Stable fixation of an osseointegated implant system for above-the-knee amputees: titel RSA and radiographic evaluation of migration and bone remodeling in 55 cases.

Background and purposeRehabilitation of patients with transfemoral amputations is particularly difficult due to problems in using standard socket prostheses. We wanted to assess long-term fixation of the osseointegrated implant system (OPRA) using radiostereometric analysis (RSA) and periprosthetic bone remodeling.Methods51 patients with transfemoral amputations (55 implants) were enrolled in an RSA study. RSA and plain radiographs were scheduled at 6 months and at 1, 2, 5, 7, and 10 years after surgery. RSA films were analyzed using UmRSA software. Plain radiographs were graded for bone resorption, cancellization, cortical thinning, and trabecular streaming or buttressing in specifically defined zones around the implant.ResultsAt 5 years, the median (SE) migration of the implant was -0.02 (0.06) mm distally. The rotational movement was 0.42 (0.32) degrees around the longitudinal axis. There was no statistically significant difference in median rotation or migration at any follow-up time. Cancellization of the cortex (plain radiographic grading) appeared in at least 1 zone in over half of the patients at 2 years. However, the prevalence of cancellization had decreased by the 5-year follow-up.InterpretationThe RSA analysis for the OPRA system indicated stable fixation of the implant. The periprosthetic bone remodeling showed similarities with changes seen around uncemented hip stems. The OPRA system is a new and promising approach for addressing the challenges faced by patients with transfemoral amputations

In vivo bioluminescence imaging using orthotopic xenografts towards patient's derived-xenograft Medulloblastoma models

BACKGROUND: Medulloblastoma is a cerebellar neoplasia of the central nervous system. Four molecular subgrups have been identified (MBWNT, MBSHH, MBgroup3 and MBgroup4) with distinct genetics and clinical outcome. Among these, MBgroup3-4 are highly metastatic with the worst prognosis. The current standard therapy includes surgery, radiation and chemotherapy. Thus, specific treatments adapted to cure those different molecular subgroups are needed. The use of orthotopic xenograft models, together with the non-invasive in vivo biolumiscence imaging (BLI) technology, is emerging during preclinical studies to test novel therapeutics for medulloblastoma treatment. METHODS: Orthotopic MB xenografts were performed by injection of Daoy-luc cells, that had been previously infected with lentiviral particles to stably express luciferase gene, into the fourth right ventricle of the cerebellum of ten nude mice. For the implantation, specific stereotactic coordinates were used. Seven days after the implantation the mice were imaged by acquisitions of bioluminescence imaging (BLI) using IVIS 3D Illumina Imaging System (Xenogen). Tumor growth was evaluated by quantifying the bioluminescence signals using the integrated fluxes of photons within each area of interest using the Living Images Software Package 3.2 (Xenogen-Perkin Elmer). Finally, histological analysis using hematoxylin-eosin staining was performed to confirm the presence of tumorigenic cells into the cerebellum of the mice. RESULTS: We describe a method to use the in vivo bioluminescent imaging (BLI) showing the potential to be used to investigate the potential antitumorigenic effects of a drug for in vivo medulloblastoma treatment. We also discuss other studies in which this technology has been applied to obtain a more comprehensive knowledge of medulloblastoma using orthotopic xenograft mouse models. CONCLUSIONS: There is a need to develop patient's derived-xenograft (PDX) model systems to test novel drugs for medulloblastoma treatment within each molecular sub-groups with a higher predictive value. Here we show how this technology should be applied with hopes on generations of new treatments to be applied then in human

Regulations and Ethical Considerations for Astronomy Education Research II: Resources and Worked Examples

This article discusses the legal and ethical requirements of human subjects research proposals in astronomy education research. We present an overview of the relevant laws, regulations, and guidelines that inform an Institutional Review Board evaluation of proposed research. We also present examples of potential research projects in astronomy education research and discuss their ethical issues

Indirect evaporative cooling systems: An experimental analysis in summer condition

Indirect evaporative coolers (IEC) are components that can be effectively installed in air handling units to increase energy efficiency of air conditioning systems. In particular, such devices can be used in summer conditions to reduce chiller load in both existing and new buildings. In this paper, an IEC system based on a cross flow heat exchanger has been tested, evaluating its cooling capacity in different operating conditions. Performance is evaluated in terms of wet bulb effectiveness, primary air temperature reduction and fraction of evaporated water. Results put in evidence that a significant cooling capacity can be achieved in many operating conditions. Therefore, IECs are a promising technology that can be effectively used to reduce primary energy consumption of conventional systems

Complete endoscopic closure (clipping) of a large esophageal perforation after pneumatic dilation in a patient with achalasia

The risk of esophageal perforation following endoscopic balloon dilation for achalasia is in the range of 1 and 5% with a mortality rate of 1-20%. Perforations need to be recognized early and, if reasonable, an immediate endoscopic repair should be pursued quickly. Herein, we report a case of successful endoscopic closure by clipping of a large iatrogenic perforation in a patient with achalasia. An 80-year-old woman with achalasia was admitted to our institution to undergo pneumatic dilation. A 40-mm balloon dilator with inflation pressure of 20 PSI was used for 2 minutes as usual. During the procedure, the patient had a transient bradycardia. Endoscopic control showed a 2-cm rupture of the distal esophagus. Prompt endoscopic repair of the perforation by endoclips (n=6) was then attempted, followed by conservative management by total parenteral nutrition and intravenous antibiotics. Endoscopic clipping closed completely the esophageal perforation. The patient was given oral nutrition 10 days later without any complications. Six months after the discharge, the patient was healthy and free of dysphagia. Endoscopy showed complete healing of the esophageal mucosa without luminal stenosis. This report highlights that prompt endoscopic clipping is a useful means to close a large esophageal perforation caused by pneumatic dilation

Hedgehog Pathway Activation Alters Ciliary Signaling in Primary Hypothalamic Cultures

Primary cilia dysfunction has been associated with hyperphagia and obesity in both ciliopathy patients and mouse models of cilia perturbation. Neurons throughout the brain possess these solitary cellular appendages, including in the feeding centers of the hypothalamus. Several cell biology questions associated with primary neuronal cilia signaling are challenging to address in vivo. Here we utilize primary hypothalamic neuronal cultures to study ciliary signaling in relevant cell types. Importantly, these cultures contain neuronal populations critical for appetite and satiety such as pro-opiomelanocortin (POMC) and agouti related peptide (AgRP) expressing neurons and are thus useful for studying signaling involved in feeding behavior. Correspondingly, these cultured neurons also display electrophysiological activity and respond to both local and peripheral signals that act on the hypothalamus to influence feeding behaviors, such as leptin and melanin concentrating hormone (MCH). Interestingly, we found that cilia mediated hedgehog signaling, generally associated with developmental processes, can influence ciliary GPCR signaling (Mchr1) in terminally differentiated neurons. Specifically, pharmacological activation of the hedgehog-signaling pathway using the smoothened agonist, SAG, attenuated the ability of neurons to respond to ligands (MCH) of ciliary GPCRs. Understanding how the hedgehog pathway influences cilia GPCR signaling in terminally differentiated neurons could reveal the molecular mechanisms associated with clinical features of ciliopathies, such as hyperphagia-associated obesity

Differential expression analysis with global network adjustment

<p>Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.</p> <p>Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.</p> <p>Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.</p&gt