Toward Automated 3D Spine Reconstruction from Biplanar Radiographs Using CNN for Statistical Spine Model Fitting.

To date, 3D spine reconstruction from biplanar radiographs involves intensive user supervision and semi-automated methods that are time-consuming and not effective in clinical routine. This paper proposes a new, fast, and automated 3D spine reconstruction method through which a realistic statistical shape model of the spine is fitted to images using convolutional neural networks (CNN). The CNNs automatically detect the anatomical landmarks controlling the spine model deformation through a hierarchical and gradual iterative process. The performance assessment used a set of 68 biplanar radiographs, composed of both asymptomatic subjects and adolescent idiopathic scoliosis patients, in order to compare automated reconstructions with ground truths build using multiple experts-supervised reconstructions. The mean (SD) errors of landmark locations (3D Euclidean distances) were 1.6 (1.3) mm, 1.8 (1.3) mm, and 2.3 (1.4) mm for the vertebral body center, endplate centers, and pedicle centers, respectively. The clinical parameters extracted from the automated 3D reconstruction (reconstruction time is less than one minute) presented an absolute mean error between 2.8° and 4.7° for the main spinal parameters and between 1° and 2.1° for pelvic parameters. Automated and expert's agreement analysis reported that, on average, 89% of automated measurements were inside the expert's confidence intervals. The proposed automated 3D spine reconstruction method provides an important step that should help the dissemination and adoption of 3D measurements in clinical routine.

An analysis of ideal and actual time to surgery after traumatic spinal cord injury in Canada.

STUDY DESIGN: Retrospective analysis of a prospective registry and surgeon survey. OBJECTIVES: To identify surgeon opinion on ideal practice regarding the timing of decompression/stabilization for spinal cord injury and actual practice. Discrepancies in surgical timing and barriers to ideal timing of surgery were explored. SETTING: Canada. METHODS: Patients from the Rick Hansen Spinal Cord Registry (RHSCIR, 2004-2014) were reviewed to determine actual timing of surgical management. Following data collection, a survey was distributed to Canadian surgeons, asking for perceived to be the optimal and actual timings of surgery. Discrepancies between actual data and surgeon survey responses were then compared using χ2 tests and logistic regression. RESULTS: The majority of injury patterns identified in the registry were treated operatively. ASIA Impairment Scale (AIS) C/D injuries were treated surgically less frequently in the RHSCIR data and surgeon survey (odds ratio (OR)= 0.39 and 0.26). Significant disparities between what surgeons identified as ideal, actual current practice and RHSCIR data were demonstrated. A great majority of surgeons (93.0%) believed surgery under 24 h was ideal for cervical AIS A/B injuries and 91.0% for thoracic AIS A/B/C/D injuries. Definitive surgical management within 24 h was actually accomplished in 39.0% of cervical and 45.0% of thoracic cases. CONCLUSION: Ideal surgical timing for traumatic spinal cord injury (tSCI) within 24 h of injury was identified, but not accomplished. Discrepancies between the opinions on the optimal and actual timing of surgery in tSCI patients suggest the need for strategies for knowledge translation and reduction of administrative barriers to early surgery.

Participatory theatre and tuberculosis: a feasibility study with South African health care workers.

SETTING: Health care workers (HCWs) in South Africa have a risk of acquiring tuberculosis (TB) that is twice that of the general population. Nonetheless, adherence to infection control and TB disclosure requirements remain problematic. OBJECTIVE: To gain insight into the feasibility of an educational participatory theatre intervention to reduce the risk of occupational TB. DESIGN: An intervention using participatory theatre was developed progressively over six consecutive sessions with different groups of HCWs, totalling 83 participants. Videos of the sessions, field notes, observations, interviews and a post-experience survey were analysed to ascertain feasibility. RESULTS: The intervention was acceptable to participants, met a defined demand, proved adaptable to the target group and was practical if done during working hours or if integrated into already existing training sessions. The theatre work shed light on where to focus educational interventions. Preliminary efficacy outcomes included strengthened social cohesion via group work and reports of subsequent greater vigilance regarding occupational TB. CONCLUSION: Participatory theatre techniques may offer a useful, culturally appropriate supplement to existing educational approaches to the prevention and management of occupational TB. Given the limitations in resources and our assessment of feasibility, training existing health care educators in such techniques would be a promising next step.

Effectiveness of braces designed using computer-aided design and manufacturing (CAD/CAM) and finite element simulation compared to CAD/CAM only for the conservative treatment of adolescent idiopathic scoliosis: a prospective randomized controlled trial.

PURPOSE: Clinical assessment of immediate in-brace effect of braces designed using CAD/CAM and FEM vs. only CAD/CAM for conservative treatment of AIS, using a randomized blinded and controlled study design. METHODS: Forty AIS patients were prospectively recruited and randomized into two groups. For 19 patients (control group), the brace was designed using a scan of patient's torso and a conventional CAD/CAM approach (CtrlBrace). For the 21 other patients (test group), the brace was additionally designed using finite element modeling (FEM) and 3D reconstructions of spine, rib cage and pelvis (NewBrace). The NewBrace design was simulated and iteratively optimized to maximize the correction and minimize the contact surface and material. RESULTS: Both groups had comparable age, sex, weight, height, curve type and severity. Scoliosis Research Society standardized criteria for bracing were followed. Average Cobb angle prior to bracing was 27° and 28° for main thoracic (MT) and lumbar (L) curves, respectively, for the control group, while it was 33° and 28° for the test group. CtrlBraces reduced MT and L curves by 8° (29 %) and 10° (40 %), respectively, compared to 14° (43 %) and 13° (46 %) for NewBraces, which were simulated with a difference inferior to 5°. NewBraces were 50 % thinner and had 20 % less covering surface than CtrlBraces. CONCLUSION: Braces designed with CAD/CAM and 3D FEM simulation were more efficient and lighter than standard CAD/CAM TLSO's at first immediate in-brace evaluation. These results suggest that long-term effect of bracing in AIS may be improved using this new platform for brace fabrication. TRIAL REGISTRATION: NCT02285621.

A physically based trunk soft tissue modeling for scoliosis surgery planning systems.

One of the major concerns of scoliotic patients undergoing spinal correction surgery is the trunk's external appearance after the surgery. This paper presents a novel incremental approach for simulating postoperative trunk shape in scoliosis surgery. Preoperative and postoperative trunk shapes data were obtained using three-dimensional medical imaging techniques for seven patients with adolescent idiopathic scoliosis. Results of qualitative and quantitative evaluations, based on the comparison of the simulated and actual postoperative trunk surfaces, showed an adequate accuracy of the method. Our approach provides a candidate simulation tool to be used in a clinical environment for the surgery planning process.

Prostate apoptosis response-4 mediates TGF-ß-induced epithelial-to-mesenchymal transition.

A growing body of evidence supports that the epithelial-to-mesenchymal transition (EMT), which occurs during cancer development and progression, has a crucial role in metastasis by enhancing the motility of tumor cells. Transforming growth factor-ß (TGF-ß) is known to induce EMT in a number of cancer cell types; however, the mechanism underlying this transition process is not fully understood. In this study we have demonstrated that TGF-ß upregulates the expression of tumor suppressor protein Par-4 (prostate apoptosis response-4) concomitant with the induction of EMT. Mechanistic investigations revealed that exogenous treatment with each TGF-ß isoform upregulates Par-4 mRNA and protein levels in parallel levels of phosphorylated Smad2 and IκB-α increase. Disruption of TGF-ß signaling by using ALK5 inhibitor, neutralizing TGF-ß antibody or phosphoinositide 3-kinase inhibitor reduces endogenous Par-4 levels, suggesting that both Smad and NF-κB pathways are involved in TGF-ß-mediated Par-4 upregulation. NF-κB-binding sites in Par-4 promoter have previously been reported; however, using chromatin immunoprecipitation assay we showed that Par-4 promoter region also contains Smad4-binding site. Furthermore, TGF-ß promotes nuclear localization of Par-4. Prolonged TGF-ß3 treatment disrupts epithelial cell morphology, promotes cell motility and induces upregulation of Snail, vimentin, zinc-finger E-box binding homeobox 1 and N-Cadherin and downregulation of Claudin-1 and E-Cadherin. Forced expression of Par-4, results in the upregulation of vimentin and Snail expression together with increase in cell migration. In contrast, small interfering RNA-mediated silencing of Par-4 expression results in decrease of vimentin and Snail expression and prevents TGF-ß-induced EMT. We have also uncovered a role of X-linked inhibitor of apoptosis protein in the regulation of endogenous Par-4 levels through inhibition of caspase-mediated cleavage. In conclusion, our findings suggest that Par-4 is a novel and essential downstream target of TGF-ß signaling and acts as an important factor during TGF-ß-induced EMT.

ERα-targeted therapy in ovarian cancer cells by a novel estradiol-platinum(II) hybrid.

As we previously showed, we have synthesized a new family of 17ß-estradiol-platinum(II) hybrids. Earlier studies revealed the VP-128 hybrid to show high efficiency compared with cisplatin toward hormone-dependent breast cancer cells. In the present research, we have studied the antitumor activity of VP-128 in vitro and in vivo against ovarian cancer. In nude mice with ovarian xenografts, VP-128 displayed selective activity toward hormone-dependent tumors and showed higher efficiency than cisplatin to inhibit tumor growth. Similarly, in vitro, transient transfection of estrogen receptor (ER)-α in ERα-negative A2780 cells increased their sensitivity to VP-128-induced apoptosis, confirming the selectivity of VP-128 toward hormone-dependent tumor cells. In agreement, Western blot analysis revealed that VP-128 induced higher caspase-9, caspase-3, and poly (ADP-ribose) polymerase cleavage compared with cisplatin. The activation of caspase-independent apoptosis was also observed in ERα-negative A2780 cells, in which VP-128 rapidly induced the translocation of apoptosis-inducing factor to the nucleus. Conversely, subcellular localization of apoptosis-inducing factor was not modified in ERα-positive Ovcar-3 cells. We also discovered that VP-128 induces autophagy in ovarian cancer cells because of the formation of acidic vesicular organelles (AVOs) and increase of Light Chain 3B-II protein responsible for the formation of autophagosomes; pathways related to autophagy (AKT and mammalian target of rapamycin) were also down-regulated, supporting this mechanism. Finally, the inhibition of autophagy using chloroquine increased VP-128 efficiency, indicating a possible combination therapy. Altogether these results highlight the beneficial value of VP-128 for the treatment of hormone-dependent ovarian cancers and provide preliminary proof of concept for the efficient targeting of ERα- by 17ß-estradiol-Pt(II)-linked chemotherapeutic hybrids in these tumors.

The Rib Vertebra Angle Difference and its Measurement in 3D for the evaluation of early onset scoliosis.

The Rib Vertebra Angle Difference (RVAD) as defined by Mehta (1972) is used to predict the progression of early onset scoliosis. No clear physical significance has been established for this measurement. The purpose of this study was to evaluate the RVAD along the thoracic spine and the equivalent measurement on 3D reconstructions of the spine and rib cage of early onset scoliosis patients in order to determine their relationship with the geometry of the chest wall and evolution along the spine. The RVAD was measured on PA radiographs of 42 infantile scoliotic patients (Cobb >20°) from T4 to T10 according to the method described by Mehta. The RVAD 3D was computed using the same landmarks from the 3D reconstruction generated from the calibrated biplanar radiographs. Cases were divided into Phase I and Phase II using Mehta's classification based on the rib head overlap with the apical vertebral body on coronal plane radiographs. A linear relationship exists between the Metha (2D) and 3D RVAD for both Phase I (r = 0.87) and Phase II (r = 0.78) patients. For more severe deformities (RVAD 3D ≥ 35°), a relationship was found between RVAD 3D and the axial rotation of the thoracic vertebrae (r = 0.51) in Phase II patients. However, no significant relationship exists between axial rotation and RVAD 3D for Phase I patients as well as Mehta's RVAD. Maximal RVAD measurements were located 2 ½ levels above the apical vertebra. Results indicated that RVAD 3D provides additional information to Mehta's RVAD on the torsional nature of the deformity. Considering the importance of clinical indices to assess the progression of early onset scoliosis, this study raises some questions on looking solely at the RVAD measured on radiographs at the apical vertebra of Phase I patients and suggests considering also levels above the apex of the scoliotic curve and 3D measurements. Further investigation is required to fully understand the 3D nature of the spine and rib cage deformities.

Recent advances in the study of candidate genes for adolescent idiopathic scoliosis.

We used a microarray approach to evaluate gene expression profiles in human AIS osteoblasts, and to identify genes that are differentially expressed following estrogen exposure in non-AIS and AIS human osteoblasts. We found that more than one gene is likely responsible for AIS. Furthermore, some of these genes are estrogen-regulated, suggesting a possible role of estrogens in the etiology of scoliosis.

Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5'-pyrophosphate) in Sprague-Dawley rats.

The dietary supplement Citicoline free-base (choline cytidine 5'-pyrophosphate) was toxicologically evaluated in Sprague-Dawley rats using oral gavage. In an acute 14-day study, 2000 mg/kg was well tolerated. In a 90-day study, 100, 350, and 1000 mg/kg/day doses resulted in no mortality. In males, slight significant increases in serum creatinine (350 and 1000 mg/kg/day), and decreases in urine volume (all treated groups) were observed. In females, slight significant increases in total white blood cell and absolute lymphocyte counts (1000 mg/kg/day), and blood urea nitrogen (BUN) (100 and 350, but not 1000 mg/kg/day) were noted. A dose-related increase in renal tubular mineralization, without degenerative or inflammatory reaction, was found in females (all treated groups) and two males (1000 mg/kg/day). Renal mineralization in rats (especially females) is influenced by calcium:phosphorus ratios in the diet. A high level of citicoline consumption resulted in increased phosphorus intake in the rats, and likely explains this result.

Anterior tarsectomy long-term results in adult pes cavus.

PURPOSE OF THE STUDY: Anterior tarsectomy for pes cavus in adults is designed to relieve pain and correct the deformity. The present study reports radiological and clinical results with anterior tarsectomy in 39 cases of pes cavus. MATERIAL AND METHODS: The study concerned 39 cavus feet in 33 patients (22 males, 11 females; mean age: 31 years, range 16-49 years). Clinical outcome was assessed in terms of pain, function and motion, using the AOFAS classification. Radiological assessment (anteroposterior and lateral stress X-ray, views with Méary superficial wire-marking) measured the Djian angle, talometatarsal alignment, talar slope, calcaneal slope, calcaneal valgus, and osteoarthritis stage in adjacent joints. RESULTS: Mean follow-up was 9.8 years (range, 1-25). Mean AOFAS score at follow-up was 69.2/100 points (range, 14-100). Pain decreased considerably in 75% of cases, and 68% of patients recovered normal activity. The foot was aligned correctly in 67% of cases. At last follow-up, pes cavus remained undercorrected in 80% of feet, but mean Djian angle had improved from 100 degrees to 111.3 degrees. Calcaneal valgus improved from 30.8 degrees to 24.8 degrees and the podoscopic footprint was normal in 51% of feet. In 74% of feet, adjacent joints presented progressive osteoarthritic degeneration. Subjectively, 70% of patients were very satisfied or satisfied with minor reservations. Objective outcome was excellent or good in 66% of feet. DISCUSSION AND CONCLUSION: Outcome in terms of function, motion, complications and satisfaction was good, although pain relief results were poor. Anterior tarsectomy is able to correct initial pes cavus deformity and compensate anomalies of the hindfoot, but its correction capacity is limited, and its efficacy in case of clawfoot is poor. Anterior tarsectomy spares the adjacent Chopart complex and Lisfranc joints while inducing hypermobility, and leads to arthritis in 74% of cases. Better results are obtained in cases of reestablishment of the Méary-Tomeno line and of hindfoot valgus, as well as in cases of correction of equinus and clawfoot deformities. Worse results are observed in case of neurological evolutive disease or insufficient correction of the preceding deformities. LEVEL OF EVIDENCE: Level IV. Therapeutic Study.

Inhibition of biological phosphorus removal in a sequencing moving bed biofilm reactor in seawater.

A new process was developed to achieve denitrifying biological phosphorus removal in wastewaters containing high levels of nitrate and phosphate with a low level of organic matter. This could particularly be useful in recirculating systems such as aquariums or fish farms to prevent accumulation of nitrate and phosphates and to avoid regular cost extensive and polluting water replacement. Phosphorus (P) was removed from the influent in a sequencing moving bed biofilm reactor, stored in the attached biomass and then cyclically removed from the biomass by filling the reactor with anaerobic water from a stock tank. Phosphate was accumulated in the stock tank which allowed for use as fertilizer. The feasibility of the experimental design was demonstrated by using the activated sludge model No. 3 (ASM3) complemented by the EAWAG Bio-P module implemented in the WEST simulation software. A pilot scale experiment was conducted in two identical reactors in two runs: one to treat water from a marine mesocosm, the other to treat a synthetic freshwater influent. No biological phosphorus removal was achieved during the seawater run. During the freshwater run, average P removal efficiency was 20%, of which 80% was attributed to biological removal and 20% to chemical precipitation. The absence of efficiency in seawater was attributed to the high concentration of calcium.

[Molecular and genetic aspects of idiopathic scoliosis. Blood test for idiopathic scoliosis]. / Molekulare und genetische Aspekte der idiopathischen Skoliose. Bluttest bei idiopathischer Skoliose.

Spinal deformities, and particularly scoliosis, are the most frequent forms of orthopedic deformities in children and adolescents. About 1-6% of the population has scoliosis. This disorder leads to severe spinal deformities and predominantly affects adolescent girls.Although the multifactorial origin of adolescent idiopathic scoliosis (AIS) is broadly recognized, the genetic causes of AIS are still largely unknown. Our previous studies suggested a generalized dysfunction of melatonin transduction (the hormone that is primarily produced in the brain and epiphysis). In the meantime we have demonstrated that such a defect of signal transduction is caused by chemical alterations, which inactivate the function of the inhibitory G protein-coupled melatonin receptors. This discovery has led to the development of the first blood test to detect children without symptoms who are at risk of developing scoliosis. Since a single function (cellular reaction to melatonin) is determined, the unique advantage of this test is that it can be performed without knowledge of mutations in defective genes that could provoke the onset of AIS.

[The mediating role of family functioning in the relationship between family adversity and preschoolers' social adjustment]. / Le rôle médiateur du fonctionnement familial dans la relation entre l'adversité familiale et l'adaptation sociale des enfants d'âge préscolaire.

Preschoolers' social adaptation is related to their degree of exposure to environnemental risks. However, the mechanisms through which the environmental risks operate their influence on social adaptation are still poorly documented. Thus, the first goal of this study is to investigate the main effect of family adversity on preschoolers' behavioral problems and attachment security. The second goal is to test the mediating effect of family functionning in the relationship between family adversity and behavioral problems or attachment security. Five hundred and seventy-two participants (n=572) were assessed on family adversity between the age of 5 and 42 months. Behavioral problems and family functionning were assesed at 42 months. Eighty of the participants were assessed on attachment security at the age of 48 months. The results show a main effect of family adversity on behavioral problems as well as a mediating effect of family functionning in the relationship of family adversity and behavioral problems. No significant effect was found for security of attachment.

Interrelations Between Maternal Smoking During Pregnancy, Birth Weight and Sociodemographic Factors in the Prediction of Early Cognitive Abilities.

Maternal prenatal smoking, birth weight and sociodemographic factors were investigated in relation to cognitive abilities of 1544 children (aged 3.5 years) participating in the Québec Longitudinal Study of Children's Development. The Peabody Picture Vocabulary Test (PPVT) was used to assess verbal ability, the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) block design test to assess visuospatial ability, and the Visually Cued Recall (VCR) task to assess short-term memory. Prenatal smoking was related to performance on the WPPSI-R, the PPVT, and the VCR, although it did not independently predict any cognitive ability after maternal education was taken into account. Birth weight was a more robust predictor of all outcome measures and independently predicted VCR-performance. Birth weight interacted significantly with family income and maternal education in predicting visuospatial ability, indicating a greater influence of birth weight under relatively poor socio-economic conditions. Parenting and family functioning mediated associations between maternal education/family income and cognitive task performance under different birth weight conditions, although there were indications for stronger effects under relatively low birth weight. We conclude that investigations of moderating and mediating effects can provide insights into which children are most at risk of cognitive impairment and might benefit most from interventions.

Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates.

An association between reduced susceptibility to echinocandins and changes in the 1,3-beta-d-glucan synthase (GS) subunit Fks1p was investigated. Specific mutations in fks1 genes from Saccharomyces cerevisiae and Candida albicans mutants are described that are necessary and sufficient for reduced susceptibility to the echinocandin drug caspofungin. One group of amino acid changes in ScFks1p, ScFks2p, and CaFks1p defines a conserved region (Phe 641 to Asp 648 of CaFks1p) in the Fks1 family of proteins. The relationship between several of these fks1 mutations and the phenotype of reduced caspofungin susceptibility was confirmed using site-directed mutagenesis or integrative transformation. Glucan synthase activity from these mutants was less susceptible to caspofungin inhibition, and heterozygous and homozygous Cafks1 C. albicans mutants could be distinguished based on the shape of inhibition curves. The C. albicans mutants were less susceptible to caspofungin than wild-type strains in a murine model of disseminated candidiasis. Five Candida isolates with reduced susceptibility to caspofungin were recovered from three patients enrolled in a clinical trial. Four C. albicans strains showed amino acid changes at Ser 645 of CaFks1p, while a single Candida krusei isolate had a deduced R1361G substitution. The clinical C. albicans mutants were less susceptible to caspofungin in the disseminated candidiasis model, and GS inhibition profiles and DNA sequence analyses were consistent with a homozygous fks1 mutation. Our results indicate that substitutions in the Fks1p subunit of GS are sufficient to confer reduced susceptibility to echinocandins in S. cerevisiae and the pathogens C. albicans and C. krusei.