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Cytokine levels are related to the aethiopathogenia of acute apical abscesses (AAA); however, the specific cytokine profiles in these cases are unclear. This study aimed to investigate the changes in systemic cytokine levels in patients with AAA and trismus onset, postantibiotic treatment, and postroot canal disinfection. In total, 46 AAA patients with trismus and 32 control subjects were included. After seven days of antibiotic therapy, root canal disinfection was performed in the AAA patients. The serum levels of cytokines were evaluated at basal, seven, and 14 days after endodontic treatment. Quantification of cytokines from T helper (Th) 1, Th2, Th17, and regulatory T cells profiles was determined using the BioPlex MagPix system, and the obtained data were analyzed using SPSS statistical software (P <.05). AAA patients showed higher tumor necrosis factor-alpha (TNF-α), interleukin (IL) -6, and IL-10 levels than control subjects, at basal measurement (P <.05); there were similar levels of interferon gamma, IL-1β, IL-4, and IL-17 between groups (P >.05). IL-6 and IL-10 levels decreased after antibiotic treatment (P <.05), which was also associated with clinical improvement in patients with AAA and trismus. Patients with AAA had a positive correlation with higher serum levels of IL-6 and IL-10. In addition, TNF-α levels decreased only after antibiotic and endodontic treatment. In conclusion, patients with AAA had increased systemic serum levels of TNF-α, IL-6, and IL-10. Moreover, increased levels of IL-6 and IL-10 are associated with acute inflammatory symptoms. However, IL-6 and IL-10 levels decreased after antibiotic treatment, while TNF-α levels decreased after antibiotic and endodontic treatment. [ABSTRACT FROM AUTHOR]

Genetic ancestry plays a role in asthma health disparities. Our aim was to evaluate the impact of ancestry on and identify genetic variants associated with asthma, total serum IgE level, and lung function. A total of 436 Peruvian children (aged 9-19 years) with asthma and 291 without asthma were genotyped by using the Illumina Multi-Ethnic Global Array. Genome-wide proportions of indigenous ancestry populations from continental America (NAT) and European ancestry from the Iberian populations in Spain (IBS) were estimated by using ADMIXTURE. We assessed the relationship between ancestry and the phenotypes and performed a genome-wide association study. The mean ancestry proportions were 84.7% NAT (case patients, 84.2%; controls, 85.4%) and 15.3% IBS (15.8%; 14.6%). With adjustment for asthma, NAT was associated with higher total serum IgE levels (P <.001) and IBS was associated with lower total serum IgE levels (P <.001). NAT was associated with higher FEV 1 percent predicted values (P <.001), whereas IBS was associated with lower FEV 1 values in the controls but not in the case patients. The HLA-DR/DQ region on chromosome 6 (Chr6) was strongly associated with total serum IgE (rs3135348; P = 3.438 × 10–10) and was independent of an association with the haplotype HLA-DQA1 ∼ HLA-DQB1 :04.01∼04.02 (P = 1.55 × 10–05). For lung function, we identified a locus (rs4410198; P = 5.536 × 10–11) mapping to Chr19, near a cluster of zinc finger interacting genes that colocalizes to the long noncoding RNA CTD-2537I9.5. This novel locus was replicated in an independent sample of pediatric case patients with asthma with similar admixture from Brazil (P =.005). This study confirms the role of HLA in atopy, and identifies a novel locus mapping to a long noncoding RNA for lung function that may be specific to children with NAT. [ABSTRACT FROM AUTHOR]

This study analyzed intra- and interobserver agreements during radiographic assessment of the different stages of root development using the dichotomous, Moorrees, Demirjian, and Cvek classifications, as well as the effect of the observer's level of experience on the result. Two hundred eighty-five digital periapical radiographs were examined via visual inspection by 3 experienced and 3 nonexperienced observers (n = 6) under strict technological and viewing conditions. After observer calibration, determination of the presence or absence of an open apex and the assignment of a root development stage according to the different subdivisions of the 4 indexes were performed. This evaluation was carried out by each observer in duplicate in the first round (n = 8) and repeated in the second round (n = 8). The 16 examinations performed by each observer (N = 96) were analyzed to determine the percentage of concordance followed by intraobserver, interobserver, and global observer agreement using the kappa coefficient and a weighted kappa. Additionally, to determine the level of concordance between the visual determination of an open or closed apex and the apical foramen width measured in millimeters, a dichotomized kappa coefficient was applied. A good level of global observer agreement was found for the dichotomous, Demirjian, and Cvek classifications. However, a significantly low percentage of total concordance and global observer agreement (6.66% and 0.498, respectively) was obtained using the Moorrees classification, which was more pronounced among nonexperienced observers (0.247). Apical foramen width measurements indicated the presence of 143 roots with an open apex (50.2%) and 142 with a closed apex (49.8%), and the dichotomized kappa coefficient test revealed a good level of agreement during the visual determination of an open or closed apex (range, 0.611–0.636). The classifications of Cvek and Demirjian provided reliable results when determining the different stages of root development. In contrast, the Moorrees classification provided the lowest agreement values, with a significant negative effect among nonexperienced observers. Finally, the visual estimation of the presence (or absence) of an open apex provided a good level of concordance with the radiographic apical foramen width. [ABSTRACT FROM AUTHOR]

Pediatric asthma has been increasing in LMICs (Low Middle-Income Countries), leading to an important burden for both children and national health systems. Implementing measures to achieve control are influenced by the degree of organization health systems have, the availability and affordability of essential asthma medications, and the effective implementation of asthma programs and asthma guidelines. In this review authors give an updated view of the current situation of these components of asthma management in LMICs. [ABSTRACT FROM AUTHOR]

Introduction A prospective, multicentered, randomized clinical trial was designed to assess if controlled irrigation with cold saline could result in less incidence and intensity of postoperative pain in patients presenting with pulp necrosis and symptomatic apical periodontitis. Methods A total of 210 patients (presenting with necrotic uniradicular teeth with a diagnosis of symptomatic apical periodontitis and a preoperative visual analog scale (VAS) score higher than 7) were randomly allocated in the control or experimental group after the completion of shaping and cleaning procedures. The experimental group received a final irrigation with 20 mL sterile cold (2.5°C) saline solution delivered to the working length with a sterile, cold (2.5°C) Endovac microcannula (Kerr Endo, Orange Country, CA) for 5 minutes. The same protocol was used in the control group with room temperature saline solution. Patients were instructed to record the presence, duration and level of postoperative pain, and analgesic medication intake. A logistic regression was used to compare the incidence of postoperative pain and the need for painkillers between groups. Differences in general pain intensity between groups were analyzed using the ordinal (linear) chi-square test. Postoperative pain after 6, 24, and 72 hours (recorded in a VAS scale) and the need for analgesic medication intake between the 2 groups were assessed using the Mann-Whitney U test. Results Patients in the control group presented a significantly higher incidence of postoperative pain, intensity, and need for medication intake ( P < .05). Conclusions Cryotherapy reduced the incidence of postoperative pain and the need for medication intake in patients presenting with a diagnosis of necrotic pulp and symptomatic apical periodontitis. [ABSTRACT FROM AUTHOR]

Malaria is caused by infection with Plasmodium parasites that have a complex life cycle. The parasite protein P47 is critical for disease transmission. P47 mediates mosquito immune evasion in both Plasmodium berghei (Pbs47) and Plasmodium falciparum (Pfs47), and has been shown to be important for optimal female gamete fertility in P. berghei . Pfs47 presents strong geographic structure in natural P. falciparum populations, consistent with natural selection of Pfs47 haplotypes by the mosquito immune system as the parasite adapted to new vector species worldwide. These key functions make Plasmodium P47 an attractive target to disrupt malaria transmission. [ABSTRACT FROM AUTHOR]

Allergic diseases are on the increase globally in parallel with a decrease in parasitic infection. The inverse association between parasitic infections and allergy at an ecological level suggests a causal association. Studies in human subjects have generated a large knowledge base on the complexity of the interrelationship between parasitic infection and allergy. There is evidence for causal links, but the data from animal models are the most compelling: despite the strong type 2 immune responses they induce, helminth infections can suppress allergy through regulatory pathways. Conversely, many helminths can cause allergic-type inflammation, including symptoms of “classical” allergic disease. From an evolutionary perspective, subjects with an effective immune response against helminths can be more susceptible to allergy. This narrative review aims to inform readers of the most relevant up-to-date evidence on the relationship between parasites and allergy. Experiments in animal models have demonstrated the potential benefits of helminth infection or administration of helminth-derived molecules on chronic inflammatory diseases, but thus far, clinical trials in human subjects have not demonstrated unequivocal clinical benefits. Nevertheless, there is sufficiently strong evidence to support continued investigation of the potential benefits of helminth-derived therapies for the prevention or treatment of allergic and other inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. Objective We sought to provide a targeted update of the ARIA guidelines. Methods The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. Results The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H 1 -antihistamines, intranasal H 1 -antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. Conclusions Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment. [ABSTRACT FROM AUTHOR]

Lipid mediators, bioactive products of polyunsaturated fatty acid metabolism, contribute to inflammation initiation and resolution in allergic diseases; however, their presence in lung-related biosamples has not been fully described. We aimed to quantify lipid mediators in the nasal airway epithelium and characterize preliminary associations with asthma. Using liquid chromatography–mass spectrometry, we conducted a pilot study to quantify 56 lipid mediators from nasal epithelial samples collected from 11 female participants of an outpatient asthma clinic and community controls (aged 30-55 years). We examined the presence of each compound using descriptive statistics to test whether lipid mediators could distinguish subjects with asthma (n = 8) from control subjects (n = 3) using linear regression and partial least squares discriminant analysis. Fifteen lipid mediators were detectable in all samples, including resolvin (Rv) D5 (RvD5), with the highest median concentrations (in pg/μg protein) of 13-HODE (126.481), 15-HETE (32.869), and 13-OxoODE (13.251). From linear regression adjusted for age, prostaglandin E 2 (PGE2) had a trend (P <.1) for higher concentrations in patients with severe asthma compared to controls (mean difference, 0.95; 95% confidence interval, −0.04 to 1.95). Asthma patients had higher scores on principal component 3 compared to controls (mean difference, 2.42; 95% confidence interval, 0.89 to 3.96), which represented lower levels of proresolving 15-HEPE, 19,20-DiHDPA, RvD5, 14-HDHA, 17-HDHA, and 13-HOTrE. Most of these compounds were best at discriminating asthma cases from controls in partial least squares discriminant analysis. Lipid mediators are detectable in the nasal epithelium, and their levels distinguish asthma cases from controls. [ABSTRACT FROM AUTHOR]

Introduction During chemomechanical instrumentation, several liquid or paste substances are used to ease the action of the files and to eliminate debris and the smear layer. The aim of this study was to evaluate whether the use of a paste containing EDTA during cleaning and shaping of the root canal helps to eliminate debris. Methods Twenty root canals in dog teeth were instrumented by a crown-down technique by using nickel-titanium rotary files. In 10 root canals (group A), sodium hypochlorite was used during instrumentation, followed by a final irrigation with 17% liquid EDTA. In another 10 canals (group B), sodium hypochlorite was again used as the irrigating solution, but Glyde File Prep paste was used with every instrument, and a final irrigation with EDTA was also carried out. Two additional teeth were used as positive and 2 as negative controls. The jaws were prepared for histologic evaluation. Results In group A where Glyde was not used during cleaning and shaping, little or no debris was found in the apical third of the instrumented root canals; however; in group B in which Glyde File Prep paste was used during chemomechanical instrumentation, moderate to high accumulation of debris was observed in the apical third. Conclusions The use of Glyde File Prep paste during rotary mechanical instrumentation favors the accumulation of debris in the apical third of the root canals. Irrigation with NaOCl and a final flush with EDTA by means of a small-gauge needle with simultaneous aspiration led to less accumulation of debris than in the Glyde File Prep group (P < .05). [ABSTRACT FROM AUTHOR]

Highlights: [•] Culicine mosquitoes are exposed to human-infectious Plasmodium spp., but do not transmit it. [•] Culicines allow partial development of several mammalian Plasmodium spp. [•] Different Plasmodium spp. encounter diverse barriers that prevent transmission. [•] The right ecological conditions might promote adaptation for transmission. [ABSTRACT FROM AUTHOR]

Background: Helminth infections are associated with protection against allergies. It is postulated that IL-10 production after helminth infection suppresses skin hypersensitivity and increases IgG4 production, protecting against allergies. Objective: We aimed to determine whether IL10 polymorphisms are associated with helminth infection and the risk of wheeze and allergy. Methods: Twelve IL10 single nucleotide polymorphisms were genotyped in 1353 children aged 4 to 11 years living in a poor urban area in Salvador, Brazil. Wheezing status, Ascaris lumbricoides and Trichuris trichiura infection, IL-10 production by peripheral blood leukocytes stimulated with A lumbricoides extract, serum total IgE levels, specific IgE levels, skin prick test responses to common aeroallergens, and IgG4 and IgE anti–A lumbricoides antibody levels were measured in all children. Association tests were performed by using logistic or linear regression when appropriate, including sex, age, helminth infection, and principal components for ancestry informative markers as covariates by using PLINK. Results: Allele G of marker rs3024496 was associated with the decreased production of IL-10 by peripheral blood leukocytes in response to A lumbricoides stimulation. Allele C of marker rs3024498 was negatively associated with helminth infection or its markers. Marker rs3024492 was positively associated with the risk of atopic wheeze, total IgE levels, and skin prick test responses to cockroach. Conclusions: Our findings suggest that IL10 polymorphisms might play a role in the production of IL-10, helminth infection, and allergy. We hypothesize that polymorphisms related to protection against helminths, which would offer an evolutionary advantage to subjects in the past, might be associated with increased risk of allergic diseases. [Copyright &y& Elsevier]

Abstract: Introduction: This study analyzed the in vivo microbiological status of the root canal systems of mesial roots of mandibular molars with primary apical periodontitis after 1- or 2-visit endodontic treatment. Methods: Mesial root canals were instrumented by using either a combination of K3 and LightSpeed instruments (mesiobuccal canals) or the ProTaper system (mesiolingual canals), with 5% NaOCl irrigation. Patency files were used. Smear layer was removed, and a final rinse with 5 mL of 2% chlorhexidine was performed. In the 2-visit group (7 roots, 14 canals), canals were medicated with calcium hydroxide for 1 week and then obturated by using the continuous wave of compaction technique. In the 1-visit group (6 roots, 12 canals), canals were immediately obturated after chemomechanical procedures. Teeth were extracted 1 week after root canal instrumentation and processed for histobacteriologic analysis. Results: In the 1-visit group, no case was completely free of bacteria; residual bacteria occurred in the main root canal (5 of 6 cases), isthmus (5 of 6), apical ramifications (4 of 6), and dentinal tubules (5 of 6). In the 2-visit group, 2 cases were rendered bacteria-free; residual bacteria were found in the main canal only in 2 cases (none of them with persistent dentinal tubule infection), in the isthmus (4 of 7 cases), and in ramifications (2 of 7). The 2 instrumentation techniques performed similarly. When filling material was observed in ramifications, it was usually intermixed with necrotic tissue, debris, and bacteria. Conclusions: The 2-visit protocol by using an interappointment medication with calcium hydroxide resulted in improved microbiological status of the root canal system when compared with the 1-visit protocol. Residual bacteria were more frequent and abundant in ramifications, isthmuses, and dentinal tubules when root canals were treated without an interappointment medication. Apical ramifications and isthmuses were never completely filled. The use of an antibacterial interappointment agent is necessary to maximize bacterial reduction before filling. [Copyright &y& Elsevier]

Asthma is a global health problem affecting around 300 million individuals of all ages, ethnic groups and countries. It is estimated that around 250,000 people die prematurely each year as a result of asthma. Concepts of asthma severity and control are important in evaluating patients and their response to treatment, as well as for public health, registries, and research (clinical trials, epidemiologic, genetic, and mechanistic studies), but the terminology applied is not standardized, and terms are often used interchangeably. A common international approach is favored to define severe asthma, uncontrolled asthma, and when the 2 coincide, although adaptation may be required in accordance with local conditions. A World Health Organization meeting was convened April 5-6, 2009, to propose a uniform definition of severe asthma. An article was written by a group of experts and reviewed by the Global Alliance against Chronic Respiratory Diseases review group. Severe asthma is defined by the level of current clinical control and risks as “Uncontrolled asthma which can result in risk of frequent severe exacerbations (or death) and/or adverse reactions to medications and/or chronic morbidity (including impaired lung function or reduced lung growth in children).” Severe asthma includes 3 groups, each carrying different public health messages and challenges: (1) untreated severe asthma, (2) difficult-to-treat severe asthma, and (3) treatment-resistant severe asthma. The last group includes asthma for which control is not achieved despite the highest level of recommended treatment and asthma for which control can be maintained only with the highest level of recommended treatment. [Copyright &y& Elsevier]

The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive a bacterial challenge better, whereas reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body after a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a Plasmodium berghei-infected meal, indicating that the oxidative stress after a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by double-stranded RNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism. [ABSTRACT FROM AUTHOR]

Background: Cold, dry air (CDA) can cause symptoms of rhinitis and obstructive airway responses. The pathophysiology of these reactions is not understood. One hypothesis is that the respiratory mucosa of individuals with CDA sensitivity cannot compensate for the loss of water that occurs on exposure to the stimulus, leading to epithelial damage. Objective: To test for an association between nasal reactions to CDA and the number of epithelial cells recovered in nasal fluids. Methods: Ten CDA-sensitive subjects received nasal provocations with CDA and warm, moist air; 10 CDA-insensitive subjects received CDA; and 10 subjects with allergic rhinitis received allergen and diluent challenges. Nasal lavage cytology was performed at baseline and after the challenge. Symptoms were recorded and histamine, [3H]-N-α-tosyl-L-arginine methyl ester-esterase activity, tryptase, and albumin were assayed in nasal lavages. Results: A 6-fold increase in nasal lavage epithelial cells was found in the CDA-sensitive group after CDA (P < .01), but not after warm, moist air. No changes were observed in the CDA-insensitive group, or after allergen or diluent in allergic rhinitis. Conclusion: Epithelial cell shedding accompanies clinical responses to CDA in the human nose. This supports the hypothesis that the airway mucosa of CDA-sensitive individuals cannot compensate for the water loss that occurs under extreme conditions leading to epithelial damage. Clinical implications: A defect in mucosal water homeostasis may need to be considered in individuals who get excessive nasal symptoms when exposed to cold and dry, windy environment. [Copyright &y& Elsevier]

The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials. [ABSTRACT FROM AUTHOR]

Molecular imprinting is the process of template-induced formation of specific recognition sites in a polymer. Synthetic receptors prepared using molecular imprinting possess a unique combination of properties such as robustness, high affinity, specificity, and low-cost production, which makes them attractive alternatives to natural receptors. Improvements in polymer science and nanotechnology have contributed to enhanced performance of molecularly imprinted polymer (MIP) sensors. Encouragingly, recent years have seen an increase in high-quality publications describing MIP sensors for the determination of biomolecules, drugs of abuse, and explosives, driving toward applications of this technology in medical and forensic diagnostics. This review aims to provide a focused overview of the latest achievements made in MIP-based sensor technology, with emphasis on research toward real-life applications. Highlights Electrochemical and optical sensing based on molecularly imprinted polymers (MIPs) has particular relevance in real-life applications and point-of-care testing in real human samples. MIPs are a leading technology for sensing molecules where there is no available bioreceptor. MIP nanoparticles can be used for direct and indirect detection (labeled or label free). The sensitivity of MIP-based sensors can be enhanced by coupling with nanomaterials such as graphene oxide, carbon nanotubes, or nanoparticles. The present challenges and perspectives of MIP-based electrochemical and optical sensors include exploring the market niches for MIP sensors and identifying the necessary steps toward commercialization. [ABSTRACT FROM AUTHOR]

• Electroactive molecularly imprinted polymer nanoparticles (nanoMIPs) are robust actuators due to their polymeric nature. • Graphene-assisted nanoMIPs-based sensors are easily integrated and compatible with the mass production of sensor devices. • Sensors were evaluated on spiked human plasma and street samples,also validated successfully using UPLC-MS. • NanoMIP-based sensors can be applied in clinical and forensic analysis. Screening drugs on the street and biological samples pose a challenge to law enforcement agencies due to existing detection methods and instrument limitations. Herein we present a graphene-assisted molecularly imprinted polymer nanoparticle-based sensor for amphetamine. These nanoparticles are electroactive by incorporating ferrocene in their structure. These particles act as specific actuators in electrochemical sensors, and the presence of a ferrocene redox probe embedded in the structure allows the detection of non-electroactive amphetamine. In a control approach, nanoparticles were covalently immobilised onto electrochemical sensors by drop-casting using silanes. Alternatively, nanoparticles were immobilised employing 3D printing and a graphene ink composite. The electrochemical performance of both approaches was evaluated. As a result, 3D printed nanoMIPs/graphene sensors displayed the highest selectivity in spiked human plasma, with sensitivity at 73 nA nM−1, LOD of 68 nM (RSD 2.4%) when compared to the silane drop cast electrodes. The main advantage of the optimised 3D printing technology is that it allows quantitative determination of amphetamine, a non-electroactive drug, challenging to detect with conventional electrochemical sensors. In addition, the cost-efficient 3D printing method makes these sensors easy to manufacture, leading to robust, highly selective and sensitive sensors. As proof of concept, sensors were evaluated on the street specimens and clinically relevant samples and successfully validated using UPLC-MS. [ABSTRACT FROM AUTHOR]

Abstract: BCG protection varies and in some places (nearest the equator) is low or absent. Understanding this variation can inform the efforts to develop new vaccines against tuberculosis. Two main hypotheses are used to explain this variation: under masking, new vaccines are unlikely to increase protection; under blocking new vaccines have a greater potential to be effective when BCG is not. We conducted a cluster randomized trial to explored the masking and blocking hypotheses by studying BCG vaccine efficacy of neonatal vaccination and when administered for the first or a second (revaccination) time at school age in two sites (Manaus close and Salvador further south from the equator). Seven hundred and sixty three state schools were matched on socio economic characteristics of the neighborhood and 239,934 children were randomized to vaccine (BCG vaccination at school age) or control group. Protection by first BCG vaccination at school age was high in Salvador (34%, 95% CI 7–53%, p =0.017) but low in Manaus (8%, 95% CI t 0 39–40%, p =0.686). For revaccination at school age, protection was modest in Salvador (19%, 95% CI 3–33%, p =0.022) and absent in Manaus (1%, 95% CI to 27–23%, p =0.932). Vaccine efficacy for neonatal vaccination was similar in Salvador (40%, 95% CI 22–54%, p <0.001) and Manaus (36%, 95% CI 11–53%, p =0.008). Variation in BCG efficacy was marked when vaccine was given at school age but absent at birth, which points towards blocking as the dominant mechanism. New tuberculosis vaccines that overcome or by pass this blocking effect could confer protection in situations where BCG is not protective. The Department of International Development, UK (DFID) and the National Health Foundation, Brazil (FUNASA) funded the trial. It is registered at Controlled Trials (ISRCTN07601391). [Copyright &y& Elsevier]

Summary: Background: Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. Methods: We assessed the effectiveness of BCG vaccination in school-age children (aged 7–14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. Findings: We randomly assigned 20 622 children from 385 schools to the BCG vaccination group and 18 507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3–66·7) per 100 000 person-years in the BCG vaccination group and 72·7 (62·8–86·8) per 100 000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3–43%). In Salvador, where vaccine effectiveness was 34% (8–53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11 980 BCG vaccinations. Interpretation: Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. Funding: UK Department for International Development, National Health Foundation. [Copyright &y& Elsevier]

Abstract: Evidence suggests that midgut trypsins in Aedes aegypti condition the mosquito''s ability to become infected with the dengue-2 flavivirus (DEN2). The activity of early trypsin protein peaks ∼3h after blood feeding and then drops within a few hours. We use association mapping to test the hypothesis that segregating sites in early trypsin condition midgut susceptibility to DEN2 virus. A total of 1642 females from throughout Mexico and the southern US were fed an artificial blood meal containing DEN2. After 2 weeks, mosquito heads and midguts were tested for DEN2. Mosquitoes with an infected head were classified as susceptible, those without a midgut infection had an infection barrier, and those with an infected gut but no head infection had an escape barrier. The early trypsin gene was amplified in two overlapping pieces from each mosquito and analyzed for single strand conformation polymorphisms (SSCPs). Unique SSCP genotypes were sequenced and 90 segregating sites were found. The dataset was divided into the four geographic regions within which Ae. aegypti is panmictic in Mexico. Heterogeneity analyses between alleles or genotypes and infection phenotypes demonstrated significant associations but allelic and genotypic effects were inconsistent among geographic regions. No consistent associations were found between segregating sites in early trypsin and susceptibility to DEN2 in Ae. aegypti in Mexico. [Copyright &y& Elsevier]

Abstract: BCG revaccination is still used in some tuberculosis endemic countries. Until now, the little evidence available suggested that BCG revaccination confers very limited additional protection, although there was no information on whether protection depends on the setting and age of revaccination, or if protection increases with time since vaccination. Here we report on an extended follow up of the BCG-REVAC trial, a cluster randomised trial conducted in the Brazilian cities Salvador and Manaus including over 200,000 children aged 7–14 years aimed to evaluate the efficacy of BCG revaccination in children who had received neonatal BCG vaccination. With the extended follow-up (9 years) and the additional cases accrued we now have enough power to report vaccine efficacy separately for the two cities (with different distances from Equator and presumably different prevalence of non-tuberculosis mycobacteria), and by age at vaccination and clinical form. The overall vaccine efficacy was 12% (−2 to 24%) as compared to 9% (−16 to 29%) for the 5-year follow up. Vaccine efficacy was higher in Salvador (19%, 3 to 33%) than in Manaus (1%, −27 to 27%) with the highest vaccine efficacy in children from Salvador aged <11 years at revaccination (33%, 3 to 54%). The findings are in line with the hypothesis that BCG vaccination offers higher efficacy in low NTMb prevalence, and show that revaccination with BCG can offer weak protection in selected subgroups. [Copyright &y& Elsevier]

• A MINA was developed for the determination of FB1 in maize. • NanoMIPs were used for recognising FB1. • The nanoMIPs production reduced time and costs, compared to antibody production. • MINA has shown high correlation with ELISA and HPLC. Fumonisin B1 (FB1) is a carcinogenic mycotoxin produced by Fusarium species contaminating maize. At present, fumonisin determination is performed using costly and demanding chromatography techniques or immunoassays. Recently, a molecularly imprinted polymer nanoparticles (nanoMIPs) – based assay (MINA) has been developed for FB1 detection. Herein, we have applied MINA for the determination of FB1 in naturally contaminated maize samples and results were compared with those obtained with ELISA and a reference HPLC method (AOAC No. 2001.04). The nanoMIPs as a recognition element mimicking antibodies used in ELISA were produced by solid phase synthesis and used in MINA for FB1 determination in 53 maize samples. As a result, 18 maize samples were contaminated with FB1 at levels higher than 0.25 mg/kg. Fumonisin concentrations from samples measured by MINA were well correlated with those using ELISA and HPLC. Therefore, MINA could be used as an alternative technique for FB1 determination in maize. [ABSTRACT FROM AUTHOR]