Trajectories of perceived economic hardship: Relations with mother's and child's mental health and the role of self-esteem.

Trajectories of poverty influence the mental health of mothers and children. Previous studies utilize objective measures despite the importance of subjective measures of poverty. Furthermore, chronic economic hardship may erode personal resources such as self-esteem which increases vulnerability to mental health issues. Trajectories of perceived family economic hardship and their relationship with common mental health disorders, as mediated by self-esteem, were investigated in 511 mother-child dyads from Singapore. Three distinct groups of economic hardship trajectories were delineated, namely the low stable, high stable and moderate decreasing group. The high stable group was found to be associated with a greater likelihood of mother's depression, mother's anxiety and child's anxiety when compared to the low stable group. The moderate decreasing group was found to be associated with a greater likelihood of mother's anxiety when compared to the low stable group. Mother's self-esteem was found to mediate all the significant relations found. These findings indicate the existence of distinct trajectories of perceived economic hardship within low-income families and their relation with mental health outcomes in mothers and children. The mediation of these relations by mother's self-esteem suggests the importance of enhancing self-esteem in mothers from low-income backgrounds.

Personal exposure assessment of pesticides in residents: The association between hand wipes and urinary biomarkers.

BACKGROUND: Residential exposure to pesticides may occur via inhalation of airborne pesticides, direct skin contacts with pesticide-contaminated surfaces, and consumption of food containing pesticide residues. The aim was to study the association of dermal exposure to pesticides between the use and non-use periods, between farmer and non-farmer families and between dermal exposure and the excretion of metabolites from urine in residents living close to treated agricultural fields. METHODS: In total, 112 hand wipes and 206 spot urine samples were collected from 16 farmer and 38 non-farmer participants living within 50 m from an agricultural field in the Netherlands. The study took place from May 2016 to December 2017 during the use as well as the non-use periods of pesticides. Hand wipes were analysed for the parent compound and urines samples for the corresponding urinary metabolite of five applied pesticides: asulam, carbendazim (applied as thiophanate-methyl), chlorpropham, prochloraz and tebuconazole. Questionnaire data was used to study potential determinants of occurrence and levels of pesticides in hand wipes according to univariate and multivariate analysis. RESULTS: Carbendazim and tebuconazole concentrations in hand wipes were statistically significantly higher in the pesticide-use period compared to the non-use period. In addition, especially during the use periods, concentrations were statistically significantly higher in farmer families compared to non-farmer families. For asulam, chlorpropham and prochloraz, the frequency of non-detects was too high (57-85%) to be included in this analysis. The carbendazim contents in urine samples and hand wipes were correlated on the first and second day after taking the hand wipe, whereas chlorpropham was only observed to be related on the second day following the spray event. CONCLUSIONS: Concentrations in hand wipes were overall higher in pesticide use periods compared to non-use periods and higher in farmer families compared to non-farmer families. Only for carbendazim a strong correlation between concentrations in hand wipes and its main metabolite in urine was observed, indicating dermal exposure via contaminated indoor surfaces. We expect this to be related to the lower vapour pressure and longer environmental lifetime of carbendazim compared to the other pesticides studies.

Recent developments in diagnosis and risk stratification of non-ST-elevation acute coronary syndrome.

In the past year, a number of important papers have been published on non-ST-elevation acute coronary syndrome, highlighting progress in clinical care. The current review focuses on early diagnosis and risk stratification using biomarkers and advances in intracoronary imaging.

Toxicokinetics of a urinary metabolite of tebuconazole following controlled oral and dermal administration in human volunteers.

Tebuconazole (TEB) is a widely used triazole fungicide, but the toxicokinetics of its human metabolites are not fully described. For proper interpretation of biological monitoring data, knowledge on the metabolism and elimination of the compound is required. A human volunteer study was performed with the aim to describe the time courses of urinary excretion after controlled oral and dermal administration of TEB. Six healthy volunteers (three males and three females) received on separate occasions a single oral dose of 1.5 mg of TEB and a single dermal dose of 2.5 mg during 1 h. In addition to a pre-exposure urine sample, complete urine voids were collected over 48 h post-administration. The main metabolite hydroxy-tebuconazole (TEB-OH) was quantified in each urine sample. Peak excretion rates after oral and dermal administration were reached after 1.4 and 21 h, mean elimination half-lives were 7.8 and 16 h, and recoveries within 48 h were 38% and 1%, respectively. The time courses of excretion were compared to simulations with an established physiologically based toxicokinetic model for TEB that was extended with a parallel model for TEB-OH. Overall, TEB-OH was rapidly excreted into urine after oral exposure, and renal elimination was considerably slower after dermal exposure. Urinary time courses between individuals were similar. The model predictions were in good agreement with the observed time courses of excretion.

[Correlation between ICIQ-UI-SF score and personality testing results over a urinary incontinent population]. / Corrélation entre le score de l'ICIQ-UI-SF et les résultats d'un test psychométrique de personnalité d'une population ayant une incontinence urinaire.

OBJECTIVE: We found out the personality pattern of an incontinent population and proceeded to a correlation between the personality inventory and the ICIQ-UI-SF (International Consultation Incontinence Questionnaire Urinary Incontinence Short Form) to demonstrate reliability and sincerity of the answers and to establish that a personality disturbance may impact the physiopathology of micturition. MATERIALS AND METHODS: We performed an observational prospective study. It included patient's answers to a computed questionnaire combining a double ICIQ-UI-SF questionnaire and the 71 questions of the Minimult questionnaire. Forty-seven patients were asked to participate. RESULTS: Over 37 patients included, Wilcoxon-Mann-Whitney non parametric test confirmed agreement of the two ICIQ-UI-SF questionnaires with P=0.1792. Twenty-three patients were validated to the Minimult inventory with F scale<70. We analysed variability of the two global ICIQ-UI-SF score in regard with the validity scale using ROC analysis. We observed an AUC of 0.559 with sensitivity 78.6% and specificity 43.5%. No L score was above 70 demonstrating absence of lie. No personality disturbance was found in 9 cases. We observed six cases with a high hypochondric value, five with a high depressive value, and four with a high hysteric value. This neurotic triad was found in two cases. We noticed five cases with psychopathic deviance relative to antisocial behaviour while values of paranoia and hypomania were high in one case without any association of these personality aspects, which demonstrated absence of behavioural problem. Psychotic profile associating schizophrenia, paranoia, depression and hypomania was not found. We outlined in half of the valid population a significant high psycho-asthenic pattern. CONCLUSION: We conclude that a correlation between the personality inventory and the ICIQ-UI-SF is feasible. The comparative study demonstrate reliability of answers. Sincerity is established by the Minimult L scale. We confirm and precise literature information over clinical personality pattern of this population and observe relevant elements concerning the psycho-asthenic pattern which depicts an anxious personality with an important feeling of the problem. These elements permit to suspect that a personality disturbance may impact the physiopathology of the micturition. LEVEL OF EVIDENCE: 4.

Spatially resolving valley quantum interference of a donor in silicon.

Electron and nuclear spins of donor ensembles in isotopically pure silicon experience a vacuum-like environment, giving them extraordinary coherence. However, in contrast to a real vacuum, electrons in silicon occupy quantum superpositions of valleys in momentum space. Addressable single-qubit and two-qubit operations in silicon require that qubits are placed near interfaces, modifying the valley degrees of freedom associated with these quantum superpositions and strongly influencing qubit relaxation and exchange processes. Yet to date, spectroscopic measurements have only probed wavefunctions indirectly, preventing direct experimental access to valley population, donor position and environment. Here we directly probe the probability density of single quantum states of individual subsurface donors, in real space and reciprocal space, using scanning tunnelling spectroscopy. We directly observe quantum mechanical valley interference patterns associated with linear superpositions of valleys in the donor ground state. The valley population is found to be within 5% of a bulk donor when 2.85 ± 0.45 nm from the interface, indicating that valley-perturbation-induced enhancement of spin relaxation will be negligible for depths greater than 3 nm. The observed valley interference will render two-qubit exchange gates sensitive to atomic-scale variations in positions of subsurface donors. Moreover, these results will also be of interest for emerging schemes proposing to encode information directly in valley polarization.

Nanoscale control of graphene electrodes.

Single layer graphene nano-gaps are fabricated by applying the method of feedback-controlled electroburning to notched ribbon devices, which are plasma etched from CVD grown graphene that is wet-transferred onto pre-patterned metal electrodes. Electrical and structural characterizations show that nanometer size gaps form at the center of the notch. We have processed a total number of 1079 devices using this method with a fabrication yield of 71%. Our results demonstrate precise control over the size and position of the nano-gaps, and open up the possibility of graphene electrodes for large-scale integrated molecular devices.

Integrated logic circuits using single-atom transistors.

Scaling down the size of computing circuits is about to reach the limitations imposed by the discrete atomic structure of matter. Reducing the power requirements and thereby dissipation of integrated circuits is also essential. New paradigms are needed to sustain the rate of progress that society has become used to. Single-atom transistors, SATs, cascaded in a circuit are proposed as a promising route that is compatible with existing technology. We demonstrate the use of quantum degrees of freedom to perform logic operations in a complementary-metal-oxide-semiconductor device. Each SAT performs multilevel logic by electrically addressing the electronic states of a dopant atom. A single electron transistor decodes the physical multivalued output into the conventional binary output. A robust scalable circuit of two concatenated full adders is reported, where by utilizing charge and quantum degrees of freedom, the functionality of the transistor is pushed far beyond that of a simple switch.

Biodegradation of ballast tank coating investigated by impedance spectroscopy and microscopy.

This research paper addresses the biodegradation process for ballast tank coatings in marine environments. As part of this new approach, a commercially available ballast tank coating was exposed to bacteria obtained from a culture collection and to a natural bacterial community isolated from a real ballast tank. The natural community was chosen to explore the interaction of natural biofilms with the coating, an aspect, which is not covered in standard procedures. It is shown that biological activity significantly affects the coating properties. Micro-cracks and holes have been identified using AFM. Acidic bacteria generated holes with 0.2-0.9 µm in depth and 4-9 µm in width. Whereas the natural community additionally caused cracks of 2-8 µm in depth and 1 µm in length. The overall effect of this degradation was examined using the EIS technique. However, the bacterial affected coatings (exposed to acid producing bacteria and a natural community) show a decrease in corrosion resistance. Impedance IZI values decreased over time from 1.18 × 10(9) to 1.87 × 10(7) Ω for acidic bacteria and from 1.71 × 10(9) to 2.24 × 10(7) Ω for the natural community, indicating a clear loss in coating resistance over time. It is also revealed that the coating corrosion resistance declines after 40 days of exposure for the natural community, leading to the formation of blisters. Bacterial settling could be linked to some specific biofilm patterns affecting different types of coating attack. It can be concluded that it is necessary to include natural communities in coating degradation studies to identify possible degradation mechanisms and the severity of the attack over time.

Extrusion-based 3D printing of biodegradable, osteogenic, paramagnetic, and porous FeMn-akermanite bone substitutes.

The development of biodegradable Fe-based bone implants has rapidly progressed in recent years. Most of the challenges encountered in developing such implants have been tackled individually or in combination using additive manufacturing technologies. Yet not all the challenges have been overcome. Herein, we present porous FeMn-akermanite composite scaffolds fabricated by extrusion-based 3D printing to address the unmet clinical needs associated with Fe-based biomaterials for bone regeneration, including low biodegradation rate, MRI-incompatibility, mechanical properties, and limited bioactivity. In this research, we developed inks containing Fe, 35 wt% Mn, and 20 or 30 vol% akermanite powder mixtures. 3D printing was optimized together with the debinding and sintering steps to obtain scaffolds with interconnected porosity of 69%. The Fe-matrix in the composites contained the γ-FeMn phase as well as nesosilicate phases. The former made the composites paramagnetic and, thus, MRI-friendly. The in vitro biodegradation rates of the composites with 20 and 30 vol% akermanite were respectively 0.24 and 0.27 mm/y, falling within the ideal range of biodegradation rates for bone substitution. The yield strengths of the porous composites stayed within the range of the values of the trabecular bone, despite in vitro biodegradation for 28 d. All the composite scaffolds favored the adhesion, proliferation, and osteogenic differentiation of preosteoblasts, as revealed by Runx2 assay. Moreover, osteopontin was detected in the extracellular matrix of cells on the scaffolds. Altogether, these results demonstrate the remarkable potential of these composites in fulfilling the requirements of porous biodegradable bone substitutes, motivating future in vivo research. STATEMENT OF SIGNIFICANCE: We developed FeMn-akermanite composite scaffolds by taking advantage of the multi-material capacity of extrusion-based 3D printing. Our results demonstrated that the FeMn-akermanite scaffolds showed an exceptional performance in fulfilling all the requirements for bone substitution in vitro, i.e., a sufficient biodegradation rate, having mechanical properties in the range of trabecular bone even after 4 weeks biodegradation, paramagnetic, cytocompatible and most importantly osteogenic. Our results encourage further research on Fe-based bone implants in in vivo.

Advantages of atmospheric pressure chemical ionization in gas chromatography tandem mass spectrometry: pyrethroid insecticides as a case study.

Gas chromatography coupled to mass spectrometry (GC/MS) has been extensively applied for determination of volatile, nonpolar, compounds in many applied fields like food safety, environment, or toxicology. The wide majority of methods reported use electron ionization (EI), which may result in extensive fragmentation of analytes compromising selectivity and sensitivity. This might also complicate the application of tandem MS due to lack of specific/abundant precursor ions. Pyrethroids are examples of compounds with this behavior. In this work, the potential of atmospheric pressure chemical ionization (APCI), a softer form of ionization, combined with GC and a triple quadrupole mass analyzer was investigated, taking pyrethroids as a case study and their determination in fruit and vegetables as example application. Ionization and fragmentation behavior of eight pyrethroids (bifenthrin, cyfluthrin, cypermethrin, permethrin, λ-cyhalothrin, fluvalinate, fenvalerate, and deltamethrin) by APCI were studied. The formation of a highly abundant (quasi) molecular ion was the main goal because of the enhanced selectivity when used as precursor ion in tandem MS. The addition of water as a modifier was tested to promote the generation of protonated molecules, resulting in notable improvement of sensitivity and selectivity for most compounds. The excellent detectability (low detection limits (LODs) <20 fg achieved) when using APCI combined with state-of-the-art tandem MS was demonstrated for real samples. Additionally, matrix effects were evaluated in terms of signal enhancement/suppression. Depending on the matrix, different degrees of suppression were observed, on average reducing the signal in matrix to 55% of that in solvent. The results presented in this paper demonstrate the potential of APCI as new source for GC/MS that could be applied to other analytical problems apart from those illustrated in this work.

Progesterone receptor isoforms in the mammary gland of cats and dogs.

Progesterone exerts its effect by binding to specific progesterone receptors (PR) within the cell. In dogs and cats, no data are available on PR isoforms as found in other species. We therefore investigated the sequence of the PR gene and encoded protein in dogs and cats, the expression of PR isoforms in mammary tissue using Western blots and the presence of PR in mammary tissue using immunohistochemistry. Comparison of the amino acid sequence of the canine and feline PR with human PR revealed major differences in the PR-B-specific upstream segment (BUS). However, the essential activation function 3 (AF3) domain was intact in the cat but mutated in the dog. The DNA and ligand-binding domains were highly similar among the species. In cats with fibroadenomatous hyperplasia (FAH), high expression of PR mRNA together with growth hormone (GH), GH receptor (GHR) and IGF-I mRNA was found in comparison with feline mammary carcinomas. Immunohistochemical analysis showed strong nuclear as well as cytoplasmic staining for PR in FAH. Western blot analysis revealed expression of the PR-A and PR-B isoforms in the feline mammary gland. In canine mammary tissue, the most abundant PR staining was found in proliferative zones of the mammary gland. Western blot analyses showed mainly staining for PR-A with lower PR-B staining. It is concluded that in dogs and cats both PR isoforms are expressed. The role of mutations found in the canine PR-B is discussed.

Poly(2-ethyl-2-oxazoline) coating of additively manufactured biodegradable porous iron.

Additively manufacturing of porous iron offers a unique opportunity to increase its biodegradation rate by taking advantage of arbitrarily complex porous structures. Nevertheless, achieving the required biodegradation profile remains challenging due to the natural passivation of iron that decrease the biodegradation rate. Moreover, the biocompatibility of iron is reported to be limited. Here, we address both challenges by applying poly(2-ethyl-2-oxazoline) coating to extrusion-based 3D printed porous iron. We characterized the specimens by performing in vitro biodegradation, electrochemical measurements, time-dependent mechanical tests, and in vitro cytocompatibility assays. The coated porous iron exhibited a biodegradation rate that was 2.6× higher than that of non-coated counterpart and maintained the bone-mimicking mechanical properties throughout biodegradation. Despite the formation of dense biodegradation products, the coating ensured a relatively stable biodegradation (i.e., 17% reduction in the degradation rate between days 14 and 28) as compared to that of non-coated specimens (i.e., 43% drop). Furthermore, the coating could be identified even after biodegradation, demonstrating the longevity of the coating. Finally, the coated specimens significantly increased the viability and supported the attachment and growth of preosteoblasts. Our results demonstrate the great potential of poly(2-ethyl-2-oxazoline) coating for addressing the multiple challenges associated with the clinical adoption of porous iron.

Additive manufacturing of bioactive and biodegradable porous iron-akermanite composites for bone regeneration.

Advanced additive manufacturing techniques have been recently used to tackle the two fundamental challenges of biodegradable Fe-based bone-substituting materials, namely low rate of biodegradation and insufficient bioactivity. While additively manufactured porous iron has been somewhat successful in addressing the first challenge, the limited bioactivity of these biomaterials hinder their progress towards clinical application. Herein, we used extrusion-based 3D printing for additive manufacturing of iron-matrix composites containing silicate-based bioceramic particles (akermanite), thereby addressing both of the abovementioned challenges. We developed inks that carried iron and 5, 10, 15, or 20 vol% of akermanite powder mixtures for the 3D printing process and optimized the debinding and sintering steps to produce geometrically-ordered iron-akermanite composites with an open porosity of 69-71%. The composite scaffolds preserved the designed geometry and the original α-Fe and akermanite phases. The in vitro biodegradation rates of the composites were improved as much as 2.6 times the biodegradation rate of geometrically identical pure iron. The yield strengths and elastic moduli of the scaffolds remained within the range of the mechanical properties of the cancellous bone, even after 28 days of biodegradation. The composite scaffolds (10-20 vol% akermanite) demonstrated improved MC3T3-E1 cell adhesion and higher levels of cell proliferation. The cellular secretion of collagen type-1 and the alkaline phosphatase activity on the composite scaffolds (10-20 vol% akermanite) were, respectively higher than and comparable to Ti6Al4V in osteogenic medium. Taken together, these results clearly show the potential of 3D printed porous iron-akermanite composites for further development as promising bone substitutes. STATEMENT OF SIGNIFICANCE: Porous iron matrix composites containing akermanite particles were produced by means of multi-material additive manufacturing to address the two fundamental challenges associated with biodegradable iron-based biomaterials, namely very low rate of biodegradation and insufficient bioactivity. Our porous iron-akermanite composites exhibited enhanced biodegradability and superior bioactivity compared to porous monolithic iron scaffolds. The murine bone cells proliferated on the composite scaffolds, and secreted the collagen type-1 matrix that stimulated bony-like mineralization. The results show the exceptional potential of the developed porous iron-based composite scaffolds for application as bone substitutes.

IFNγ-Stimulated B Cells Inhibit T Follicular Helper Cells and Protect Against Atherosclerosis.

B and T cells are interconnected in the T follicular helper-germinal center B cell (TFH-GC B cell) axis, which is hyperactive during atherosclerosis development and loss of control along this axis results in exacerbated atherosclerosis. Inhibition of the TFH-GC B cell axis can be achieved by providing negative co-stimulation to TFH cells through the PD-1/PD-L1 pathway. Therefore, we investigated a novel therapeutic strategy using PD-L1-expressing B cells to inhibit atherosclerosis. We found that IFNγ-stimulated B cells significantly enhanced PD-L1 expression and limited TFH cell development. To determine whether IFNγ-B cells can reduce collar-induced atherosclerosis, apoE -/- mice fed a Western-type diet were treated with PBS, B cells or IFNγ-B cells for a total of 5 weeks following collar placement. IFNγ-B cells significantly increased PD-L1hi GC B cells and reduced plasmablasts. Interestingly, IFNγ-B cells-treated mice show increased atheroprotective Tregs and T cell-derived IL-10. In line with these findings, we observed a significant reduction in total lesion volume in carotid arteries of IFNγ-B cells-treated mice compared to PBS-treated mice and a similar trend was observed compared to B cell-treated mice. In conclusion, our data show that IFNγ-stimulated B cells strongly upregulate PD-L1, inhibit TFH cell responses and protect against atherosclerosis.

Extrusion-based 3D printing of ex situ-alloyed highly biodegradable MRI-friendly porous iron-manganese scaffolds.

Additively manufactured biodegradable porous iron has been only very recently demonstrated. Two major limitations of such a biomaterial are very low biodegradability and incompatibility with magnetic resonance imaging (MRI). Here, we present a novel biomaterial that resolves both of those limitations. We used extrusion-based 3D printing to fabricate ex situ-alloyed biodegradable iron-manganese scaffolds that are non-ferromagnetic and exhibit enhanced rates of biodegradation. We developed ink formulations containing iron and 25, 30, or 35 wt% manganese powders, and debinding and sintering process to achieve Fe-Mn scaffolds with 69% porosity. The Fe25Mn scaffolds had the ε-martensite and γ-austenite phases, while the Fe30Mn and Fe35Mn scaffolds had only the γ-austenite phase. All iron-manganese alloys exhibited weakly paramagnetic behavior, confirming their potential to be used as MRI-friendly bone substitutes. The in vitro biodegradation rates of the scaffolds were very much enhanced (i.e., 4.0 to 4.6 times higher than that of porous iron), with the Fe35Mn alloy exhibiting the highest rate of biodegradation (i.e., 0.23 mm/y). While the elastic moduli and yield strengths of the scaffolds decreased over 28 days of in vitro biodegradation, those values remained in the range of cancellous bone. The culture of preosteoblasts on the porous iron-manganese scaffolds revealed that cells could develop filopodia on the scaffolds, but their viability was reduced by the effect of biodegradation. Altogether, this research marks a major breakthrough and demonstrates the great prospects of multi-material extrusion-based 3D printing to further address the remaining issues of porous iron-based materials and, eventually, develop ideal bone substitutes. STATEMENT OF SIGNIFICANCE: 3D printed porous iron biomaterials for bone substitution still encounter limitations, such as the slow biodegradation and magnetic resonance imaging incompatibility. Aiming to solve the two fundamental issues of iron, we present ex-situ alloyed porous iron-manganese scaffolds fabricated by means of multi-material extrusion-based 3D printing. Our porous iron-manganese possessed enhanced biodegradability, non-ferromagnetic property, and bone-mimicking mechanical property throughout the in vitro biodegradation period. The results demonstrated a great prospect of multi-material extrusion-based 3D printing to further address the remaining challenges of porous iron-based biomaterials to be an ideal biodegradable bone substitutes.

Extrusion-based 3D printed magnesium scaffolds with multifunctional MgF2 and MgF2-CaP coatings.

Additively manufactured (AM) biodegradable magnesium (Mg) scaffolds with precisely controlled and fully interconnected porous structures offer unprecedented potential as temporary bone substitutes and for bone regeneration in critical-sized bone defects. However, current attempts to apply AM techniques, mainly powder bed fusion AM, for the preparation of Mg scaffolds, have encountered some crucial difficulties related to safety in AM operations and severe oxidation during AM processes. To avoid these difficulties, extrusion-based 3D printing has been recently developed to prepare porous Mg scaffolds with highly interconnected structures. However, limited bioactivity and a too high rate of biodegradation remain the major challenges that need to be addressed. Here, we present a new generation of extrusion-based 3D printed porous Mg scaffolds that are coated with MgF2 and MgF2-CaP to improve their corrosion resistance and biocompatibility, thereby bringing the AM scaffolds closer to meeting the clinical requirements for bone substitutes. The mechanical properties, in vitro biodegradation behavior, electrochemical response, and biocompatibility of the 3D printed Mg scaffolds with a macroporosity of 55% and a strut density of 92% were evaluated. Furthermore, comparisons were made between the bare scaffolds and the scaffolds with coatings. The coating not only covered the struts but also infiltrated the struts through micropores, resulting in decreases in both macro- and micro-porosity. The bare Mg scaffolds exhibited poor corrosion resistance due to the highly interconnected porous structure, while the MgF2-CaP coatings remarkably improved the corrosion resistance, lowering the biodegradation rate of the scaffolds down to 0.2 mm y-1. The compressive mechanical properties of the bare and coated Mg scaffolds before and during in vitro immersion tests for up to 7 days were both in the range of the values reported for the trabecular bone. Moreover, direct culture of MC3T3-E1 preosteoblasts on the coated Mg scaffolds confirmed their good biocompatibility. Overall, this study clearly demonstrated the great potential of MgF2-CaP coated porous Mg prepared by extrusion-based 3D printing for further development as a bone substitute.

Extrusion-based 3D printed biodegradable porous iron.

Extrusion-based 3D printing followed by debinding and sintering is a powerful approach that allows for the fabrication of porous scaffolds from materials (or material combinations) that are otherwise very challenging to process using other additive manufacturing techniques. Iron is one of the materials that have been recently shown to be amenable to processing using this approach. Indeed, a fully interconnected porous design has the potential of resolving the fundamental issue regarding bulk iron, namely a very low rate of biodegradation. However, no extensive evaluation of the biodegradation behavior and properties of porous iron scaffolds made by extrusion-based 3D printing has been reported. Therefore, the in vitro biodegradation behavior, electrochemical response, evolution of mechanical properties along with biodegradation, and responses of an osteoblastic cell line to the 3D printed iron scaffolds were studied. An ink formulation, as well as matching 3D printing, debinding and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, a pore interconnectivity of 96%, and a strut density of 89% after sintering. X-ray diffracometry confirmed the presence of the α-iron phase in the scaffolds without any residuals from the rest of the ink. Owing to the presence of geometrically designed macropores and random micropores in the struts, the in vitro corrosion rate of the scaffolds was much improved as compared to the bulk counterpart, with 7% mass loss after 28 days. The mechanical properties of the scaffolds remained in the range of those of trabecular bone despite 28 days of in vitro biodegradation. The direct culture of MC3T3-E1 preosteoblasts on the scaffolds led to a substantial reduction in living cell count, caused by a high concentration of iron ions, as revealed by the indirect assays. On the other hand, the ability of the cells to spread and form filopodia indicated the cytocompatibility of the corrosion products. Taken together, this study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial.

Transcriptomic analysis by RNA sequencing characterises malignant progression of canine insulinoma from normal tissue to metastatic disease.

Insulinomas (INS) are the most common human and canine functioning pancreatic neuroendocrine tumours. The long-term prognosis for malignant INS is poor, because micrometastases are frequently missed during surgery. As human and canine malignant INS share clinical and histopathological features, dogs have been proposed as models for INS research. Using RNA-sequencing, we conducted a pilot study to better understand the underlying molecular mechanisms of canine INS. Normal canine pancreas and lymph node control tissues were compared with primary INS and INS-metastatic lymph nodes, revealing more than 3,000 genes differentially expressed in normal pancreas compared to primary INS. Only 164 genes were differentially expressed between primary INS and INS-metastatic lymph nodes. Hierarchical clustering analysis demonstrated similar genetic profiles in normal pancreas and early clinical stage primary INS, whereas late clinical stage primary INS resembled the genetic profile of INS-metastatic lymph nodes. These findings suggest that markers of malignant behaviour could be identified at the primary site of the disease. Finally, using the REACTOME pathways database, we revealed that an active collagen metabolism, extracellular matrix remodelling, beta-cell differentiation and non-beta-cell trans-differentiation might cause disease progression and hyperinsulinism in INS, identifying major pathways worthy of future research in this currently poorly controlled disease.

Additively manufactured biodegradable porous zinc.

Additively manufacturing (AM) opens up the possibility for biodegradable metals to possess uniquely combined characteristics that are desired for bone substitution, including bone-mimicking mechanical properties, topologically ordered porous structure, pore interconnectivity and biodegradability. Zinc is considered to be one of the promising biomaterials with respect to biodegradation rate and biocompatibility. However, no information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is yet available. Here, we applied powder bed fusion to fabricate porous zinc with a topologically ordered diamond structure. An integrative study was conducted on the static and dynamic biodegradation behavior (in vitro, up to 4 weeks), evolution of mechanical properties with increasing immersion time, electrochemical performance, and biocompatibility of the AM porous zinc. The specimens lost 7.8% of their weight after 4 weeks of dynamic immersion in a revised simulated body fluid. The mechanisms of biodegradation were site-dependent and differed from the top of the specimens to the bottom. During the whole in vitro immersion time of 4 weeks, the elastic modulus values of the AM porous zinc (E = 700-1000 MPa) even increased and remained within the scope of those of cancellous bone. Indirect cytotoxicity revealed good cellular activity up to 72 h according to ISO 10,993-5 and -12. Live-dead staining confirmed good viability of MG-63 cells cultured on the surface of the AM porous zinc. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that will enable reconstruction and regeneration of critical-size load-bearing bone defects. STATEMENT OF SIGNIFICANCE: No information regarding the biodegradability and biocompatibility of topologically ordered AM porous zinc is available. We applied selective laser melting to fabricate topologically ordered porous zinc and conducted a comprehensive study on the biodegradation behavior, electrochemical performance, time-dependent mechanical properties, and biocompatibility of the scaffolds. The specimens lost 7.8% of their weight after4 weeks dynamic biodegradation while their mechanical properties surprisingly increased after 4 weeks. Indirect cytotoxicity revealed good cellular activity up to 72 h. Intimate contact between MG-63 cells and the scaffolds was also observed. These important findings could open up unprecedented opportunities for the development of multifunctional bone substituting materials that mimic bone properties and enable full regeneration of critical-size load-bearing bony defects.