Acetabular fracture: Long-term follow-up and factors associated with secondary implantation of total hip arthroplasty

SummaryHypothesisThe present study sought to determine long-term outcome in acetabular fracture and the factors associated with secondary implantation of a total hip arthroplasty and/or with poor functional results.Material and methodsSeventy-two patients admitted between 2000 and 2005 were followed up for a maximum 11years (mean, 6.8years): 16 females, 56 males; mean age at injury, 41.6years (median, 40years). There were 45 simple acetabular fractures, 27 complex fractures and 27 dislocations. Late complications were: osteoarthritis (n=29), osteonecrosis of the femoral head (ONFH: n=8) and heterotopic ossification (n=2).Results and discussionTwenty-five total hip arthroplasties (THA) were performed, with a mean time to surgery of 3.7years. Associated factors for THA were: VAS (P<0.0001), PMA (P<0.0001), osteoarthritis (P<0.0001), ONFH (P<0.0002), initial dislocation (P=0.0002), no functional treatment (P=0.0014), surgical treatment (P=0.0065), initial traction (P=0.0068), anterior and posterior congruency defect (P=0.0072 and P<0.0001), and initial intra-articular foreign body (P=0.045). Factors associated with poor or bad functional results were the same, plus: etiology (P=0.0021), BMI (P=0.03) and posterior wall fracture (P=0.0325).Level of evidence4; retrospective study

Genetic Dissection of Strain Dependent Paraquat-induced Neurodegeneration in the Substantia Nigra Pars Compacta

The etiology of the vast majority of Parkinson's disease (PD) cases is unknown. It is generally accepted that there is an interaction between exposures to environmental agents with underlying genetic sensitivity. Recent epidemiological studies have shown that people living in agricultural communities have an increased risk of PD. Within these communities, paraquat (PQ) is one of the most utilized herbicides. PQ acts as a direct redox cycling agent to induce formation of free radicals and when administered to mice induces the cardinal symptoms of parkinsonism, including loss of TH+-positive dopaminergic (DA) neurons in the ventral midbrain's substantia nigra pars compacta (SNpc). Here we show that PQ-induced SNpc neuron loss is highly dependent on genetic background: C57BL/6J mice rapidly lose ∼50% of their SNpc DA neurons, whereas inbred Swiss-Webster (SWR/J) mice do not show any significant loss. We intercrossed these two strains to map quantitative trait loci (QTLs) that underlie PQ-induced SNpc neuron loss. Using genome-wide linkage analysis we detected two significant QTLs. The first is located on chromosome 5 (Chr 5) centered near D5Mit338, whereas the second is on Chr 14 centered near D14Mit206. These two QTLs map to different loci than a previously identified QTL (Mptp1) that controls a significant portion of strain sensitivity to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), suggesting that the mechanism of action of these two parkinsonian neurotoxins are different

Visualization of Glutamine Transporter Activities in Living Cells Using Genetically Encoded Glutamine Sensors

Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells) is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET) glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP)1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level