Predictive power of modified frailty index score for pulmonary complications after major abdominal surgery in the elderly: a single centre prospective cohort study.

OBJECTIVE: The primary aim of this prospective cohort study was to evaluate the usefulness of the modified Frailty Index (mFI) score to predict postoperative pulmonary complications (PPCs) in elderly patients undergoing major open abdominal surgery. The secondary purpose was to compare the prediction power of mFI, Ariscat (Assess Respiratory Risk in Surgical Patients in Catalonia), and American Society physical status classification (ASA) scores. PATIENTS AND METHODS: After local Ethical Committee approval, 105 patients aged ≥65 years undergoing open major abdominal surgery were enrolled. Clinical data were compared between patients with or without PPCs (including respiratory failure, aspiration pneumonia, pulmonary infection, pleural effusion, pneumothorax, atelectasis, bronchospasm or un-planned re-intubation). t-test or χ2-test were performed for univariate analyses. Logistic regression analysis was used to identify independent predictors of PPCs. Non parametric ROC (Receiver Operating Characteristic) was used for cut-off calculation. AUCs (areas under ROC curve) of preoperative scores were compared using χ2-test. RESULTS: PPCs prevalence (11.3%) was associated with increased mFI, ASA, and Ariscat scores, greater age, hemoglobin levels <10 g/dl, peripheral oxygen saturation <95% (p=0.0001) and longer surgery duration. Logistic regression showed that mFI (p=0.0001) and Ariscat (p=0.04) were independent predictors of PPCs. The predictive power of mFI (AUC=0.90) was similar to that of Ariscat (AUC=0.81) (χ2=2.53; p=0.11) but greater than that of ASA (AUC=0.69) (χ2=9.85; p=0.002). An mFI≥0.18 was predictive of PPCs (sensitivity=90.91%; specificity=79.07%). An Ariscat score of 27 was the cut-off identified as determining factor for PPCs occurrence (sensitivity=90.91%; specificity=51.16%). CONCLUSIONS: Elderly patients with an mFI ≥0.18 and/or an Ariscat score ≥27 were at higher risk of PPCs after open major abdominal surgery. More attention should be paid to these patients by implementing both strict monitoring and strategies for PPCs prevention in the perioperative period.

p-Coumaric acid loaded into liquid crystalline systems as a novel strategy to the treatment of vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is an extremely common type of vaginal infection, which is mainly caused by Candida albicans. However, non-albicans Candida species are frequently more resistant to conventional antifungal agents and can represent up to 30% of cases. Due to side effects and increasing antifungal resistance presented by standard therapies, phenolic compounds, such as p-coumaric acid (p-CA), have been studied as molecules from natural sources with potential antifungal activity. p-CA is a poorly water-soluble compound, thus loading it into liquid crystals (LCs) may increase its solubility and effectiveness on the vaginal mucosa. Thereby, here we propose the development of mucoadhesive liquid crystalline systems with controlled release of p-CA, for the local treatment of VVC. Developed LCs consisted of fixed oily and aqueous phases (oleic acid and cholesterol (5:1) and poloxamer dispersion 16%, respectively), changing only the surfactant phase components (triethanolamine oleate (TEA-Oleate) or triethanolamine (TEA), the latter producing TEA-Oleate molecules when mixed with oleic acid). Systems were also diluted in artificial vaginal mucus (1:1 ratio) to mimic the vaginal environment and verify possible structural changes on formulations upon exposure to the mucosa. From the characterization assays, p-CA loaded TEA-Oleate systems presented mucoadhesive profile, liquid crystalline mesophases, well-organized structures and pseudoplastic behaviour, which are desirable parameters for topical formulations. Moreover, they were able to control the release of p-CA throughout the 12 h assay, as well as decrease its permeation into the vaginal mucosa. p-CA showed antifungal activity in vitro against reference strains of C. albicans (SC5314), C. glabrata (ATCC 2001) and C. krusei (ATCC 6258), and exhibited higher eradication of mature biofilms than amphotericin B and fluconazole. In vivo experiments demonstrated that the formulations reduced the presence of filamentous forms in the vaginal lavages and provided an improvement in swelling and redness present in the mice vaginal regions. Altogether, here we demonstrated the potential and feasibility of using p-CA loaded liquid crystalline systems as a mucoadhesive drug delivery system for topical treatment of VVC.

Variation in Inflammatory Biomarkers Among Demographic Groups Significantly Affects Their Accuracy in Diagnosing Periprosthetic Joint Infection.

BACKGROUND: Diagnosis of periprosthetic joint infection (PJI) is a multistep process that involves performing various tests including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The latter two tests, despite being used at all times for PJI diagnosis, are known to be nonspecific and substantially affected by demographic characteristics, including age, gender, race, and body mass index. It is unknown how these variations affect the diagnostic utility of serological markers for PJI. METHODS: Institutional databases were queried to identify patients undergoing revision arthroplasty between 2010 and 2018, in whom preoperative serum ESR and CRP was performed. Patient demographics were collected, and patients were cross-referenced with an internal database to determine their infection status. Analyses were performed to determine how ESR and CRP varied with respect to demographic factors, including age, gender, race, and infection status. Given that patient infection status was known at the time of revision, conclusions were drawn about the effect of these variations in inflammatory markers on the diagnostic utility of ESR and CRP. RESULTS: The value of ESR increased by age was higher in females and African American race. No significant differences were observed in the value of CRP among the demographic factors, although a slight positive trend was observed with respect to age. The variation in inflammatory markers significantly affected the sensitivity, specificity, and accuracy of ESR and CRP for PJI diagnosis. CONCLUSION: Understanding how the accuracy of diagnostic tests varies with respect to demographic factors can help physicians avoid subjecting patients to unnecessary additional testing and reach more accurate diagnoses of PJI.

Tranexamic Acid Reduces the Rate of Periprosthetic Joint Infection After Aseptic Revision Arthroplasty.

BACKGROUND: Revision total joint arthroplasty (TJA) has a higher rate of periprosthetic joint infection (PJI) compared with primary TJA, possibly as the result of increased allogeneic blood transfusion. Tranexamic acid (TXA) is gaining popularity in revision TJA to minimize blood loss and the need for transfusion; however, its effect on PJI reduction has yet to be investigated. The hypothesis of this study was that the administration of TXA during revision arthroplasty is protective against subsequent PJI. METHODS: A prospectively maintained institutional database was used to identify patients who underwent revision TJA for aseptic failure from 2009 to 2018 and had a minimum follow-up of 90 days. Patients who developed PJI following revision arthroplasty were identified. All patients with PJI met Musculoskeletal Infection Society (MSIS) criteria. A multivariate analysis was performed to identify variables independently associated with PJI after aseptic revision TJA. RESULTS: Overall, 1,731 patients who underwent aseptic revision were identified; of these patients, 83 (4.8%) developed PJI. Patients who received TXA had significantly lower rates (p = 0.029) of PJI postoperatively at 3.30% compared with those who did not receive TXA at 5.73%. After controlling for relevant confounding variables, TXA remained a significant independent factor that protected against PJI (odds ratio [OR], 0.47 [95% confidence interval (CI), 0.23 to 0.90]; p = 0.030). Female sex was also identified as a significant independent factor that protected against PJI (OR, 0.52 [95% CI, 0.30 to 0.88]; p = 0.016). However, preoperative anemia was independently associated with an increased risk of subsequent PJI (OR, 2.37 [95% CI, 1.34 to 4.16]; p = 0.003). CONCLUSIONS: Based on this study conducted at a single institution, the use of TXA during aseptic revision arthroplasty was independently associated with a reduced risk of subsequent acute PJI after adjusting for multiple patient characteristics and surgical factors. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Treatment Outcomes in Patients Undergoing Surgical Treatment for Arthritis of the Distal Radioulnar Joint.

Objective Surgical treatment options for distal radioulnar joint (DRUJ) arthritis include distal ulnar resection (DUR), DRUJ arthrodesis, and ulnar head replacement. Ulnar convergence leading to persistent pain and clicking is a relatively common complication of complete DUR and DRUJ arthrodesis with distal ulnar segment resection (DRUJA). This led to the development of the distal ulna hemiresection (DUHR) and distal ulnar stump stabilization techniques to reduce the risk of this complication. Patients may experience incomplete relief of pain and limited range of motion (ROM) with these procedures. We hypothesized that there would be no differences in outcomes between the treatment groups, but patients undergoing DUHR, tendon interposition, or distal ulnar stump stabilization would be at lower risk of complications. Methods Records were retrospectively reviewed for 121 patients undergoing DRUJ procedures between 2000 and 2018 at a single institution to collect patient demographics, surgical details, preoperative diagnosis, and outcomes including complications, revision procedures, ROM, pain, and swelling. Patients were grouped for analysis by procedure type: DUR (Darrach procedure), DUHR (Bowers procedure), and DRUJA (Sauve-Kapandji procedure). Continuous variables were compared using an analysis of variance test and categorical variables using the Freeman-Halton extension of the Fisher's exact test. A multivariate logistic regression analysis was performed to identify significant predictors of outcomes. Results Seventy-three patients underwent a DUR procedure, while 33 patients underwent a DUHR procedure and 11 underwent a DRUJA procedure. Mean follow-up was 70.6 months. Patients undergoing DRUJA were significantly younger than those undergoing DUR or DUHR procedure (42.4 vs. 60.0 vs. 62.1, p < 0.001). No significant differences between groups were demonstrated in measured outcomes. Posttraumatic arthritis was the most common preoperative diagnosis (43.4%). Persistent pain was the most common negative outcome (25.6%) followed by limited ROM (19.7%). Five patients (4.3%) suffered postoperative complications, most common being rupture of extensor tendons. Five patients (4.3%) underwent revision procedures. Body mass index (BMI) was a significant predictor of persistent pain (odds ratio = 1.09, p = 0.031). Conclusion The results of our study suggest that outcomes are equivalent between the three distinct treatment groups. Despite the potential benefits, hemiresection, tendon interposition, and distal stump stabilization had no significant effect on outcomes in this study. More than a quarter (25.6%) of patients undergoing DRUJ procedures experience persistent pain postoperatively, while one-fifth (19.7%) experienced limited ROM. Patients with higher BMI are at a significantly greater risk of experiencing persistent postoperative pain. Level of Evidence This is a Level III, retrospective comparative study.

BMI Does Not Affect Complications or Patient Reported Outcomes After Lumbar Decompression Surgery.

STUDY DESIGN: This is a retrospective comparative review. OBJECTIVE: The objective of this study was to identify the influence of body mass index (BMI) on postsurgical complications and patient reported outcomes measures (PROMs) following lumbar decompression surgery. SUMMARY OF BACKGROUND DATA: Current literature does not accurately identify the impact of BMI on postsurgical complications or outcomes. MATERIALS AND METHODS: Records from a single-center, academic hospital were used to identify patients undergoing 1 to 3-level lumbar decompression surgery. Patients under 18 years of age, those undergoing surgery for infection, trauma, tumor, or revision, and those with <1-year follow-up were excluded. Patients were split into groups based on preoperative BMI: class I: BMI <25.0 kg/m; class II: BMI 25.0-29.9 kg/m; class III: BMI 30.0-34.9 kg/m; and class IV: BMI >35.0 kg/m. Absolute PROM scores, the recovery ratio and the percent of patients achieving minimum clinically important difference between groups were compared and a multiple linear regression analysis was performed. RESULTS: A total of 195 patients were included with 34 (17.4%) patients in group I, 80 (41.0%) in group II, 49 (25.1%) in group III, and 32 (16.5%) in group IV. Average age was 60.0 (58.0, 62.0) years and average follow-up was 13.0 (12.6, 13.4) months. All patients improved significantly within each group, except for class III and class IV patients, who did not demonstrate significant improvements in terms of Mental Component Score (MCS-12) scores (P=0.546 and 0.702, respectively). There were no significant differences between BMI groups for baseline or postoperative PROM values, recovery ratio, or the percent of patients reaching minimum clinically important difference. Multiple linear regression analysis revealed that BMI was not a significant predictor for change in outcomes for any measure. The 30-day readmission rate was 6.2% and overall revision rate at final follow-up was 5.1%, with no significant differences between groups. CONCLUSION: This study's results suggest that BMI may not significantly affect complications or patient outcomes at 1-year in those undergoing lumbar decompression surgery. LEVEL OF EVIDENCE: Level III.

Nanofiber membranes as biomimetic and mechanically stable surface coatings.

Elastomers have been extensively exploited to study cell physiology in fields such as mechanobiology, however, their intrinsic high hydrophobicity renders their surfaces incompatible for prolonged cell adhesion and proliferation. Electrospun fiber networks on the other side provide a promising environment for enhanced cell adhesion and growth due to their architecture closely mimicking the structure of the extracellular matrix present within tissues of the human body. Here, we explored the stable integration of electrospun fibers onto the surfaces of elastomeric materials to promote cytocompatibility of these composites. Elastomers based on room temperature vulcanizing silicone (RTV), polydimethylsiloxane (PDMS) as well as functionalized PDMS-based materials were chosen as wafer substrates for attachment of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDFhfp) fibers, a well-known antithrombotic polymer. Electrospinning the fibers onto uncured interfaces acted as bonding agents on the wafers, enabling penetration and formation of a stable bond between the fibers surfaces and the elastomers after curing the interface. Dimensional analysis revealed a relationship between peeling force, intrusion depth and the elastic modulus of the wafers. A design parameter Πα was extrapolated to be used as a predictive tool of the peeling force when intrusion depth of PVDFhfp fibers and elastic modulus of the wafers are known. Cultivating fibroblasts on these hybrid membranes showed cell attachment and growth over 7 days regardless of the composition of the substrate, confirming high cytocompatibility for all composite materials. The presented approach opens avenues to establish nanofiber morphologies as a novel, stable surface texturing tool for tissue engineering, cell biology, medical devices and textiles.

Random auxetics from buckling fibre networks.

Auxetic materials have gained increasing interest in the last decades, fostered by auspicious applications in various fields. While the design of new auxetics has largely focused on meta-materials with deterministic, periodically arranged structures, we show here by theoretical and numerical analysis that pronounced auxetic behaviour with negative Poisson's ratios of very large magnitude can occur in random fibre networks with slender, reasonably straight fibre segments that buckle and deflect. We further demonstrate in experiments that such auxetic fibre networks, which increase their thickness by an order of magnitude and more than quintuple their volume when moderately extended, can be produced by electrospinning. Our results thus augment the class of auxetics by a large group of straightforwardly fabricable meta-materials with stochastic microstructure.

Correlating diameter, mechanical and structural properties of poly(l-lactide) fibres from needleless electrospinning.

The development and application of nanofibres requires a thorough understanding of the mechanical properties on a single fibre level including respective modelling tools for precise fibre analysis. This work presents a mechanical and morphological study of poly-l-lactide nanofibres developed by needleless electrospinning. Atomic force microscopy (AFM) and micromechanical testing (MMT) were used to characterise the mechanical response of the fibres within a diameter range of 200-1400 nm. Young's moduli E determined by means of both methods are in sound agreement and show a strong increase for thinner fibres below a critical diameter of 800 nm. Similar increasing trends for yield stress and hardening modulus were measured by MMT. Finite element analyses show that the common practice of modelling three-point bending tests with either double supported or double clamped beams is prone to significant bias in the determined elastic properties, and that the latter is a good approximation only for small diameters. Therefore, an analytical formula based on intermediate boundary conditions is proposed that is valid for the whole tested range of fibre diameters, providing a consistently low error in axial Young's modulus below 10%. The analysis of fibre morphology by differential scanning calorimetry and 2D wide-angle X-ray scattering revealed increasing polymer chains alignment in the amorphous phase and higher crystallinity of fibres for decreasing diameter. The combination of these observations with the mechanical characterisation suggests a linear relationship between Young's modulus and both crystallinity and molecular orientation in the amorphous phase. STATEMENT OF SIGNIFICANCE: Fibrous membranes have rapidly growing use in various applications, each of which comes with specific property requirements. However, the development and production of nanofibre membranes with dedicated mechanical properties is challenging, in particular with techniques suitable for industrial scales such as needleless electrospinning. It is therefore a key step to understand the mechanical and structural characteristics of single nanofibres developed in this process, and to this end, the present work presents changes of internal fibre structure and mechanical properties with diameter, based on dedicated models. Special attention was given to the commonly used models for analyzing Young's modulus of single nanofibers in three-point bending tests, which are shown to be prone to large errors, and an improved robust approach is proposed.

Electrospraying of microfluidic encapsulated cells for the fabrication of cell-laden electrospun hybrid tissue constructs.

The fabrication of functional 3D tissues is a major goal in tissue engineering. While electrospinning is a promising technique to manufacture a structure mimicking the extracellular matrix, cell infiltration into electrospun scaffolds remains challenging. The robust and in situ delivery of cells into such biomimetic scaffolds would potentially enable the design of tissue engineered constructs with spatial control over cellular distribution but often solvents employed in the spinning process are problematic due to their high cytotoxicity. Herein, microfluidic cell encapsulation is used to establish a temporary protection vehicle for the in situ delivery of cells for the development of a fibrous, cell-laden hybrid biograft. Therefore a layer-by-layer process is used by alternating fiber electrospinning and cell spraying procedures. Both encapsulation and subsequent electrospraying of capsules has no negative effect on the viability and myogenic differentiation of murine myoblast cells. Propidium iodide positive stained cells were analyzed to quantify the amount of dead cells and the presence of myosin heavy chain positive cells after the processes was shown. Furthermore, encapsulation successfully protects cells from cytotoxic solvents (such as dimethylformamide) during in situ delivery of the cells into electrospun poly(vinylidene fluoride-co-hexafluoropropylene) scaffolds. The resulting cell-populated biografts demonstrate the clear potential of this approach in the creation of viable tissue engineering constructs. STATEMENT OF SIGNIFICANCE: Infiltration of cells and their controlled spatial distribution within fibrous electrospun membranes is a challenging task but allows for the development of functional highly organized 3D hybrid tissues. Combining polymer electrospinning and cell electrospraying in a layer-by-layer approach is expected to overcome current limitations of reduced cell infiltration after traditional static seeding. However, organic solvents, used during the electrospinning process, impede often major issues due to their high cytotoxicity. Utilizing microfluidic encapsulation as a mean to embed cells within a protective polymer casing enables the controlled deposition of viable cells without interfering with the cellular phenotype. The presented techniques allow for novel cell manipulation approaches being significant for enhanced 3D tissue engineering based on its versatility in terms of material and cell selection.

A review of the application of reinforced hydrogels and silk as biomaterials for intervertebral disc repair.

The degeneration of the intervertebral disc (IVD) within the spinal column represents a major pain source for many patients. Biological restoration or repair of the IVD using "compressive-force-resistant" and at the same time "cytocompatible" materials would be desirable over current purely mechanical solutions, such as spinal fusion or IVD implants. This review provides an overview of recent research on the repair of the inner (nucleus pulposus = NP) and the outer (annulus fibrous = AF) parts of the IVD tissue. Many studies have addressed NP repair using hydrogel-like materials. However, only a few studies have so far focused on AF repair. As the AF possesses an extremely low self-healing capacity and special attention to shear-force resistance is essential, special repair designs are required. In our review, we stated the challenges in IVD repair and highlighted the use of composite materials such as silk biomaterials and fibrin cross-linked reinforced hydrogels. We elaborated on the origin of silk and its many in tissue engineering. Furthermore, techniques such as electrospinning and 3D printing technologies allow the fabrication of versatile and functionalised 3D scaffolds. We summarised the research that has been conducted in the field of regenerative medicine over the recent years, with a special focus on the potential application and the potential of combining silk and reinforced - and thus mechanically tailored - hydrogels for IVD repair.

Functional characterization of mutant genes associated with autosomal dominant familial hypercholesterolemia: integration and evolution of genetic diagnosis.

AIMS: Familial Hypercholesterolemia (FH) is one of the most frequent dyslipidemias, the autosomal dominant form of which is primarily caused by mutations in the LDL receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes, although in around 20% of patients the genetic cause remains unidentified. Genetic testing has notably improved the identification of patients suffering from FH, the most frequent cause of which is the presence of mutations in the LDLR gene. Although more than 1200 different mutations have been identified in this gene, about 80% are recognized to be pathogenic. We aim to overview the current methods used to perform the functional characterization of mutations causing FH and to highlight the conditions requiring a functional characterization of the variant in order to obtain a diagnostic report. DATA SYNTHESIS: In the current review, we summarize the different types of functional assays - including their advantages and disadvantages - performed to characterize mutations in the LDLR, APOB and PCSK9 genes helping to better define their pathogenic role. We describe the evaluation of splicing alterations and two major procedures for functional characterization: 1. ex vivo methods, using cells from FH patients; 2. in vitro methods using cell lines. CONCLUSIONS: Functional characterization of the LDLR, APOB and PCSK9 mutant genes associated with FH can be considered a necessary integration of its genetic diagnosis.

General theory of frictional heating with application to rubber friction.

The energy dissipation in the contact regions between solids in sliding contact can result in high local temperatures which may strongly effect friction and wear. This is the case for rubber sliding on road surfaces at speeds above 1 mm s(-1). We derive equations which describe the frictional heating for solids with arbitrary thermal properties. The theory is applied to rubber friction on road surfaces and we take into account that the frictional energy is partly produced inside the rubber due to the internal friction of rubber and in a thin (nanometer) interfacial layer at the rubber-road contact region. The heat transfer between the rubber and the road surface is described by a heat transfer coefficient which depends on the sliding speed. Numerical results are presented and compared to experimental data. We find that frictional heating results in a kinetic friction force which depends on the orientation of the sliding block, thus violating one of the two basic Leonardo da Vinci 'laws' of friction.

Covalent immobilisation of VEGF on plasma-coated electrospun scaffolds for tissue engineering applications.

Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 µm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations.

Plasma-functionalized electrospun matrix for biograft development and cardiac function stabilization.

Cardiac tissue engineering approaches can deliver large numbers of cells to the damaged myocardium and have thus increasingly been considered as a possible curative treatment to counteract the high prevalence of progressive heart failure after myocardial infarction (MI). Optimal scaffold architecture and mechanical and chemical properties, as well as immune- and bio-compatibility, need to be addressed. We demonstrated that radio-frequency plasma surface functionalized electrospun poly(ɛ-caprolactone) (PCL) fibres provide a suitable matrix for bone-marrow-derived mesenchymal stem cell (MSC) cardiac implantation. Using a rat model of chronic MI, we showed that MSC-seeded plasma-coated PCL grafts stabilized cardiac function and attenuated dilatation. Significant relative decreases of 13% of the ejection fraction (EF) and 15% of the fractional shortening (FS) were observed in sham treated animals; respective decreases of 20% and 25% were measured 4 weeks after acellular patch implantation, whereas a steadied function was observed 4 weeks after MSC-patch implantation (relative decreases of 6% for both EF and FS).

ß-Blockers associated with no class-specific survival benefit in acute intracerebral hemorrhage.

OBJECTIVES: Despite the high mortality, there is currently no specific treatment for intracerebral hemorrhage (ICH). Research investigating optimum degree of blood pressure control in patients presenting with ICH and hypertension is ongoing. However, there is limited understanding of the potential benefits of specific classes of antihypertensive therapy. ß-Adrenergic antagonists may provide neuroprotection from inflammation-induced injury by inhibiting sympathetic nervous system mediated immune activation. We examined mortality in ICH patients receiving ß-adrenergic antagonists to determine whether this class of antihypertensive therapy was associated with improved survival. METHODS: A retrospective analysis of a large, prospectively collected database of patients presenting with acute ICH was performed. Patients were grouped by inpatient ß-blocker treatment to determine an effect on mortality during the inpatient stay and at 3 months of follow-up. Additional analysis was conducted comparing ß-blocker therapy to any other antihypertensive treatment to determine a class-specific association of ß-blocker treatment with mortality. RESULTS: The study population included 426 patients with acute, spontaneous ICH. Inpatient ß-blocker use was independently associated with decreased rates of inpatient death and mortality at 3 months of follow-up. However, univariate and multivariable analyses comparing ß-blocker use to other antihypertensives failed to show any class-specific reduction in mortality at either time point. DISCUSSION: Our study demonstrates that the improvement seen in patients treated with ß-adrenergic antagonists is not an effect unique to this class. This supports ongoing trials to determine optimum levels of blood pressure control using multiple classes of antihypertensives.

Rubber friction for tire tread compound on road surfaces.

We have measured the surface topography and calculated the surface roughness power spectrum for an asphalt road surface. For the same surface we have measured the friction for a tire tread compound for velocities 10(-6) m s(-1) < v < 10(-3) m s(-1) at three different temperatures (at -8 °C, 20 °C and 48 °C). The friction data was shifted using the bulk viscoelasticity shift factor a(T) to form a master curve. We have measured the effective rubber viscoelastic modulus at large strain and calculated the rubber friction coefficient (and contact area) during stationary sliding and compared it to the measured friction coefficient. We find that for the low velocities and for the relatively smooth road surface we consider, the contribution to friction from the area of real contact is very important, and we interpret this contribution as being due to shearing of a very thin confined rubber smear film.

Alterations in pulmonary structure by elastase administration in a model of emphysema in mice is associated with functional disturbances.

Several experimental studies of pulmonary emphysema using animal models have been described in the literature. However, only a few of these studies have focused on the assessment of ergometric function as a non-invasive technique to validate the methodology used for induction of experimental emphysema. Additionally, functional assessments of emphysema are rarely correlated with morphological pulmonary abnormalities caused by induced emphysema. The present study aimed to evaluate the effects of elastase administered by tracheal puncture on pulmonary parenchyma and their corresponding functional impairment. This was evaluated by measuring exercise capacity in C57Bl/6 mice in order to establish a reproducible and safe methodology of inducing experimental emphysema. Thirty six mice underwent ergometric tests before and 28 days after elastase administration. Pancreatic porcine elastase solution was administered by tracheal puncture, which resulted in a significantly decreased exercise capacity, shown by a shorter distance run (-30.5%) and a lower mean velocity (-15%), as well as in failure to increase the elimination of carbon dioxide. The mean linear intercept increased significantly by 50% in tracheal elastase administration. In conclusion, application of elastase by tracheal function in C57Bl/6 induces emphysema, as validated by morphometric analyses, and resulted in a significantly lower exercise capacity, while resulting in a low mortality rate.

Fine-tuning of substrate architecture and surface chemistry promotes muscle tissue development.

Tissue engineering has been increasingly brought to the scientific spotlight in response to the tremendous demand for regeneration, restoration or substitution of skeletal or cardiac muscle after traumatic injury, tumour ablation or myocardial infarction. In vitro generation of a highly organized and contractile muscle tissue, however, crucially depends on an appropriate design of the cell culture substrate. The present work evaluated the impact of substrate properties, in particular morphology, chemical surface composition and mechanical properties, on muscle cell fate. To this end, aligned and randomly oriented micron (3.3±0.8 µm) or nano (237±98 nm) scaled fibrous poly(ε-caprolactone) non-wovens were processed by electrospinning. A nanometer-thick oxygen functional hydrocarbon coating was deposited by a radio frequency plasma process. C2C12 muscle cells were grown on pure and as-functionalized substrates and analysed for viability, proliferation, spatial orientation, differentiation and contractility. Cell orientation has been shown to depend strongly on substrate architecture, being most pronounced on micron-scaled parallel-oriented fibres. Oxygen functional hydrocarbons, representing stable, non-immunogenic surface groups, were identified as strong triggers for myotube differentiation. Accordingly, the highest myotube density (28±15% of total substrate area), sarcomeric striation and contractility were found on plasma-coated substrates. The current study highlights the manifold material characteristics to be addressed during the substrate design process and provides insight into processes to improve bio-interfaces.