Demonstration of nuclear gamma-ray polarimetry based on a multi-layer CdTe Compton camera.

To detect and track structural changes in atomic nuclei, the systematic study of nuclear levels with firm spin-parity assignments is important. While linear polarization measurements have been applied to determine the electromagnetic character of gamma-ray transitions, the applicable range is strongly limited due to the low efficiency of the detection system. The multi-layer Cadmium-Telluride (CdTe) Compton camera can be a state-of-the-art gamma-ray polarimeter for nuclear spectroscopy with the high position sensitivity and the detection efficiency. We demonstrated the capability to operate this detector as a reliable gamma-ray polarimeter by using polarized 847-keV gamma rays produced by the [Formula: see text]([Formula: see text]) reaction. By combining the experimental data and simulated calculations, the modulation curve for the gamma ray was successfully obtained. A remarkably high polarization sensitivity was achieved, compatible with a reasonable detection efficiency. Based on the obtained results, a possible future gamma-ray polarimetery is discussed.

Assessment of maxillary sinus fluid volume for postmortem diagnosis of drowning.

INTRODUCTION: Drowning is a comprehensive and exclusive diagnosis at autopsy. Autopsy findings such as pleural effusion and waterlogged lungs contribute to the diagnosis. Herein, we aim to reveal the practical usefulness and postmortem changes of the maxillary sinus fluid volume to diagnose drowning. METHODS: We evaluated 52 drowning and 59 nondrowning cases. The maxillary sinus fluid volume was measured using a computed tomography (CT) scan, and pleural effusion volume and lung weight were manually measured at autopsy. The utility of these three indices for diagnosing drowning and its postmortem changes was evaluated. RESULTS: The maxillary sinus fluid volume was significantly higher in drowning cases than in other external causes and cardiovascular death cases. Receiver operating characteristic curve analysis revealed that a total maxillary sinus fluid volume >1.04 mL more usefully indicated drowning (odds ratio, 8.19) than a total pleural effusion volume >175 mL (odds ratio, 7.23) and a total lung weight >829 g (odds ratio, 2.29). The combination of maxillary sinus fluid volume and pleural effusion volume more effectively predicted drowning than one index alone. Moreover, the maxillary sinus fluid volume was less influenced by the postmortem interval than the other two indices up to a week after death. CONCLUSION: Maxillary sinus fluid volume can be more useful than pleural effusion volume and lung weight with higher sensitivity and odds ratio for diagnosing drowning. IMPLICATIONS FOR PRACTICE: Fluid accumulation in both the maxillary sinuses strongly predicts drowning in the postmortem imaging.

Methionine: An Indispensable Amino Acid in Cellular Metabolism and Health of Atlantic Salmon.

Methionine is an indispensable amino acid with an important role as the main methyl donor in cellular metabolism for both fish and mammals. Metabolization of methionine to the methyl donor S-adenosylmethionine (SAM) has consequence for polyamine, carnitine, phospholipid, and creatine synthesis as well as epigenetic modifications such as DNA- and histone tail methylation. Methionine can also be converted to cysteine and contributes as a precursor for taurine and glutathione synthesis. Moreover, methionine is the start codon for every protein being synthetized and thereby serves an important role in initiating translation. Modern salmon feed is dominated by plant ingredients containing less taurine, carnitine, and creatine than animal-based ingredients. This shift results in competition for SAM due to an increasing need to endogenously synthesize associated metabolites. The availability of methionine has profound implications for various metabolic pathways including allosteric regulation. This necessitates a higher nutritional need to meet the requirement as a methyl donor, surpassing the quantities for protein synthesis and growth. This comprehensive review provides an overview of the key metabolic pathways in which methionine plays a central role as methyl donor and unfolds the implications for methylation capacity, metabolism, and overall health particularly emphasizing the development of fatty liver, oxidation, and inflammation when methionine abundance is insufficient focusing on nutrition for Atlantic salmon (Salmo salar).

N=16 Magicity Revealed at the Proton Drip Line through the Study of

The last proton bound calcium isotope ^{35}Ca has been studied for the first time, using the ^{37}Ca(p,t)^{35}Ca two neutron transfer reaction. The radioactive ^{37}Ca nuclei, produced by the LISE spectrometer at GANIL, interacted with the protons of the liquid hydrogen target CRYPTA, to produce tritons t that were detected in the MUST2 detector array, in coincidence with the heavy residues Ca or Ar. The atomic mass of ^{35}Ca and the energy of its first 3/2^{+} state are reported. A large N=16 gap of 4.61(11) MeV is deduced from the mass measurement, which together with other measured properties, makes ^{36}Ca a doubly magic nucleus. The N=16 shell gaps in ^{36}Ca and ^{24}O are of similar amplitude, at both edges of the valley of stability. This feature is discussed in terms of nuclear forces involved, within state-of-the-art shell model calculations. Even though the global agreement with data is quite convincing, the calculations underestimate the size of the N=16 gap in ^{36}Ca by 840 keV.

Geriatric nutritional risk index as the prognostic factor in older patients with fragility hip fractures.

This study investigated the long-term survival and incidence of secondary fractures after fragility hip fractures. The 5-year survival rate was 62%, and the mortality risk was seen in patients with GNRI < 92. The 5-year incidence of secondary fracture was 22%, which was significantly higher in patients with a BMI < 20. BACKGROUND: Malnutrition negatively influences the postoperative survival of patients with fragility hip fractures (FHFs); however, little is known about their association over the long term. OBJECTIVE: This study evaluated the ability of the geriatric nutritional risk index (GNRI) as a risk factor for long-term mortality after FHFs. METHODS: This study included 623 Japanese patients with FHFs over the age of 60 years. We prospectively collected data on admission and during hospitalization and assessed the patients' conditions after discharge through a questionnaire. We examined the long-term mortality and the incidence of secondary FHFs and assessed the prognostic factors. RESULTS: The mean observation period was 4.0 years (range 0-7 years). The average age at the time of admission was 82 years (range 60-101 years). The overall survival after FHFs (1 year, 91%; 5 years, 62%) and the incidence of secondary FHFs were high (1 year, 4%; 5 years, 22%). The multivariate Cox proportional hazard analysis revealed the risk factors for mortality as older age (hazard ratio [HR] 1.04), male sex (HR 1.96), lower GNRI score (HR 0.96), comorbidities (malignancy, HR 2.51; ischemic heart disease, HR 2.24; revised Hasegawa dementia scale ≤ 20, HR 1.64), no use of active vitamin D3 on admission (HR 0.46), and a lower Barthel index (BI) (on admission, HR 1.00; at discharge, HR 0.99). The GNRI scores were divided into four risk categories: major risk (GNRI, < 82), moderate risk (82-91), low risk (92-98), and no risk (> 98). Patients at major and moderate risks of GNRI had a significantly lower overall survival rate (p < 0.001). Lower body mass index (BMI) was also identified as a prognostic factor for secondary FHFs (HR 0.88 [p = 0.004]). CONCLUSIONS: We showed that older age, male sex, a lower GNRI score, comorbidities, and a lower BI are risk factors for mortality following FHFs. GNRI is a novel and simple predictor of long-term survival after FHFs.

Reopening of ductus arteriosus in idiopathic premature constriction or closure of ductus arteriosus: A case series.

BACKGROUND: There is no consensus on managing pregnancy when the fetus is diagnosed with idiopathic premature constriction or closure of the ductus arteriosus (PCDA). Knowing whether the ductus reopens is valuable information for managing idiopathic PCDA. We conducted a case-series study to investigate the natural perinatal course of idiopathic PCDA and examined factors associated with ductal reopening. METHODS: We retrospectively collected information about the perinatal course and echocardiographic findings at our institution, which, on principle, does not determine delivery timing based on fetal echocardiographic results. We also examined perinatal factors related to the reopening of the ductus arteriosus. RESULTS: Thirteen cases of idiopathic PCDA were included in the analysis. The ductus reopened in 38% of cases. Among cases diagnosed in < 37 weeks of gestation, 71% reopened, which was confirmed seven days after diagnosis (interquartile range 4-7). Diagnosis earlier in gestation was associated with ductal reopening (p = 0.006). Two cases (15%) developed persistent pulmonary hypertension. No fetal hydrops or death occurred. CONCLUSIONS: The ductus is likely to reopen when prenatally diagnosed before 37 weeks gestation. There were no complications due to our pregnancy management policy. In idiopathic PCDA, especially if the prenatal diagnosis is made before 37 weeks of gestational age, continuing the pregnancy with careful monitoring of the fetus's well-being is recommended.

Reduced Autophagy in Aged Trigeminal Neurons Causes Amyloid ß Diffusion.

The relationship between oral health and the development of Alzheimer's disease (AD) in the elderly is not yet well understood. In this regard, the association between aging or neurodegeneration of the trigeminal nervous system and the accumulation of amyloid-ß(1-42) (Aß42) oligomers in the pathogenesis of AD is unknown. We focused on selective autophagy in the trigeminal mesencephalic nucleus (Vmes) and the diffusion of Aß42 oligomers with respect to aging of the trigeminal nervous system and whether the degeneration of Vmes neurons affects the diffusion of Aß42 oligomers. We used female 2- to 8-mo-old transgenic 3xTg-AD mice and AppNL-G-F knock-in mice and immunohistochemically examined aging-related changes in selective autophagy and Aß42 oligomer processing in the Vmes, which exhibits high amyloid-ß (Aß) expression. We induced degeneration of Vmes neurons by extracting the maxillary molars and examined the changes in Aß42 oligomer kinetics. Autophagosome-like membranes, which stained positive for Aß, HO-1, and LC3B, were observed in Vmes neurons of 3xTg-AD mice, while there was weak immunoreactivity of the membranes for intraneuronal Aß in AppNL-G-F mice. By contrast, there was strong immunopositivity for extracellular Aß42 oligomers with the formation of Aß42 oligomer clusters in AppNL-G-F mice. The expression of Rubicon, which indicates age-related deterioration of autophagy, increased the diffusion of Aß42 oligomer with the age of Vmes neurons. Tooth extraction increased the extracellular immunopositivity for Aß42 oligomers in AppNL-G-F mice. These results suggest that autophagy maintains homeostasis in Vmes neurons and that deterioration of autophagy due to aging or neurodegeneration leads to the diffusion of Aß42 oligomers into the extracellular space and possibly the development of AD.

Structure of

Detailed spectroscopy of the neutron-deficient nucleus ^{36}Ca was obtained up to 9 MeV using the ^{37}Ca(p,d)^{36}Ca and the ^{38}Ca(p,t)^{36}Ca transfer reactions. The radioactive nuclei, produced by the LISE spectrometer at GANIL, interacted with the protons of the liquid hydrogen target CRYPTA, to produce light ejectiles (the deuteron d or triton t) that were detected in the MUST2 detector array, in coincidence with the heavy residues identified by a zero-degree detection system. Our main findings are (i) a similar shift in energy for the 1_{1}^{+} and 2_{1}^{+} states by about -250 keV, as compared with the mirror nucleus ^{36}S; (ii) the discovery of an intruder 0_{2}^{+} state at 2.83(13) MeV, which appears below the first 2^{+} state, in contradiction with the situation in ^{36}S; and (iii) a tentative 0_{3}^{+} state at 4.83(17) MeV, proposed to exhibit a bubble structure with two neutron vacancies in the 2s_{1/2} orbit. The inversion between the 0_{2}^{+} and 2_{1}^{+} states is due to the large mirror energy difference (MED) of -516(130) keV for the former. This feature is reproduced by shell model calculations, using the sd-pf valence space, predicting an almost pure intruder nature for the 0_{2}^{+} state, with two protons (neutrons) being excited across the Z=20 magic closure in ^{36}Ca (^{36}S). This mirror system has the largest MEDs ever observed, if one excludes the few cases induced by the effect of the continuum.

Temporal Profiles of Symptom Scores After Palliative Radiotherapy for Bleeding Gastric Cancer With Adjustment for the Palliative Prognostic Index: An Exploratory Analysis of a Multicentre Prospective Observational Study (JROSG 17-3).

AIMS: Although palliative radiotherapy for gastric cancer may improve some symptoms, it may also have a negative impact due to its toxicity. We investigated whether symptoms improved after radiotherapy with adjustment for the Palliative Prognostic Index (PPI) considering that patients with limited survival tend to experience deterioration of symptoms. MATERIALS AND METHODS: This study was an exploratory analysis of the Japanese Radiation Oncology Study Group study (JROSG 17-3). We assessed six symptom scores (nausea, anorexia, fatigue, shortness of breath, pain at the irradiated area and distress) at registration and 2, 4 and 8 weeks thereafter. We tested whether symptoms linearly improved after adjusting for the baseline PPI. Shared parameter models were used to adjust for potential bias in missing data. RESULTS: The present study analysed all 55 patients enrolled in JROSG 17-3. With time from registration as the only explanatory variable in the model, a significant linear decrease was observed in shortness of breath, pain and distress (slopes, -0.26, -0.22 and -0.19, respectively). Given that the interaction terms (i.e. PPI × time) were not significantly associated with symptom scores in any of the six symptoms, only PPI was included as the main effect in the final multivariable models. After adjusting for the PPI, shortness of breath, pain and distress significantly improved (slope, -0.25, -0.19 and -0.17; P < 0.001, 0.002 and 0.047, respectively). An improvement in fatigue and distress was observed only in patients treated with a biologically effective dose ≤14.4 Gy. CONCLUSION: Shortness of breath, pain and distress improved after radiotherapy. Moreover, a higher PPI was significantly associated with higher symptom scores at all time points, including baseline. In contrast, PPI did not seem to influence the improvement of these symptoms. Regardless of the expected survival, patients receiving radiotherapy for gastric cancer can expect an improvement in shortness of breath, pain and distress over 8 weeks. Multiple-fraction radiotherapy might hamper the improvement in fatigue and distress by its toxicity or treatment burden.

Does radical trachelectomy (RT) during pregnancy have higher obstetrical and oncological risks than RT before pregnancy?

PURPOSE: Radical trachelectomy (RT) with pelvic lymphadenectomy has become a new treatment option for young patients with uterine cervical cancer stages 1A2-1B1 who desire the preservation of their fertility. However, the application of RT for pregnant patients is still controversial. We comparatively studied both obstetrical and oncological outcomes of pregnant patients who underwent vaginal RT during pregnancy and those who underwent vaginal RT before pregnancy. METHODS: Both obstetrical and oncological results of eight patients who underwent vaginal RT with pelvic lymphadenectomy during pregnancy in our institute between 2010 and 2020 (Group A), and ten pregnant patients who underwent vaginal RT with pelvic lymphadenectomy before pregnancy during the same period (Group B) were reviewed based on their medical charts. RESULTS: There were neither significant differences in blood loss, surgical time, or surgical completeness between Group A and Group B, nor were there significant differences in obstetrical outcomes between the two groups. However, two of the eight patients in Group A had recurrence of the cancer. None of the patients in Group B has shown any signs of recurrence thus far. CONCLUSION: Vaginal RT during pregnancy does not affect the obstetrical prognoses of patients with early invasive uterine cervical cancer, and it might be a tolerable treatment modality for them. However, oncologically, it should be performed carefully as there is a risk of recurrence.

Improvement of patient localization repeatability using a light-section based optical surface guidance system in a pre-positioning procedure.

PURPOSE: Surface-guided radiotherapy is useful for the pre-positioning and monitoring of radiotherapy. The purpose of this study was to investigate the impact of surface guidance on the repeatability of patient localization and to estimate the specific point at which high positional errors occur. MATERIALS AND METHODS: Ten patients without the VOXELAN system (non-VXLN group) and 10 patients with the VOXELAN as the pre-positioning procedure (VXLN group) were included in this analysis. Twelve regions of interest (ROI) were defined in all the patients to verify any misalignment during radiotherapy. Thirteen ROIs were defined on the isocenter. RESULTS: Compared with the non-VXLN group, the translational positional errors of the VXLN group were the same for all the ROIs. The mean translational positional errors of the VXLN group in the longitudinal direction were approximately 0.1mm, and the standard deviation was the largest among the three directions in all the ROIs. The magnitude of the standard deviation in the non-VXLN group varied independently of the ROI and direction. The standard deviations of the VXLN group in the longitudinal direction were large in all the ROIs, while the standard deviations in the vertical and lateral directions were small. CONCLUSION: Pre-positioning with a surface guidance system reduced the body twist and rotation, which could not be corrected by image-guided radiotherapy alone. Since the VOXELAN can detect positioning errors quickly and without additional radiation exposure to the patient, it can be used as a tool for pre-positioning in radiotherapy.

Therapeutic indications for sinonasal topical steroid treatment and its effects on eosinophilic chronic rhinosinusitis after endoscopic sinus surgery.

OBJECTIVE: This study evaluated the post-operative indications for sinonasal topical steroid treatment using a corticosteroid (steroid)-eluting, sinus-bioabsorbable device and its effects in patients with eosinophilic chronic rhinosinusitis. METHOD: Post-operative courses were investigated in two groups: group A with patients who underwent sinonasal topical steroid treatment, and group B with control patients who did not. RESULTS: Group A was significantly younger than group B (p < 0.01), and the pre-operative computed tomography score was significantly higher in group A than in group B (p < 0.05). In the post-operative stage, the nasal symptoms questionnaire component of olfactory loss and the post-operative endoscopic appearance score were significantly worse in group A than in group B (p < 0.01). CONCLUSION: These data suggest that younger age, more severe rhinosinusitis and post-operative olfactory loss led to the need for sinonasal topical steroid treatment to prevent relapsing inflammation after functional endoscopic sinus surgery in patients with eosinophilic chronic rhinosinusitis.

W-band millimeter-wave back-scattering system for high wavenumber turbulence measurements in LHD.

A 90 GHz W-band millimeter-wave back-scattering system is designed and installed for measuring electron scale turbulence (k⊥ρs ∼ 40). A metal lens relay antenna is used for in-vessel beam focusing, and a beam diameter of less than 40 mm is achieved in the plasma core region. This antenna can be steered at an angle of 159° ± 6°, which almost covers the plasma radius. The estimated size of the scattering volume is ∼105 mm at the edge and 135 mm at the core, respectively. A 60 m corrugated waveguide is used to achieve a low transmission loss of ∼8 dB. A heterodyne detection system for millimeter-wave circuits with probing power modulation can distinguish the scattered signal from background noise.

Shape Changes in the Mirror Nuclei

We studied the proton-rich T_{z}=-1 nucleus ^{70}Kr through inelastic scattering at intermediate energies in order to extract the reduced transition probability, B(E2;0^{+}→2^{+}). Comparison with the other members of the A=70 isospin triplet, ^{70}Br and ^{70}Se, studied in the same experiment, shows a 3σ deviation from the expected linearity of the electromagnetic matrix elements as a function of T_{z}. At present, no established nuclear structure theory can describe this observed deviation quantitatively. This is the first violation of isospin symmetry at this level observed in the transition matrix elements. A heuristic approach may explain the anomaly by a shape change between the mirror nuclei ^{70}Kr and ^{70}Se contrary to the model predictions.

First-principles based theoretical calculations of atomic structures of hydroxyapatite surfaces and their charge states in contact with aqueous solutions.

Surface charge states of biomaterials are often important for the adsorption of cells, proteins, and foreign ions on their surfaces, which should be clarified at the atomic and electronic levels. First-principles calculations were performed to reveal thermodynamically stable surface atomic structures and their charge states in hydroxyapatite (HAp). Effects of aqueous environments on the surface stability were considered using an implicit solvation model. It was found that in an air atmosphere, stoichiometric {0001} and P-rich {101̄0} surfaces are energetically favorable, whereas in an aqueous solution, a Ca-rich {101̄0} surface is the most stable. This difference suggests that preferential surface structures strongly depend on chemical environments with and without aqueous solutions. Their surface potentials at zero charge were calculated to obtain the isoelectric points (pHPZC). pHPZC values for the {0001} surface and the Ca-rich {101̄0} surface were obtained to be 4.8 and 8.7, respectively. This indicates that in an aqueous solution at neutral pH, the {0001} and Ca-rich {101̄0} surfaces are negatively and positively charged, respectively. This trend agrees with experimental data from chromatography and zeta potential measurements. Our methodology based on first-principles calculations enables determining macroscopic charge states of HAp surfaces from atomic and electronic levels.

Multicenter prospective trial of total gastrectomy versus proximal gastrectomy for upper third cT1 gastric cancer.

BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.

Microbiome taxonomic and functional profiles of two domestic sewage treatment systems.

Anaerobic systems for domestic sewage treatment, like septic tanks and anaerobic filters, are used in developing countries due to favorable economic and functional features. The anaerobic filter is used for the treatment of the septic tank effluent, to improve the COD removal efficiency of the system. The microbial composition and diversity of the microbiome from two wastewater treatment systems (factory and rural school) were compared through 16S rRNA gene sequencing using MiSeq 2 × 250 bp Illumina sequencing platform. Additionally, 16S rRNA data were used to predict the functional profile of the microbial communities using PICRUSt2. Results indicated that hydrogenotrophic methanogens, like Methanobacterium, were found in higher abundance in both systems compared to acetotrophic methanogens belonging to Methanosaeta genus. Also, important syntrophic microorganisms (Smithella, Syntrophus, Syntrophobacter) were found in the factory and rural school wastewater treatment systems. Microbial communities were also compared between stages (septic tank and anaerobic filter) of each wastewater treatment stage, revealing that, in the case of the rural school, both microbial communities were quite similar most likely due to hydraulic short-circuit issues. Meanwhile, in the factory, microbial communities from the septic tank and anaerobic filter were different. The school system showed lower COD removal rates (2-30%), which were probably related to a higher abundance of Firmicutes members in addition to the hydraulic short-circuit and low abundance of Chloroflexi members. On the other hand, the fiberglass factory presented higher COD removal rates (60-83%), harboring phyla reported as the core microbiome of anaerobic digesters (Bacteroidetes, Chloroflexi, and Proteobacteria phyla). The knowledge of the structure and composition of wastewater treatment systems may provide support for the improvement of the pollutant removal in anaerobic process.

Discovery of ONO-8590580: A novel, potent and selective GABAA α5 negative allosteric modulator for the treatment of cognitive disorders.

The identification and SAR development of a series of negative allosteric modulators of the GABAA α5 receptor is described. This novel series of compounds was optimised to provide analogues with high GABAA α5 binding affinity, high α5 negative allosteric modulatory activity, good functional subtype selectivity and low microsomal turnover, culminating in identification of ONO-8590580.

Functional Analysis of PTH1R Variants Found in Primary Failure of Eruption.

Although many variants of the parathyroid hormone 1 receptor (PTH1R) gene are known to be associated with primary failure of eruption (PFE), the mechanisms underlying the link remains poorly understood. We here performed functional analyses of PTH1R variants reported in PFE patients-namely, 356C>T (P119L), 395C>T (P132L), 439C>T (R147C), and 1148G>A (R383Q)-using HeLa cells with a lentiviral vector-mediated genetic modification. Two particular variants, P119L and P132L, had severe reduction in a level of N-linked glycosylation when compared with wild-type PTH1R, whereas the other 2 showed modest alteration. PTH1R having P119L or P132L showed marked decrease in the affinity to PTH1-34, which likely led to severely impaired cAMP accumulation upon stimulation in cells expressing these mutants, highlighting the importance of these 2 amino acid residues for ligand-mediated proper functioning of PTH1R. To further gain insights into PTH1R functions, we established the induced pluripotent stem cell (iPSC) lines from a patient with PFE and the heterozygous P132L mutation. When differentiated into osteoblastic-lineage cells, PFE-iPSCs showed no abnormality in mineralization. The mRNA expression of RUNX2, SP7, and BGLAP, the osteoblastic differentiation-related genes, and that of PTH1R were augmented in both PFE-iPSC-derived cells and control iPSC-derived cells in the presence of bone morphogenetic protein 2. Also, active vitamin D3 induced the expression of RANKL, a major key factor for osteoclastogenesis, equally in osteoblastic cells derived from control and PFE-iPSCs. In sharp contrast, exposure to PTH1-34 resulted in no induction of RANKL mRNA expression in the cells expressing P132L variant PTH1R, consistent with the idea that a type of heterozygous PTH1R gene mutation would spoil PTH-dependent response in osteoblasts. Collectively, this study demonstrates a link between PFE-associated genetic alteration and causative functional impairment of PTH1R, as well as a utility of iPSC-based disease modeling for future elucidation of pathogenesis in genetic disorders, including PFE.

A novel bio-active adhesive monomer induces odontoblast differentiation: a comparative study.

AIM: To evaluate the in vitro effect of the novel adhesive monomer CMET, a calcium salt of 4-methacryloxyethyl trimellitate (4-MET), on the proliferation, mineralization and differentiation of odontoblast-like cells, comparing with 4-MET, calcium hydroxide (CH) and mineral trioxide aggregate (MTA). METHODOLOGY: Rat odontoblast-like MDPC-23 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 5% foetal bovine serum. The powder of four tested materials (CMET, 4-MET, CH and MTA) was first dissolved in distilled water (dH2O) and then was diluted by DMEM to yield final concentrations. Solvent (dH2O) was used as a control. Cell viability was assessed using CCK-8 assay. Real-time RT-PCR was used to quantify the mRNA expression of odontogenic markers, cytokines and integrins. Mineralization inducing capacity was evaluated by alkaline phosphatase (ALPase) activity and alizarin red S staining. Statistical analyses were performed using one-way anova and post hoc Tukey's HSD test, with the significance level at 1%. RESULTS: Cell viability was significantly greater in the CMET- (83 to 828 mmol L-1), CH- and MTA-treated (low concentrations) groups than that in the control group (P < 0.01). Higher concentrations of each material decreased the viable cells to different extents (P < 0.01). CMET treatment augmented the expression of several integrin subunits and exhibited the highest mRNA expression levels of odontogenic markers among all groups (P < 0.01). CH and MTA treatment caused significantly greater upregulation of pro-inflammatory cytokines expression than the other groups (P < 0.01). The calcific deposition of MDPC-23 cells was dose-dependently accelerated by the addition of CMET (P < 0.01); the enhancement of mineralization was also found in the fresh prepared CH and MTA treatments. Besides, CMET showed consistency in mineralization induction after 8 weeks storage. Exposure to SB202190, a specific p38 mitogen-activated protein kinases inhibitor, significantly decreased the ALPase activity as well as the mineral deposition which was enhanced by CMET treatment (P < 0.01). CONCLUSIONS: The novel bio-active monomer had the lowest cytotoxicity among all groups and it induced the proliferation, mineralization and differentiation of odontoblast-like cells under appropriate concentrations. This adhesive monomer possesses excellent biocompatibility and hence exhibits great potential in dentine regeneration.