中荷两所大学口腔医学教育的比较与启示

荷兰拉德堡德大学牙学院的口腔医学教育是欧洲医学教育中的典范,通过对荷兰拉德堡德大学牙学院与中国武汉大学口腔医学院的学制设置、培养目标、课程安排、教学方法以及考核方式的比较与分析发现,中国的口腔医学教育与荷兰比较存在很大的差异。借鉴国外先进的教学模式与经验,对于推动口腔医学教学改革和提高口腔医学教育水平都有极其重要的意义。

Gene expression profiles of human adipose-derived mesenchymal stem cells dynamically seeded on clinically available processed nerve allografts and collagen nerve guides

It was hypothesized that mesenchymal stem cells(MSCs) could provide necessary trophic factors when seeded onto the surfaces of commonly used nerve graft substitutes. We aimed to determine the gene expression of MSCs when influenced by Avance■ Nerve Grafts or Neura Gen■ Nerve Guides. Human adipose-derived MSCs were cultured and dynamically seeded onto 30 Avance■ Nerve Grafts and 30 Neura Gen■ Nerve Guides for 12 hours. At six time points after seeding, quantitative polymerase chain reaction analyses were performed for five samples per group. Neurotrophic [nerve growth factor(NGF), glial cell line-derived neurotrophic factor(GDNF), pleiotrophin(PTN), growth associated protein 43(GAP43) and brain-derived neurotrophic factor(BDNF)], myelination [peripheral myelin protein 22(PMP22) and myelin protein zero(MPZ)], angiogenic [platelet endothelial cell adhesion molecule 1(PECAM1/CD31) and vascular endothelial cell growth factor alpha(VEGFA)], extracellular matrix(ECM) [collagen type alpha I(COL1A1), collagen type alpha III(COL3A1), Fibulin 1(FBLN1) and laminin subunit beta 2(LAMB2)] and cell surface marker cluster of differentiation 96(CD96) gene expression was quantified. Unseeded Avance■ Nerve Grafts and Neura Gen■ Nerve Guides were used to evaluate the baseline gene expression, and unseeded MSCs provided the baseline gene expression of MSCs. The interaction of MSCs with the Avance■ Nerve Grafts led to a short-term upregulation of neurotrophic(NGF, GDNF and BDNF), myelination(PMP22 and MPZ) and angiogenic genes(CD31 and VEGFA) and a long-term upregulation of BDNF, VEGFA and COL1A1. The interaction between MSCs and the Neura Gen■ Nerve Guide led to short term upregulation of neurotrophic(NGF, GDNF and BDNF) myelination(PMP22 and MPZ), angiogenic(CD31 and VEGFA), ECM(COL1A1) and cell surface(CD96) genes and long-term upregulation of neurotrophic(GDNF and BDNF), angiogenic(CD31 and VEGFA), ECM genes(COL1A1, COL3A1, and FBLN1) and cell surface(CD96) genes. Analysis demonstrated MSCs seeded onto Neura Gen■ Nerve Guides expressed significantly higher levels of neurotrophic(PTN), angiogenic(VEGFA) and ECM(COL3A1, FBLN1) genes in the long term period compared to MSCs seeded onto Avance■ Nerve Grafts. Overall, the interaction between human MSCs and both nerve graft substitutes resulted in a significant upregulation of the expression of numerous genes important for nerve regeneration over time. The in vitro interaction of MSCs with the Neura Gen■ Nerve Guide was more pronounced, particularly in the long term period(> 14 days after seeding). These results suggest that MSC-seeding has potential to be applied in a clinical setting, which needs to be confirmed in future in vitro and in vivo research.

Health-related quality of life in autoimmune hepatitis

Autoimmune hepatitis(AIH)is a severe chronic autoimmune disease and has a significant impact on the patient’s quality of life,in particular regarding psychological problems such as anxiety and depression.Consistent evidence on which patient-related,disease-related or physician-related factors cause health-related quality of life(HRQoL)impairment in patients with AIH is lacking.Current studies on HRQoL in AIH are mainly single-centered,comprising small numbers of patients,and difficult to compare because of the use of different questionnaires,patient populations,and cutoff values.Literature in the pediatric field is sparse,but suggests that children/adolescents with AIH have a lower HRQoL.Knowledge of HRQoL and cohesive factors in AIH are important to improve healthcare for AIH patients,for example by developing an AIH-specific chronic healthcare model.By recognizing the importance of quality of life beyond the concept of biochemical and histological remission,clinicians allow us to seek enhancements and possible interventions in the management of AIH,aiming at improved health.

Thiol-ene conjugation of a VEGF peptide to electrospun scaffolds for potential applications in angiogenesis

Vascular endothelial growth factor(VEGF)plays a vital role in promoting attachment and proliferation of endothelial cells,and induces angiogenesis.In recent years,much research has been conducted on the functionalization of tissue engineering scaffolds with VEGF or a VEGF-mimetic peptide to promote angiogenesis.However,most chemical reactions are nonspecific and require organic solvents,which can compromise control over functionalization and alter peptide/protein activity.An attractive alternative is the fabrication of functionalizable electrospun fibers,which can overcome these hurdles.In this study,we used thiol-ene chemistry for the conjugation of a VEGF-mimetic peptide to the surface of poly(ε-caprolactone)(PCL)fibrous scaffolds with varying amounts of a functional PCL-diacrylate(PCL-DA)polymer.30%PCL-DA was selected due to homogeneous fiber morphology.A VEGF-mimetic peptide was then immobilized on PCL-DA fibrous scaffolds by a light-initiated thiol-ene reaction.7-Mercapto-4-methylcoumarin,RGD-FITC peptide and VEGF-TAMRA mimetic peptide were used to validate the thiol-ene reaction on the fibrous scaffolds.Tensile strength and elastic modulus of the 30%PCL-DA fibrous scaffolds were significantly increased after the reaction.Conjugation of the 30%PCL-DA fibrous scaffolds with the VEGF peptide increased the surface water wettability of the scaffolds.Patterned structures could be obtained after using a photomask on the fibrous film.Moreover,in vitro studies indicated that scaffolds functionalized with the VEGF-mimetic peptide were able to induce phosphorylation of the VEGF receptor and enhanced HUVECs survival,proliferation and adhesion.A chick chorioallantoic membrane(CAM)assay further indicated that the VEGF peptide functionalized scaffolds were able to promote angiogenesis in vivo.These results show that scaffold functionalization can be controlled via a simple polymer mixing approach,and that the functionalized VEGF peptide-scaffolds have potential for vascular tissue regeneration.

Enzymatic co-crosslinking of star-shaped poly(ethylene glycol)tyramine and hyaluronic acid tyramine conjugates provides elastic biocompatible and biodegradable hydrogels

A combination of the viscoelastic properties of hyaluronic acid(HA)and the elastic properties of star shaped 8-arm poly(ethylene glycol)(8-arm PEG)was used to design in-situ forming hydrogels.Hydrogels were prepared by the enzymatic crosslinking of a partially tyramine modified 8-arm PEG and a tyramine conjugated HA using horseradish peroxidase in the presence of hydrogen peroxide.Hydrogels of the homopolymer conjugates and mixtures thereof were rapidly formed within seconds under physiological conditions at low polymer and enzyme concentrations.Elastic hydrogels with high gel content(≥95%)and high storage moduli(up to 22.4 kPa)were obtained.An in vitro study in the presence of hyaluronidase(100 U/mL)revealed that with increasing PEG content the degradation time of the hybrid hydrogels increased up to several weeks,whereas hydrogels composed of only hyaluronic acid degraded within 2 weeks.Human mesenchymal stem cells(hMSCs)incorporated in the hybrid hydrogels remained viable as shown by a PrestoBlue and a live-dead assay,confirming the biocompatibility of the constructs.The production of an extracellular matrix by re-differentiation of encapsulated human chondrocytes was followed over a period of 28 days.Gene expression indicated that these highly elastic hydrogels induced an enhanced production of collagen type II.At low PEG-TA/HA-TA ratios a higher expression of SOX 9 and ACAN was observed.These results indicate that by modulating the ratio of PEG/HA,injectable hydrogels can be prepared applicable as scaffolds for tissue regeneration applications.

The fat and the furious:fatty acids fuel hyperproliferative germinal center B cells

The germinal center(GC)reaction is considered the cornerstone of our humoral immune response.Localized in specialized follicles inside secondary lymphoid organs,germinal center B cells(GCBCs)execute a pivotal task.Following an infection,the number of GCBCs is rapidly expanded,and subsequently GCBCs differentiate into specialized antibody-secreting factories.This intricate process is driven by the positive selection of GCBCs via the B-cell receptor with the highest affinity for the respective antigen.During this period of extensive proliferation,GCBCs are among the fastest dividing cells in our body.It has been established that cell proliferation requires tremendous amounts of energy and building blocks.However,there remains a paucity of evidence to explain how proliferating GCBCs meet these metabolic demands.In their latest publication in Nature Immunology,Weisel et al.provided new insights that may have a far-reaching impact on the evolution of the immunometabolism field.

Bone regeneration using coculture of mesenchymal stem cells and angiogenic cells

Cellular strategies remain a crucial component in bone tissue engineering （BTE）. So far, the outcome of cell-based strategies from initial clinical trials is far behind compared to animal studies, which is suggested to be related to insufficient nutrient and oxygen supply inside the Ussue-engineered constructs. Cocultures, by introducing angiogenic cells into osteogenic cell cultures, might provide a solution for improving vascularization and hence increasing bone formation for cell-based constructs. So far, pre-clinical studies demonstrated that cocultures enhance vascularization and bone formation compared to monocultures. However, there has been no report on the application of cocultures in clinics. Therefore, this mini-review aims to provide an overview regarding （i） critical parameters in cocultures and the outcomes of cocultures compared to monocultures in the currently available pre-clinical studies using human mesenchymal stem cells implanted in orthotopic animal models; and （ii） the usage of monocultures in clinical application in BTE.

Phylogeny,ecology and taxonomy of systemic pathogens and their relatives in Ajellomycetaceae(Onygenales):Blastomyces,Emergomyces,Emmonsia,Emmonsiellopsis

The family Ajellomycetaceae(Onygenales)includes mammal-associated pathogens within the genera Blastomyces,Emmonsia,Histoplasma and Paracoccidioides,as well as the recently described genera,Emergomyces that causes disease in immunocompromised hosts,and Emmonsiellopsis,known only from soil.To further assess the phylogenetic relationships among and between members of these genera and several previously undescribed species,we sequenced and analyzed the DNA-directed RNA polymerase II(rPB2),translation elongation factor 3-a(TEF3),b-tubulin(TUB2),28S large subunit rDNA(LSU)and the internal transcribed spacer regions(ITS)in 68 strains,in addition to morphological and physiological investigations.To better understand the thermal dimorphism among these fungi,the dynamic process of transformation from mycelial to yeast-like or adiaspore-like forms was also assessed over a range of temperatures(6–42C).Molecular data resolved the relationships and recognized five major well-supported lineages that correspond largely to the genus level.Emmonsia,typified by Emmonsia parva,is a synonym of Blastomyces that also accommodates Blastomyces helicus(formerly Emmonsia helica).Emmonsia crescens is phylogenetically distinct,and found closely related to a single strain from soil without known etiology.Blastomyces silverae,Emergomyces canadensis,Emergomyces europaeus and Emmonsia sola are newly described.Almost all of the taxa are associated with human and animal disease.Emmonsia crescens,B.dermatitidis and B.parvus are prevalently associated with pulmonary disease in humans or animals.Blastomyces helicus,B.percursus,Emergomyces africanus,Es.canadensis,Es.europaeus,Es.orientalis and Es.pasteurianus(formerly Emmonsia pasteuriana)are predominantly found in human hosts with immune disorders;no animal hosts are known for these species except B.helicus.

Intraneuronal tau aggregation induces the integrated stress response in astrocytes

Progressive aggregation of tau protein in neurons is associated with neurodegeneration in tauopathies.Cell non-autonomous disease mechanisms in astrocytes may be important drivers of the disease process but remain largely elusive.Here,we studied cell type-specific responses to intraneuronal tau aggregation prior to neurodegeneration.To this end,we developed a fully human co-culture model of seed-independent intraneuronal tau pathology,which shows no neuron and synapse loss.Using high-content microscopy,we show that intraneuronal tau aggregation induces oxidative stress accompanied by activation of the integrated stress response specifically in astrocytes.This requires the direct co-culture with neurons and is not related to neurodegeneration or extracellular tau levels.Tau-directed antisense therapy reduced intraneuronal tau levels and aggregation and prevented the cell non-autonomous responses in astrocytes.These data identify the astrocytic integrated stress response as a novel disease mechanism activated by intraneuronal tau aggregation.In addition,our data provide the first evidence for the efficacy of tau-directed antisense therapy to target cell autonomous and cell non-autonomous disease pathways in a fully human model of tau pathology.

The world’s ten most feared fungi

An account is provided of the world’s ten most feared fungi.Within areas of interest,we have organized the entries in the order of concern.We put four human pathogens first as this is of concern to most people.This is followed by fungi producing mycotoxins that are highly harmful for humans;Aspergillus flavus,the main producer of aflatoxins,was used as an example.Problems due to indoor air fungi may also directly affect our health and we use Stachybotrys chartarum as an example.Not everyone collects and eats edible mushrooms.However,fatalities caused by mushroom intoxications often make news headlines and therefore we include one of the most poisonous of all mushrooms,Amanita phalloides,as an example.We then move on to the fungi that damage our dwellings causing serious anxiety by rotting our timber structures and flooring.Serpula lacrymans,which causes dry rot is an excellent example.The next example serves to represent all plant and forest pathogens.Here we chose Austropuccinia psidii as it is causing devastating effects in Australia and will probably do likewise in New Zealand.Finally,we chose an important amphibian pathogen which is causing serious declines in the numbers of frogs and other amphibians worldwide.Although we target the top ten most feared fungi,numerous others are causing serious concern to human health,plant production,forestry,other animals and our factories and dwellings.By highlighting ten feared fungi as an example,we aim to promote public awareness of the cost and importance of fungi.

Proposed nomenclature for Pseudallescheria,Scedosporium and related genera

As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi,generic names of many groups should be reconsidered.Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria,Scedosporium and allied taxa.The generic names Parascedosporium,Lomentospora,Petriella,Petriellopsis,and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy,annellidic conidia.Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species,some name changes are proposed.Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S.desertorum,respectively.Scedosporium prolificans is renamed as Lomentospora prolificans.