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This study aimed to establish a three-dimensional (3D) cephalometric analysis of craniofacial morphology and discuss its theoretical usefulness in orthognathic patients. Cone-beam computed tomography (CBCT) images of Japanese subjects with skeletal Class I malocclusion before treatment were selected from among 1000 patients so that samples matched a historic 2D cephalometric cohort with normal occlusion using propensity score matching. In each CBCT image, 67 3D measurements were calculated based on manually identified landmarks. The mean and standard deviation of the measurements were calculated and used as the normative range for each sex. To confirm the usefulness of the 3D measurements, pre- and post-treatment CT data of nine jaw deformity patients who underwent orthognathic surgery with two-dimensional planning (2DP) in the past were used. Pre- and post-treatment CT values were evaluated with a paired t-test as well as a Z-score, which was calculated using the aforementioned normative range, and then categorized into five groups ("deteriorated", "no improvement", "over-treatment", "no change", "improvement") with -1 Z-score1 considered normal. Fifty-six patients were matched to normal skeletal 1 subjects. The normative range of 67 items indicating 3D craniofacial morphology of the Japanese was calculated. Postoperatively, the horizontal position of the pogonion to the mid-sagittal plane significantly decreased (p = 0.043) and "improved"; however, the ramus axis on the right side significantly increased (p = 0.005) and "deteriorated". Maxillary yaw and the horizontal position of the gonion also tended to "deteriorated". The normative range for the 3D cephalometric analysis in Japanese has been established. Given findings of deteriorated maxillomandibular yawing after surgery when using conventional 2DP, 3D cephalometric measurements should be used when planning jaw positions after surgery for orthognathic patients.

In the external dacryocystorhinostomy (DCR), a sutured anastomosis technique performed between the nasal mucosal and lacrimal sac flaps reported by Dupuy-Dutemps and Bourguet was the gold standard and was believed to lead to the success of the surgery. However, because of the small working space, a flap suturing technique has not been completely established in endonasal DCR (END-DCR).The effect of the modified flap suture anastomosis technique using a Sonopet ultrasonic bone aspirator was retrospectively compared to that using a diamond burr in patients with nasolacrimal duct obstruction.One hundred ten patients underwent the modified flap suturing technique using the Sonopet, and 30 patients were operated on using a diamond burr.Successful patency of the lacrimal ostium (LO) was obtained in all patients in both groups. The rates of successful suturing during the operation and of a large diameter of the LO 3 months after the operation were significantly higher in patients in whom the Sonopet rather than the burr was used.The Sonopet might offer similar surgical outcome to the traditional microdrill DCR and is a safer means of bone removal in END-DCR in the small working space.

Background Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. Methods This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal prognosis in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and other antihypertensive drugs-treated group over 2 years. Results Antihypertensive treatment effectively reduced blood pressure from 222 ± 4/142 ± 3 to 140 ± 3/87 ± 2 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 3.3 to 41.1 ± 4.1mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34–0.92] for RASi(+) and RASi(-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB, β-blocker, α-blockers, or diuretics. Conclusions Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with other antihypertensive drugs.

Delayed endolymphatic hydrops (DEH) is a rare disease, and the actual number of patients in Japan remains unknown.To investigate the number and prevalence of patients with DEH in Japan.In total, 781 departments of otolaryngology in Japan were selected for survey by stratified random sampling according to the total number of hospital beds. We sent questionnaires to the target departments and collected data regarding the number of patients with DEH who visited those departments in 2019.The overall response rate was 68.0% (531 departments). The estimate number of patients with DEH in Japan was 962, and the prevalence was calculated to be 0.8 per 100,000 population.Patients with DEH were extremely rare in Japan.This may be the first nationwide epidemiological study on the number and prevalence of patients with DEH in Japan or in the world.

Polycomb repressive complex 1 (PRC1) and PRC2 are responsible for epigenetic gene regulation. PRC1 ubiquitinates histone H2A (H2Aub), which subsequently promotes PRC2 to introduce the H3 lysine 27 tri-methyl (H3K27me3) repressive chromatin mark. Although this mechanism provides a link between the two key transcriptional repressors, PRC1 and PRC2, it is unknown how histone-tail dynamics contribute to this process. Here, we have examined the effect of H2A ubiquitination and linker-DNA on H3-tail dynamics and H3K27 methylation by PRC2. In naïve nucleosomes, the H3-tail dynamically contacts linker DNA in addition to core DNA, and the linker-DNA is as important for H3K27 methylation as H2A ubiquitination. H2A ubiquitination alters contacts between the H3-tail and DNA to improve the methyltransferase activity of the PRC2-AEBP2-JARID2 complex. Collectively, our data support a model in which H2A ubiquitination by PRC1 synergizes with linker-DNA to hold H3 histone tails poised for their methylation by PRC2-AEBP2-JARID2.

Delayed endolymphatic hydrops (DEH) is an inner ear disease that causes recurrent vertigo in the ipsilateral ear or fluctuating hearing in the contralateral ear due to endolymphatic hydrops secondary to preceding deafness. There are few reports of large, multicentre studies investigating the clinical-epidemiological characteristics of DEH.This study aimed to clarify the characteristics of DEH in Japan.Clinical data on 662 patients with DEH were analysed by nationwide, multicentre surveys conducted by the Peripheral Vestibular Disorders Research Group of Japan.The proportion of ipsilateral DEH (IDEH) was slightly higher than that of contralateral DEH (CDEH) at 55.4%. The time delay between onset of precedent deafness and onset of DEH was significantly longer for CDEH than for IDEH. The most common cause of precedent deafness was a disease of unknown cause with onset in early childhood (33.1%). Epidemiological characteristics were not significantly different between CDEH with and without vertigo.DEH appearing to be caused by viral labyrinthitis has a high rate of onset within 40 years of precedent deafness. Clinical and epidemiological characteristics of IDEH, CDEH with vertigo, and CDEH without vertigo were very similar.The clinical-epidemiological characteristics of DEH in Japan were clarified.

Background: Although anti-TNF-α monoclonal antibody (BP) agents are widely used as an established treatment tool for refractory ulcerative colitis (UC), whether leukocytapheresis/granulocytapheresis (L/G-CAP) has similar beneficial impact on the disease activity remains undetermined. Furthermore, the costs defrayed for the treatment with these two modalities have not been compared. Methods: We retrospectively evaluated whether L/G-CAP offered sustained beneficial effects over 2-year period. The patients who had moderately to severely active UC (Rachmilewitz Clinical Activity Index (CAI)≧5) and were treated with a series (10 sessions) of L/G-CAP (n=19) or BP (n=7) as an add-on therapy to conventional medications were followed. Furthermore, the cost-effectiveness pertaining to the treatment with L/G-CAP and BP was assessed over 12 months. Results: At baseline, L/G-CAP and BP groups manifested similar disease activity (CAI, L/G-CAP; 7.0 [6.0-10.0], BP; 10.0 [6.0-10.0], p=0.207). The L/G-CAP and BP treatment suppressed the activity, with CAI 1 or less attained on day 180. When the L/G-CAP group was dichotomized into L/G-CAP-high and L/G-CAP-low group based on CAI values (≥3 or Conclusions: L/G-CAP is as effective as BP in a substantial number of patients over two years. The cost for the treatment of UC favors L/G-CAP although the correction of anemia may prefer BP. Thus, L/G-CAP can effectively manage the disease activity with no additional implementation for two years although further therapeutic modalities might be required in a certain population with high CAI observed on day 365. Trial registration: This study is a retrospective analysis evaluating the long-term efficacy of L/G-CAP and anti-TNF-α monoclonal antibody agents on the disease activity during a total of two years, and also assessing the costs of the treatment for UC over 12-month period (UMIN trial No. 000036954). The study was approved by the Ethics Committee of Tokyo Bay Urayasu Ichikawa Medical Center (Chiba, institutional approval No. 376) and Keiyu Hospital (Yokohama, Kanagawa, institutional approval No. R3-26) with waiver of the requirement for obtaining informed consent, and was conducted in accordance with the Declaration of Helsinki. Information from medical records was anonymized and de-identified prior to final analysis.

Eukaryotic gene expression is regulated through chromatin conformation, in which enhancers and promoters physically interact (E–P interactions). How such chromatin-mediated E–P interactions affect gene expression is not yet fully understood, but the roles of histone acetylation and methylation, pioneer transcription factors, and architectural proteins such as CCCTC binding factor (CTCF) and cohesin have recently attracted attention. Moreover, accumulated data suggest that E–P interactions are mechanistically involved in biophysical events, including liquid–liquid phase separation, and in biological events, including cancers. In this review, we discuss various mechanisms that regulate eukaryotic gene expression, focusing on emerging views regarding chromatin conformations that are involved in E–P interactions and factors that establish and maintain them.

Recent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (−2.29 ± 0.90 vs −5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and β blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.

Sensory conflict among visual, vestibular, and somatosensory information induces vertiginous sensation and postural instability. To elucidate the cognitive mechanisms of the integration between the visual and vestibular cues in humans, we analyzed the cortical hemodynamic responses during sensory conflict between visual and horizontal rotatory vestibular stimulation using a multichannel near-infrared spectroscopy (NIRS) system. The subjects sat on a rotatory chair that was accelerated at 3°/s2 for 20 s to the right or left, kept rotating at 60°/s for 80 s, and then decelerated at 3°/s2 for 20 s. The subjects were instructed to watch white stripes projected on a screen surrounding the chair during the acceleration and deceleration periods. The white stripes moved in two ways; in the “congruent” condition, the stripes moved in the opposite direction of chair rotation at 3°/s2 (i.e., natural visual stimulation), whereas in the “incongruent” condition, the stripes moved in the same direction of chair rotation at 3°/s2 (i.e., conflicted visual stimulation). The cortical hemodynamic activity was recorded from the bilateral temporoparietal regions. Statistical analyses using NIRS-SPM software indicated that hemodynamic activity increased in the bilateral temporoparietal junctions (TPJs) and human MT+ complex, including the medial temporal (MT) area and medial superior temporal (MST) area in the incongruent condition. Furthermore, the subjective strength of the vertiginous sensation was negatively correlated with hemodynamic activity in the dorsal part of the supramarginal gyrus (SMG) in and around the intraparietal sulcus (IPS). These results suggest that sensory conflict between the visual and vestibular stimuli promotes cortical cognitive processes in the cortical network consisting of the TPJ, the medial temporal gyrus (MTG), and IPS, which might contribute to self-motion perception to maintain a sense of balance or equilibrioception during sensory conflict.

Polycomb repressive complexes-1 and -2 (PRC1 and 2) silence developmental genes in a spatiotemporal manner during embryogenesis. How Polycomb group (PcG) proteins orchestrate down-regulation of target genes upon differentiation, however, remains elusive. Here, by differentiating embryonic stem cells into embryoid bodies, we reveal a crucial role for the PCGF1-containing variant PRC1 complex (PCGF1-PRC1) to mediate differentiation-associated down-regulation of a group of genes. Upon differentiation cues, transcription is down-regulated at these genes, in association with PCGF1-PRC1-mediated deposition of histone H2AK119 mono-ubiquitination (H2AK119ub1) and PRC2 recruitment. In the absence of PCGF1-PRC1, both H2AK119ub1 deposition and PRC2 recruitment are disrupted, leading to aberrant expression of target genes. PCGF1-PRC1 is, therefore, required for initiation and consolidation of PcG-mediated gene repression during differentiation. Polycomb repressive complexes (PRC1 and PRC2) repress genes that are crucial for development via epigenetic modifications; however, their role in differentiation is not well known. Here the authors reveal that a PCGF1-containing PRC1 variant facilitates exit from pluripotency by downregulating target genes and recruiting PRC2.

This research uses individual data from Japan’s National Survey of Family Income and Expenditure to examine the impact of residential area and real estate prices on employment, i.e. individuals’ choice to work. The results show a significant negative impact of real assets on employment. This result indicates a theoretical possibility that an accumulation of household assets induces non-working. This research also finds that the influence of real assets on employment is different depending on the area. In the Kanto, Kitakyushu, and Fukuoka metropolitan areas there is a negative influence of real assets on employment. This result reflects the differences in real estate and land prices in these areas, and suggests that if there is the negative effect of real assets on employment in metropolitan areas, tax benefits on land and housing could have an adverse effect on the labor market in these areas.

Rapid response systems (RRS) have been introduced worldwide to reduce unpredicted in-hospital cardiac arrest (IHCA) and in-hospital mortality. The role of advance care planning (ACP) in the management of critical patients has not yet been fully determined in Japan.We retrospectively assessed the characteristics of all inpatients with unpredicted IHCA in our hospital between 2016 and 2018. Yearly changes in the number of RRS activations and the incidence of unpredicted IHCA with or without code status discussion were evaluated from 2014 to 2018. Hospital standardized mortality ratios were assessed from the data reported in the annual reports by the National Hospital Organization.A total of 81 patients (age: 70.9 ± 13.3 years) suffered an unpredicted IHCA and had multiple background diseases, including heart disease (75.3%), chronic kidney disease (25.9%), and postoperative status (cardiovascular surgery, 18.5%). Most of the patients manifested non-shockable rhythms (69.1%); survival to hospital discharge rate was markedly lower than that with shockable rhythms (26.8% vs 72.0%, P

RimOnO Prototype 01, a tiny electric car with a textile body, won the highest award at the 4th Kawaii Award in 2016 hosted by the Japan Society of Kansei Engineering. In this chapter, Shinsuke Ito, the CEO of RimOnO Corporation, explains how a group of people with different backgrounds teamed up to create this tiny, appealing car and how the prototype came to have its current design.

The metazoan-specific acetyltransferase p300/CBP is involved in activating signal-induced, enhancer-mediated transcription of cell-type-specific genes. However, the global kinetics and mechanisms of p300/CBP activity-dependent transcription activation remain poorly understood. We performed genome-wide, time-resolved analyses to show that enhancers and super-enhancers are dynamically activated through p300/CBP-catalyzed acetylation, deactivated by the opposing deacetylase activity, and kinetic acetylation directly contributes to maintaining cell identity at very rapid (minutes) timescales. The acetyltransferase activity is dispensable for the recruitment of p300/CBP and transcription factors but essential for promoting the recruitment of TFIID and RNAPII at virtually all enhancers and enhancer-regulated genes. This identifies pre-initiation complex assembly as a dynamically controlled step in the transcription cycle and reveals p300/CBP-catalyzed acetylation as the signal that specifically promotes transcription initiation at enhancer-regulated genes. We propose that p300/CBP activity uses a "recruit-and-release" mechanism to simultaneously promote RNAPII recruitment and pause release and thereby enables kinetic activation of enhancer-mediated transcription.

Cardiac hypertrophy is a life-threatening disorder and is frequently observed in patients with chronic kidney disease (CKD). Much attention has been focused on the derangement in hormonal factors, including aldosterone and FGF23, as novel causes of cardiac hypertrophy in CKD. Plasma aldosterone concentrations are elevated as renal function declines. Although aldosterone antagonists are available for the treatment of hypertension with cardiac hypertrophy, concern remains regarding the possible occurrence of serious hyperkalemia. Alternatively, certain types of calcium channel blockers suppress aldosterone synthesis or exert blocking action for mineralocorticoid receptors and could halt the progression of cardiac dysfunction. Recently, FGF23 is shown to be elevated as CKD progresses and may be responsible for the development of cardiac hypertrophy and heart failure. Furthermore, FGF23 not only inhibits the renal expression of angiotensin converting enzyme 2 but also enhances renin gene transcription, both of which could accelerate renin-angiotensin-aldosterone system. Although the increase in serum phosphate concentrations is a pivotal stimulus for FGF23 production, recent studies suggest that reduced iron status and elevated aldosterone levels, frequently seen in patients with CKD or on dialysis, might also contribute to the elevation in serum FGF23 levels. Conversely, phosphate binders and appropriate iron status could reduce serum FGF23, potentially leading to the alleviation of cardiac hypertrophy and heart failure. In conclusion, novel therapeutic strategies associated with aldosterone and FGF23 may confer a benefit in the management of cardiac disorders in CKD.

The Statistics Bureau of Japan currently creates and provides anonymized microdata for six surveys. Anonymized microdata from the Population Census of Japan are created using non-perturbative methods such as recoding, top coding, and record deletion as well as the perturbative method of swapping.

Methylation of cytosine at the C5 position (5mC) represents an epigenetic modification that plays a fundamental role in embryonic development, transcriptional regulation, and other processes. It can also be a mutational hotspot at CpG dinucleotides as a result of spontaneous hydrolytic deamination of 5mC to thymine. The resulting G · T mismatch pair is recognized by thymine DNA glycosylase (TDG) and revereted to a G · C pair. Recent studies have shown that 5mC is consecutively catalyzed into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by a DNA dioxygenase from the ten-eleven translocation (TET) family. Two oxidative cytosine derivatives, 5fC and 5caC, are eliminated by TDG during active DNA demethylation. Therefore, TDG has versatile roles in epigenetic regulation to control the gene expression as well as the DNA repair pathway to prevent mutagenesis. 5fC and 5caC serve as intermediate products of active DNA demethylation and also behave as DNA damages that threaten genomic integrity. Here, we discuss the potential functions of 5mC oxidative derivatives in epigenetic modification and DNA damage.

Summary The polycomb repressive complex 2 (PRC2) consists of core subunits SUZ12, EED, RBBP4/7, and EZH1/2 and is responsible for mono-, di-, and tri-methylation of lysine 27 on histone H3. Whereas two distinct forms exist, PRC2.1 (containing one polycomb-like protein) and PRC2.2 (containing AEBP2 and JARID2), little is known about their differential functions. Here, we report the discovery of a family of vertebrate-specific PRC2.1 proteins, "PRC2 associated LCOR isoform 1" (PALI1) and PALI2, encoded by the LCOR and LCORL gene loci, respectively. PALI1 promotes PRC2 methyltransferase activity in vitro and in vivo and is essential for mouse development. Pali1 and Aebp2 define mutually exclusive, antagonistic PRC2 subtypes that exhibit divergent H3K27-tri-methylation activities. The balance of these PRC2.1/PRC2.2 activities is required for the appropriate regulation of polycomb target genes during differentiation. PALI1/2 potentially link polycombs with transcriptional co-repressors in the regulation of cellular identity during development and in cancer.