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A study on neural genes examines the genome sequencing of strongylocentrotus purpuratus.

The evolution of genetic regulatory interactions is considered a driving force in generating evolutionary novelty because alterations to the regulatory milieu can lead to new gene expression patterns. Consistent with this view, homologous genes with highly conserved expression patterns can have conserved aspects of regulation, even in cross-species comparisons. The Spec gene family in sea urchins presents an intriguing counterpoint, genes with a highly conserved expression pattern but profound enhancer divergence. Promoter regions are completely dissimilar between the Strongylocentrotus purpuratus Spec2a gene and its homolog in Lytechinus pictus, species which diverged ~40 million years ago. One conspicuous difference is a repeat sequence, termed the RSR enhancer element, which contributes to transcriptional control of at least 3 S. purpuratus Spec genes but is absent in L. pictus, which presumably has the ancestral regulatory control. Here we further dissect the evolutionary history of the Spec regulatory region by determining (i) the phylogenetic expansion of the Spec gene family and (ii) the emergence and proliferation of the RSR element, as inferred by cloning these sequences from phylogenetic intermediates of S. purpuratus and L. pictus. Our results indicate a complicated history of gene family proliferation and RSR functionality, however there is evidence for correlated evolution of Spec orthologs and the RSR regulatory cassette, which first became associated at least ~17 million years ago.

Aims: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA., Methods and Results: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA., Conclusion: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF., Competing Interests: Conflict of interest: H.K. has received grants from Medtronic Japan, Nihon Kohden, Abbott Medical Japan, Fukuda Denshi, Boston Scientific Japan, Japan Lifeline, Nipro, and Biotronik Japan. K.T. has received honoraria from Bayer Yakuhin, Daiichi Sankyo, Kowa, MSD, Sanofi, and Takeda Pharmaceutical and grants from Astellas Pharma, Abbott Vascular Japan, Bayer Yakuhin, Boehringer Ingelheim Japan, Boston Scientific Japan, Bristol-Myers, Chugai Pharmaceutical, Daiichi Sankyo, Goodman, Japan Lifeline, Medtronic Japan, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Sanofi, Takeda Pharmaceutical, and Terumo. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cases of macadamia nut-induced anaphylactic shock have been rarely reported. We report the case of a three-year-old girl with anaphylactic shock who presented with generalized erythema two hours after ingesting macadamia nuts. She required two doses of intramuscular adrenaline for the treatment of anaphylactic shock. The diagnosis of macadamia nut allergy was confirmed by a prick-by-prick skin test using roasted and raw macadamia nut paste extracts and elevated serum macadamia nut-specific immunoglobulin E (IgE) levels. Appropriately using a prick-by-prick test may contribute to accurately diagnosing macadamia nut allergy, thus preventing the unnecessary avoidance of other nuts. Considering the potential for severe shock induced by macadamia nut allergy, vigilant monitoring of blood pressure changes is imperative in children presenting with immediate-type allergic reactions, such as vomiting and skin symptoms, following macadamia nut ingestion., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Kiyama et al.)

A 52-year-old woman patient, who presented with lower abdominal pain, was suspected of having colonic intussusception. An enhanced CT examination indicated that the end of the small intestine or appendix tumor had invaginated into the transverse colon. The CT revealed no evidence of intestinal ischemia, the emergency operation was performed on the following day. After relieving a colonic intussusception, a mass of the appendix was found and we performed laparoscope-assisted ileocolic resection and D3 dissection because of a strong possibility of carcinoma. The patient was discharged 8 days after the surgery and showed no evidence of recurrence for 6 months after the surgery. In postoperative histopathological examination, appendix tumor was diagnosed as a low-grade appendiceal mucinous neoplasm(LAMN). Adult intussusception is a rare disease and most of the cases are caused by malignant lesions, and a treatment strategy for LAMN has not yet been established. We report this case , as there are very few reported cases of adult intussusception caused by LAMN, with a review of the relevant literature.

Molecular hydrogen (H 2 ) is produced by human colon microbiomes and exhaled. End-tidal H 2 sampling is a simple method of measuring alveolar H 2 . The logarithm of the hydrogen ion (H + )/H 2 ratio suggests the electrode potential in the solution according to the Nernst equation. As pH is defined as the negative logarithm of the H + concentration, pH 2 is defined as the negative logarithm of the H 2 effective pressure in this study. We investigated whether changes in pH 2 indicated the variation of electrode potential in the solution and whether changes in end-tidal pH 2 could be measured using a portable breath H 2 sensor. Changes in the electrode potential were proportional to ([Formula: see text]) in phosphate-buffered solution (pH = 7.1). End-tidal H 2 was measured in the morning (baseline) and at noon (after daily activities) in 149 healthy Japanese subjects using a handheld H 2 sensor. The median pH 2 at the baseline was 4.89, and it increased by 0.15 after daily activities. The variation of electrode potential was obtained by multiplying the pH 2 difference, which suggested approximately + 4.6 mV oxidation after daily activities. These data suggested that changes in end-tidal pH 2 indicate the variation of electrode potential during daily activities in healthy human subjects., (© 2023. Springer Nature Limited.)

Competing Interests: Competing interests: None declared.

Aims: This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients., Methods and Results: This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32., Conclusions: According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results., Competing Interests: Conflict of interest: Dr Kanazawa and Dr Kaneko have received grants from Medtronic Japan, Nihon Kohden, Abbott Medical Japan, Fukuda Denshi, Boston Scientific Japan, Japan Lifeline, Nipro, and Biotronik Japan. Dr Tsujita has received honoraria from Bayer Yakuhin, Daiichi-Sankyo, Kowa, MSD, Sanofi, and Takeda Pharmaceutical; and grants from Astellas Pharma, Abbott Vascular Japan, Bayer Yakuhin, Boehringer Ingelheim Japan, Boston Scientific Japan, Bristol-Myers, Chugai Pharmaceutical, Daiichi-Sankyo, Goodman, Japan Lifeline, Medtronic Japan, Mitsubishi Tanabe Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Sanofi, Takeda Pharmaceutical, and Terumo. All remaining authors have declared no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Antiangiogenic treatment targeting the vascular endothelial growth factor (VEGF) pathway is a powerful tool to combat tumor growth and progression; however, drug resistance frequently emerges. We identify CD5L (CD5 antigen-like precursor) as an important gene upregulated in response to antiangiogenic therapy leading to the emergence of adaptive resistance. By using both an RNA-aptamer and a monoclonal antibody targeting CD5L, we are able to abate the pro-angiogenic effects of CD5L overexpression in both in vitro and in vivo settings. In addition, we find that increased expression of vascular CD5L in cancer patients is associated with bevacizumab resistance and worse overall survival. These findings implicate CD5L as an important factor in adaptive resistance to antiangiogenic therapy and suggest that modalities to target CD5L have potentially important clinical utility., (© 2023. The Author(s).)

More than 40 retinal ganglion cell (RGC) subtypes have been categorized in mouse based on their morphologies, functions, and molecular features. Among these diverse subtypes, orientation-selective Jam2-expressing RGCs (J-RGCs) has two unique morphologic characteristics: the ventral-facing dendritic arbor and the OFF-sublaminae stratified terminal dendrites in the inner plexiform layer. Previously, we have discovered that T-box transcription factor T-brain 1 ( Tbr1 ) is expressed in J-RGCs. We further found that Tbr1 is essential for the expression of Jam2 , and Tbr1 regulates the formation and the dendritic morphogenesis of J-RGCs. However, Tbr1 begins to express in terminally differentiated RGCs around perinatal stage, suggesting that it is unlikely involved in the initial fate determination for J-RGC and other upstream transcription factors must control Tbr1 expression and J-RGC formation. Using the Cleavage Under Targets and Tagmentation technique, we discovered that Pou4f1 binds to Tbr1 on the evolutionary conserved exon 6 and an intergenic region downstream of the 3'UTR, and on a region flanking the promoter and the first exon of Jam2 . We showed that Pou4f1 is required for the expression of Tbr1 and Jam2 , indicating Pou4f1 as a direct upstream regulator of Tbr1 and Jam2 . Most interestingly, the Pou4f1-bound element in exon 6 of Tbr1 possesses high-level enhancer activity, capable of directing reporter gene expression in J-RGCs. Together, these data revealed a Pou4f1-Tbr1-Jam2 genetic hierarchy as a critical pathway in the formation of J-RGC subtype., Competing Interests: Disclosures: The authors declare no conflicts of interest

Lignite is an obsolete and less commercially circulated natural resource due to its low calorific value worldwide. The effective conversion of lignite into methane is important considering the global energy crunch. This study reported the effective bioconversion of organic matter released from chemically solubilized lignite to methane using two methanogenic consortia types: mixed methanogenic enrichment culture (mMEC) and SAL25-2. We demonstrated in a microcosm study that the start of methane generation was observed within seven days. Furthermore, the methane yield increased as the total organic carbon concentration of the chemically solubilized lignite solution increased. Surprisingly, methane production using mMEC was drastically enhanced by approximately 50-fold when pulverized lignite was added as conductive material (CM) to the microcosms. To the best of our knowledge, this is the highest number of times methane production increased relative to the control. Our results demonstrated that bioaugmentation using a methanogenic consortium and adding pulverized lignite as CM could facilitate the bioconversion of chemically solubilized lignite solution to methane and lead to effective utilization of subterranean lignite, regarded as a neglected natural resource, without any further excavation processes., Competing Interests: The authors declare no conflicts of interest.

The retina, the accessible part of the central nervous system, has served as a model system to study the relationship between energy utilization and metabolite supply. When the metabolite supply cannot match the energy demand, retinal neurons are at risk of death. As the powerhouse of eukaryotic cells, mitochondria play a pivotal role in generating ATP, produce precursors for macromolecules, maintain the redox homeostasis, and function as waste management centers for various types of metabolic intermediates. Mitochondrial dysfunction has been implicated in the pathologies of a number of degenerative retinal diseases. It is well known that photoreceptors are particularly vulnerable to mutations affecting mitochondrial function due to their high energy demand and susceptibility to oxidative stress. However, it is unclear how defective mitochondria affect other retinal neurons. Nuclear respiratory factor 1 (Nrf1) is the major transcriptional regulator of mitochondrial biogenesis, and loss of Nrf1 leads to defective mitochondria biogenesis and eventually cell death. Here, we investigated how different retinal neurons respond to the loss of Nrf1 . We provide in vivo evidence that the disruption of Nrf1 -mediated mitochondrial biogenesis results in a slow, progressive degeneration of all retinal cell types examined, although they present different sensitivity to the deletion of Nrf1 , which implicates differential energy demand and utilization, as well as tolerance to mitochondria defects in different neuronal cells. Furthermore, transcriptome analysis on rod-specific Nrf1 deletion uncovered a previously unknown role of Nrf1 in maintaining genome stability.

Background/objective: Beta-tricalcium phosphate (β-TCP) is often used as a gap filler in open-wedge high tibial osteotomy (OWHTO). The aim of the present study was to investigate the effects of using β-TCP with different porosities on bone remodelling after OWHTO.Methods: We evaluated 29 knees in 26 patients that underwent OWHTO using β-TCP with porosities of 60% and 75% (combined group). A further 30 knees in 28 patients that underwent OWHTO using β-TCP with 60% porosity alone were allocated as a control group. In the combined group, a β-TCP block with 75% porosity was inserted into the gap at the cancellous bone site and a β-TCP block with 60% porosity was inserted into the medial cortical bone side. In the control group, a β-TCP block with 60% porosity was inserted into the osteotomy gap. The bone remodelling phases of the inserted β-TCP blocks were evaluated on standard anteroposterior radiographs using the modified van Hemert classification at 3 and 6 months post-operatively., Results: The rate of satisfactory bone remodelling at the cancellous bone sites was 86.2% (25/29) in the combined group and 0% (0/30) in the control group at 3 months post-operatively (p<0.05), progressing to 96.6% (28/29) in the combined group and 20% (6/30) in the control group at 6 months post-operatively (p<0.05)., Conclusion: The present study demonstrated that combined use of β-TCP with high and low porosities can significantly enhance bone formation. The combined use of artificial bones with different porosities is useful for early bone remodelling in OWHTO., Competing Interests: A conflict of interest occurs when an individual's objectivity is potentially compromised by a desire for financial gain, prominence, professional advancement or a successful outcome. AP-SMART Editors strive to ensure that what is published in the Journal is as balanced, objective and evidence-based as possible. Since it can be difficult to distin-guish between an actual conflict of interest and a perceived conflict of interest, the Journal requires authors to dis-close all and any potential conflicts of interest., (© 2022 Asia Pacific Knee, Arthroscopy and Sports Medicine Society. Published by Elsevier (Singapore) Pte Ltd.)

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its HX repeat domain gives rise to misregulation of a subset of developmental genes and curtails motor neuron differentiation of mouse embryonic stem cells. The transcription factor nuclear respiratory factor 1 (NRF1) has a novel and integral role in this neurodevelopmental process, being required for ncPRC1.3 recruitment to chromatin., Competing Interests: Declaration of interests D.R. is a cofounder of Constellation and Fulcrum Pharmaceuticals., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The mammalian retina contains more than 40 retinal ganglion cell (RGC) subtypes based on their unique morphologies, functions, and molecular profiles. Among them, intrinsically photosensitive RGCs (ipRGCs) are the first specified RGC type emerging from a common retinal progenitor pool during development. Previous work has shown that T-box transcription factor T-brain 2 (Tbr2) is essential for the formation and maintenance of ipRGCs, and that Tbr2-expressing RGCs activate Opn4 expression upon native ipRGC ablation, suggesting that Tbr2 + RGCs contain a reservoir for ipRGCs. However, the identity of Tbr2 + RGCs has not been fully vetted. Here, using genetic sparse labeling and single cell recording, we showed that Tbr2-expressing retinal neurons include RGCs and a subset of GABAergic displaced amacrine cells (dACs). Most Tbr2 + RGCs are intrinsically photosensitive and morphologically resemble native ipRGCs with identical retinofugal projections. Tbr2 + RGCs also include a unique and rare Pou4f1-expressing OFF RGC subtype. Using a loss-of-function strategy, we have further demonstrated that Tbr2 is essential for the survival of these RGCs and dACs, as well as maintaining the expression of Opn4. These data set a strong foundation to study how Tbr2 regulates ipRGC development and survival, as well as the expression of molecular machinery regulating intrinsic photosensitivity., (© 2021 Wiley Periodicals LLC.)

Background The clinical implication of vascular endothelial dysfunction in patients with atrial fibrillation (AF) remains unclear. This study aimed to elucidate the correlation between changes in vascular endothelial function assessed by reactive hyperemia-peripheral arterial tonometry and the effect of sinus rhythm restoration after catheter ablation (CA) for AF. Methods and Results Consecutive 214 patients who underwent CA for AF were included in this single center, retrospective study. The natural logarithmic transformed reactive hyperemia-peripheral arterial tonometry index (LnRHI) of all patients was measured before CA as well as 3 and 6 months after CA. LnRHI in sinus rhythm was significantly higher than that in AF before CA. Multivariate logistic regression analysis revealed that the presence of AF was an independent risk factor for lowering of LnRHI (odds ratio, 4.092; P =0.002) before CA. The LnRHI was significantly improved 3 and 6 months after CA in patients without AF recurrence. Multivariate Cox hazard analysis revealed that changes in LnRHI from before to 3 months after CA independently correlated with recurrence of AF (hazard ratio, 0.106; P =0.001). Receiver operating characteristic analysis showed the decrease in LnRHI levels from before to 3 months after CA as a significant marker that suspects AF recurrence (area under the curve, 0.792; log-rank test, P <0.001). Conclusions The presence of AF was independently correlated with the impaired vascular endothelial function assessed by the reactive hyperemia-peripheral arterial tonometry. Long-term sinus rhythm restoration after CA for AF might contribute to the improvement of vascular endothelial function, which may reflect the nonrecurrence of AF.

Mitochondrial cardiomyopathy can be described as a condition characterized by abnormal heart-muscle structure and/or function, secondary to mutations in nuclear or mitochondrial DNA. Its severity can range from subclinical to critical conditions. We presented three cases of mitochondrial cardiomyopathy with m.3243A > G mutation and compared the clinical manifestations with the histological findings for each of these cases. All cases showed cardiac hypertrophy, juvenile-onset diabetes mellitus, and hearing loss. Case 1 (43-year-old male) showed less cardiac involvement and shorter duration of mitochondrial disease-related symptoms than case 2 (67-year-old female) and case 3 (51-year-old male), who showed the most advanced cardiac condition and longest duration from the manifestation of heart failure. The histological findings revealed that cardiomyocytes from case 1 showed no hypertrophy and mitochondrial degeneration in electron microscopy. Alternatively, cases 2 and 3 showed hypertrophy in their cardiomyocytes, and mitochondrial degeneration (e.g. onion-like lesions, swollen cristae, and lamellar bodies) was most apparent in case 3. These results suggested that mitochondrial degeneration, as evaluated by electron microscopy, might be correlated with impaired heart function in patients with mitochondrial cardiomyopathy.

A novel mesophilic sulfate-reducing bacterium, strain HN2 T , was isolated from groundwater sampled from the subsurface siliceous mudstone of the Wakkanai Formation located in Horonobe, Hokkaido, Japan. The bacterium was Gram-negative and vibrio-shaped, and its motility was conferred by a single polar flagellum. Cells had desulfoviridin. Catalase and oxidase activities were not detected. It grew in the temperature range of 25-40 °C (optimum, 35 °C) and pH range of 6.3-8.1 (optimum, pH 7.2-7.6). It used sulfate, thiosulfate, dimethyl sulfoxide, anthraquinone-2,6-disulfonate, Fe 3+ , and manganese oxide, but not elemental sulfur, nitrite, nitrate, or fumarate as electron acceptors. The strain showed weak growth with sulfite as the electron acceptor. Fermentative growth with pyruvate, lactate and cysteine was observed in the absence of sulfate, but not with malate or fumarate. NaCl was not required, but the strain tolerated up to 40 g l -1 . Strain HN2 T did not require vitamins. The major cellular fatty acids were iso-C 15 : 0 (23.8 %), C 18 : 1  ω 9 t (18.4 %), C 18 : 0 (15.0 %), C 16 : 0 (14.5 %), and anteiso-C 17 :0 (10.1 %). The major respiratory quinone was menaquinone MK-6(H 2 ). The G+C content of the genomic DNA was 56.7 mol%. Based on 16S rRNA gene sequence analysis, the closest phylogenetic relative of strain HN2 T is Desulfovibrio psychrotolerans JS1 T (97.0 %). Digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values of the strains HN2 T and D. psychrotolerans JS1 T were 22.2 and 79.8 %, respectively. Based on the phenotypic and molecular genetic evidence, we propose a novel species, D. subterraneus sp. nov. with the type strain HN2 T (=DSM 101010 T =NBRC 112213 T ).

Mouse photoreceptors are electrically coupled via gap junctions, but the relative importance of rod/rod, cone/cone, or rod/cone coupling is unknown. Furthermore, while connexin36 (Cx36) is expressed by cones, the identity of the rod connexin has been controversial. We report that FACS-sorted rods and cones both express Cx36 but no other connexins. We created rod- and cone-specific Cx36 knockout mice to dissect the photoreceptor network. In the wild type, Cx36 plaques at rod/cone contacts accounted for more than 95% of photoreceptor labeling and paired recordings showed the transjunctional conductance between rods and cones was ~300 pS. When Cx36 was eliminated on one side of the gap junction, in either conditional knockout, Cx36 labeling and rod/cone coupling were almost abolished. We could not detect direct rod/rod coupling, and cone/cone coupling was minor. Rod/cone coupling is so prevalent that indirect rod/cone/rod coupling via the network may account for previous reports of rod coupling., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

In order to assess the long-term impact of the Great East Japan Earthquake on the oral health of disaster victims and to evaluate gene-environmental interactions in the development of major oral diseases and oral-systemic associations, the oral part of two large-scale genome cohort studies by the Tohoku Medical Megabank Organization (ToMMo), including the Community-based cohort (CommCohort) study and the Birth and Three-Generation cohort (BirThree) study, have been conducted. The study population comprised 32,185 subjects, including 16,886 participants in the CommCohort study and 15,299 participants in the BirThree cohort study, recruited from 2013 to 2017. The oral studies consist of a questionnaire regarding oral hygiene behavior, clinical examinations by dentists, and oral plaque and saliva sampling for microbiome analyses, which were carried out at seven community support centers in Miyagi prefecture. The median age of all participants was 55.0 years, and 66.1% of participants were women. Almost all participants reported that they brushed their teeth more than once a day. The median number of present teeth was 27.0, and the decayed, missing and filled tooth number was 16.0, with a significant difference according to age and sex. The median periodontal pocket and clinical attachment level was 2.48 mm and 4.00 mm, respectively. Periodontal parameters increased significantly according to age, except for the accumulation of dental calculus. The oral part of these extensive cross-sectional studies provides a unique and important platform for future studies on oral health and diseases that elicit through interactions with systemic diseases, lifestyles, life events and genetic backgrounds, and contributes to researches clarifying the long-term effects of disasters on oral health.

Background: It has been shown that most paroxysmal atrial fibrillation (AF) can be terminated by pulmonary vein (PV) isolation alone, suggesting that rapid discharges from PV drive AF. To define the driving mechanism of AF, we compared the activation sequence in the body of left atrium (LA) to that within PV., Methods: Endocardial noncontact mapping of LA body (LA group; n = 16) and selective endocardial mapping of left superior PV (LSPV) (PV group; n = 13) were performed in 29 paroxysmal AF patients. The frequency of pivoting activation, wave breakup, and wave fusion observed in LA were compared to those in LSPV to define the driving mechanism of AF. Circumferential ablation lesion around left PV was performed after right PV isolation to examine the effect of linear lesion around PV on AF termination both in LA and PV groups., Results: The frequency of pivoting activation, wave breakup, and wave fusion in PV group were significantly higher than those in LA group (36.5 ± 17.7 vs 5.0 ± 2.2 times/seconds, p < 0.001, 10.1 ± 4.3 vs 5.0 ± 2.2 times/seconds, p = 0.004, 18.1 ± 5.7 vs 11.0 ± 5.2, p = 0.002). Especially in the PV group, the frequency of pivoting activation was significantly higher than that of wave breakup and wave fusion (36.5 ± 17.7 vs 10.1 ± 4.3 times/seconds, p < 0.001, 36.5 ± 17.7 vs 18.1 ± 5.7 times/seconds, p < 0.001). These disorganized activations in LSPV were eliminated by the circumferential ablation lesion around left PV (pivoting activation; 36.5 ± 17.7 vs 9.3 ± 2.3 times/seconds, p < 0.001, wave breakup; 10.1±1.3 times/seconds, p = 0.003, wave fusion; 18.1 ± 5.7 vs 5.7 ± 1.8, p < 0.001), resulted in AF termination in all patients in both LA and PV groups., Conclusions: Activation sequence within PV was more disorganized than that in LA body. Frequent episodes of pivoting activation rather than wave breakup and fusion observed within PV acted as the driving sources of paroxysmal AF., (Copyright © 2020 Japanese College of Cardiology. Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of intra-atrial conduction delay on the recurrence of atrial tachyarrhythmia after radio frequency catheter ablation (RFCA) has not been fully elucidated., Methods: We retrospectively analyzed 155 AF patients who were sinus rhythm at the start of RFCA. The conduction time from the onset of the earliest atrial electrogram at the high right atrium (HRA) to the end of the latest electrogram at the coronary sinus (CS) during sinus rhythm was defined as HRA-CS conduction time. Pulmonary vein isolation (PVI) was performed followed by linear roof lesion and complex fractionated atrial electrogram (CFAE) ablation until AF termination. We evaluated atrial tachyarrhythmia recurrence 12 months after RFCA., Results: The follow-up data were available for 148 patients. The recurrence of atrial tachyarrhythmia was noted in 28 (18.9%) patients. Atrial tachyarrhythmia recurrence patients had longer HRA-CS conduction times (151.3 ± 22.1 ms vs 160.1 ± 32.6 ms, p = .017). The patients were divided into the long or short HRA-CS conduction time group. The Kaplan-Meier analysis revealed that the long HRA-CS conduction time group held a higher risk of atrial tachyarrhythmia recurrence (log-rank test, p = .019). The multivariable Cox hazard analysis revealed that a long HRA-CS conduction time was a significant risk factor for the recurrence of atrial tachyarrhythmia, despite a long AF duration, persistent AF, and larger left atrial diameter (LAD) were not statistically significant., Conclusions: The HRA-CS conduction time was the primary influencing factor that predicted the recurrence of atrial tachyarrhythmia after catheter ablation., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone-resorptive effect. BPs are divided into nitrogen-containing BPs (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). N-BPs have far stronger anti-bone-resorptive effects than non-N-BPs, and BRONJ is caused by N-BPs. Our murine experiments have revealed the following. N-BPs, but not non-N-BPs, exhibit direct and potent inflammatory/necrotic effects on soft-tissues. These effects are augmented by lipopolysaccharide (the inflammatory component of bacterial cell-walls) and the accumulation of N-BPs in jawbones is augmented by inflammation. N-BPs are taken into soft-tissue cells via phosphate-transporters, while the non-N-BPs etidronate and clodronate inhibit this transportation. Etidronate, but not clodronate, has the effect of expelling N-BPs that have accumulated in bones. Moreover, etidronate and clodronate each have an analgesic effect, while clodronate has an anti-inflammatory effect via inhibition of phosphate-transporters. These findings suggest that BRONJ may be induced by phosphate-transporter-mediated and infection-promoted mechanisms, and that etidronate and clodronate may be useful for preventing and treating BRONJ. Our clinical trials support etidronate being useful for treating BRONJ, although additional clinical trials of etidronate and clodronate are needed.

The stereotypic dendritic morphology is one of the landmark characteristics for classifying retinal ganglion cell (RGC) subtypes. These unique dendritic morphologies and their corresponding stratification level in the inner plexiform layer are indicators of their physiological function and presynaptic connection with other neurons. Mis-patterned dendritic morphologies underlie many neurological disease conditions. To streamline the morphological analysis of RGCs, here, we describe a simple protocol using Cre-/lox-dependent genetically directed sparse labeling strategy on flat-mounted retinas to inspect dendritic morphology of specific RGC subtypes.

In situ hybridization (ISH) techniques provide important information regarding gene expression in cells and tissues. Especially, ISH details complex spatial RNA expression in highly heterogeneous tissues, such as developing and mature central nervous systems, where rare genes involved in many fundamental developmental or biological events are expressed. Although several techniques have been developed to detect low levels of RNA expression, there are still problematic issues caused by a low signal-to-noise ratio after signal amplification. RNAscope is a recently developed ISH technique with high sensitivity and low background. RNAscope utilizes a unique probe system (double Z probe) to amplify signal from rare RNAs. Additionally, the double Z probe enables a significant reduction in nonspecific signal amplification. Here we report detailed procedures of the brown-color RNAscope ISH on embryonic and adult mouse retinas.

It remains unclear whether AF is maintained by rotor. We evaluated the significance of rotor during atrial fibrillation (AF). Prevalence, location, and stability of rotational reentry (RR) in the left atrium were clarified by endocardial non-contact mapping in 66 AF patients. RR was classified into three categories: RR continued at stable site (Stable-RR), RR observed intermittently at the same site (Intermittent-RR), and RR observed at different locations (Different-RR). Catheter ablation was performed in a stepwise fashion (linear roof lesion and complex fractionated atrial electrogram ablation following pulmonary vein isolation) until AF termination and elucidated the consequence of radiofrequency lesion delivered within RR site on AF termination and recurrence. One hundred and nineteen RRs were observed. There were 54 patients with RR (RR Group) and 22 patients without RR (Non-RR Group). Prevalence of Different-RR (n = 81) was significantly higher than Stable-RR (n = 16, p < 0.001) and Intermittent-RR (n = 22, p < 0.001). The intervals involved in RR occupied only 22.4% of total activation time. There was no significant difference in the prevalence of AF termination nor AF/atrial tachycardia recurrence between RR and non-RR Groups (46 vs. 9 patients, p = 0.317, and 13 vs. 1 patients, p = 0.271) and between patients in whom radiofrequency lesion was involved in RR and those was not (24 vs. 22 patients, p = 0.210, and 6 vs. 7 patients, p = 0.506). In conclusion, most RRs were observed transiently and often shifted its locations. Radiofrequency lesion delivered within RR site did not correlate with AF termination nor recurrence, suggesting that RR is not a driving source during AF.

Purpose: The purpose of this study was to clarify the indication for opening wedge high tibial osteotomy (OWHTO) in terms of lower limb alignment to achieve satisfactory clinical results., Methods: Ninety-two patients (98 knees) with medial compartment knee osteoarthritis were investigated in this study. The average follow-up period was 34 months (range, 24-68 months). The average age of the patients at the time of surgery was 63 years (range, 41-77 years)., Results: The patients were divided into the following two groups according to the preoperative femorotibial angle (FTA) on anteroposterior full-length radiographs of the lower limbs while weight bearing: 29 knees with a preoperative FTA of ≥185° were defined as those with severe varus (S group), and the remaining 69 knees with a preoperative FTA of <185° were defined as those with mild varus (M group). Knees with a postoperative FTA of >175° were defined as undercorrected. The Lysholm score was used to assess the clinical results. The average postoperative FTA was 175.7° ± 4.1° in the S group and 174.6° ± 3.1° in the M group ( p = 0.013). Significantly, more undercorrected knees were observed in the S than M group ( p = 0.00035). The postoperative Lysholm score was 85.6 ± 8.5 in the S group and 88.5 ± 5.7 in the M group at the last follow-up ( p = 0.0033)., Conclusion: Based on these results, we recommend that a preoperative FTA of <185° should be included as a criterion for OWHTO alone.