Impact of rectal gas on the planning target volume margin for pelvic bone and prostate matching in prostate cancer patients receiving volumetric-modulated arc therapy.

We performed daily cone-beam computed tomography (CBCT) to determine the impact of rectal gas on the movements of prostate and seminal vesicles (SVs). We aimed to determine the relationship between planning target volume (PTV) margins and rectal gas. In 30 treatments of 15 prostate cancer patients, excessive rectal gas was removed and CBCT images were analyzed. Image registration between planning CT and daily CBCT images before and after rectal gas removal was performed for pelvic bone and prostate matching. The couch movement distance between each matching was considered the prostate movement. In addition, we measured SV tip movement between each matching. The anterior-posterior movement of the prostate before rectal gas removal (3.1 ± 2.9 mm) was significantly greater than that after rectal gas removal (1.2 ± 1.2 mm; p < 0.01). The left-right and superior-inferior movements were similar regardless of the presence or absence of rectal gas. The SV movement distances before and after rectal gas removal were 11.0 ± 5.8 mm and 4.6 ± 3.8 mm, respectively (p < 0.01), in pelvic bone matching, and 8.0 ± 4.2 mm and 3.8 ± 3.2 mm, respectively (p < 0.01), in prostate matching. After rectal gas removal, the SV position did not differ significantly between each matching. In 26 of the 30 treatments, SV movement distance in the presence of rectal gas was >6 mm, which is the minimum PTV margin at our institution. In comparison, after rectal gas removal and prostate matching, only 6 treatments demonstrated an SV movement distance of >6 mm. In the presence of rectal gas, the SVs require greater PTV margins than the prostate. Rectal gas removal should be considered if the movement distance on prostate matching is greater than the minimum PTV margin at treating institution.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical T stage based on 4D computed tomography.

PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3­year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

Escalated Maximum Dose in the Planning Target Volume Improves Local Control in Stereotactic Body Radiation Therapy for T1-2 Lung Cancer.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4-109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax < 125 Gy (BED10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax < 125 Gy (BED10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax < 125 Gy (BED10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume.

HER2 Gene Amplification in ER-positive HER2 Immunohistochemistry 0 or 1+ Breast Cancer With Early Recurrence.

BACKGROUND/AIM: In estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, standard chemotherapies as well as adjuvant endocrine therapy might not be enough for prevention of early relapse. MATERIALS AND METHODS: We focused on ER-positive, HER2 immunohistochemistry (IHC) 0 or 1+ breast cancer, and retrospectively examined HER2 gene amplification and TP53 mutation in breast cancer tissues in patients with or without early recurrence. Post-relapse survival in patients with early recurrence was also analyzed by mutation status of HER2 and TP53. RESULTS: Surprisingly, amplification of the HER2 gene was found in 15% of patients with early recurrence. None of the patients without relapse had HER2-amplified tumors. Post-relapse survival in patients with HER2 gene amplification and/or TP53 mutation in primary tumors was shorter than that in patients without these mutations, especially among postmenopausal women. CONCLUSION: HER2 gene amplification exists in ER-positive, HER2 IHC 0 or 1+ breast cancer in patients who developed early distant metastasis.

Associations in tumor infiltrating lymphocytes between clinicopathological factors and clinical outcomes in estrogen receptor-positive/human epidermal growth factor receptor type 2 negative breast cancer.

The value of assessing tumor infiltrating lymphocytes (TILs) in estrogen receptor (ER) positive/human epidermal growth factor receptor type 2 (HER2) negative breast cancer has yet to be determined. In the present study, a total of 184 cases with early distant recurrence detected within 5 years following the primary operation, 134 with late distant recurrence diagnosed following 5 years or longer and 321 controls without recurrence for >10 years following starting the initial treatment for ER-positive/HER2 negative breast cancer, registered in 9 institutions, were analyzed. The distributions of TILs and their clinical relevance were investigated. TIL distributions did not differ significantly among the early, late and no recurrence groups, employing a 30% cut-off point as a dichotomous variable. In those who had received adjuvant chemotherapy as well as endocrine therapy, a trend toward higher TIL proportions was detected when the early recurrence group was compared with the no recurrence group employing the 30% cut-off point (P=0.064). The TIL distributions were significantly associated with nodal metastasis (P=0.004), ER status (P=0.045), progesterone receptor (PgR) status (P=0.002), tumor grade (P=0.021), and the Ki67 labeling index (LI) (P=0.002) in the no recurrence group and with the Ki67 LI in the recurrence groups (P=0.002 in early recurrence group, P=0.023 in late recurrence group). High TIL distributions also predicted shorter survival time following the detection of recurrence (P=0.026). However, these prognostic interactions were not significant in multivariate analysis (P=0.200). The present retrospective study demonstrated no significant interaction between TIL proportions and the timing of recurrence. However, higher TIL proportions were observed in breast cancer patients with aggressive biological phenotypes, which tended to be more responsive to chemotherapy. The clinical relevance of stromal TILs for identifying patients who would likely benefit from additional therapies merits further investigation in a larger patient population.

PIK3CA mutation, reduced AKT serine 473 phosphorylation, and increased ERα serine 167 phosphorylation are positive prognostic indicators in postmenopausal estrogen receptor-positive early breast cancer.

Although endocrine therapy is the most important treatment option in estrogen receptor (ER)-positive breast cancer, new strategies, such as molecular targeted agents together with endocrine therapy are required to improve survival. PIK3CA is the most frequent mutated gene in ER-positive early breast cancers, and PIK3CA mutation status is reported to affect activation of AKT and ERα. Moreover, recent studies demonstrate that patients had a better prognosis when tumors expressed ER, androgen receptor (AR), and vitamin D receptor (VDR). In this study, we examined expression of AR and VDR, phosphorylation of AKT serine (Ser) 473 (AKT phospho-Ser473) and ERα Ser167 (ERα phospho-Ser167) by immunohistochemistry in ER-positive, HER2-negative early breast cancer. PIK3CA gene mutations were also detected in genomic DNA extracted from tumor blocks. Correlations between these biological markers, clinicopathological factors and prognosis were analyzed. Levels of AKT phospho-Ser473 were significantly higher in premenopausal women than in postmenopausal women. In contrast, AR expression was significantly higher in postmenopausal women than in premenopausal women. PIK3CA mutations were detected in 47% in premenopausal women and 47% in postmenopausal women. Postmenopausal women with PIK3CA wild-type tumors had significantly worse disease-free survival than patients with PIK3CA mutant tumors. Low levels of AKT phospho-Ser473 and high levels of ERα phospho-Ser167 were strongly associated with increased disease-free survival in postmenopausal women. Evaluation of ERα activation, in addition to PIK3CA mutation status, might be helpful in identifying patients who are likely to benefit from endocrine therapy alone versus those who are not in postmenopausal ER-positive early breast cancer.

Tamoxifen withdrawal in women with progressive metastatic breast cancer: a case series of six patients.

Estrogen receptor (ER)-positive metastatic breast cancers after a period of response to tamoxifen develop resistance, and the disease progresses clinically. Domination of partial agonistic activity of tamoxifen over its antagonist activity has been implicated as one of the mechanisms for acquired tamoxifen resistance. Six patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer who were treated with tamoxifen withdrawal were retrospectively reviewed. Three patients were premenopausal and three were postmenopausal at the beginning of this treatment. Three patients had stage IV disease and three had recurrent breast cancers with median disease-free intervals of 153 months. The treatment lines of tamoxifen therapy were first-line in two, second-line in two, and third-line in one patient. One patient had relapsed during adjuvant tamoxifen therapy. The median duration of tamoxifen therapy was 16 months. The metastatic disease sites at the time of tamoxifen withdrawal were lymph nodes in six, bone in three, chest wall in one, lung in two, pleura in one, and liver in one patient. The median duration of tamoxifen withdrawal was 6.5 months (range 5-> 23 months). Five of six patients had clinical benefits with tamoxifen withdrawal: partial response in one, long stable disease (SD) in four, and SD in one patient. Five patients were treated with aromatase inhibitors after tamoxifen withdrawal. Two patients had metastatic lymph nodes examined by multi-gene panel testing, and both of their tumors had the AKT1 E17K somatic mutation. One patient also had a BRCA1 germline mutation. Tamoxifen withdrawal at the time of tumor progression while on treatment might be an important treatment option, especially for women with highly endocrine-responsive disease.

Genetic and environmental factors and serum hormones, and risk of estrogen receptor-positive breast cancer in pre- and postmenopausal Japanese women.

Breast cancer incidence in Japanese women has more than tripled over the past two decades. We have previously shown that this marked increase is mostly due to an increase in the estrogen receptor (ER)-positive, HER2-negative subtype. We conducted a case-control study; ER-positive, HER2-negative breast cancer patients who were diagnosed since 2011 and women without disease were recruited. Environmental factors, serum levels of testosterone and 25-hydroxyvitamin D, and common genetic variants reported as predictors of ER-positive breast cancer or found in Asian women were evaluated between patients and controls in pre- and postmenopausal women. To identify important risk predictors, risk prediction models were created by logistic regression models. In premenopausal women, two environmental factors (history of breastfeeding, and history of benign breast disease) and four genetic variants (TOX3-rs3803662, ESR1-rs2046210, 8q24-rs13281615, and SLC4A7-rs4973768) were considered to be risk predictors, whereas three environmental factors (body mass index, history of breastfeeding, and hyperlipidemia), serum levels of testosterone and 25-hydroxyvitamin D, and two genetic variants (TOX3-rs3803662 and ESR1-rs2046210) were identified as risk predictors. Inclusion of common genetic variants and serum hormone measurements as well as environmental factors improved risk assessment models. The decline in the birthrate according to recent changes of lifestyle might be the main cause of the recent notable increase in the incidence of ER-positive breast cancer in Japanese women.

Post-relapse survival in patients with the early and late distant recurrence in estrogen receptor-positive HER2-negative breast cancer.

BACKGROUND: Few studies have been performed on post-relapse survival in patients with the early and late distant recurrence in estrogen receptor (ER)-positive, HER2-negative breast cancer. METHODS: A total of 205 patients with the early distant recurrence and 134 patients with the late distant recurrence of ER-positive, HER2-negative breast cancer who had undergone breast surgery or neoadjuvant chemotherapy between January 2000 and December 2004 were registered from nine institutions. Prognostic factors for post-relapse survival in patients with the early and late recurrence were analyzed. RESULTS: Post-relapse survival was significantly longer in patients with the late recurrence than in patients with the early recurrence. Predictive factors for post-relapse survival in patients with the early recurrence were lack of adjuvant chemotherapy, a long disease-free interval, and long durations of endocrine therapies and chemotherapies after relapse. In patients with the late recurrence, post-relapse survival was significantly improved for those individuals with one metastatic organ at relapse and individuals who were treated with the first-line and subsequent endocrine therapies for prolonged periods. Moreover, ER expression in primary breast tumors of late recurrence patients was significantly higher with a duration of the first-line endocrine therapy >6 months than in those with a duration ≤6 months. CONCLUSION: Predictors for prognosis after relapse differed between patients with the early and late distant recurrence. Endocrine responsiveness after relapse is a key factor for improved post-relapse survival, and it is thus important to establish whether metastatic tumors are endocrine-resistant in ER-positive, HER2-negative recurrent breast cancer.

Differences in expression of the cancer stem cell marker aldehyde dehydrogenase 1 among estrogen receptor-positive/human epidermal growth factor receptor type 2-negative breast cancer cases with early, late, and no recurrence.

BACKGROUND: The significance of the expression of aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, for predicting the recurrence of estrogen receptor (ER)-positive/human epidermal growth factor receptor type 2 (HER2)-negative breast cancer is still poorly understood. The value of ALDH1 in predicting the time of recurrence remains unknown. METHODS: In total, 184 patients with early distant recurrence, 134 patients with late distant recurrence, and 321 control patients without recurrence for more than 10 years after starting initial treatment for ER-positive/HER2-negative breast cancer, registered in 9 institutions, were analyzed. We assessed relationships between ALDH1 and other clinicopathological features, and ALDH1 expression was compared among the three groups. The relationship between ALDH1 expression and overall survival after recurrence was also evaluated in each group. RESULTS: The rates of ALDH1 expression positivity (more than 1 %) in the early, late, and no recurrence groups were 18.4 %, 13.4 %, and 8.4 %, respectively. ALDH1 expression correlated significantly with lymph node metastases (p = 0.048) and the Ki-67 labeling index (p < 0.001) in the early recurrence group. Multivariate analysis revealed ALDH1 expression to be significantly higher in the early recurrence group than in the no recurrence group (adjusted OR 2.140, 95 % CI 1.144-4.003, p = 0.016). Moreover, there was a significant difference in ALDH1 expression between the early and no recurrence groups receiving adjuvant endocrine therapy and chemotherapy (adjusted OR 4.625, 95 % CI 1.881-12.474, p < 0.001). However, there was no difference in ALDH1 expression between the late and no recurrence groups in univariate analysis (OR 1.507, 95 % CI 0.738-2.998, p = 0.253). In multivariate analysis, ALDH1 was not a factor independently predicting overall survival after the detection of recurrence (adjusted OR 1.451, 95 % CI 0.985-2.085, p = 0.059). CONCLUSIONS: Among patients with ER-positive/HER2-negative breast cancer, ALDH1 expression was more common in those with early recurrence, and this expression was found to be associated with a more aggressive breast cancer phenotype than that in the patients without recurrence. Further study is needed to clarify the prognostic significance of the heterogeneity of cancer stem cells and to confirm their role in resistance to chemotherapy.

Clinicopathological factors predicting early and late distant recurrence in estrogen receptor-positive, HER2-negative breast cancer.

BACKGROUND: Most studies analyzing prognostic factors for late relapse have been performed in postmenopausal women who received tamoxifen or aromatase inhibitors as adjuvant endocrine therapy for estrogen receptor (ER)-positive breast cancer. METHODS: A total of 223 patients (108 premenopausal and 115 postmenopausal) with early distant recurrence and 149 patients (62 premenopausal and 87 postmenopausal) with late distant recurrence of ER-positive, HER2-negative breast cancer who were given their initial treatment between 2000 and 2004 were registered from nine institutions. For each late recurrence patient, approximately two matched control patients without relapse for more than 10 years were selected. Clinicopathological factors and adjuvant therapies were compared among the three groups by menopausal status and age. RESULTS: Factors predicting early recurrence in premenopausal women were large tumor size, high lymph node category and high tumor grade, whereas predictors for late recurrence were large tumor size and high lymph node category. In postmenopausal women under 60 years of age, factors predicting early recurrence were bilateral breast cancer, large tumor size, high lymph node category, low PgR expression and high Ki67 labeling index (LI), while predictors for late recurrence were large tumor size and high lymph node category. On the other hand, in postmenopausal women aged 60 years or older, factors predicting early recurrence were bilateral breast cancer, large tumor size, high lymph node category, high tumor grade, low ER expression and high Ki67 LI, whereas predictors for late recurrence were high lymph node category, low ER expression and short duration of adjuvant endocrine therapy. CONCLUSION: Predictors of early and late distant recurrence might differ according to menopausal status and age.

Fulvestrant 500 mg in postmenopausal patients with metastatic breast cancer: the initial clinical experience.

BACKGROUND: Fulvestrant 500 mg is currently approved for the treatment of postmenopausal women with hormone receptor-positive metastatic breast cancer after failure of prior endocrine therapies. METHODS: A total of 117 postmenopausal women with metastatic breast cancer, who experienced progression after previous endocrine therapies, were treated with fulvestrant 500 mg between January 2012 and June 2014. Clinical response, time to progression (TTP) and adverse events were investigated. RESULTS: Ninety-nine patients had recurrent breast cancer and 18 patients had stage IV disease. Patients had received a median of two endocrine therapies and a median of two chemotherapies, prior to fulvestrant. There were 10 patients with partial response, 39 patients with long stable disease, 18 patients with stable disease, and 50 patients with progressive disease, so that the objective response rate was 8.5 %, with a clinical benefit rate of 41.9 %. The median TTP was 6.1 months. The absence of liver metastases, a small number of previous chemotherapies, and the longer duration of first-line endocrine therapy were positively correlated with TTP in univariate analysis. In multivariate analysis, a significant association was observed between TTP and duration of first-line endocrine therapy. Serious adverse events were observed in one patient with pulmonary embolism and in one patient with psychiatric symptoms. CONCLUSIONS: Fulvestrant 500 mg is an effective and well-tolerated treatment for postmenopausal women with metastatic breast cancer that had progressed after prior endocrine therapies. Patients with acquired resistance to endocrine therapies might be good candidates for fulvestrant therapy regardless of the number of prior endocrine treatments.

Efficacy of fulvestrant 500 mg in Japanese postmenopausal advanced/recurrent breast cancer patients and factors associated with prolonged time-to-treatment failure.

OBJECTIVE: We aimed to confirm the efficacy of fulvestrant in Japanese postmenopausal advanced/recurrent breast cancer (ABC) patients, and investigate factors contributing to time-to-treatment failure (TTF) prolongation. RESEARCH DESIGN AND METHODS: This retrospective study included 194 ABC patients who received fulvestrant (500 mg) from January 2012 to December 2014. MAIN OUTCOME MEASURES: TTF (efficacy measure), overall survival (OS), factors prolonging TTF and adverse events were evaluated. RESULTS: The median age was 65 (42 - 90) years. Overall, TTF was 5.48 months. In patients without prior chemotherapy (n = 59), OS was significantly longer (p = 0.0131) than in patients with prior chemotherapy (n = 135). There was no strong correlation between TTF with fulvestrant and other endocrine therapies, total duration of endocrine therapy and maximum duration of endocrine therapy. TTF was significantly longer in patients with less than two prior chemotherapy regimens (p = 0.0093), de novo metastatic disease (p = 0.0124) and without liver metastasis (p = 0.0024). We observed one case each of pulmonary infarction and psychiatric disorder. CONCLUSIONS: Fulvestrant is effective for ABC patients and may show greater efficacy in patients with few prior chemotherapy regimens, de novo metastatic disease and absence of liver metastasis. Prior endocrine therapy duration might not be a predictive factor for fulvestrant TTF in heavily treated ABC patients.

Porphyromonas bronchialis sp. nov. Isolated from Intraoperative Bronchial Fluids of a Patient with Non-Small Cell Lung Cancer.

Porphyromonas strains, including Porphyromonas-like strains, have been isolated from oral and various other systemic infections. The characterization of such strains is a crucial issue, because such information contributes to both the taxonomy of anaerobic bacteria and the clinical aspects of infectious diseases. We previously isolated four Porphyromonas-like strains from intraoperative bronchial fluids of a patient with non-small cell lung cancer. This study aimed to characterize the genetic, biochemical and chemotaxonomic aspects of these isolates. Each strain only grew under anaerobic conditions and their colony morphology was convex, 0.1-1.0 mm in diameter, light gray, and slightly glistening colony, with no black or brown pigmentation on blood agar plates after five-day incubation. The pigmentation was helpful to differentiate the isolates from other Porphyromonas, as most of Porphyromonas species show the pigmentation. In the 16S rRNA gene phylogenetic analysis (98% sequence identity of isolates indicates the same species), the four isolates were closely related to one another (99.7-100.0%), but not related to Porphyromonas (P.) catoniae, the closest species (96.9%). In addition, the DNA-DNA hybridization data revealed less than 16% similarity values between a representative isolate and the P. catoniae, indicating that the strains were genetically independent. Biochemically, the isolates could be differentiated from closely related species, i.e., P. catoniae, P. gingivalis, P. gulae, and P. pogonae, with trypsin activity (negative only in the isolates) and leucine arylamidase activity (positive only in the isolates). We therefore propose a new species to include these isolates: Porphyromonas bronchialis sp. nov.

Detection and identification of oral anaerobes in intraoperative bronchial fluids of patients with pulmonary carcinoma.

Postoperative pneumonia may occur when upper respiratory tract protective reflexes such as cough and/or swallowing reflexes are impaired; thus, silent aspiration of oral bacteria may be a causative factor in postoperative pneumonia. This study aimed to quantify and identify bacteria in intraoperative bronchial fluids and to evaluate the relationship between impairment of cough/swallowing reflexes and silent aspiration of oral bacteria in elderly patients. After obtaining informed consent, cough and swallowing reflexes were assessed using an ultrasonic nebulizer and a nasal catheter, respectively. Using a micro-sampling probe, intraoperative bronchial fluids were collected from nine subjects with pulmonary carcinoma and cultured anaerobically on blood agar plates. After 7 days, CFUs were counted and isolated bacteria were identified by 16S rRNA gene sequencing. Four subjects (aged 71.0 ± 8.4 years) had impaired swallowing reflexes with normal cough reflexes, whereas five subjects (73.6 ± 6.5 years) had normal cough and swallowing reflexes. The bacterial counts (mean CFU ± SD) tended to be higher in intraoperative bronchial fluids of subjects with impaired swallowing reflexes ([5.1 ± 7.7] × 10(5)) than in those of subjects with normal reflexes ([1.2 ± 1.9] × 10(5)); however, this difference was not statistically significant. Predominant isolates from intraoperative bronchial fluids were Streptococcus (41.8%), Veillonella (11.4%), Gemella (8.9%), Porphyromonas (7.6%), Olsenella (6.3%) and Eikenella (6.3%). These findings indicate that intraoperative bronchial fluids contain bacteria, probably derived from the oral microbiota, and suggest that silent aspiration of oral bacteria occurs in elderly patients irrespective of impairment of swallowing reflex.

Tongue pressure during swallowing in adults with down syndrome and its relationship with palatal morphology.

In individuals with Down syndrome, hypotonicity of the tongue and an underdeveloped maxilla may lead to poor oral motor coordination, which adversely affects the oral phase of swallowing. This study aimed to evaluate the characteristics of pressure produced by the tongue against the hard palate during swallowing in individuals with Down syndrome. In addition, the relationship between tongue pressure and palatal morphology was examined. We studied nine adults with Down syndrome and ten healthy adults as controls. Tongue pressure while swallowing 5 mL water was recorded by a sensor sheet system with five measuring points attached to the hard palate. Palatal length, depth, width, curvature, and slope were measured by three-dimensional digital maxillary imaging. The order of onset of tongue pressure on the median line of the hard palate was the same in all participants, except for three with Down syndrome. The duration and maximal magnitude of tongue pressure on the median line in nine participants with Down syndrome were significantly shorter and lower than those of controls. In participants with Down syndrome, significant positive correlations were observed between the duration of tongue pressure at the mid-median part of the hard palate and palatal depth and width, and between the duration and maximal magnitude of tongue pressure at the posterior-median part and palatal length. These findings suggest that impaired tongue activity, poor tongue control, and constrained tongue motion due to a short and narrow palate contribute to swallowing difficulty in individuals with Down syndrome.

Rapid quantification of bacteria in infected root canals using fluorescence reagents and a membrane filter: a pilot study on its clinical application to the evaluation of the outcomes of endodontic treatment.

Objective. The bacterial examination has been performed during the course of the root canal treatment. In the present pilot study, the new developed method, using fluorescence reagents and a membrane filter, was applied to the detection and quantification of bacteria in infected root canals, in order to evaluate the outcomes of the treatment. Methods. Six infected root canals with periapical lesions from 5 subjects were included. Informed consent was obtained from all subjects (age ranges, 23-79 years). Samples from infected root canals were collected at the beginning of the treatment (termed #25 First), the end of the first day of treatment (termed #55 First), and the next appointment day (termed #55 Second). Then, the bacterial count (CFU) was measured using fluorescence reagents (4',6'-diamidino-2-phenylindole and propidium iodide) and the polycarbonate membrane filter by Bioplorer. Results. The mean ± SD of CFU in the sample of "#25 First" was (1.0 ± 1.4) × 10(5). As the root canal treatment progressed, the CFU decreased as 7.9 × 10(3) (#55 First) and 4.3 × 10(2) (#55 Second). Conclusion. In the present pilot study, rapid detection and quantification of bacteria in infected root canals were found to be successfully performed using fluorescence reagents and a membrane filter (Bioplorer analysis).

Influence of the PsbA1/PsbA3, Ca(2+)/Sr(2+) and Cl(-)/Br(-) exchanges on the redox potential of the primary quinone Q(A) in Photosystem II from Thermosynechococcus elongatus as revealed by spectroelectrochemistry.

Ca(2+) and Cl(-) ions are essential elements for the oxygen evolution activity of photosystem II (PSII). It has been demonstrated that these ions can be exchanged with Sr(2+) and Br(-), respectively, and that these ion exchanges modify the kinetics of some electron transfer reactions at the Mn4Ca cluster level (Ishida et al., J. Biol. Chem. 283 (2008) 13330-13340). It has been proposed from thermoluminescence experiments that the kinetic effects arise, at least in part, from a decrease in the free energy level of the Mn(4)Ca cluster in the S3 state though some changes on the acceptor side were also observed. Therefore, in the present work, by using thin-layer cell spectroelectrochemistry, the effects of the Ca(2+)/Sr(2+) and Cl(-)/Br(-) exchanges on the redox potential of the primary quinone electron acceptor Q(A), E(m)(Q(A)/Q(A)(-)), were investigated. Since the previous studies on the Ca(2+)/Sr(2+) and Cl(-)/Br(-) exchanges were performed in PsbA3-containing PSII purified from the thermophilic cyanobacterium Thermosynechococcus elongatus, we first investigated the influences of the PsbA1/PsbA3 exchange on E(m)(Q(A)/Q(A)(-)). Here we show that i) the E(m)(Q(A)/Q(A)(-)) was up-shifted by ca. +38mV in PsbA3-PSII when compared to PsbA1-PSII and ii) the Ca(2+)/Sr(2+) exchange up-shifted the E(m)(Q(A)/Q(A)(-)) by ca. +27mV, whereas the Cl(-)/Br(-) exchange hardly influenced E(m)(Q(A)/Q(A)(-)). On the basis of the results of E(m)(Q(A)/Q(A)(-)) together with previous thermoluminescence measurements, the ion-exchange effects on the energetics in PSII are discussed.