ADA-deficient SCID is associated with a specific microenvironment and bone phenotype characterized by RANKL/OPG imbalance and osteoblast insufficiency

Adenosine deaminase (ADA) deficiency is a disorder of the purine metabolism leading to combined immunodeficiency and systemic alterations, including skeletal abnormalities. We report that ADA deficiency in mice causes a specific bone phenotype characterized by alterations of structural properties and impaired mechanical competence. These alterations are the combined result of an imbalanced receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin axis, causing decreased osteoclastogenesis and an intrinsic defect of osteoblast function with subsequent low bone formation. In vitro, osteoblasts lacking ADA displayed an altered transcriptional profile and growth reduction. Furthermore, the bone marrow microenvironment of ADA-deficient mice showed a reduced capacity to support in vitro and in vivo hematopoiesis. Treatment of ADA-deficient neonatal mice with enzyme replacement therapy, bone marrow transplantation, or gene therapy resulted in full recovery of the altered bone parameters. Remarkably, untreated ADA-severe combined immunodeficiency patients showed a similar imbalance in RANKL/osteoprotegerin levels alongside severe growth retardation. Gene therapy with ADA-transduced hematopoietic stem cells increased serum RANKL levels and children`s growth. Our results indicate that the ADA metabolism represents a crucial modulatory factor of bone cell activities and remodeling. The trials were registered at www.clinicaltrials.gov as #NCT00598481 and #NCT00599781. (Blood. 2009; 114: 3216-3226)

Quantitative CT analysis of the glabellar and anterior nasal spine regions for the placement of implants for nasal prosthesis retention

Objectives: The aim of this study was to determine the precision of the measurements of 2 craniometric anatomic points-glabella and anterior nasal spine-in order to verify their possibility as potential locations for placing implants aimed at nasal prostheses retention. Methods: Twenty-six dry human skulls were scanned in a high-resolution spiral tomography with 1-mm axial slice thickness and 1-mm interval reconstruction using a bone tissue filter. Images obtained were stored and transferred to an independent workstation containing e-film imaging software. The measurements (in the glabella and anterior nasal fossa) were made independently by 2 observers twice for each measurement. Data were submitted to statistical analysis (parametric t test). Results: The results demonstrated no statistically significant difference between interobserver and intraobserver measurements (P > .05). The standard error was found to be between 0.49 mm and 0.84 mrn for measurements in bone protocol, indicating a high /eve/ of precision. Conclusions: The measurements obtained in anterior nasal spine and glabella were considered precise and reproducible. Mean values of such measurements pointed to the possibility of implant placement in these regions, particularly in the anterior nasal spine.

Incidence, morphology and morphometry of the foramen of Vesalius: complementary study for a safer planning and execution of the trigeminal rhizotomy technique

The foramen of Vesalius (FV) is located in the greater wing of the sphenoid bone between the foramen ovale (FO) and the foramen rotundum in an intracranial view. The FO allows the passage of the mandibular branch of trigeminal nerve, which is the target of the trigeminal radiofrequency rhizotomy. We analyzed its location, morphology, morphometry and interrelation among other foramina. 400 macerated adult human skulls were examined. A digital microscope (Dino-Lite plus(A (R))) was used to capture images from the FV. A digital caliper was used to perform the measurements of the distance between the FV and other foramina (FO, foramen spinosum and the carotid canal) in an extracranial view of the skull base. In the 400 analyzed skulls, the FV was identified in 135 skulls (33.75%) and absent on both sides in 265 skulls (66.25%). The FV was observed present bilaterally in 15.5% of the skulls. The incidence of unilateral foramen was 18.25% of the skulls of which 7.75% on right side and 10.5% on left side. The diameter of the FV was measured and we found an average value of 0.65 mm, on right side 0.63 mm and on the left side 0.67 mm. We verified that positive correlations were statistically significant among the three analyzed distances. This study intends to offer specific anatomical data with morphological patterns (macroscopic and mesoscopic) to increase the understanding of the FV features as frequency, incidence and important distances among adjacent foramina.

Use of cone-beam volumetric tomography in the diagnosis of root fractures

Objectives. The diagnosis of root fractures by conventional radiographs is still difficult because of limitations of 2D images. Cone-beam volumetric tomography improves the diagnosis capacity in dentistry, such as increased radiation dose to the patient and presence of artifacts on the image. Study design. This study compared the images obtained on conventional periapical radiographs and 3D scans (Accuitomo 3DX) for the diagnosis of root fractures. Twenty patients with suspected root fractures were submitted to examination by periapical radiography and CBCT. Two professionals, unaware of the symptomatology, examined these radiographs and CBCT images according to pre-established scores, which were later checked against the signs and symptoms. Results. The results revealed statistical difference for cone-beam volumetric tomography compared with conventional radiographs in the diagnosis of root fractures. Conclusion. It could be concluded that cone-beam volumetric tomography was better than conventional radiography in the diagnosis of root fractures, thereby constituting an excellent alternative for diagnosis in general practice. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: 270-277)

Long-Term Effects of Specific Stabilizing Exercises for First-Episode Low Back Pain

Study Design. A randomized clinical trial with 1-year and 3-year telephone questionnaire follow-ups. Objective. To report a specific exercise intervention’s long-term effects on recurrence rates in acute, first-episode low back pain patients. Summary of Background Data. The pain and disability associated with an initial episode of acute low back pain (LBP) is known to resolve spontaneously in the short-term in the majority of cases. However, the recurrence rate is high, and recurrent disabling episodes remain one of the most costly problems in LBP. A deficit in the multifidus muscle has been identified in acute LBP patients, and does not resolve spontaneously on resolution of painful symptoms and resumption of normal activity. Any relation between this deficit and recurrence rate was investigated in the long-term. Methods. Thirty-nine patients with acute, first-episode LBP were medically managed and randomly allocated to either a control group or specific exercise group. Medical management included advice and use of medications. Intervention consisted of exercises aimed at rehabilitating the multifidus in cocontraction with the transversus abdominis muscle. One year and three years after treatment, telephone questionnaires were conducted with patients. Results. Questionnaire results revealed that patients from the specific exercise group experienced fewer recurrences of LBP than patients from the control group. One year after treatment, specific exercise group recurrence was 30%, and control group recurrence was 84% (P , 0.001). Two to three years after treatment, specific exercise group recurrence was 35%, and control group recurrence was 75% (P , 0.01). Conclusion. Long-term results suggest that specific exercise therapy in addition to medical management and resumption of normal activity may be more effective in reducing low back pain recurrences than medical management and normal activity alone. [Key Words: multifidus, low back pain, rehabilitation]

Cultural Specific Training in Corruption Reporting for Pacific Island Journalists

Notes that very few journalists have formal training in corruption reporting. Discusses workshops held in 2000 and 2001 on the subject of corruption reporting for Pacific Island journalists. Explains the role of the media as an anti-corruption mechanism and the difficulty journalists face in identifying and sometimes stamping out corruption. Looks at the programs adopted and explains the responses of journalists.

Discovery and structure of a potent and highly specific blockerof insect calcium channels

We have isolated a novel family of insect-selective neurotoxins that appear to be the most potent blockers of insect voltage-gated calcium channels reported to date. These toxins display exceptional phylogenetic specificity, with at least a 10,000-fold preference for insect versus vertebrate calcium channels. The structure of one of the toxins reveals a highly structured, disulfide-rich core and a structurally disordered C-terminal extension that is essential for channel blocking activity. Weak structural/functional homology with omega -agatoxin-IVA/B, the prototypic inhibitor of vertebrate P-type calcium channels, suggests that these two toxin families might share a similar mechanism of action despite their vastly different phylogenetic specificities.

Design of clinical pharmacology trials

1. There are a variety of methods that could be used to increase the efficiency of the design of experiments. However, it is only recently that such methods have been considered in the design of clinical pharmacology trials. 2. Two such methods, termed data-dependent (e.g. simulation) and data-independent (e.g. analytical evaluation of the information in a particular design), are becoming increasingly used as efficient methods for designing clinical trials. These two design methods have tended to be viewed as competitive, although a complementary role in design is proposed here. 3. The impetus for the use of these two methods has been the need for a more fully integrated approach to the drug development process that specifically allows for sequential development (i.e. where the results of early phase studies influence later-phase studies). 4. The present article briefly presents the background and theory that underpins both the data-dependent and -independent methods with the use of illustrative examples from the literature. In addition, the potential advantages and disadvantages of each method are discussed.

A novel bioassay for human somatogenic activity in serum samples supports the clinical reliability of immunoassays

OBJECTIVE Because there is discordance between different immunoassay values for serum hGH, and because clinical state may not correlate with immunoreactive hGH, we have developed an assay to accurately measure serum hGH somatogenic bioactivity. The results of this assay were compared with the Elegance two-site ELISA assay across 135 patient samples in a variety of clinical states. DESIGN The somatogenic assay was based on stable expression of hGH receptor in the murine BaF line, allowing these cells to proliferate in response to hGH. To eliminate interference by other growth factors in serum, we created a specific antagonist of the hGH receptor (similar to Trovert or Pegvisomant) which allowed us to obtain a true measure of hGH somatogenic activity by subtraction of the activity in the presence of the antagonist. The assay was carried out in microtiter plates over 24 h, with oxidation of a chromogenic tetrazolium salt (MTT) as the endpoint. PATIENTS These encompassed a number of different clinical conditions related to short stature, including idiopathic short stature, neurosecretory dysfunction and renal failure, as well as obese patients on dietary restriction and normal volunteers. MEASUREMENTS In addition to the colourimetric (MTT) response to hGH, we measured free hGH by stripping out GHBP-bound hGH using beads coupled to a monoclonal antibody to the GHBP (GH binding protein). All samples were measured in both bioassay and ELISA assay. RESULTS This bioassay was sensitive (5 mU/l or 2 mug/l) and precise, and not subject to interference by the GHBP. There was a good correlation (r = 0.95) between bioactivity and immunoactivity across clinical states. There was, however, an increased bioactivity during secretory peaks (over 25 mU/l), which has been reported previously for the Nb2 bioassay. Free hGH did not correlate with clinical state. CONCLUSIONS Because the results of the Elegance ELISA and the bioassay correlate well, even though there is greater bioactivity at higher hormone concentrations, it is evident that an appropriate immunoassay is able to act as a reliable indicator for clinical assessment. In those rare cases where bio-inactive GH exists, our bioassay should provide an appropriate means to demonstrate this.

Randomized comparison of the quality of realtime fetal ultrasound images transmitted by ISDN and by IP videoconferencing

We compared the quality of realtime fetal ultrasound images transmitted using ISDN and IP networks. Four experienced obstetric ultrasound specialists viewed standard recordings in a randomized trial and rated the appearance of 30 fetal anatomical landmarks, each on a seven-point scale. A total of 12 evaluations were performed for various combinations of bandwidths (128, 384 or 768 kbit/s) and networks (ISDN or IF). The intraobserver coefficient of variation was 2.9%, 5.0%, 12.7% and 14.7% for the four observers. The mean overall ratings by each of the four observers were 4.6, 4.8, 5.0 and 5.3, respectively (a rating of 4 indicated satisfactory visualization and 7 indicated as good as the original recording). Analysis of variance showed that there were no significant interobserver variations nor significant differences in the mean scores for the different types of videoconferencing machines used. The most significant variable affecting the mean score was the bandwidth used. For ISDN, the mean score was 3.7 at 128 kbit/s, which was significantly worse than the mean score of 4.9 at 384 kbit/s, which was in turn significantly worse than the mean score of 5.9 at 768 kbit/s. The mean score for transmission using IP was about 0.5 points lower than that using ISDN across all the different bandwidths, but the differences were not significant. It appears that IP transmission in a private (non-shared) network is an acceptable alternative to ISDN for fetal tele-ultrasound and one deserving further study.

A study of five cervicocephalic relocation tests in three different subject groups

Objective: To compare head relocation accuracy in traumatic ( whiplash), insidious onset neck pain patients and asymptomatic subjects when targeting a natural head posture (NHP) and complex predetermined positions. Design: A case-control study. Setting: University-based musculoskeletal research clinic. Participants: Sixty-three volunteers divided into three groups of similar gender and age: Group 1 (n=21) an asymptomatic group; group 2 (n=20) insidious onset neck pain; group 3 (n=22) a history of whiplash injury. Intervention: Five randomly ordered tests designed to detect relocation accuracy of the head. Outcome measures: A 3-Space Fastrak system measured the mean absolute relocation error of three trials of each relocation test. Results: A significant difference was found between groups in one of the tests targeting the NHP (p=0.001). Post-hoc pairwise comparisons revealed a significant difference (pless than or equal to0.05) between the asymptomatic group and each symptomatic group. The difference between the symptomatic groups just failed to reach significance (p=0.07). None of the other four tests revealed significant differences. Conclusion: The test of targeting the NHP indicates that relocation inaccuracy exists in patients with neck pain with a trend to suggest that the deficit may be greater in whiplash patients. Tests employing unfamiliar postures or more complex movement were not successful in differentiating subject groups.

Key issues in determining the ethics of research subject payment: the special case of drug abuse epidemiology

The authors identify key issues that researchers, funding bodies, ethics committees and ethicists might consider in contemplating research subject payment ethics. They argue that what is missing from the broader debate is due consideration of ethics committee decision processes; research subject reasons for participation; and current research practices. The authors explore these issues and how they relate to existing guidelines on voluntary consent, and arguments that have been proposed for and against research subject payments. (non- author abstract)

Cidades sob clichê imagético imaginação espacial e experimentações em poesias visuais

Esse trabalho procurou caracterizar o clichê imagético, articulando-o a exemplos relacionados às cidades provindas de pesquisas iconográficas realizadas no Google Imagens, dando-se, a partir desse contexto, se deram as rasuras dos clichês imagéticos por poesias visuais. A pesquisa iconográfica específica para a palavra “cidades” direcionou o estudo viabilizando a constatação deste clichê, que, por sua vez, foi enunciado como intermediador de imaginação espacial. As constatações empíricas sobre esta temática fez a pesquisa ser conduzida a cinco nomes de capitais brasileiras, que foram contrastadas com as imagens destas cidades caracterizadas fora do clichê imagético, sendo o formato padrão e estático da propagação das imagens foi o universo sobre o qual orbitou este estudo. Uma vez realizadas as observações sobre esta temática, passou-se à discussão poética referente às imagens captadas, e a partir de então foi feito um diálogo com artistas e poetas ao ponto de se delimitar uma justificativa para que poesias visuais fossem elaboradas rumando para outras grafias de mundo, passando, assim, a enfatizar novas possibilidades, para essas imagens identificadas como clichês. Então, este estudo visa possibilitar novas versões a serem produzidas sobre o mundo, optando pela temática “cidade” para melhor categorizar e referenciar a pesquisa iconográfica, direcionando a discussão acerca de espaços e paisagens urbanas. Para tanto, foram adotados os autores Deleuze e Guatarri, articulando seus diálogos com McLuhan e Watson, adentrando-se à dimensão do clichê e aparando-se na iconografia Google e na sua configuração repetida que então passa a evidenciar as características opostas das considerações elaboradas por Doreen Massey, para a imaginação espacial em seu processo fluídico, e não engessado. Pensando nas reverberações de dizeres que se contradizem dessas versões, a imaginação foi evidenciada para além desses processos, atentando-se, assim, às obras poéticas e artísticas de Manoel de Barros ou Valdelino Gonçalves, em que foram verificadas possibilidades de abertura de canais de diálogos com tais clichês, com poesias visuais, em um lançamento para a imaginação, rompendo-os. Em conclusão, foram observadas possibilidades de construções poéticas como dizeres de uma Geografia constituída no imaginário, mas que também possui suas significações perante a realidade, formuladas em rupturas com o dizer totalizante, repetido e homogêneo. Foram evidenciadas, então, essas características como contribuição aos estudos que tangem à temática “Geografia e Imagens”, possibilitando novas reverberações em universos de estudos para essa linha de pesquisa, que procura inovar nas percepções sobre o entendimento das imagens como canal de construção dos espaços geográficos de uma maneira geral.

A política do ensino médio integrado no Espírito Santo e a experiência de sua implantação na Escola Estadual de Ensino Médio Arnulpho Mattos

Esta dissertação teve como objeto o Ensino Médio Integrado no Espírito Santo, sua trajetória e implantação a partir do Decreto 5.154/2004. O objetivo principal foi analisar a política do ensino médio integrado à educação profissional técnica de nível médio implementada no Espírito Santo. Investigar a educação pública pressupõe contextualizar a sociedade e as construções sociais que se projetam. O ensino médio no Brasil, enquanto etapa intermediária entre o ensino fundamental e a educação superior constitui-se de grande complexidade na estruturação de políticas públicas, no que tange à sua expansão qualitativa e quantitativa. Foram estabelecidos os seguintes objetivos específicos: identificar os pressupostos teóricos e pedagógicos contidos na Proposta Pedagógica da unidade escolar EEEFM Arnulpho Mattos; analisar a matriz curricular e a proposta pedagógica; relacionar o projeto pedagógico do curso com a prática educacional relatada nos encontros com os alunos; analisar a organização escolar e sua gestão política e pedagógica em face da proposta do EMI; relacionar a proposta do EMI, o princípio da politecnia e os relatos dos alunos; mapear a oferta do EMI no estado e o seu investimento financeiro. Nesse cenário, identificamos a relação entre trabalho e educação que contextualiza a relação da escola com a sociedade no sistema capitalista, em especial no ensino médio. Assim, nossa hipótese foi que esta política tem dificuldades de alcançar seus objetivos porque sua estrutura material segue a lógica da escola capitalista, assentada na perspectiva da Teoria do Capital Humano. A formação profissional no ensino médio é uma demanda social e histórica da classe trabalhadora, que necessita ingressar mais rápido no mercado de trabalho do que os filhos das elites brasileiras. A metodologia empregada foi uma pesquisa do tipo qualitativa, sendo um estudo de caso da EEEF Arnulpho Mattos. Os procedimentos metodológicos adotados para a investigação foram: observação, entrevistas semi-estruturadas, a análise documental, a revisão bibliográfica e os princípios metodológicos inscritos na sociologia da experiência (DUBET, 1994). Na articulação desses procedimentos, verificamos que a política do ensino médio integrado no ES teve, em seu início, um planejamento de implantação bem estruturado mas interrompido e, posteriormente, caracterizou-se pela descontinuidade das ações. Ademais, constatamos que os alunos ingressam e permanecem no curso sem compreenderem de fato o que significa a formação integrada entre a área geral e a técnica/profissional. Nos grupos de discussão percebemos que bastaram alguns encontros para que se pudesse estabelecer uma visão e relação diferenciadas com a experiência social do ensino médio integrado, principalmente por serem alunos trabalhadores. Acrescentamos às nossas conclusões que há iniciativas da escola acerca da integração entre as disciplinas de formação geral e técnicas, mas sem apoio ou orientação da unidade gestora, ou seja, a Sedu. A ampliação da oferta do EMI ocorreu no estado sem investimento na formação e valorização dos professores, sem concurso público e sem uma infra-estrutura necessária para a formação de jovens e adultos com capacidade de entender e de interferir no mundo do trabalho.