Prediction of severe adverse neonatal outcomes at the second stage of labour using machine learning: a retrospective cohort study.

OBJECTIVE: To create a personalised machine learning model for prediction of severe adverse neonatal outcomes (SANO) during the second stage of labour. DESIGN: Retrospective Electronic-Medical-Record (EMR) -based study. POPULATION: A cohort of 73 868 singleton, term deliveries that reached the second stage of labour, including 1346 (1.8%) deliveries with SANO. METHODS: A gradient boosting model was created, analysing 21 million data points from antepartum features (e.g. gravidity and parity) gathered at admission to the delivery unit, and intrapartum data (e.g. cervical dilatation and effacement) gathered during the first stage of labour. Deliveries were allocated to high-risk and low-risk groups based on the Youden index to maximise sensitivity and specificity. MAIN OUTCOME MEASURES: SANO was defined as either umbilical cord pH levels ≤7.1 or 1-minute or 5-minute Apgar score ≤7. RESULTS: The model for prediction of SANO yielded an area under the receiver operating curve (AUC) of 0.761 (95% CI 0.748-0.774). A third of the cohort (33.5%, n = 24 721) were allocated to a high-risk group for SANO, which captured up to 72.1% of these cases (odds ratio 5.3, 95% CI 4.7-6.0; high-risk versus low-risk groups). CONCLUSIONS: Data acquired throughout the first stage of labour can be used to predict SANO during the second stage of labour using a machine learning model. Stratifying parturients at the beginning of the second stage of labour in a 'time out' session, can direct a personalised approach to management of this challenging aspect of labour, as well as improve allocation of staff and resources. TWEETABLE ABSTRACT: Personalised prediction score for severe adverse neonatal outcomes in labour using machine learning model.

Responsiveness of patient-reported outcomes in shoulder arthroplasty: what are we actually measuring?

HYPOTHESIS: The purpose of this study was to determine the prevalence and responsiveness of common patient-reported outcome (PRO) tools in patients undergoing primary total shoulder arthroplasty (TSA) for glenohumeral arthritis. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of anatomic and reverse TSA studies from PubMed, SportDiscus, Cochrane, and CINAHL was performed. Studies on primary TSA for glenohumeral arthritis that reported at least 1 PRO tool were included in the final analysis. A subgroup analysis of studies that reported preoperative and postoperative PRO scores with at least 2-year follow-up data was evaluated to compare the responsiveness between the different PRO instruments. RESULTS: After full-text review of 490 articles, 74 articles met all inclusion criteria and were included in the final analysis. Anatomic TSA was evaluated in 35 studies, reverse TSA in 32 studies, and both anatomic and reverse in 7 studies. There were a total of 7624 patients, and 25 different PRO tools were used. The most commonly reported PRO tools were the American Shoulder and Elbow Surgeons (44 studies), Constant (42 studies), the visual analog scale for pain (23 studies), and the Simple Shoulder Test (17 studies). A median of 3.0 PRO instruments were used in each study. All instruments had large effect sizes. The University of California at Los Angeles (UCLA) score was found to be the most responsive instrument, and the Single Assessment Numeric Evaluation score was least responsive. The American Shoulder and Elbow Surgeons score was the most responsive instrument that required only patient-reported data. CONCLUSION: Overall, the UCLA score was found to be the most responsive followed by the Adjusted Constant. However, both the UCLA and Adjusted Constant scores require strength and range of motion assessment that may limit their widespread clinical use. The increased responsiveness of these measures, which include objective clinical testing, speaks to the predicted increases in strength and range of motion after shoulder arthroplasty. Of the measures that can be administered without in-person clinical evaluation, the American Shoulder and Elbow Surgeons score and Western Ontario Osteoarthritis of the Shoulder index were the most responsive.

Secondary Injuries After Pediatric Anterior Cruciate Ligament Reconstruction: A Systematic Review With Quantitative Analysis.

BACKGROUND: In the skeletally mature anterior cruciate ligament (ACL) reconstruction population, patients aged <25 years are at significantly increased risk of graft failure and injury to the contralateral ACL. Skeletal immaturity often affects graft selection and reconstruction technique. PURPOSE: To examine the incidence of ipsilateral graft failure and contralateral ACL injury in the skeletally immature patient population. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Using the PRISMA (Preferred Reporting Items for Systematic Meta-Analyses) guidelines, we reviewed all literature that involved ACL reconstruction performed on skeletally immature patients between May 1976 and May 2019. Patient demographics, surgical technique, and the prevalence of ipsilateral graft failure or subsequent contralateral ACL injury were recorded. Ipsilateral, contralateral, and secondary ACL injuries were then compared between sexes via chi-square tests. RESULTS: A total of 24 articles (1254 children; 1258 knees) met inclusion criteria for analysis. Ipsilateral graft failures occurred in 105 of 1258 patients (8.3%), and there were no statistically significant sex differences in the prevalence of graft failures (female, 9.7%; male patients, 7.1%; P = .14). The prevalence of contralateral ACL injury was significantly greater in female (29/129; 22.5%) than male (18/206; 8.7%; P = .0004) patients in the 9 studies that reported contralateral injury. Skeletally immature female patients were at significantly increased risk of contralateral ACL injury (odds ratio = 3.0; P = .0006) when compared with their male counterparts. CONCLUSION: In the literature to date, 1 in 3 female skeletally immature patients experienced an ipsilateral graft failure or contralateral ACL injury. Regardless of sex, the 24% prevalence of secondary injury after pediatric ACL reconstruction is almost identical to previously published secondary injury rates in skeletally mature patients <25 years old. As such, skeletal maturity alone does not seem to be a determinant of secondary injury; however, there is a clear need to improve postoperative rehabilitation, activity progression, and return-to-play testing to allow a safe return to sports that protects the long-term health of the reconstructed and contralateral limbs, especially for female patients.

The Responsiveness of Patient- Reported Outcome Tools in Shoulder Surgery Is Dependent on the Underlying Pathological Condition.

BACKGROUND: Given the high number of available patient-reported outcome (PRO) tools for patients undergoing shoulder surgery, comparative information is necessary to determine the most relevant forms to incorporate into clinical practice. PURPOSE: To determine the utilization and responsiveness of common PRO tools in studies involving patients undergoing arthroscopic rotator cuff repair or operative management of glenohumeral instability. STUDY DESIGN: Systematic review. METHODS: A systematic review of rotator cuff and instability studies from multiple databases was performed according to PRISMA guidelines. Means and SDs of each PRO tool utilized, study sample sizes, and follow-up durations were collected. The responsiveness of each PRO tool compared with other PRO tools was determined by calculating the effect size and relative efficiency (RE). RESULTS: After a full-text review of 238 rotator cuff articles and 110 instability articles, 81 studies and 29 studies met the criteria for final inclusion, respectively. In the rotator cuff studies, 25 different PRO tools were utilized. The most commonly utilized PRO tools were the Constant (50 studies), visual analog scale (VAS) for pain (44 studies), American Shoulder and Elbow Surgeons (ASES; 39 studies), University of California, Los Angeles (UCLA; 20 studies), and Disabilities of the Arm, Shoulder and Hand (DASH; 13 studies) scores. The ASES score was found to be more responsive than all scores including the Constant (RE, 1.94), VAS for pain (RE, 1.54), UCLA (RE, 1.46), and DASH (RE, 1.35) scores. In the instability studies, 16 different PRO tools were utilized. The most commonly used PRO tools were the ASES (13 studies), Rowe (10 studies), Western Ontario Shoulder Instability Index (WOSI; 8 studies), VAS for pain (7 studies), UCLA (7 studies), and Constant (6 studies) scores. The Rowe score was much more responsive than both the ASES (RE, 22.84) and the Constant (RE, 33.17) scores; however, the ASES score remained more responsive than the Constant (RE, 1.93), VAS for pain (RE, 1.75), and WOSI (RE, 0.97) scores. CONCLUSION: Despite being frequently used in the research community, the Constant score may be less clinically useful as it was less responsive. Additionally, it is a greater burden on the provider because it requires objective strength and range of motion data to be gathered by the clinician. In contrast, the ASES score was highly responsive after rotator cuff repair and requires only subjective patient input. Furthermore, separate PRO scoring methods appear to be necessary for patients undergoing rotator cuff repair and surgery for instability as the instability-specific Rowe score was much more responsive than the ASES score.

Paraoxonase 1 (PON1) attenuates sperm hyperactivity and spontaneous acrosome reaction.

BACKGROUND: Sperm capacitation is essential for proper fertilization and is associated with increased sperm hyperactivity (HA) and acrosome reaction (AR). For successful fertilization, AR timing is critical; accordingly, early spontaneous AR may not facilitate fertilization. Paraoxonase 1 (PON1) possesses antioxidant properties which affect sperm capacitation. The association between PON1, semen parameters, and capacitation is not fully understood. OBJECTIVE: To study PON1 activity in relation to human sperm hyperactivity and AR. MATERIALS AND METHODS: Semen samples were collected, and parameters were determined (volume, concentration, total sperm count, percentage total motility, and percentage normal morphology) according to World Health Organization (WHO) guidelines. AR and hyperactivity were evaluated using FITC-PSA, staining, and computer-aided sperm analysis (CASA). PON1 activity was assessed using arylesterase activity assay. RESULTS: Purified PON1 inhibited both sperm hyperactivity and AR in a dose-dependent manner. Native semen PON1 activity was positively associated with higher sperm concentration and negatively associated with spontaneous acrosome reaction (sAR). DISCUSSION AND CONCLUSION: PON1 may have a positive effect on fertility via its ability to prevent early spontaneous sperm capacitation and AR before reaching the female genital tract.

Mechanical, degradation and drug-release behavior of nano-grained Fe-Ag composites for biomedical applications.

An original fabrication route of high-strength bulk Fe-5Ag and Fe-10Ag nanocomposites with enhanced degradation rate is reported. Near fully dense materials with fine nanostructures and uniform distribution of Ag nanoparticles were obtained employing high energy attrition milling of Fe-Ag2O powder blends followed by cold sintering - high pressure consolidation at ambient temperature that allowed the retention of the nanoscale structure. Annealing in hydrogen flow at 550 °C resulted in enhanced ductility without coarsening the nanostructure. The strength in compression of Fe5Ag and Fe10Ag nanocomposites was several-fold higher than the values reported for similar composites with micrometer grain size. The galvanic action of finely dispersed Ag nanoparticles greatly increased the corrosion rate and degradation kinetics of iron. Following four weeks immersion of Fe-Ag nanocomposites in saline solution, a more than 10% weight loss accompanied by less than 25% decrease in bending strength were measured. The interconnected nanoporosity of cold sintered Fe-Ag nanocomposites was utilized for incorporation of vancomycin that was gradually released upon immersion. In cell culture experiments, the Fe-Ag nanocomposites supported the attachment of osteoblast cells and exhibited no signs of cytotoxicity. The results suggest that the proposed Fe-Ag nanocomposites could be developed into attractive biodegradable load-bearing implant materials with drug delivery capability.

Bioresorbable ß-TCP-FeAg nanocomposites for load bearing bone implants: High pressure processing, properties and cell compatibility.

In this paper, the processing and properties of iron-toughened bioresorbable ß-tricalcium phosphate (ß-TCP) nanocomposites are reported. ß-TCP is chemically similar to bone mineral and thus a good candidate material for bioresorbable bone healing devices; however intrinsic brittleness and low bending strength make it unsuitable for use in load-bearing sites. Near fully dense ß-TCP-matrix nanocomposites containing 30vol% Fe, with and without addition of silver, were produced employing high energy attrition milling of powders followed by high pressure consolidation/cold sintering at 2.5GPa. In order to increase pure iron's corrosion rate, 10 to 30vol% silver were added to the metal phase. The degradation behavior of the developed composite materials was studied by immersion in Ringer's and saline solutions for up to 1month. The mechanical properties, before and after immersion, were tested in compression and bending. All the compositions exhibited high mechanical strength, the strength in bending being several fold higher than that of polymer toughened ß-TCP-30PLA nanocomposites prepared by the similar procedure of attrition milling and cold sintering, and of pure high-temperature sintered ß-TCP. Partial substitution of iron with silver led to an increase in both strength and ductility. Furthermore, the galvanic action of silver particles dispersed in the iron phase significantly accelerated in vitro degradation of ß-TCP-30(Fe-Ag) nanocomposites. After 1month immersion, the composites retained about 50% of their initial bending strength. In cell culture experiments, ß-TCP-27Fe3Ag nanocomposites exhibited no signs of cytotoxicity towards human osteoblasts suggesting that they can be used as an implant material.

Gold nanoparticle interactions with endothelial cells cultured under physiological conditions.

PEGylated gold nanoparticles (AuNPs) have an extended circulation time after intravenous injection in vivo and exhibit favorable properties for biosensing, diagnostic imaging, and cancer treatment. No impact of PEGylated AuNPs on the barrier forming properties of endothelial cells (ECs) has been reported, but recent studies demonstrated that unexpected effects on erythrocytes are observed. Almost all studies to date have been with static-cultured ECs. Herein, ECs maintained under physiological cyclic stretch and flow conditions and used to generate a blood-brain barrier model were exposed to 20 nm PEGylated AuNPs. An evaluation of toxic effects, cell stress, the release profile of pro-inflammatory cytokines, and blood-brain barrier properties showed that even under physiological conditions no obvious effects of PEGylated AuNPs on ECs were observed. These findings suggest that 20 nm-sized, PEGylated AuNPs may be a useful tool for biomedical applications, as they do not affect the normal function of healthy ECs after entering the blood stream.

Monocyte preseeding leads to an increased implant bed vascularization of biphasic calcium phosphate bone substitutes via vessel maturation.

The present study analyzes the influence of the addition of monocytes to a biphasic bone substitute with two granule sizes (400-700 µm and 500-1000 µm). The majority of the added monocytes was detectable as mononuclear cells, while also low amounts of (chimeric) multinucleated giant cells (MNGCs) were found. No increase in the total number of MNGCs was established, but a significantly increased percent vascularization. Altogether, the results show that the added monocytes become involved in the tissue response to a biomaterial without marked changes in the overall reaction. Monocyte addition enables an increased implant bed vascularization especially via induction of vessel maturation and, thus intervenes positively in the healing reaction to a biomaterial. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2928-2935, 2016.

Tissue engineered pre-vascularized buccal mucosa equivalents utilizing a primary triculture of epithelial cells, endothelial cells and fibroblasts.

Artificial generated buccal mucosa equivalents are a promising approach for the reconstruction of urethral defects. Limiting in this approach is a poor blood vessel supply after transplantation, resulting in increased morbidity and necrosis. We generated a pre-vascularized buccal mucosa equivalent in a tri-culture of primary buccal epithelial cells, fibroblasts and microvascular endothelial cells, using a native collagen membrane as a scaffold. A successful pre-vascularization and dense formation of capillary-like structures at superficial areas was demonstrated. The lumen size of pre-formed blood vessels corresponded to the capillary size in vivo (10-30 µm). Comparing native with a highly cross-linked collagen membrane we found a distinct higher formation of capillary-like structures on the native membrane, apparently caused by higher secretion of angiogenic factors such as PDGF, IL-8 and angiopoietin by the cells. These capillary-like structures became functional blood vessels through anastomosis with the host vasculature after implantation in nude mice. This in vitro method should result in an accelerated blood supply to the biomaterial with cells after transplantation and increase the succes rates of the implant material.

Characteristics of clinical shoulder research over the last decade: a review of shoulder articles in The Journal of Bone & Joint Surgery from 2004 to 2014.

BACKGROUND: The purpose of this study was to determine characteristics and trends in published shoulder research over the last decade in a leading orthopaedic journal. METHODS: We examined all clinical shoulder articles published in The Journal of Bone & Joint Surgery from 2004 to 2014. The number of citations, authorship, academic degrees of the authors, country and institution of origin, topic, level of evidence, positive or nonpositive outcome, and inclusion of validated patient-reported outcome measures were assessed for each article. RESULTS: Shoulder articles that included an author with an advanced research degree (MD [Doctor of Medicine] with a PhD [Doctor of Philosophy] or other advanced degree) increased during the study period (p = 0.047). Level-I, II, and III studies were more likely to have an author with an advanced research degree, and Level-IV studies were more likely to have MDs only (p = 0.03). Overall, there was great variability of outcome measures, with at least thirty-nine different validated or nonvalidated outcome measures reported. CONCLUSIONS: Over the last decade, there was an improvement in the level of evidence of shoulder articles published in The Journal of Bone & Joint Surgery that corresponds with recent emphasis on evidence-based medicine. A consensus is needed in shoulder research for more consistent application of validated patient-reported outcome measurement tools.

Alveolar-capillary adaptation to chronic hypoxia in the fatty lung.

AIM: Obese diabetic (ZDF fa/fa) rats with genetic leptin resistance suffer chronic lipotoxicity associated with age-related lung restriction and abnormal alveolar ultrastructure. We hypothesized that these abnormalities impair adaptation to ambient hypoxia. METHODS: Male fa/fa and lean (+/+) ZDF rats (4-months old) were exposed to 21 or 13% O2 for 3 weeks. Lung function was measured under anaesthesia. Lung tissue was assayed for DNA damage and ultrastructure measured by morphometry. RESULTS: In normoxia, lung volume, compliance and diffusing capacity were lower, while blood flow was higher in fa/fa than +/+ rats. In hypoxia, fa/fa animals lost more weight, circulating hematocrit rose higher, and lung volume failed to increase compared to +/+. In fa/fa, the hypoxia-induced increase in post-mortem lung volume was attenuated (19%) vs. +/+ (39%). Alveolar ducts were 35% smaller in normoxia but enlarged twofold more in hypoxia compared to +/+. Hypoxia induced broad increases (90-100%) in the volumes and surface areas of alveolar septal components in +/+ lungs; these increases were moderately attenuated in fa/fa lungs (58-75%), especially that of type II epithelium volume (16 vs. 61% in +/+). In fa/fa compared to +/+ lungs, oxidative DNA damage was greater with increased hypoxia induced efflux of alveolar macrophages. Harmonic mean thickness of the diffusion barrier was higher, indicating higher structural resistance to gas transfer. CONCLUSION: Chronic lipotoxicity impaired hypoxia-induced lung expansion and compensatory alveolar growth with disproportionate effect on resident alveolar progenitor cells. The moderate structural impairment was offset by physiological adaptation primarily via a higher hematocrit.

New generation super alloy candidates for medical applications: corrosion behavior, cation release and biological evaluation.

Three super alloy candidates (X1 CrNiMoMnW 24-22-6-3-2 N, NiCr21 MoNbFe 8-3-5 AlTi, CoNiCr 35-20 Mo 10 BTi) for a prolonged contact with skin are evaluated in comparison with two reference austenitic stainless steels 316L and 904L. Several electrochemical parameters were measured and determined (E(oc), E(corr), i(corr), b(a), b(c), E(b), R(p), E(crev) and coulometric analysis) in order to compare the corrosion behavior. The cation release evaluation and in vitro biological characterization also were performed. In terms of corrosion, the results reveal that the 904L steels presented the best behavior followed by the super austenitic steel X1 CrNiMoMnW 24-22-6-3-2 N. For the other two super alloys (NiCr and CoNiCr types alloys) tested in different conditions (annealed, work hardened and work hardened+age hardened) it was found that their behavior to corrosion was weak and close to the other reference stainless steel, 316L. Regarding the extraction a mixture of cations in relatively high concentrations was noted and therefore a cocktail effect was not excluded. The results obtained in the biological assays WST-1 and TNF-alpha were in correlation with the corrosion and extraction evaluation.

Transient CD15-positive endothelial phenotype in the human placenta correlates with physiological and pathological fetoplacental immaturity.

OBJECTIVE: Placental growth and villous maturation are critical parameters of placental function at the end of pregnancy. A failure in these processes leads to the development of placental dysfunction, as well as fetal and neonatal mortality and morbidity. The aim of the study was to determine the relevant diagnostic markers associated with pathological placental development. STUDY DESIGN: Forty tissue samples from normal placentas of different gestational age and 68 pathological term placentas with defective villous maturation (GDM, idiopathic IUFD, preeclamsia, HELLP syndrome) comprised the comparative immunohistochemical study (CD15, CD45 and CD34). Positive immunohistochemical reactions were quantitatively assessed in the chorionic plate and vessels of the villi of different histological type. RESULTS: Physiologically immature placentas of the first and second trimester and pathologically immature term placentas were characterized by marked endothelial CD15-immunostaining. A significant loss of CD15-positive endothelium of the placentas was associated with a physiological and accelerated villous maturity. A spatio-temporal correlation was shown for CD15+ endothelial cells (ECs) and the number of CD45+ stromal cells (SCs). A negative temporal correlation was shown for CD15+ ECs and CD15+ myelomonocytes in the fetal blood. CD34 expression in the ECs was stable during the pregnancy. CONCLUSION: A correlation between a transient CD15-positive endothelial phenotype and a physiological and pathological fetoplacental immaturity was demonstrated. Physiological and accelerated placental maturation was accompanied by a significant disappearance of CD15-positive endothelium. We propose that "immature" CD15+ endothelium is an important diagnostic marker of the physiological and pathological fetoplacental immaturity.

Macrophage-mediated angiogenic activation of outgrowth endothelial cells in co-culture with primary osteoblasts.

The successful vascularisation of complex tissue engineered constructs for bone regeneration is still a major challenge in the field of tissue engineering. In this context, co-culture systems of endothelial cells and osteoblasts represent a promising approach to advance the formation of a stable vasculature as well as an excellent in vitro model to identify factors that positively influence bone healing processes, including angiogenesis. Under physiological conditions, the activation phase of angiogenesis is mainly induced by hypoxia or inflammation. Inflammatory cells such as macrophages secrete proinflammatory cytokines and proangiogenic growth factors, finally leading to the formation of new blood vessels. The aim of this study was to investigate if macrophages might positively influence the formation of microvessel-like structures via inflammatory mechanisms in a co-culture system consisting of human outgrowth endothelial cells (OECs) and primary osteoblasts. Treatment of co-cultures with macrophages (induced from THP-1) resulted in a higher number of microvessel-like structures formed by OECs compared to the co-culture. This change correlated with a significantly higher concentration of the proangiogenic VEGF in cell culture supernatants of triple-cultures and was accompanied by an increase in the expression of different proinflammatory cytokines, such as IL-6, IL-8 and TNFα. In addition, the expression of E-selectin and ICAM-1, adhesion molecules which are strongly involved in the interaction between leukocytes and endothelial cells during the process of inflammation was also found to be higher in triple-cultures compared to the double co-cultures, documenting an ongoing proinflammatory stimulus. These results raise the possibility of actively using pro-inflammatory stimuli in a tissue engineering context to accelerate healing mechanisms.

Application of machine learning algorithms for clinical predictive modeling: a data-mining approach in SCT.

Data collected from hematopoietic SCT (HSCT) centers are becoming more abundant and complex owing to the formation of organized registries and incorporation of biological data. Typically, conventional statistical methods are used for the development of outcome prediction models and risk scores. However, these analyses carry inherent properties limiting their ability to cope with large data sets with multiple variables and samples. Machine learning (ML), a field stemming from artificial intelligence, is part of a wider approach for data analysis termed data mining (DM). It enables prediction in complex data scenarios, familiar to practitioners and researchers. Technological and commercial applications are all around us, gradually entering clinical research. In the following review, we would like to expose hematologists and stem cell transplanters to the concepts, clinical applications, strengths and limitations of such methods and discuss current research in HSCT. The aim of this review is to encourage utilization of the ML and DM techniques in the field of HSCT, including prediction of transplantation outcome and donor selection.

Improving cytocompatibility of Co28Cr6Mo by TiO2 coating: gene expression study in human endothelial cells.

Cobalt-based materials are widely used for coronary stents, as well as bone and joint implants. However, their use is associated with high corrosion incidence. Titanium alloys, by contrast, are more biocompatible owing to the formation of a relatively inactive titanium oxide (TiO2) layer on their surface. This study was aimed at improving Co28Cr6Mo alloy cytocompatibility via sol-gel TiO2 coating to reduce metal corrosion and metal ion release. Owing to their role in inflammation and tissue remodelling around an implant, endothelial cells present a suitable in vitro model for testing the biological response to metallic materials. Primary human endothelial cells seeded on Co28Cr6Mo showed a stress phenotype with numerous F-actin fibres absent on TiO2-coated material. To investigate this effect at the gene expression level, cDNA microarray analysis of in total 1301 genes was performed. Compared with control cells, 247 genes were expressed differentially in the cells grown on Co28Cr6Mo, among them genes involved in proliferation, oxidative stress response and inflammation. TiO2 coating reduced the effects of Co28Cr6Mo on gene expression in endothelial cells, with only 34 genes being differentially expressed. Quantitative real-time polymerase chain reaction and protein analysis confirmed microarray data for selected genes. The effect of TiO2 coating can be, in part, attributed to the reduced release of Co(2+), because addition of CoCl2 resulted in similar cellular responses. TiO2 coating of cobalt-based materials, therefore, could be used in the production of cobalt-based devices for cardiovascular and skeletal applications to reduce the adverse effects of metal corrosion products and to improve the response of endothelial and other cell types.

Imbalance of expression of bFGF and PK1 is associated with defective maturation and antenatal placental insufficiency.

OBJECTIVE: Defective placental maturation is associated with restricted functional capacity and adverse perinatal fetal outcomes. The aim of the study was a comparative analysis of the role of mRNA expression of various angiogenic factors in placental maturation defects. STUDY DESIGN: We examined the mRNA expression patterns of prokineticin 1 (PK1), its receptors (PKRs), basic-fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) in tissue from third-trimester placentae that exhibited delayed or accelerated villous maturation. RESULTS: The expression of PK1 and PKR2 was elevated in placental tissue exhibiting accelerated maturation and a predominant differentiation of terminal villi. The opposite was found in tissue exhibiting delayed maturation and deficiency of the terminal villi. In addition, low expression of bFGF correlated with the predominant differentiation of terminal villi, whereas the opposite was observed when terminal villi were deficient. The expression of VEGF, PIGF, and PKR1 showed no significant differences between the groups. CONCLUSION: Defective placental maturation is associated with an imbalance of expression of bFGF and PK1. Our results demonstrate an involvement of the PK1/PKR2-signalling pathway in the regulation of the functional adequate capillarization in late pregnancy. We propose the bFGF/PK1-ratio as a monitor of placental function and a possible indicator of latent clinical problems, such as placental dysfunction leading to fetal hypoxia.

In vitro evaluation of biomimetic chitosan-calcium phosphate scaffolds with potential application in bone tissue engineering.

This work reports on the physicochemical properties and in vitro cytotoxicity assessment of chitosan-calcium phosphate (Cs-CP) scaffolds for bone tissue engineering, which were synthesized by a novel biomimetic co-precipitation method. X-ray diffraction (XRD) along with scanning electron microscopy (SEM) analysis confirmed the porous morphology of the scaffolds and the amorphous nature of the inorganic phase with different crystallite sizes and the formation of various forms of calcium phosphate. Compressive mechanical testing revealed that the Young's modulus of the biomaterials is in the range of human trabecular bone. In vitro tests were performed on the biomaterials for up to 14 days to study the behavior of the osteoblast-like human cell line (MG63), primary human osteoblasts (HOS) and human dermal microvascular endothelial cells (HDMEC). The cytotoxicity was evaluated by the MTS assay for cell metabolism and the detection of membrane integrity (lactate dehydrogenase-LDH release). An expression of the vascular endothelial growth factor (VEGF) in the cell supernatants was quantified by ELISA. Cell viability gave values close to untreated controls for MG63 and HOS, while in the case of HDMEC the viability after 2 weeks in the cell culture was between 80-90%. The cytotoxicity induced by the Cs-CP scaffolds on MG63, HOS and HDMEC in vitro was evaluated by the amount of LDH released, which is a sensitive and accurate marker for cellular toxicity. The increased levels of VEGF obtained in the osteoblast culture highlights its important role in the regulation of vascularization and bone remodeling. The biological responses of the Cs-CP scaffolds demonstrate a similar proliferation and differentiation characteristics of the cells comparable to the controls. These results reveal that biomimetic Cs-CP composite scaffolds are promising biomaterials for bone tissue engineering; their in vivo response remains to be tested.

Risk factors of infection after ORIF of bicondylar tibial plateau fractures.

OBJECTIVES: This study was designed to evaluate risk factors of infection after bicondylar tibial plateau fractures. We hypothesized that open fractures and smoking would be associated with deep infection requiring reoperation. DESIGN: We retrospectively identified all bicondylar (AO/OTA 41-C) tibial plateau fractures treated operatively over an 8-year period from 2002 to 2010. SETTING: Single, high-volume, level 1 trauma center. PATIENTS/PARTICIPANTS: A total of 302 patients aged 18 years and older were identified as undergoing operative fixation of bicondylar (AO/OTA 41-C) tibial plateau fractures during this time period. INTERVENTION: Open reduction internal fixation of bicondylar (AO/OTA 41-C) tibial plateau fractures. MAIN OUTCOME MEASUREMENTS: Bivariate and multivariable logistic regression analyses were used to assess the association between patient demographics and clinical characteristics and deep infection requiring reoperation. Variables that were significant at P < 0.05 in bivariate analyses were entered into a multivariable logistic regression model. RESULTS: Forty-three (14.2%) of 302 patients developed deep infection requiring reoperation. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured in 20 (46.5%) of 43 patients with deep infections. An external fixator was initially placed before definitive fixation in 81.4% of patients and definitive surgical treatment was delayed by an average of 17.5 days. Eighty-five (28.1%) patients required a reoperation after definitive fixation.Open fracture (OR, 3.44; P = 0.003), smoking (OR, 2.40; P = 0.02), compartment syndrome requiring fasciotomies (OR, 3.81; P = 0.01), and fractures requiring 2 incisions and 2 plates (OR, 3.19; P = 0.01) were all risk factors for deep infection requiring reoperation. CONCLUSIONS: In spite of a staged protocol with temporizing external fixation and delayed fixation, deep infection rate remained high. A disproportionate amount of MRSA (47%) was cultured from deep infections in this population, and MRSA prophylaxis may be considered. Smoking was the only patient modifiable predictor identified of deep infection, and patients should be informed of the increased risk of deep infection associated with their choice to continue smoking. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.