Super Resolution Fluorescence Microscopy and Tracking of Bacterial Flotillin (Reggie) Paralogs Provide Evidence for Defined-Sized Protein Microdomains within the Bacterial Membrane but Absence of Clusters Containing Detergent-Resistant Proteins.

Biological membranes have been proposed to contain microdomains of a specific lipid composition, in which distinct groups of proteins are clustered. Flotillin-like proteins are conserved between pro-and eukaryotes, play an important function in several eukaryotic and bacterial cells, and define in vertebrates a type of so-called detergent-resistant microdomains. Using STED microscopy, we show that two bacterial flotillins, FloA and FloT, form defined assemblies with an average diameter of 85 to 110 nm in the model bacterium Bacillus subtilis. Interestingly, flotillin microdomains are of similar size in eukaryotic cells. The soluble domains of FloA form higher order oligomers of up to several hundred kDa in vitro, showing that like eukaryotic flotillins, bacterial assemblies are based in part on their ability to self-oligomerize. However, B. subtilis paralogs show significantly different diffusion rates, and consequently do not colocalize into a common microdomain. Dual colour time lapse experiments of flotillins together with other detergent-resistant proteins in bacteria show that proteins colocalize for no longer than a few hundred milliseconds, and do not move together. Our data reveal that the bacterial membrane contains defined-sized protein domains rather than functional microdomains dependent on flotillins. Based on their distinct dynamics, FloA and FloT confer spatially distinguishable activities, but do not serve as molecular scaffolds.

Femoral nerve palsy after pelvic fracture treated with INFIX: a case series.

OBJECTIVE: The treatment of some pelvic injuries has evolved recently to include the use of a subcutaneous anterior pelvic fixator (INFIX). We present 8 cases of femoral nerve palsy in 6 patients after application of an INFIX to highlight this potentially devastating complication to pelvic surgeons using this technique and discuss how it might be avoided in the future. DESIGN: Retrospective chart review. Case series. SETTING: Five level 1 and 2 trauma centers, tertiary referral hospitals. PATIENTS/PARTICIPANTS: Six patients with anterior pelvic ring injury treated with an INFIX who experienced 8 femoral nerve palsies (2 bilateral). INTERVENTION: Removal of internal fixator, treatment for femoral nerve palsy. MAIN OUTCOME MEASUREMENTS: Clinical and electromyographic evaluation of patients. RESULTS: All 6 patients with a total of 8 femoral nerve palsies had their INFIX removed. Variable resolution of the nerve injuries was observed. CONCLUSIONS: Application of an INFIX for the treatment of pelvic ring injury carries a potentially devastating risk to the femoral nerve(s). Despite early implant removal after detection of nerve injury, some patients had residual quadriceps weakness, disturbance of the thigh's skin sensation, and/or gait disturbance attributable to femoral nerve palsy at the time of early final follow-up. LEVEL OF EVIDENCE: Therapeutic level IV. See Instructions for Authors for a complete description of levels of evidence.

Effect of bone type on clinical and radiographic outcomes of a proximally-coated cementless stem in primary total hip arthroplasties.

We determined the effect of pre-operative bone structure upon the temporal effects of remodeling after total hip arthroplasty (THA) in a series of uncemented implants. We evaluated 345 patients (375 hips), who had either Dorr Type-A (238 hips) or Type-B (137 hips) bone, and who received a proximally-coated cementless THA and were followed for a mean of 6 years. Outcomes evaluated included aseptic survivorship, Harris hip scores, and radiographic evaluation for patterns of remodeling. The aseptic survivorship (97.5% vs. 98%) and the mean final Harris hip scores (92 vs. 94 points) were similar between Types-A and -B bone, respectively. Bone remodeling was seen significantly earlier and over a longer duration for patients who had Type-B bone. At 5-years, periprosthetic condensation (78% vs. 54%) and cortical hypertrophy (53% vs. 37%) were significantly higher and radiolucencies at any zone were lower (53% vs. 37%) in Type-B compared to Type-A bone. There was increased condensation in men and higher cortical hypertrophy in women. Various radiographic remodeling differences may not negatively impact clinical outcome at mid-term follow-up. Morphologic bone type appears to be predictive of physiologic response to loading.

Proximally coated cementless bipolar hemiarthroplasty in Dorr type C bone.

The current study was conducted to examine the clinical and radiographic outcomes of cementless bipolar arthroplasty in patients who had type C bone at the time of the procedure. A total of 87 patients (105 hips) who had type C femora and had undergone cementless bipolar hemiarthroplasty with a proximally coated cementless prosthesis for the treatment of displaced femoral neck fractures at a single institution were reviewed. Patients included 83 women and 4 men who had a mean age of 84 years (range, 72-100 years) and were followed for a mean of 6 years (range, 2-11 years). Outcomes evaluated included aseptic implant survivorship, surgical complications, Harris Hip scores, and radiographic findings. At final follow-up, there were no revisions for aseptic implant loosening. The overall aseptic implant survivorship was 95%, with 5 patients undergoing revision surgery for aseptic reasons. Three revisions were because of periprosthetic fractures after falls, 1 revision was because of intractable groin pain, and 1 revision was because of recurrent dislocations. The surgical complication rate was 8.5%, which included 3 septic revisions, 2 avulsion fractures of the greater trochanter after falls, 2 superficial wound infections, 1 recurrent dislocation, and 1 wound hematoma. The mean Harris Hip score had improved to 80 points (range, 30-97 points) at final follow-up. Despite generally poor bone quality and medical comorbidities, elderly patients with displaced femoral neck fractures achieved excellent clinical outcomes, with few perioperative complications, through the use of proximally coated cementless bipolar hemiarthroplasty.

Dual-mobility bearings: a review of the literature.

Dislocation after total hip arthroplasty remains a major problem and hip instability is the most common reason for revision. These complications are costly to both patients and the healthcare system, and efforts to reduce them have had varied degrees of success. Although there are well documented patient and surgical risk factors for dislocation, the typical surgical solutions offered (constrained liners, large femoral heads) have the drawbacks of reduced range-of-motion and high rates of revision. Dual-mobility prostheses (unconstrained tripolar prostheses) are hip design solutions to dislocation that aim to provide a greater stability with an increased range-of-motion, along with potentially reduced wear. The mean overall dislocation rate from multiple combined studies using dual-mobility prostheses was 0.1% for primary total hip arthroplasty and 3.5% for revisions, compared with 2-7% for standard primary total hip arthroplasties and up to 16% for revisions. Dual-mobility prostheses offer a viable option for treating recurrent dislocation as well as for primary and revision arthroplasty.

Serological markers can lead to false negative diagnoses of periprosthetic infections following total knee arthroplasty.

Periprosthetic infections following total knee arthroplasty (TKA) are diagnostically challenging. We evaluated the sensitivity and specificity of ESR and CRP, false negative rates, whether false negative rates differed between early post-operative and late infections, and the predictive ability of ESR and CRP to differentiate infected patients. Between 2000 and 2007, a prospectively collected database was reviewed to identify patients with suspected periprosthetic infections, and who had ESR and CRP laboratory values. One hundred and thirteen patients were identified. False negative rates were calculated. Finally, receiver operating characteristic curves were used to determine the predictive ability of ESR and CRP to differentiate infected from non-infected patients. CRP had a sensitivity of 95% and specificity of 20%. ESR had a sensitivity of 91% and a specificity of 33%. The false negative rate was 9.2% for ESR, 5.3% for CRP, and 11.1% for combined ESR and CRP. False negative rates were higher for early post-operative infections. Although ESR and CRP can be excellent adjunctive diagnostic tools, we emphasise that because some patients may not mount a sufficient immune response, the entire clinical picture must be evaluated, and periprosthetic infection should not be ruled out on the basis of ESR and CRP results alone.

Evaluation of subcortical pathology and clinical correlations in FTLD-U subtypes.

Frontotemporal lobar degeneration (FTLD) can be classified as tau-positive (FTLD-tau) and tau-negative FTLD. The most common form of tau-negative FTLD is associated with neuronal inclusions that are composed of TAR DNA-binding protein 43 (TDP-43) (FTLD-TDP). Recent evidence suggests that FTLD-TDP can be further subdivided into at least three major histologic variants based on patterns of TDP-43 immunoreactive neuronal cytoplasmic inclusions (NCI) and dystrophic neurites (DN) in neocortex and hippocampus. The aim of this study was to extend the histologic analysis to other brain regions and to determine if there were distinct clinical and pathologic characteristics of the FTLD-TDP subtypes. Thirty-nine FTLD-TDP cases were analyzed (Mackenzie type 1 n = 24, Mackenzie type 2 n = 9, Mackenzie type 3 n = 6). There was a highly significant association between clinical syndrome and FTLD-TDP subtype, with progressive non-fluent aphasia associated with type 1, semantic dementia with type 2, and behavioral variant frontotemporal dementia with types 1, 2 and 3. Semi-quantitative analysis of NCI and DN demonstrated different patterns of involvement in cortical, subcortical and brainstem areas that were characteristic for each of the three types of FTLD-TDP. Type 1 had a mixture of NCI and DN, as well as intranuclear inclusions in most cases and TDP-43 pathology at all levels of the neuraxis, but less in brainstem than supratentorial structures. Type 2 cases were characterized by predominance of long, thick DN in the cortex, as well as numerous NCI in hippocampus, amygdala and basal ganglia, but virtually no NCI and only sparse DN in diencephalon and brainstem. Type 3 had a paucity of DN at all levels of the neuraxis and significantly more NCI in the hypoglossal nucleus than the other types. These findings extend previously described clinicopathological associations of FTLD-TDP subtypes and support the notion that FTLD-TDP subtypes may be distinct clinicopathologic disorders.