Caries Increment and Salivary Microbiome during University Life: A Prospective Cohort Study

The purpose of this 3-year prospective cohort study was to explore the relationship between an increase in dental caries and oral microbiome among Japanese university students. We analyzed 487 students who volunteered to receive oral examinations and answer baseline (2013) and follow-up (2016) questionnaires. Of these students, salivary samples were randomly collected from 55 students at follow-up and analyzed using next-generation sequencing. Students were divided into two groups: increased group (Delta decayed, missing, and filled teeth (Delta DMFT) score increased during the 3-year period) and non-increased group (Delta DMFT did not increase). Thirteen phyla, 21 classes, 32 orders, 48 families, 72 genera, and 156 species were identified. Microbial diversity in the increased group (n = 14) was similar to that in the non-increased group (n = 41). Relative abundances of the family Prevotellaceae (p = 0.007) and genera Alloprevotella (p = 0.007) and Dialister (p = 0.039) were enriched in the increased group compared with the non-increased group. Some bacterial taxonomic clades were differentially present between the two groups. These results may contribute to the development of new dental caries prevention strategies, including the development of detection kits and enlightenment activities for these bacteria

BRCAness Predicts Resistance to Taxane-Containing Regimens in Triple Negative Breast Cancer During Neoadjuvant Chemotherapy

AbstractBackgroundTo provide optimal treatment of heterogeneous triple negative breast cancer (TNBC), we need biomarkers that can predict the chemotherapy response.Patients and MethodsWe retrospectively investigated BRCAness in 73 patients with breast cancer who had been treated with taxane- and/or anthracycline-based neoadjuvant chemotherapy (NAC). Using multiplex, ligation-dependent probe amplification on formalin-fixed core needle biopsy (CNB) specimens before NAC and surgical specimens after NAC. BRCAness status was assessed with the assessor unaware of the clinical information.ResultsWe obtained 45 CNB and 60 surgical specimens from the 73 patients. Of the 45 CNB specimens, 17 had BRCAness (38.6% of all subtypes). Of the 23 TNBC CNB specimens, 14 had BRCAness (61% of TNBC cases). The clinical response rates were significantly lower for BRCAness than for non-BRCAness tumors, both for all tumors (58.8% vs. 89.3%, P = .03) and for TNBC (50% vs. 100%, P = .02). All tumors that progressed with taxane therapy had BRCAness. Of the patients with TNBC, those with non-BRCAness cancer had pathologic complete responses significantly more often than did those with BRCAness tumors (77.8% vs. 14.3%, P = .007). After NAC, the clinical response rates were significant lower for BRCAness than for non-BRCAness tumors in all subtypes (P = .002) and in TNBC cases (P = .008). After a median follow-up of 26.4 months, 6 patients—all with BRCAness—had developed recurrence. Patients with BRCAness had shorter progression-free survival than did those with non- BRCAness (P = .049).ConclusionIdentifying BRCAness can help predict the response to taxane, and changing regimens for BRCAness TNBC might improve patient survival. A larger prospective study is needed to further clarify this issue

Significance of Ki-67 Expression and Risk Category (St. Gallen 2007) in Elderly Breast Cancer Patients, with Emphasis on the Need for Postoperative Adjuvant Therapy

Breast cancer is increasing in the elderly. Although elderly breast cancer patients frequently receive less invasive therapy, its appropriateness is debatable. Ki-67 expression is a controversial prognostic factor and predictor of the efficacy of postoperative adjuvant therapy. This study investigated the value of the Ki-67 labeling index (LI) in elderly breast cancer patients, especially with respect to adjuvant therapy. This retrospective study investigated 82 primary breast cancer patients aged 70 years who underwent surgery between 1995 and 2005. Their clinicopathological findings were reviewed and their Ki-67 LIs were determined. The patients\u27 mean age was 78 years, the mean observation period was 53.8 months, and 60 patients (73.2%) underwent adjuvant therapy. The St. Gallen (2007) risk category and the Ki-67 LI (mean, 15.3%) were both significantly correlated with relapse and prognosis. In the 31 cases with a low Ki-67 LI (< 10%), 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. Among the intermediate- and high-risk patients, Ki-67 was low in 15; 1 patient who underwent adjuvant treatment relapsed, but there were no deaths. For elderly breast cancer patients aged 70 years categorized low risk by St. Gallen (2007) or with a low Ki-67 LI, the risk of relapse and death appears to be low regardless of adjuvant therapy. Though further investigation is needed to determine a method of measuring the Ki-67 LI and determining a cut-off value, our findings suggest that the Ki-67 LI helps with the selection of adjuvant therapy in elderly patients

BRCA1/2 Mutation Frequency is HIGH in Japanese Triple-Negative Breast Cancer Patients

Germline mutations of BRCA1/2 genes cause hereditary breast and/or ovarian cancer. However, whether guidelines like those of the National Comprehensive Cancer Network (NCCN) can suitably predict the likelihood of BRCA1/2 mutations in the Japanese population is unclear. Methods BRCA1/2 gene mutation frequencies were investigated in relation to parameters such as age, family history (FH), and breast cancer subtype using data collected from 922 Japanese breast cancer patients who underwent surgery between September 2010 and June 2013. BRCA1/2 mutations were present in 15 of 57 (26.3%) tested patients. The frequency of the mutations was not significantly related to age. Among the 180 patients who reported an FH of breast cancer, 11 of the 37 who were tested (29.7%) were positive for BRCA1/2 mutations. Of those with an FH of ovarian cancer (n = 34), seven of 12 patients tested (58.3%) were carriers of BRCA1/2 (P = 0.013). Six of these seven carriers were triple-negative breast cancer (TNBC) patients. In all, there were 97 TNBC patients, and the presence of the BRCA1/2 mutation in this subgroup was significantly greater than in non-TNBC patients, with 12 of 17 TNBC patients (70.5%) testing positive (P = 0.03). There were 59 TNBC patients < 60 years of age, and of the 16 (27.1%) who underwent BRCA1/2 genetic testing, 11 (68.8%) were found to have mutations in BRCA1/2. Among the TNBC patients, 29 also reported an FH of breast or ovarian cancer; of these, nine of the 13 tested (69.2%) were positive for a BRCA1/2 mutation. The data demonstrate that BRCA1/2 mutations are observed more frequently in TNBC patients, especially those < 60 years of age or in combination with an FH of breast and/or ovarian cancer, suggesting that some of the NCCN guidelines can adequately predict BRCA1/2 carriers in the Japanese population

A Case of Androgen Receptor-positive Triple Negative Breast Cancer with Good Response to Anti-androgen Therapy

Anti-androgen therapy has been proposed to be effective in the treatment of androgen receptor (AR)-positive triple negative breast cancer (TNBC). Herein, we report on the case of a 91-year-old female patient with AR-positive TNBC who underwent anti-androgen therapy and had a good response. Because of dementia, the patient lives in an aged care facility. It was here that a staff member noticed a mass with a rash on the patient\u27s breast. Consequently, the patient was sent for further examination. Ultrasonography revealed an irregularly shaped, indistinct hypoechoic mass measuring 19×18×9mm located in the upper outer quadrant of the left breast. Core needle biopsy (CNB) was performed and the mass was diagnosed as apocrine carcinoma. Further immunohistochemical analysis showed that the mass was AR-positive TNBC. Anti-androgen therapy was determined to be the optimal treatment option for this patient. The Institutional Review Board approval the off-label use of an anti-androgen for the treatment of this patient, who was subsequently treated with the anti-androgen flutamide. After 8 months, the size of the tumor had reduced to 15×9×5mm

The antiretroviral potency of APOBEC1 deaminase from small animal species

Although the role of the APOBEC3-dependent retroelement restriction system as an intrinsic immune defense against human immunodeficiency virus type1 (HIV-1) infection is becoming clear, only the rat ortholog of mammalian APOBEC1s (A1) thus far has been shown to possess antiviral activity. Here, we cloned A1 cDNAs from small animal species, and showed that similar to rat A1, both wild-type and Δvif HIV-1 infection was inhibited by mouse and hamster A1 (4- to 10-fold), whereas human A1 had negligible effects. Moreover, rabbit A1 significantly reduced the infectivity of both HIV-1 virions (>300-fold), as well as that of SIVmac, SIVagm, FIV and murine leukemia virus. Immunoblot analysis showed that A1s were efficiently incorporated into the HIV-1 virion, and their packaging is mediated through an interaction with the nucleocapsid Gag domain. Interestingly, there was a clear accumulation of particular C-T changes in the genomic RNAs of HIV-1 produced in their presence, with few G-A changes in the proviral DNA. Together, these data reveal that A1 may function as a defense mechanism, regulating retroelements in a wide range of mammalian species

The Japanese Clinical Practice Guideline for acute kidney injury 2016

Acute kidney injury (AKI) is a syndrome which has a broad range of etiologic factors depending on different clinical settings. Because AKI has significant impacts on prognosis in any clinical settings, early detection and intervention are necessary to improve the outcomes of AKI patients. This clinical guideline for AKI was developed by a multidisciplinary approach with nephrology, intensive care medicine, blood purification, and pediatrics. Of note, clinical practice for AKI management which was widely performed in Japan was also evaluated with comprehensive literature search

Heterogeneous distribution of doublecortin-expressing cells surrounding the rostral migratory stream in the juvenile mouse

In the postnatal mammalian brain, neural stem cells of the ventricular-subventricular zone continue to generate doublecortin (Dcx)-expressing immature neurons. Throughout life, these immature neurons migrate to the olfactory bulb through the rostral migratory stream (RMS). In this study, we investigated the distribution of these putative immature neurons using enhanced green fluorescent protein (EGFP) expression in the area surrounding the RMS of the juvenile Dcx-EGFP mice. Through the combined use of an optical clearing reagent (a 2,2 '-thiodiethanol solution) and two-photon microscopy, we visualized three-dimensionally the EGFP-positive cells in the entire RMS and its surroundings. The resulting wide-field and high-definition images along with computational image processing methods developed in this study were used to comprehensively determine the position of the EGFP-positive cells. Our findings revealed that the EGFP-positive cells were heterogeneously distributed in the area surrounding the RMS. In addition, the orientation patterns of the leading process of these cells, which displayed the morphology of migrating immature neurons, differed depending on their location. These novel results provide highly precise morphological information for immature neurons and suggest that a portion of immature neurons may be detached from the RMS and migrate in various directions

Visualizing hippocampal neurons with in vivo two-photon microscopy using a 1030 nm picosecond pulse laser

In vivo two-photon microscopy has revealed vital information on neural activity for brain function, even in light of its limitation in imaging events at depths greater than several hundred micrometers from the brain surface. We developed a novel semiconductor-laser-based light source with a wavelength of 1030 nm that can generate pulses of 5-picosecond duration with 2-W output power, and a 20-MHz repetition rate. We also developed a system to secure the head of the mouse under an upright microscope stage that has a horizontal adjustment mechanism. We examined the penetration depth while imaging the H-Line mouse brain and demonstrated that our newly developed laser successfully images not only cortex pyramidal neurons spreading to all cortex layers at a superior signal-to-background ratio, but also images hippocampal CA1 neurons in a young adult mouse

Satisfaction with Decision Regarding BRCA1/2 Genetic Testing and Willingness to Undergo BRCA1/2 Genetic Testing in the Future Among Breast Cancer Patients who Had not Previously Undergone BRCA1/2 Genetic Testing in Japan

Breast cancer patients must make their own decision of whether or not to undergo BRCA1/2 genetic testing. The present study investigated satisfaction surrounding this decision and the willingness to undergo BRCA1/2 genetic testing in the future among breast cancer patients who had not previously undergone BRCA1/2 testing despite a family history of breast cancer. Consent was obtained from 103 eligible patients selected from breast cancer patients who had presented with suspected hereditary breast and ovarian cancer and attended genetic counseling sessions at our institution. Consenting patients were then asked to complete a survey by questionnaire. Irrespective of their decision to undergo BRCA1/2 genetic testing, no patient reported being “not satisfied at all” or “not very satisfied”. Among the patients opting to not undergo BRCA1/2 genetic testing, 64％ responded that they would like to undergo BRCA1/2 genetic testing in the future. Compared with the patients who did not want to undergo testing, those who wanted to undergo were more likely to harbor impressions that BRCA1/2 genetic testing is “conducive to the selection of therapeutic modalities”, “helpful in deciding whether to undergo prophylactic surgery （oophorectomy, salpingectomy, and mastectomy）”, and “expensive”. Genetic counseling can improve satisfaction regarding the decision to undergo or not undergo BRCA1/2 genetic testing. However, there were some patients who opted not to undergo testing, but they were willing to undergo BRCA1/2 genetic testing in the future. Many of these patients might have found it cost-prohibitive to undergo testing immediately, despite realizing its benefits