Fixation of a double-coated titanium-hydroxyapatite focal knee resurfacing implant A 12-month study in sheep

SummaryObjectiveFocal cartilage lesions according to International Cartilage Repair Society (ICRS) grade 3–4 in the medial femoral condyle may progress to osteoarthritis. When treating such focal lesions with metallic implants a sound fixation to the underlying bone is mandatory. We developed a monobloc unipolar cobalt-chrome (Co-Cr) implant with a double coating; first a layer of commercially pure titanium (c.p.Ti) on top of which a layer of hydroxyapatite (HA) was applied. We hypothesised that such a double coating would provide long-lasting and adequate osseointegration.Design (materials and methods)Unilateral medial femoral condyles of 10 sheep were operated. The implants were inserted in the weight-bearing surface and immediate weight-bearing was allowed. Euthanasia was performed at 6 (three animals) or 12 months (six animals). Osseointegration was analysed with micro-computer tomography (CT), light microscopy and histomorphometric analyses using backscatter scanning electron microscopy (B-SEM) technique.ResultsAt 6 months one specimen out of three showed small osteolytic areas at the hat and at 12 months two specimens out of six showed small osteolytic areas at the hat, no osteolytical areas were seen around the peg at any time point. At both time points, a high total bone-to-implant contact was measured with a mean (95% confidence interval – CI) of 90.6 (79–102) at 6 months and 92.3 (89–95) at 12 months, respectively.ConclusionsA double coating (Ti + HA) of a focal knee resurfacing Co-Cr implant was presented in a sheep animal model. A firm and consistent bond to bone under weight-bearing conditions was shown up to 1 year

Potential of heart fatty-acid binding protein, neurofilament light, interleukin-10 and S100 calcium-binding protein B in the acute diagnostics and severity assessment of traumatic brain injury

Background: There is substantial interest in blood biomarkers as fast and objective diagnostic tools for traumatic brain injury (TBI) in the acute setting. Methods: Adult patients (≥18) with TBI of any severity and indications for CT scanning and orthopaedic injury controls were prospectively recruited during 2011–2013 at Turku University Hospital, Finland. The severity of TBI was classified with GCS: GCS 13–15 was classified as mild (mTBI); GCS 9–12 as moderate (moTBI) and GCS 3–8 as severe (sTBI). Serum samples were collected within 24 hours of admission and biomarker levels analysed with high-performance kits. The ability of biomarkers to distinguish between severity of TBI and CT-positive and CT-negative patients was assessed. Results: Among 189 patients recruited, neurofilament light (NF-L) was obtained from 175 patients with TBI and 40 controls. S100 calcium-binding protein B (S100B), heart fatty-acid binding protein (H-FABP) and interleukin-10 (IL-10) were analysed for 184 patients with TBI and 39 controls. There were statistically significant differences between levels of all biomarkers between the severity classes, but none of the biomarkers distinguished patients with moTBI from patients with sTBI. Patients with mTBI discharged from the ED had lower levels of IL-10 (0.26, IQR=0.21, 0.39 pg/mL), H-FABP (4.15, IQR=2.72, 5.83 ng/mL) and NF-L (8.6, IQR=6.35, 15.98 pg/mL) compared with those admitted to the neurosurgical ward, IL-10 (0.55, IQR=0.31, 1.42 pg/mL), H-FABP (6.022, IQR=4.19, 20.72 ng/mL) and NF-L (13.95, IQR=8.33, 19.93 pg/mL). We observed higher levels of H-FABP and NF-L in older patients with mTBI. None of the biomarkers or their combinations was able to distinguish CT-positive (n=36) or CT-negative (n=58) patients with mTBI from controls. Conclusions: S100B, H-FABP, NF-L and IL-10 levels in patients with mTBI were significantly lower than in patients with moTBI and sTBI but alone or in combination, were unable to distinguish patients with mTBI from orthopaedic controls. This suggests these biomarkers cannot be used alone to diagnose mTBI in trauma patients in the acute setting. Data availability statement: Data are available on reasonable request. De-identified clinical, imaging and biochemical data not published within the article can be shared with a qualified investigator by request

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma

PurposeThe two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16.MethodsIn total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data.ResultsTumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups.ConclusionTumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.</div

Admission Levels of Interleukin 10 and Amyloid β 1–40 Improve the Outcome Prediction Performance of the Helsinki Computed Tomography Score in Traumatic Brain Injury

BACKGROUND: Blood biomarkers may enhance outcome prediction performance of head computed tomography scores in traumatic brain injury (TBI). OBJECTIVE: To investigate whether admission levels of eight different protein biomarkers can improve the outcome prediction performance of the Helsinki computed tomography score (HCTS) without clinical covariates in TBI. MATERIALS AND METHODS: ighty-two patients with computed tomography positive TBIs were included in this study. Plasma levels of β-amyloid isoforms 1–40 (Aβ40) and 1–42 (Aβ42), glial fibrillary acidic protein, heart fatty acid-binding protein, interleukin 10 (IL-10), neurofilament light, S100 calcium-binding protein B, and total tau were measured within 24 h from admission. The patients were divided into favorable (Glasgow Outcome Scale—Extended 5–8, n = 49) and unfavorable (Glasgow Outcome Scale—Extended 1–4, n = 33) groups. The outcome was assessed 6–12 months after injury. An optimal predictive panel was investigated with the sensitivity set at 90–100%. RESULTS: The HCTS alone yielded a sensitivity of 97.0% (95% CI: 90.9–100) and specificity of 22.4% (95% CI: 10.2–32.7) and partial area under the curve of the receiver operating characteristic of 2.5% (95% CI: 1.1–4.7), in discriminating patients with favorable and unfavorable outcomes. The threshold to detect a patient with unfavorable outcome was an HCTS > 1. The three best individually performing biomarkers in outcome prediction were Aβ40, Aβ42, and neurofilament light. The optimal panel included IL-10, Aβ40, and the HCTS reaching a partial area under the curve of the receiver operating characteristic of 3.4% (95% CI: 1.7–6.2) with a sensitivity of 90.9% (95% CI: 81.8–100) and specificity of 59.2% (95% CI: 40.8–69.4). CONCLUSION: Admission plasma levels of IL-10 and Aβ40 significantly improve the prognostication ability of the HCTS after TBI

A 3D cellular context for the macromolecular world

We report the outcomes of the discussion initiated at the workshop entitled A 3D Cellular Context for the Macromolecular World and propose how data from emerging three-dimensional (3D) cellular imaging techniques—such as electron tomography, 3D scanning electron microscopy and soft X-ray tomography—should be archived, curated, validated and disseminated, to enable their interpretation and reuse by the biomedical community

A new resorbable device for ligation of blood vessels - A pilot study

<p>Abstract</p> <p>Background</p> <p>During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency.</p> <p>Methods</p> <p>The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version.</p> <p>The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs.</p> <p>Results</p> <p>The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, <it>n </it>= 11) and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, <it>n </it>= 11). Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance.</p> <p>Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached to the ovarian pedicle could be seen with ultrasound, and vessel compression and occlusion were verified by histology.</p> <p>Conclusions</p> <p>Tests of functionality of the device showed complete haemostasis and good tissue grip. Devices with a band of sufficient length were easily applied and tightened in tissue.</p

Genome-wide linkage scan for colorectal cancer susceptibility genes supports linkage to chromosome 3q

Background: Colorectal cancer is one of the most common causes of cancer-related mortality. The disease is clinically and genetically heterogeneous though a strong hereditary component has been identified. However, only a small proportion of the inherited susceptibility can be ascribed to dominant syndromes, such as Hereditary Non-Polyposis Colorectal Cancer (HNPCC) or Familial Adenomatous Polyposis (FAP). In an attempt to identify novel colorectal cancer predisposing genes, we have performed a genome-wide linkage analysis in 30 Swedish non-FAP/non-HNPCC families with a strong family history of colorectal cancer.Methods: Statistical analysis was performed using multipoint parametric and nonparametric linkage.Results: Parametric analysis under the assumption of locus homogeneity excluded any common susceptibility regions harbouring a predisposing gene for colorectal cancer. However, several loci on chromosomes 2q, 3q, 6q, and 7q with suggestive linkage were detected in the parametric analysis under the assumption of locus heterogeneity as well as in the nonparametric analysis. Among these loci, the locus on chromosome 3q21.1- q26.2 was the most consistent finding providing positive results in both parametric and nonparametric analyses Heterogeneity LOD score (HLOD) = 1.90, alpha = 0.45, Non-Parametric LOD score (NPL) = 2.1).Conclusion: The strongest evidence of linkage was seen for the region on chromosome 3. Interestingly, the same region has recently been reported as the most significant finding in a genome-wide analysis performed with SNP arrays; thus our results independently support the finding on chromosome 3q

PDBe: Protein Data Bank in Europe

The Protein Data Bank in Europe (PDBe; pdbe.org) is a partner in the Worldwide PDB organization (wwPDB; wwpdb.org) and as such actively involved in managing the single global archive of biomacromolecular structure data, the PDB. In addition, PDBe develops tools, services and resources to make structure-related data more accessible to the biomedical community. Here we describe recently developed, extended or improved services, including an animated structure-presentation widget (PDBportfolio), a widget to graphically display the coverage of any UniProt sequence in the PDB (UniPDB), chemistry- and taxonomy-based PDB-archive browsers (PDBeXplore), and a tool for interactive visualization of NMR structures, corresponding experimental data as well as validation and analysis results (Vivaldi)