Osteoinductive 3D scaffolds prepared by blend centrifugal spinning for long-term delivery of osteogenic supplements

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems. The current study delivers a three-dimensional (3D) scaffold prepared by blend centrifugal spinning loaded with the osteogenic supplements (OS) β-glycerol phosphate, ascorbate-2-phosphate and dexamethasone. The OS were successfully encapsulated into a fibrous scaffold and showed sustained release for 30 days. Furthermore, biological testing showed the osteoinductive properties of the scaffolds on a model of human mesenchymal stem cells and stimulatory effect on a model of osteoblasts. The osteoinductive properties were further proved in vivo in critical size defects of rabbits. The amount of bone trabecules was bigger compared to control fibers without OS. The results indicate that due to its long-term drug releasing properties, single step fabrication process and 3D structure, the system shows ideal properties for use as a cell-free bone implant in tissue-engineering.

Bone regeneration is a long-term process requiring proper scaffolding and drug delivery systems.     

MgTiO3:Mn4+ a multi-reading temperature nanoprobe

MgTiO₃ nanoparticles doped with Mn⁴⁺, with homogeneous size ranging about 63.1 ± 9.8 nm, were synthesized by a molten salt assisted sol gel method. These nanoparticles have been investigated as optical thermal sensors. The luminescence of tetravalent manganese ion in octahedral environment within the perovskite host presents drastic variations with temperature. Three different thermometry approaches have been proposed and characterized. Two luminescence intensity ratios are studied. Firstly between the two R-lines of Mn⁴⁺ emission at low temperature (−250 °C and −90 °C) with a maximal sensitivity of 0.9% °C⁻¹, but also secondly between ²E → ⁴A₂ (R-line) and the ⁴T₂ → ⁴A₂ transitions. This allows studying the temperature variation within a larger temperature range (−200 °C to 50 °C) with a sensitivity between 0.6% °C⁻¹ and 1.2% °C⁻¹ over this range. The last proposed method is the study of the lifetime variation versus temperature. The effective lifetime value corresponds to a combination of transitions from two excited energy levels of the tetravalent manganese (²E and ⁴T₂) in thermal equilibrium toward the fundamental ⁴A₂ state. Since the more energetic transition (⁴T₂ → ⁴A₂) is spin-allowed, contrary to the ²E → ⁴A₂ one, the lifetime drastically decreases with the increase in temperature leading to an impressive high sensitivity value of 4.1% °C⁻¹ at 4 °C and an exceptional temperature resolution of 0.025 °C. According to their optical features, MgTiO₃:Mn⁴⁺ nanoparticles are indeed suitable candidates for the luminescence temperature probes at the nanoscale over several temperature ranges.

Luminescence properties of MgTiO₃ nanoparticles doped with Mn⁴⁺ ions are investigated for precise temperature determination.     

High expression of the RNA-binding protein RBPMS2 in gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are often associated with KIT or PDGFRA gene mutations. GIST cells might arise from the interstitial cells of Cajal (ICCs) or from a mesenchymal precursor that is common to ICCs and smooth muscle cells (SMCs). Here, we analyzed the mRNA and protein expression of RNA-Binding Protein with Multiple Splicing-2 (RBPMS2), an early marker of gastrointestinal SMC precursors, in human GISTs (n = 23) by in situ hybridization, quantitative RT-PCR analysis and immunohistochemistry. The mean RBPMS2 mRNA level in GISTs was 42-fold higher than in control gastrointestinal samples (p < 0.001). RBPMS2 expression was not correlated with KIT and PDGFRA expression levels, but was higher in GISTs harboring KIT mutations than in tumors with wild type KIT and PDGFRA or in GISTs with PDGFRA mutations that were characterized by the lowest RBPMS2 levels. Moreover, RBPMS2 levels were 64-fold higher in GIST samples with high risk of aggressive behavior than in adult control gastrointestinal samples and 6.2-fold higher in high risk than in low risk GIST specimens. RBPMS2 protein level was high in 87% of the studied GISTs independently of their histological classification. Finally, by inhibiting the KIT signaling pathway in GIST882 cells, we show that RBPMS2 expression is independent of KIT activation. In conclusion, RBPMS2 is up-regulated in GISTs compared to normal adult gastrointestinal tissues, indicating that RBPMS2 might represent a new diagnostic marker for GISTs and a potential target for cancer therapy.     

Functionalities and input methods for recording food intake: A systematic review

BackgroundIncreasing healthcare costs related to lifestyle-related chronic diseases require new solutions. Research on self-management tools is expanding and many new tools are emerging. Recording food intake is a key functionality in many of these tools. Nutrition monitoring is a relevant method to gain an overview of factors influencing health. However, keeping a food diary often constitutes a challenge for a patient, and developing a user-friendly and useful electronic food diary is not straightforward.PurposeTo gain insight into the existing approaches to recording food intake, and to analyze current functionalities and input methods.MethodsWe searched digital libraries, vendor markets and social networks focusing on nutrition. Selection criteria were publications written in English, and patient-oriented tools that offered recording of food intake or nutrition. The system properties that we searched for were types of data, types of terminal, target population, and types of reports and sharing functionalities. We summarized the properties based on their frequency in the reviewed sample.Results31 publications met the selection criteria. The majority of the identified food recording systems (67%) facilitated entry of food type and the consumed quantity of food; 16% of the systems were able to record more than one type of data. The three most frequent target populations were people with obesity, diabetes and overweight. Mobile phones were used as terminals in 35% of the cases, personal computers (PCs) in 29%, and personal digital assistants in 23%. Only 10% supported both PCs and mobile phones. Data sharing was provided by 71% and reports by 51% of the systems. We searched for apps in Google Play and the Apple Store and tested 45 mobile applications that stored food intake data, of which 62% supported recording of types of food, 24% recording of carbohydrate intake and 15% recording of calorie intake. The majority of the mobile applications offered some kind of reports and data sharing, mainly via All of the tested social-network-enabled applications supported access from a personal computer and a mobile phone, search in a food database, reports, graphical presentation, listing of favorite foods, overview of own meals, and entering of consumed food type and quantity.ConclusionThe analyzed apps reflected a variety of approaches to recording food intake and nutrition using different terminals – mostly mobile phones (35%), followed by PCs (29%) and PDAs (23%) for older studies, designed mainly for users with obesity (45%), diabetes mellitus (42%) and overweight (32%), or people who want to stay healthy (10%). The majority of the reviewed applications (67%) offered only input of food type and quantity. All approaches (n = 31), except for two, relied on manual input of data, either by typing or by selecting a food type from a database. The exceptions (n = 2) used a barcode scanning function. Users of mobile phone applications were not limited to data recording, but could view their data on the screen and send it via email. The tested web applications offered similar functionalities for recording food intake. The systems studied provided some degree of personalization: users can access some systems via PCs or mobile phones and they can choose among various types of data input content for recording food intake. Many functions, such as search in a food database, reports, graphical presentation, listing of favorite foods, and overview of the user's own meals, are optimized to simplify the recording process and save time. Data sharing and reports are common features of the reviewed systems. However, none use the user's recorded food history to make suggestions on new nutritional intake, during the food recording process. This may be an area for future research.     

On the monitoring of dabigatran treatment in “real life” patients with atrial fibrillation

Introduction

The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.

Material and methods

Ninety AF patients (68 ± 9 years, 67% men, mean CHADS₂ score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT.

Results

Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r² = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels.

Conclusions

HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke.     

Clinical picture of cardiogenic shock as primary manifestation of sepsis originating in the knee joint

This is a case report of a male with infection in the right knee joint progressing to sepsis. However, the patient initially complained mainly of dysarthria and breathlessness. He rapidly developed respiratory insufficiency with the loss of consciousness. Echocardiography revealed severe dysfunction of the left ventricle, suggesting acute failure of the chronically failing heart. The patient was referred to a coronary care unit. Only the further course of the disease, particularly progression of the local finding on the right leg and development of fever, together with significantly elevated inflammatory parameters in laboratory findings, resulted in the diagnosis of sepsis which also included myocardial dysfunction and brain hypoperfusion manifested as dysarthria.     

Survivin gene promoter polymorphism -31G/C as a risk factor for keratocystic odontogenic tumor development

Several single nucleotide polymorphisms in survivin gene promoters, notably -31G/C, have been shown to modulate the expression and activity of the survivin protein. Consequently, the -31G/C polymorphism has been identified as a risk factor for the development of several types of tumors. The aim of this study was to investigate a possible association between the -31G/C polymorphism and the risk for keratocystic odontogenic tumor (KCOT) development. DNA from 52 biopsy specimens of KCOTs and from 82 buccal swabs of healthy individuals was subjected to PCR restriction fragment length polymorphism analysis to identify individual genotypes. The distribution of genotypes in KCOT and control groups, respectively, was: GG: 30 (57.7%) vs. 26 (31.7%); CG: 17 (32.7%) vs. 45 (54.9%); and CC: 5 (9.6%) vs. 11 (13.4%), respectively. These differences were statistically significant. The G allele was more common in the KCOT group than in the control group: 76 (74%) vs. 96 (59%), respectively. Logistic regression analysis showed that GC heterozygotes had a considerably decreased susceptibility for KCOTs compared with GG homozygotes. The same was true for GC+CC vs. GG. The GG genotype of the -31G/C polymorphism might be a risk factor for KCOT development.