Perceptions of shared decision making among health care professionals.

RATIONALE AND AIMS: Scholars have progressively promoted shared decision making (SDM) as an optimal model of treatment decision making in clinical practice. Nevertheless, it is unclear whether health care professionals (a) understand SDM well, (b) believe that SDM is helpful in their daily practice, and (c) are willing to practice SDM during their daily activities. These are crucial research topics; however, such research is still limited. The aim of this study was to apply the knowledge-attitude-behavior (KAB) model to probe health care professionals' perceptions of SDM. METHODS: A questionnaire was delivered to health care professionals working in various hospitals in southern Taiwan from 9 November 2018 to 8 January 2019. In addition to KAB constructs, this study explored the barriers to SDM practice and willingness to practice SDM among health care professionals. Predictive variables were subjected to multiple linear regression analysis to investigate health care professionals' views of SDM. RESULTS: Valid respondents numbered 400, including physicians, pharmacists, nurses, and other health care professionals. The characteristics of these health care professionals significantly affected the mean scores of the KAB model. A correlation analyses indicated that the KAB constructs were positively correlated with each other. The top three barriers reported were lack of time (57.50%), lack of knowledge (38.25%), and difficulty of developing patient decision aids (37.75%). Respondents who were willing to practice SDM opined that SDM can provide the best health care for patients (81.62%), can maintain and improve individual clinical expertise (77.38%), and can meet patient and social expectations (48.40%). CONCLUSIONS: Continuous emphasis on education regarding SDM and continuous promotion of a positive attitude of SDM acceptance can influence the behaviour of practicing SDM among health care professionals. Further study is required to assess the SDM practices of various health care professionals in different settings.

Iron oxide nanoparticles suppress the production of IL-1beta via the secretory lysosomal pathway in murine microglial cells.

BACKGROUND: Superparamagnetic iron oxide nanoparticles (IONPs) have been used as magnetic resonance imaging contrast agents for various research and diagnostic purposes, such as the detection of neuroinflammation and blood-brain-barrier integrity. As the central resident macrophage-like cells, microglia are responsible for managing foreign agents invading the CNS. The present study investigated the direct effect of IONPs on the production of pro-inflammatory cytokines by murine microglia stimulated with lipopolysaccharide (LPS). METHODS: Primary murine microglial cells were pretreated with IONPs (1-50 µg Fe/mL) for 30 min and then stimulated with LPS (100 ng/mL) for 24 h. Confocal microscopy is used to visualize the intracellular IONP distribution and secretory lysosomes after staining with LysoTracker and Rab27a, respectively. The production of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α was quantified by ELISA. The activity of IL-1ß converting enzyme (ICE) and TNF-α converting enzyme (TACE) was measured by fluorescent microplate assay using specific substrates. The lysosomal number, alkalinity, permeability and cathepsin B activity were determined by flow cytometry with ectodermal dysplasia-1, lysosensor and acridine orange staining, and using cathepsin B specific substrate, respectively. RESULTS: Confocal imaging revealed that IONPs were markedly engulfed by microglia. Exposure to IONPs attenuated the production of IL-1ß, but not TNF-α. Concordantly, the activity of ICE, but not the TACE, was suppressed in IONP-treated cells. Mechanistic studies showed that IONPs accumulated in lysosomes and the number of lysosomes was increased in IONP-treated cells. In addition, exposure to IONPs increased lysosomal permeability and alkalinity, but decreased the activity of cathepsin B, a secretory lysosomal enzyme involved in the activation of ICE. CONCLUSIONS: Our results demonstrated a contrasting effect of IONPs on the production of IL-1ß and TNF-α by LPS-stimulated microglia, in which the attenuation of IL-1ß by IONPs was mediated by inhibiting the secretory lysosomal pathway of cytokine processing.

Progression of periodontal destruction and the roles of advanced glycation end products in experimental diabetes.

BACKGROUND: Progression of diabetes-associated periodontal destruction and the roles of advanced glycation end products (AGEs) are investigated. METHODS: Diabetes was induced by streptozocotin injection, and periodontitis was induced via silk ligature placement with Porphyromonas gingivalis lipopolysaccharide injection in 64 Sprague-Dawley rats for 7 to 21 days. The quality of alveolar bone and attachment loss (AL) were measured by microcomputed tomography and histology. Destruction profiles were evaluated by histology, histochemistry, immunohistochemistry, and quantitative assessments of inflammatory cells, expression of receptors for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen. RESULTS: Without periodontitis induction, there was no obvious morphologic change in the periodontium, although slight elevations of AGEs and RAGE levels were noted in animals with diabetes. In the group with experimental periodontitis, significant periodontal bone loss was noted in animals both with and without diabetes from day 7, with more progressive bone loss in animals with diabetes during days 14 to 21. Histologically, the disruption of attachment and inflammation were observed from day 7, but subsequently subsided in animals without diabetes. A stronger and more prolonged response with significant AL was observed in animals with diabetes. Stronger inflammation, attenuated and persistent resorptive activity, and weaker proliferating potential were demonstrated by animals with diabetes. AGE deposition and RAGE expression were noted in animals without diabetes but with periodontitis, although levels were considerably elevated in the later stages in animals with diabetes. CONCLUSIONS: Diabetes augments periodontal destruction by reducing the proliferating capability and activating resorptive activities. Presence of the AGE-RAGE axis without diabetes implies that it is involved in the regulation of inflammation.

Controlling the proliferation and differentiation stages to initiate periodontal regeneration.

The success of periodontal regeneration depends on the coordination of early cell proliferation and late cell differentiation. The aim of this study was to investigate whether the proliferation or differentiation stage predominantly promotes the initiation of periodontal regeneration. Critical-sized periodontal defects were surgically created on rat maxillae and filled with poly-(D,L-lactide-co-glycolide)-poly-d,l-lactide hybrid microspheres encapsulating platelet-derived growth factor (PDGF, a promoter of mitogenesis), simvastatin (a promoter of osteogenic differentiation), or bovine serum albumin (a control). The encapsulation efficiency and in vitro release profiles of the microspheres were determined by high-performance liquid chromatography and enzyme-linked immunosorbent assay. The maxillae were harvested after 10 or 14 days and assessed by micro-computed tomography, histology, and immunohistochemistry for regeneration efficacy and cell viability. The rapid release of PDGF was observed within the first week, whereas a slow release profile was noted for simvastatin. The PDGF-treated specimens demonstrated a significantly higher bone volume fraction compared with bovine serum albumin- (p < 0.05) or simvastatin-treated (p < 0.05) specimens at day 14. Histologically, active bone formation originating from the defect borders was noted in both the PDGF- and the simvastatin-treated specimens, and functionally aligned periodontal ligament fiber insertion was only observed in the PDGF-treated specimens. The significant promotion of mitogenesis by PDGF treatment was also noted at day 14 (p < 0.05). In conclusion, increased mitogenesis or osteogenic differentiation may stimulate osteogenesis, and the upregulation of mitogenesis by PDGF appears to play a role in the initiation of periodontal regeneration.

Biocompatibility of PDGF-simvastatin double-walled PLGA (PDLLA) microspheres for dentoalveolar regeneration: a preliminary study.

Proper coordination of local signal to harmonize mitogenesis and osteogenic differentiation is one of the prerequisites to optimize dentoalveolar regeneration. In the study, we purpose to fabricate controlled-release microspheres encapsulating platelet-derived growth factor (PDGF) and simvastatin by coaxial electrohydrodynamic atomization. The microspheres demonstrated a distinct core and shell structure encapsulating PDGF and simvastatin respectively, and the encapsulation efficiency was 82.45-92.16% in-core and 51.37-71.34% in-shell. Sequential release of PDGF and simvastatin was seen in simvastatin-in-core and PDGF-in-shell (SP) design, and simultaneous release was achieved in PDGF-in-core and simvastatin-in-shell (PS) design. All microspheres demonstrated acceptable biocompatibility in vivo, with increased proliferation, reduced apoptosis, and reduced inflammation while PDGF or simvastatin was encapsulated. The PS design significantly reduced apoptosis than control, whereby significant and persistent enhanced proliferation was noted in SP group. The thickness of fibrotic capsules surrounding microspheres significantly reduced in both SP and PS group at day 14. The finding demonstrates that synergism of PDGF and simvastatin favored biocompatibility. Further investigations will aim on confirming the regenerative effect of SP and PS microspheres in a more clinically relevant model.

Patterns of diabetic periodontal wound repair: a study using micro-computed tomography and immunohistochemistry.

BACKGROUND: Diabetes is known to impair wound healing and deteriorate the periodontal condition. There is limited information about the patterns and events associated with periodontal wound repair. In this study, we evaluate the dynamics of periodontal wound repair using micro-computed tomography (microCT) and immunohistochemistry. METHODS: Thirty-six male rats were used, and diabetes was induced by streptozotocin. The maxillary first molars were extracted, and a tooth-associated osseous defect was created in the extraction area. Animals were sacrificed after 7, 14, and 21 days. Volumetry and distribution of bone trabeculae were evaluated by microCT imaging. The patterns of healing and collagen alignment were evaluated by histology. Advanced glycation end-product (AGE) deposition and expression of the receptor for AGEs (RAGE), tartrate-resistant acid phosphatase, and proliferating cell nuclear antigen were evaluated by histochemical and immunohistochemical staining. RESULTS: Diabetic animals demonstrated a significantly reduced bone volume and trabecular number as well as thinner trabeculae and more trabecular separation in osseous defects. The early stage was characterized by significantly reduced cellular proliferation and prolonged active inflammation without evident bone resorption, whereas delayed recovery of collagen realignment, matrix deposition, and bone turnover was noted in later stages. Although AGEs and RAGE were present during healing in diabetes and controls, a stronger and more persistent level of expression was observed in the group with diabetes CONCLUSIONS: Diabetes significantly delayed osseous defect healing by augmenting inflammation, impairing proliferation, and delaying bone resorption. The AGE-RAGE axis can be activated under metabolic disturbance and inflammation.

The effects of acellular amniotic membrane matrix on osteogenic differentiation and ERK1/2 signaling in human dental apical papilla cells.

The amniotic membrane (AM) has been widely used in the field of tissue engineering because of the favorable biological properties for scaffolding material. However, little is known about the effects of an acellular AM matrix on the osteogenic differentiation of mesenchymal stem cells. In this study, it was found that both basement membrane side and collagenous stroma side of the acellular AM matrix were capable of providing a preferential environment for driving the osteogenic differentiation of human dental apical papilla cells (APCs) with proven stem cell characteristics. Acellular AM matrix potentiated the induction effect of osteogenic supplements (OS) such as ascorbic acid, ß-glycerophosphate, and dexamethasone and enhanced the osteogenic differentiation of APCs, as seen by increased core-binding factor alpha 1 (Cbfa-1) phosphorylation, alkaline phosphatase activity, mRNA expression of osteogenic marker genes, and mineralized matrix deposition. Even in the absence of soluble OS, acellular AM matrix also could exert the substrate-induced effect on initiating APCs' differentiation. Especially, the collagenous stroma side was more effective than the basement membrane side. Moreover, the AM-induced effect was significantly inhibited by U0126, an inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling. Taken together, the osteogenic differentiation promoting effect on APCs is AM-specific, which provides potential applications of acellular AM matrix in bone/tooth tissue engineering.

Anti-inflammatory effects of IL-4 and IL-10 on Human Polymorphonuclear Leukocytes

Inflammatory responses are strictly regulated by coordination of pro-inflammatory and anti-inflammatory mediators. Interleukin-4 (IL-4) and interleukin-10 (IL-10) have typically the biologic anti-inflammatory effects on monocytes, but uncertain effects on polymorphonuclear leukocytes (PMNs). The PMNs are the first line of cellular response for host defense during acute inflammation. To modify hyper-inflammatory reaction with biologic anti-inflammatory mediators, we have determined the biologic anti-inflammatory activities of IL-4 and IL-10 on human PMNs. Human PMNs were pretreated with IL-4 or IL-10 and then stimulated with formyl methionyl leucyl phenylalanine (fMLP) for times indicated. The level of H2O2, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were determined in the each cell free supernatants. fMLP plays the role of a typical pro-inflammatory agent and, at least in determined conditions, down-regulated TNF release. IL-4 acts as an anti-inflammatory mediator but IL-10 did not show its anti-inflammatory activities on fMLP-stimulated human PMNs. IL-4 and IL-10 have different anti-inflammatory mechanisms. Perhaps, IL-10 needs co-factors to act as an anti-inflammatory mediator.

Limited Motion of Arms in Uncommunicable Children

PURPOSE: The study was designed to identify the necessity of radiographs and to decrease overutilization of radiographs in uncommunicable children who do not move their arms. This study provides clinical guidelines on radiographic evaluation and treatment of children with limited motion in the upper extremity. METHODS: The cases of one hundred thirteen pediatric patients under 36 months of age, who had visited the Emergency Center of Korea University Ansan Hospital from January 2000 to December 2001, were retrospectively reviewed. Pediatric patients with upper extremity injuries due to multiple trauma, laceration or motor vehicle accident were excluded. Parameters analyzed were age, sex, mechanism of injury, physical findings, radiographic finding, and injuried upper extremity region. We described focal tenderness and regional edema as physical finding. Each patient without regional edema was classified into an improved or a not-improved group depending on the outcomes after manual reduction. All statistical tests were conducted with twotailed levels of 0.05. RESULTS: Of the 113 patients, the mean age was 18.6+/-0.89 months. The most common injury mechanisms were unknown and traction. Minimal edema in the elbow joint was seen in 5 cases, and supracondylar fractures due to short falls were seen in 4 (80%) of those cases (p<0.05). The improved group was finally confined to radial head subluxation in 88 patients. Although all the not-improved-group patients had received radiographs, no abnormal findings were seen in the elbow. However, clavicle fracture due to fall above or from a level surface were seen in 4 cases (20%) of the not-improved group (p<0.05). No difference of injury mechanism existed between the improved and the not-improved groups. CONCLUSION: Recommand Radiographic evaluations in Children not-used arm with regional edema before manual reduction. But without regional edema, manual reduction of elbow is first. If children without regional edema do not improve after manual reduction of elbow and they are injuried due to fall, children should be assessed for fractures of clavicle.

Lack of IL-10 Release from Human Polymorphonuclear Leukocytes

PURPOSE: Polymorphonuclear leukocytes (PMNs) are the first line of cellular response for host defense during acute inflammation. The ability of PMNs to produce and release numerous pro-inflammatory cytokines is now estabilished and plays an important role in triggering and maintaining the inflammatory response. We studied the autocrine downregulation of this process by invesgating the potential production by human PMNs of the major anti-inflammatory cytokine, interleukine 10 (IL-10). METHODS: Human PMNs were isolated from the peripheral blood of health volunteers by using the modified boyum method. Human PMNs were incubated at 37 degrees Cwith and without formyl Met-Leu-Phe (fMLP) for 30 minute, 2 hours, 4 hours, and 20 hours. The level of IL-10 was determined in each of the cell-free supernatants by using the enzyme linked immunosorbent assay (ELISA) method. RESULTS: Non-stimulated PMNs generated 1.40 +/- 1.791pg/mL to 3.46 +/- 1.607 pg/mL of IL-10 over the time course. Stimulation with fMLP resulted in an increase in the constitutive PMN-derived IL-10 by 2.74 +/- 0.762 pg/mL, 1.27 +/- 0.262 pg/mL, 1.19 +/- 0.364 pg/mL, and 2.44 +/- 1.317 pg/mL at 30 min, 2 hr, 4 hr, and 20 hr after stimulation, respectively, but these increases were not statiscally significant. CONCLUSION: Human PMNs seem unable to induce release of the most potent anti-inflammatory cytokine, IL-10, and down-regulate inflammatory response due to the autocrine mechanism. This could partly account for the persistence of local inflammation, when PMNs are the main infiltrating cells.

Prognostic Factors of Geriatric Trauma Patients

BACKGROUND: It has been documented that certain prognostic factors may affect the outcomes of the old aged victims by trauma. Considering that trauma is the sixth most common cause of death in people over the age of 65 years and there is a rapid growth of elderly population, it is paramount to understand the prognostic factors when dealing with geriatric trauma patients. Hypothesis and Goals : It can be hypothesized that the prognostic factors should be determined independently between populations being consisted of different races, countries, socio-economic states, cultures, or so on. Thus, study was designed to evaluate the factors affecting the outcomes of elderly Korean trauma patients. METHODS: One hundred forty six patients aged over 65 years were retrospectively reviewed, who visited the Emergency Canter of Korea University from January, 1997 to June, 1998. Of 146 patients, 7 were excluded due to discharge against advice or transfer to the other hospitals. Parameters analysed were age, sex, mechanism of injuries, body region injured, Injury Severity Score (ISS), previous medical illness, hospital morbidity, duration of hospital stay, and cost. Each patient was classified into improved or not-improved groups depending on the outcomes, and young-old or old-old group depending on the age. The factors affecting the hospital stay in improved patients were analyzed in the parameters of previous medical illness, hospital morbidity, multiple injuries, ISS, and age. All statistical tests were conducted with two-tailed levels of 0.05. RESULTS: Of 139 patients, the mean age was 74+/-7.1 years, mean ISS 9.3+/-7.26, mean hospital stay 27+/-27.1 days. Most commonly injured body region was the extremities due to fall from a level surface. Rate of previous illness showed 0.94 medical diseases per person and were aggravated after trauma in 39 patients (60.9%). Hospital morbidity rate was 0.46 incidents per person. There were no differences in age and duration of hospital stay between the improved and the not-improved group. Substantial differences were noted in affected body region, incidence of previous illness, and hospital morbidity between the groups (p=NS). Not-improved group had higher ISS (p<0.05). ISS, previous illness and hospital morbidity affected the duration of hospital stay in the improved group. Hospital stay was 40+/-25.1 days in patients with ISS over 6 while 6+/-8.6 days in those with ISS 5 (p<0.05). Hospital stay in the improved was 26+/-26.9 days while 31+/- 24.8 days in the improved old-old group (P=NS). Hospital stay in the young-old minor trauma (ISS5) patients with previous illness and hospital morbidity was 26+/-10.1 days while 4+/-7.3 days in those without previous illness and hospital morbidity (p<0.05). CONCLUSION: Previous medical illness and hospital morbidity, not age, are predictive of outcomes of geriatric trauma patients with respect to hospital stay. As most of the hospital morbidity was a trauma-induced aggravation of previous medical illness and hospital morbidity contributing poor outcomes can be potentially avoidable, routine aggressive care far the geriatric trauma patients with previous medical illnesses is needed.