External fixation of the thalamic portion of a fractured calcaneus: A new surgical technique

AbstractThe optimal treatment for intra-articular calcaneus fractures remains controversial, despite internal fixation techniques providing good results. The major point of contention is the need to reconstruct the overall morphology versus to restore the anatomy of the subtalar joint perfectly. We will describe a two-stage technique for treating intra-articular calcaneus fractures in which the primary fracture line goes through the thalamic fragment. The first procedure focuses on the overall morphology by restoring the height and length with osteotaxis being accomplished with a medial external fixator. The second procedure consists of internal fixation through a minimally invasive lateral approach to restore the anatomy of the articular facets. Any defects are filled with injectable bone substitute. This novel technique is compared to the complication rates and radiology and anatomy outcomes in published studies. This two-stage surgical technique reduces the length of hospital stays and the number of complications

Bayesian mapping of pulmonary tuberculosis in Antananarivo, Madagascar

<p>Abstract</p> <p>Background</p> <p>Tuberculosis (TB), an infectious disease caused by the <it>Mycobacterium tuberculosis </it>is endemic in Madagascar. The capital, Antananarivo is the most seriously affected area. TB had a non-random spatial distribution in this setting, with clustering in the poorer areas. The aim of this study was to explore this pattern further by a Bayesian approach, and to measure the associations between the spatial variation of TB risk and national control program indicators for all neighbourhoods.</p> <p>Methods</p> <p>Combination of a Bayesian approach and a generalized linear mixed model (GLMM) was developed to produce smooth risk maps of TB and to model relationships between TB new cases and national TB control program indicators. The TB new cases were collected from records of the 16 Tuberculosis Diagnostic and Treatment Centres (DTC) of the city from 2004 to 2006. And five TB indicators were considered in the analysis: number of cases undergoing retreatment, number of patients with treatment failure and those suffering relapse after the completion of treatment, number of households with more than one case, number of patients lost to follow-up, and proximity to a DTC.</p> <p>Results</p> <p>In Antananarivo, 43.23% of the neighbourhoods had a standardized incidence ratio (SIR) above 1, of which 19.28% with a TB risk significantly higher than the average. Identified high TB risk areas were clustered and the distribution of TB was found to be associated mainly with the number of patients lost to follow-up (SIR: 1.10, CI 95%: 1.02-1.19) and the number of households with more than one case (SIR: 1.13, CI 95%: 1.03-1.24).</p> <p>Conclusion</p> <p>The spatial pattern of TB in Antananarivo and the contribution of national control program indicators to this pattern highlight the importance of the data recorded in the TB registry and the use of spatial approaches for assessing the epidemiological situation for TB. Including these variables into the model increases the reproducibility, as these data are already available for individual DTCs. These findings may also be useful for guiding decisions related to disease control strategies.</p

Human dentin characteristics of patients with osteogenesis imperfecta: insights into collagen-based biomaterials

International audienceOsteogenesis imperfecta (OI), also known as "brittle bone disease", is a rare genetic disorder of the skeleton, whose most benign form I corresponds to autosomal dominant mutations in the genes encoding type I collagen (COLA1, COLA2). Several associated skeletal manifestations are often observed but, surprisingly, while dentin defects often reflect genetic bone disorders, about half of OI patients have no obvious oral manifestations. Here, we investigated the collagen, mineral and mechanical properties of dentin from deciduous teeth collected from patients with mild form of OI and displaying no obvious clinical signs of dentinogenesis imperfecta. For the first time, an increase in the hardness of OI dentin associated with an increase in mineral content compared to healthy patients was reported. In addition, OI altered the tissue characteristics of the dentin-enamel junction but the interfacial gradient was preserved. The impact of changes in molecular structure due to mutations in OI was assessed by Raman microspectroscopy. Our results highlighted a change in the hydroxyproline-proline ratio in direct association with collagen mineralization. Our findings suggest that the evaluation of teeth could be an important aid for mild types of OI that are often difficult to diagnose clinically and provide experimental evidence that hydroxyproline content should be considered in future studies on collagen-based biomaterials

Doublecortin-like kinase 3 (DCLK3), a novel striatum-enriched species, is amodulator of mutant huntingtin in vivo: L. GALVAN1, M.-C. GAILLARD2, M. DE CHALDÉE2, G. AUREGAN1, N.DUFOUR1, M. GUILLERMIER1, D. HOUITTE1, F. PETIT1, C. MALGORN1,G. LIOT3, S. HUMBERT3, J. ELALOUF2, N. DÉGLON1, *E. P. BROUILLET1;1CEA, MIRCen, URA CEA-CNRS 2210, Fontenay-aux-Roses, France; 2CEAIBITec-S/SBIGeM, Saclay, France; 3Inst. Curie, UMR 146, CNRS, Orsay, France

International audienceHuntington's disease (HD) is a neurodegenerative disorder caused by an abnormalCAG repeat expansion coding for an expanded polyglutamine tract in the protein"huntingtin" (Htt). Although this mutant Htt (mHtt) is expressed ubiquitouslythroughout the brain, the striatum is found preferentially affected. One hypothesisto explain this particular vulnerability is that striatal neurons express a particularset of proteins that make them highly vulnerable to mHtt. In order to furtherexamine this hypothesis, we carried out a transcriptome analysis of different brainterritories and identified more than 100 molecular markers i.e. transcripts that arehighly enriched in the mouse striatum. We recently focused our interest on asubset of striatal-enriched transcripts of poorly characterized transcripts.We here report the study of one of these markers, the CAMKII family-relatedkinase DCLK3. We found that DCLK3 is mainly expressed in the adult striatum inrodent with low level of expression in the newborn and striatal primary cultures.Reduced mRNA levels of DCLK3 were found in the striatum of transgenic mousemodels of HD. We thus studied the effect of DCLK3 overexpression and knockdownin a mouse model of HD using lentiviral vectors coding for a N-terminalfragment of mHtt. DCLK3 and its related siRNA were delivered using lentiviralvectors. Striatal degeneration produced by mHtt was characterized usingimmunohistochemistry of DARPP32, Cytochrome oxidase and ubiquitin followedby quantitative histological evaluation. Results showed that lenti-siRNA targetingDCLK3 increased mHtt toxicity when compared to the control. On the contrary,overexpression of DCLK3 reduced the striatal lesions produced by mHtt in vivo.DCLK3 also decreased the number and size of ubiquitin-containing nuclearinclusions. Current experiments are examining the mechanisms that could underliethe neuroprotective effect of DCLK3 in striatal neurons. The present study suggests that DCLK3 is a potential modifier of the disease and might beconsidered in HD therapy to slow disease progression

Doublecortin-like kinase 3 (DCLK3), a novel striatum-enriched species, is amodulator of mutant huntingtin in vivo: L. GALVAN1, M.-C. GAILLARD2, M. DE CHALDÉE2, G. AUREGAN1, N.DUFOUR1, M. GUILLERMIER1, D. HOUITTE1, F. PETIT1, C. MALGORN1,G. LIOT3, S. HUMBERT3, J. ELALOUF2, N. DÉGLON1, *E. P. BROUILLET1;1CEA, MIRCen, URA CEA-CNRS 2210, Fontenay-aux-Roses, France; 2CEAIBITec-S/SBIGeM, Saclay, France; 3Inst. Curie, UMR 146, CNRS, Orsay, France

International audienceHuntington's disease (HD) is a neurodegenerative disorder caused by an abnormalCAG repeat expansion coding for an expanded polyglutamine tract in the protein"huntingtin" (Htt). Although this mutant Htt (mHtt) is expressed ubiquitouslythroughout the brain, the striatum is found preferentially affected. One hypothesisto explain this particular vulnerability is that striatal neurons express a particularset of proteins that make them highly vulnerable to mHtt. In order to furtherexamine this hypothesis, we carried out a transcriptome analysis of different brainterritories and identified more than 100 molecular markers i.e. transcripts that arehighly enriched in the mouse striatum. We recently focused our interest on asubset of striatal-enriched transcripts of poorly characterized transcripts.We here report the study of one of these markers, the CAMKII family-relatedkinase DCLK3. We found that DCLK3 is mainly expressed in the adult striatum inrodent with low level of expression in the newborn and striatal primary cultures.Reduced mRNA levels of DCLK3 were found in the striatum of transgenic mousemodels of HD. We thus studied the effect of DCLK3 overexpression and knockdownin a mouse model of HD using lentiviral vectors coding for a N-terminalfragment of mHtt. DCLK3 and its related siRNA were delivered using lentiviralvectors. Striatal degeneration produced by mHtt was characterized usingimmunohistochemistry of DARPP32, Cytochrome oxidase and ubiquitin followedby quantitative histological evaluation. Results showed that lenti-siRNA targetingDCLK3 increased mHtt toxicity when compared to the control. On the contrary,overexpression of DCLK3 reduced the striatal lesions produced by mHtt in vivo.DCLK3 also decreased the number and size of ubiquitin-containing nuclearinclusions. Current experiments are examining the mechanisms that could underliethe neuroprotective effect of DCLK3 in striatal neurons. The present study suggests that DCLK3 is a potential modifier of the disease and might beconsidered in HD therapy to slow disease progression

Doublecortin-like kinase 3 (DCLK3), a novel striatum-enriched species, is amodulator of mutant huntingtin in vivo

International audienceHuntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG repeat expansion coding for an expanded polyglutamine tract in the protein "huntingtin" (Htt). Although this mutant Htt (mHtt) is expressed ubiquitously throughout the brain, the striatum is found preferentially affected. One hypothesis to explain this particular vulnerability is that striatal neurons express a particular set of proteins that make them highly vulnerable to mHtt. In order to further examine this hypothesis, we carried out a transcriptome analysis of different brain territories and identified more than 100 molecular markers i.e. transcripts that are highly enriched in the mouse striatum. We recently focused our interest on a subset of striatal-enriched transcripts of poorly characterized transcripts. We here report the study of one of these markers, the CAMKII family-related kinase DCLK3. We found that DCLK3 is mainly expressed in the adult striatum in rodent with low level of expression in the newborn and striatal primary cultures. Reduced mRNA levels of DCLK3 were found in the striatum of transgenic mouse models of HD. We thus studied the effect of DCLK3 overexpression and knock-down in a mouse model of HD using lentiviral vectors coding for a N-terminal fragment of mHtt. DCLK3 and its related siRNA were delivered using lentiviral vectors. Striatal degeneration produced by mHtt was characterized using immunohistochemistry of DARPP32, Cytochrome oxidase and ubiquitin followed by quantitative histological evaluation. Results showed that lenti-siRNA targeting DCLK3 increased mHtt toxicity when compared to the control. On the contrary, overexpression of DCLK3 reduced the striatal lesions produced by mHtt in vivo. DCLK3 also decreased the number and size of ubiquitin-containing nuclear inclusions. Current experiments are examining the mechanisms that could underlie the neuroprotective effect of DCLK3 in striatal neurons. The present study 4/6/202