentado à sociedade brasileira em 2007 pelo Ministério da Educação. O plano, composto por programas e ações com o objetivo declarado de promover a melhoria da qualidade da educação básica brasileira, é, entre outras medidas, operacionalizado pelo Plano de Metas Compromisso Todos pela Educação, discutido neste trabalho a partir de um de seus aspectos: o estabelecimento de convênios entre os municípios e a União, por meio da elaboração local de um Plano de Ações Articuladas. Por esse instrumento, os gestores municipais se comprometem a promover um conjunto de ações no campo educacional, responsabilizando-se pelo alcance das metas estabelecidas pelo âmbito federal. Em contrapartida, passam a contar com transferências voluntárias e assessoria técnica da União. Considera-se, na análise, o contexto de reforma do Estado e das políticas de descentralização na oferta educacional.

Impact of etanercept-methotrexate therapy on patient-reported outcomes in rheumatoid arthritis patients with up to 12 months of symptoms.

Background/Purpose: Patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) are critical in evaluating RA treatment effects on function and health-related quality of life (HR-QoL). Significant improvement in PROs has been reported in RA studies of biologic agents, including etanercept (ETN), but most studies have been conducted in patients with established disease. In addition to assessing treatment effects in early RA, there is interest in therapeutic strategies that allow dose reduction or withdrawal of biologic therapy (biologic-free) after induction of response. The PRIZE trial is an ongoing, 3-period study to evaluate the efficacy of combined ETN and methotrexate (MTX) therapy in patients with early, moderate-to-severe RA and to assess whether efficacy (remission) can be maintained with ETN dose reduction or biologic-free (Period 2) or drug-free (Period 3). Herein we report PROs associated with ETN 50 mg QW plus MTX (ETN50/MTX) therapy administered for 52 wks in Period 1 (induction) of the PRIZE trial. Methods: In Period 1, MTX- and biologic-naı‥ve patients with early, active RA (symptom onset 12 mo from enrollment; DAS28 _3.2) received open-label ETN50/MTX for 52 wks. The starting dose of MTX was 10 mg QW; at the discretion of the investigator, titration was permitted up to a maximum of 25 mg QW to achieve remission. Corticosteroid boosts were administered to patients not achieving low disease state at wks 13 and 26, unless contraindicated or not tolerated. PROs were assessed using the Health Assessment Questionnaire (HAQ) total score; Patient Acceptable Symptom State (PASS); EuroQol-5 Dimensions (EQ-5D) total index; Short Form Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue; Work Instability Scale for Rheumatoid Arthritis (RAWIS); and Work Productivity and Activity Impairment Questionnaire: Rheumatoid Arthritis (WPAI:RA). Results: A total of 306 patients received treatment in Period 1 (mITT population); 222 (73%) patients completed the period. The majority of patients were female (70%), with a mean age of 50 y, mean DAS28 of 6.0 (median, 6.0), and duration of disease symptoms from onset of 6.5 months (median, 6.3 mo). Significant and clinically meaningful improvements in PROs, including in HAQ, EQ-5D, SF-36, and FACIT-Fatigue, were demonstrated with ETN50/MTX therapy from baseline to the final on therapy visit (Table; P_0.0001). Similar improvements were observed in all dimensions of RA-WIS and WPAI:RA (Table; P_0.0001). Conclusion: Combination therapy with ETN50/MTX for 52 wks in patients with _12 mo of symptomatic, active RA resulted in significant, clinically important improvements in measures of physical function, including normal HAQ (66.6% of patients), HR-QoL, fatigue, and work productivity. These outcomes are consistent with those reported in prior studies in patients with more established disease.

Crohn's disease-associated polymorphism within the PTPN2 gene affects muramyl-dipeptide-induced cytokine secretion and autophagy.

BACKGROUND: The single nucleotide polymorphism (SNP) rs2542151 within the gene locus region encoding protein tyrosine phosphatase non-receptor type 2 (PTPN2) has been associated with Crohn's disease (CD), ulcerative colitis (UC), type-I diabetes, and rheumatoid arthritis. We have previously shown that PTPN2 regulates mitogen-activated protein kinase (MAPK) signaling and cytokine secretion in human THP-1 monocytes and intestinal epithelial cells (IEC). Here, we studied whether intronic PTPN2 SNP rs1893217 regulates immune responses to the nucleotide-oligomerization domain 2 (NOD2) ligand, muramyl-dipeptide (MDP). MATERIALS AND METHODS: Genomic DNA samples from 343 CD and 663 non-IBD control patients (male and female) from a combined German, Swiss, and Polish cohort were genotyped for the presence of the PTPN2 SNPs, rs2542151, and rs1893217. PTPN2-variant rs1893217 was introduced into T(84) IEC or THP-1 cells using a lentiviral vector. RESULTS: We identified a novel association between the genetic variant, rs1893217, located in intron 7 of the PTPN2 gene and CD. Human THP-1 monocytes carrying this variant revealed increased MAPK activation as well as elevated mRNA expression of T-bet transcription factor and secretion of interferon-γ in response to the bacterial wall component, MDP. In contrast, secretion of interleukin-8 and tumor necrosis factor were reduced. In both, T(84) IEC and THP-1 monocytes, autophagosome formation was impaired. CONCLUSIONS: We identified a novel CD-associated PTPN2 variant that modulates innate immune responses to bacterial antigens. These findings not only provide key insights into the effects of a functional mutation on a clinically relevant gene, but also reveal how such a mutation could contribute to the onset of disease.

Kertomuksia tanssien ja tutkijoiden historiasta

Kirjallisuusarvostelu

Predicting performance on fluid intelligence from speed of processing, working memory, and controlled attention

Fluid inteliigence has been defined as an innate ability to reason which is measured commonly by the Raven's Progressive Matrices (RPM). Individual differences in fluid intelligence are currently explained by the Cascade model (Fry & Hale, 1996) and the Controlled Attention hypothesis (Engle, Kane, & Tuholski, 1999; Kane & Engle, 2002). The first theory is based on a complex relation among age, speed, and working memory which is described as a Cascade. The alternative to this theory, the Controlled Attention hypothesis, is based on the proposition that it is the executive attention component of working memory that explains performance on fluid intelligence tests. The first goal of this study was to examine whether the Cascade model is consistent within the visuo-spatial and verbal-numerical modalities. The second goal was to examine whether the executive attention component ofworking memory accounts for the relation between working memory and fluid intelligence. Two hundred and six undergraduate students between the ages of 18 and 28 completed a battery of cognitive tests selected to measure processing speed, working memory, and controlled attention which were selected from two cognitive modalities, verbalnumerical and visuo-spatial. These were used to predict performance on two standard measures of fluid intelligence: the Raven's Progressive Matrices (RPM) and the Shipley Institute of Living Scales (SILS) subtests. Multiple regression and Structural Equation Modeling (SEM) were used to test the Cascade model and to determine the independent and joint effects of controlled attention and working memory on general fluid intelligence. Among the processing speed measures only spatial scan was related to the RPM. No other significant relations were observed between processing speed and fluid intelligence. As 1 a construct, working memory was related to the fluid intelligence tests. Consistent with the predictions for the RPM there was support for the Cascade model within the visuo-spatial modality but not within the verbal-numerical modality. There was no support for the Cascade model with respect to the SILS tests. SEM revealed that there was a direct path between controlled attention and RPM and between working memory and RPM. However, a significant path between set switching and RPM explained the relation between controlled attention and RPM. The prediction that controlled attention mediated the relation between working memory and RPM was therefore not supported. The findings support the view that the Cascade model may not adequately explain individual differences in fluid intelligence and this may be due to the differential relations observed between working memory and fluid intelligence across different modalities. The findings also show that working memory is not a domain-general construct and as a result its relation with fluid intelligence may be dependent on the nature of the working memory modality.

Gilbert McMicken document, n.d.

Gilbert McMicken emigrated to Upper Canada in 1832 and settled in Chippawa. In 1835 he was married to Ann Theresa Duff. In 1837 the family moved to Queenston where he was directly involved in the Kingston-Queenston trade endeavours begun by Robert Hamilton. He had a variety of interests, including a partnership with James Hamilton, son of Robert Hamilton. He was also a collector of customs in Queenston and operated the Niagara Suspension Bridge Bank for a time. He entered politics and represented Niagara as well as becoming mayor of Clifton, now part of Niagara Falls, Ont., in 1856. McMicken went on to have an illustrious career, serving as land agent and leader of Canada’s first undercover agency. McMicken moved to Manitoba and was active in business and politics. He died in Winnipeg in 1891. Source: Dictionary of Canadian Biography – Gilbert McMicken website (March 22, 2010)

Soil-Transmitted Helminth Infections, Nutrition and Growth in School-age Children from Rural Communities in Honduras

Background: Soil-transmitted helminth (STH) infections are endemic in Honduras but their impact on children’s health is not well studied. Objectives: To evaluate the prevalence and intensity of STH infections and their association with nutrition and growth in a sample of Honduran children. Methodology: A cross-sectional study was done among Honduran rural school-age children in 2011. Blood and stool samples and anthropometric measurements were obtained to determine nutritional status, STH infection and growth status, respectively. Results: The STH prevalence among 320 studied children was 72.5%. Prevalence by species was 30%, 67% and 16% for Ascaris, Trichuris and 16% hookworms, respectively. High intensity infections were associated with decreased growth scores but regardless of intensity, co-infections negatively affected growth indicators. Conclusions: The health burden of STH infections is related to high parasitic load but also to the presence of low-intensity concurrent infections. The synergistic effects of polyparasitism in underprivileged children warrants more attention.

Soil-Transmitted Helminth Infections and Nutritional Status in School-age Children from Rural Communities in Honduras

Background: Soil-transmitted helminth (STH) infections are endemic in Honduras and efforts are underway to decrease their transmission. However, current evidence is lacking in regards to their prevalence, intensity and their impact on children’s health. Objectives: To evaluate the prevalence and intensity of STH infections and their association with nutritional status in a sample of Honduran children. Methodology: A cross-sectional study was done among school-age children residing in rural communities in Honduras, in 2011. Demographic data was obtained, hemoglobin and protein concentrations were determined in blood samples and STH infections investigated in single-stool samples by Kato-Katz. Anthropometric measurements were taken to calculate heightfor- age (HAZ), BMI-for-age (BAZ) and weight-for-age (WAZ) to determine stunting, thinness and underweight, respectively. Results: Among 320 children studied (48% girls, aged 7–14 years, mean 9.7661.4) an overall STH prevalence of 72.5% was found. Children .10 years of age were generally more infected than 7–10 year-olds (p = 0.015). Prevalence was 30%, 67% and 16% for Ascaris, Trichuris and hookworms, respectively. Moderate-to-heavy infections as well as polyparasitism were common among the infected children (36% and 44%, respectively). Polyparasitism was four times more likely to occur in children attending schools with absent or annual deworming schedules than in pupils attending schools deworming twice a year (p,0.001). Stunting was observed in 5.6% of children and it was associated with increasing age. Also, 2.2% of studied children were thin, 1.3% underweight and 2.2% had anemia. Moderate-to-heavy infections and polyparasitism were significantly associated with decreased values in WAZ and marginally associated with decreased values in HAZ. Conclusions: STH infections remain a public health concern in Honduras and despite current efforts were highly prevalent in the studied community. The role of multiparasite STH infections in undermining children’s nutritional status warrants more research.

Dinner with Julia Child Menu

A menu for a dinner with Julia Child 4 November, 1993. The list of invites includes: Julia Child, John Honderich, Josh Josephson, Marion Kane, Franco Prevedello, Bonnie Stern, Michael Vaughn, Margaret Visser, Donald Ziraldo. Also, handwritten on top left corner of menu: " To Donald Julia Child"