Endobronchial Ultrasound under Moderate Sedation versus General Anesthesia

BACKGROUND: Different anesthetic protocols may influence endobronchial ultrasound-guided needle aspiration (EBUS-TBNA) outcomes, patient comfort, and even safety. In this study, two anesthesia techniques were assessed and compared for EBUS-TBNA. METHODS: A prospective, multicenter study was carried out. Patients were allocated to Group 1 (general anesthesia with neuromuscular blockade and controlled ventilation) and Group 2 (intravenous sedation). EBUS-TBNA accuracy was the primary outcome. Safety, patient comfort and satisfaction, and operators' difficulties were defined as secondary outcomes. RESULTS: Of the 115 patients enrolled (Group 1 = 59, Group 2 = 56), EBUS-TBNA was performed for hilar or mediastinal lesion diagnosis and lung cancer staging in, respectively, 77 (67%) and 38 (33%) patients. The numbers of lymph nodes stations (1.8 ± 1.0 vs. 1.7 ± 1.0, p = 0.472) and punctures per station (6.9 ± 3.1 vs. 6.0 ± 2.5, p = 0.084) were similar between groups. Adequate samples were obtained from 109 patients (97.3%) with similar diagnostic accuracy. Procedure duration was not significantly different (p = 0.348). Hemodynamic parameters and systolic and diastolic blood pressures were higher in Group 1 at the beginning and at the end of the procedure. Adverse events were equally distributed, and no significant differences were found regarding patient satisfaction and bronchoscopist/anesthesiologist difficulties. CONCLUSIONS: The type of anesthesia used did not influence EBUS-TBNA outcomes. EBUS-TBNA performed under sedation or general anesthesia did not affect the diagnostic yield, complication rate, and patients' comfort and satisfaction.info:eu-repo/semantics/publishedVersio

CONHECIMENTOS E PRÁTICAS DOS CIRURGIÕES DENTISTAS DA CIDADE DE ANÁPOLIS NO TRATAMENTO DE PACIENTES QUE FIZERAM OU FAZEM USO DE BISFOSFONATOS

Pacientes  com  câncer  avançado  frequentemente  apresentam complicações  ósseas  que  podem  comprometer  consideravelmente  sua qualidade  de  vida.  Com  isso  os  bisfosfonatos  tornaram-se  a  principal  arma terapêutica  na  prevenção  de  complicações  ósseas  de  doença  maligna,  com eficácia  na  normalização  do  cálcio  sérico,  além  de  aliviar  a  dor  óssea.  Em contra  partida,  houve  um  aumento  de  osteonecrose  nos  maxilares  durante  o tratamento  odontológico  cirúrgico,  como  por  exemplo,  extrações  dentárias  e implantes  dentários

B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization. © 2013 Kozakiewicz et al

Theory to Practice: Performance Preparation Models in Contemporary High-Level Sport Guided by an Ecological Dynamics Framework

Abstract: A fundamental challenge for practitioners in high-level sporting environments concerns how to support athletes in adapting behaviours to solve emergent problems during competitive performance. Guided by an ecological dynamics framework, the design and integration of competitive performance preparation models that place athlete-environment interactions at the heart of the learning process may address this challenge. This ecological conceptualisation of performance preparation signifies a shift in a coach’s role; evolving from a consistent solution provider to a learning environment designer who fosters local athlete-environment interactions. However, despite the past decades of research within the ecological dynamics framework developing an evidence-based, theoretical conceptualisation of skill acquisition, expertise and talent development, an ongoing challenge resides within its practical integration into sporting environments. This article provides two case examples in which high-level sports organisations have utilised an ecological dynamics framework for performance preparation in Australian football and Association Football. A unique perspective is offered on experiences of professional sport organisations attempting to challenge traditional ideologies for athlete performance preparation by progressing the theoretical application of ecological dynamics. These case examples intend to promote the sharing of methodological ideas to improve athlete development, affording opportunities for practitioners and applied scientists to accept, reject or adapt the approaches presented here to suit their specific ecosystems

Heterozygous Mutations of FREM1 Are Associated with an Increased Risk of Isolated Metopic Craniosynostosis in Humans and Mice

The premature fusion of the paired frontal bones results in metopic craniosynostosis (MC) and gives rise to the clinical phenotype of trigonocephaly. Deletions of chromosome 9p22.3 are well described as a cause of MC with variably penetrant midface hypoplasia. In order to identify the gene responsible for the trigonocephaly component of the 9p22.3 syndrome, a cohort of 109 patients were assessed by high-resolution arrays and MLPA for copy number variations (CNVs) involving 9p22. Five CNVs involving FREM1, all of which were de novo variants, were identified by array-based analyses. The remaining 104 patients with MC were then subjected to targeted FREM1 gene re-sequencing, which identified 3 further mutant alleles, one of which was de novo. Consistent with a pathogenic role, mouse Frem1 mRNA and protein expression was demonstrated in the metopic suture as well as in the pericranium and dura mater. Micro-computed tomography based analyses of the mouse posterior frontal (PF) suture, the human metopic suture equivalent, revealed advanced fusion in all mice homozygous for either of two different Frem1 mutant alleles, while heterozygotes exhibited variably penetrant PF suture anomalies. Gene dosage-related penetrance of midfacial hypoplasia was also evident in the Frem1 mutants. These data suggest that CNVs and mutations involving FREM1 can be identified in a significant percentage of people with MC with or without midface hypoplasia. Furthermore, we present Frem1 mutant mice as the first bona fide mouse model of human metopic craniosynostosis and a new model for midfacial hypoplasia

The effects of adding zoledronic acid to neoadjuvant chemotherapy on tumour response: exploratory evidence for direct anti-tumour activity in breast cancer

Background: Pre-clinical studies have demonstrated synergistic anti-tumour effects of chemotherapy (CT) and zoledronic acid (ZOL). Within the AZURE trial, designed to determine whether the addition of ZOL to neoadjuvant therapy improves disease outcomes, a subgroup received neoadjuvant CT. We report a retrospective evaluation comparing pathological response in the primary tumour between treatment groups. Methods: In total, 205 patients received neoadjuvant CT±ZOL (CT+ZOL, n=102; CT, n=103). The primary end point was pathologically assessed residual invasive tumour size (RITS) at surgery. Secondary end points were pathological complete response (pCR) rate and axillary nodal involvement. Following review of surgical pathology reports (n=195), outcome differences between groups were assessed adjusting for potential response modifiers. Results: Baseline characteristics and CT treatments were similar. In multivariate analysis, allowing for biological and clinical factors known to influence tumour response, the adjusted mean RITS in CT and CT+ZOL groups were 27.4 and 15.5 mm, respectively, giving a difference in means of 12 mm (95% confidence interval: 3.5–20.4 mm; P=0.006). The pCR rate was 6.9% in the CT group and 11.7% in the CT+ZOL group (P=0.146). There was no difference in axillary nodal involvement (P=0.6315). Conclusion: These data suggest a possible direct anti-tumour effect of ZOL in combination with CT, warranting formal evaluation in prospective studies

Fishing the Molecular Bases of Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development

In vitro evaluation of modified surface microhardness measurement, focus variation 3D microscopy and contact stylus profilometry to assess enamel surface loss after erosive-abrasive challenges

The aim of the study was to compare surface loss values after erosion-abrasion cycles obtained with modified surface microhardness measurement (mSMH), focus variation 3D microscopy (FVM) and contact stylus profilometry (CSP). We cut human molars into buccal and lingual halves, embedded them in resin and ground 200 μm of enamel away. The resulting surfaces were polished. To maintain a reference area, we applied Block-Out resin to partly cover the enamel surface. The samples were incubated in artificial saliva (37°C; 1 h), then rinsed in deionized water (10 s) and dried with oil-free air (5 s). We immersed the specimens individually in 30 mL citric acid (1%, pH 3.6) for 2 min (25°C, 70 rpm dynamic conditions) before brushing them (50 strokes, 200 g) in an automatic brushing machine with toothpaste-slurry. We calculated the surface loss as per mSMH, by re-measuring the length of the same six indentations made before the abrasive challenge. The experiment consisted of five experimental groups that received between 2 and 10 erosion-abrasion cycles. Each group contained 15 specimens and samples in groups 1, 2, 3, 4 and 5 underwent a total of 2, 4, 6, 8 and 10 cycles, respectively. The resin was removed from the reference area in one piece under 10× magnification and the FVM and CSP were performed. Agreement between the methods was calculated with the intraclass correlation coefficient (ICC) and depicted in Bland-Altman plots. All methods presented a linear pattern of surface loss measurements throughout the experiment, leading overall to a strong, statistically significant correlation between the methods (ICC = 0.85; p<0.001). So, despite the different surface loss values, all methods presented consistent results for surface loss measurement

The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells

We thank S.S. Marelli for discussions. Supported by the Medical Research Council (A.L.), the Biotechnology and Biological Science Research Council (BB/J006750/1 to A.N.A. and S.M.H.) and the Instituto de Salud Carlos III, Spain (D.E.)