Dispersal and survival of Nyssomyia intermedia and Nyssomyia neivai (Diptera: Psychodidae: Phlebotominae) in a cutaneous leishmaniasis endemic area of the speleological province of the Ribeira Valley, state of São Paulo, Brazil

The dispersal and survival of the phlebotomines Nyssomyia intermedia and Nyssomyia neivai (both implicated as vectors of the cutaneous leishmaniasis agent) in an endemic area was investigated using a capture-mark-release technique in five experiments from August-December 2003 in municipality of Iporanga, state of São Paulo, Brazil. A total of 1,749 males and 1,262 females of Ny. intermedia and 915 males and 411 females of Ny. neivai were marked and released during the five experiments. Recapture attempts were made using automatic light traps, aspiration in natural resting places and domestic animal shelters and Shannon traps. A total of 153 specimens (3.48%) were recaptured: 2.59% (78/3,011) for Ny. intermedia and 5.35% (71/1,326) for Ny. neivai. Both species were recaptured up to 144 h post-release, with the larger part of them recaptured within 48 h. The median dispersion distances for Ny. intermedia and Ny. neivai, respectively, were 109 m and 100 m. The greatest dispersal range of Ny. intermedia was 180 m, while for Ny. neivai one female was recaptured in a pasture at 250 m and another in a pigsty at 520 m, showing a tendency to disperse to more open areas. The daily survival rates calculated based on regressions of the numbers of marked insects recaptured on the six successive days after release were 0.746 for males and 0.575 for females of Ny. intermedia and 0.649 for both sexes of Ny. neivai. The size of the populations in the five months ranged from 8,332-725,085 for Ny. intermedia males, 2,193-104,490 for Ny. intermedia females, 1,687-350,122 for Ny. neivai males and 254-49,705 for Ny. neivai females.

Sexually dimorphic melanin-based colour polymorphism, feather melanin content, and wing feather structure in the barn owl (Tyto alba)

Feathers confer protection against biophysical agents and determine flying ability. The geometry and arrangement of the barbs, together with the keratin and pigments deposited in the feathers, determine the mechanical stability of the vane, and its stiffness and resistance to abrasive agents. In colour-polymorphic species, individuals display alternative colour morphs, which can be associated with different foraging strategies. Each morph may therefore require specific flying abilities, and their feathers may be exposed to different abrasive agents. Feathers of differently coloured individuals may thus have a specific structure, and colour pigments may help resist abrasive agents and improve stiffness. We examined these predictions in the barn owl (Tyto alba), a species for which the ventral body side varies from white to dark reddish pheomelanic, and in the number and size of black spots located at the tip of the feathers. White and reddish birds show different foraging strategies, and the size of black feather spots is associated with several phenotypic attributes. We found that birds displaying a darker reddish coloration on the ventral body side deposit more melanin pigments in their remiges, which also have fewer barbs. This suggests that wear resistance increases with darkness, whereas feathers of lighter coloured birds may bend less easily. Accordingly, individuals displaying a lighter reddish coloration on the ventral body side, and those displaying larger black spots, displayed more black transverse bars on their remiges: as larger-spotted individuals are heavier and longer-winged birds also have more transverse bars, these bars may reduce feather bending when flying. We conclude that differently coloured individuals produce wing feathers of different strengths to adopt alternative behavioural and life history strategies

Kenny syndrome: evidence for idiopathic hypoparathyroidism in two patients and for abnormal parathyroid hormone in one.

We report three unrelated patients with Kenny syndrome. Clinical symptoms included severe dwarfism, with internal cortical thickening and medullary stenosis of the tubular bones, normal bone age, macrocephaly, absent diploic space, delayed closure of the anterior fontanel, and normal intelligence; two of the patients had hyperopia and papillary edema. The patients also had episodic hypocalcemic tetany and low serum levels of magnesium. In two patients the diagnosis of idiopathic hypoparathyroidism was established on the basis of undetectable serum parathyroid hormone (PTH) levels (N- and C-terminal RIAs); one of these had normal urinary cyclic adenosine monophosphate (cAMP) response to exogenous PTH. Circulating calcitonin was undetectable in either patient. In a third patient, who had abnormal body proportions, serum levels of PTH were increased in an RIA detecting predominantly intact PTH (N-RIA) and undetectable in another RIA recognizing carboxy-terminal fragments (C-RIA). Administration of PTH promptly increased urinary cAMP excretion. In this patient, serum levels of calcitonin were increased, whereas values for 25-OHD and 1,25(OH)2D were normal.

Mansonella ozzardi in Amazonas, Brazil: prevalence and distribution in the municipality of Coari, in the middle Solimões River

This study investigated some epidemiological aspects of the Mansonella ozzardi in municipality of Coari, Amazonas. Clinical symptoms were correlated with the filarial infection and the parasitic infection rates (PIR) were estimated in simuliid vectors. The general M. ozzardi human prevalence rate was 13.3% (231/1733), of which 10.2% (109/1069) were from the urban area and 18.4% (122/664) from the rural area. The prevalence rates were higher in men (14.5% urban and 19.7% rural) than in women (6.7% urban and 17.2% rural) and occurred in most age groups. The indices of microfilaremics were higher in people > 51 years old (26.9% urban and 61.5% rural). High prevalence rates were observed in retired people (27.1% urban area), housewives and farmer (41.6% and 25%, respectively, in rural area). The main clinical symptoms were joint pains and sensation of leg coldness. Only Cerqueirellum argentiscutum (Simuliidae) transmits M. ozzardi in this municipality (PIR = 5.6% urban and 7.1% rural). M. ozzardi is a widely distributed parasitic disease in Coari. Thus, temporary residency in the region of people from other localities involved with the local gas exploitation might be a contributing factor in spreading the disease.

Formulation and Implementation of Air Quality Control Pogrammes : Patterns of Interest Consideration

This article investigates some central aspects of the relationships between programme structure and implementation of sulphur dioxide air quality control policies. Previous implementation research, primarily adopting American approaches, has neglected the connections between the processes of programme formulation and implementation. 'Programme', as the key variable in implementation studies, has been defined too narrowly. On the basis of theoretical and conceptual reflections and provisional empirical results from studies in France, Italy, England, and the Federal Republic of Germany, the authors demonstrate that an integral process analysis using a more extended programme concept is necessary if patterns of interest recognition in policies are to be discovered. Otherwise, the still important question of critical social science cannot be answered, namely, what is the impact of special interests upon implementation processes.

Regulation of the intracellular distribution, cell surface expression, and protein levels of AMPA receptor GluR2 subunits by the monocarboxylate transporter MCT2 in neuronal cells.

The neuronal monocarboxylate transporter, MCT2, is not only an energy substrate carrier but it is also purported to be a binding partner for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit. To unravel a putative role of MCT2 in the regulation of GluR2 subcellular distribution, Neuro2A cells and primary cultures of mouse cortical neurons were co-transfected with plasmids containing sequences to express the fluorescent proteins mStrawberry (mStb)-fused MCT2 and Venus-fused GluR2. Subsequently, their subcellular distribution was visualized by fluorescence microscopy. GluR2 was led to form perinuclear and dendritic clusters together with MCT2 when co-transfected in Neuro2A cells or in neurons, following the original distribution of MCT2. MCT2 co-transfection had no effect on the intracellular distribution of several other post-synaptic proteins, although it partially affected the intracellular distribution of GluR1 similarly to GluR2. Both cell surface and total protein expression levels of GluR2 were significantly reduced by co-expression with MCT2. Finally, partial perinuclear and dendritic co-localization between MCT2 and Rab8, a member of the small GTPase family involved in membrane trafficking of AMPA receptors, was also observed in co-transfected neurons. These results suggest that MCT2 could influence AMPA receptor trafficking within neurons by modulating GluR2 sorting between different subcellular compartments.

IVA in addition to BMD can change the osteoporosis management in 25% of clinical routine patients.

Vertebral fracture is one of the major osteoporotic fractures which are unfortunately very often undetected. In addition, it is well known that prevalent vertebral fracture increases dramatically the risk of future additional fracture. Instant Vertebral Assessment (IVA) has been introduced in DXA device couple years ago to ease the detection of such fracture when routine DXA are performed. To correctly use such tool, ISCD provided clinical recommendation on when and how to use it. The aim of our study was to evaluate the ISCD guidelines in clinical routine patients and see how often it may change of patient management. During two months (March and April 2010), a medical questionnaire was systematically given to our clinical routine patient to check the validity of ISCD IVA recommendations in our population. In addition, all women had BMD measurement at AP spine, Femur and 1/3 radius using a Discovery A System (Hologic, Waltham, USA). When appropriate, IVA measurement had been performed on the same DXA system and had been centrally evaluated by two trained Doctors for fracture status according to the semi-quantitative method of Genant. The reading had been performed when possible between L5 and T4. Out of 210 women seen in the consultation, 109 (52%) of them (mean age 68.2±11.5 years) fulfilled the necessary criteria to have an IVA measurement. Out of these 109 women, 43 (incidence 39.4%) had osteoporosis at one of the three skeletal sites and 31 (incidence 28.4%) had at least one vertebral fracture. 14.7% of women had both osteoporosis and at least one vertebral fracture classifying them as "severe osteoporosis" while 46.8% did not have osteoporosis not vertebral fracture. 24.8% of the women had osteoporosis but no vertebral fracture while 13.8% of women did have osteoporosis but vertebral fracture (Clinical osteoporosis). In conclusion, in 52% of our patients, IVA was needed according to ISCD criteria. In half of them the IVA test influenced of patient management either my changing the type of treatment of simply by classifying patient as "clinical osteoporosis". IVA appears to be an important tool in clinical routine but unfortunately is not yet very often use in most of the centers.

Diagnostic et prise en charge de la thrombocytopénie immune primaire

La thrombocytopénie immune primaire (ITP) est une affection auto-immune acquise avec diminution de la survie des plaquettes et perturbation de la production plaquettaire. Il n'existe aucun test clinique simple permettant de prouver la nature auto-immune de l'affection. Pour cette raison, il s'agit presque toujours d'un diagnostic par exclusion d'autres causes. Bien que les plaquettes soient souvent inférieures à 10 x 109/l lors de la présentation initiale, la tendance hémorragique est étonnamment modérée chez la majorité des patients. Le traitement initial fait toujours appel aux corticostéroïdes, combinés à des immunoglobulines intraveineuses et à des transfusions de plaquettes dans les formes compliquées avec hémorragies significatives. Chez l'enfant, la maladie est souvent induite par des infections virales et son évolution est bénigne et spontanément régressive dans la majorité des cas. Chez l'adulte, la maladie est plus souvent persistante ou chroniquement récidivante, et le taux de plaquettes se situe souvent à un taux suffisant pour prévenir des hémorragies spontanées. Seule une faible proportion de patients souffre d'une thrombocytopénie sévère prolongée accompagnée de saignements réguliers avec risque d'hémorragies potentiellement fatales. C'est probablement ce groupe de patients restreint qui tirera surtout profit des nouvelles options thérapeutiques telles que les agonistes du récepteur de la thrombopoïétine. A la lumière de ces nouvelles possibilités, un groupe d'hématologues suisses s'est réuni pour élaborer des directives concernant la prise en charge de l'ITP conformément aux besoins et aux habitudes de notre pays.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BACKGROUND Cerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor. METHODS Adults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS). RESULTS 228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0.76 to 2.46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures. CONCLUSION This trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness. TRIAL REGISTRATION This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Methods for the ex vivo characterization of human CD8+ T subsets based on gene expression and replicative history analysis.

The generation of an antigen-specific T-lymphocyte response is a complex multi-step process. Upon T-cell receptor-mediated recognition of antigen presented by activated dendritic cells, naive T-lymphocytes enter a program of proliferation and differentiation, during the course of which they acquire effector functions and may ultimately become memory T-cells. A major goal of modern immunology is to precisely identify and characterize effector and memory T-cell subpopulations that may be most efficient in disease protection. Sensitive methods are required to address these questions in exceedingly low numbers of antigen-specific lymphocytes recovered from clinical samples, and not manipulated in vitro. We have developed new techniques to dissect immune responses against viral or tumor antigens. These allow the isolation of various subsets of antigen-specific T-cells (with major histocompatibility complex [MHC]-peptide multimers and five-color FACS sorting) and the monitoring of gene expression in individual cells (by five-cell reverse transcription-polymerase chain reaction [RT-PCR]). We can also follow their proliferative life history by flow-fluorescence in situ hybridization (FISH) analysis of average telomere length. Recently, using these tools, we have identified subpopulations of CD8+ T-lymphocytes with distinct proliferative history and partial effector-like properties. Our data suggest that these subsets descend from recently activated T-cells and are committed to become differentiated effector T-lymphocytes.

Role of the paclitaxel-eluting stent and tirofiban in patients with ST-elevation myocardial infarction undergoing postfibrinolysis angioplasty: the GRACIA-3 randomized clinical trial.

BACKGROUND A catheter-based approach after fibrinolysis is recommended if fibrinolysis is likely to be successful in patients with acute ST-elevation myocardial infarction. We designed a 2x2 randomized, open-label, multicenter trial to evaluate the efficacy and safety of the paclitaxel-eluting stent and tirofiban administered after fibrinolysis but before catheterization to optimize the results of this reperfusion strategy. METHODS AND RESULTS We randomly assigned 436 patients with acute ST-elevation myocardial infarction to (1) bare-metal stent without tirofiban, (2) bare-metal stent with tirofiban, (3) paclitaxel-eluting stent without tirofiban, and (4) paclitaxel-eluting stent with tirofiban. All patients were initially treated with tenecteplase and enoxaparin. Tirofiban was started 120 minutes after tenecteplase in those patients randomly assigned to tirofiban. Cardiac catheterization was performed within the first 3 to 12 hours after inclusion, and stenting (randomized paclitaxel or bare stent) was applied to the culprit artery. The primary objectives were the rate of in-segment binary restenosis of paclitaxel-eluting stent compared with that of bare-metal stent and the effect of tirofiban on epicardial and myocardial flow before and after mechanical revascularization. At 12 months, in-segment binary restenosis was similar between paclitaxel-eluting stent and bare-metal stent (10.1% versus 11.3%; relative risk, 1.06; 95% confidence interval, 0.74 to 1.52; P=0.89). However, late lumen loss (0.04+/-0.055 mm versus 0.27+/-0.057 mm, P=0.003) was reduced in the paclitaxel-eluting stent group. No evidence was found of any association between the use of tirofiban and any improvement in the epicardial and myocardial perfusion. Major bleeding was observed in 6.1% of patients receiving tirofiban and in 2.7% of patients not receiving it (relative risk, 2.22; 95% confidence interval, 0.86 to 5.73; P=0.14). CONCLUSIONS This trial does not provide evidence to support the use of tirofiban after fibrinolysis to improve epicardial and myocardial perfusion. Compared with bare-metal stent, paclitaxel-eluting stent significantly reduced late loss but appeared not to reduce in-segment binary restenosis. CLINICAL TRIAL REGISTRATION URL: http://clinicaltrials.gov. Unique identifier: NCT00306228.

Association of hepatitis C virus NS5B variants with resistance to new antiviral drugs among untreated patients

Mutations located in the 109-amino acid fragment of NS5B are typically associated with resistance to interferon (IFN) and ribavirin (RIB) and to new antiviral drugs. The prevalence of these mutations was examined in 69 drug-naïve individuals with hepatitis C virus (HCV) infections in Rio de Janeiro, Brazil. Mutations related to non-response to IFN/RIB were observed in all subtypes studied (1a, 1b, 2b, 3a and 4). The most common mutation was Q309R, present in all subtypes, except subtype 2b with frequency above 20%. D244N was detected only in subtype 3a and A333E was detected only in subtype 2b. We did not detect the S282T, S326G or T329I mutations in any of the samples analysed. Of note, the C316N mutation, previously related to a new non-nucleoside compound (HCV796 and AG-021541), was observed in only eight of 33 (24%) samples from subtype 1b. Site 316 was under positive selection in this HCV variant. Our data highlight the presence of previously described resistance mutations in HCV genotypes from drug-naïve patients.