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In recent years Muslim extremist groups have sought to establish a contemporary Islamic caliphate. Such groups have not historically sought to establish such a territory; this form of sovereignty did not exist in the Prophet’s time, and is quite unlike the traditional Islamic model or that practiced by the Prophet in Medina. Moreover, this ideal state incorporates elements of the modern, sovereign nation-state. It is ironic that, although such groups criticize Western systems and laws, their concept of ‘the state’ derives from the very European ideology that they so violently oppose. This paper examines how notions of modern statehood have influenced the ideologies of state and law espoused by contemporary extremist groups.

Cell culture media influence the characteristics of human osteogenic periosteal sheets. We have previously found that a stem cell medium facilitates growth and collagen matrix formation in vitro and osteogenesis in vivo. However, it has not yet been demonstrated which culture medium is superior for osteoclastogenesis, a prerequisite for reconstruction of normal bone metabolic basis. To address this question, we compared chemotaxis and osteoclastogenesis in tissue-engineered periosteal sheets (TPSs) prepared with two types of culture media. Periosteal tissues obtained from adult volunteers were expanded with the conventional Medium 199 or with the stem cell medium, MesenPRO. Hematopoietic enhanced-green-fluorescent-protein (EGFP)-nude mice were prepared by γ-irradiation of Balb/c nu/nu mice and subsequent transplantation of bone marrow cells from CAG-EGFP C57BL/6 mice. TPSs were implanted subcutaneously into the chimeric mice and retrieved after intervals for immunohistopathological examination. EGFP+ cells were similarly recruited to the implantation site in both the TPSs prepared, whereas the distribution of CD11b+ cells was significantly lower in the TPS prepared with the stem cell medium. Instead, osteoclastogenesis was higher in the TPS prepared with the stem cell medium than in the one prepared with the conventional medium. These findings suggest that the stem cell medium is preferable for the preparation of more functional TPSs.

Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. Cebpb and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

Modern extremist groups have revived the use of certain concepts of Islamic dogma and wilfully misinterpreted them as a means of achieving their own ends. Dae‘sh (Islamic State of Iraq and Syria) is the most striking example. They have made declarations of takfir (excommunication) regarding Muslim rulers, maintaining that only Dae‘sh land is a dar al-Islam (abode of Islam) and that other lands are dar al-kufr or harb (abodes of unbelief or war), just as the Khawarij sect believed in the 7th century ce. They do not employ the concept of hijra (migration) in its traditional, defensive sense, but rather as a means of strengthening their own power by recruiting from around the world and launching military jihads, all in order to ‘reclaim’ the dar al-kufr and establish an Islamic state. This article examines the evolution of these terms throughout Islamic history, their misinterpretation by extremist groups, and their modern legal status.

Objective Although the pathogeneses of Alzheimer’s disease (AD) and periodontal diseases have overlapping features, including ageing and chronic inflammation, the association between AD and periodontitis remains unclear. To explore the pathogenesis of periodontitis, a comprehensive gene expression/transcriptome analysis in periodontitis-affected gingival tissues found that the AD pathway was significantly up-regulated in periodontitis-affected gingival tissues. AD-related genes, amyloid beta precursor protein (APP), interleukin-1 beta and compliment 1QA, were significantly elevated in periodontitis. In the present study, balance between mRNA expression of APP and a potent amyloid degradation enzyme, neprilysin (NEP), as well as protein localisation of APP and NEP were analysed. Design Eighteen periodontitis-affected and 18 clinically healthy control gingival tissues were taken from patients with severe chronic periodontitis or undergoing tooth extraction. Total RNA was purified and used for quantitative reverse transcription real-time polymerase chain reaction (qRT-PCR). The localisation of APP and NEP was analysed by immunohistochemistry (IHC). Results Both APP and NEP genes were up-regulated in periodontitis-affected gingival tissues. APP-expressing macrophages and NEP-expressing neutrophils and fibroblasts, reflecting inflammatory stages, were detected in inflamed gingival tissues by IHC. Conclusion The up-regulation of APP and NEP mRNA levels in periodontitis-affected gingival tissues compared with healthy controls was confirmed by qRT-PCR analyses. Since NEP is one of the primary enzymes that degrades amyloid beta, increased NEP mRNA levels in periodontitis may act as an inhibitor of amyloid beta accumulation in gingival tissues, balancing increased APP mRNA expression. However, NEP has several effects including degradation of vasoactive substances; therefore, further sresearch is needed.

The ideology and actions of certain militant groups in the Middle East are often condemned as a perversion of Islamic precepts. In order to achieve a theologically ideal society, these groups espouse takfirism, a minority ideology that endorses violence, and in particular advocates the killing of other Muslims who are declared to be unbelievers. These groups justify their words and deeds with direct quotations from the Qur’an and the Sunna, which are the sources of Islamic law (Shari‘a), as well as by citing historical precedents such as the Khawarij movement and Ibn Taymiyya’s fatawa. This article aims to analyse how these groups (and in some cases state actors) defend their actions in legal terms and how mainstream Islamic scholars respond to what they consider to be doctrinal deviations.

To assure the quality of cells to be used in cell therapy, we examined the applicability of digital holographic microscopy (DHM) for non-invasive, quantitative assessment of changes in cell morphology.Mesenchymal stem cells derived from adipose tissue (MSC-AT) and bone marrow (MSC-BM), in addition to human alveolar periosteal cells (PC) as a reference, were γ-ray irradiated (1 and 4 Gy), and their morphological changes were quantified without fixation using holographic microscopy. After detachment and fixation with ethanol, cell number and surface antigen expression were determined using an automated cell counter kit and flow-cytometry, respectively.Among various indexes, only indexes related to cell size were significantly changed after γ-irradiation. Both BMC-AT and BMC-BM were enlarged and more sensitive to a low dose of γ-irradiation than PC. In contrast to PC, proteins related to DNA damage repair (γ-H2AX, p21Instead of DNA damage markers, we suggest that cell morphological parameters (e.g. cell volume) that are monitored by DHM could be a useful and more stable marker of MSC quality.

Herein a vibration test method is discussed based on a non-contact, non-destructive excitation input using a laser-induced plasma (LIP) shock wave and a non-contact input estimation using Newton’s second law of motion. We have previously introduced a non-contact vibration test method using an excitation force generated by laser ablation, but it cannot be used when the target structure is lightweight, fragile, and small-sized because a crater with a diameter of several micrometers is created. The LIP generates a highly reproducible shock wave, which become an excitation force to a target structure. This shock wave depends on the gas density, gas specific heat ratio, laser fluence, and ambient environment. If these parameters are constant, the LIP excitation force can be estimated beforehand, allowing only the output measurement to determine the frequency response measurement of an input–output relationship of the target structure. After calibrating the LIP excitation, the frequency response function of a target structure can be obtained.

A safety confirmation system is a system intended to enable users to share information about the extent of damage in the event of a disaster. In recent years, these systems have generally been implemented as a Web system using cloud computing. The configuration used for the safety confirmation system included a Web server and DB server, amongst others, and these resources can be easily procured by cloud computing. In addition, implementation in the cloud has many merits such as a shortened development period and accelerated service start time. However, cloud computing is a system on the Internet; thus, there is concern about the risk of illegal access from the outside and information leakage. The safety confirmation system requires a secure system infrastructure in which to store attribute information and users’ personal information. Therefore, a cloud-based safety confirmation system would need to be convenient to use and secure. In this paper, we propose to improve the safety by constructing the safety confirmation system in a virtual private cloud environment. The evaluation of the system showed that it was possible to prevent external illegal access and information leakage and to operate the safety confirmation system such that it was highly convenient to use.

Objective To elucidate the mechanism underlying secretion of human immunodeficiency virus type 1 (HIV-1) into the oral cavity, by examining the relationships between various oral and systemic factors and the viral load in saliva. Methods Plasma and saliva samples from HIV-1 infected patients were assayed using the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Test, version 1.0 and a Poisson distribution-based polymerase chain reaction (PCR) method for quantifying HIV-1 RNA and DNA. Results Forty-four pairs of samples were obtained from 18 patients. Salivary viral load was approximately 10% of the plasma viral load, but higher than the plasma load in two patients. The salivary viral DNA load was Conclusions The present results suggest that excretion through salivary glands, but not occult bleeding, may be a major pathway of HIV-1 into the oral cavity.

Background and Purpose Sinus lift (SL) using cultured autogenous periosteal cells (CAPCs) combined with autogenous bone and platelet-rich plasma (PRP) was performed to evaluate the effect of cell administration on bone regeneration, by using high-resolution three-dimensional computed tomography (CT). Materials and Methods SL with autogenous bone and PRP plus CAPC [CAPC(+)SL] was performed in 23 patients. A piece of periosteum taken from the mandible was cultured in M199 medium with 10% fetal bovine serum (FBS) for 6 weeks. As control, 16 patients received SL with autogenous bone and PRP [CAPC(−)SL]. Three-dimensional CT imaging was performed before and 4 months and 1 year after SL, and stratification was performed based on CT numbers (HUs) corresponding to soft tissue and cancellous or cortical bone. Results The augmented bone in CAPC(+)SL revealed an increase in HUs corresponding to cancellous bone as well as a decrease in HUs corresponding to grafted cortical bone. In addition, HUs corresponding to cancellous bone in the graft bed were increased in CAPC(+)SL but were decreased in CAPC(−)SL. Insertion torque during implant placement was significantly higher in CAPC(+)SL. Conclusion By promoting bone anabolic activity both in augmented bone and graft bed, CAPCs are expected to aid primary fixation and osseointegration of implants in clinical applications.

Hydrogen peroxide is produced commercially by the sequential hydrogenation and oxidation of anthraquinone (AQ) and tetrahydroanthraquinone (THAQ). The hydrogenation of AQ and THAQ on the Pd(111) surface is investigated with periodic density functional theory (DFT) calculations in this work. Dihydrogen is preferentially adsorbed on the top of a Pd atom, and the produced hydrogen atoms are on two neighboring 3-fold hollow fcc positions. The three benzene rings of AQ are located at bridge sites on the Pd(111) surface. The two carbonyl oxygen atoms of AQ and THAQ successively abstract the surface hydrogen atoms to produce anthrahydroquinone (AHQ) and tetrahydroanthrahydroquinone (THAHQ), respectively. The formation of unwanted byproducts, anthrone (AN), tetrahydroanthrone (THAN), oxanthrone (OAN), and tetrahydro-oxanthrone (THOAN), in the hydrogenation step of the AQ process is also studied to consider the suppression of these byproducts.

Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. Cebpb and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.

Improving accuracy ofthe gear tooth surface has become an important challenge, because the toothsurface accuracy greatly influences vibration of gears. However, for the spiralbevel gear, the tooth surface accuracy is considered to be very difficult toevaluate because the geometrical theory is difficult. Generally, the managementof tooth surface accuracy has conventionally been substituted by the toothsurface contact evaluation with red lead, which is a kind of paint. However,the results of visual examinations are too subjective. We therefore focused onthe infrared ray imagery to investigate the gear tooth meshing. In this research,a high response infrared thermography was used to estimate the tooth contact ofa hypoid gear under running conditions. Specifically, we looked at the increasein temperature on the tooth surface caused by gear meshing. The results clearlyshowed that the temperature was affected by load, sliding speed between toothsurfaces, and the average peripheral speed of tooth surface. We also proposedan equation that predicts tooth surface temperature rise and showed its utility.Thus, the proposed method effectively evaluates the tooth surface accuracy ofhypoid gear.

This paper proposes a method of acoustic testing based on a point source generated by laser-induced breakdown in air. A high-power neodymium–yttrium–aluminum–garnet pulse laser is used in this system for generating the laser-induced breakdown in acoustic fields. Plasma formation can be realized by the laser-induced breakdown if the local intensity of the laser beam reaches 10 15 W/m 2 . The shock wave that is yielded by consuming a part of the plasma energy becomes a sound source. Assuming that the laser beam is focused to a small volume through a convex lens and the sound source by the laser induced-breakdown has nondirectional property, it is possible to create a point source with this technique. Securing the laser light path installs no device for acoustic excitation in acoustic fields. The system is validated by comparing the resonant frequencies of a very small space measured by the laser-induced breakdown and calculated by theoretical model.

We previously demonstrated that thicker periosteal sheets with enhanced cell layering maintain their component cells at relatively immature stages of differentiation but express a high in vivo osteogenic potential. As it has been recently proposed that stiff scaffolds provide a mechanical cue to various cell types that promotes differentiation, we postulated that the maintenance of immature cells in our periosteal sheets is due to the mechanical stiffness of the multilayered-cell architecture. To demonstrate the biomechanical characteristics of our periosteal sheets, we have determined their stiffnesses with atomic force microscopy (AFM) and evaluated the expression of extracellular matrix (ECM) components specifically by both immunocytochemistry and a complementary DNA microarray technology. Compared to osteoblastic Saos2 cells, the cytoskeletal fibers were developed more in the periosteal cells, but the periosteal cells in monolayer culture developed before either the cells in the peripheral or central regions of the periosteal sheets developed. However, the nanoindentation by AFM distinguished the central region from the peripheral region. The peak stiffness values of cells were ordered as follows: tissue culture polystyrene (1.66GPa)≫dispersed (9.99kPa)>central region (5.20kPa)>peripheral regions (3.67kPa). Similarly, the degree of development of α-smooth muscle actin (αSMA) filaments within cells was dispersed>central region>peripheral region. In conjunction with the abundantly deposited ECM in the periosteal sheets, these findings suggest that the order of cell stiffness may depend on the integration of the stiffness of individual ECM components and the extent of cytoskeletal fiber formation. Because recently published data have demonstrated that the optimal stiffness for osteogenic differentiation is 25-40kPa, it is plausible that the periosteal cells residing in the less-stiff multilayer regions could be maintained at relatively immature stages under the control of the stem-cell medium in vitro but start differentiating when exposed to the proper stiffness upon release from the culture conditions at the implantation site.

Jawa Bali 500 kV power system grid comprises of two large areas which are connected by two double circuit transmission lines. However, under high power transfer from east to west area on October 19, 2012 resulted in Jawa Bali power system experienced voltage drop until 0.86 pu in west area. Very low voltage may lead to voltage stability phenomenon. This paper would analyze maximum power transfer capability without and with introducing shunt compensators. Static analysis using P-V Curve method is aimed to assess voltage stability phenomenon. P-V Curve corresponds with total active power transfer (P) of two transmission lines connecting west and east area compared to voltage system (V) behavior in west area. The study also includes investigation of power transfer capability limit enhancement with use of shunt compensator compare to initial condition. Various options of shunt compensators considered are MSCs, SVC, and STATCOM. Power Transfer Stability Index and Q-V Curve sensitivity were considered to acquire list ranking location of shunt compensator. Based on static voltage analyses result, use of shunt compensators was proven to increase power transfer limit.

We have previously demonstrated that multilayered periosteal sheets prepared from the explant culture of alveolar periosteum serve as a promising osteogenic grafting material in periodontal tissue regeneration. For the preparation of more potent periosteal sheets, we examined the applicability of stem-cell culture media. Compared to the control medium (Medium 199+10% FBS), periosteal sheets expanded with MesenPRO-RS™ medium exhibited these features: Cells grew three-dimensionally and deposited collagen in the extracellular spaces to form thicker multilayers of cells. Chondrocytic markers were not significantly upregulated. Contractile force was generated in proportion with the increased thickness of the periosteal sheets and the formation of cytoplasmic α-smooth muscle actin fibers. However, myofibroblastic markers were not significantly upregulated. The surface marker CD146 was substantially upregulated, while both CD73 and CD105 were downregulated. Alkaline phosphatase, a representative osteoblastic marker, was not upregulated by osteogenic induction. However, these expanded periosteal sheets exhibited substantially stronger osteogenic differentiation when implanted in nude mice. Therefore, despite our reservations, MesenPRO medium effectively expanded the cells contained in periosteal sheets to promote the formation of thicker multilayers of cells in vitro, and these enhanced periosteal sheets expressed increased osteogenic potential at implantation sites in vivo. In conjunction with data indicating that CD146-positive cells were notably expanded and the recently proposed concept that CD146 is a marker for osteogenic progenitor cells found in the bone marrow stroma, our findings suggest that MesenPRO medium improves the preparation of highly osteogenic periosteal sheets suitable for clinical application largely through the induction of CD146-positive cells.

OBJECTIVES To investigate clinical and microbiological characteristics of community-acquired bacteremia (CAB). METHODS We retrospectively analyzed subjects with CAB hospitalized at Saga University Hospital between January 2009 and September 2011. We investigated causative organisms, primary infection sites, and subject summaries and complications, and analyzed the mortality factor. RESULTS CAB incidence was 185 cases, with 192 organisms cultured. Causative organisms were gram-positive bacteria in 81 strains (42%), 9 (11%) of which were methicillin-resistant Staphylococcus aureus (MRSA). Gram-negative bacteria were identified in 111 strains (58%), with 80% Enterobacteriaceae. Five of the 111 (5%) were caused by extended-spectrum beta-lactamase (ESBL) producing bacteria. The most frequent bacteremia portal was intraabdominal infection (29%, 54/185). During hospitalization of 1-180 days, 20 subjects eventually died. Neutropenia on admission was associated with significantly higher mortality than without (30% vs. 3%, p < 0.001). Septic shock rates were higher in non-survivors than survivors (45% vs. 14%, p = 0.002), and more complications were documented in non-survivors than survivors (50% vs. 25%, p = 0.017). No specific pathogen or primary infection site was associated with higher mortality. CONCLUSIONS Antimicrobial-resistant pathogens such as MRSA and ESBL producers should be considered even in CAB, especially in subjects with healthcare-associated infection, regardless of how small the number. The CAB treatment course should consider subjects summaries, severity, and complications.

In preparing cell-based products for regenerative therapy, cell quality should be strictly controlled. Methodologies for evaluating cell viability, identity, and purity are established and used routinely, whereas current methodologies for evaluating cell safety, particularly genetic integrity or tumorigenicity, are time-consuming and relatively insensitive. As part of developing a more practical screening system, the authors previously demonstrated that γ-H2AX and p53 were useful markers for evaluating the history of DNA damage. To validate these markers further and develop a more quantitative methodology, single cell-based expression of these markers and two additional candidates have now been examined using flow cytometry (FCM). FCM analysis and immunofluorescent staining demonstrated that γ-ray-irradiation suppressed proliferation, enlarged cells, and cell nuclei, and immediately upregulated γ-H2AX and p21(waf1) in large numbers of cells for up to 12 days. Gamma-H2AX foci were formed in the nuclei of many affected cells. An initial sharp increase in p53 expression declined slowly over 12 days, while Rb expression increased linearly. The present findings suggest that this high-throughput, cell-based, combinational evaluation of protein markers and cell size enables a small number of cells with a history of DNA damage to be detected quickly and routinely from within a very large cell population. Using this screening methodology will improve the ability to verify the quality of cell-based products used in regenerative therapy.

The development of diabetic cardiomyopathy is accompanied with a high membrane-bound protein kinase C (PKC) levels. Curcumin is a naturally occurring compound which is known to inhibit PKC activity. However, the effects of curcumin on ameliorating diabetic cardiomyopathy are still undefined. We evaluated whether curcumin treatment is associated with the modulation of PKC-α and -β₂-mitogen-activated protein kinase (MAPK) pathway in experimental diabetic cardiomyopathy. Diabetes was induced in male Sprague-Dawley rats by streptozotocin (STZ). Curcumin (100mg/kg/day) was started three weeks after STZ injection and was given for 8 weeks. We demonstrate that curcumin significantly prevented diabetes-induced translocation of PKC-α and -β2 to membranous fraction and diabetes-induced increased phosphorylation of p38MAPK and extracellular regulated-signal kinase (ERK)1/2 in left ventricular tissues of diabetic rats. Curcumin treatment also markedly decreased NAD(P)H oxidase subunits (p67phox, p22phox, gp91phox), growth factors (transforming growth factor-β, osteopontin) and myocyte enhancer factor-2 protein expression as well as inhibited NF-κB activity at nuclear level. Furthermore, curcumin decreased the mRNA expression of transcriptional coactivator p300 and atrial natriuretic peptide, decreased accumulation of ECM protein and reversed the increment of superoxide production in left ventricular tissues, as evidenced by dihydroethidium staining. It is also significantly lowered plasma glucose and attenuated oxidative stress, as determined by lipid peroxidation and activity of anti-oxidant enzyme, and as a result attenuated cardiomyocyte hypertrophy, myocardial fibrosis and left ventricular dysfunction. Taken together, it is suggested that curcumin by inhibiting PKC-α and -β₂-MAPK pathway may be useful as an adjuvant therapy for the prevention of diabetic cardiomyopathy.

Edaravone, a novel antioxidant, acts by trapping hydroxyl radicals, quenching active oxygen and so on. Its cardioprotective activity against experimental autoimmune myocarditis (EAM) was reported. Nevertheless, it remains to be determined whether edaravone protects against cardiac remodelling in dilated cardiomyopathy (DCM). The present study was undertaken to assess whether edaravone attenuates myocardial fibrosis, and examine the effect of edaravone on cardiac function in rats with DCM after EAM. Rat model of EAM was prepared by injection with porcine cardiac myosin 28 days after immunization, we administered edaravone intraperitoneally at 3 and 10 mg/kg/day to rats for 28 days. The results were compared with vehicle-treated rats with DCM. Cardiac function, by haemodynamic and echocardiographic study and histopathology were performed. Left ventricular (LV) expression of NADPH oxidase subunits (p47(phox), p67(phox), gp91(phox) and Nox4), fibrosis markers (TGF-β(1) and OPN), endoplasmic reticulum (ER) stress markers (GRP78 and GADD 153) and apoptosis markers (cytochrome C and caspase-3) were measured by Western blotting. Edaravone-treated DCM rats showed better cardiac function compared with those of the vehicle-treated rats. In addition, LV expressions of NADPH oxidase subunits levels were significantly down-regulated in edaravone-treated rats. Furthermore, the number of collagen-III positive cells in the myocardium of edaravone-treated rats was lower compared with those of the vehicle-treated rats. Our results suggest that edaravone ameliorated the progression of DCM by modulating oxidative and ER stress-mediated myocardial apoptosis and fibrosis.

In ongoing clinical research into the use of cultured autogenous periosteal cells (CAPCs) in alveolar bone regeneration, CAPCs were grafted into 33 sites (15 for alveolar ridge augmentation and 18 for maxillary sinus lift) in 25 cases. CAPCs were cultured for 6weeks, mixed with particulate autogenous bone and platelet-rich plasma, and then grafted into the sites. Clinical outcomes were determined from high-resolution three-dimensional computed tomography (3D-CT) images and histological findings. No serious adverse events were attributable to the use of grafted CAPCs. Bone regeneration was satisfactory even in cases of advanced atrophy of the alveolar process. Bone biopsy after bone grafting with CAPCs revealed prominent recruitment of osteoblasts and osteoclasts accompanied by angiogenesis around the regenerated bone. 3D-CT imaging suggested that remodeling of the grafted autogenous cortical bone particles was faster in bone grafting with CAPCs than in conventional bone grafting. The use of CAPCs offers cell-based bone regeneration therapy, affording complex bone regeneration across a wide area, and thus expanding the indications for dental implants. Also, it enables the content of particulate autogenous bone in the graft material to be reduced to as low as 40%, making the procedure less invasive, or enabling larger amounts of graft materials to be prepared. It may also be possible to dispense with the use of autogenous bone altogether in the future. The results suggest that CAPC grafting induces bone remodeling, thereby enhancing osseointegration and consequently reducing postoperative waiting time after dental implant placement.

In this in vitro study, novel porous poly(l-lactic acid) membranes were developed to improve periosteal sheets by promoting initial adhesion of periosteal tissue segments and stimulating the formation of a viable multilayered cellular sheet. The biocompatibility, biodegradability, and osteogenicity were evaluated using human periosteal tissue segments cultured on porous poly(l-lactic acid) membranes; the periosteal sheets were osteogen induced and were then implanted in the dorsal subcutaneous tissue of nude mice. In vivo, the membrane degraded into clusters of membrane particles separated by wide cracks; fibroblastic cells invaded along with small blood vessels from the surrounding mouse connective tissue. In osteoinduced periosteal sheets, the membrane clusters were surrounded by numerous capillaries and a number of tartrate-resistant acid phosphatase–positive, multinucleated cells. Neither severe inflammation nor fibrous encapsulation was observed throughout the implantation (~12 weeks). These porous poly(l-lactic acid) membranes were highly biocompatible and functioned well as biodegradable scaffolds that could enhance the use of osteogenic periosteal sheets in therapy.

There are evidences that the activation of AMPK is playing pivotal role in the lipid and glucose metabolism. It has been reported that both the AMPK and angiotensin-II acts as a negative regulator for each protein. It has been well proven that the MAPK cascade could be modulated by the presence of angiotensin-II. Moreover, studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation. Therefore, we speculate and tried to demonstrate that the modulation of AT-R/MAPK pathway through AMPK might play crucial roles for the pathogenesis of diabetic cardiomyopathy, using the transgenic (Spontaneous Diabetic Torii-SDT) rats. We performed Western blot analysis for the measurement of myocardial AT-R, AMPK and MAPK cascades-related protein expressions, p67-phox and caspase-12. In addition, we employed dihydroethidium (DHE), Azan Mallory and hemotoxylin eosin (HE) staining methods to demonstrate the superoxide radical production, fibrosis and hypertrophy, respectively. The protein expressions, such as AT-1R, p-ERK1/2, p67-phox and caspase-12 were found to be significantly increased and conversely, the Ang-(1-7) mas R, Tak1, LKB1 and p-AMPKα1, p-p38 MAPK and p-JNK protein expressions were found to be considerably decreased in the SDT rats, in comparison to the normal rats. The DHE, Azan Mallory and HE stainings also revealed that the SDT rats have more superoxide radical production, fibrosis and hypertrophy, respectively than the normal rats. Taken together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy.

Human cultured periosteal sheets, which are developed from small excised periosteum tissue segments (PTSs) in culture dishes by simple expansion culture, have been applied as a promising autologous osteogenic grafting material for periodontal regenerative therapy. However, the weak initial adhesion of PTSs to dish surfaces often hampers cellular outgrowth and limits the number of preparations. To correct this weakness and still avoid the use of animal-derived adhesion biomolecules, we have developed a novel, biodegradable, porous poly(L-lactic acid) (pPLLA) membrane. Freshly excised PTSs bound well to the highly porous pPLLA membrane, possibly due to the presence of semihemispheric 20-30 μm diameter openings on the upper surface. Global gene expression analysis demonstrated that periosteal sheets cultured on pPLLA membranes upregulated expression of many adhesion molecules. Osteogenic induction stimulated the production of proteoglycans by these cells and concomitantly enhanced their expansion and penetration into the deep pore regions of the membrane in parallel with the progression of in vitro mineralization. These findings suggest that our pPLLA membranes not only facilitate initial adhesion, primarily mediated by adsorbed proteins, but also enhance biological adhesion by inducing endogenous adhesion molecules in periosteal sheet cultures. Therefore, the efficacy of periosteal sheets in therapy should be greatly enhanced by using this new pPLLA membrane.

Fibrogenic mesenchymal cells including fibroblasts and myofibroblasts play a key role in intestinal fibrosis, however, their precise role is largely unknown. To investigate their role in intestinal fibrosis, we analyzed the lesions of chronic colitis in C57BL/6 (B6) mice induced by dextran sulfate sodium (DSS). B6 mice exposed to single cycle administration of DSS for 5 days developed acute colitis that progressed to severe chronic inflammation with dense infiltrates of mononuclear cells, irregular epithelial structure, thickening of colonic wall, and persistent deposits of collagen. Increased mRNA expressions of proinflammatory cytokines are correlated with extensive cellular infiltration, and the mRNA expressions of collagen 1, transforming growth factor (TGF)-β, and matrix metalloproteinases were also enhanced in the colon. In the colon of chronic DSS colitis, fibroblasts (vimentin(+), α-smooth muscle actin (α-SMA)(-)) were increased in both mucosal and submucosal layers, while myofibroblasts (vimentin(+), α-SMA(+)) were increased in mucosal but not in submucosal layers. Primary mouse subcutaneous fibroblast cultures experiments revealed that exogenously added TGF-β 1 substantially augmented the expressions of both vimentin and α-SMA proteins with increased production of collagen. In conclusion, profibrogenic mesenchymal cells play an important role in the development of intestinal fibrosis in this chronic DSS-induced colitis model.

The patient is a 54-year-old man with severe thermal burn injury involving 45.5% of the total body-surface area, complicated with bacteremia caused by Pseudomonas aeruginosa with a cefepime MIC of 8 µg/ml. The plasma concentrations of cefepime 1 g every 6 h measured by validated high performance liquid chromatography were 25.8 µg/ml at 1 h and 6.28 µg/ml at 5 h after infusion, and 3.9 µg/ml before the infusion, when creatinine clearance was increased to 136 ml/min by vigorous fluid replacement. The pharmacokinetic–pharmacodynamic analyses in the one-compartment model with use of the Sawchuk–Zaske method revealed marked increase in the volume of distribution (28.9 l), total clearance (10.7 l/h), and shortening of plasma half- life (1.79 h) of cefepime, with time >MIC and 24-h area under the concentration–time-curve being 58% and 358, respectively. These pharmacokinetic parameters of cefepime quantified in the patient estimated a time >MIC of 87% if administered every 4 h. P. aeruginosa, however, was successfully eradicated without revision of the dosing regimen of cefepime. Decrease in creatinine clearance by correction of the fluid imbalance and wound closure by skin graft surgery likely contributed to the restoration of fluid shift, resulting in normal disposition of cefepime and favorable clinical outcome of the patient.

We have been investigating the spin motive force induced by magnetization dynamics in ferromagnetic materials. Ferrimagnetic materials are expected to exhibit even larger spin motive force due to their spatially staggered magnetic structure and high frequency spin wave modes. We believe that magnetite (Fe3O4) is one of the candidates for this purpose. Here, we report magnetic resonance in Fe3O4 thin films epitaxially grown on a MgO (001) substrate. The gyromagnetic ratio and the effective saturation magnetization are estimated to be 1.71 ×1011 s-1T-1 and 364 emu/cm3, respectively. The Gilbert damping constant of 0.02 is obtained from the magnetic field dependence of the linewidth. We expect to investigate the spin motive force induced from this magnetic resonance.

We previously demonstrated that human periosteal sheets prepared on culture dishes function as an osteogenic "graft material" applicable to periodontal regenerative therapy. However, a lower level of initial adhesion of the excised periosteum tissue segments to culture dishes was a critical point that compromised the successful preparation of functional periosteal sheets. To improve on this weakness, we developed a transparent, biodegradable poly(L-lactide-co-ɛ-caprolactone) (LCL) film and tested its function as a scaffold and carrier of periosteal sheets.Human periosteum tissue segments excised from alveolar bone of healthy donors were cultured on type I atelocollagen-coated LCL films. Initial adhesion was examined by simple agitation. Cell outgrowth and in vitro mineralization were cytohistochemically examined. Osteogenic activity was histochemically examined in an animal implantation model using nude mice.Surface collagen-coating modified the hydrophobic nature of LCL and substantially improved the initial adhesion. Compared to cultures in plastic dishes, the growth rate was delayed in non-coated films, but not in collagen-coated films. In the trimming process for animal implantation, periosteal sheets were frequently detached from non-coated films, but not from collagen-coated films. Regardless of collagen-coating, LCL films did not cause any significant infiltration of inflammatory cells, or negatively impact mineralized tissue formation.Collagen-coating improved the initial adhesion of periosteum segments, which facilitated cell outgrowth and also handling efficiency on implantation. Therefore, we believe that once evaluated in human studies, our collagen-coated LCL film will contribute to improving the periodontal regenerative methodology with the application of cultured autologous periosteal sheets.