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Background: X‐linked dystrophin‐deficient muscular dystrophy (MD) is a form of MD caused by variants in the DMD gene. It is a fatal disease characterized by progressive weakness and degeneration of skeletal muscles. Hypothesis/Objectives: Identify deleterious genetic variants in DMD by whole‐genome sequencing (WGS) using a next‐generation sequencer. Animals: One MD‐affected cat, its parents, and 354 cats from a breeding colony. Methods: We compared the WGS data of the affected cat with data available in the National Center for Biotechnology Information database and searched for candidate high‐impact variants by in silico analyses. Next, we confirmed the candidate variants by Sanger sequencing using samples from the parents and cats from the breeding colony. We used 2 genome assemblies, the standard felCat9 (from an Abyssinian cat) and the novel AnAms1.0 (from an American Shorthair cat), to evaluate genome assembly differences. Results: We found 2 novel high‐impact variants: a 1‐bp deletion in felCat9 and an identical nonsense variant in felCat9 and AnAms1.0. Whole genome and Sanger sequencing validation showed that the deletion in felCat9 was a false positive because of misassembly. Among the 357 cats, the nonsense variant was only found in the affected cat, which indicated it was a de novo variant. Conclusion and Clinical Importance: We identified a de novo variant in the affected cat and next‐generation sequencing‐based genotyping of the whole DMD gene was determined to be necessary for affected cats because the parents of the affected cat did not have the risk variant. [ABSTRACT FROM AUTHOR]

In recent years, there is growing evidence of associations between antibodies against myelin oligodendrocyte glycoprotein (MOG) and several phenotypes of acute inflammatory demyelinating diseases such as acute disseminated encephalomyelitis (ADEM), optic neuritis, brainstem, and cerebral cortical encephalitis, called MOG antibody associated disorders (MOGAD). Monophasic course is known in about half of cases especially in pediatric onset ADEM and optic neuritis, mainly in cases with transient positivity of MOG antibody. Pathological features of MOGAD are considered as acute demyelinating lesions with CD4 dominant cell infiltrations, the deposition of humoral immunity, perivascular inflammation and perivenous demyelination, which is distinct from multiple sclerosis. Now the diagnosis of MOGAD is based on the international panel criteria of MOGAD launched in 2023, which the diagnostic frameworks are three parts, including MOGAD‐specific clinical features, MOG antibody positivity, and the exclusion of other diseases. The prognosis of MOGAD patients is considered relatively mild, but the problem is refractory relapsing cases. For its prevention, there are no approved drugs, but oral tapering corticosteroids, immunosuppressants such as azathioprine and mycophenolic mofetil, rituximab, and the maintenance intravenous immunoglobulin are recommended, and now there are a few clinical trials of promising biological drugs already approved in other neurological disorders. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Even in a country where vancomycin–resistant enterococcus is rare, multidrug‐resistant organism precautions are necessary when admitting patients with a history of medical exposure in other countries. On admission, screening is necessary and if infection is confirmed, a multidisciplinary approach involving different specialists is required. The patient was a 49‐year‐old Japanese female living in the United States. Total pelvic exenteration for cervical carcinoma, Miami pouch formation, and ileostomy had been performed in the United States. She returned to Japan to undergo postoperative adjuvant chemotherapy. Fever and abdominal pain occurred 42 days after surgery. She consulted the fever outpatient clinic, and a diagnosis of urinary retention‐associated acute renal failure and pyelonephritis was made. We detected vancomycin‐resistant enterococcus on urine/blood culture 5 days after admission. Infection control measures were implemented, and the ward was closed for 3 days. We administered linezolid, which was effective for pyelonephritis and bacteremia. [ABSTRACT FROM AUTHOR]

Background: DNA methylation analysis might identify prognostic CpG sites in CHOP‐treated dogs with multicentric high‐grade B‐cell lymphoma (MHGL) with heterogenous prognosis. Objective: To identify prognostic CpG sites of MHGL through genome‐wide DNA methylation analysis with pyrosequencing validation. Animals: Test group: 24 dogs. Validation group: 100 dogs. All client‐owned dogs were diagnosed with MHGL and treated with CHOP chemotherapy. Methods: Cohort study. DNA was extracted from lymph node samples obtained via FNA. Genome‐wide DNA methylation analysis using Digital Restriction Enzyme Analysis of Methylation (DREAM) was performed on the test group to identify differentially methylated CpG sites (DMCs). Bisulfite pyrosequencing was used to measure methylation status of candidate DMCs in the validation group. Median survival times (MST) were analyzed using Kaplan‐Meier (log‐rank) product limit method. Results: DREAM analyzed 101 576 CpG sites. Hierarchical clustering of 16 262 CpG sites in test group identified group with better prognosis (MST = 55‐477 days vs 10‐301 days, P =.007). Volcano plot identified 1371 differentially methylated CpG sites (DMCs). DMC near the genes of FAM213A (DMC‐F) and PHLPP1 (DMC‐P) were selected as candidates. Bisulfite‐pyrosequencing performed on validation group showed group with methylation level of DMC‐F < 40% had favorable prognosis (MST = 11‐1072 days vs 8‐1792 days, P =.01), whereas group with the methylation level combination of DMC‐F < 40% plus DMC‐P < 10% had excellent prognosis (MST = 18‐1072 days vs 8‐1792 days, P =.009). Conclusion and Clinical Importance: Methylation status of prognostic CpG sites delineate canine MGHL cases with longer MST, providing owners with information on expectations of potential improved treatment outcomes. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection among all infants worldwide and remains a significant cause of morbidity and mortality. To address this unmet medical need, MK‐1654, a half‐life extended RSV neutralizing monoclonal antibody, is in clinical development for the prevention of RSV disease in infants. This was a phase I, randomized, placebo‐controlled, single‐site, double‐blind trial of MK‐1654 in 44 healthy Japanese adults. The safety, tolerability, pharmacokinetics, antidrug antibodies (ADAs), and serum neutralizing antibody (SNA) titers against RSV were evaluated for 1 year after a single intramuscular (i.m.) or intravenous (i.v.) dose of MK‐1654 or placebo in five groups (100 mg i.m., 300 mg i.m., 300 mg i.v., 1000 mg i.v., or placebo). MK‐1654 was generally well‐tolerated in Japanese adults. There were no serious drug‐related adverse events (AEs) reported in any MK‐1654 recipient and no discontinuations due to any AEs in the study. The half‐life of MK‐1654 ranged from 76 to 91 days across dosing groups. Estimated bioavailability was 86% for 100 mg i.m. and 77% for 300 mg i.m. One participant out of 33 (3.0%) developed detectable ADA with no apparent associated AEs. The RSV SNA titers increased in a dose‐dependent manner among participants who received MK‐1654. These data support the development of MK‐1654 for use in Japanese infants. [ABSTRACT FROM AUTHOR]

Tameness is a major element of animal domestication and involves two components: motivation to approach humans (active tameness) and reluctance to avoid humans (passive tameness). To understand the behavioral and genetic mechanisms of active tameness in mice, we had previously conducted selective breeding for long durations of contact and heading toward human hands in an active tameness test using a wild‐derived heterogeneous stock. Although the study showed a significant increase in contacting and heading with the 12th generation of breeding, the effect on other behavioral indices related to tameness and change of gene expression levels underlying selective breeding was unclear. Here, we analyzed nine tameness‐related traits at a later stage of selective breeding and analyzed how gene expression levels were changed by the selective breeding. We found that five traits, including contacting and heading, showed behavioral change in the selective groups comparing to the control through the generations. Furthermore, we conducted cluster analyses to evaluate the relationships among the nine traits and found that contacting and heading combined in an independent cluster in the selected groups, but not in the control groups. RNA‐Seq of hippocampal tissue revealed differential expression of 136 genes between the selection and control groups, while the pathway analysis identified the networks associated with these genes. These results suggest that active tameness was hidden in the control groups but became apparent in the selected populations by selective breeding, potentially driven by changes in gene expression networks. [ABSTRACT FROM AUTHOR]

Bengal Fan Miocene sediments were collected during International Ocean Discovery Program Expedition 354 and investigated using petrographic and detrital garnet chemistry analyses. The Miocene Siwalik Group, which is composed of sediments deposited in the Himalayan foreland basin, was also analyzed for comparison with the Bengal Fan data for the provenance change during the Miocene. Our petrographic analyses revealed that the Miocene sediments of the Bengal Fan and Siwalik Group consist predominantly of Higher Himalayan Crystalline (HHC)‐derived detritus such as chloritoid, staurolite, sillimanite, and/or kyanite, which appear among the accessory minerals. The chemistry of the detrital garnet varies across the stratigraphy; most of the garnet is rich in almandine and poor in spessartine and pyrope. However, pyrope‐rich garnet, which is considered to originate from the HHC core (granulite facies), was found in the lower to upper Miocene deposits. The deposition of HHC‐derived detrital garnet began before the Middle Miocene (15 Ma) and before the Late Miocene (10–9 Ma) in the Siwalik Group. The Bengal Fan data, by contrast, indicated that pyrope‐rich garnet appeared in the Early Miocene (17.3 Ma) and Late Miocene (8.5–6.5 Ma). We conclude that the Bengal Fan sediments record the erosion of the HHC zone since the Early Miocene that appears in the Siwalik sediments. Furthermore, we found that the HHC‐derived inputs decreased from the late Middle Miocene (12 Ma) to the early Middle Miocene (10 Ma) in both the Nepal Himalaya foreland basin and the Bengal Fan. The disappearance of the HHC‐derived detritus is probably the result of dilution by Lesser Himalayan detritus, which suggests that the Lesser Himalayan zone, which is composed of metamorphosed and unmetamorphosed sedimentary rocks, was uplifted. [ABSTRACT FROM AUTHOR]

An S‐shaped double azahelicene (1) was synthesized in excellent yield by a palladium‐catalyzed double dehydrogenative C−H coupling reaction. The stereochemistry of 1 was confirmed to be dl by single‐crystal X‐ray diffraction analysis. Selective formation of dl‐1 was attributed to the isomerization of the kinetically controlled product (meso‐1) into the more thermodynamically stable dl‐1 under the applied reaction conditions. dl‐1 can coordinate to palladium(II) in a bidentate trans‐chelating fashion, which was confirmed by X‐ray absorption fine structure (XAFS) as well as by X‐ray photoelectron spectroscopy (XPS), diffuse reflectance (DR) UV/Vis, and far‐infrared (FIR) absorption spectroscopy. Theoretical calculations of palladium complex 16 revealed a weak attractive interaction between palladium and carbon atoms on the central dimethoxynaphthalene core, which could facilitate a disproportionation between a trans‐chelating (dl‐1)⋅PdCl2 complex and PdCl2 to form 16. [ABSTRACT FROM AUTHOR]

Pleomorphic xanthoastrocytomas (PXAs) are rare low‐grade astrocytic tumors that typically present as superficial nodular cystic tumors of the cerebrum attached to the leptomeninx. Histologically, they are pleomorphic, hypercellular glial neoplasms. Despite the presence of microscopic pleomorphism, patients' postoperative prognosis is generally good. Anaplastic PXAs (APXAs) have a high mitotic index and patients with APXAs have a worse prognosis than patients with PXAs. Here, we report an autopsy case of APXA initially diagnosed as PXA. After gross total resection, the tumor recurred and was diagnosed as an APXA; thereafter, the patient died. An autopsy revealed that the tumor had relapsed at the primary site and had spread to the leptomeningeal space while concurrently invading the cerebrum including the periventricular area forming multifocal lesions. The histological findings of the autopsy were similar to those for epithelioid glioblastoma (EGBM) and small cell glioblastoma (SCGBM). In particular, the periventricular area with multifocal lesions was composed of SCGBM‐like cells. It has been shown that multifocal lesions are frequently identified in patients with SCGBM. This is the first histopathologically confirmed case of APXA‐related tumor presenting with periventricular extension and multifocal lesion formation. The periventricular extension might be a feature of PXAs and APXAs. However, suspected periventricular spread on imaging in past cases of PXAs and APXAs might instead represent the malignant transformation of these tumors to glioblastoma‐like high‐grade tumors, which often show SCGBM‐like histological patterns. [ABSTRACT FROM AUTHOR]

Certain patient populations are unable to achieve the recommended low‐density lipoprotein cholesterol goals with statin monotherapy alone. Such patients may benefit from concomitant therapy with ezetimibe (EZE) 10 mg added on to a statin. To this end, fixed‐dose combination (FDC) tablets containing EZE 10 mg and rosuvastatin (ROS) 2.5 mg (EZE/ROS2.5) and EZE 10 mg and ROS 5 mg (EZE/ROS5) have been developed for treatment of hypercholesterolemia. The purpose of the series of clinical studies reported herein was to evaluate the potential food effect (MK‐0653H, protocol 836 (P836)) and the bioequivalence between FDC and co‐administration of EZE and ROS in healthy Japanese subjects under fasted and fed conditions (MK‐0653H, protocol 835 (P835) and MK‐0653H, protocol 846 (P846), respectively). These studies show there is no clinically relevant food effect on EZE exposure following single oral administration of the FDC EZE/ROS5 in healthy Japanese subjects; however, ROS exposure was decreased in the fed state under conditions used to evaluate the maximum food effect. Following single oral administration of individual ROS tablets under the same conditions, the magnitude of decrease in ROS exposure was comparable to that seen with FDC, suggesting that the effect of food on ROS exposure was similar between the FDC tablet and co‐administration of individual EZE and ROS tablets. The FDC EZE/ROS5 was generally well tolerated in healthy Japanese subjects under fasted and fed conditions. [ABSTRACT FROM AUTHOR]

Hybridization and backcrossing of native populations with introduced species can lead to introgression and genetic alteration. In this study, we evaluated introgression in 43 deer from a potential hybrid zone around Okinoshima Island, Kinki District, Japan. This region witnessed the migration of a hybrid population (cross between the Formosan sika deer [Cervus nippon taiouanus] and other deer species) that could potentially breed with the native Japanese sika deer (C. n. centralis). We used an existing genetic marker for the mitochondrial cytochrome b gene and two novel markers for nuclear DNA, developed using publicly available next‐generation sequencing data. We identified one mainland deer with a mitochondrial haplotype identical to that of the Formosan sika deer as well as nuclear heterozygous sequences identical to those of Formosan and Japanese sika deer. This suggests that the mainland deer is a hybrid offspring of the Okinoshima population and native deer. However, only Japanese sika deer sequences were found in the other 42 samples, indicating limited introgression. Nevertheless, hybridization pre‐ and postintroduction in the Okinoshima population could cause multispecies introgression among Japanese sika deer, negatively affecting genetic integrity. We developed a simple test based on polymerase chain reaction–restriction fragment length polymorphism to detect introgression in natural populations. Our method can accelerate genetic monitoring of Japanese sika deer in Kinki District. In conclusion, to prevent further introgression and maintain genetic integrity of Japanese sika deer, we recommend establishing fences around Okinoshima Island to limit migration, besides a continued genetic monitoring of the native deer. [ABSTRACT FROM AUTHOR]

Pharmacokinetics (PKs) in Japanese healthy subjects were simulated for nine compounds using physiologically based PK (PBPK) models parameterized with physicochemical properties, preclinical absorption, distribution, metabolism, and excretion (ADME) data, and clinical PK data from non‐Japanese subjects. For each dosing regimen, 100 virtual trials were simulated and predicted/observed ratios for peak plasma concentration (Cmax) and area under the curve (AUC) were calculated. As qualification criteria, it was prespecified that >80% of simulated trials should demonstrate ratios to observed data ranging from 0.5–2.0. Across all compounds and dose regimens studied, 93% of simulated Cmax values in Japanese subjects fulfilled the criteria. Similarly, for AUC, 77% of single‐dosing regimens and 100% of multiple‐dosing regimens fulfilled the criteria. In summary, mechanistically incorporating the appropriate ADME properties into PBPK models, followed by qualification using non‐Japanese clinical data, can predict PKs in the Japanese population and lead to efficient trial design and conduct of Japanese phase I studies. [ABSTRACT FROM AUTHOR]

Background: Fingolimod is an effective disease‐modifying drug for relapsing–remitting multiple sclerosis (RRMS), but drug discontinuation might cause rebound syndrome, defined as massive and prolonged exacerbation of MS. We report a case of intractable MS with rebound syndrome after fingolimod cessation. Case presentation: A 54‐year‐old patient with RRMS had been disease activity‐free for 9 years during fingolimod treatment. However, she discontinued fingolimod by her own decision out of concern for progressive multifocal leukoencephalopathy. Five weeks after drug cessation, she developed progressive weakness in the left leg. Expanded Disability Status Scale scores worsened from 2.0 to 6.0. Blood tests showed recovery of lymphocyte count (1000/mm3) from the previous counts. Cerebrospinal fluid examination showed almost normal results, except for marked elevation of myelin basic protein (1420 pg/mL). Brain magnetic resonance imaging showed a massive lesion in the right frontal lobe with open‐ring enhancement and a small enhancing lesion in the left parietal lobe. Based on diagnosis as exacerbation of RRMS, the patient was treated with intravenous methylprednisolone, followed by oral dimethyl fumarate. However, 5‐month use of DMF could not remit the disease activity, leading to fingolimod reinitiation. Conclusions: Rebound syndrome is an intractable complication of exit strategy for fingolimod‐treated RRMS patients. To lower the risk for rebound syndrome, specific mechanisms of rebound syndrome are to be clarified. Furthermore, concise risk stratification for progressive multifocal leukoencephalopathy in fingolimod treatment is imperative. Taken together, the risk–benefit analysis for fingolimod treatment, including rebound syndrome as well as progressive multifocal leukoencephalopathy, is required to initiate the drug. [ABSTRACT FROM AUTHOR]

Square‐planar coordinate Ni2+ ions in oxides are exclusively limited to a low‐spin state (S=0) owing to extensive crystal field splitting. Layered oxychalcogenides A2NiIIO2Ag2Se2 (A=Sr, Ba) with the S=1 NiO2 square lattice are now reported. The structural analysis revealed that the Ni2+ ion is under‐bonded by a significant tensile strain from neighboring Ag2Se2 layers, leading to the reduction in crystal field splitting. Ba2NiO2Ag2Se2 exhibits a G‐type spin order at 130 K, indicating fairly strong in‐plane interactions. The high‐pressure synthesis employed here possibly assists the expansion of NiO2 square lattice by taking the advantage of the difference in compressibility in oxide and selenide layers. [ABSTRACT FROM AUTHOR]

Post‐mortem detection of pathogenetic microorganisms in severe infectious death is significantly important for diagnosing the cause of death as well as for public health. However, it is difficult to recognize whether a microorganism detected from post‐mortem materials is truly pathogenic or not. We report a case of severe soft tissue infection due to Streptococcus oralis subsp. tigurinus (S. tigurinus), a recently reported species, in which whole‐genome analysis was performed to clarify its pathogenicity. A 46‐year‐old woman had died with symptoms of a severe infectious disease. A post‐mortem examination was performed by a medical examiner. The external findings suggested a soft tissue infection; subsequently, pathological specimens sampled by necropsy revealed findings compatible with necrotizing fasciitis. In the post‐mortem bacterial test, S. tigurinus was detected from the localized autopsy sample. Whole‐genome sequencing was performed to analyze its pathogenicity and detected a strain of S. tigurinus with genetic determinants that were specific and unique to its highly virulent strains as a result of gene annotation. Utilizing various technologies, such as whole‐genome sequencing, may be a powerful tool for diagnosing the cause of infectious death accurately and safely. [ABSTRACT FROM AUTHOR]

Abstract: Myelin oligodendrocyte glycoprotein (MOG) is localized at the outermost layer of the myelin sheath and is accessible for autoantibodies. Although experimental autoimmune encephalitis induced with MOG immunization has been studied for 30 years, the results of previous reports on MOG immunoglobulin G (IgG) detection with enzyme‐linked immunosorbent assay and Western blot are confusing. However, after the development of human MOG‐transfected cell‐based assay to detect conformational‐sensitive MOG‐IgG, unique groups of patients have been found seropositive, and MOG‐IgG‐associated disease has become a hot topic in clinical neuroimmunology. Currently, the clinical spectrum of MOG‐IgG‐associated disease includes idiopathic optic neuritis, acute disseminated encephalomyelitis, encephalitides (brainstem and cerebral cortical), idiopathic myelitis, atypical multiple sclerosis, aquaporin‐4 IgG‐negative neuromyelitis optica spectrum disorders and others. MOG‐IgG‐associated disease occurs in both children and adults, and the female:male ratio is almost 1:1. Pleocytosis in the cerebrospinal fluids during acute exacerbation is often seen, but oligoclonal IgG bands are usually negative. T helper cell 17, B cells and neutrophil‐related cytokines appear to be upregulated intrathecally. The pathology of acute lesions is characterized by active inflammation demyelination with deposition of immunoglobulins and complements. Just like aquaporin 4 IgG‐positive neuromyelitis optica spectrum disorders, some disease‐modifying drugs for multiple sclerosis seem to be inefficacious in MOG‐IgG‐associated disease, and chronic immunosuppression is required to prevent relapse, especially in patients persistently positive for MOG‐IgG. Our understanding of this newly recognized disease remains insufficient, and the progress of research is much expected. [ABSTRACT FROM AUTHOR]

Abstract: The asymmetric hydrogenation of aromatic γ‐ and δ‐keto esters into optically active hydroxy esters or diols under the catalysis of a novel DIPSkewphos/3‐AMIQ–RuII complex was studied. Under the optimized conditions (8 atm H2 , Ru complex/t‐C4H9OK=1:3.5, 25 °C) the γ‐ and δ‐hydroxy esters (including γ‐lactones) were obtained quantitatively with 97–99 % ee. When the reaction was conducted under somewhat harsh conditions (20 atm H2 , [t‐C4H9OK]=50 m m, 40 °C), the 1,4‐ and 1,5‐diols were obtained predominantly with 95–99 % ee. The reactivity of the ester group was notably dependent on the length of the carbon spacer between the two carbonyl moieties of the substrate. The reaction of β‐ and ϵ‐keto esters selectively afforded the hydroxy esters regardless of the reaction conditions. This catalyst system was applied to the enantioselective and regioselective (for one of the two ester groups) hydrogenation of a γ‐ϵ‐diketo diester into a trihydroxy ester. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives The objectives of this study were to: (1) examine differences in the use of dental clinical practice guidelines among Japanese dentists, and (2) identify characteristics associated with the number of guidelines used by participating dentists. Methods We conducted a cross-sectional study consisting of a questionnaire survey in Japan between July 2014 and May 2015. The study queried dentists working in outpatient dental practices who are affiliated with the Dental Practice-Based Research Network Japan ( n = 148). They were asked whether they have used each of 15 Japanese dental clinical guidelines. Associations between the number of guidelines used by participants and specific characteristics were analysed via negative binomial regression analysis. Results The mean number of guidelines used by participating dentists was 2.5 ± 2.9 [standard deviation (SD)]. Rate of use of guidelines showed substantial variation, from 5% to 34% among dentists. The proportion of dentists that used guidelines was the highest among oral medicine specialists, who had the highest proportion for 10 of 15 guidelines. Negative binomial regression analysis identified three factors significantly associated with the number of guidelines used: 'years since graduation from dental school', 'specialty practice' and 'practice busyness'. Conclusions These results suggest that the use of clinical practice guidelines by Japanese dentists may still be inadequate. Training in the use of the guidelines could be given to dental students as undergraduate education and to young clinicians as continuing education. [ABSTRACT FROM AUTHOR]

Aims/Introduction Omarigliptin is a novel, potent, long-acting oral dipeptidyl peptidase-4 inhibitor being developed as a once-weekly (q.w.) treatment for type 2 diabetes mellitus patients, with 25 mg and 12.5 mg tablets recently being approved as market formulations in Japan. Materials and Methods This was a two-part, double-blind, randomized, placebo-controlled study in healthy Japanese men to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of omarigliptin after single dose (5-100 mg) and multiple dose (1-50 mg q.w. for 3 weeks) administration. Results Omarigliptin was rapidly absorbed with a time to maximum concentration of 0.5-4 h. The pharmacokinetic profile was biphasic with a long terminal half-life >100 h. The area under the concentration-time curve from 0 to 168 h, maximum concentration and the concentration at 168 h post-dose increased dose-dependently after 3 weeks of once-weekly dosing for doses ranging 1-50 mg, with accumulation ratios ranging 1.03-1.35 and 0.87-1.36 for the area under the concentration-time curve from 0 to 168 h and maximum concentration, respectively. Plasma dipeptidyl peptidase-4 inhibition levels 1 week post-dose increased with dose, ranging 79.2-94.0% after 5-100 mg single dose administration and 51.3-90.2% after 1-50 mg multiple once-weekly dose administration. Administration with food did not meaningfully alter the pharmacokinetics of omarigliptin. Omarigliptin was generally well tolerated, with no hypoglycemia being reported. Conclusion The results of the present study in healthy Japanese men showed that omarigliptin was well tolerated and had a pharmacokinetic and dipeptidyl peptidase-4 inhibition profile that supports once-weekly dosing in Japanese patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

SUMMARY We designed and evaluated ASICs (application-specific integrated circuits) for a human activity monitoring system in order to reduce total power consumption. The ASIC extracts the HR from the measured electrocardiogram (ECG) raw signal. To create an ASIC with ultra-low power consumption, we used a novel algorithm based on fuzzy logic that is very simple and requires minimal processing power. The fabricated ASIC shows sufficient functionality and a power level as low as 2 [ABSTRACT FROM AUTHOR]

Objective: The aims of this study were to examine dentists' recommendations for in-office fluoride to patients and identify dentists' characteristics associated with these recommendations.Study Design and Setting: The study was conducted using a cross-sectional questionnaire survey in Japan. The survey queried dentists (n = 282) in outpatient dental practices affiliated with the Dental Practice-based Research Network Japan (JDPBRN). This network aims to assist dentists in investigating research questions and sharing their experience and expertise.Results: The responses were obtained by 189 dentists (67 percent). Among valid response, 54 percent of dentists (n = 98) recommend in-office fluoride to more than 50 percent of their patients aged 6-18 years and 15 percent (n = 29) recommended this care to more than 50 percent of their patients aged over 18 years. Multiple logistic regression analysis suggested that factors associated with the percentage of patients who are recommended in-office fluoride included patient's interest in caries prevention and dentist's belief in the effectiveness of caries risk assessment.Conclusions: Dentist practice patterns for recommending in-office fluoride vary widely. Recommendation was significantly related to having a higher percentage of patients interested in caries prevention and to the dentist's belief about the effectiveness of caries risk assessment. (Clinicaltrials.gov registration number NCT01680848). [ABSTRACT FROM AUTHOR]

Distinctive survival strategies, specialized in regulation and in quality control, were observed in thermal adaptive evolution with a laboratory Escherichia coli strain. The two specialists carried a single mutation either within rpoH or upstream of gro ESL, which led to the activated global regulation by sigma factor 32 or an increased amount of Gro EL/ ES chaperonins, respectively. Although both specialists succeeded in thermal adaptation, the common winner of the evolution was the specialist in quality control, that is, the strategy of chaperonin-mediated protein folding. To understand this evolutionary consequence, multilevel analyses of cellular status, for example, transcriptome, protein and growth fitness, were carried out. The specialist in quality control showed less change in transcriptional reorganization responding to temperature increase, which was consistent with the finding of that the two specialists showed the biased expression of molecular chaperones. Such repressed changes in gene expression seemed to be advantageous for long-term sustainability because a specific increase in chaperonins not only facilitated the folding of essential gene products but also saved cost in gene expression compared with the overall transcriptional increase induced by rpoH regulation. Functional specialization offered two strategies for successful thermal adaptation, whereas the evolutionary advantageous was more at the points of cost-saving in gene expression and the essentiality in protein folding. [ABSTRACT FROM AUTHOR]

Objectives (i) To quantify the importance that dentists place on caries risk factors when developing a caries treatment plan and (ii) to test the hypothesis that the ratings of importance for specific factors are significantly associated with whether or not the dentist performs caries risk assessment ( CRA). Methods This study used a cross-sectional study design consisting of a questionnaire survey. The study queried dentists who worked in outpatient dental practices who were affiliated with the Dental Practice-Based Research Network Japan ( JDPBRN), which seeks to engage dentists in investigating research questions and sharing experiences and expertise ( n = 282). Participants ( n = 189) were asked to rate the importance of caries risk factors when developing a caries treatment plan in both adult and pediatric patients. Results Oral hygiene status was rated as the most important risk factor when developing a treatment plan in both adult and pediatric patients, whereas the use of fluorides was rated as the least important. Results of multiple logistic regression analysis showed that the odds ratios for the decision to perform CRA in the adult patient for past caries experience and use of fluorides were 2.61 (95% confidence interval [ CI]: 1.29-5.29) and 1.85 (95% CI: 1.12-3.04), respectively, whereas that for oral hygiene was 3.84 (95% CI: 1.15-12.79) and use of fluorides 1.79 (95% CI: 1.06-3.03) in the pediatric patient. Conclusions These results suggest that enhancing dentists' concept of the importance of current use of fluorides when developing a treatment plan may increase the percentage of dentists who conduct CRA in both adult and pediatric patients (clinicaltrials.gov registration number: NCT01680848). [ABSTRACT FROM AUTHOR]

Driving benzene round the twist: Azahelicene derivatives were synthesized in high yields by utilizing palladium‐catalyzed CH annulation reactions (see scheme). Functionalization at the C5 position in 6‐azahelicene by using palladium‐catalyzed CH arylation also gave coupling products in good yields. A tandem intra‐ and intermolecular double CH coupling reaction was performed to give a functionalized helicene in a one‐pot procedure. [ABSTRACT FROM AUTHOR]

The new catalyst system of RuBr2[( S, S)-xyl-skewphos][( S, S)-dpen] and potassium tert-butoxide shows high reactivity and enantioselectivity in the hydrogenation of N-arylimines [Xyl-Skewphos=2,4-bis(di-3,5-xylylphosphino)pentane, DPEN=1,2-diphenylethylenediamine]. A range of imines derived from aromatic and heteroaromatic ketones as well as some ferrocenyl and vinylic imines are hydrogenated with a turnover number as high as 18,000 under 10-50 atm of hydrogen to afford the amine products in up to 99% enantiomeric excess. The reaction is applied to the synthesis of a chiral N-arylamine, which is the synthetic intermediate of a biologically active compound. The mode of enantioselection is interpreted by using transition-state models based on the X-ray structure of the Xyl-Skewphos/DPEN-RuBr2 complex. [ABSTRACT FROM AUTHOR]

The ultrasonic technique for measuring travel times of compressional and shear waves using dual-mode transducers was adapted to a piston cylinder apparatus, allowing simultaneous measurements of travel times of compressional and shear waves of island arc samples under the high pressure and temperature conditions of island arcs. This method enables us to determine elastic properties and their pressure and temperature derivatives simultaneously. Furthermore, Vp/Vs can be directly determined from travel times of compressional and shear waves independently of length change due to compression or thermal expansion of rock samples under deep crustal conditions, providing more accurate Vp/Vs values than those determined from individual measurements of travel times of both elastic wave types using single-mode transducers. Experimental techniques and results are demonstrated using data on silicified pelitic schist from the Ryoke Belt to 0.6 GPa. The simultaneous measurement gives Vp = 5.60 km/s, ∂ Vp/∂ P = 0.090 (km/s)/GPa, Vs = 3.37 km/s, ∂ Vs/∂ P = 0.05 (km/s)/GPa, σ = 0.216, and Vp/ Vs = 1.66 at ambient conditions. The temperature derivatives were constrained from fitting using linear functions of temperature, yielding ∂ Vp/∂ T = −0.518 × 10−3 (km/s)/K and ∂ Vs/∂ T = −0.182 × 10−3 (km/s)/K. Performing simultaneous measurements of travel times of compressional and shear waves using dual-mode transducers, it is possible to accurately determine Vp/ Vs and Poisson's ratio of crustal minerals and rocks at deep crustal conditions to study the composition of the crustal interior, e.g. rock types and fluids below the hypocentral region of earthquakes or around bright spots. [ABSTRACT FROM AUTHOR]

Arachidonic acid mobilization in platelets activated by low concentrations (≤ 1.6 μg/ml) of TP 82, a monoclonal antibody against CD9, appears to consist of two distinct phases. In the first phase, limited arachidonic acid release occurs concomitantly with a shape change induced by TP 82. This appears to be dependent upon phospholipase A2 activation, since it is well preserved in the presence of aspirin, which completely blocked both intracellular Ca2+ elevation and phosphatidic acid formation which would indicate phospholipase C activation. The Na+/H+ exchange was also found to participate in the first phase of arachidonic acid mobilization, since extracellular Na+ depletion and ethylisopropylamiloride, a specific inhibitor of the Na+/H+ exchanger, effectively blocked this limited mobilization of arachidonic acid. The second, much larger, phase of arachidonic acid mobilization occurs with the beginning of platelet aggregation. A limited amount of thromboxane A2 formed during the first phase of arachidonic acid release plays an important role in induction of the massive arachidonic mobilization in the second phase. Factors, as yet unidentified, also appear to work synergistically with thromboxane A2 to induce the full picture of arachidonic acid mobilization. [ABSTRACT FROM AUTHOR]

The electron correlation effects on the multimode Peierls (MMP) state in the Peierls Hubbard model on the two-dimensional square lattice with the half-filled electronic band is investigated, taking account of the on-site interaction ( U) and the nearest neighbor interaction ( V), by using the variational Monte Carlo method based on the Gutzwiller wave function. The Peierls distortion amplitude is enhanced as U is increased, showing the first-order phase transition from the MMP state to the antiferromagnetic state. The Peierls distortion amplitude is also enhanced by V. The first-order phase transition from the MMP state to the charge-ordered state occurs at a critical value of V. There is no coexistence of the Peierls distortion and the charge order. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

The products can be further substituted in a slightly modified protocol using aryl bromides as substrates [products (IV)]. [ABSTRACT FROM AUTHOR]

Spiraling up the rings according to K. Kamikawa and co‐workers in their Communication on page 11837 ff.; they report that azahelicenes with a unique helical‐shaped backbone can be efficiently synthesized in high yields by utilizing palladium‐catalyzed CH annulation reactions. Functionalization at the C5 position in azahelicenes by using palladium‐catalyzed CH arylation also gave coupling products in good yields. These two CH bond activation processes can also be performed in one pot. [ABSTRACT FROM AUTHOR]