Mode of Antibacterial Action of Tomatidine C3-Diastereoisomers.

Tomatidine (TO) is a natural narrow-spectrum antibiotic acting on the Staphylococcus aureus small colony variant (SCV) with a minimal inhibitory concentration (MIC) of 0.06 µg/mL while it shows no activity against prototypical strains (MIC > 128 µg/mL). To expand the spectrum of activity of TO, the 3ß-hydroxyl group was substituted with an ethane-1,2-diamine, resulting in two diastereoisomers, TM-02 (C3-ß) and TM-03 (C3-α). These molecules are equally potent against prototypical S. aureus and E. coli strains (MIC 8 and 32 µg/mL, respectively), whereas TM-02 is more potent against SCV (MIC 0.5 µg/mL) and hyperpermeable E. coli strains (MIC 1 µg/mL). The differences in their modes of action were investigated. We used membrane vesicles to confirm the inhibition of the bacterial ATP synthase, the documented target of TO, and measured effects on bacterial cell membranes. Both molecules inhibited E. coli ATP synthase, with Ki values of 1.1 µM and 3.5 µM for TM-02 and TM-03, respectively, and the bactericidal effect of TM-02 was linked to ATP synthase inhibition. Furthermore, TM-02 had no major effect on the membrane fluidity and gradually reduced membrane potential. In contrast, TM-03 caused structural damages to membranes and completely disrupted the membrane potential (>90%). We were successful in broadening the spectrum of activity of TO. C3-ß-diastereoisomers may have more specific antibacterial action than C3-α.

Pre-operative templating in THA. Part I: a classification of architectural hip deformities.

INTRODUCTION: While numerous classifications of hip arthritis have been proposed, none considered the magnitude and direction of femoral head translation relative to the native acetabulum. A more precise classification of architectural hip deformities is necessary to improve preoperative templating and anticipate surgical challenges of total hip arthroplasty (THA). The purpose of the present study was to introduce a classification system to distinguish different types of architectural hip deformities, based on femoral head translation patterns, and to evaluate its repeatability using plain radiographs (qualitative) and Computed Tomography (CT) measurements (quantitative). MATERIALS AND METHODS: We studied pre-operative frontal and lateral hip radiographs and CT scans of 191 hips (184 patients) that received primary THA. The distance between the femoral head center (FC) and the acetabular center (AC) was measured, as well as femoral offset, acetabular offset, head center height, acetabular floor distance and femoral neck angle. The hips were classified qualitatively using frontal plain radiographs, and then quantitatively using CT scans (with an arbitrary threshold of 3 mm as Centered, Medialized, Lateralized, Proximalized or Proximo-lateralized. The agreement between qualitative and quantitative classification methods was compared for applying the same classification. RESULTS: Qualitative classification identified 120 centered (63%), 8 medialized (4%), 49 lateralized (26%), 3 proximalized (2%), and 11 proximo-lateralized (6%) hips, while quantitative classification identified 116 centered (61%), 8 medialized (4%), 51 lateralized (27%), 5 proximalized (3%), and 11 proximo-lateralized (6%) hips. The agreement between the two methods was excellent (0.94; CI 0.90-0.98). Medialization reached 9.7 mm, while lateralization reached 10.9 mm, and proximalization reached 8.5 mm. Proximalized and proximo-lateralized hips had more valgus necks, while medialized hips had more varus necks (p = 0.003). CONCLUSIONS: The classification system enabled repeatable distinction of 5 types of architectural hip deformities. The excellent agreement between quantitative and qualitative methods suggests that plain radiographs are sufficient to classify architectural hip deformities.

Tomatidine Is a Lead Antibiotic Molecule That Targets Staphylococcus aureus ATP Synthase Subunit C.

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of deadly hospital-acquired infections. The discovery of anti-Staphylococcus antibiotics and new classes of drugs not susceptible to the mechanisms of resistance shared among bacteria is imperative. We recently showed that tomatidine (TO), a steroidal alkaloid from solanaceous plants, possesses potent antibacterial activity against S. aureus small-colony variants (SCVs), the notoriously persistent form of this bacterium that has been associated with recurrence of infections. Here, using genomic analysis of in vitro-generated TO-resistant S. aureus strains to identify mutations in genes involved in resistance, we identified the bacterial ATP synthase as the cellular target. Sequence alignments were performed to highlight the modified sequences, and the structural consequences of the mutations were evaluated in structural models. Overexpression of the atpE gene in S. aureus SCVs or introducing the mutation found in the atpE gene of one of the high-level TO-resistant S. aureus mutants into the Bacillus subtilis atpE gene provided resistance to TO and further validated the identity of the cellular target. FC04-100, a TO derivative which also possesses activity against non-SCV strains, prevents high-level resistance development in prototypic strains and limits the level of resistance observed in SCVs. An ATP synthesis assay allowed the observation of a correlation between antibiotic potency and ATP synthase inhibition. The selectivity index (inhibition of ATP production by mitochondria versus that of bacterial ATP synthase) is estimated to be >105-fold for FC04-100.

Spatiotemporal characterization of brain infarction by sequential multimodal MR imaging following transient focal ischemia in a Rat model of intra-arterial middle cerebral artery occlusion.

OBJECTIVES: To assess spatiotemporal brain infarction evolution by sequential multimodal magnetic resonance (MR) imaging in an endovascular model of acute stroke in rats. MATERIALS AND METHODS: A microwire was selectively placed in the middle cerebral artery (MCA) in 16 consecutives rats during 90 minutes occlusion. Longitudinal 7-T MR imaging, including angiography, diffusion, and perfusion was performed during ischemia, immediately after reperfusion, 3 h and 24 h after subsequent reperfusion. RESULTS: MCA occlusion was complete in 75 % and partial in 18.7 %. Hypoperfusion (mean ± SD) was observed in all animals during ischemia (-59 ± 18 % of contralateral hemisphere, area 31 ± 5 mm2). Infarction volume (mean ± SD) was 90 ± 64 mm3 during ischemia and 57 ± 67 mm3 at 24 h. Brain infarction was fronto-parietal cortical in five animals (31 %), striatal in four animals (25 %), and cortico-striatal in seven animals (44 %) at 24 h. All rats survived at 24 h. CONCLUSION: This model is suitable to neuroprotection studies because of possible acute and close characterization of spatiotemporal evolution of brain infarction by MR imaging techniques, and evidence of ischemic penumbra, the target of neuroprotection agents. However, optimization of the brain infarct reproducibility needs further technical and neurointerventional tools improvements. KEY POINTS: • Nitinol microwire is MRI compatible allowing spatiotemporal characterization of brain infarction in rats. • Microwire selective placement in middle cerebral artery allows complete artery occlusion in 75 %. • A diffusion/perfusion mismatch during arterial occlusion is observed in 77 % of rats.

Intra-prosthetic dislocation of dual-mobility cups after total hip arthroplasty: potential causes from a clinical and biomechanical perspective.

INTRODUCTION: Recurrent dislocation of total hip arthroplasty is a frequent indication for revision surgery. Hip joint stability depends on implant design, cup position and crucially on femoral head diameter. Due to an effective ultra-large diameter femoral head, dual-mobility cups are considered an attractive solution to prevent dislocation in unstable conditions. Although patients obviously benefit for many years in terms of mobility and pain, an increase of intra-prosthetic dislocation reports using dual-mobility cups has been recently observed. However, the failure mechanism of this implant-specific complication, which is characterized by the loss of the positive-locking between the femoral head and the mobile liner, is not yet completely understood. METHODS: A comprehensive search was performed with the PubMed database and a search engine to overview this topic and to identify potential causes for this implant-specific failure from a clinical and biomechanical perspective. RESULTS: Peri-operative findings indicate extensive fibrosis at the large articulation as well as cup loosening as potential causes. In addition, current research has shown that the failure mechanism is affected by the surface topography of the femoral neck and in particular by the design of the mobile liner. DISCUSSION: In clinical practice it is necessary to differentiate a classic dislocation between the mobile liner and the metallic shell from an intra-prosthetic dislocation between the femoral head and the liner. CONCLUSION: Due to the increasing popularity of dual-mobility cups in total hip arthroplasty, the understanding of which implant-specific features or tissue response may increase the risk of intra-prosthetic dislocation is of major importance for reduced revision rates by using optimized surgical techniques and implant designs.

Telomerase inhibition improves tumor response to radiotherapy in a murine orthotopic model of human glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most frequent and aggressive type of adult brain tumor. Most GBMs express telomerase; a high level of intra-tumoral telomerase activity (TA) is predictive of poor prognosis. Thus, telomerase inhibitors are promising options to treat GBM. These inhibitors increase the response to radiotherapy (RT), in vitro as well as in vivo. Since typical treatments for GBM include RT, our objective was to evaluate the efficiency of Imetelstat (TA inhibitor) combined with RT. FINDINGS: We used a murine orthotopic model of human GBM (N = 8 to11 mice per group) and µMRI imaging to evaluate the efficacy of Imetelstat (delivered by intra-peritoneal injection) alone and combined with RT. Using a clinically established protocol, we demonstrated that Imetelstat significantly: (i) inhibited the TA in the very center of the tumor, (ii) reduced tumor volume as a proportion of TA inhibition, and (iii) increased the response to RT, in terms of tumor volume regression and survival increase. CONCLUSIONS: Imetelstat is currently evaluated in refractory brain tumors in young patients (without RT). Our results support its clinical evaluation combined with RT to treat GBM.

Spatial abilities and technical skills performance in health care: a systematic review.

OBJECTIVES: The aim of this study was to conduct a systematic review and meta-analysis of the relationship between spatial abilities and technical skills performance in health care in beginners and to compare this relationship with those in intermediate and autonomous learners. METHODS: Search criteria included 'spatial abilities' and 'technical skills'. Keywords related to these criteria were defined. A literature search was conducted to 20 December, 2013 in Scopus (including MEDLINE) and in several databases on EBSCOhost platforms (CINAHL Plus with Full Text, ERIC, Education Source and PsycINFO). Citations were obtained and reviewed by two independent reviewers. Articles related to retained citations were reviewed and a final list of eligible articles was determined. Articles were assessed for quality using the Scottish Intercollegiate Guidelines Network-50 assessment instrument. Data were extracted from articles in a systematic way. Correlations between spatial abilities test scores and technical skills performance were identified. RESULTS: A series of 8289 citations was obtained. Eighty articles were retained and fully reviewed, yielding 36 eligible articles. The systematic review found a tendency for spatial abilities to be negatively correlated with the duration of technical skills and positively correlated with the quality of technical skills performance in beginners and intermediate learners. Pooled correlations of studies were -0.46 (p = 0.03) and -0.38 (95% confidence interval [CI] -0.53 to -0.21) for duration and 0.33 (95% CI 0.20-0.44) and 0.41 (95% CI 0.26-0.54) for quality of technical skills performance in beginners and intermediate learners, respectively. However, correlations between spatial abilities test scores and technical skills performance were not statistically significant in autonomous learners. CONCLUSIONS: Spatial abilities are an important factor to consider in selecting and training individuals in technical skills in health care.

Do oxidized zirconium femoral heads reduce polyethylene wear in cemented THAs? A blinded randomized clinical trial.

BACKGROUND: Charnley low-friction torque total hip arthroplasty (THA) remains the gold standard in THA. The main cause for failure is wear of the socket. Highly crosslinked polyethylene (HXLPE) has been associated with reduced wear rates. Also, oxidized zirconium has shown in vitro reduced wear rates. However, to our knowledge, there are no data comparing oxidized zirconium femoral heads with metal heads against HXLPE or ultrahigh-molecular-weight polyethylene (UHMWPE) when 22.25-mm bearings were used, which was the same size that performed so well in Charnley-type THAs. QUESTIONS/PURPOSES: We hypothesized that after a minimal 4-year followup (1) use of HXLPE would result in lower radiographic wear than UHMWPE when articulating with a stainless steel head or with an oxidized zirconium head; (2) use of oxidized zirconium would result in lower radiographic wear than stainless steel when articulating with UHMWPE and HXLPE; and (3) there would be no difference in terms of Merle d'Aubigné scores between the bearing couple combinations. METHODS: One hundred patients were randomized to receive cemented THA with either oxidized zirconium or a stainless steel femoral head. UHMWPE was used in the first 50 patients, whereas HXLPE was used in the next 50 patients. There were 25 patients in each of the four bearing couple combinations. All other parameters were identical in both groups. Complete followup was available in 86 of these patients. Femoral head penetration was measured using a validated computer-assisted method dedicated to all-polyethylene sockets. Clinical results were compared between the groups using the Merle d'Aubigné score. RESULTS: In the UHMWPE series, the median steady-state penetration rate from 1 year onward was 0.03 mm/year (range, 0.003-0.25 mm/year) in the oxidized zirconium group versus 0.11 mm/year (range, 0.03-0.29 mm/year) in the metal group (difference of medians 0.08, p < 0.001). In the HXLPE series, the median steady-state penetration rate from 1 year onward was 0.02 mm/year (range, -0.32 to 0.07 mm/year) in the oxidized zirconium group versus 0.05 mm/year (range, -0.39 to 0.11 mm/year) in the metal group (difference of medians 0.03, p < 0.001). The Merle d'Aubigné scores were no different between the groups with a median of 18 in each of the groups (range, 16-18). CONCLUSIONS: This study demonstrated femoral head penetration was reduced by oxidized zirconium when compared with metal on both UHMWPE and HXLPE. However, apart the metal-UHMWE group, all other groups had a steady-state penetration rate well below the osteolysis threshold with a low difference between groups that might not be clinically important at this point. Longer-term followup is needed to warrant whether wear reduction will generate less occurrence of osteolysis and aseptic loosening. LEVEL OF EVIDENCE: Level II, therapeutic study.

Predictors of flexion using the rotating concave-convex total knee arthroplasty: preoperative range of motion is not the only determinant.

PURPOSE: The range of motion achieved after a total knee arthroplasty (TKA) affects many daily activities and overall patients' satisfaction. This study aims to define the determinants affecting post-operative midterm active flexion according to a specific cruciate-sacrificing prosthesis, the rotating concave-convex (ROCC(®)) TKA. METHOD: Four hundred and eighty-four consecutive patients (584 TKAs) were prospectively followed. After baseline patient demographics and anatomical characteristics, clinical and radiological post-operative assessments were periodically recorded. The rotational alignment of the femoral component was additionally reported for 120 patients. Eligibility for final inclusion was a minimum of 5-year follow-up. Univariate analyses followed by a multivariate model were fitted to determine the independent predictors of midterm active knee flexion. RESULTS: Thirty-four TKA (5.8%) were excluded for a secondary surgery before their 50 years, 69 patients died (11.8%), and 21 (3.6%) were lost to follow-up. Overall, 460 TKAs were included. The post-operative mean knee flexion angle was measured at 127.7° ± 9.3°. Significant factors affecting final flexion under univariate analyses were the patient height and body mass index, the absence of previous surgery, a depressive state, the preoperative flexion angle, a preoperative flexion contracture, a patellar residual subluxation, the reconstructed patellar height, and the rotation of the femoral component. The multivariate model confirmed the patient's height, a depression, the preoperative flexion angle, a patellar residual subluxation, and the patellar height as statistically significant determinants. CONCLUSION: Aside from the preoperative flexion angle, numerous predictors of flexion, both patient- and procedure-related were identified. Surgeons should take these into account both when adequately informing their patient before surgery and when performing the arthroplasty itself. LEVEL OF EVIDENCE: Prognostic, Level II.

Functional Results of the ROCC® Mobile Bearing Knee. 602 Cases at Midterm Follow-Up (5 to 14 Years).

UNLABELLED: We report midterm results of a prospective continuous cohort of ROCC® Total Knee Arthroplasties (TKA). Between 2001 and 2008, all primary TKA patients (n=500) received 602 ROCC saddle-shaped rotating platform TKAs. Mean follow-up was 7.5 years (5-13) (>10 years in 123 knees). 82 patients (93 knees) died; 20 patients (21 knees) were lost to follow-up. Active flexion improved from 119° (10°-150°) to 127° (90°-155°) and Knee Society knee score from 39±11 to 94±9. Two knees were reoperated for aseptic loosening: Kaplan-Meier 14-year survivorship with aseptic loosening as end-point was 99.4% (95% CI, 99.8-100). UCLA mean score increased from 3.8/10 at baseline to 7.3/10 at last FU, 91% recovering pre-disease activity, and 27% with UCLA score ≥8/10. ROCC TKA demonstrated solid midterm survivorship without activity-related complications. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Minimum five-year wear rate of metal-on-highly cross-linked polyethylene in primary total hip arthroplasty.

PURPOSE: Highly cross-linked polyethylenes (PE) have been developed with encouraging results in terms of wear. Another body of the literature has indicated potential catastrophic failures related to reduced fatigue properties and oxidation. Each PE available on the market has its own processing characteristics. The aim of this retrospective study was to evaluate the minimum five-year wear properties of an original highly cross-linked PE in a consecutive series of primary THAs. METHODS: Between August 2005 and December 2007, 80 patients with a mean age of 62.7 years were included. All patients had a 28-mm CoCr femoral head articulating with a highly cross-linked insert (Highcross®, Medacta SA) that was 100 Mrads gamma radiated, remelted at 150 °C, and ethylene oxide sterilized. The primary criterion for evaluation was the femoral head penetration, as measured by Hip Analysis Suite software. The steady state wear was also calculated. Functional results were evaluated according to the WOMAC score. RESULTS: Complete data were available for analysis in 67 patients at a mean follow-up of 5.5 years. The mean femoral head penetration was 0.128 ± 0.62 mm and the steady state wear was-0.025 ± 0.22 mm/year. The WOMAC score significantly decreased from 16.5 ± 5.93 pre-operatively to 4.12 ± 5.5 at the latest follow-up (p <0.001). CONCLUSIONS: The minimal five-year results of this retrospective study indicate that this particular highly cross-linked and remelted polyethylene had a low wear rate. Longer-term results are needed to warrant that these mid-term data will generate less osteolysis and resultant aseptic loosening.

Randomized controlled trial of conventional versus modern surgical dressings following primary total hip and knee replacement.

PURPOSE: We prospectively compared two types of dressing (conventional gauze-based versus absorbing hydrofibre) after primary total hip (THA) or knee (TKA) arthroplasties. METHODS: Eighty candidates for THA (n = 40) or TKA (s = 40) were randomized: gauze-based versus hydrofibre absorbing (Aquacel®, ConvaTec). The two groups were comparable at baseline. RESULTS: There was a statistically significant decrease of dressing changes in the hydrofibre group (p = 0.0006). Two patients from the conventional group presented minor wound complications. Nurses' satisfaction was significantly higher in the hydrofibre group considering the adherence (p = 0.04) and flexibility (p = 0.03). Patients experienced a higher satisfaction with respect to ease of movement (p = 0.01) in the hydrofibre group. The cosmetic appearance of the scars six weeks after surgery was found to be similar between groups. CONCLUSIONS: Our findings support an overall improved comfort for the patients and the medical staff by using hydrofibre dressings after primary THA and TKA. The reduction of required dressing changes was observed also.

Direct anterior Hueter approach is a safe and effective approach to perform a bipolar hemiarthroplasty for femoral neck fracture: outcome in 82 patients.

BACKGROUND AND PURPOSE: The direct anterior (DA) approach in total hip arthroplasty has recently been associated with faster functional recovery than the posterolateral (PL) approach. We hypothesized that the same should hold for the DA approach in bipolar hemiarthroplasty for femoral neck fractures. PATIENTS AND METHODS: 82 patients with a displaced femoral neck fracture and candidates for bipolar hemiarthroplasty were enrolled after IRB approval in this prospective non-randomized comparative study (DA: n = 38; PL: n = 44). The postoperative protocols were similar in both groups. Evaluation included surgical complications, component placement, and early functional outcomes, assessed 6 weeks postoperatively using a timed up-and-go (TUG) test. The incidence of dislocation was assessed by telephone interview at least 1 year after the surgery. RESULTS: The DA-group patients had better results in the TUG test than the PL-group patients 6 weeks after surgery: half were under 19 seconds as opposed to only one third for PL (p = 0.06). We did not record any intraoperative femoral fracture or any lateral femoral cutaneous neuropraxia in the DA group. We observed a significant difference (p = 0.04) in lateral offset between the PL group (4.2 (SD 6.4) mm) and the DA group (-1.6 (SD 8.5) mm). Stem alignment was similar between groups. The dislocation rate for DA patients was lower than for PL patients (1 of 38 cases vs. 9 of 44 cases; p = 0.02). INTERPRETATION: Our findings indicate that relative to the posterolateral approach, the direct anterior approach for bipolar hemiarthroplasty may improve gait in the early postoperative period and decrease the dislocation rate.

Glycemic instability of non-diabetic patients after spine surgery: a prospective cohort study.

PURPOSE: Blood glucose (BG) dysregulation is a well-known condition for patients sustaining medical adverse events, such as sepsis or myocardial infarction. However, it has never been described following spine surgery. Our purpose was to assess postoperative glycemic dysregulation of non-diabetic patients undergoing spine surgery and determine if this is related to any complications within a 3-month postoperative period. METHODS: All the non-diabetic patients undergoing spine surgery in our center were prospectively included over a 6-month period. BG capillary measures were collected from the preoperative fasting period to the end of postoperative Day 3, six times a day. Patients were followed for 3 months after surgery. RESULTS: Data collected from 75 patients were eventually analyzed. A significant increase of BG level was observed from the preoperative to the second postoperative hour (P < 0.0001), remaining significantly elevated until Day 3 (P < 0.0001). Significant correlations were found between perioperative factors (age, smoking, revision status, instrumentation, operation time, blood loss and transfusion) and glycemic parameters. Day 2 mean BG level was found significantly higher for patients surgically revised than those not revised (P = 0.04). CONCLUSIONS: Non-diabetic patients experience a statistically significant increase in BG levels in the first 3 days following a spine surgery. This increase in BG might be correlated with postsurgical complications.

Intraprosthetic dislocation: a potentially serious complication of dual mobility acetabular cups.

Though dual mobility cups have gained growing popularity as a solution for instability in total hip replacements, these promising devices are subject to a specific implant failure mode, named intraprosthetic dislocation. We present the case of a patient sustaining such an adverse event. The planned revision surgery was postponed 12 months due to a severe heart condition, allowing a rare opportunity to document the natural history of this unusual complication. The small femoral head was found dislodged in the superior part of the metallic shell and had remarkably lost its sphericity. Severe metallic debris and granuloma were found in the proximal femoral region, associated with major periprosthetic bony and soft tissue damage. Surgeons, radiologists, and general practitioners should be aware of this specific complication, its incidence (almost 5%) and mechanisms (femoral neck to mobile polyethylene insert impingement, leading to rim fatigue and wear of the insert at the capturing area). Diagnosis is mainly based on anteroposterior and modified Lowenstein lateral radiographs of the hip, as an eccentric position of the small femoral head, lying against the concave inner surface of the shell. Prompt component revision should be planned, since delayed management could lead to severe irretrievable damages.

Objects drawn from haptic perception and vision-based spatial abilities.

Haptic perception is used in the anatomy laboratory with the handling of three-dimensional (3D) prosections, dissections, and synthetic models of anatomical structures. Vision-based spatial ability has been found to correlate with performance on tests of 3D anatomy knowledge in previous studies. The objective was to explore whether haptic-based spatial ability was correlated with vision-based spatial ability. Vision-based spatial ability was measured in a study group of 49 medical graduates with three separate tests: a redrawn Vandenberg and Kuse Mental Rotations Tests in two (MRT A) and three (MRT C) dimensions and a Surface Development Test (SDT). Haptic-based spatial ability was measured using 18 different objects constructed from 10 cubes glued together. Participants were asked to draw these objects from blind haptic perception, and drawings were scored by two independent judges. The maximum score was 24 for each of MRT A and MRT C, 60 for SDT, and 18 for the drawings. The drawing score based on haptic perception [median = 17 (lower quartile = 16, upper quartile = 18)] correlated with MRT A [14 (9, 17)], MRT C [9 (7, 12)] and SDT [44 (36, 52)] scores with a Spearman's rank correlation coefficient of 0.395 (p = 0.0049), 0.507 (p = 0.0002) and 0.606 (p < 0.0001), respectively. Spatial abilities assessed by vision-based tests were correlated with a drawing score based on haptic perception of objects. Future research should investigate the contribution of haptic-based and vision-based spatial abilities on learning 3D anatomy from physical models.

The PREMISE database of 20 Macaca fascicularis PET/MRI brain images available for research.

Non-human primate studies are unique in translational research, especially in neurosciences where neuroimaging approaches are the preferred methods used for cross-species comparative neurosciences. In this regard, neuroimaging database development and sharing are encouraged to increase the number of subjects available to the community, while limiting the number of animals used in research. Here we present a simultaneous positron emission tomography (PET)/magnetic resonance (MR) dataset of 20 Macaca fascicularis images structured according to the Brain Imaging Data Structure standards. This database contains multiple MR imaging sequences (anatomical, diffusion and perfusion imaging notably), as well as PET perfusion and inflammation imaging using respectively [15O]H2O and [11C]PK11195 radiotracers. We describe the pipeline method to assemble baseline data from various cohorts and qualitatively assess all the data using signal-to-noise and contrast-to-noise ratios as well as the median of intensity and the pseudo-noise-equivalent-count rate (dynamic and at maximum) for PET data. Our study provides a detailed example for quality control integration in preclinical and translational PET/MR studies with the aim of increasing reproducibility. The PREMISE database is stored and available through the PRIME-DE consortium repository.

Surface modification effect on contrast agent efficiency for X-ray based spectral photon-counting scanner/luminescence imaging: from fundamental study to in vivo proof of concept.

X-Ray imaging techniques are among the most widely used modalities in medical imaging and their constant evolution has led to the emergence of new technologies. The new generation of computed tomography (CT) systems - spectral photonic counting CT (SPCCT) and X-ray luminescence optical imaging - are examples of such powerful techniques. With these new technologies the rising demand for new contrast agents has led to extensive research in the field of nanoparticles and the possibility to merge the modalities appears to be highly attractive. In this work, we propose the design of lanthanide-based nanocrystals as a multimodal contrast agent with the two aforementioned technologies, allowing SPCCT and optical imaging at the same time. We present a systematic study on the effect of the Tb3+ doping level and surface modification on the generation of contrast with SPCCT and the luminescence properties of GdF3:Tb3+ nanocrystals (NCs), comparing different surface grafting with organic ligands and coatings with silica to make these NCs bio-compatible. A comparison of the luminescence properties of these NCs with UV revealed that the best results were obtained for the Gd0.9Tb0.1F3 composition. This property was confirmed under X-ray excitation in microCT and with SPCCT. Moreover, we could demonstrate that the intensity of the luminescence and the excited state lifetime are strongly affected by the surface modification. Furthermore, whatever the chemical nature of the ligand, the contrast with SPCCT did not change. Finally, the successful proof of concept of multimodal imaging was performed in vivo with nude mice in the SPCCT taking advantage of the so-called color K-edge imaging method.

Tif1γ suppresses murine pancreatic tumoral transformation by a Smad4-independent pathway.

Transcriptional intermediary factor 1γ (TIF1γ; alias, TRIM33/RFG7/PTC7/ectodermin) belongs to an evolutionarily conserved family of nuclear factors that have been implicated in stem cell pluripotency, embryonic development, and tumor suppression. TIF1γ expression is markedly down-regulated in human pancreatic tumors, and Pdx1-driven Tif1γ inactivation cooperates with the Kras(G12D) oncogene in the mouse pancreas to induce intraductal papillary mucinous neoplasms. In this study, we report that aged Pdx1-Cre; LSL-Kras(G12D); Tif1γ(lox/lox) mice develop pancreatic ductal adenocarcinomas (PDACs), an aggressive and always fatal neoplasm, demonstrating a Tif1γ tumor-suppressive function in the development of pancreatic carcinogenesis. Deletion of SMAD4/DPC4 (deleted in pancreatic carcinoma locus 4) occurs in approximately 50% of human cases of PDAC. We, therefore, assessed the genetic relationship between Tif1γ and Smad4 signaling in pancreatic tumors and found that Pdx1-Cre; LSL-Kras(G12D); Smad4(lox/lox); Tif1γ(lox/lox) (alias, KSSTT) mutant mice exhibit accelerated tumor progression. Consequently, Tif1γ tumor-suppressor effects during progression from a premalignant to a malignant state in our mouse model of pancreatic cancer are independent of Smad4. These findings establish, for the first time to our knowledge, that Tif1γ and Smad4 both regulate an intraductal papillary mucinous neoplasm-to-PDAC sequence through distinct tumor-suppressor programs.

Charnley-Kerboull total hip arthroplasty combining zirconia on polyethylene. A minimum eight-year follow-up prospective study.

PURPOSE: Zirconia was introduced in the 1980s for total hip arthroplasty (THA) with the expectation of lower polyethylene wear. The purpose of this prospective study was to evaluate the results of a continuous series of total hip arthroplasties combining a zirconia head with polyethylene socket at a minimum eight-year follow-up. METHODS: We performed an open prospective clinical trial in 1997. Our study involved 51 consecutive patients (55 hips) with a mean age of 52.5 ± 12 years (range, 25-76 years). All patients had a Charnley-Kerboull all-cemented hip replacement. A 22-mm stabilised yttrium tetragonal polycrystalline zirconia head (Y-TZP) was used in association with moderately cross-linked and annealed polyethylene. Clinical and radiological outcomes were assessed yearly. A survival analysis was performed using revision for any reason as the end-point. RESULTS: At a minimum eight-year follow-up, 12 patients (13 hips) were lost to follow-up (mean 26.8 months), two patients (two hips) had died, and six patients (six hips) were revised. The remaining 31 patients (34 hips) were alive and had not been revised on either the femoral or acetabular side at a mean follow-up of 117.1 months (range, 96-150 months). Mean functional score at last follow-up was 17.7. Mean linear head penetration was 0.23 mm/year. More than 90% of the remaining hips had signs of periprosthetic osteolysis. Five stems were loosened. The survival at eight years was 87.3% (95% IC: 76.7-97.8). CONCLUSION: This study confirms earlier short-terms results, and demonstrates that zirconia should no longer be used in THA.