Adipose-derived stem cells (ASCs) have been introduced as an alternative to bone marrow mesenchymal stem cells (BMSCs) for cell-based therapy. However, different studies comparing ASCs and BMSCs have ...shown conflicting results. In fact, harvesting ASCs and BMSCs from different individuals might influence the results, making comparison difficult. Therefore, this study aimed to characterize donor-matched ASCs and BMSCs in order to investigate proliferation, differentiation potential and possible effects of donor variation on these mesenchymal stem cells (MSCs).
Human bone marrow and adipose tissue samples were obtained from nine donors aged 8-14. ASCs and BMSCs were isolated and characterized based on expression of surface markers using flow cytometry. The proliferation up to 21 days was investigated. Multi-lineage differentiation was induced using osteogenic, chondrogenic and adipogenic differentiation media. Alkaline phosphatase (ALP) activity was monitored and collagen type I formation was evaluated by immunofluorescence staining. In vitro multi-potency was studied using tissue-specific stains and lineage-specific gene expression. In addition, the osteogenic lineage was evaluated at protein level.
Isolated ASCs and BMSCs from all donors demonstrated morphologic and immunophenotypic characteristics of MSCs, with expression of MSCs markers and negative expression of hematopoietic markers. Unlike BMSCs, ASCs showed high expression of CD49d and low expression of Stro-1. In general, ASCs showed significantly higher proliferation and adipogenic capacity with more lipid vesicle formation and expression of the adipogenesis-related genes than BMSCs. In contrast, BMSCs showed significantly higher osteogenic and chondrogenic capacity compared to ASCs. BMSCs had earlier and higher ALP activity, calcium deposition, and expression of the osteogenesis- and chondrogenesis-related genes and the osteogenesis-related protein osteopontin. Proliferation and differentiation capacity of ASCs and BMSCs varied significantly among the donors.
ASCs and BMSCs showed tissue-specific differentiation abilities, but with significant variation between donors. The similarities and differences in the properties of ASCs and BMSCs should be taken into consideration when planning stem cell-based therapy.
Objective
Pigs are emerging as a preferred experimental in vivo model for bone regeneration. The study objective was to answer the focused PEO question: in the pig model (P), what is the capacity of ...experimental alveolar bone defects (E) for spontaneous regeneration in terms of new bone formation (O)?
Methods
Following PRISMA guidelines, electronic databases were searched for studies reporting experimental bone defects or extraction socket healing in the maxillae or mandibles of pigs. The main inclusion criteria were the presence of a control group of untreated defects/sockets and the assessment of regeneration via 3D tomography radiographic defect fill (RDF) or 2D histomorphometry new bone formation (NBF). Random effects meta‐analyses were performed for the outcomes RDF and NBF.
Results
Overall, 45 studies were included reporting on alveolar bone defects or extraction sockets, most frequently in the mandibles of minipigs. Based on morphology, defects were broadly classified as ‘box‐defects’ (BD) or ‘cylinder‐defects’ (CD) with a wide range of healing times (10 days to 52 weeks). Meta‐analyses revealed pooled estimates (with 95% confidence intervals) of 50% RDF (36.87%–63.15%) and 43.74% NBF (30.47%–57%) in BD, and 44% RDF (16.48%–71.61%) and 39.67% NBF (31.53%–47.81%) in CD, which were similar to estimates of socket‐healing 48.74% RDF (40.35%–57.13%) and 38.73% NBF (28.57%–48.89%). Heterogeneity in the meta‐analysis was high (I2 > 90%).
Conclusion
A substantial body of literature revealed a high capacity for spontaneous regeneration in experimental alveolar bone defects of (mini)pigs, which should be considered in future studies of bone regeneration in this animal model.
Therapy of recurrent glioblastoma (GBM) is challenging due to lack of standard treatment. We investigated physicians' treatment choice at recurrence and prognostic and predictive factors for survival ...in GBM patients from Norway's two largest regional hospitals. Clinicopathological data from n = 467 patients treated at Haukeland and Oslo university hospitals from January 2015 to December 2017 was collected. Data included tumour location, promoter methylation of O6 methylguanine-DNA methyltransferase (MGMT) and mutation of isocitrate dehydrogenase (IDH), patient age, sex, extent of resection at primary diagnosis and treatment at successive tumour recurrences. Cox-proportional hazards regression adjusting for multiple risk factors was used. Median overall survival (OS) was 12.1 months and 21.4% and 6.8% of patients were alive at 2 and 5 years, respectively. Median progression-free survival was 8.1 months. Treatment at recurrence varied but was not associated with difference in overall survival (OS) (p = 0.201). Age, MGMT hypermethylation, tumour location and extent of resection were independent prognostic factors. Patients who received 60 Gray radiotherapy with concomitant and adjuvant temozolomide at primary diagnosis had 16.1 months median OS and 9.3% were alive at 5 years. Patients eligible for gamma knife/stereotactic radiosurgery alone or combined with chemotherapy at first recurrence had superior survival compared to chemotherapy alone (p<0.001). At second recurrence, combination chemotherapy with or without bevacizumab were both superior to no treatment. Treatment at recurrence differed between the institutions but there was no difference in median OS, indicating that it is the disease biology that dictates patient outcome.
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3D-printed templates are being used for bone tissue regeneration (BTR) as temporary guides. In the current review, we analyze the factors considered in producing potentially ...bioresorbable/degradable 3D-printed templates and their influence on BTR in calvarial bone defect (CBD) animal models. In addition, a meta-analysis was done to compare the achieved BTR for each type of template material (polymer, ceramic or composites). Database collection was completed by January 2018, and the inclusion criteria were all titles and keywords combining 3D printing and BTR in CBD models. Clinical trials and poorly-documented in vivo studies were excluded from this study. A total of 45 relevant studies were finally included and reviewed, and an additional check list was followed before inclusion in the meta-analysis, where material type, porosity %, and the regenerated bone area were collected and analyzed statistically.
Overall, the capacity of the printed templates to support BTR was found to depend in large part on the amount of available space (porosity %) provided by the printed templates. Printed ceramic and composite templates showed the best BTR capacity, and the optimum printed template structure was found to have total porosity >50% with a pore diameter between 300 and 400 µm. Additional features and engineered macro-channels within the printed templates increased BTR capacity at long time points (12 weeks). Although the size of bone defects in rabbits was larger than in rats, BTR was greater in rabbits (almost double) at all time points and for all materials used.
In the present study, we reviewed the factors considered in producing degradable 3D-printed templates and their influence on bone tissue regeneration (BTR) in calvarial bone defects through the last 15 years. A meta-analysis was applied on the collected data to quantify and analyze BTR related to each type of template material.
The concluded data states the importance of 3D-printed templates for BTR and indicates the ideal design required for an effective clinical translation. The evidence-based guidelines for the best BTR capacity endorse the use of printed composite and ceramic templates with total porosity >50%, pore diameter between 300 and 400 µm, and added engineered macro-channels within the printed templates.
Most patients in palliative care have problems with dry mouth caused by medication or as a direct result of their condition. Dry mouth may cause problems that affect the primary disease negatively ...and contribute to poorer quality of life in palliative patients. This randomized controlled trial compared the efficacy of three different oral moisturizers: 17% watery solution of glycerol; oxygenated glycerol triester (marketed as Aequasyal in Europe and as Aquoral in the USA); and a newly developed product, Salient. Of the three products, glycerol provided the best relief from xerostomia directly after application, but had no effect after 2 h. By contrast, the effects of Aequasyal and Salient were largely maintained over the same period. The findings for oral discomfort and pain and speech problems showed a similar pattern. Despite its poor effect after 2 h, patients preferred glycerol over Salient and Aequasyal, probably because of the unpleasant taste of Aequasyal and the consistency and mode of application of Salient. Within the limitations of this study, none of the three products tested was found to be clinically completely adequate. However, the glycerol solution was preferred by this group of patients, and its short‐lived effect can be compensated for by frequent applications.
Aim
To investigate the association between periodontitis and lung function in the Malmö Offspring Dental Study.
Materials and Methods
In all 1001 individuals (49.9% female, mean age: 44.6) from Malmö ...Offspring Dental Study were included. Periodontitis was assessed by a full‐mouth examination protocol including bleeding on probing and classified according to the American Academy of Periodontology/Center for Disease Control definitions. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were expressed as absolute values and %predicted according to Global Lung Function Initiative reference values. FEV1, FVC and FEV1/FVC were analysed in relation to periodontal status using linear regression.
Results
Severe periodontitis was found in 7% of the population. Adjusted regression models showed significant associations between lung function and severe periodontitis with 2.1 unit lower FEV1/FVC ratio (95% CI: −3.91, –0.23) and odds ratio (adjusted) of 2.56 (95% CI: 1.40, 4.75, p = .003) for airflow obstruction (FEV1/FVC less than the lower limit of normal) if having severe periodontitis. Lower values of %predicted FEV1 and %predicted FVC, but not FEV1/FVC, were found in individuals with >25% bleeding on probing.
Conclusions
Severe periodontitis was associated with lower FEV1/FVC ratio and airflow obstruction in the present cohort. More large‐scale prospective studies and intervention studies are required for a comprehensive evaluation.
BACKGROUND AND OBJECTIVES: Acetabular dysplasia in young adults occurs, despite screening for developmental hip dysplasia (DDH) in the neonatal period. We aimed to examine how early life factors ...predict radiographic measurements of acetabular dysplasia at 18-19 years of age.
From a previous randomized trial (n = 12,014; 1988-90) evaluating the role of hip ultrasound in newborn screening of DDH, 4469 participants (2193 males) were invited to a follow-up 18 years later (2007-09), of which 2370 (53% attendance; 932 males) met. We examined associations between early life factors and four radiographic measurements for acetabular dysplasia at skeletal maturity. Hierarchical regressions, with addition of variables observed/measured consecutively in time, were analyzed using mixed effects models considering hip as the unit in the analyses. The study is approved by the Regional Ethics Committee.
In total, 2340 participants (921 boys), mean age 18.7 years, (SD 0.6) had hip radiographs performed at follow-up and were included. Early life factors significantly predicting radiographic acetabular dysplasia at age 18-19-years included female gender, breech, low acetabular inclination (alpha) angle and sonographic instability, abduction treatment, as well as the velocity of growth during childhood. A positive family history of DDH was not associated with acetabular dysplasia at skeletal maturity.
The acetabular inclination (alpha) angle as measured on ultrasound at birth turned out to be a significant predictor of dysplasia at 18-19 years of age. The discordant role of a positive family history in early versus adult hip dysplasia is intriguing, warranting further studies on the genetic mechanisms of DDH.
There are currently no established radiological parameters that predict response to immunotherapy. We hypothesised that multiparametric, longitudinal magnetic resonance imaging (MRI) of physiological ...parameters and pharmacokinetic models might detect early biological responses to immunotherapy for glioblastoma targeting NG2/CSPG4 with mAb9.2.27 combined with natural killer (NK) cells. Contrast enhanced conventional T1-weighted MRI at 7±1 and 17±2 days post-treatment failed to detect differences in tumour size between the treatment groups, whereas, follow-up scans at 3 months demonstrated diminished signal intensity and tumour volume in the surviving NK+mAb9.2.27 treated animals. Notably, interstitial volume fraction (ve), was significantly increased in the NK+mAb9.2.27 combination therapy group compared mAb9.2.27 and NK cell monotherapy groups (p = 0.002 and p = 0.017 respectively) in cohort 1 animals treated with 1 million NK cells. ve was reproducibly increased in the combination NK+mAb9.2.27 compared to NK cell monotherapy in cohort 2 treated with increased dose of 2 million NK cells (p<0.0001), indicating greater cell death induced by NK+mAb9.2.27 treatment. The interstitial volume fraction in the NK monotherapy group was significantly reduced compared to mAb9.2.27 monotherapy (p<0.0001) and untreated controls (p = 0.014) in the cohort 2 animals. NK cells in monotherapy were unable to kill the U87MG cells that highly expressed class I human leucocyte antigens, and diminished stress ligands for activating receptors. A significant association between apparent diffusion coefficient (ADC) of water and ve in combination NK+mAb9.2.27 and NK monotherapy treated tumours was evident, where increased ADC corresponded to reduced ve in both cases. Collectively, these data support histological measures at end-stage demonstrating diminished tumour cell proliferation and pronounced apoptosis in the NK+mAb9.2.27 treated tumours compared to the other groups. In conclusion, ve was the most reliable radiological parameter for detecting response to intralesional NK cellular therapy.
Abstract
Background
Oral streptococci represent the causing microorganism for infective endocarditis (IE) in many patients. The impact of oral infections is questioned, and it has been suggested that ...bacteraemia due to daily routines may play a bigger part in the aetiology of IE. The aim of this study was to examine the association between oral health and infective endocarditis caused by oral bacteria in comparison with bacteria of other origin than the oral cavity.
Methods
A retrospective study was conducted at Haukeland University Hospital from 2006- 2015. All consecutive adult patients admitted to hospital for treatment of IE and subjected to an oral focus screening including orthopantomogram, were included. The clinical, radiological and laboratory characteristics of the patients, collected during oral infectious focus screening, were analysed. Patient survival was calculated using Kaplan–Meier and mortality rates were compared using Cox-regression.
Results
A total of 208 patients were included, 77% (
n
= 161) male patients and 23% (
n
= 47) female, mean age was 58 years. A total of 67 (32%) had IE caused by viridans streptococci. No statistically significant correlation could be found between signs of oral infection and IE caused by viridans streptococci. The overall mortality at 30 days was 4.3% (95% CI: 1.6–7.0). There was no statistical difference in mortality between IE caused by viridans streptococci or
S. aureus
(HRR = 1.16, 95% CI: 0.57–2.37,
p
= 0.680).
Conclusion
The study indicates that the association between origin of the IE causing bacteria and findings during oral infection screening might be uncertain and may suggest that the benefit of screening and elimination of oral infections in patients admitted with IE might be overestimated. However, the results should be interpreted with caution and further studies are needed before any definite conclusions can be drawn.
Disability benefits and sick leave benefits represents huge costs in western countries. The pathways and prognostic factors for receiving these benefits seen in recent years are complex and manifold. ...We postulate that mental health and IQ, both alone and concurrent, influence subsequent employment status, disability benefits and mortality.
A cohort of 918 888 Norwegian men was followed for 16 years from the age of 20 to 55. Risk for health benefits, emigration, and mortality were studied. Indicators of mental health and IQ at military enrolment were used as potential risk factors. Multi-state models were used to analyze transitions between employment, sick leave, time limited benefits, disability benefits, emigration, and mortality.
During follow up, there were a total of 3 908 397 transitions between employment and different health benefits, plus 12 607 deaths. Men with low IQ (below 85), without any mental health problems at military enrolment, had an increased probability of receiving disability benefits before the age of 35 (HRR = 4.06, 95% CI: 3.88-4.26) compared to men with average IQ (85 to 115) and no mental health problems. For men with both low IQ and mental health problems, there was an excessive probability of receiving disability benefits before the age of 35 (HRR = 14.37, 95% CI: 13.59-15.19), as well as an increased probability for time limited benefits and death before the age of 35 compared to men with average IQ (85 to 115) and no mental health problems.
Low IQ and mental health problems are strong predictors of future disability benefits and early mortality for young men.
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