Polysomnographic evaluation of obstructive sleep apnea syndrome in children, before and after adenotonsillectomy

Introduction: In the last years the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) has much interested because it has not been completed established. Many criteria defined for OSAS in adults and children are different. We know that patient's clinical story is not sufficient for the diagnosis of OSAHS. In childhood, the most common cause of OSAHS is adenotonsillar hypertrophy, clinically characterised by snoring, apnea episodes, restless sleep, mouth breathing and daytime somnolence. Aim: This study has the purpose of comprovating, by objective way, the OSAS improving in children who underwent adenotonsillectomy. Study design: Clinical prospective. Material and method: For that, 23 children, among 2 and 13 years old, with adenotonsillar hypertrophy, were analysed. After endoscopy and polysomnography, they were submitted to adenotonsillectomy. Results: The polysomnography was repeated 2 months after surgery. The polysomnographic findings were compared through statistic study. Conclusion: All the patients had an important improve after adenotonsillectomy. Only two children (8.69%) persisted with light OSAHS, but they had moderate and important OSAHS before. We concluded that OSAHS is a precise indication for adenotonsillectomy in children.Introdução: Nos últimos anos a Síndrome da Apnéia/Hipopnéia Obstrutiva do Sono (SAHOS) tem despertado muito interesse por tratar-se de uma condição não totalmente estabelecida. Muitos critérios usados para definir SAHOS em adultos e crianças são diferentes entre si. Em 1995 Sabe-se que a história clínica do paciente não era suficiente para estabelecer o diagnóstico de SAHOS. Na criança a causa mais comum de SAOS é a hipertrofia adenoamigdaliana, normalmente caracterizada clinicamente pela presença de roncos noturnos, episódios de apnéia, sono agitado, respiração bucal e hipersonolência diurna4. Objetivo: Este estudo tem o intuito de comprovar de forma objetiva a melhora da SAHOS em crianças submetidas a adenoamigdalectomia. Forma de estudo: Clínico prospectivo. Material e método: Para isso, foram avaliadas 23 crianças entre 2 e 13 anos (1999-2001), com hipertrofia adenoamigdaliana, que após nasofibroscopia e polissonografia foram submetidas a cirurgia de adenoamigdalectomia. A polissonografia foi repetida após 2 meses de pós-operatório. Foi então realizado estudo estatístico dos dados obtidos na polissonografia pré- e pós-operatória. Resultado: Observamos que todos os pacientes tiveram melhora importante após adenoamigdalectomia. Duas crianças (8,69%) persistiram com SAOS leve, que anteriormente eram de grau moderado e acentuado. Conclusão: Concluímos assim que SAOS é uma indicação precisa para cirurgia de adenoamigdalectomia em crianças.UNIFESP-EPM Disciplina de Otorrinolaringologia PediátricaUNIFESP, EPM, Disciplina de Otorrinolaringologia PediátricaSciEL

The Synthetic Plasmodium falciparum Circumsporozoite Peptide PfCS102 as a Malaria Vaccine Candidate: A Randomized Controlled Phase I Trial

BACKGROUND: Fully efficient vaccines against malaria pre-erythrocytic stage are still lacking. The objective of this dose/adjuvant-finding study was to evaluate the safety, reactogenicity and immunogenicity of a vaccine candidate based on a peptide spanning the C-terminal region of Plasmodium falciparum circumsporozoite protein (PfCS102) in malaria naive adults. METHODOLOGY AND PRINCIPAL FINDINGS: Thirty-six healthy malaria-naive adults were randomly distributed into three dose blocks (10, 30 and 100 microg) and vaccinated with PfCS102 in combination with either Montanide ISA 720 or GSK proprietary Adjuvant System AS02A at days 0, 60, and 180. Primary end-point (safety and reactogenicity) was based on the frequency of adverse events (AE) and of abnormal biological safety tests; secondary-end point (immunogenicity) on P. falciparum specific cell-mediated immunity and antibody response before and after immunization. The two adjuvant formulations were well tolerated and their safety profile was good. Most AEs were local and, when systemic, involved mainly fatigue and headache. Half the volunteers in AS02A groups experienced severe AEs (mainly erythema). After the third injection, 34 of 35 volunteers developed anti-PfCS102 and anti-sporozoite antibodies, and 28 of 35 demonstrated T-cell proliferative responses and IFN-gamma production. Five of 22 HLA-A2 and HLA-A3 volunteers displayed PfCS102 specific IFN-gamma secreting CD8(+) T cell responses. Responses were only marginally boosted after the 3(rd) vaccination and remained stable for 6 months. For both adjuvants, the dose of 10 microg was less immunogenic in comparison to 30 and 100 microg that induced similar responses. AS02A formulations with 30 microg or 100 microg PfCS102 induced about 10-folds higher antibody and IFN-gamma responses than Montanide formulations. CONCLUSIONS/SIGNIFICANCE: PfCS102 peptide was safe and highly immunogenic, allowing the design of more advanced trials to test its potential for protection. Two or three immunizations with a dose of 30 microg formulated with AS02A appeared the most appropriate choice for such studies. TRIAL REGISTRATION: Swissmedic.ch 2002 DR 1227

A Genetic Screen for Anchorage-Independent Proliferation in Mammalian Cells Identifies a Membrane-Bound Neuregulin

Anchorage-independent proliferation is a hallmark of oncogenic transformation and is thought to be conducive to proliferation of cancer cells away from their site of origin. We have previously reported that primary Schwann cells expressing the SV40 Large T antigen (LT) are not fully transformed in that they maintain a strict requirement for attachment, requiring a further genetic change, such as oncogenic Ras, to gain anchorage-independence. Using the LT-expressing cells, we performed a genetic screen for anchorage-independent proliferation and identified Sensory and Motor Neuron Derived Factor (SMDF), a transmembrane class III isoform of Neuregulin 1. In contrast to oncogenic Ras, SMDF induced enhanced proliferation in normal primary Schwann cells but did not trigger cellular senescence. In cooperation with LT, SMDF drove anchorage-independent proliferation, loss of contact inhibition and tumourigenicity. This transforming ability was shared with membrane-bound class III but not secreted class I isoforms of Neuregulin, indicating a distinct mechanism of action. Importantly, we show that despite being membrane-bound signalling molecules, class III neuregulins transform via a cell intrinsic mechanism, as a result of constitutive, elevated levels of ErbB signalling at high cell density and in anchorage-free conditions. This novel transforming mechanism may provide new targets for cancer therapy

Mapping differential interactomes by affinity purification coupled with data independent mass spectrometry acquisition

Characterizing changes in protein-protein interactions associated with sequence variants (e.g. disease-associated mutations or splice forms) or following exposure to drugs, growth factors or hormones is critical to understanding how protein complexes are built, localized and regulated. Affinity purification (AP) coupled with mass spectrometry permits the analysis of protein interactions under near-physiological conditions, yet monitoring interaction changes requires the development of a robust and sensitive quantitative approach, especially for large-scale studies where cost and time are major considerations. To this end, we have coupled AP to data-independent mass spectrometric acquisition (SWATH), and implemented an automated data extraction and statistical analysis pipeline to score modulated interactions. Here, we use AP-SWATH to characterize changes in protein-protein interactions imparted by the HSP90 inhibitor NVP-AUY922 or melanoma-associated mutations in the human kinase CDK4. We show that AP-SWATH is a robust label-free approach to characterize such changes, and propose a scalable pipeline for systems biology studies

A randomized controlled trial to assess the clinical and cost effectiveness of a nurse-led Antenatal Asthma Management Service in South Australia (AAMS study)

Background: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service. Methods/design: Design: Multicentre, randomized controlled trial. Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition. Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the ‘Standard Care Group’ or the ‘Intervention Group’. Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the ‘Standard Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate. Primary study outcome: Asthma exacerbations during pregnancy. Sample size: A sample size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up). Discussion: The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes.Luke E Grzeskowiak, Gustaaf Dekker, Karen Rivers, Kate Roberts-Thomson, Anil Roy, Brian Smith, Jeffery Bowden, Robert Bryce, Michael Davies, Justin Beilby, Anne Wilson, Philippa Middleton, Richard Ruffin, Jonathan Karnon, Vicki L Clifton and for the AAMS study grou

Resilience to Disturbance Despite Limited Dispersal and Self-Recruitment in Tropical Barrel Sponges: Implications for Conservation and Management

While estimates of connectivity are important for effective management, few such estimates are available for reef invertebrates other than for corals. Barrel sponges are one of the largest and most conspicuous members of the coral reef fauna across the Indo-Pacific and given their large size, longevity and ability to process large volumes of water, they have a major role in reef functioning. Here we used a panel of microsatellite markers to characterise the genetic structure of two barrel sponge species, Xestospongia testudinaria and a currently undescribed Xestospongia species. We sampled across seven populations in the Wakatobi Marine National Park, SE Sulawesi (Indonesia) spanning a spatial scale of approximately 2 to 70 km, and present the first estimates of demographic connectivity for coral reef sponges. Genetic analyses showed high levels of genetic differentiation between all populations for both species, but contrasting patterns of genetic structuring for the two species. Autocorrelation analyses showed the likely dispersal distances of both species to be in the order of 60 and 140 m for Xestopongia sp. and Xestospongia testudinaria, respectively, which was supported by assignment tests that showed high levels of self-recruitment (>80%). We also found consistently high inbreeding coefficients across all populations for both species. Our study highlights the potential susceptibility of barrel sponges to environmental perturbations because they are generally long-lived, slow growing, have small population sizes and are likely to be reliant on self-recruitment. Surprisingly, despite these features we actually found the highest abundance of both barrel sponge species (although they were generally smaller) at a site that has been severely impacted by humans over the last fifty years. This suggests that barrel sponges exhibit environmental adaptation to declining environmental quality and has important implications for the management and conservation of these important reef species. © 2014 Bell et al

Proteomic Analysis of Neisseria gonorrhoeae Biofilms Shows Shift to Anaerobic Respiration and Changes in Nutrient Transport and Outermembrane Proteins

Neisseria gonorrhoeae, the causative agent of gonorrhea, can form biofilms in vitro and in vivo. In biofilms, the organism is more resistant to antibiotic treatment and can serve as a reservoir for chronic infection. We have used stable isotope labeling by amino acids in cell culture (SILAC) to compare protein expression in biofilm and planktonic organisms. Two parallel populations of N. gonorrhoeae strain 1291, which is an arginine auxotroph, were grown for 48 h in continuous-flow chambers over glass, one supplemented with 13C6-arginine for planktonic organisms and the other with unlabeled arginine for biofilm growth. The biofilm and planktonic cells were harvested and lysed separately, and fractionated into three sequential protein extracts. Corresponding heavy (H) planktonic and light (L) biofilm protein extracts were mixed and separated by 1D SDS-PAGE gels, and samples were extensively analyzed by liquid chromatography-mass spectrometry. Overall, 757 proteins were identified, and 152 unique proteins met a 1.5-fold cutoff threshold for differential expression with p-values <0.05. Comparing biofilm to planktonic organisms, this set included 73 upregulated and 54 downregulated proteins. Nearly a third of the upregulated proteins were involved in energy metabolism, with cell envelope proteins making up the next largest group. Of the downregulated proteins, the largest groups were involved in protein synthesis and energy metabolism. These proteomics results were compared with our previously reported results from transcriptional profiling of gonococcal biofilms using microarrays. Nitrite reductase and cytochrome c peroxidase, key enzymes required for anaerobic growth, were detected as highly upregulated in both the proteomic and transcriptomic datasets. These and other protein expression changes observed in the present study were consistent with a shift to anaerobic respiration in gonococcal biofilms, although changes in membrane proteins not explicitly related to this shift may have other functions

Classification and nomenclature of all human homeobox genes

<p>Abstract</p> <p>Background</p> <p>The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.</p> <p>Results</p> <p>We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive <it>DUX1 </it>to <it>DUX5 </it>homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.</p> <p>Conclusion</p> <p>We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.</p

Immune mechanisms in malaria: new insights in vaccine development.

Early data emerging from the first phase 3 trial of a malaria vaccine are raising hopes that a licensed vaccine will soon be available for use in endemic countries, but given the relatively low efficacy of the vaccine, this needs to be seen as a major step forward on the road to a malaria vaccine rather than as arrival at the final destination. The focus for vaccine developers now moves to the next generation of malaria vaccines, but it is not yet clear what characteristics these new vaccines should have or how they can be evaluated. Here we briefly review the epidemiological and immunological requirements for malaria vaccines and the recent history of malaria vaccine development and then put forward a manifesto for future research in this area. We argue that rational design of more effective malaria vaccines will be accelerated by a better understanding of the immune effector mechanisms involved in parasite regulation, control and elimination

Ballet injuries: injury incidence and severity over 1 year.

STUDY DESIGN: Prospective, descriptive single-cohort study. OBJECTIVE: To assess the incidence and severity of injuries to a professional ballet company over 1 year. METHODS: Data for an elite-level ballet company of 52 professional dancers were collected by an in-house medical team using a time-loss injury definition. RESULTS: A total of 355 injuries were recorded, with an overall injury incidence of 4.4 injuries per 1000 hours (female, 4.1; male, 4.8; P>.05) and a mean of 6.8 injuries per dancer (female, 6.3; male, 7.3; P>.05). Mean injury severity was 7 days (female, 4; male, 9; P.05); mean severity of injury was 3 days for females and 9 days for males (P<.05). The percentage of traumatic injuries was 32% for females and 40% for males (P<.05); the corresponding severity was 6 and 10 days, respectively (P<.05). CONCLUSION: The relatively high number of injuries reported and the resulting loss of dance time support the need to introduce interventions to reduce the risk of injury in professional dancers