Porous scaffold architecture guides tissue formation

Critical‐sized bone defect regeneration is a remaining clinical concern. Numerous scaffold‐based strategies are currently being investigated to enable in vivo bone defect healing. However, a deeper understanding of how a scaffold influences the tissue formation process and how this compares to endogenous bone formation or to regular fracture healing is missing. It is hypothesized that the porous scaffold architecture can serve as a guiding substrate to enable the formation of a structured fibrous network as a prerequirement for later bone formation. An ovine, tibial, 30‐mm critical‐sized defect is used as a model system to better understand the effect of the scaffold architecture on cell organization, fibrous tissue, and mineralized tissue formation mechanisms in vivo. Tissue regeneration patterns within two geometrically distinct macroscopic regions of a specific scaffold design, the scaffold wall and the endosteal cavity, are compared with tissue formation in an empty defect (negative control) and with cortical bone (positive control). Histology, backscattered electron imaging, scanning small‐angle X‐ray scattering, and nanoindentation are used to assess the morphology of fibrous and mineralized tissue, to measure the average mineral particle thickness and the degree of alignment, and to map the local elastic indentation modulus. The scaffold proves to function as a guiding substrate to the tissue formation process. It enables the arrangement of a structured fibrous tissue across the entire defect, which acts as a secondary supporting network for cells. Mineralization can then initiate along the fibrous network, resulting in bone ingrowth into a critical‐sized defect, although not in complete bridging of the defect. The fibrous network morphology, which in turn is guided by the scaffold architecture, influences the microstructure of the newly formed bone. These results allow a deeper understanding of the mode of mineral tissue formation and the way this is influenced by the scaffold architecture. © 2012 American Society for Bone and Mineral Research.     

Frequent attenders in general practice and immigrant status in Norway: A nationwide cross-sectional study

Objective. To compare the likelihood of being a frequent attender (FA) to general practice among native Norwegians and immigrants, and to study socioeconomic and morbidity factors associated with being a FA for natives and immigrants. Design, setting and subjects. Linked register data for all inhabitants in Norway with at least one visit to the general practitioner (GP) in 2008 (2 967 933 persons). Immigrants were grouped according to their country of origin into low- (LIC), middle- (MIC), and high-income countries (HIC). FAs were defined as patients whose attendance rate ranked in the top 10% (cut-off point > 7 visits). Main outcome measures. FAs were compared with other GP users by means of multivariate binary logistic analyses adjusting for socioeconomic and morbidity factors. Results. Among GP users during the daytime, immigrants had a higher likelihood of being a FA compared with natives (OR (95% CI): 1.13 (1.09–1.17) and 1.15 (1.12–1.18) for HIC, 1.84 (1.78–1.89) and 1.66 (1.63–1.70) for MIC, and 1.77 (1.67–1.89) and 1.65 (1.57–1.74) for LIC for men and women respectively). Pregnancy, middle income earned in Norway, and having cardiologic and psychiatric problems were the main factors associated with being a FA. Among immigrants, labour immigrants and the elderly used GPs less often, while refugees were overrepresented among FAs. Psychiatric, gastroenterological, endocrine, and non-specific drug morbidity were relatively more prevalent among immigrant FA compared with natives. Conclusion. Although immigrants account for a small percentage of all FAs, GPs and policy-makers should be aware of differences in socioeconomic and morbidity profiles to provide equality of health care.Key Words: Emigrants and immigrants, general practice, health care research, morbidity, Norway, primary health care, registries, socioeconomic factors

• Immigrants are a heterogeneous growing group in Europe and they seem to use primary care differently than natives.
• Immigrants more often become frequent attenders, especially those coming from middle- and low-income countries.
• However, elderly immigrants are underrepresented among frequent attenders in general practice.
• Gastrological, endocrine, and non-specific morbidity are relatively more prevalent among immigrant frequent attenders compared with natives.

     

Development of explicit criteria for prioritization of hip and knee replacement

RATIONALE AND AIMS: Among the problems to the publicly funded national health services are the waiting lists. Patients who need elective surgery generally have long waiting times before treatment. We aimed to develop a new prioritization tool for primary hip and knee replacement. METHODS: Criteria were developed using a modified Delphi panel process. We convened a panel of nine members who scored the scenarios created by the research team and by patient focus groups. We studied the level of agreement among the panelists and the contribution of the variables to the ratings of the panel using linear and logistic regression models. The priority scores of the variables and their levels were synthesized using the optimal scaling and standard linear regression methods. RESULTS: Seven variables, pain on motion, walking functional limitations, abnormal findings on physical examination, pain at rest, other functional limitations, social role, and other pathologies that could improve with joint replacement, were considered to create the different scenarios. The panel scored 192 scenarios. The disagreement among the panelists was very low (1%) with an intra-class correlation coefficient of 0.72. Of the 192 scenarios, 45.8% were scored as urgent, 35.4% as preferred and 18.8% as ordinary. The variables that contributed most to the scores were pain on motion and walking functional limitations. When optimal scaling and regression techniques were applied, similar results were obtained. CONCLUSION: This tool can evaluate and prioritize patients on a waiting list for hip or knee replacement. We also provide a simple and easy way to use an algorithm to estimate the treatment priority for individual patients.     

Is clindamycin effective in preventing infectious complications after oral surgery? Systematic review and meta-analysis of randomized controlled trials

Clinical Oral Investigations - To determine the effect of clindamycin in the prevention of infection after oral surgery. This systematic review and meta-analysis followed the PRISMA statement, the...     

S1P(1) overexpression stimulates S1P-dependent chemotaxis of human CD34+ hematopoietic progenitor cells but strongly inhibits SDF-1/CXCR4-dependent migration and in vivo homing

The CXC chemokine receptor 4 (CXCR4) and its ligand stromal derived factor 1 (SDF-1) regulate egress and homing of hematopoietic stem cells. Activation of sphingosine-1-phosphate (S1P) receptors (S1P(1-5)) modulates chemokine-induced migration of lymphocytes and hematopoietic stem cells. To analyze the influence of S1P(1) on SDF-1-dependent chemotaxis and trafficking, we overexpressed S1P(1) in CD34+ mobilized peripheral blood progenitor cells (PBPCs). Using a gamma-retroviral vector, transgene overexpression was achieved in more than 90% of target cells. S1P(1) transgene positive PBPCs showed enhanced chemotaxis towards S1P. S1P(1) overexpression resulted in reduced CXCR4 surface expression levels and strong inhibition of SDF-1-dependent ERK1/2 phosphorylation and Ca(2+) flux. Furthermore, SDF-1-dependent migration of S1P(1) overexpressing PBPCs or Jurkat cells was reduced up to 10-fold. Sublethally irradiated NOD/SCID mice were transplanted with 6-day cultured PBPCs overexpressing either S1P(1)-IRES-GFP or GFP alone. Screening for GFP positive human cells in the mouse bone marrow 20h after transplantation revealed an eightfold reduction in bone marrow homing of S1P(1) transgene expressing cells. Our data suggest that S1P(1) acts as an inhibitor of CXCR4-dependent migration of hematopoietic cells to sites of SDF-1 production.     

The comet assay: topical issues

The comet assay is a versatile and sensitive method for measuring single- and double-strand breaks in DNA. The mechanism of formation of comets (under neutral or alkaline conditions) is best understood by analogy with nucleoids, in which relaxation of DNA supercoiling in a structural loop of DNA by a single DNA break releases that loop to extend into a halo-or, in the case of the comet assay, to be pulled towards the anode under the electrophoretic field. A consideration of the simple physics underlying electrophoresis leads to a better understanding of the assay. The sensitivity of the assay is only fully appreciated when it is calibrated: between one hundred and several thousand breaks per cell can be determined. By including lesion-specific enzymes in the assay, its range and sensitivity are greatly increased, but it is important to bear in mind that their specificity is not absolute. Different approaches to quantitation of the comet assay are discussed. Arguments are presented against trying to apply the comet assay to the study of apoptosis. Finally, some of the advantages and disadvantages of using the comet assay on lymphocyte samples collected in human studies are rehearsed.     

Missense MED12 variants in 22 males with intellectual disability: From nonspecific symptoms to complete syndromes

We describe the phenotype of 22 male patients (20 probands) carrying a hemizygous missense variant in MED12. The phenotypic spectrum is very broad ranging from nonspecific intellectual disability (ID) to the three well-known syndromes: Opitz–Kaveggia syndrome, Lujan–Fryns syndrome, or Ohdo syndrome. The identified variants were randomly distributed throughout the gene (p = 0.993, χ² test), but mostly outside the functional domains (p = 0.004; χ² test). Statistical analyses did not show a correlation between the MED12-related phenotypes and the locations of the variants (p = 0.295; Pearson correlation), nor the protein domain involved (p = 0.422; Pearson correlation). In conclusion, establishing a genotype–phenotype correlation in MED12-related diseases remains challenging. Therefore, we think that patients with a causative MED12 variant are currently underdiagnosed due to the broad patients' clinical presentations.