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One of the most widely used materials for bone graft substitution is β-Tricalcium phosphate (β-TCP; β-Ca 3 (PO 4 ) 2 ). β-TCP is typically produced by sintering in air or vacuum. During this process, evaporation of phosphorus (P) species occurs, leading to the formation of a calcium-rich alkaline layer. It was recently shown that the evaporation of P species could be prevented by co-sintering β-TCP with dicalcium phosphate (DCPA; CaHPO 4 ; mineral name: monetite). The aim of this study was to see how a change of sintering atmosphere could affect the physico-chemical and biological properties of β-TCP. For this purpose, three experimental groups were considered: β-TCP cylinders sintered in air and subsequently polished to remove the surface layer (control group); the same polished cylinders after subsequent annealing at 500 °C in air to generate a calcium-rich alkaline layer (annealed group); and finally, β-TCP cylinders sintered in a monetite-rich atmosphere and subsequently polished (monetite group). XPS analysis confirmed that cylinders from the annealed group had a significantly higher Ca/P molar ratio at their surface than that of the control group while this ratio was significantly lower for the cylinders from the monetite group. Sintering β-TCP in the monetite-rich atmosphere significantly reduced the grain size and increased the density. Changes of surface composition affected the activity of osteoclasts seeded onto the surfaces, since annealed β-TCP cylinders were significantly less resorbed than β-TCP cylinders sintered in the monetite-rich atmosphere. This suggests that an increase of the surface Ca/P molar ratio leads to a decrease of osteoclastic resorption. STATEMENT OF SIGNIFICANCE: Minimal changes of surface and bulk (< 1%) composition have major effects on the ability of osteoclasts to resorb β-tricalcium phosphate (β-TCP), one of the most widely used ceramics for bone substitution. The results presented in this study are thus important for the calcium phosphate community because (i) β-TCP may have up to 5% impurities according to ISO and ASTM standards and still be considered to be "pure β-TCP", (ii) β-TCP surface properties are generally not considered during biocompatibility assessment and (iii) a rationale can be proposed to explain the various inconsistencies reported in the literature on the biological properties of β-TCP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction : Cryopreservation of bipronuclear (2PN) stage zygotes is an integral part of IVF laboratory practice in countries with strict embryo culture legislation. Vitrification of zygotes is compatible with several strategies in infertility treatments holding a freeze-all indication and allows for effective workload management in settings with limited resources. Although it yields high survival rates and clinical outcomes, the ideal timing to commence vitrification of zygotes is elusive while it is empirically practiced in the window between 17 and 21 h post-insemination (hpi). We aimed to deduce the association between pregnancy rate and the time interval from insemination (IVF and ICSI) to vitrification to contribute to the standardization ofzygote cryopreservation. Methods : A retrospective analysis of data on vitrification timings and pregnancy outcomes collected between 2011 and 2019 was performed. All included women received an embryo transfer after warming of vitrified zygotes at the 2PN stage. Results : A total of 468 embryo transfers were included of which 182 (38.9%) resulted in pregnancy and 286 (61.1%) not. Vitrification was on average performed 18.74 ±0.63 hpi in the pregnant group and 18.62 ± 0.64 hpi in the non-pregnant group (OR 1.36, 95% CI 1.01; 1.83, p = 0.045). A multivariate analysis controlling for uterine pathologies, maternal age, AMH, the number of MII oocytes, previous history of pregnancy success, endometriosis, AFC, nicotine intake and male factor infertility showed no predictive value of vitrification timing on pregnancy rate. Three time intervals between insemination and vitrification were defined: 17:00 to 18:00 hpi (Group A), 18:01 to 19:00 hpi (Group B) and 19:01 to 21:00 hpi (Group C). Pregnancy occurred in 40/130 women (30.80%) in Group A, in 115/281 women (40.90%) in Group B and in 27/57 women (47.40%) in Group C. Univariate but not multivariate analysis showed a significantly higher pregnancy rate after the latest time interval between insemination and 2PN vitrification when compared to the earliest (Group C vs . A, OR 2.03, 95% CI 1.07; 3.84, p = 0.031). Discussion: These findings encourage further investigation on the impact of vitrification timing on clinical outcomes and hold the potential to standardize cryopreservation of zygotes from IVF/ICSI cycles to eventually improve the quality of long-term ART outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Makieva, Stähli, Xie, Gil, Sachs and Leeners.)

Purpose: Surgery remains the only treatment allowing for a significant and sustainable weight loss in case of severe obesity. Patients undergo a specific multidisciplinary preparation and selection before the operation. This study aims to correlate the psychosocial profile with the likelihood of undergoing bariatric surgery in patients enrolled in the preparation program of a Swiss reference center., Methods: All patients referred to an obesity center between January 1, 2016, and June 30, 2017, seeking a first bariatric procedure were included. Socio-demographic data, BMI, preoperative psychological and dietary evaluations were collected. Usually, the preoperative process lasts 1 year. Patients who left the preparation or who had not undergone surgery after more than 2 years of follow-up were considered withdrawers. Surgery completion predictors were reviewed with bivariate analysis and socio-demographic clusters established using the K-means method., Results: Out of a total of 221 patients, 99 (45%) patients had not undergone bariatric surgery 2 years after their first consultation. The patients were divided into four distinct socio-demographic clusters, among which a particularly deprived one. Criteria such as unfavorable psychological (p < 0.001) and dietary (p < 0.001) evaluations, and male gender (p < 0.05) were significantly associated with non-operation, unlike socio-demographic indicators and clusters (p > 0.1)., Conclusion: Almost half of the patients starting a bariatric program are not operated on, which is related to an unfavorable psychological or dietary evaluation and to the male gender. This study also demonstrates that a significant share of patients combines several factors of social deprivation, without influencing the likelihood of surgery completion., Level of Evidence: Level V: Descriptive study., (© 2021. The Author(s).)

Biomaterials can interact with cells directly, that is, by direct contact of the cells with the material surface, or indirectly, through soluble species that can be released to or uptaken from the surrounding fluids. However, it is difficult to characterise the relevance of this fluid-mediated interaction separately from the topography and composition of the substrate, because they are coupled variables. These fluid-mediated interactions are amplified in the case of highly reactive calcium phosphates (CaPs) such as biomimetic calcium deficient hydroxyapatite (CDHA), particularly in static in vitro cultures. The present work proposes a strategy to decouple the effect of ion exchange from topographical features by adjusting the volume ratio between the cell culture medium and biomaterial (V CM /V B ). Increasing this ratio allowed mitigating the drastic ionic exchanges associated to the compositional changes experienced by the material exposed to the cell culture medium. This strategy was validated using rat mesenchymal stem cells (rMSCs) cultured on CDHA and beta-tricalcium phosphate (β-TCP) discs using different V CM /V B ratios. Whereas in the case of β-TCP the cell response was not affected by this ratio, a significant effect on cell adhesion and proliferation was found for the more reactive CDHA. The ionic exchange, produced by CDHA at low V CM /V B , altered cell adhesion due to the reduced number of focal adhesions, caused cell shrinkage and further rMCSs apoptosis. This was mitigated when using a high V CM /V B , which attenuated the changes of calcium and phosphate concentrations in the cell culture medium, resulting in rMSCs spreading and a viability over time. Moreover, rMSCs showed an earlier expression of osteogenic genes on CDHA compared to sintered β-TCP when extracellular calcium fluctuations were reduced., Statement of Significance: Fluid mediated interactions play a significant role in the bioactivity of calcium phosphates. Ionic exchange is amplified in the case of biomimetic hydroxyapatite, which makes the in vitro characterisation of cell-material interactions especially challenging. The present work proposes a novel and simple strategy to explore the mechanisms of interaction of biomimetic and sintered calcium phosphates with mesenchymal stem cells. The effects of topography and ion exchange are analysed separately by modifying the volume ratio between cell culture medium and biomaterial. High ionic fluctuations interfered in the maturation of focal adhesions, hampering cell adhesion and leading to increased apoptosis and reduced proliferation rate., (Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

β-Tricalcium phosphate (β-TCP) platelets synthesized in ethylene glycol offer interesting geometries for nano-structured composite bone substitutes but were never crystallographically analyzed. In this study, powder X-ray diffraction and Rietveld refinement revealed a discrepancy between the platelet structure and the known β-TCP crystal model. In contrast, a model featuring partial H for Ca substitution and the inversion of P1O 4 tetrahedra, adopted from the whitlockite structure, allowed for a refinement with minimal misfits and was corroborated by HPO 4 2- absorptions in Fourier-transform IR spectra. The Ca/P ratio converged to 1.443 ± 0.003 (n = 36), independently of synthesis conditions. As a quantitative verification, the platelets were thermally decomposed into hydrogen-free β-TCP and β-calcium pyrophosphate which resulted in a global Ca/P ratio in close agreement with the initial β-TCP Ca/P ratio (ΔCa/P = 0.003) and with the chemical composition measured by inductively coupled plasma (ΔCa/P = 0.003). These findings thus describe for the first time a hydrogen-substituted β-TCP structure, i.e. a Mg-free whitlockite, represented by the formula Ca 21 - x (HPO 4 ) 2x (PO 4 ) 14 - 2x , where x = 0.80 ± 0.04, and may have implications for resorption properties of bone regenerative materials.

Objectives: In 2015, the International League Against Epilepsy (ILAE) issued a new status epilepticus (SE) classification, including a detailed semiologic axis. This study assesses frequencies of SE forms in a cohort of adult patients, and explores differences and practical implications as compared to a seizure-type-bound classification., Methods: The prospective adult SE registry of the Lausanne University Hospital (CHUV) was considered over 5 years (2011-2015); each SE episode was retrospectively reclassified for its semiology according to the new ILAE scheme. Mortality rates were retrieved for each subgroup of SE., Results: Among 488 SE episodes, according to the seizure-type-bound classification, 230 (47%) had a generalized convulsive, and 29 (6%) had a nonconvulsive SE in coma; both categories overlapped almost perfectly between the two classifications. However, the 84 episodes with focal SE without consciousness impairment and the 141 episodes with consciousness impairment were each translated into two major (and five sub-) categories of the new ILAE classification, having markedly different mortality rates. In addition, of 140 episodes labeled as focal motor SE according to the new classification, 54% had concomitant consciousness impairment, whereas 46% did not; again, mortality rates were heterogeneous., Significance: Although generalized convulsive and nonconvulsive SE in coma show an almost perfect correspondence across SE semiologic classifications, focal SE is markedly heterogeneous and appears to be better reflected in the new classification, offering more clinically relevant subdivisions, also differing in mortality rates. This refined knowledge may allow the development of clinical prognostic scores that are more precise than existing tools, and should be taken into account for epidemiologic studies., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Over the last years a new type of tubular plug flow reactor, the segmented flow tubular reactor (SFTR), has proven its versatility and robustness through the water-based synthesis of precipitates as varied as CaCO3, BaTiO3, Mn(1-x)NixC2O4·2H2O, YBa oxalates, copper oxalate, ZnS, ZnO, iron oxides, and TiO2 produced with a high powder quality (phase composition, particle size, and shape) and high reproducibility. The SFTR has been developed to overcome the classical problems of powder production scale-up from batch processes, which are mainly linked with mass and heat transfer. Recently, the SFTR concept has been further developed and applied for the synthesis of metals, metal oxides, and salts in form of nano- or micro-particles in organic solvents. This has been done by increasing the working temperature and modifying the particle carrying solvent. In this paper we summarize the experimental results for four materials prepared according to the polyol synthesis route combined with the SFTR. CeO2, Ni, Ag, and Ca3(PO4)2 nanoparticles (NPs) can be obtained with a production rate of about 1-10 g per h. The production was carried out for several hours with constant product quality. These findings further corroborate the reliability and versatility of the SFTR for high throughput powder production.

Both silicate-based bioactive glasses and copper ions have demonstrated angiogenic activity and therefore represent promising bioinorganic agents for the promotion of vascularization in tissue-engineered scaffolds. This study examined the effect of ionic release products from 45S5 Bioglass® doped with 0 and 2.5 wt.% CuO (BG and Cu-BG respectively) on the formation of capillary-like networks by SVEC4-10 endothelial cells (ECs) seeded in a three-dimensional (3D) type I collagen matrix. Copper and silicon release following 24h dissolution increased non-proportionally with Cu-BG concentration in cell culture medium, while calcium levels were decreased below the initial medium concentration. EC network length, connectivity, branching, quantified by means of a 3D morphometric image analysis method, as well as proliferation and metabolic activity were reduced in a dose-dependent fashion by BG and Cu-BG ionic release products. This reduction was less prominent for BG compared to an equivalent concentration of Cu-BG, which was attributed to a lower extent of silicon release and calcium consumption. Moreover, a CuCl2 dose equivalent to the highest concentration of Cu-BG exhibited no effect on ECs. In conclusion, while the previously reported pro-angiogenic activity of both Bioglass® and copper may not be reflected in a direct response of ECs, this study provides a maximum glass concentration for non-harmful angiogenic stimulation to be examined in future work., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Sodium-free phosphate-based glasses (PGs) doped with both SiO2 and TiO2 (50P2O5-40CaO-xSiO2-(10-x)TiO2, where x=10, 7, 5, 3, and 0mol%) were developed and characterised for controlled ion release applications in bone tissue engineering. Substituting SiO2 with TiO2 directly increased PG density and glass transition temperature, indicating a cross-linking effect of Ti on the glass network which was reflected by significantly reduced degradation rates in an aqueous environment. X-ray diffraction confirmed the presence of Ti(P2O7) in crystallised TiO2-containing PGs, and nuclear magnetic resonance showed an increase in Q(1) phosphate species with increasing TiO2 content. Substitution of SiO2 with TiO2 also reduced hydrophilicity and surface energy. In biological assays, MC3T3-E1 pre-osteoblasts effectively adhered to the surface of PG discs and the incorporation of TiO2, and hence higher stability of the PG network, significantly increased cell viability and metabolic activity indicating the biocompatibility of the PGs. Addition of SiO2 increased ionic release from the PG, which stimulated alkaline phosphatase (ALP) activity in MC3T3-E1 cells upon ion exposure. The incorporation of 3mol% TiO2 was required to stabilise the PG network against unfavourable rapid degradation in aqueous environments. However, ALP activity was greatest in PGs doped with 5-7mol% SiO2 due to up-regulation of ionic concentrations. Thus, the properties of PGs can be readily controlled by modifying the extent of Si and Ti doping in order to optimise ion release and osteoblastic differentiation for bone tissue engineering applications., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Owing to their adjustable dissolution properties, phosphate-based glasses (PGs) are promising materials for the controlled release of bioinorganics, such as copper ions. This study describes a vapour sorption method that allowed for the investigation of the kinetics and mechanisms of aqueous interactions of PGs of the formulation 50P2O5-30CaO-(20-x)Na2O-xCuO (x=0, 1, 5 and 10mol.%). Initial characterization was performed using (31)P magic angle spinning nuclear magnetic resonance and attenuated total reflectance-Fourier transform infrared spectroscopy. Increasing CuO content resulted in chemical shifts of the predominant Q(2) NMR peak and of the (POP)as and (PO(-)) Fourier transform infrared absorptions, owing to the higher strength of the POCu bond compared to PONa. Vapour sorption and desorption were gravimetrically measured in PG powders exposed to variable relative humidity (RH). Sorption was negligible below 70% RH and increased exponentially with RH from 70 to 90%, where it exhibited a negative correlation with CuO content. Vapour sorption in 0% and 1% CuO glasses resulted in phosphate chain hydration and hydrolysis, as evidenced by protonated Q(0)(1H) and Q(1)(1H) species. Dissolution rates in deionized water showed a linear correlation (R(2)>0.99) with vapour sorption. Furthermore, cation release rates could be predicted based on dissolution rates and PG composition. The release of orthophosphate and short polyphosphate species corroborates the action of hydrolysis and was correlated with pH changes. In conclusion, the agreement between vapour sorption and routine characterization techniques in water demonstrates the potential of this method for the study of PG aqueous reactions., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Three monoclonal antibodies [MAb], b-8, b-12, and b-15, have previously been shown to react with mammary carcinomas and with a restricted set of cells in normal human tissues [C. Stähli et al., Experientia (Basel), 41: 1377-1381, 1985; H. R. Zenklusen et al., Virchows Arch. Abt. A Pathol. Anat., 413: 3-10, 1988]. They are shown here to recognize the same high molecular weight acid soluble glycoprotein antigen. Lectin binding, biolabeling, and deglycosylation experiments demonstrate that it contains O-linked carbohydrate side chains with sialic acid and hexoses including fucose, galactose, and/or galactosamine but little if any mannose. These properties, typical of mucin-like glycoproteins, agree with the antigen expression on mucin-secreting epithelial surfaces (H. R. Zenklusen et al., Virchows Arch. Abt. A Pathol. Anat., 413:3-10, 1988). The antigen is thus named mucin-like carcinoma-associated antigen (MCA). The three MAb are shown to bind to three different epitopes on MCA. Two of these epitopes (MCA-b-8 and MCA-b-15) are O-linked carbohydrates, and one (MCA-b-15) contains sialic acid. The epitope MCA-b-12 is of peptide nature. Of various two-site sandwich enzyme immunoassays composed of different combinations of the three MAb, the one with MAb b-12 in both positions is selected for a serum assay. Analyses of tumor patients' sera demonstrate that this MCA enzyme immunoassay can be of use as a tumor marker assay for mammary carcinomas. The parameter MCA enzyme immunoassay is shown to differ from other parameters described in the literature.

Purified plasma fibronectin was digested sequentially by thrombin and cathepsin G or by cathepsin G alone and the degradation products and their gelatin-binding and heparin-binding fractions were analyzed in NaDodSO4-polyacrylamide gel electrophoresis followed by immunoblotting with a defined monoclonal anti-fibronectin antibody. In early cathepsin G digests, several gelatin-binding fragments were detected: a few large (Mr greater than or equal to 150 000) polypeptides and fragments of Mr = 85 000, 72 000, 64 000 and 40 000. The 85 000-Mr and 64 000-Mr fragments appeared as closely spaced doublets and reacted with the antibody while the 72 000-Mr and 40 000-Mr fragments did not. Therefore the 64 000-Mr fragments are likely to be derived from the 85 000-Mr fragments. Three large fragments that bound to heparin, but not to gelatin were detected: Mr = 145 000, 135 000 and 120 000. Of these only the 135 000-Mr peptide reacted with the antibody. When fibronectin was digested with thrombin, polypeptides of Mr = 180 000-200 000 and a 30 000-Mr NH2-terminal fragment were produced. Cathepsin G added to this mixture further cleaved the fragments to a digestion pattern resembling that obtained from intact fibronectin except that the 85 000-Mr and 64 000-Mr fragments appeared as single bands and the amount of the 72 000-Mr fragment was reduced. The results suggest that thrombin cleaves the 30 000-Mr fragment preferentially from the NH2-terminal end of one of the two subunits of fibronectin and that the 85 000-Mr, 72 000-Mr and 64 000-Mr fragments obtained by the additional cathepsin G digestion were derived from the other chain. The results are consistent with the model that the antigenic determinant resides 72 000-85 000 Da from the NH2-terminus and is cleaved by cathepsin G alternatively at one of its sides. Thus, the components of the 85 000-Mr and 64 000-Mr doublets are derived from different subunits and the region located by the antibody may be responsible for the difference in their migration in the polyacrylamide gel.