In vitro assessment of motility and proliferation of human osteogenic cells on different isolated extracellular matrix components compared with enamel matrix derivative by continuous single-cell observation

OBJECTIVES: The composition of the extracellular matrix (ECM) plays a substantial role in bone remodelling, fracture healing and osseointegration of dental implants by regulating proliferation, migration and finally differentiation of osteogenic cell populations. Emdogain, a composition of an enamel matrix derivative (EMD), has been introduced as a potential candidate to promote tissue regeneration. We investigated whether EMD could serve as a potential promoter of cell proliferation and motility as a dynamic cell response and compared the results with the ubiquitous single ECM components type I collagen and laminin. MATERIAL AND METHODS: In the investigation presented, we used a continuous observation method for the analysis of migratory and proliferative patterns of individual cells. We analyzed the response of four osteoblastic cell lines to specific extracellular ligands (type I collagen, laminin and EMD) over a period of 24 h compared with untreated glass surface and bovine serum albumin (BSA) as control groups. RESULTS: Type I collagen and laminin promoted cell motility significantly compared with the control groups and, in part, compared with EMD as well. The analysis of all 451 investigated cells revealed the following mean values for cell motiliy: untreated glass (n=99): 5.46+/-2.74 microm/h, BSA (n=89): 6.35+/-2.43 microm/h, type I collagen (n=108): 8.77+/-3.42 microm/h, laminin (n=74): 9.89+/-5.10 microm/h and EMD (n=81): 7.92+/-3.35 microm/h. Proliferation rates on the different surfaces were heterogenous for all investigated cell lines and varied from 0% to 50% within 24 h without a correlation to cell motility. CONCLUSION: In our study, EMD promotes cell motility better than the control groups. The two investigated single ECM components type I collagen and laminin promoted cell motility superior to EMD. This supports the hypothesis that EMD promotes a less mobile but more differentiated osteogenic phenotype.     

Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C,p.Leu97Pro (hemoglobin Wareham)

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.     

False-positive results in transcranial motor evoked potentials for outcome prognostication during surgery for supratentorial lesions

During monitoring of motor evoked potentials (MEP) elicited by transcranial electrical stimulation (TES) for prognostication of postoperative motor deficit, significant MEP changes without postoperative deterioration of motor function represent false-positive results. We aimed to investigate this phenomenon in a large series of patients who underwent resection of supratentorial lesions. TES was applied in 264 patients during resection of motor-eloquent supratentorial lesions. MEP were recorded bilaterally from arm, leg, and/ or facial muscles. The threshold criterion was applied assessing percentage increase in threshold level, which was considered significant if being?>?20% higher on affected side than on the unaffected side. Subcortical stimulation was additionally applied to estimate the distance to corticospinal tract. Motor function was evaluated at 24 h after surgery and at 3-month follow-up. Patients with false-positive results were analyzed regarding tumor location, tumor volume, and characteristics of the monitoring. MEP were recorded from 399 muscles (264 arm muscles, 75 leg muscles, and 60 facial muscles). Motor function was unchanged postoperatively in 359 muscles in 228 patients. Among these cases, the threshold level did not change significantly in 354 muscles in 224 patients, while it increased significantly in the remaining 5 muscles in 4 patients (abductor pollicis brevis in all four patients and orbicularis oris in one patient), leading to a false-positive rate of 1.1%. Tumor volume, opening the ventricle, and negative subcortical stimulation did not significantly correlate with false-positive results, while the tumor location in the parietal lobe dorsal to the postcentral gyrus correlated significantly (p?=?0.012, odds ratio 11.2, 95% CI 1.8 to 69.8). False-negative results took place in 1.1% of cases in a large series of TES-MEP monitoring using the threshold criterion. Tumor location in the parietal lobe dorsal to the postcentral gyrus was the only predictor of false-positive results.

     

Expression of decitabine-targeted oncogenes in meningiomas in vivo

Neurosurgical Review - Treatment of meningiomas refractory to surgery and irradiation is challenging and effective chemotherapies are still lacking. Recently, in vitro analyses revealed decitabine...     

Microsurgical clipping vs Woven EndoBridge (WEB) device for the management of unruptured wide-neck bifurcation aneurysms

Neurosurgical Review - The Woven EndoBridge device (WEB) was introduced in 2010 to treat wide-neck bifurcation aneurysms (WNBAs). Three landmark studies have been conducted to assess its safety and...     

Factors influencing defensive medicine-based decision-making in primary care: A scoping review

Rationale, Aims and Objectives

Medical decision-making processes in primary care are influenced by defensive medical practice. This involves a high possibility for negative consequences on many levels, for example, patient's health, health care system costs and a crisis of trust in the patient−doctor relationship. Aim of this review was to identify factors of defensive medicine-based decision-making in primary care.

Methods

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping reviews (PRISMA-ScR) guidelines and included systematic research on MEDLINE, Google Scholar and two German databases for additional grey literature. References provided further literature. Articles in English and German published from 1 January 1982 to 15 June 2022 were assessed.

Results

From 911 publications screened, 13 publications [6 qualitative studies and 7 quantitative (3 cross-sectional) studies] were included. In these, four main categories of factors influencing defensive medical practice were identified: (social) media, patients adopting a consumer attitude, health care system based working conditions and physician's tolerance for uncertainty. Pressure deriving from these four different sources is exerted on the general practitioner and may result in a defensive medical decision behaviour.

Conclusions

Four categories on influencing factors of defensive medicine could be identified. Strategies to tolerate uncertainty should be trained in under- and postgraduate training.     

Evolutionary demographic models for mortality plateaus.

Plateaus in the age pattern of hazard functions at extreme ages have been discovered in large populations of medflies, Drosophila, nematodes, and people. Mueller and Rose [(1996) Proc. Natl. Acad. Sci. USA 93, 15249-15253] have proposed several age-structured demographic models to represent effects of mutation accumulation and antagonistic pleiotropy on randomly evolving schedules of demographic rates. They assert that "evolutionary theory [as embodied in their models] predicts late-life mortality plateaus." This paper defines a class of Markovian models that includes those of Mueller and Rose and obtains a characterization of the possible limiting states. For the basic model, the result implies that schedules with late-life mortality plateaus above a minimal threshold are not limiting states. The models fail, but not for reasons previously conjectured. Transient states, visited early by the process, do display mortality plateaus. Other models from this class may have a role to play in reconciling observed plateaus with evolutionary theory.     

Regulation of human peripheral blood erythroid burst-forming unit growth by T lymphocytes and T lymphocyte subpopulations defined by OKT4 and OKT8 monoclonal antibodies

To reexamine the influence that T lymphocytes have on the regulation of human peripheral blood burst-forming unit (BFU-E) proliferation in the absence of a statistically significant number of monocytes, very low numbers (3 to 10 X 10(3)/mL) of a null cell fraction highly enriched for BFU-E were cultured alone and in the presence of 5 X 10(5) sheep erythrocyte-purified, autologous T lymphocytes in a methylcellulose culture system containing erythropoietin. T lymphocytes consistently enhanced the growth of BFU-E from the null cell fraction, as reflected in both their number and size. Irradiation of T lymphocytes prior to coculture with null cells markedly reduced this enhancement, strongly suggesting that T lymphocytes synthesize erythroid burst-promoting factors (BPA). To determine whether there were functional differences between the two major T lymphocyte populations as defined by OKT4 (T helper/inducer) and OKT8 (T suppressor/cytotoxic) murine monoclonal antibodies to stimulate the growth of BFU-E, both T cell subpopulations were isolated by negative (panning) or positive (fluorescence-activated cell sorting) selection and cocultured with null cells. No statistically significant differences emerged between unseparated, OKT4+ and OKT8+ T lymphocytes in their ability to stimulate the growth of BFU-E. Thus, these studies provide further evidence that T lymphocytes are a major population of BPA-producing cells and further that OKT4+ and OKT8+ T lymphocytes equally elaborate these factors.