Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Hydrogen irradiation-driven computational surface chemistry of lithium oxide and hydroxide.

We have investigated, using molecular dynamics, the surface chemistry of hydrogen incident on the amorphous and crystalline lithium oxide and lithium hydroxide surfaces upon being slowed down by a collision cascade and retained in the amorphous surface of either Li2O or LiOH. We looked for the bonding of H to the resident structures in the surface to understand a possible chain of chemical reactions that can lead to surface transformation upon H atom impact. Our findings, using Density-Functional Theory (DFT) trained ReaxFF force field/electronegativity equalization method potentials, stress the importance of inclusion of polarization in the dynamics of a Li-O-H system, which is also illustrated by DFT energy minimization and quantum-classical molecular dynamics using tight binding DFT. The resulting polar-covalent chemistry of the studied systems is complex and very sensitive to the instantaneous positions of all atoms as well as the ratio of concentrations of various resident atoms in the surface.

Search for Gamma-Ray Spectral Lines from Dark Matter Annihilation up to 100 TeV toward the Galactic Center with MAGIC.

Linelike features in TeV γ rays constitute a "smoking gun" for TeV-scale particle dark matter and new physics. Probing the Galactic Center region with ground-based Cherenkov telescopes enables the search for TeV spectral features in immediate association with a dense dark matter reservoir at a sensitivity out of reach for satellite γ-ray detectors, and direct detection and collider experiments. We report on 223 hours of observations of the Galactic Center region with the MAGIC stereoscopic telescope system reaching γ-ray energies up to 100 TeV. We improved the sensitivity to spectral lines at high energies using large-zenith-angle observations and a novel background modeling method within a maximum-likelihood analysis in the energy domain. No linelike spectral feature is found in our analysis. Therefore, we constrain the cross section for dark matter annihilation into two photons to ⟨σv⟩≲5×10^{-28} cm^{3} s^{-1} at 1 TeV and ⟨σv⟩≲1×10^{-25} cm^{3} s^{-1} at 100 TeV, achieving the best limits to date for a dark matter mass above 20 TeV and a cuspy dark matter profile at the Galactic Center. Finally, we use the derived limits for both cuspy and cored dark matter profiles to constrain supersymmetric wino models.

Search for the Majorana Nature of Neutrinos in the Inverted Mass Ordering Region with KamLAND-Zen.

The KamLAND-Zen experiment has provided stringent constraints on the neutrinoless double-beta (0νßß) decay half-life in ^{136}Xe using a xenon-loaded liquid scintillator. We report an improved search using an upgraded detector with almost double the amount of xenon and an ultralow radioactivity container, corresponding to an exposure of 970 kg yr of ^{136}Xe. These new data provide valuable insight into backgrounds, especially from cosmic muon spallation of xenon, and have required the use of novel background rejection techniques. We obtain a lower limit for the 0νßß decay half-life of T_{1/2}^{0ν}>2.3×10^{26} yr at 90% C.L., corresponding to upper limits on the effective Majorana neutrino mass of 36-156 meV using commonly adopted nuclear matrix element calculations.

Cavitation processes in a space filled with loose mesenchymal tissues: a comparison between the retrosternal space and the middle ear tympanic cavity in human fetuses.

BACKGROUND: During the expansion of the pleural cavity in early fetuses, a thick sheet of loose mesenchymal tissue (SLMT) appears between the lung bud and body wall. Subsequently, the growing lung bud invades into the SLMT and the latter becomes fragmented to disappear. To compare this with the tympanic cavity filled with loose mesenchymal tissues, the present study aimed to demonstrate the development, establishment, and breaking of the SLMT in the retrosternal space. MATERIALS AND METHODS: Although the retrosternal tissue was almost absent or very thin at 7 weeks, the SLMT appeared behind the manubrium sterni at 8 weeks. Accordingly, at 9-10 weeks, cavitation occurred in the SLMT to expand the pleural cavity. Therefore, the volume of SLMT was not determined by the adjacent structures such as the pericardium and sternum. Likewise, mesenchymal tissues filling the middle ear disappeared after 26 weeks. RESULTS: There were considerable individual variations in the timing of beginning and location of the tympanic cavitation. However, in contrast to the retrosternal SLMT, the volume of the future tympanic cavity is determined by the adjacent hard tissue and tympanic membrane much earlier than the cavitation. The mesenchymal tissue carried abundant vessels in the middle ear but none or few veins in the retrosternal SLMT. CONCLUSIONS: The concept that the lung bud invades into the splanchnic mesoderm to expand the pleural cavity seems oversimplified. Mechanical stresses from the pleural cavity might induce retrosternal cavitation, while a loss in blood supply might cause tympanic cavitation.

Novel Functional Peptide for Next-Generation Vital Pulp Therapy.

Although vital pulp therapy should be performed by promoting the wound-healing capacity of dental pulp, existing pulp-capping materials were not developed with a focus on the pulpal repair process. In previous investigations of wound healing in dental pulp, we found that organic dentin matrix components (DMCs) were degraded by matrix metalloproteinase-20, and DMC degradation products containing protein S100A7 (S100A7) and protein S100A8 (S100A8) promoted the pulpal wound-healing process. However, the direct use of recombinant proteins as pulp-capping materials may cause clinical problems or lead to high medical costs. Thus, we hypothesized that functional peptides derived from recombinant proteins could solve the problems associated with direct use of such proteins. In this study, we identified functional peptides derived from the protein S100 family and investigated their effects on dental pulp tissue. We first performed amino acid sequence alignments of protein S100 family members from several mammalian sources, then identified candidate peptides. Next, we used a peptide array method that involved human dental pulp stem cells (hDPSCs) to evaluate the mineralization-inducing ability of each peptide. Our results supported the selection of 4 candidate functional peptides derived from proteins S100A8 and S100A9. Direct pulp-capping experiments in a rat model demonstrated that 1 S100A8-derived peptide induced greater tertiary dentin formation compared with the other peptides. To investigate the mechanism underlying this induction effect, we performed liquid chromatography-tandem mass spectrometry analysis using hDPSCs and the S100A8-derived peptide; the results suggested that this peptide promotes tertiary dentin formation by inhibiting inflammatory responses. In addition, this peptide was located in a hairpin region on the surface of S100A8 and could function by direct interaction with other molecules. In summary, this study demonstrated that a S100A8-derived functional peptide promoted wound healing in dental pulp; our findings provide insights for the development of next-generation biological vital pulp therapies.

Effects of Timing of Medium-Chain Triglycerides (8:0 and 10:0) Supplementation during the Day on Muscle Mass, Function and Cognition in Frail Elderly Adults.

OBJECTIVES: Supplementation with 6 g/day of medium-chain triglycerides (MCTs) at dinnertime increases muscle function and cognition in frail elderly adults relative to supplementation with long-chain triglycerides. However, suitable timing of MCT supplementation during the day is unknown. DESIGN: We enrolled 40 elderly nursing home residents (85.9 ± 7.7 years) in a 1.5-month randomized intervention trial. Participants were randomly allocated to two groups: one received 6 g/day of MCTs at breakfast (breakfast group) as a test group and the other at dinnertime (dinner group) as a positive control group. MEASUREMENTS: Muscle mass, strength, function, and cognition were monitored at baseline and 1.5 months after initiation of intervention. RESULTS: Thirty-seven participants completed the study and were included in the analysis. MCT supplementation in breakfast and dinner groups respectively increased right arm muscle area from baseline by 1.1 ± 0.8 cm2 (P<0.001) and 1.6 ± 2.5 cm2 (P<0.001), left arm muscle area by 1.1 ± 0.7 cm2 (P<0.001) and 0.9 ± 1.0 cm2 (P<0.01), right knee extension time by 39 ± 42 s (P<0.01) and 20 ± 32 s (P<0.05), leg open and close test time by 1.74 ± 2.00 n/10 s (P<0.01) and 1.67 ± 2.01 n/10 s (P<0.01), and Mini-Mental State Examination score by 1.5 ± 3.0 points (P=0.06) and 1.0 ± 2.1 points (P=0.06). These increases between two groups did not differ statistically significantly. CONCLUSION: Supplementation with 6 g MCTs/day for 1.5 months, irrespective of ingestion at breakfast or dinnertime, could increase muscle mass and function, and cognition in frail elderly adults.

Inferior oblique muscle of the eye: its foetal development with special reference to understanding of the frequent variants in adults.

BACKGROUND AND MATERIALS AND METHODS: To provide better understanding of frequent variations of the inferior oblique (IO) of adult extraocular muscles, we observed sagittal and horizontal histological sections of the eye and orbits from 32 foetuses (7-34 weeks of gestational age; 24-295 mm of crown-rump length). RESULTS: In early foetuses (7-8 weeks), the IO was restricted at an antero-infero-medial angle of the future orbit. In contrast to extraocular recti, the IO appeared to extend along the mediolateral axis and had no definite tendon. At midterm, the IO tendon became evident. Sometimes, the IO muscle belly attached to the inferior rectus or, the IO tendon divided into two laminae to enclose the lateral rectus. At late-term, a multilayered sheath was evident around the sclera and, via one or some of the fascial layers, the IO was communicated with a fascia enclosing the inferior rectus. At midterm and late-term, the IO originated not only from the maxilla near the orbicularis oculi origin but also from a vein-rich fibrous tissue around the lacrimal sac. Both origins were muscular without intermittent tendon or ligament. Therefore, the fascial connection as well as a direct contact between the IO and the inferior or lateral rectus seemed to provide variant muscular bridges as reported in adults. Moreover, the two attachment sites at the origin seemed to provide double muscle bellies of the adult IO. CONCLUSIONS: Consequently, the present specimens contained seeds of any types of adult variations. The muscle fibres from the lacrimal sac might play a role for the lacrimal drainage.

Assessment of genetic diversity and structure of Bambara groundnut [Vigna subterranea (L.) verdc.] landraces in South Africa.

With its drought tolerant and protein-rich properties, Bambara groundnut [Vigna subterranea (L.) Verdc.], an indigenous African legume crop can contribute immensely to food security. This miracle crop is used as food and for the enhancement of soil fertility in South Africa. Knowledge on the genetic diversity and structure among the Bambara groundnut landraces can pave the way for the effective use and cultivation of this crop in southern Africa, especially South Africa. The aim of this study was to assess the genetic diversity and structure among Bambara groundnut landraces collected across South Africa and compared to a limited number of accessions from southern Africa using SSR markers. Seventy-eight Bambara groundnut accessions were genotyped using 19 Bambara specific SSR markers. SSR loci explored in this study, were all polymorphic. A total of 127 alleles were detected with a mean of 6.7 alleles per locus. Allele diversity and frequency among genotypes varied from 0.21 to 0.85 with an average of 0.62 per locus. Genetic variation as described by the analysis of molecular variance indicated higher genetic diversity (92%) within landraces than between (8%) different landraces. Population structure analysis showed that three subpopulations existed, and most of the South African accessions were restricted to one subpopulation, indicating that Bambara landraces has the ability to form unique haplotypes in different environments. Information harnessed in this study is helpful for further use in breeding programs for crop improvement.

Humanized NOD/SCID/IL2rγnull mice exhibit functionally augmented human regulatory T cells associated with enzymatic up-regulation of H3K27me3 in comparison with humans.

Humanized non-obese diabetic/severe combined immunodeficiency/interleukin-2 receptor-γ-null (NOD/SCID/IL2rγnull ) [humanized (huNSG)] mice engrafted with human hematopoietic cells have been used for investigations of the human immune system. However, the epigenetic features of the human regulatory T (Treg ) cells of huNSG mice have not been studied. The objective of this study was to clarify the characteristics of human Treg cells in huNSG mice, especially in terms of the epigenetic aspects. We compared the populations, inhibitory molecule expression and suppressive capacity of human Treg cells in spleens harvested from the huNSG mice 120 days after the engraftment of human umbilical cord blood CD34+ cells with human peripheral blood mononuclear cells (PBMCs). Histone modifications and enhancer of zeste homolog 2 (Ezh2), an H3K27 methyltransferase, of human Treg cells were quantified in huNSG mice and human PBMCs. The effect of Ezh2 inhibitor on human Treg cells exposed to interleukin (IL)-6 was also compared between them. Human Treg cells in the spleens of huNSG mice showed an increased proportion among CD4+ T cells, higher expressions of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor-related protein (GITR), a higher production of IL-10 and enhanced suppressive capacity when compared with those in human PBMCs. H3K27me3 and Ezh2 were specifically up-regulated in human Treg cells of huNSG mice in comparison with those of human PBMCs. The decrease in Treg cells induced by IL-6 exposure was attenuated in huNSG mice when compared with human PBMCs, while the difference between them was cancelled by addition of Ezh2 inhibitor. In conclusion, huNSG mice exhibit functionally augmented human Treg cells owing to enzymatic up-regulation of H3K27me3.

Comparison of artificial tooth position in dentures fabricated by heat curing and additive manufacturing.

BACKGROUND: The purpose of this study was to compare the displacement of tooth arrangement in dentures fabricated by additive manufacturing (AM) and heat curing. METHODS: Three-dimensional (3D) scanning was performed for edentulous jaw models. After the teeth were arranged, 3D scanning for the wax denture was performed. Heat-cured dentures were fabricated with heat-cure polymer resin. Based on data obtained by subtracting the model data from wax denture data, AM dentures were fabricated from ultraviolet-cured acrylic resin. Accuracy was verified by superimposing heat-cured and AM dentures on the tooth region data from the wax dentures and measuring displacement of the tooth arrangement. RESULTS: In the maxillary dentures, the amount of tooth displacement for the heat-cured dentures and for the AM dentures ranged from -0.08 to +0.06 mm and from -0.25 to +0.06 mm respectively. A significant difference was observed between two dentures. In the mandibular dentures, the amount of tooth displacement for the heat-cured dentures and for the AM dentures ranged from -0.09 to +0.07 mm and from -0.03 to +0.07 mm respectively. No significant difference was observed between two dentures. CONCLUSIONS: The artificial teeth of the maxillary dentures fabricated by AM showed a greater displacement compared to those by heat curing.

Accuracy of Le Fort I osteotomy with combined computer-aided design/computer-aided manufacturing technology and mixed reality.

The aim of this study was to verify the reproducibility and accuracy of preoperative planning in maxilla repositioning surgery performed with the use of computer-aided design/manufacturing technologies and mixed reality surgical navigation, using new registration markers and the HoloLens headset. Eighteen patients with a mean age of 26.0 years were included. Postoperative evaluations were conducted by comparing the preoperative virtual operation three-dimensional image (Tv) with the 1-month postoperative computed tomography image (T1). The three-dimensional surface analysis errors ranged from 79.9% to 97.1%, with an average error of 90.3%. In the point-based analysis, the errors at each point on the XYZ axes were calculated for Tv and T1 in all cases. The median signed value deviation of all calculated points on the XYZ axes was -0.03mm (range -2.93mm to 3.93mm). The median absolute value deviation of all calculated points on the XYZ axes was 0.38mm (range 0mm to 3.93mm). There were no statistically significant differences between any of the points on any of the axes. These values indicate that the method used was able to reproduce the maxilla position with high accuracy.

Physicochemical and structural characterization of resistant starch isolated from Vigna unguiculata.

In this study, characterization was conducted on resistant starch, isolated from different cultivars of V. unguiculata (Bechuana White, Fahari, PAN 311, TVU 11424 and DT 129-4). The fraction of resistant starch obtained was found in the range of 9.42-13.74%, with DT 129-4 yielding the highest fraction. Amylose content of the starches varied between 18.72 and 19.67%. Swelling power, solubility index and syneresis was directly proportional to the different temperatures. A correlation between amylose content and swelling power was observed as swelling power was indirectly proportional to amylose content. Water and oil absorption capacity was 31.93-88.06% and 10.29-27.71% respectively. Foaming, emulsion capacity, and stability were done, however, due to the lack of protein in the resistant starch samples, results obtained were relatively low, ranging between 0.00 and 22.41%. The degree of whiteness during colour analysis ranged between 80.81 and 84.61%. The FTIR-spectra displayed no distinctive difference amongst the vibration bands on the hydroxyl, methine and carbonyl frequency stretches and confirmed the polysaccharide nature of the resistant starch. The XRD spectra displayed a Ca-type crystalline structure for all 5 cultivars. Overall, this study shows that resistant starch has the potential to be used in many food applications and as a microencapsulation membrane.

Detection of the Metastable Ice Phase during Water Crystallization.

BACKGROUND: Under atmospheric pressure, the identifiable phases of ice crystals are hexagonal (stable) and cubic (metastable). OBJECTIVE: This study aimed to test the hypothesis that water crystallizes into the cubic phase at the beginning and then changes to the hexagonal phase. MATERIALS AND METHODS: Aqueous solutions of 40% (w/w) and 50% (w/w) glucose, and 40% (w/w) ammonium hydrogen sulfate, as well as emulsified water, were investigated. RESULTS: The cubic-to-hexagonal ice phase transition was detected in 40% (w/w) glucose solution within a 1 s integration interval, whereas the cubic ice formed in 50% (w/w) glucose solution did not transition to the hexagonal phase. The cubic phase was also confirmed in the 40% (w/w) ammonium hydrogen sulfate solution, but not in emulsified water. CONCLUSION: The cubic-to-hexagonal ice phase transition was detected in three aqueous solutions tested upon freezing. It was not possible to clearly capture the transition process in emulsified water under the study condition.

The Space Physics Environment Data Analysis System (SPEDAS).

With the advent of the Heliophysics/Geospace System Observatory (H/GSO), a complement of multi-spacecraft missions and ground-based observatories to study the space environment, data retrieval, analysis, and visualization of space physics data can be daunting. The Space Physics Environment Data Analysis System (SPEDAS), a grass-roots software development platform (www.spedas.org), is now officially supported by NASA Heliophysics as part of its data environment infrastructure. It serves more than a dozen space missions and ground observatories and can integrate the full complement of past and upcoming space physics missions with minimal resources, following clear, simple, and well-proven guidelines. Free, modular and configurable to the needs of individual missions, it works in both command-line (ideal for experienced users) and Graphical User Interface (GUI) mode (reducing the learning curve for first-time users). Both options have "crib-sheets," user-command sequences in ASCII format that can facilitate record-and-repeat actions, especially for complex operations and plotting. Crib-sheets enhance scientific interactions, as users can move rapidly and accurately from exchanges of technical information on data processing to efficient discussions regarding data interpretation and science. SPEDAS can readily query and ingest all International Solar Terrestrial Physics (ISTP)-compatible products from the Space Physics Data Facility (SPDF), enabling access to a vast collection of historic and current mission data. The planned incorporation of Heliophysics Application Programmer's Interface (HAPI) standards will facilitate data ingestion from distributed datasets that adhere to these standards. Although SPEDAS is currently Interactive Data Language (IDL)-based (and interfaces to Java-based tools such as Autoplot), efforts are under-way to expand it further to work with python (first as an interface tool and potentially even receiving an under-the-hood replacement). We review the SPEDAS development history, goals, and current implementation. We explain its "modes of use" with examples geared for users and outline its technical implementation and requirements with software developers in mind. We also describe SPEDAS personnel and software management, interfaces with other organizations, resources and support structure available to the community, and future development plans. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11214-018-0576-4) contains supplementary material, which is available to authorized users.

Endoscopic submucosal dissection for superficial esophageal cancer.

Endoscopic submucosal dissection (ESD) has evolved into a viable treatment modality for superficial esophageal cancer. ESD offers a distinct advantage given the ability to perform en bloc resection enabling accurate histopathologic assessment. Data from published literature has established ESD as the preferred option in the treatment of superficial squamous cell carcinoma with complete resection rates of 78-100%, and a low rate recurrence of 0-2.6%. En bloc resection for esophageal SCC is curative for tumors with M1 (intrapethelial) or M2 (invasion into the lamina propria) involvement with no lymphovascular invasion. Tumors that contain lymphovascular invasion or submucosal invasion greater than 200 µm should be treated as advanced carcinomas due to the increased risk of lymph node metastasis. In contrast, the role of ESD in Barrett's esophagus is more limited due to the high rate of efficacy of EMR. A randomized control trial comparing EMR and ESD strategies found a higher R0 resection rate for ESD, but no significant difference in complete remission from neoplasia at 3 month follow up. Endoscopic ultrasound (EUS) has a limited role in the evaluation of superficial esophageal cancer. Alternatively, detailed endoscopic assessment along with magnification endoscopy or narrow band imaging, may provide greater utility than EUS. The most common adverse events of ESD in the esophagus include perforation and stricture. Perforation can often be managed by defect closure along with non-operative conservative management. Steroid administration with either topical or local injection can be effective management in stricture prevention. Continued refinement of ESD technique and innovation will overcome some of the current limitations of ESD and enable curative resection of superficial esophageal cancer as an alternative to invasive surgery.

Effect of brefelamide on proliferation of 1321N1 human astrocytoma cells induced by glial cell line-derived neurotrophic factor.

Malignant gliomas are highly resistant to chemotherapy and radiation and more effective options for treatment are urgently needed. We reported previously that the aromatic amide brefelamide, which is isolated from methanolic extracts of the cellular slime molds Dictyostelium giganteum and D. brefeldianum, hinders cellular proliferation in a glioma model utilizing 1321N1 human astrocytoma cells. Herein, we examined the mechanisms underlying the inhibition of 1321N1 cell proliferation by brefelamide. Glial cell line-derived neurotrophic factor (GDNF) was found to enhance the rate of proliferation of serum-free cultured 1321N1 cells, but did not affect proliferation in PC12 cells. Brefelamide pretreatment inhibited GDNF-induced cell proliferation and expression of rearranged during transfection (RET). GDNF enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), AKT, and c-jun-N-terminal kinase (JNK); however, brefelamide pretreatment inhibited these effects. Brefelamide also reduced the expression of GDNF mRNA and GDNF secretion. Together, the findings from this study indicate that brefelamide inhibits the proliferation of 1321N1 cell via several mechanisms including reduced GDNF receptor expression and GDNF secretion, and reduced phosphorylation of ERK, AKT, and JNK.

Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult hippocampal neurogenesis.

Working memory capacity, a critical component of executive function, expands developmentally from childhood through adulthood. Anomalies in this developmental process are seen in individuals with autism spectrum disorder (ASD), schizophrenia and intellectual disabilities (ID), implicating this atypical process in the trajectory of developmental neuropsychiatric disorders. However, the cellular and neuronal substrates underlying this process are not understood. Duplication and triplication of copy number variants of 22q11.2 are consistently and robustly associated with cognitive deficits of ASD and ID in humans, and overexpression of small 22q11.2 segments recapitulates dimensional aspects of developmental neuropsychiatric disorders in mice. We capitalized on these two lines of evidence to delve into the cellular substrates for this atypical development of working memory. Using a region- and cell-type-selective gene expression approach, we demonstrated that copy number elevations of catechol-O-methyl-transferase (COMT) or Tbx1, two genes encoded in the two small 22q11.2 segments, in adult neural stem/progenitor cells in the hippocampus prevents the developmental maturation of working memory capacity in mice. Moreover, copy number elevations of COMT or Tbx1 reduced the proliferation of adult neural stem/progenitor cells in a cell-autonomous manner in vitro and migration of their progenies in the hippocampus granular layer in vivo. Our data provide evidence for the novel hypothesis that copy number elevations of these 22q11.2 genes alter the developmental trajectory of working memory capacity via suboptimal adult neurogenesis in the hippocampus.

Educational effects using a robot patient simulation system for development of clinical attitude.

INTRODUCTION: The aim of this study was to assess the effectiveness of improving the attitude of dental students towards the use of a full-body patient simulation system (SIMROID) compared to the traditional mannequin (CLINSIM) for dental clinical education. MATERIALS AND METHODS: The participants were 10 male undergraduate dental students who had finished clinical training in the university hospital 1 year before this study started. They performed a crown preparation on an upper pre-molar tooth using SIMROID and CLINSIM as the practical clinical trials. The elapsed time for preparation was recorded. The taper of the abutment teeth was measured using a 3-dimensional shape-measuring device after this trial. In addition, a self-reported questionnaire was collected that included physical pain, treatment safety and maintaining a clean area for each simulator. Qualitative data analysis of a free format report about SIMROID was performed using text mining analysis. This trial was performed twice at 1-month intervals. RESULTS: The students considered physical pain, treatment safety and a clean area for SIMROID significantly better than that for CLINSIM (P < .01). The elapsed time of preparation in the second practical clinical trial was significantly lower than in the first for SIMROID and CLINSIM (P < .01). However, there were no significant differences between the abutment tapers for both systems. For the text mining analysis, most of the students wrote that SIMROID was similar to real patients. CONCLUSION: The use of SIMROID was proven to be effective in improving the attitude of students towards patients, thereby giving importance to considerations for actual patients during dental treatment.