Merkel cell carcinoma in Taiwan: A rare tumour with a better prognosis in those harbouring Merkel cell polyomavirus.

Merkel cell carcinoma (MCC) is a rare malignant cutaneous neuroendocrine tumour affecting mainly elderly patients and is more common in the West than in Asia. It is associated with Merkel cell polyomavirus (MCPyV), immunosuppression, and ultraviolet light. In this study, we retrospectively investigated the first series of MCC from Taiwan and identified 19 cases from three tertiary centres. All patients were males with a median age of 67.5. Twelve (63%) cases occurred in the extremities, with one unique case presenting initially as nodal metastasis of unknown primary. Immunohistochemically, the great majority of tumours expressed CK20 (89%), synaptophysin (89%), and INSM1 (84%), with none positive for TTF1. Eleven (58%) cases were positive for MCPyV by immunohistochemistry (clone CM2B4). All patients were treated with excision, including four with additional radiotherapy and one with radiotherapy and chemotherapy. Nodal status and treatment modalities significantly affected survival. The median survival time of MCPyV-positive cases was much longer than the negative cases (median 40 vs. 10 months). In summary, we presented the first report on the clinicopathological features of MCC in Taiwan, with 58% cases associated with MCPyV. The prognosis of patients with MCPyV-positive tumours was better than those negative for MCPyV.

Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation.

OBJECTIVE: Low molecular weight compounds that reduce the expression of MMP13 at the mRNA level might serve as disease-modifying osteoarthritis (OA) drugs (DMOADs). The objective of this study was to identify a candidate DMOAD that targets MMP13 expression. DESIGN: High-throughput screening was performed to identify compounds that suppress inflammatory cytokine-induced MMP13 expression. Ingenuity pathway analysis (IPA) using isobaric tags for relative and absolute quantification (iTRAQ)-based proteomic analysis was conducted to identify signaling pathways related to cytokines. MMP13 expression in chondrocytes was evaluated through RT-qPCR and western blotting analyses. Additionally, 10-week-old mice were subjected to destabilization of the medial meniscus (DMM) surgery to induce OA and were sacrificed 12 weeks post-surgery for pathological examination. OA was evaluated using the OARSI scoring system. RESULTS: Colchicine was identified as a DMOAD candidate as it inhibited inflammatory cytokine-induced MMP13 expression in vitro, and the colchicine-administered mice with DMM presented significantly lower OARSI scores (adjusted P: 0.0242, mean difference: 1.6, 95% confidence interval (CI) of difference: 0.1651-3.035) and significantly lower synovial membrane inflammation scores (adjusted P: 0.0243, mean difference: 0.6, 95% CI of difference: 0.06158-1.138) than mice with DMM. IPA further revealed that components of the Rho signaling pathways are regulated by cytokines and colchicine. IL-1ß and TNF-α activate RAC1 and SRC signals, respectively, leading to the phosphorylation of PLC-γ1 and synergistic induction of MMP13 expression. Most notably, colchicine abrogates inflammatory cytokine-induced phosphorylation of PLC-γ1, leading to the induction of MMP13 expression. CONCLUSIONS: Colchicine is a potential DMOAD candidate that inhibits MMP13 expression and consequent cartilage degradation by disrupting the SRC/RAC1-phospho-PLCγ1-Ca2+ signaling pathway.

Posterior teeth occlusion and dysphagia risk in older nursing home residents: a cross-sectional observational study.

The total number of natural teeth was related to swallowing function among older adults; however, limited information is available regarding the impact of occluding pairs of teeth on swallowing function. This study aimed to examine the association between posterior teeth occlusion and dysphagia risk in older nursing home residents. This cross-sectional study included 238 residents aged ≥60 years from eight nursing homes in Aso City, Japan. Swallowing function was evaluated using the modified water swallowing test (MWST); the primary outcome was dysphagia risk (MWST score ≤3). Posterior teeth occlusion was assessed using number of functional tooth units (FTUs), determined based on number and location of the remaining natural and artificial teeth on implant-supported, fixed or removable prostheses. Univariate and multivariate logistic regression analyses were performed to examine the association between posterior teeth occlusion and dysphagia risk, adjusted for the covariates of number of natural teeth, demographic characteristics, comorbidities, physical function, body mass index and cognitive function. Of the 238 subjects, 44 (18·5%) were determined to be at risk of dysphagia based on the MWST scores. The odds ratio (OR) of dysphagia risk decreased in subjects with higher total FTUs [OR = 0·92, 95% confidence interval (CI) 0·87-0·98]. After adjusting for covariates, this association remained significant (OR = 0·90, 95% CI 0·84-0·97). Loss of posterior teeth occlusion was independently associated with dysphagia risk in older nursing home residents. Maintaining and restoring posterior teeth occlusion may be an effective measure to prevent dysphagia.

Swallowing disorders and 1-year functional decline in community-dwelling older adults receiving home care.

The purpose of this study was to clarify the effect of swallowing disorders on functional decline in community-dwelling older adults receiving home care. This was a 1-year follow-up survey of 176 individuals ≥60 years living at home and receiving homecare services, without total dependence in basic daily living activities, in two mid-sized municipalities in Fukuoka, Japan. Functional decline was measured using the Barthel index (BI), and the primary outcome was total dependence in basic daily living activities (BI ≤ 20 points). Swallowing function was assessed using cervical auscultation, and the primary predictor was swallowing disorders. Logistic regression models were used to assess univariate and multivariate associations between baseline swallowing function and functional decline during follow-up. During follow-up 16 (9.1%), the participants became totally dependent in basic daily living activities. The participants with swallowing disorders had 6.41 times higher odds of total dependence in basic daily living activities compared to participants with normal swallowing function. After adjusting for potential confounders, swallowing disorders were significantly associated with higher odds of total dependence in basic daily living activities (odds ratio = 5.21, 95% confidence interval = 1.33-20.44). Regarding swallowing disorders, the corresponding population attributable fraction (%) of the incidence of total dependence in basic daily living activities was 50.4%. The current findings demonstrated that swallowing disorders were associated with greater risk of functional decline in basic daily living activities among older adults living at home and receiving home nursing care. Maintenance and improvement of swallowing function may prevent late-life functional decline.

Prospective and clinical validation of ALK immunohistochemistry: results from the phase I/II study of alectinib for ALK-positive lung cancer (AF-001JP study).

BACKGROUND: Anaplastic lymphoma kinase (ALK) fusions need to be accurately and efficiently detected for ALK inhibitor therapy. Fluorescence in situ hybridization (FISH) remains the reference test. Although increasing data are supporting that ALK immunohistochemistry (IHC) is highly concordant with FISH, IHC screening needed to be clinically and prospectively validated. PATIENTS AND METHODS: In the AF-001JP trial for alectinib, 436 patients were screened for ALK fusions through IHC (n = 384) confirmed with FISH (n = 181), multiplex RT-PCR (n = 68), or both (n = 16). IHC results were scored with iScore. RESULT: ALK fusion was positive in 137 patients and negative in 250 patients. Since the presence of cancer cells in the samples for RT-PCR was not confirmed, ALK fusion negativity could not be ascertained in 49 patients. IHC interpreted with iScore showed a 99.4% (173/174) concordance with FISH. All 41 patients who had iScore 3 and were enrolled in phase II showed at least 30% tumor reduction with 92.7% overall response rate. Two IHC-positive patients with an atypical FISH pattern responded to ALK inhibitor therapy. The reduction rate was not correlated with IHC staining intensity. CONCLUSIONS: Our study showed (i) that when sufficiently sensitive and appropriately interpreted, IHC can be a stand-alone diagnostic for ALK inhibitor therapies; (ii) that when atypical FISH patterns are accompanied by IHC positivity, the patients should be considered as candidates for ALK inhibitor therapies, and (iii) that the expression level of ALK fusion is not related to the level of response to ALK inhibitors and is thus not required for patient selection. REGISTRATION NUMBER: JapicCTI-101264 (This study is registered with the Japan Pharmaceutical Information Center).

Estimating the Dimension of an Inertial Manifold from Unstable Periodic Orbits.

We provide numerical evidence that a finite-dimensional inertial manifold on which the dynamics of a chaotic dissipative dynamical system lives can be constructed solely from the knowledge of a set of unstable periodic orbits. In particular, we determine the dimension of the inertial manifold for the Kuramoto-Sivashinsky system and find it to be equal to the "physical dimension" computed previously via the hyperbolicity properties of covariant Lyapunov vectors.

Effects of oral care with tongue cleaning on coughing ability in geriatric care facilities: a randomised controlled trial.

Methods for preventing aspiration pneumonia are needed soon in order to reduce mortality from aspiration pneumonia and promote the health of the elderly. The aim of this randomised controlled trial was to examine whether oral care with tongue cleaning improves coughing ability in elderly individuals living in geriatric care facilities. Participants comprised of 114 residents of 11 group homes and private nursing homes in Aso City in Kumamoto Prefecture. Participants were randomly assigned to either (i) a group that underwent routine oral care with tongue cleaning (intervention group; n = 58) or (ii) a group that underwent routine oral care alone (control group; n = 56). Coughing ability was evaluated by measuring peak expiratory flow (PEF) before and after 4 weeks of intervention. Before the intervention, PEF did not differ significantly between the intervention group (1·65 ± 1·11 L s-1 ) and control group (1·59 ± 1·05 L s-1 ; P = 0·658). However, on termination of the intervention, PEF was significantly higher in the intervention group (2·54 ± 1·42 L s-1 ) than in the control group (1·90 ± 1·20 L s-1 ; P = 0·014). After the intervention, PEF had increased significantly in both groups; however, this increase was significantly greater in the intervention group (0·90 ± 0·95 L s-1 ) than in the control group (0·31 ± 0·99 L s-1 ; P < 0·001). Oral care with tongue cleaning led to increased PEF, suggesting improved coughing ability. Oral care incorporating tongue cleaning appears to be important for preventing aspiration pneumonia.

A mild hand cleanser, alkyl ether sulphate supplemented with alkyl ether carboxylic acid and alkyl glucoside, improves eczema on the hand and prevents the growth of Staphylococcus aureus on the skin surface.

OBJECTIVE: Washing the hands using cleansers with antiseptic materials is the most popular method for hand hygiene and helps maintain health by preventing food poisoning and bacterial infections. However, repeated hand washing tends to induce eczema of the hand, such as dryness, cracking and erythema. Moreover, eczema on the hand leads to increased levels in Staphylococcus aureus (S. aureus) on the skin surface in contrast to expectations. Thus, mild hand cleansers which induce less eczema even with repeated washings are desired. Here, we evaluated the efficacy of a hand cleanser formulated with alkyl ether sulphate (AES), alkyl ether carboxylic acid (AEC) and alkyl glucoside (AG) that contains isopropyl methylphenol (IPMP) on skin symptoms and S. aureus levels. METHODS: Eczema of the hand and the presence of S. aureus on the skin surface were analysed prior to and following 4 weeks of usage of the hand cleanser. A soap-based hand cleanser with IPMP was used as a reference cleanser. Eczema and cutaneous conditions were evaluated by visual grading, transepidermal water loss (TEWL), stratum corneum moisture-retention ability (MRA) and skin surface pH. RESULTS: The repeated use of the soap-based hand cleanser significantly worsened the hand dryness, scaling and cracks on the tips of the fingers and significantly increased the TEWL and decreased the MRA. In contrast, usage of the test cleanser only induced a significant increase in skin dryness but did not induce skin scaling or cracking and did not increase TEWL or decrease the MRA. Corresponding to these changes in skin symptoms, the presence of S. aureus increased the following use of the reference cleanser but not the test cleanser. There was no significant difference in skin surface pH between the two cleansers. Moreover, the increase in S. aureus was significantly correlated to the worsening of skin dryness and scaling. CONCLUSION: These results suggest that not only antimicrobial activity but also the mildness, which minimizes cutaneous effects, are important for hand cleansers to prevent the growth of S. aureus. The cleanser formulated with AES, AEC and AG containing IPMP is mild and is effective to promote hand hygiene.

Effect of heat stress soon after muscle injury on the expression of MyoD and myogenin during regeneration process.

Heat stress could promote skeletal muscle regeneration. But, in the regeneration process, effects of heat stress on myogenic cells and the regulating factors is unknown. Therefore, Influences of heat stress soon after injury on distribution of the myogenic cells and chronological changes in expression of MyoD and myogenin were examined. The first peak of MyoD expression was temporally correlated with the time when proliferating satellite cells began to appear, and the rapid decline of the MyoD expression from the first peak, with the appearance time of myoblasts, respectively in both the non-Heat and Heat groups. The first peak of myogenin expression was temporally correlated with the time when multinuclear cells began to form in the both groups. Due to the heat stress, proliferation and differentiation of myogenic cells and chronological changes in these factors were accelerated one day earlier than in the non-Heat group. As MyoD and myogenin are regulating factor of proliferation and differentiation, heat stress soon after the muscle injury could accelerate the proliferation and differentiation of myogenic cells and the expression of their regulating factors MyoD and myogenin.

Non-physician communities in Japan: are they still disadvantaged?

INTRODUCTION: Non-physician community' (NPC) is a policy term that indicates a medically underserved area in Japan. Designated NPCs are politically targeted as the foci of medical resource allocation. NPC is defined as a specified district where 50 or more persons dwell within a geographic diameter of 4 km and medical care is not easily accessible. The definition of NPC was first introduced in 1960 and has been unchanged for more than half a century despite radical social changes in rural Japan. This study examines whether designated NPCs are still more disadvantaged in terms of geographical access to healthcare in comparison to other communities. METHODS: Hiroshima prefecture, which has the largest number of NPCs in terms of tertiary healthcare areas of Japan, was used as the study area. Targeted communities were all the NPCs in the prefecture, and, as controls, two community groups were selected: non-NPC adjacent to NPC, and municipal center. We measured driving time from NPCs and control communities to the nearest healthcare facilities, which were classified into the following two types: primary or secondary care facilities (n=2636) and tertiary care facilities (equal to tertiary emergency care centers; n=6). We further calculated the driving time to the nearest facilities for secondary emergency care (n=246) extracted from the 2636 primary or secondary care facilities. RESULTS: The median driving times to the nearest primary or secondary healthcare facility for NPC, non-NPC, and municipal center were 11 minutes, 11 minutes, and 1 minute, respectively; the times to a tertiary healthcare facility (equal to an accident and emergency care center) were 80 minutes, 84 minutes, and 68 minutes, respectively; and the times to a secondary emergency care facility were 24 minutes, 18 minutes, and 15 minutes, respectively. Although a municipal center was significantly more advantageous in driving time compared to a primary or secondary care facility, the disadvantage of a NPC in access was no more obvious than an adjacent non-NPC for any type of healthcare facility. CONCLUSIONS: NPCs had a disadvantage in access time to primary, secondary and tertiary medical care compared with a municipal center. NPCs, however, did not have a greater access disadvantage in comparison to adjacent rural communities for any type of medical facility. As such, future resource allocation policies in Japan need to redefine medically underserved communities.

Regional Inequalities in Oral Frailty and Social Capital.

INTRODUCTION: Oral frailty leads to poor nutritional status, which, in turn, leads to frailty. This cross-sectional study aimed to determine regional differences in the prevalence of oral frailty and to identify factors associated with oral frailty using 3-level multilevel models. METHODS: This study comprised 165,164 participants aged ≥65 y without long-term care requirements in the Japan Gerontological Evaluation Study. The dependent variable was oral frailty, which was calculated based on age, number of teeth, difficulty in eating tough foods, and choking. The individual-level independent variables included sociodemographics, present illness, social participation, frequency of meeting friends, and social capital. The local district-level independent variable was social capital (n = 1,008) derived from exploratory factor analyses. The municipality-level independent variable was population density (n = 62). Three-level multilevel Poisson regression analysis was performed to calculate the prevalence ratios (PRs). RESULTS: The prevalence of oral frailty in municipalities ranged from 39.9% to 77.6%. Regarding district-level factors, higher civic participation was significantly associated with a lower probability of oral frailty. At the municipality level, the PR of the rural-agricultural area was 1.17 (95% confidence interval, 1.11-1.23) (reference: metropolitan). CONCLUSION: These results highlight the usefulness of oral frailty prevention measures in encouraging social participation in rural areas. KNOWLEDGE TRANSFER STATEMENT: The results of the present study showed regional differences in oral frailty. In particular, rural-agricultural areas show higher prevalence rates of oral frailty than those in metropolitan cities. Promoting measures of social participation among older adults may help prevent oral frailty in rural areas.

Functional variants in the thromboxane A2 receptor gene are associated with lung function in childhood-onset asthma.

BACKGROUND: The thromboxane A2 receptor (TBXA2R) gene is associated with asthma, but no functional genetic variations are known to associate with the disease or its related phenotypes. OBJECTIVE: To investigate the association of TBXA2R polymorphisms with asthma susceptibility and related phenotypes and to identify functionally relevant polymorphisms. METHODS: We performed comprehensive sequencing of the TBXA2R gene in 48 Japanese control subjects and found a set of variants (SNP1 G>T rs2238634, SNP2 T>G rs2238633, SNP3 C>T rs2238632 and SNP4 G>A rs2238631) in intron 1 in linkage disequilibrium with c.795 T>C rs1131882, which was previously reported to be associated with asthma and related phenotypes. To investigate the effect of four common haplotypes (H1, H2, H3 and H4) on transcriptional activity, we performed a luciferase assay in primary bronchial smooth muscle cells (BSMCs) and human airway epithelial cells (BEAS-2B). We also studied the haplotype association with lung function, TBXA2R mRNA levels, and eosinophil fraction/count in peripheral blood in childhood-onset asthma patients and/or controls. RESULTS: H2 and H4, containing minor alleles of SNP2 and SNP3, had significantly higher transcriptional activities than H1 consisting of major alleles (P < 0.001 in BSMCs and BEAS-2B). Homozygotes for redefined haplotype h2 corresponding to minor alleles of SNP2 and SNP3 were associated with lower lung function in childhood-onset asthma patients compared to other zygotes (baseline Forced expiratory volume in one second (FEV1)/ Forced vital capacity (FVC) and Forced expiratory flow between 25% and 75% of the FVC (%FEF(25-75%)): P = 0.00201 and 0.0128, respectively, and post-bronchodilator FEV1/FVC and %FEF(25-75%): P = 0.00224 and 0.0393 respectively). Haplotype h2 was also associated with higher mRNA levels in control peripheral blood cells and higher blood eosinophil fractions and counts in female controls. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic variants were identified in the TBXA2R gene that influenced transcriptional activity and were associated with asthma-related phenotypes. Thromboxane pathways may therefore play important roles in airway inflammation and remodelling in asthma patients.

ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

Optimal selection of learning data for highly accurate QSAR prediction of chemical biodegradability: a machine learning-based approach.

Prior to the manufacture of new chemicals, regulations mandate a thorough review of the chemicals under risk management. This review involves evaluating their effects on the environment and human health. To assess these effects, a review report that conforms to the OECD Test Guidelines must be submitted to the regulatory body. One of the essential components of the report is an assessment of the biodegradability of chemicals in the environment. In addition to conventional methods, quantitative structure-activity relationship (QSAR) models have been developed to predict the properties of chemicals based on their structural features. Although a greater number of chemicals in the learning set may enhance the prediction accuracy, it may also lead to a decrease in accuracy due to the mixing of different structural features and properties of the chemicals. To improve the prediction performance, it is recommended to use only the appropriate data for biodegradability prediction as a training set. In this study, we propose a novel approach for the optimal selection of training set that enables a highly accurate prediction of the biodegradability of chemicals by QSAR. Our findings indicate that the proposed method effectively reduces the root mean squared error and improves the prediction accuracy.

Weight Loss Mediated the Relationship between Tooth Loss and Mortality Risk.

Tooth loss is a risk factor for increased mortality; however, the underlying mechanism remains unclear. This study aimed to evaluate the mediating effect of weight change on the relationship between tooth loss and mortality risk. This was a 10-y follow-up prospective cohort study using the data from the Japan Gerontological Evaluation Study (JAGES). The participants were independent older adults aged ≥65 y at baseline and were followed up from 2010 to 2020. The incidence of death in 2013 and 2020, incidence of >5% weight loss/gain in 2010 and 2013, and the number of remaining teeth in 2010 were used as the outcome, mediator, and explanatory variables, respectively. We conducted causal mediation analysis by fitting the Cox proportional hazard model, including possible confounders. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the total effect (TE), natural indirect effect (NIE), and proportion mediated (PM) were estimated. Among the 34,510 participants, the mean age was 72.6 (SD = 5.4) y, and 47.6% were men. From 2013 to 2020, 14.0% of the participants (n = 4,825) died, 60.5% (n = 20,871) had 0 to 19 remaining teeth, and 17.2% (n = 5,927) and 8.4% (n = 2,907) experienced >5% weight loss and gain, respectively. The mortality rate was 0.016 per person-year among those with ≥20 remaining teeth and 0.027 per person-year among those with 0 to 19 remaining teeth. Weight loss of >5% significantly mediated the association between tooth loss and higher mortality risk (TE: HR, 1.28 [95% CI, 1.16 to 1.40]; NIE: HR, 1.03 [95% CI, 1.02 to 1.04]; PM, 13.1%); however, we observed a slight mediating effect for >5% weight gain (NIE: HR, 1.003 [95%CI, 1.0001 to 1.01]; PM, 1.3%). The present study suggests that a clinically meaningful level of weight loss mediated the association between tooth loss and increased risk of mortality among independent older adults.

Impact of Teeth on Social Participation: Modified Treatment Policy Approach.

Social participation prevents social isolation and loneliness among older adults while having numerous positive effects on their health and well-being in rapidly aging societies. We aimed to estimate the effect of retaining more natural teeth on social participation among older adults in Japan. The analysis used longitudinal data from 24,872 participants in the Japan Gerontological Evaluation Study (2010, 2013, and 2016). We employed a longitudinal modified treatment policy approach to determine the effect of several hypothetical scenarios (preventive scenarios and tooth loss scenarios) on frequent social participation (1 = at least once a week/0 = less than once a week) after a 6-y follow-up. The corresponding statistical parameters were estimated using targeted minimum loss-based estimation (TMLE) method. Number of teeth category (edentate/1-9/10-19/≥20) was treated as a time-varying exposure, and the outcome estimates were adjusted for time-varying (income, self-rated health, marital status, instrumental activities of daily living, vision loss, hearing loss, major comorbidities, and number of household members) and time-invariant covariates (age, sex, education, baseline social participation). Less frequent social participation was associated with older age, male sex, lower income, low educational attainment, and poor self-rated health at the baseline. Social participation improved when tooth loss prevention scenarios were emulated. The best preventive scenario (i.e., maintaining ≥20 teeth among each participant) improved social participation by 8% (risk ratio [RR] = 1.08; 95% confidence interval [CI], 1.05-1.11). Emulated tooth loss scenarios gradually decreased social participation. A hypothetical scenario in which all the participants were edentate throughout the follow-up period resulted in a 11% (RR = 0.89; 95% CI, 0.84-0.94) reduction in social participation. Subsequent tooth loss scenarios showed 8% (RR = 0.92; 95% CI, 0.88-0.95), 6% (RR = 0.94; 95% CI, 0.91-0.97), and 4% (RR = 0.96; 95% CI, 0.93-0.98) reductions, respectively. Thus, among Japanese older adults, retaining a higher number of teeth positively affects their social participation, whereas being edentate or having a relatively lower number of teeth negatively affects their social participation.

Search for antihelium with the BESS-Polar spectrometer.

In two long-duration balloon flights over Antarctica, the Balloon-borne Experiment with a Superconducting Spectrometer (BESS) collaboration has searched for antihelium in the cosmic radiation with the highest sensitivity reported. BESS-Polar I flew in 2004, observing for 8.5 days. BESS-Polar II flew in 2007-2008, observing for 24.5 days. No antihelium candidate was found in BESS-Polar I data among 8.4×10(6) |Z|=2 nuclei from 1.0 to 20 GV or in BESS-Polar II data among 4.0×10(7) |Z|=2 nuclei from 1.0 to 14 GV. Assuming antihelium to have the same spectral shape as helium, a 95% confidence upper limit to the possible abundance of antihelium relative to helium of 6.9×10(-8)} was determined combining all BESS data, including the two BESS-Polar flights. With no assumed antihelium spectrum and a weighted average of the lowest antihelium efficiencies for each flight, an upper limit of 1.0×10(-7) from 1.6 to 14 GV was determined for the combined BESS-Polar data. Under both antihelium spectral assumptions, these are the lowest limits obtained to date.

A case of primary squamous cell carcinoma of the endometrium associated with extensive "ichthyosis uteri".

BACKGROUND: Ichthyosis uteri is an uncommon entity in which the entire endometrium is replaced by stratified squamous epithelium. Though the condition often is considered as benign, dysplastic changes have been reported. CASE: We describe herein an exceedingly rare case of primary squamous cell carcinoma of the endometrium (PSCCE) associated with extensive ichthyosis uteri with chronic pyometra, who presented with blood-stained vaginal discharge of six-seven months duration. Although repeated endometrial biopsies revealed only strips of stratified squamous epithelium showing moderate to severe dysplastic changes, the tumor markers and magnetic resonance imaging strongly suggested advanced uterine body malignancy. Exploratory laparotomy was performed, and histologic findings of the superficial layer were consistent with ichthyosis uteri; in contrast the lesion of invasive squamous cell carcinoma was located in the deeper layer and lymph nodes. No dysplastic changes of the cervix were noted. CONCLUSIONS: It is suggested that PSCCE could be associated with pre-existing ichthyosis uteri and deeper biopsies should be performed for the accurate preoperative diagnosis of cases with chronic pyometra.

Does the insufficient supply of physicians worsen their urban-rural distribution? A Hiroshima-Nagasaki comparison.

INTRODUCTION: Studies have suggested that a rapid increase in physicians does not necessarily change an urban-rural inequity in their distribution. However, it is unknown whether an insufficient supply of physicians worsens an inequity. Spatial competition and attraction-repulsion hypotheses were applied to the geographic distribution of physicians during a time of insufficient physician supply in Japan. METHODS: Trends of physician distribution as well as urban-rural physician flow were compared using Hiroshima Prefecture which had the lowest increase in physician-to-population ratios between 2002 and 2008 (2.7%), and Nagasaki Prefecture where the increase was one of the highest (12.0%) among the 47 Japanese prefectures. RESULTS: The Gini coefficient of physicians compared with population in Hiroshima increased by 4.1%. Movement toward inequity was greater in Hiroshima compared with Nagasaki where the increase was 2.5%. Approximately 245 physicians or 18.8% moved from rural to urban locations in Hiroshima compared with 143 (14.6%) for Nagasaki (p=0.01). In contrast, 228 (7.6%) urban physicians moved to rural areas in Hiroshima compared with 175 (11.6%) in Nagasaki (p<0.001). CONCLUSIONS: In a time of insufficient supply of physicians, a region with a smaller increase in physicians may experience worsening of the urban-rural distribution of physicians compared with a region where there is a more rapid increase in physicians. One strategy for achieving a more equitable distribution of physicians is to increase in the physician supply relative to demand in order to stimulate competition among urban physicians and maintain the power equilibrium between attraction-to and repulsion-from urban areas.

Visualization of surface plasmon polariton waves in two-dimensional plasmonic crystal by cathodoluminescence.

A cathodoluminescence technique using a 200-keV transmission electron microscope revealed the dispersion patterns of surface plasmon polaritons (SPPs) in a two-dimensional plasmonic crystal with cylindrical hole arrays. The dispersion curves of the SPP modes involving the Γ point were derived from the angle-resolved spectrum patterns. The contrast along the dispersion curves changed with the polarization direction of the emitted light due to the property of the SPP modes. The SPP modes at the Γ point were identified from the photon maps, which mimicked standing SPP waves in a real space. The beam-scan spectral images across the plasmonic crystal edge clearly demonstrated the dependence of the SPP to light conversion efficiency on the emission angle and polarization of light.