Development of a synthetic tissue engineered three‐dimensional printed bioceramic‐based bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro

Over the last decade there have been increasing efforts to develop three‐dimensional (3D) scaffolds for bone tissue engineering from bioactive ceramics with 3D printing emerging as a promising technology. The overall objective of the present study was to generate a tissue engineered synthetic bone graft with homogenously distributed osteoblasts and mineralizing bone matrix in vitro, thereby mimicking the advantageous properties of autogenous bone grafts and facilitating usage for reconstructing segmental discontinuity defects in vivo. To this end, 3D scaffolds were developed from a silica‐containing calcium alkali orthophosphate, using, first, a replica technique – the Schwartzwalder–Somers method – and, second, 3D printing, (i.e. rapid prototyping). The mechanical and physical scaffold properties and their potential to facilitate homogenous colonization by osteogenic cells and extracellular bone matrix formation throughout the porous scaffold architecture were examined. Osteoblastic cells were dynamically cultured for 7 days on both scaffold types with two different concentrations of 1.5 and 3 × 10⁹ cells/l. The amount of cells and bone matrix formed and osteogenic marker expression were evaluated using hard tissue histology, immunohistochemical and histomorphometric analysis. 3D‐printed scaffolds (RPS) exhibited more micropores, greater compressive strength and silica release. RPS seeded with 3 × 10⁹ cells/l displayed greatest cell and extracellular matrix formation, mineralization and osteocalcin expression. In conclusion, RPS displayed superior mechanical and biological properties and facilitated generating a tissue engineered synthetic bone graft in vitro, which mimics the advantageous properties of autogenous bone grafts, by containing homogenously distributed terminally differentiated osteoblasts and mineralizing bone matrix and therefore is suitable for subsequent in vivo implantation for regenerating segmental discontinuity bone defects. Copyright © 2016 John Wiley & Sons, Ltd.     

Fatigue is cross-sectionally not associated with objective assessments of inflammation,but changes in fatigue are associated with changes of disease activity assessments during biologic treatment of patients with established rheumatoid arthritis

Clinical Rheumatology - The associations between fatigue and disease activity in patients with rheumatoid arthritis (RA) have not been defined. The present objectives were to explore in RA patients...     

Health correlates of overweight and obesity in adults aged 50 years and over: results from the Survey of Health, Ageing and Retirement in Europe (SHARE). Obesity and health in Europeans aged > or = 50 years

QUESTIONS UNDER STUDY: To examine the association between overweight/obesity and several self-reported chronic diseases, symptoms and disability measures. METHODS: Data from eleven European countries participating in the Survey of Health, Ageing and Retirement in Europe were used. 18,584 non-institutionalised individuals aged 50 years and over with BMI > or = 18.5 (kg/m2) were included. BMI was categorized into normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9) and obesity (BMI > or = 30). Dependent variables were 13 diagnosed chronic conditions, 11 health complaints, subjective health and physical disability measures. For both genders, multiple logistic regressions were performed adjusting for age, socioeconomic status and behaviour risks. RESULTS: The odds ratios for high blood pressure, high cholesterol, diabetes, arthritis, joint pain and swollen legs were significantly increased for overweight and obese adults. Compared to normal-weight individuals, the odds ratio (OR) for reporting > or = 2 chronic diseases was 2.4 (95% CI 1.9-2.9) for obese men and 2.7 (95% CI 2.2-3.1) for obese women. Overweight and obese women were more likely to report health symptoms. Obesity in men (OR 0.5, 95% CI 0.4-0.6), and overweight (OR 0.5, 95% CI 0.4-0.6) and obesity (OR 0.4, 95% CI 0.3-0.5) in women, were associated with poorer subjective health (i.e. a decreased risk of reporting excellent, very good or good subjective health). Disability outcomes were those showing the greatest differences in strength of association across BMI categories, and between genders. For example, the OR for any difficulty in walking 100 metres was non-significant at 0.8 for overweight men, at 1.9 (95% CI 1.3-2.7) for obese men, at 1.4 (95% CI 1.1-1.8) for overweight women, and at 3.5 (95% CI 2.6-4.7) for obese women. CONCLUSIONS: These results highlight the impact of increased BMI on morbidity and disability. Healthcare stakeholders of the participating countries should be aware of the substantial burden that obesity places on the general health and autonomy of adults aged over 50.     

Expression profile of the telomeric complex discriminates between benign and malignant pheochromocytoma

Telomerase, a ribonucleoprotein complex that includes the telomerase RNA component, the telomerase-associated protein (TP1), the telomerase catalytic subunit (hTERT), and the heat shock protein 90 (HSP90), is closely related to the malignant potential of human tumors. In pheochromocytomas (PC) it is very difficult to predict malignant potential by conventional histology or immunohistochemical and molecular markers. To test whether the expression of telomerase subunits is reflected in the malignant transition of PCs, we determined their mRNA and/or protein expression in 28 benign and nine malignant PCs and compared the results with telomerase activity. RT-PCR analysis revealed that TP1 was ubiquitously expressed. The telomerase RNA component was found in all malignant (100%) and in 13 of 28 (46%) benign PCs. In contrast, hTERT was clearly associated with aggressive biological behavior. All of the malignant (100%), but only two of 28 benign (7%) PCs expressed hTERT. HSP90 was increased in malignant PCs, but was also expressed at a lower level in benign tumors. High telomerase activity was measurable in hTERT-positive tissues only. Our data indicate that hTERT, HSP90, and telomerase activity are up-regulated in malignant cells of the adrenal medulla. The common expression of hTERT and telomerase activity thus represents an additional prognostic marker that may identify more aggressive tumors.     

Heart assist systems--current status

BACKGROUND: Heart failure is the leading cause of death in the developed countries. Organ-preserving operative procedures on the failing heart like coronary artery bypass procedures or resection of left ventricular aneurysms are part of the routine care in cardiac surgery today. Terminal heart failure refractory to optimized drug therapy, however, will require a heart transplantation or the implantation of artificial blood pumps. While heart transplantation has proven to provide excellent long-term results with 10-year survival rates at 50%, it will remain a casuistic therapy, limited by the comparatively small number of procedures which can be performed. ARTIFICIAL BLOOD PUMPS: The current status of development of artificial blood pumps is represented by the broad availability of partially-implantable electric motor-driven left ventricular assist devices (LVAD), which still require a percutaneous cable for energy supply and device control from external sources while the blood pump itself resides inside the body. The recently introduced axial-flow devices (DeBakey, Jarvik 2000 and HeartMate II LVADs) deliver a continuous blood flow and obviously provide distinct advantages with regard to a reduction in size, weight and energy demands, simplified implantation technique and device control when compared to the previously available partially-implantable electric motor-driven pulsatile blood pumps (Novacor N100, TCl Heart Mate LVADs). The first systems designed for long-term or permanent use (Lion Heart LVAD, AbioCor replacement heart) are completely implantable devices featuring percutaneous energy transmission and device control. However, the latter are more complex devices and their clinical application is still limited to a small number of cases, which precludes a judgment about their potential at this time. INDICATIONS: The use of paracorporeal pneumatically accentuated blood pump systems is still indicated in cases of most severe biventricular heart failure and multiorgan failure or if only short- to mid-term circulatory support is anticipated. Well established indications for utilization of artificial blood pumps are the bridge-to-transplant procedure, which yields results comparable to primary heart transplantation, and acute cardiac failure following myocardial infarction or cardiac surgical procedures. In newborns and children, encouraging results were obtained when miniaturized blood pumps of the Berlin Heart System were utilized for heart failure in myocarditis or dilative cardiomyopathy. With advanced reliability of artificial blood pumps and in face of the high incidence of heart failure, especially in the older age group, the long-term application of artificial bloods pump appears to be justified.     

A thyroid nodule revealing a paraganglioma in a patient with a new germline mutation in the succinate dehydrogenase B gene

A 32-year-old asymptomatic female was diagnosed with an isolated thyroid nodule of 2.5 cm diameter. Fine needle aspiration suggested a medullary thyroid carcinoma. Consequently, a total thyroidectomy was performed. The nodule stained positive for chromogranin A, neurone-specific enolase and synaptophysin, but not for calcitonin. Finally, pathological analysis showed a thyroid paraganglioma. Although the tumour appeared to be sporadic in a patient with no personal or familial history of paraganglioma and/or pheochromocytoma, we have identified a new mutation (392delC) of the succinate dehydrogenase-B (SDHB) gene in the genomic DNA extracted from the leukocytes of the patient. That mutation induced a shift in the reading frame of the gene creating a premature stop codon (P131fsX135) which was predicted to result in a truncated SDHB protein of 135 amino acids.This report highlights the difficulties of this unexpected diagnosis of hereditary thyroid paraganglioma. It also discusses the clinical involvements in terms of familial screening and the necessary follow-up of the patient.