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To investigate and compare the safety of letrozole and natural cycles in fresh early embryo transfers.A retrospective cohort study.A large fertility treatment center.Women who underwent natural and letrozole cycles during fresh early embryo transfer at Kato Ladies Clinic between January 2008 and December 2017.None.Perinatal complications and congenital anomalies.No significant differences were observed in pregnancy complications, gestational age, birth weight, small for gestational age, large for gestational age, and congenital anomalies between the the women who underwent natural and letrozole cycles.The perinatal outcomes and congenital anomaly rates associated with letrozole and natural cycles in fresh early embryo transfers were comparable. Therefore, our data support the safe use of letrozole in fresh early embryo transfers in assisted reproductive technology.

Background: In Japan, genetic testing, surveillance, and risk-reducing surgery for hereditary breast and ovarian cancer (HBOC) syndrome have been covered by the Japanese national insurance system since April 2020. On the other hand, the current situation is that medical care, including surveillance of undiagnosed (cancer-free) patients, is self-funded even for individuals with HBOC. We report a case in which breast cancer was diagnosed at an early stage during surveillance for cancer-free HBOC at the patient's own expense, and risk-reducing surgery was performed at the same time as treatment for breast cancer. Case presentation: The patient was a 63-year-old woman. Her sister had a history of breast cancer in her 30s and was found to be a BRCA2 pathogenic variant carrier by genetic testing. The patient therefore presented to the genetic department of our hospital and underwent genetic testing (out-of-pocket). A pathogenic variant was found at the same site. During annual breast and ovarian surveillance at the patient’s own expense, the physician with sufficient expertise in contrast-enhanced breast magnetic resonance imaging (MRI) noticed a change in the contrast enhancement pattern on breast MRI and performed needle biopsy, revealing ductal carcinoma in situ. At her request, she underwent concurrent contralateral risk-reducing mastectomy and risk-reducing salpingo-oophorectomy in addition to breast cancer treatment. Conclusions: We have seen a case in which cancer treatment and risk-reducing surgery were performed at the same time for a pathogenic variant carrier who was very anxious about developing cancer. Surveillance of cancer-free BRCA1/2 mutation carriers and expansion of insurance coverage for surgery are important future issues.

Background: The semi-dry dot-blot (SDB) method, a diagnostic procedure for detecting lymph node (LN) metastases using an anti-cytokeratin (CK) antibody, is based on the theory that epithelial components, such as CK, are not found in normal LNs. Thus, metastases are diagnosed according to the presence of CK in the lavage fluid of sectioned LNs. We prospectively evaluated novel SDB kits that use a newly developed anti-CK19 antibody and an automatic reader for diagnosing sentinel LN metastases in patients with breast cancer as a multi-center study. Methods: We obtained 924 sentinel LNs dissected from 405 patients with breast cancer between January 2021 and December 2021 at six institutes in Japan. We excluded patients who underwent neoadjuvant chemotherapy and neoadjuvant endocrine therapy. LNs were sectioned at 2-mm intervals and washed with phosphate-buffered saline. Cells suspended in the lavage fluid of sectioned LNs were centrifuged and lysed to extract protein. The extracted protein was applied to the SDB kit to diagnose LN metastasis using an automatic absorbance reader. Hematoxylin and eosin (H&E) stained and washed LNs were blindly examined by pathologists using intraoperative and permanent histological examination. Diagnoses based on SDB kit and automatic reader findings were compared with diagnoses made by permanent histological examination of paraffin-embedded H&E-stained sections of LNs. Primary endpoints were the sensitivity, specificity, and overall agreement of the SDB kit for distinguishing macrometastases from non-macrometastases. Results: Ninety-four of the 924 LNs were assessed as macrometastases, 40 as micrometastases, and 790 as isolated tumor cells by histological examination. Compared with patients with non-macrometastases, those with macrometastases had significantly younger age (p< 0.01), larger primary tumor (p< 0.01), higher nuclear grade (p=0.04), increased lymphatic invasion (p< 0.01), and increased venous invasion (p=0.01). Using a borderline CK19 absorbance of 11.9 milli-absorbance for detecting macrometastases with an area under the curve of 0.989, the sensitivity, specificity, and overall agreement of the SDB kit were 94.7%, 98.3%, and 97.9%, respectively. Moreover, the sensitivity, specificity, and overall agreement of the intraoperative histological examination compared with permanent histological examination for distinguishing macrometastases from non-macrometastases were 91.4%, 99.1%, and 98.3%, respectively. Furthermore, the kits and automatic reader yielded diagnoses within approximately 20 min at a cost of < 30 USD for the SDB kit and < 3,000 USD for the automatic reader. Conclusions: The kits with an automatic reader used in our study were accurate, quick, and cost-effective in diagnosing LN metastases without the loss of LN tissue and were particularly useful for distinguishing macrometastases. We plan to make the SDB kit and automatic reader commercially available worldwide soon. Citation Format: Megumi Matsumoto, Masaaki Baba, Aya Tanaka, Sayaka Kuba, Michi Morita, Fujiko Kaseida, Hiroko Hayashi, Shigeto Maeda, Hiroshi Yano, Eiko Inamasu, Akiko Ogiya, Kenta Sekiya, Masahiro Nakashima, Hideki Ikari, Shinji Ohno, Hiroyuki Takei, Katsunori Yanagihara, Susumu Eguchi, Takeshi Nagayasu, Ryota Otsubo. Evaluation of novel diagnostic kits using the semi-dry dot-blot method combined with an automatic reader for detecting metastases in sentinel lymph nodes of patients with breast cancer: a multi-center prospective study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-01-03.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a specific, tumor-forming, non-neoplastic, vascular lesion with few reported cases worldwide. Herein, we describe the case of a patient who underwent laparoscopic splenectomy for SANT. A 47-year-old woman underwent upper gastrointestinal endoscopy for suspected gastric submucosal tumor. Contrast-enhanced abdominal computed tomography revealed the presence of a gradually enhancing lesion in the splenic hilum. Although we suspected splenic fibrotic hamartoma, malignancy could not be ruled out. Therefore, the patient underwent laparoscopic splenectomy, resulting in the histopathological diagnosis of SANT. Although SANT is a benign tumor, it may be difficult to obtain definitive diagnosis using preoperative imaging alone. Because the long-term natural history of SANT is unknown, we believe that splenectomy could be an appropriate technique for the diagnosis and treatment of SANT.

A 66-year-old woman underwent partial mastectomy and a sentinel lymph node biopsy for left breast cancer; the pathological diagnosis was invasive ductal carcinoma (pT1aN0, pStage I, triple-negative subtype). Postoperative radiotherapy was performed. Two years later, she developed redness and induration at both breasts. The diagnosis was bilateral inflammatory breast cancer. After four cycles of dose-dense epirubicin and cyclophosphamide followed by 12 weekly paclitaxel cycles, bilateral total mastectomy and axillary lymph node dissection were performed. At the one-year follow-up after undergoing operation and radiotherapy, she remained alive without recurrence. Dose-dense treatment regimens may help patients achieve complete resection without short-term recurrence.

STUDY QUESTION Is the embryo transfer (ET) method associated with maternal and perinatal outcomes after minimal stimulation IVF using clomiphene citrate (CC)? SUMMARY ANSWER The incidence of pregnancy complications and adverse perinatal outcomes was influenced by the developmental stage (cleavage versus blastocyst stages) and cryopreservation (fresh versus vitrified) of the transferred embryos. WHAT IS KNOWN ALREADY Pregnancies resulting from IVF are associated with higher risks of adverse perinatal outcomes compared to natural conceptions; therefore, the next focus in reproductive medicine should be to assess whether these increased risks are attributable to IVF. Pregnancy complications and perinatal outcomes should be considered in addition to pregnancy outcomes when selecting the ET method, however, studies that describe the influence of transfer methods on perinatal and maternal outcomes are limited. STUDY DESIGN, SIZE, DURATION This study retrospectively analysed a large single-centre cohort. The clinical records of 36 827 women who underwent oocyte retrieval (during a CC-based minimal stimulation cycle) followed by their first ET at the fertility treatment centre between January 2008 and December 2017 were retrospectively analysed. The patients underwent a single fresh cleavage-stage ET (SFCT), single vitrified-warmed cleavage-stage ET (SVCT) or single vitrified-warmed blastocyst transfer (SVBT). This study only included one cycle per patient. PARTICIPANTS/MATERIALS, SETTING, METHODS Oocyte retrieval was performed following CC-based minimal ovarian stimulation. The embryos were transferred 2–3 days after retrieval or vitrified at the cleavage or blastocyst stage. The vitrified embryos were then warmed and transferred within the natural cycles. Pregnancy complications and perinatal outcomes were stratified according to the transfer methods used. Multivariate logistic regression analysis was performed to evaluate the effect of ET methods on the prevalence of pregnancy complications and congenital anomalies. MAIN RESULTS AND THE ROLE OF CHANCE The rates of clinical pregnancy and delivery were significantly different among the groups. We analysed pregnancy complications in 7502 singleton births (SFCT, 3395 cycles; SVCT, 586 cycles; and SVBT, 3521 cycles). Multivariate logistic regression analysis revealed that the adjusted odds ratio (AOR) for hypertensive disorders in pregnancy was significantly lower in the SVBT group than in the SFCT group [AOR, 0.72; 95% CI, 0.56–0.92]. The AOR for low-lying placenta was lower in the SVBT group than in the SFCT group (AOR, 0.34; 95% CI, 0.19–0.60). The AOR for placenta previa was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.21; 95% CI, 0.07–0.58 versus AOR, 0.53; 95% CI, 0.38–0.75, respectively). A total of 7460 follow-up data on neonatal outcomes was analysed. The AOR for preterm delivery was lower in the SVBT group than in the SFCT group (AOR, 0.78; 95% CI, 0.64–0.94). The AOR for low birthweight was significantly lower after SVCT and SVBT than after SFCT (AOR, 0.68; 95% CI, 0.46–0.98 versus AOR, 0.57; 95% CI, 0.48–0.66, respectively). The AOR for small for gestational age was lower in the SVCT and SVBT groups than in the SFCT group (AOR, 0.68; 95% CI, 0.46–0.98 versus AOR, 0.44; 95% CI, 0.36–0.55, respectively). The AOR for large for gestational age babies was higher in the SVBT group than in the SFCT group (AOR, 1.88; 95% CI, 1.62–2.18). The incidence of each congenital anomaly was similar among the groups. LIMITATIONS, REASONS FOR CAUTION The study data were collected through self-reported parental questionnaires on maternal and neonatal outcomes. Our findings were not compared with the incidence of pregnancy complications and congenital anomalies in natural pregnancies. Furthermore, this study was retrospective in nature; therefore, further studies are required to ascertain the generalizability of these findings to other clinics with different protocols and/or different patient demographics. WIDER IMPLICATIONS OF THE FINDINGS This study demonstrated reassuring outcomes for SVBT (in terms of a lower incidence of pregnancy complications) compared to SFCT. Our findings provide valuable knowledge that will help improve perinatal and maternal outcomes in CC-based stimulation and inform couples of the possible benefits and risks of each type of ET method. STUDY FUNDING/COMPETING INTEREST(S) This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.

Obesity is associated with an increased risk of non-alcoholic fatty liver disease (NAFLD), which is initiated by adipocyte-macrophage crosstalk. Among the possible molecules regulating this crosstalk, we focused on neuropeptide Y (NPY), which is known to be involved in hypothalamic appetite and adipose tissue inflammation and metabolism. In this study, the NPY−/− mice showed a marked decrease in body weight and adiposity, and lower free fatty acid and adipose inflammation without food intake alteration during a high fat diet (HFD). Moreover, NPY deficiency increased the thermogenic genes expression in brown adipose tissue. Notably, NPY-mRNA expression was upregulated in macrophages from the HFD mice compared to that from the mice on a standard diet. The NPY-mRNA expression also positively correlated with the liver mass/body weight ratio. NPY deletion alleviated HFD-induced adipose inflammation and liver steatosis. Hence, our findings point toward a novel intracellular mechanism of NPY in the regulation of adipocyte-macrophage crosstalk and highlight NPY antagonism as a promising target for therapeutic approaches against obesity and NAFLD., Biomedicines, 9(11), art. no. 1739; 2021

A 68-year-old woman developed systemic blisters while receiving treatment for nephrotic syndrome. As she also developed marked liver dysfunction and disseminated intravascular coagulation, she was admitted to our hospital. She was diagnosed with varicella zoster virus (VZV) infection. Treatment was administered in the intensive-care unit, but the patient died on day 24 post-admission after severe VZV infection. A post-mortem examination showed micro-abscesses and necrosis caused by varicella zoster infection in multiple organs, including the liver, kidneys, and gastrointestinal tract. Because VZV infection can become severe in immunocompromised patients, careful consideration is needed for the prevention and treatment of the viral infection.

Aims: Gut-associated lymphoid tissue (GALT) carcinoma is a rare colorectal tumour that arises in the epithelium covering GALT. GALT carcinoma is a differentiated tubular adenocarcinoma with dense lymphoid tissue with a characteristically well-demarcated margin. To date, 26 cases of GALT carcinoma, including the three cases discussed here, have been reported. Most (24 of 26) were discovered at early stages and none of the cases have documented any metastases. This suggests that GALT carcinoma may have a favourable prognosis. It is hypothesised that GALT carcinoma originates from M cells in specialised epithelia covering GALT. However, this hypothesis has yet to be confirmed. Methods and results: In this study, we examined three cases of GALT carcinoma by immunohistochemistry detection of glycoprotein 2, a specific marker for M cells, and electron microscopy. Our findings showed that the tumour cells of GALT carcinoma in all three cases were negative for M cells. We thus concluded that GALT carcinoma may be a tubular adenocarcinoma arising by chance in the GALT. This unique carcinoma is a diferentiated adenocarcinoma that grows slowly with the development of GALT. Conclusions: We propose that GALT carcinoma should be classified separately because of its histological setting and good prognosis., Histopathology, 73(3), pp.521-528; 2018

Several reports on immunoglobulin (Ig)G4-related disease (IgG4-RD) with gastrointestinal involvement (IgG4-related gastrointestinal disease; IgG4-GID) have been published, although this entity has not been fully established clinicopathologically. Thus, we carried out a multicenter survey. Patients with possible IgG4-GID who underwent resection were collected. Histologic slides were reevaluated, and eight cases with diffuse lymphoplasmacytic infiltration but without numerous neutrophils, granulations or epithelioid granulomas were further analyzed. Overall, the IgG4 counts (87–345/high-power field) and IgG4/IgG-positive ratio were high (44–115%). The demographic findings included advanced age among the patients (55–80 years) and male preponderance (six cases). Six lesions (five gastric, one esophageal), consisting of lymphoplasmacytic infiltration with neural involvement in the muscularis propria and/or bottom-heavy plasmacytosis in the gastric mucosa, were histologically regarded as highly suggestive of IgG4-RD. Storiform fibrosis and obliterative phlebitis were found in two cases, and the former gave rise to a 7-cm-sized inflammatory pseudotumor (IPT) in one case. Ulceration and carcinoma co-existed in three and two lesions, respectively. All the patients had other organ involvement (OOI), and serum IgG4 levels were markedly elevated (four of five patients). The remaining two cases with gastric IPTs featuring reactive nodular fibrous pseudotumor or nodular lymphoid hyperplasia were regarded as possible cases of IgG4-RD because of the histologic findings and lack of OOI. IgG4-GID is found in the setting of IgG4-RD, often with ulceration or cancer. Characteristic histologic findings are observed in the muscularis propria and gastric mucosa. Cases with IPT may be heterogeneous, and there may be mimickers of IgG4-GID.

Pneumomediastinum is defined as the presence of extraluminal gas within the mediastinum. Hamman described a diabetic ketoacidosis (DKA) patient with subcutaneous emphysema and spontaneous pneumomediastinum, a case known in current times as Hamman's syndrome and now pneumomediastinum is known to be one of the accompanying findings of DKA. We describe two cases with diabetes mellitus in which postmortem computed tomography (CT) could detect pneumomediastinum prior to autopsy. One was a woman in her 40 s, who had type II diabetes mellitus with bronchopneumonia in the middle and lower lobes of the right lung (Case 1) and the other also aged in her 40 s with type I diabetes mellitus (Case 2). In these cases with diabetic mellitus, the finding of pneumomediastinum at postmortem CT gave differential diagnostic considerations of DKA in addition to common cause such as decomposition or cardiopulmonary resuscitation. Autopsy with histopathological and biochemical examination suggested the cause of death in both cases were fatal DKA. The main cause of pneumomediastinum in Case 1 was pulmonary emphysema, and DKA was an exacerbation factor of pneumomediastinum. In contrast, DKA could have caused pneumomediastinum in Case 2, so called Hamman's syndrome. Pneumomediastinum is an obvious morphological abnormality, and thus we should pay attention to the information of pneumomediastinum from postmortem CT scanning.

Epithelial type malignant mesothelioma with a clear cell morphology is rare, and no case arising in the peritoneum of a female patient has been reported. Here we report a case of clear cell mesothelioma that developed in the peritoneum of a 61-year-old female. The patient died from massive ascites and respiratory failure 11days after her hospital admission. The autopsy demonstrated marked thickening of the omentum and a yellowish-whitish tumor diffusely covering the abdominal organs. The predominantly solid tumor was characterized microscopically by the growth of atypical cells with an abundant clear cytoplasm. The immunohistochemical study suggested mesothelioma rather than carcinoma. Electron microscopy showed the long and slender villi of the tumor cells, confirming the diagnosis. Primary clear cell carcinoma of the peritoneum, like clear cell mesothelioma, is rare and was also a diagnostic consideration in this patient. The differentiation between these two tumors is discussed herein.

Summary Neuropeptide Y (NPY) is an orexigenic peptide that plays an essential role in caloric restriction (CR)‐mediated lifespan extension. However, the mechanisms underlying the NPY‐mediated effects in CR are poorly defined. Here, we report that NPY deficiency in male mice during CR increases mortality in association with lipodystrophy. NPY −/− mice displayed a rapid decrease in body weight and fat mass, as well as increased lipolysis during CR. These alterations in fat regulation were inhibited by the lipolysis inhibitor, acipimox, a treatment associated with reduced mortality. The lipolytic/thermogenic signaling, β3‐adrenergic receptor/hormone sensitive lipase, was markedly activated in white adipose tissue of NPY −/− mice compared with that of NPY +/+ mice, and thermogenesis was controlled by NPY under negative energy balance. These results demonstrate the critical role of NPY in the regulation of lipid metabolic homeostasis and survival via control of lipolysis and thermogenesis in a state of negative energy balance.

Management of constipation in patients receiving cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) or CHOP-like chemotherapy regimens is important for prevention of paralytic ileus. We reported earlier that the laxative action of magnesium oxide is reversed by the concomitant use of antacids in cancer patients receiving opioid analgesics. Here, we assessed the prevalence of prophylactic laxative medication for the control of constipation in patients receiving CHOP or CHOP-like regimens for non-Hodgkin's lymphoma. Data obtained from 211 eligible patients were retrospectively analyzed. Almost all patients (99%) received anti-ulcer agents such as proton pump inhibitors and H2 receptor antagonists for the prophylaxis of gastric disorders associated with prednisolone. Prophylactic laxatives were prescribed in 86 patients (40.8%), in which magnesium oxide was used most predominantly (88.4%). However, magnesium oxide at doses of ≦2000 mg/d was not effective for prevention of constipation, although the compound totally inhibited the incidence of constipation at doses higher than 2000 mg/d. Therefore, it is important to avoid negative drug interaction between magnesium oxide and antacids in patients receiving CHOP chemotherapy.

This review focuses on mechanisms of calorie restriction (CR), particularly the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis as an evolutionary conserved signal that regulates aging and lifespan, underlying the effects of CR in mammals. Topics include (1) the relation of the GH-IGF-1 signal with chronic low-level inflammation as one of the possible causative factors of aging, that is, inflammaging, (2) the isoform specificity of the forkhead box protein O (FoxO) transcription factors in CR-mediated regulation of cancer and lifespan, (3) the role for FoxO1 in the tumor-inhibiting effect of CR, (4) pleiotropic roles for FoxO1 in the regulation of disorders, and (5) sirtuin (Sirt) as a molecule upstream of FoxO. From the evolutionary view, the necessity of neuropeptide Y (Npy) for the effects of CR and the pleiotropic roles for Npy in life stages are also emphasized. Genes for mediating the effects of CR and regulating aging are context-dependent, particularly depending on nutritional states.

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn&rsquo, s disease, are chronic disorders of the gastrointestinal tract, although the exact causes of IBD remain unknown. Present treatments for IBDs have poor tolerability and insufficient therapeutic efficacy, thus, alternative therapeutic approaches are required. Soybean-derived isoflavones have multiple bioactivities such as anti-inflammation. However, the low water solubility of soybean isoflavones limits their bioavailability and practical use. Therefore, in order to study the preventive effects of water-soluble soybean isoflavones on colonic inflammatory status, we examined soybean-derived isoflavone glycosides (SIFs) in a dextran sodium sulfate (DSS)-induced murine colitis model and in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Oral administration of SIF (0.5 w/v%) attenuated DSS-induced colitis in terms of body weight decrease, colon shortening, epithelial apoptosis, histological score, mRNA levels of inflammatory cytokines, and immune cell infiltration in colon tissues. In the in vitro assessment, we observed the inhibitory effects of SIF on the production of nitric oxide and prostaglandin E2, via suppression of inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW264.7 macrophages in response to LPS. Furthermore, we confirmed that the expression of inflammatory cytokines and chemokines were decreased by pre-treatment with SIF in LPS-activated RAW264.7 macrophages. Moreover, we demonstrated that SIF suppressed inflammatory mediators involved in nuclear factor-&kappa, B signaling pathway via inhibitory &kappa, B kinase phosphorylation and degradation of inhibitory &kappa, B. Our results suggested that SIF may be beneficial for the remission of colonic inflammatory status including IBDs.

Forty-six reciprocal and six Robertsonian translocation carrier couples who experienced recurrent pregnancy loss underwent fluorescence in situ hybridization-based preimplantation genetic diagnosis (PGD) for the presence of the two translocated chromosomes. Out of 52 couples, 17 (33%) were undergoing infertility treatment. In total, 239 PGD cycles as oocyte retrieval (OR) were applied. The transferrable rate of negatively diagnosed embryos at the cleavage stage was 26.3%; 71 embryos were transferred as single blastocysts. The clinical pregnancy rate per transfer was 60.6%. We obtained 41 healthy live births with 3 incidences of miscarriage (7.0%). The average cumulative live birth rate was 76.9% during 4.6 OR cycles using a mild ovarian stimulation strategy. The outcomes were classified into four groups based on carrier gender and maternal age (young (

SummaryWhat is known and objective Antimicrobial stewardship is required to ensure the appropriate use of antimicrobials. However, no reports have been published on clinical outcomes of implementation of antimicrobial stewardship in patients receiving pathogen-specific antibiotics. Method To evaluate the clinical outcomes of patients who received drugs, we conducted a single-centre, retrospective study of the effects of an antimicrobial stewardship programme targeting methicillin-resistant Staphylococcus aureus (MRSA). Results The time to administer effective antimicrobials was significantly (median number of days, 3 before vs. 0 after, P < 0·001) shortened, and the rate of de-escalation was significantly elevated (47·1% vs. 96·2%, P < 0·001) after implementation of daily review. The 60-day clinical failure associated with Gram-positive bacterial infection was significantly reduced (33·3% vs. 17·6%, P = 0·007) after intervention. What is new and conclusions Daily review of administration of antimicrobials targeting MRSA was highly effective in improving clinical outcomes by optimizing early antimicrobial therapy.

Argonaute 2 bound mature microRNA (Ago2‐miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation‐related Ago2‐miRNAs ( miR‐139‐5p , miR‐142‐3p , miR‐142‐5p , and miR‐223 ) and show that miR‐223 is critical for infection control. miR‐223 Y /− mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin‐6 expression, and markedly improved repair of Staphylococcus aureus ‐infected wounds. We also showed that the expression of miR‐223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR‐223 Y /− ‐derived neutrophils, or miR‐223 antisense oligodeoxynucleotides in S. aureus ‐infected wild‐type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR‐223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR‐223 might be of therapeutic benefit for infected wounds in the clinic.

As English-medium instruction (EMI) spreads around the world, university teachers and students who are non-native speakers of English (NNS) need to put much effort into the delivery or reception of content. Construction of scientific meaning in the process of learning is already complex when instruction is delivered in the first language of the teachers and students, and may become even more challenging in a second language, because science education depends greatly on language. In order to identify important pedagogical functions that teachers use to deliver content and to present different ways to realise each function, a corpus of lectures related to science and engineering courses was created and analysed. NNS teachers and students in science and engineering involved in EMI higher education can obtain insights for delivering and listening to lectures from the Online Corpus of Academic Lectures (OnCAL).

Adiponectin (Adipoq), a peptide hormone secreted from the white adipose tissue, may play a role in the anti-aging and/or anti-tumor effects of calorie restriction (CR). We analyzed metabolic traits in Adipoq gene-overexpressing mice fed ad libitum with a regular diet (RD) or a high-fat diet (HFD), or fed 30% CR of RD initiated at 12. weeks of age. Adipoq-RD and -HFD mice at 6. months of age showed reduced blood glucose and insulin concentrations, and thus increased insulin sensitivity, compared with WT mice fed a RD or a HFD. In the epididymal white adipose tissue in Adipoq mice, senescence-like changes such as upregulation of p53 protein and of biomarkers of inflammation, Cd68 and Ccl2 mRNA, were ameliorated compared with WT-RD and WT-HFD mouse tissues. Resistance to stress induced by lipopolysaccharide was also strengthened in Adipoq mice compared with WT mice. These metabolic changes and stress resistance were also noted in the WT-CR mice, suggesting that Adipoq plays a part in the effect of CR. In contrast, in an allograft tumor growth model, tumor growth was not inhibited in Adipoq mice. The present findings suggest that Adipoq plays a part in the anti-aging, but not in the anti-tumor, effects of CR., Experimental Gerontology, 64, pp.46-54; 2015

This study examines the language used by researchers in science and engineering, where clarity is essential. We prepared The Japanese-English Corpus of Presentations in Science and Engineering (JECPRESE) to examine how language is used in science and engineering to clearly and accurately present information. JECPRESE contains transcriptions of presentations given in Japanese and English by researchers. Analyses revealed vagueness in Japanese arising from the tendencies of the Japanese language to sometimes omit subjects and to lack specificity in conveying discourse strategies, verb tense, and mood. Such vagueness is considered to have roots in traditional Japanese society and culture that aim to maintain harmony in a community. However, in an age of global communications, this can be an obstacle to projecting an understandable message. Suggestions are made as to how to make scientific Japanese present clearer messages to a professional community based on linguistic considerations.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate protein translation by binding to complementary target mRNAs. We previously identified two mature members of the miR-142 family, miR-142-5p and miR-142-3p, as inflammation-related miRNAs with potential roles in wound healing. Here, we demonstrated that these two miRNAs are prominently expressed in wound-infiltrated neutrophils and macrophages and play central roles in wound healing. We generated miR-142−/− mice using the exchangeable gene-trap method and showed that healing of Staphylococcus aureus-infected skin wounds was significantly delayed in miR-142−/− mice compared with that in wild-type mice. MiR-142−/− mice exhibited abnormal abscess formation at S. aureus-infected skin wound sites and were also more susceptible to horizontal transmission of wound infections. MiR-142−/− neutrophils showed altered phagocytosis as a consequence of chemotactic behavior, including enhanced F-actin assembly, disturbed cell polarity, and increased cell motility. We showed that these changes were linked to cytoskeletal regulation, and that expression of the small GTPases was markedly increased in miR-142−/− neutrophils. Collectively, our data demonstrate that the miR-142 family is indispensable for protection against S. aureus infection and its clearance at wound sites. MiR-142-3p and miR-142-5p play nonredundant roles in actin cytoskeleton regulation by controlling small GTPase translation in neutrophils at wound sites.

A rare case of a patient with primary adenocarcinoma of the middle lobe bronchus that was successfully treated with rigid bronchoscopy followed by middle sleeve lobectomy is reported. The patient was a 75-year-old man who presented with low-grade fever and cough. Chest computed tomography showed obstructive pneumonia of the lower lobe and a polypoid lesion in the truncus intermedius. Middle sleeve lobectomy and mediastinal lymphadenectomy were performed following recovery of respiratory function after partial resection of the tumor with rigid bronchoscopy. There was no sign of tumor recurrence and metastasis over 32 months of follow-up. We should be aware of tracheal or bronchial tumor in patients with prolonged asthma-like symptoms. Palliative resection with rigid bronchoscopy was useful to make the correct diagnosis, evaluate the extent of the tumor, and protect the right lower lobe.

Intraductal/intracystic papillary carcinoma (IPC) of the breast is defined as a malignant non-invasive papillary tumor arising from the ductal-lobular system. Based on the presence of myoepithelial cells in the cystic wall, IPC is distinguished from encapsulated papillary carcinoma (EPC). Here, we report a case of an intracystic apocrine papillary tumor in the breast of a 49-year-old woman. Histopathologic examination revealed that the entire papillary structures and cyst wall were comprised of apocrine cells, some of which showed nuclear atypia with macronucleoli. Immunohistochemical examination revealed a lack of myoepithelial cells in the papillary fronds and cyst wall. Although the dense proliferation of apocrine cells mimicked a cribriform pattern, detailed examination identified a delicately intermingled interstitium in the cribriform-like growth area in the present case. We judged the current case to be benign apocrine papilloma. Only a few apocrine variants of IPC or EPC have been reported to be malignant or potentially malignant. Since even benign apocrine lesions are known to lack myoepithelial cells, histopathologic evaluation regarding malignant potential requires caution in apocrine variants. The detection of clearly benign areas and knowledge of the "pseudo-cribriform" pattern should provide clues to distinguish between benign and malignant apocrine papillary tumors., Pathology - Research and Practice, 209(12), pp.808-811; 2013

Introduction: Previous studies have suggested that sleep‑disordered breathing (SDB frequently develops after myocardial infarction (MI and leads to a poor prognosis. However the details remain unclear. Therefore we examined the clinical backgrounds and the time course of SDB in patients after MI. Methods: The subjects were 92 consecutive patients (mean age 65 � 12 years who had MI without decompensated heart failure or uncontrolled myocardial ischemia. All subjects underwent overnight sleep studies and we investigated baseline clinical characteristics. Among the patients with confirmed SDB the 38 patients who agreed underwent nighttime multichannel respiratory monitoring at both 14 days and 2 months after the onset of MI and we investigated their clinical features. Results: The percentage of patients with SDB 14 days after MI was high (93.5%. Among all patients 6.5% had no SDB 39.1% had mild SDB 29.3% had moderate SDB and 25.0% had severe SDB. The clinical features of patients with moderate‑to‑severe SDB (apnea‑hypopnea index [AHI] 15 times hour did not differ significantly from those of patients with mild SDB or patients without SDB (AHI

A solitary fibrous tumor is a neoplasm generally arising from the mesothelial surfaces of the pleura and mesothelium. In this paper, we describe three cases of rare solitary fibrous tumors arising from the orbit and discuss the management of the tumors, including diagnosis and treatment. All three cases were treated by surgical resection and showed satisfactory aesthetic and functional results. For a definitive diagnosis, immunohistochemical staining for proteins such as vimentin, CD34 and bcl-2 and hematoxylin and eosin (H&E) staining for identifying the morphological characteristics of spindle cell tumors with a partially storiform pattern and staghorn vessels are indispensable. The principle of treatment for orbital solitary fibrous tumor is complete resection because the prognosis depends on controlling tumor progression, which can be difficult with chemotherapy and radiotherapy alone.

We previously reported that oral ingestion of polaprezinc, a zinc-L-carnosine, suspended in sodium alginate solution prevents oral mucositis in patients receiving radiotherapy or high-dose chemotherapy. In the present study, we developed a novel preparation of polaprezinc and evaluated clinical effect of the lozenge preparation in patients receiving high-dose chemotherapy for hematopoietic stem cell transplantation. The preparation contained 18.75 mg polaprezinc in a tablet and showed an excellent uniformity and stability up to 24 weeks after storage under room temperature. The incidence rate of grade ≥ 2 oral mucositis was 74 % in patients without premedication, whereas the rate was remarkably reduced in patients receiving the suspension (23 %) or lozenge (13 %) of polaprezinc (P

Oral communication skills are essential for engineers today and, as they are included in accreditation criteria of educational programmes, their teaching and evaluation deserve attention. However, concrete aspects as to what should be taught and evaluated in relation to oral communication skills have not been sufficiently established. In this paper, a method to aid the efficient teaching of oral presentation skills is proposed, from the presentation structure level to word and sentence level choices, through the use of JECPRESE, The Japanese–English Corpus of Presentations in Science and Engineering. As of June 2012, the corpus is composed of transcriptions of 74 presentations delivered in Japanese by students graduating from the Master's programme of various engineering departments and 31 presentations delivered in English, 16 by experienced researchers at an international conference on chemistry, and 15 by undergraduate engineering students of a mid-sized American university. The utterances were classif...

Background Past reports showed that the baroreflex continuously regulates hemodynamics during exercise. However, it is still clinically unclear. If baroreflex mechanism is able to influence actually exercise cardiovascular control, baroreflex sympathetic and/or parasympathetic function relates to response to exercise. Therefore, we examined the relationship of heat rate changes to both blood pressure increment and decrement with tolerance and chronotropic response to peak exercise in patients with heart disease. Methods In 25 male heart disease patients (60 ± 9 years) without decompensated heart failure, baroreceptor reflex sensitivity (BRS ms mmHg−1) was measured by reflex heart rate responses to changes in blood pressure after phenylephrine (P-BRS) and nitroglycerin (N-BRS) injection, respectively. Symptom-limited treadmill exercise test was performed according to Bruce's protocol. Results (i) The absolute values of blood pressure change after the administrations were similar between the agents because the dosages of nitroglycerin and phenylephrine were set to equalize absolute changes in blood pressure. (ii) In this study population, the ratio of N-BRS to P-BRS was not significantly correlated with hypertension and diabetes mellitus. (iii) Exercise capacity (METs) (r = −0·626) and heart rate response to exercise per METs (r = 0·670) was significantly related to N-BRS but not to P-BRS. Conclusion We found that the abnormality of baroreflex function in the presence of blood pressure decrements can lead to insufficient capacity and easy sympathetic activation during exercise.

We present what is believed to be the first report of heterogeneous carcinoma arising from breast ductal adenoma. A 57-year-old woman presented with a nodule in her right breast. Histological examination of a vacuum-assisted biopsy specimen revealed epithelial tubular proliferation and papillary apocrine epithelium. The myoepithelial cells lining the tubules were confirmed by immunohistochemistry. The nodule had increased in size 18 months later and tumorectomy was performed. The surgical specimen revealed proliferating apocrine epithelium with sheet-like and cribriform architecture within a mammary duct. Some myoepithelial cells showed irregular proliferation around the tubular epithelium. All three components, including apocrine, myoepithelial and glandular cells, showed prominent nuclear atypia and significant mitotic activity. The patient was diagnosed with malignant transformation of ductal adenoma. The malignant potential of ductal adenoma has not previously been discussed, but this heterogeneous carcinoma could represent a serious pitfall in the diagnosis of ductal adenomas.

Invasive micropapillary carcinoma (IMPC) is a rare subtype of epithelial tumor of the breast listed in the 2003 World Health Organization histologic classification of tumors of the breast. It is characterized by inside-out micropapillary morphology, frequent lymph vessel invasion (LVI), and lymph node metastasis; however, its etiology remains unknown. This study investigated the incomplete inside-out growth pattern (IGP) in invasive ductal carcinoma, not otherwise specified (NOS), and examined the association between incomplete IGP and clinicopathologic features, including the presence of intratumoral lymph vessels (ILV), LVI, nodal metastasis, and prognosis. Tumor tissues from 166 invasive duct carcinomas NOS and 10 IMPCs were immunostained using an anti-epithelial membrane antigen antibody to detect IGP and with D2-40 antibody to determine the presence of ILV and LVI. Incomplete IGP was detected focally in 88 (53%) of 166 invasive duct carcinomas NOS. Transition areas between IMPC and invasive duct carcinoma NOS also showed prominent incomplete IGP in 9 (90%) of 10 IMPCs. Incomplete IGP in invasive duct carcinomas NOS was associated with larger tumor size, higher frequencies of ILV, LVI, nodal metastasis, and poorer recurrence-free survival by univariate analysis. Incomplete IGP, ILV, and tumor size independently affected LVI by multivariate analysis. These findings indicate that incomplete IGP of tumor cell clusters is not uncommon and is a useful tool for predicting LVI in invasive duct carcinoma NOS of the breast., Virchows Archiv, 458(2), pp.159-169; 2011

The FoxO transcription factors may be involved in the antiaging effect of calorie restriction (CR) in mammals. To test the hypothesis, we used FoxO1 knockout heterozygotic (HT) mice, in which the FoxO1 mRNA level was reduced by 50%, or less, of that in wild-type (WT) mouse tissues. The WT and HT mice were fed ad libitum (AL) or 30% CR diets from 12 weeks of age. Aging- and CR-related changes in body weight, food intake, blood glucose, and insulin concentrations were similar between the WT and HT mice in the lifespan study. The response to oxidative stress, induced by intraperitoneal injection of 3-nitropropionic acid (3-NPA), was evaluated in the liver and hippocampus at 6 months of age. Several of the selected FoxO1-target genes for cell cycle arrest, DNA repair, apoptosis, and stress resistance were up-regulated in the WT-CR tissues after 3-NPA injection, while the effect was mostly diminished in the HT-CR tissues. Of these gene products, we focused on the nuclear p21 protein level in the liver and confirmed its up-regulation only in the WT-CR mice in response to oxidative stress. The lifespan did not differ significantly between the WT and HT mice in AL or CR conditions. However, the antineoplastic effect of CR, as indicated by reduced incidence of tumors at death in the WT-CR mice, was mostly abrogated in the HT-CR mice. The present results suggest a role for FoxO1 in the antineoplastic effect of CR through the induction of genes responsible for protection against oxidative and genotoxic stress., Aging cell, 9(3), pp.372-382; 2010