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High-resolution seismic reflection profiles delineated the distribution of mound-shaped reflections, which were interpreted as reefs, beneath the insular shelf western off Irabu Island, Ryukyus, southwestern Japan. A sediment core through one of the mounded structures was recovered from the sea floor at a depth of −118.2 m by offshore drilling and was dated by radiometric methods. The lithology and coral fauna of the core indicate that the mounded structure was composed of coral–algal boundstone suggesting a small-scaled coral reef. High-precision α-spectrometric 230Th/234U dating coupled with calibrated accelerator mass spectrometric 14C ages of corals obtained reliable ages of this reef ranging from 22.18 ± 0.63 to 30.47 ± 0.98 ka. This proves that such a submerged reef was formed during the lowstand stage of marine oxygen isotope stages 3–2. The existence of low-Mg calcite in the aragonitic coral skeleton of 22.18 ± 0.63 ka provides evidence that the reef had once been exposed by lowering of the relative sealevel to at least −126 m during the last glacial maximum in the study area. There is no room for doubt that a coral reef grew during the last glacial period on the shelf off Irabu Island of Ryukyus in the subtropical region of western Pacific. [ABSTRACT FROM AUTHOR]

Analyzes the forward linkage formed by small firms in central Java, Indonesia. Effects of linkage to promotion of development in the firm; Improvement on technological capabilities in subcontracting linkages; Support on linkages with wholesalers by trade credits.

BackgroundObjectiveCase DescriptionOutcomesConclusionBody lateropulsion (BL) is a phenomenon in which the body involuntarily falls to one side; however, its detailed postural control characteristics remain unclear.This case report aimed to measure the surface electromyography (EMG) of the lower limbs while standing in a patient with severe BL on the affected side due to pontine infarction and to investigate the characteristics of postural control.We evaluated a patient with severe BL due to pontine infarction at two-time points, 6 and 20 days after onset, to assess static standing balance under open and closed eye conditions and measure the center of pressure (COP) and lower extremity EMG during these tasks.There were minimal changes in COP position and total locus length during the eyes closed condition compared to the eyes open condition. However, the head and trunk to the non-BL side of the tilt and bilateral medial hamstring muscle activity tended to be higher when the eyes were closed. At the final evaluation, head and trunk tilt and EMG changes were reduced during the eyes-closed condition compared to the eyes-open condition. The initial postural response was considered to reflect a compensatory postural strategy for BL, characterized by the body involuntarily tilting to one side.The change in posture over time may indicate a reduction in the compensatory postural response as the condition improves. In this case, characteristic postural findings were identified through EMG measurements, suggesting the possibility of future studies involving multiple cases. [ABSTRACT FROM AUTHOR]

Myelosuppression is a major side effect of chemotherapy. Although decreased blood cells are restored with the recovery of bone marrow cells, insufficient recovery of decreased lymphocytes was observed in mice given azacitidine (AZA), a DNA methyltransferase (DNMT) inhibitor, even following the restoration of bone marrow cells. To understand the mechanisms behind this sustained lymphopenia, we examined AZA's impact on the hematopoietic progenitor cells and the expression of Dnmts and differentiation-related genes. An antimetabolite of cytidine analog, cytarabine (Ara-C), was used as a reference compound. Decreases in almost all blood parameters and common lymphoid progenitors (CLPs) and the downregulation of Dnmts and differentiation-related genes in Lineage-Sca-1+c-kit+ (LSK) cells were observed in mice administered AZA or Ara-C for 7 d. In the posttreatment observation, all parameters, except for lymphocytes and monocytes, exhibited recovery within 3 wk after the final dosing in both treated groups. However, no recovery from the decreases in lymphocytes, especially B cells, and monocytes occurred even after 5 wk. The number of CLPs was elevated after 3 wk. There was a tendency toward recovery from the decreased expression of Dnmt1 and differentiation-related genes, but the expression levels of Dnmt3a and Dnmt3b did not fully recover even 5 wk after the final dosing. Taken together, the findings revealed that the mechanism of sustained lymphopenia observed in mice treated with AZA or Ara-C is associated, at least in part, with the abnormal differentiation of CLPs into B cells accompanied by the prolonged suppression of Dnmt3a and Dnmt3b expression on LSK cells., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Campylobacter jejuni causes gastroenteritis in humans and is a major concern in food safety. Commercially prepared chicken meats are frequently contaminated with C. jejuni, which is closely associated with the diffusion of intestinal contents in poultry processing plants. Sodium hypochlorite (NaClO) is commonly used during chicken processing to prevent food poisoning; however, its antimicrobial activity is not effective in the organic-rich solutions. In this study, we investigated the potential of a new photo-disinfection system, UVA-LED, for the disinfection of C. jejuni-contaminated chicken surfaces. The data indicated that UVA irradiation significantly killed C. jejuni and that its killing ability was significantly facilitated in NaClO-treated chickens. Effective inactivation of C. jejuni was achieved using a combination of UVA and NaClO, even in the organic-rich condition. The results of this study show that synergistic disinfection using a combination of UVA and NaClO has potential beneficial effects in chicken processing systems.

An 89-year-old woman with recurrent hormone receptor-positive and HER2-negative breast cancer was treated with fulvestrant-palbociclib combination therapy. However, 3 months after therapy initiation, she presented to our emergency room with dyspnea and fever and was admitted to our hospital because of respiratory failure. After radiological and microbiological evaluation, she was diagnosed with palbociclib-related pneumonitis. Accordingly, corticosteroids were administered, and the patient exhibited initial clinical and radiological improvement. However, pneumonitis recurred following corticosteroid tapering; her condition did not improve with high-dose intravenous corticosteroid administration, leading to death. Palbociclib- related pneumonitis is rare, but clinicians need to pay attention to this potentially lethal adverse event.

Germline MUTYH mutations were investigated in 14 Japanese colorectal polyposis patients without germ line adenomatous polyposis coli (APC) gene mutations. Three patients had a heterozygous IVS10-2A>G MUTYH mutation. The onset of MUTYH-associated polyposis (MAP) occurs later than that of familial adenomatous polyposis with germline APC mutation. Thus, we compared the carrier frequency of MUTYH IVS10-2A>G heterozygote in the APC mutation negative cases with that in 115 controls over 70 years of age who showed no apparent clinical manifestations of cancer and claimed that they had no history of cancer at the time of enrollment. The frequency of IVS10-2A>G heterozygote in APC germline mutation negative polyposis patients was significantly higher than control subject (p = 0.012, Chi square test). Although the sample size is still too small to conclude, the IVS10-2A>G MUTYH heterozygote might add to the risk of developing germline APC mutation negative polyposis.

Purpose: To evaluate the influence of renal function on the efficacy and safety of the sodium glucose cotransporter 2 inhibitor luseogliflozin (TS-071) in Japanese patients with type 2 diabetes mellitus (T2DM)., Methods: Study 1 was a 52-week, Phase III study to evaluate the efficacy and safety of 2.5 mg/d luseogliflozin (or increased to 5 mg/d) in patients with T2DM with moderate renal impairment. During the initial 24 weeks, efficacy and safety of luseogliflozin were compared with placebo. Study 2 was a pooled analysis of four 52-week, Phase III studies of luseogliflozin, including Study 1, to evaluate the efficacy and safety of luseogliflozin in patients with various degrees of renal function. Patients were stratified into 3 groups by baseline estimated glomerular filtration rate (eGFR): normal renal function (≥90 mL/min/1.73 m(2)), mild impairment (≥60 to <90 mL/min/1.73 m(2)), and moderate impairment (≥30 to <60 mL/min/1.73 m(2)). Patients with moderate impairment were further divided into those with mild-moderate (≥45 to <60 mL/min/1.73 m(2)) and moderate-severe (≥30 to <45 mL/min/1.73 m(2)). In both studies, efficacy end points included changes in glycated hemoglobin (HbA1c) level, fasting plasma glucose (FPG) level, and body weight. The safety end points included adverse events (AEs) and laboratory parameters., Findings: In Study 1, HbA1c, FPG, and body weight significantly decreased at Week 24 in patients treated with luseogliflozin compared with patients treated with placebo, with the decrease in these parameters also observed with luseogliflozin at Week 52. The incidence of AEs was similar between groups. In Study 2, 1030 patients were included (normal, 275; mildly impaired, 598; and moderately impaired, 157). At Week 52, HbA1c, FPG, and body weight were significantly decreased from baseline in all groups. In between-group comparisons, the decreases in HbA1c and body weight were significantly smaller in patients with moderate impairment than in those with normal function; however, the HbA1c-lowering efficacy was reduced by nearly half, whereas the efficacy of body weight lowering was not so much diminished in the moderate impairment group. Furthermore, a scatter plot showed that changes in HbA1c were more influenced by baseline HbA1c than by baseline eGFR. The incidence of AEs during 52 weeks was similar among all groups, with the majority being mild., Implications: Luseogliflozin improved glycemic control and reduced body weight in all eGFR groups, and its efficacy on HbA1c lowering was reduced in those with moderate renal impairment. Luseogliflozin was well tolerated and safe, with no significant safety issues identified, regardless of baseline eGFR. The study is registered with Clinical Trials Information/JapicCTI of the Japan Pharmaceutical Information Center, and the study registry identification numbers are JapicCTI-111507, JapicCTI-111508, JapicCTI-111509, and JapicCTI-111543., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Heterozygous deleterious mutation of the PMS2 gene is a cause of Lynch syndrome, an autosomal dominant cancer disease. However, the frequency of PMS2 mutation is rare compared with that of the other causative genes; MSH2, MLH1 and MSH6. PMS2 mutation has so far only been reported once from a Japanese facility. Detection of PMS2 mutation is relatively complicated due to the existence of 15 highly homologous pseudogenes, and its gene conversion event with the pseudogene PMS2CL. Therefore, for PMS2 mutation analysis, it is crucial to clearly distinguish PMS2 from its pseudogenes. We report here a novel deleterious 11 bp deletion mutation of exon 11 of PMS2 distinguished from PMS2CL in a 34-year-old Japanese female with rectal cancer. PMS2 mutated at c.1492del11 results in a truncated 500 amino acid protein rather than the wild-type protein of 862 amino acids. This is supported by the fact that, although there is usually concordance between MLH1 and PMS2 expression, cells were immunohistochemically positive for MLH1, whereas PMS2 could not be immunohistochemically stained using an anti-C-terminal PMS2 antibody, or effective PMS2 mRNA degradation with NMD caused by the frameshift mutation., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Lynch syndrome is an autosomal dominantly inherited disease that is characterized by a predisposition to cancers, mainly colorectal cancer. Germline mutations of DNA mismatch repair genes such as MLH1, MSH2, MSH6 and PMS2 have been described in patients with Lynch syndrome. Here, we report deletion of 2 bp in the splice donor site of the MLH1 exon 6 (c.545+4&#95;545+5delCA) in a 48-year-old Japanese woman with Lynch syndrome. RT-PCR direct sequencing analysis revealed that this mutation led to an increase in the level of an MLH1 transcript in which exon 6 was skipped, and may cause a frameshift (p.E153FfsX8). Therefore, this mutation appears to be pathogenic and is responsible for Lynch syndrome. Additionally, analysis of the patient's tumor cells indicated microsatellite instability high phenotype and loss of the MLH1 and PMS2 proteins. To our knowledge, this is a germline splice site mutation of MLH1 that has not been reported previously., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Campylobacter jejuni causes foodborne disease associated with abdominal pain, gastroenteritis, and diarrhea. These symptoms are induced by bacterial adherence and invasion of host epithelial cells. C. jejuni infection can occur with a low infective dose, suggesting that C. jejuni may have evolved strategies to cope with the bacterial clearance system in the gastrointestinal tract. The mucosa layer is the first line of defense against bacteria. Mucus conditions are maintained by water and anion (especially Cl(-)) movement. Cystic fibrosis transmembrane conductance regulator (CFTR) is the main Cl(-) channel transporting Cl(-) to the lumen. Mutations in CFTR result in dehydrated secreted mucus and bacterial accumulation in the lungs, and recent studies suggest that closely related pathogenic bacteria also may survive in the intestine. However, the relationship between C. jejuni infection and CFTR has been little studied. Here, we used an (125)I(-) efflux assay and measurement of short-circuit current to measure Cl(-) secretion in C. jejuni-infected T-84 human intestinal epithelial cells. The basic state of Cl(-) secretion was unchanged by C. jejuni infection, but CFTR activator was observed to induce Cl(-) secretion suppressed in C. jejuni-infected T-84 cells. The suppression of activated Cl(-) secretion was bacterial dose-dependent and duration-dependent. A similar result was observed during infection with other C. jejuni strains. The mechanism of suppression may occur by affecting water movement or mucus condition in the intestinal tract. A failure of mucus barrier function may promote bacterial adhesion or invasion of host intestinal epithelial cells, thereby causing bacterial preservation in the host intestinal tract., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Inhaled nitric oxide (NO) has been reported to decrease the infarct size in cardiac ischemia-reperfusion (I/R) injury. However, reactive nitrogen species (RNS) produced by NO cause myocardial dysfunction and injury. Because H₂ is reported to eliminate peroxynitrite, it was expected to reduce the adverse effects of NO. In mice, left anterior descending coronary artery ligation for 60 min followed by reperfusion was performed with inhaled NO [80 parts per million (ppm)], H₂ (2%), or NO + H₂, starting 5 min before reperfusion for 35 min. After 24 h, left ventricular function, infarct size, and area at risk (AAR) were assessed. Oxidative stress associated with reactive oxygen species (ROS) was evaluated by staining for 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal, that associated with RNS by staining for nitrotyrosine, and neutrophil infiltration by staining for granulocyte receptor-1. The infarct size/AAR decreased with breathing NO or H₂ alone. NO inhalation plus H₂ reduced the infarct size/AAR, with significant interaction between the two, reducing ROS and neutrophil infiltration, and improved the cardiac function to normal levels. Although nitrotyrosine staining was prominent after NO inhalation alone, it was eliminated after breathing a mixture of H₂ with NO. Preconditioning with NO significantly reduced the infarct size/AAR, but not preconditioning with H₂. In conclusion, breathing NO + H₂ during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H₂ gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.

Electrolysis of a 0.1% (17.1 mM) solution of NaCl using separate anode and cathode compartments gives rise to solutions containing active chemical species. The strongly acidic "anode solution" (EW+) has high levels of dissolved oxygen and available chlorine in a form of hypochlorous acid (HOCl) with a strong potential for sterilization, which we have investigated here. Exposing Aspergillus parasiticus at an initial density of 10(3)spores in 10 microL to a 50-fold volume (500 microL) of EW+ containing ca. 390 micromol HOCl for 15 min at room temperature resulted in a complete inhibition of fungal growth, whereas the cathode solution (EW-) had negligible inhibitory effects. Moreover, the mutagenicity of aflatoxin B(1) (AFB(1)) for Salmonella typhimurium TA-98 and TA-100 strains was strongly reduced after AFB(1) exposure to the EW+ but not with the EW-. In high-performance liquid chromatography analysis, the peak corresponding to AFB(1) disappeared after treatment with the EW+, indicating decomposition of the aflatoxin. In contrast, the routinely used disinfectant sodium hypochlorite, NaOCl, of the same available chlorine content as that of EW+ but in a different chemical form, hypochlorite (OCl-) ion, did not decompose AFB(1) at pH 11. However, NaOCl did decompose AFB(1) at pH 3, which indicated that the principle chemical formula to participate in the decomposition of AFB(1) is not the OCl- ion but HOCl. Furthermore, because the decomposition of AFB(1) was suppressed by pretreating the EW+ with the OH radical scavenger thiourea, the chemical species responsible for the AFB(1)-decomposing property of the EW+ should be at least due to the OH radical originated from HOCl. The OH in EW+ was proved by electron spin resonance analysis.

Electrolyzed anodic NaCl solutions [EW+], prepared by the electrolysis of 0.1% NaCl, have been shown to instantly inactivate most pathogens that cause food-borne disease. Elimination of food-borne pathogens does not necessarily guarantee food safety because enterotoxins produced by pathogens may remain active. We have tested whether EW+ can inactivate Staphylococcal enterotoxin A (SEA), one of the major enterotoxins responsible for food poisoning. Fixed quantities of SEA were mixed with increasing molar ratios of EW+, and SEA was evaluated by reversed-phase passive latex agglutination (RPLA) test, immunoassay, native polyacrylamide gel electrophoresis (PAGE), and amino acid analysis after 30 min incubations. Exposure of 70 ng, or 2.6 pmol, of SEA in 25 microL of PBS to a 10-fold volume of EW+, or ca. 64.6 x 10(3)-fold molar excess of HOCl in EW+, caused a loss of immuno-reactivity between SEA and a specific anti-SEA antibody. Native PAGE indicated that EW+ caused fragmentation of SEA, and amino acid analysis indicated a loss in amino acid content, in particular Met, Tyr, Ile, Asn, and Asp. Staphylococcal enterotoxin-A excreted into culture broth was also inactivated by exposure to an excess molar ratio of EW+. Thus, EW+ may be a useful management tool to ensure food hygiene by food processing industries.