Enzyme-functionalized biomimetic apatites: concept and perspectives in view of innovative medical approaches

Biomimetic nanocrystalline calcium-deficient apatite compounds are particularly attractive for the setup of bioactive bone-repair scaffolds due to their high similarity to bone mineral in terms of chemical composition, structural and substructural features. As such, along with the increasingly appealing development of moderate temperature engineered routes for sample processing, they have widened the armamentarium of orthopedic and maxillofacial surgeons in the field of bone tissue engineering. This was made possible by exploiting the exceptional surface reactivity of biomimetic apatite nanocrystals, capable of easily exchanging ions or adsorbing (bio)molecules, thus leading to highly-versatile drug delivery systems. In this contribution we focus on the preparation of hybrid materials combining biomimetic nanocrystalline apatites and enzymes (lysozyme and subtilisin). This paper reports physico-chemical data as well as cytotoxicity evaluations towards Cal-72 osteoblast-like cells and finally antimicrobial assessments towards selected strains of interest in bone surgery. Biomimetic apatite/enzyme hybrids could be prepared in varying buffers. They were found to be non-cytotoxic toward osteoblastic cells and the enzymes retained their biological activity (e.g. bond cleavage or antibacterial properties) despite the immobilization and drying processes. Release properties were also examined. Beyond these illustrative examples, the concept of biomimetic apatites functionalized with enzymes is thus shown to be useable in practice, e.g. for antimicrobial purposes, thus widening possible therapeutic perspectives

Permafrost and active layer research on James Ross Island: An overview

This study summarizes the current state of the active layer and permafrost research on James Ross Island. The analysis of climate parameters covers the reference period 2011–2017. The mean annual air temperature at the AWS-JGM site was -6.9°C (ranged from -3.9°C to -8.2°C). The mean annual ground temperature at the depth of 5 cm was -5.5°C (ranged from -3.3°C to -6.7°C) and it also reached -5.6°C (ranged from -4.0 to -6.8°C) at the depth of 50 cm. The mean daily ground temperature at the depth of 5 cm correlated moderately up to strongly with the air temperature depending on the season of the year. Analysis of the snow effect on the ground thermal regime confirmed a low insulating effect of snow cover when snow thickness reached up to 50 cm. A thicker snow accumulation, reaching at least 70 cm, can develop around the hyaloclastite breccia boulders where a well pronounced insulation effect on the near-surface ground thermal regime was observed. The effect of lithology on the ground physical properties and the active layer thickness was also investigated. Laboratory analysis of ground thermal properties showed variation in thermal conductivity (0.3 to 0.9 W m-1 K-1). The thickest active layer (89 cm) was observed on the Berry Hill slopes site, where the lowest thawing degree days index (321 to 382°C·day) and the highest value of thermal conductivity (0.9 W m-1 K-1) was observed. The clearest influence of lithological conditions on active layer thickness was observed on the CALM-S grid. The site comprises a sandy Holocene marine terrace and muddy sand of the Whisky Bay Formation. Surveying using a manual probe, ground penetrating radar, and an electromagnetic conductivity meter clearly showed the effect of the lithological boundary on local variability of the active layer thickness

Continuous Adaptive Evolution of a Fast-Growing Corynebacterium glutamicum Strain Independent of Protocatechuate

Graf M, Haas T, Mueller F, et al. Continuous Adaptive Evolution of a Fast-Growing Corynebacterium glutamicum Strain Independent of Protocatechuate. Frontiers in Microbiology . 2019;10: 1648.Corynebacterium glutamicum is a commonly applied host for the industrial production of amino acids. While valued for its robustness, it is somewhat inferior to competing strains such as Escherichia coli because of the relatively low growth rate of 0.40 h(-1) in synthetic, industrial media. Accordingly, adaptive laboratory evolution (ALE) experiments were performed in continuous cultivation mode to select for a growth-improved host. To ensure industrial attractiveness, this ALE study aimed at a reduction of dependency on costly growth-boosting additives such as protocatechuate (RCA) or complex media supplements. Consequently, double selection pressures were installed consisting of a steady increase in growth rate demands and a parallel reduction of complex medium fractions. Selection yielded C. glutamicum EVO5 achieving 0.54 h(-1) and 1.03g(Glc) g(CDW)(-1) h(-1) in minimal medium without above mentioned supplements. Sequencing revealed 10 prominent mutations, three of them in key regulator genes

Mitochondrial Haplogroups, Control Region Polymorphisms and Malignant Melanoma: A Study in Middle European Caucasians

Because mitochondria play an essential role in energy metabolism, generation of reactive oxygen species (ROS), and apoptosis, sequence variation in the mitochondrial genome has been postulated to be a contributing factor to the etiology of multifactorial age-related diseases, including cancer. The aim of the present study was to compare the frequencies of mitochondrial DNA (mtDNA) haplogroups as well as control region (CR) polymorphisms of patients with malignant melanoma (n = 351) versus those of healthy controls (n = 1598) in Middle Europe.Using primer extension analysis and DNA sequencing, we identified all nine major European mitochondrial haplogroups and known CR polymorphisms. The frequencies of the major mitochondrial haplogroups did not differ significantly between patients and control subjects, whereas the frequencies of the one another linked CR polymorphisms A16183C, T16189C, C16192T, C16270T and T195C were significantly higher in patients with melanoma compared to the controls. Regarding clinical characteristics of the patient cohort, none of the nine major European haplogroups was associated with either Breslow thickness or distant metastasis. The CR polymorphisms A302CC-insertion and T310C-insertion were significantly associated with mean Breslow thickness, whereas the CR polymorphism T16519C was associated with metastasis.Our results suggest that mtDNA variations could be involved in melanoma etiology and pathogenesis, although the functional consequence of CR polymorphisms remains to be elucidated

Mesenchymal stromal cells for treatment of steroid-refractory GvHD : a review of the literature and two pediatric cases

Severe acute graft versus host disease (GvHD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. Human mesenchymal stromal cells (MSCs) play an important role in endogenous tissue repair and possess strong immune-modulatory properties making them a promising tool for the treatment of steroid-refractory GvHD. To date, a few reports exist on the use of MSCs in treatment of GvHD in children indicating that children tend to respond better than adults, albeit with heterogeneous results. We here present a review of the literature and the clinical course of two instructive pediatric patients with acute steroid-refractory GvHD after haploidentical stem cell transplantation, which exemplify the beneficial effects of third-party transplanted MSCs in treatment of acute steroid-refractory GvHD. Moreover, we provide a meta-analysis of clinical studies addressing the outcome of patients with steroid-refractory GvHD and treatment with MSCs in adults and in children (n = 183; 122 adults, 61 children). Our meta-analysis demonstrates that the overall response-rate is high (73.8%) and confirms, for the first time, that children indeed respond better to treatment of GvHD with MSCs than adults (complete response 57.4% vs. 45.1%, respectively). These data emphasize the significance of this therapeutic approach especially in children and indicate that future prospective studies are needed to assess the reasons for the observed differential response-rates in pediatric and adult patients. Additional file 1: MSCs expansion and release criteria.his file contains a detailed description of the MSCs expansion and release criteria for Case A and Case B

Touch Medicine - a complementary therapeutic approach exemplified by the treatment of depression

Skin-to-skin-contact presents the earliest sensory experience of men and animals. Deprivation of age-relevant touch experiences during infancy results in compromised psychosocial and biological development. The 2021 Nobel Prize in Physiology or Medicine has been awarded for the discoveries of receptors for temperature and touch. Clinical studies have demonstrated the benefit of professional salutary touch for prevention and treatment of various illnesses. However, in the present practice of medicine the application of salutary touch does not meet adequate interest. Proposing a new medical discipline "Touch Medicine" we link the findings of modern touch research to clinical medicine. The treatment of depression which we conceive primarily as a disease afflicting the body will serve as an example to demonstrate the usefulness of touch therapy. Controlled studies and systematic reviews have convincingly shown antidepressive, anxiolytic and analgesic effects of salutary touch. The effectiveness and efficacy of touch therapy has also been demonstrated in many areas such as neonatology, pediatrics, oncology, and geriatrics. We discuss the underlying mechanisms on various explanatory levels including interoceptive and oxytocinergic mechanisms as well as the role of C tactile afferent nerve fibers

Lignin-based polyurethane materials

Four technical lignins (Alcell, Indulin AT, Sarkanda and Curan 27-11P) were used as macromonomers in the synthesis of polyurethane materials following two global approaches. In the first one Alcell and Indulin AT lignins were used directly as co-monomers in combination with a linear polycaprolactone (PCL) in order to produce polyurethane elastomers where lignin content varied between 10 and 25% (w/w) with respect to polyol mixture (PCL+lignin). The thermomechanical properties of the resulting materials were determined by dynamical mechanical analysis (DMA), differential scanning calorimetry (DSC) and swelling tests. In lignin-based elastomers Indulin AT showed to be more efficiently incorporated in the polyurethane network compared with Alcell lignin. Elastomers prepared with Indulin AT lignin exhibited a cross-linking density and storage modulus (rubbery plateau) higher than those of Alcell lignin-based counterpart and a lower soluble fraction. For both Alcell and Indulin AT based elastomers the glass transition temperature increased and extended over a wide temperature range with the increase of lignin content. The second approach consisted of producing rigid polyurethane foams (RPU) using ligninbased polyols obtained after chemical modification by an oxypropylation procedure. Two polyol formulations (20/80 and 30/70, in what concerns the weight ratios between lignin and propylene oxide, PO), were used in RPU formulations and their content varied from 0 to 100% (w/w with respect to a commercial polyol, used as a reference). The resulting RPU foams were characterized in terms of density, mechanical properties, conductivity and morphology. The prepared RPU foams with lignin-based polyols presented properties, very similar to those obtained from conventional commercial polyols. RPU foams prepared with 30/70 polyols exhibited improved properties comparatively to those arising from 20/80 formulations. Exceptions were however detected in RPU foams prepared with all Sarkanda lignin based polyols and Curan 27-11P 30/70 formulation, which were found to be inadequate for RPU formulation

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with 5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research