Online survey of genital and urinary symptoms among Japanese women aged between 40 and 90 years.

OBJECTIVE: The purpose of this survey was to assess the prevalence of genital and urinary tract symptoms among Japanese women with declining estrogen levels. METHODS: A health-related questionnaire survey was conducted among women in their 40s or older to inquire about their genital, intercourse-related, and urinary symptoms and concern over their symptoms. RESULTS: Of the consecutive 10,000 respondents recruited, 4488 (44.9%) reported having symptoms: 3546 (79.0%) expressed concern over their symptoms. Furthermore, 2173 women (21.7%) had incontinence, 1999 (20.0%) had urinary frequency, 1648 (16.5%) had itching, and 1560 (15.6%) reported odor; these were followed by looseness, dryness, and burning. Of the 2518 (25.2%) sexually active women, 518 (20.6%) reported having dyspareunia and more reported having urinary symptoms than genital symptoms. Of the symptomatic respondents, 33.1% had genital symptoms alone, 28.4% had urinary symptoms alone, and 38.4% had both. More sexually active women had genital symptoms, while more sexually inactive women had urinary symptoms. CONCLUSIONS: Genital and urinary symptoms were shown to be common and coexist in a considerable proportion of the respondents, highlighting the pathology of genitourinary syndrome of menopause. Again, dyspareunia and lower urinary tract symptoms were shown to be quite common among postmenopausal women.

Construction and usability of community health nursing database in rural north-eastern Thailand.

INTRODUCTIONS: Digitization could be incorporated in rural areas of resource-poor countries because information gathered by nurses working on-site could be better used. BACKGROUND: For effective management of community health information, the usage and maintenance of digital records are important. Digitization of information provides essential information for informing health policy. AIM: To develop a sustainable database to effectively collect and manage community health information and nursing practice. METHODS: This study used a mixed method design. Phase 1 involved the development of a database system through repeated systematic focus group discussions with community health nurses. Phase 2 involved a practical trial examination of the developed system with both objective and subjective evaluations. RESULTS: A nursing database system was developed with templates designed for the major health problems of communities. The templates were composed of multiple-choice items and a free-text field that allowed records to be more detailed than handwritten records and maintained in standardized formats. This enables accumulation of data that were less likely to be influenced by the variance of ability in each nurse. DISCUSSION AND CONCLUSION: A multifaceted evaluation of the database system suggested that it could improve the efficiency of information management and contribute to the improvement of nursing care quality through standardization of the recording pattern. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The nursing database will enable high-quality information storage that will potentially better inform health and healthcare policies as well as enable visualization of data concerning nursing care challenges and activities within the relevant communities. This information is essential for policy development and implementation in areas of human and fiscal resource allocations and meeting training/education needs.

The effect of bolus volume on laryngeal closure and UES opening in swallowing: Kinematic analysis using 320-row area detector CT study.

This study investigated the effects of three different volumes of honey-thick liquid on the temporal characteristics of swallowing. Twenty-six healthy subjects (15 males, 11 females) underwent 320-row area detector CT scan while swallowing 3, 10 and 20 mL of honey-thick liquid barium. Three-dimensional images were created at 10 images/s. Kinematic events involving six structures (velopharynx, hyoid bone, epiglottis, laryngeal vestibule (LV), true vocal cords (TVC), upper esophageal sphincter (UES)) and timing of bolus movement were timed using frame by frame analysis. The overall sequence of events did not differ across three volumes; however, increasing bolus volume significantly changed the onset and termination of events. The bolus head reached to pharynx and esophagus earlier and the duration of bolus passing through UES was significantly longer in 10 and 20 mL compared to 3 mL (P < .05). Consequently, the onset of UES opening was significantly earlier with increased volume (P < .05). LV and TVC closure occurred later in 20 mL compared to 3 mL (P < .05). These changes in motion of pharynx and larynx appeared to promote swallow safety by preventing aspiration, suggesting that anatomical structure movements adapt in response to bolus volume. Our findings also suggest that the pharyngeal swallow behaviours may be modified by afferents in the oral cavity. The three-dimensional visualization and quantitative measurements provided by 320-ADCT provide essential benchmarks for understanding swallowing, both normal and abnormal.

Clinical Courses of Graft Failure Caused by Chronic Allograft Dysfunction in Kidney Transplantation.

BACKGROUND: Chronic allograft dysfunction (CAD) is a main cause of graft failure in kidney transplantation. METHODS: We retrospectively analyzed 279 kidney transplant recipients who survived with a functioning graft for at least 2 years. CAD was defined as chronic graft deterioration, excluding other specific causes. We defined the pattern of decline in estimated glomerular filtration rate (eGFR), as follows: (1) "plateau" was defined as decline in eGFR ≤2 mL/min/1.73 m2/year; "long plateaus" were those lasting more than 5 years; (2) "rapid decline" was a decrease in eGFR ≥20 mL/min/1.73 m2/year. Patients diagnosed with CAD were categorized according to the occurrence of rapid decline and/or long plateau as follows: group 1, neither rapid decline nor long plateau; group 2, rapid decline only; group 3, long plateau only; and group 4, both rapid decline and long plateau. RESULTS: From a total of 81 graft losses, 51 (63%) failed because of CAD, with a median of 9.4 years. Sixteen patients belonged to group 1, 14 to group 2, 12 to group 3, and nine to group 4. Mean graft survival times in the four groups were 7.7 ± 1.1, 6.1 ± 3.1, 16.2 ± 2.5, and 10.8 ± 3.6 years, respectively (P < .001). There were significant differences among groups in donor age, year of transplantation, mean eGFR at baseline, and acute rejection rate after transplantation. CONCLUSIONS: The results indicate that this cohort of kidney transplant recipients who had CAD comprised subgroups with different clinical courses.

Body size evolution of a shell-brooding cichlid fish from Lake Tanganyika.

The substrate-brooding cichlid fish Telmatochromis temporalis in Lake Tanganyika demonstrates a simple example of ecological speciation between normal and dwarf morphs through divergent natural selection on body size. The dwarf morph most likely evolved from the ancestral normal morph; therefore, elucidating the evolution of its small body size is a key to understanding this ecological speciation event. Previous studies suggest that the small body size of the dwarf morph is an adaptation to the use of empty snail shells as shelters (males) and spawning sites (females), but this idea has not been fully evaluated. Combining original and previously published information, this study compared likelihood values to determine the primary factor that would be responsible for regulating the body size of the dwarf morph. Male body size is most likely regulated by the ability to turn within shells, which may influence the predation avoidance of adult fish. Females are smaller than males, and their body size is most likely regulated by the ability to lay eggs in the small spaces within shells close to the shell apices where predation risk on eggs is lower. This study provides new evidence supporting the hypothesis that different natural selection factors affected body size of the different sexes of the dwarf morph, which has not been reported in other animal species.

Role of mitogen-activated protein kinase pathways in migration of gingival epithelial cells in response to stimulation by cigarette smoke condensate and infection by Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Previous studies have shown that cigarette smoke (CS) and periodontal pathogens could alter wound healing responses of gingival epithelial cells. To elucidate molecular mechanisms leading to these epithelial changes, we studied the signaling pathway involved in the modulation of cell migration by CS condensate (CSC) and the infection by a prominent periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC or vehicle control for 24 h. Activation of mitogen-activated protein kinases (MAPK) in cells with or without infection by P. gingivalis was assessed by polymerase chain reaction array and immunoblotting using phospho-specific antibodies. Cell migration was assessed using in vitro wound closure model, and specific pharmacologic inhibitors of MAPK pathways were used to characterize further the extent of involvement of the MAPK pathways. RESULTS: Polymerase chain reaction array showed that gene expression of several members of the MAPK, particularly p38 and JNK, was upregulated more than twofold in Ca9-22 cells stimulated with 10 µg/mL CSC. Coincubation with P. gingivalis induced a different pattern of gene expression for MAPK pathways, but it did not suppress the MAPK-related genes upregulated by CSC. A significant phosphorylation of ERK1/2 and p38 was observed in cells stimulated with 10 µg/mL CSC (p < 0.05), whereas coincubation with a higher concentration of CSC (250 µg/mL) evoked no such activation. P. gingivalis infection resulted in a tendency to reduce the phosphorylation of ERK1/2 and p38, which had been enhanced by stimulation with 10 µg/mL CSC. Incubation with ERK1/2 and p38 inhibitors significantly reduced the wound closure of CSC-stimulated cells, by approximately 43% and 46%, respectively (p < 0.05). CONCLUSION: CSC exerts effects on the migration of human gingival epithelial cells through the activation of the MAPK ERK1/2 and p38 signaling pathways. P. gingivalis infection attenuates the CSC-induced migration at least partly by suppressing the phosphorylation of ERK1/2 and p38, but other pathways are likely to be involved in this modulatory process.

Synthesis of nano-TaO(x) oxygen reduction reaction catalysts on multi-walled carbon nanotubes connected via a decomposition of oxy-tantalum phthalocyanine.

Nano-TaOx particles were supported on multi-walled carbon nanotubes via the thermal decomposition of oxy-tantalum phthalocyanine. The phthalocyanine-derived carbon connected TaOx particles with the nanotube-support to provide a conductive path. The oxygen reduction reaction activity, which solely originated from TaOx, was above 0.9 V with larger currents than conventional TaOx particles in acidic media.

Cigarette smoke condensate modulates migration of human gingival epithelial cells and their interactions with Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Epithelial cells are recognized as the first line of defense against bacterial infection and environmental harmful stimuli such as cigarette smoke (CS). Although previous studies explored the effects of nicotine on host cells, mechanisms by which CS affects cellular functions remain uncertain. The present study investigated the effects of CS condensate (CSC) on in vitro wound closure of gingival epithelial cells and their potential interactions with a major periodontal pathogen, Porphyromonas gingivalis. MATERIAL AND METHODS: Human gingival epithelial cells (Ca9-22) were treated with CSC for 24 h. Cell proliferation was determined using a WST-1 assay. Cell migration was assessed using a wound closure model. The expression of integrins was analyzed by confocal scanning laser microscopy and real-time PCR. Intracellular invasion of P. gingivalis was evaluated by confocal scanning laser microscopy and an antibiotic protection assay. RESULTS: Low concentrations (1-10 µg/mL) of CSC showed no significant effect on cell proliferation. CSC demonstrated dual effects on epithelial wound closure of Ca9-22 cells: high concentrations (i.e. 250 µg/mL) significantly inhibited the wound closure whereas low concentrations (i.e. 10 µg/mL) promoted it (p < 0.01). CSC induced distinct changes in cytoskeleton. When CSC-exposed cells were infected with P. gingivalis for 2 h, a significant inhibition of wound closure was observed concurrent with a decrease in integrin α3 expression near the wound area. A significantly increased P. gingivalis invasion into Ca9-22 was observed when exposed to low concentrations of CSC. CONCLUSION: Low concentrations of CSC increased invasion of human gingival epithelial cells by P. gingivalis and induced changes in cytoskeleton and integrin expression, thereby modulating the cell migration.

Bower-building behaviour is associated with increased sperm longevity in Tanganyikan cichlids.

We investigated the evolutionary relationship between spawning behaviour and sperm motility traits among Tanganyikan mouth-brooding cichlid species that have developed diverse mating behaviours and male sexual traits. Mouth-brooding behaviour is common among these fish, but different species demonstrate a range of spawning behaviours, bower construction, male sexual traits and timing of gamete release. We observed spawning behaviours and compared sperm motility traits of 28 Tanganyikan mouth-brooding cichlids to elucidate the evolutionary correlations between these traits. Sperm longevity was considerably longer in bower-building species that construct crater-shaped spawning sites compared with species that do not build bowers. Male bower builders released sperm in the pit of the bower prior to spawning, and the time from ejaculation to fertilization was longer. Conversely, most mouth-brooding cichlids deposited semen directly into the female buccal cavity, and spawned eggs were immediately picked up to be placed inside the cavity; thus, the time from ejaculation to fertilization was short. These observations suggest that increased sperm longevity is favoured in bower builders. Comparative phylogenetic analyses suggested that bower-building behaviour and greater time from ejaculation to fertilization are associated with the extension of sperm longevity, whereas sperm competition rank does not play a major role. In addition, bower-building behaviour preceded the emergence of increased sperm longevity. These results indicate that the extension of sperm longevity as a result of the emergence of bower builders may have acted as an evolutionary attractor for sperm longevity.

Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer.

BACKGROUND: Recent clinical trials have shown that immune-checkpoint blockade yields a clinical response in a subset of individuals with advanced nonsmall-cell lung cancer (NSCLC). We examined whether the expression of programmed death-ligand 1 (PD-L1) is related to clinicopathologic or prognostic factors in patients with surgically resected NSCLC. PATIENTS AND METHODS: The expression of PD-L1 was evaluated by immunohistochemical analysis in 164 specimens of surgically resected NSCLC. Cell surface expression of PD-L1 in NSCLC cell lines was quantified by flow cytometry. RESULTS: Expression of PD-L1 in tumor specimens was significantly higher for women than for men, for never smokers than for smokers, and for patients with adenocarcinoma than for those with squamous cell carcinoma. Multivariate analysis revealed that the presence of epidermal growth factor receptor gene (EGFR) mutations and adenocarcinoma histology were significantly associated with increased PD-L1 expression in a manner independent of other factors. Cell surface expression of PD-L1 was also significantly higher in NSCLC cell lines positive for activating EGFR mutations than in those with wild-type EGFR. The EGFR inhibitor erlotinib downregulated PD-L1 expression in the former cell lines but not in the latter, suggesting that PD-L1 expression is increased by EGFR signaling conferred by activating EGFR mutations. A high level of PD-L1 expression in resected tumor tissue was associated with a significantly shorter overall survival for NSCLC patients. CONCLUSIONS: High expression of PD-L1 was associated with the presence of EGFR mutations in surgically resected NSCLC and was an independent negative prognostic factor for this disease.

Bach1 is critical for the transformation of mouse embryonic fibroblasts by Ras(V12) and maintains ERK signaling.

Reactive oxygen species (ROS), by-products of aerobic respiration, promote genetic instability and contribute to the malignant transformation of cells. Among the genes related to ROS metabolism, Bach1 is a repressor of the oxidative stress response, and a negative regulator of ROS-induced cellular senescence directed by p53 in higher eukaryotes. While ROS are intimately involved in carcinogenesis, it is not clear whether Bach1 is involved in this process. We found that senescent Bach1-deficient mouse embryonic fibroblasts (MEFs) underwent spontaneous immortalization the same as did the wild-type cells. When transduced with constitutively active Ras (H-Ras(V12)), the proliferation and colony formation of these cells in vitro were markedly reduced. When transplanted into athymic nude mice, the growth and vascularization of tumors derived from Bach1-deficient cells were also decreased. Gene expression profiling of the MEFs revealed a new H-Ras(V12) signature, which was distinct from the previously reported signatures in epithelial tumors, and was partly dependent on Bach1. The Bach1-deficient cells showed diminished phosphorylation of MEK and ERK1/2 in response to H-Ras(V12), which was consistent with the alterations in the gene expression profile, including phosphatase genes. Finally, Bach1-deficient mice were less susceptible to 4-nitroquinoline-1-oxidide (4-NQO)-induced tongue carcinoma than wild-type mice. Our data provide evidence for a critical role of Bach1 in cell transformation and tumor growth induced by activated H-Ras(V12).

Cardiac metastasis of head and neck squamous cell carcinoma.

Two patients with cardiac metastasis from head and neck cancer are reported. Cardiac metastasis located in the left atrium was detected on a follow-up computed tomography (CT) scan 15 months after partial glossectomy for a tongue carcinoma in a 60-year-old man. The diagnosis was confirmed as cardiac metastasis of squamous cell carcinoma (SCC) by surgical excision of the cardiac lesion. The patient died 3 weeks after surgery. In a 69-year-old man with a partial maxillectomy for primary soft palate cancer, a follow-up CT scan 5 months after surgery revealed a mass in the right atrium and ventricle, and multiple lung metastases. He died of heart failure 3 weeks after the diagnosis of cardiac metastasis. Information on these cases should add to knowledge about rarely encountered cardiac metastasis.

Interleukin-33 induces interleukin-17F in bronchial epithelial cells.

BACKGROUND: IL-33 is clearly expressed in the airway of patients with asthma, but its role in asthma has not yet been fully understood. IL-17F is also involved in the pathogenesis of asthma. However, the regulatory mechanisms of IL-17F expression remain to be defined. To further indentify the role of IL-33 in asthma, we investigated the expression of IL-17F by IL-33 in bronchial epithelial cells and its signaling mechanisms. METHODS: Bronchial epithelial cells were stimulated with IL-33. The levels of IL-17F expression were analyzed using real-time PCR and ELISA. Next, the involvement of ST2, MAP kinases, and mitogen- and stress-activated protein kinase1 (MSK1) was determined by Western blot analyses. Various kinase inhibitors and anti-ST2 neutralizing Abs were added to the culture to identify the key signaling events leading to the expression of IL-17F, in conjunction with the use of short interfering RNAs (siRNAs) targeting MSK1. RESULTS: IL-33 significantly induced IL-17F gene and protein expression. The receptor for IL-33, ST2, was expressed in bronchial epithelial cells. Among MAP kinases, IL-33 phosphorylated ERK1/2, but not p38MAPK and JNK. It was inhibited by the pretreatment of anti-ST2 neutralizing (blocking) Abs. MEK inhibitor significantly blocked IL-17F production. Moreover, IL-33 phosphorylated MSK1, and MEK inhibitor diminished its phosphorylation. Finally, MSK1 inhibitors and transfection of the siRNAs targeting MSK1 significantly blocked the IL-17F expression. CONCLUSIONS: IL-33 induces IL-17F via ST2-ERK1/2-MSK1 signaling pathway in bronchial epithelial cells. These data suggest that the IL-33/IL-17F axis is involved in allergic airway inflammation and may be a novel therapeutic target.

Prolonged matrix metalloproteinase-3 high expression after cyclic compressive load on human synovial cells in three-dimensional cultured tissue.

Excessive mechanical stress is thought to be a factor in the development of joint disorders through the expression of matrix metalloproteinases (MMPs) and related cytokines. Although studies revealed that mechanical stress on the synovium induces MMP expression, it is still not known which MMPs prolonged high level expression. The authors focused on MMP-3, which is one of the major factors in joint disorders such as rheumatism and temporomandibular joint disorders. They examined mRNA and protein levels of MMP-3, other MMPs and related cytokines after loading stress. Human synovial cells were seeded onto a collagen scaffold and different magnitudes of cyclic compressive load were applied for 1h. Time-dependent mRNA and protein levels for catabolic genes were examined after loading. mRNA expressions of MMP-1, MMP-3, MMP-9, IL-6, IL-8 and IL-1ß increased after excessive compression. In particular, only mRNA of MMP-3 was up-regulated and maintained at a high level for 24h after excessive loading. The concentrations of MMP-3, IL-6 and IL-8 in culture media after loading increased with excessive compression. These results may account for the pathomechanism of MMP-3 induced by cyclic load on synovial cells in joint disorders.

Overexpression of cIAP2 contributes to 5-FU resistance and a poor prognosis in oral squamous cell carcinoma.

BACKGROUND: Resistance to 5-fluorouracil (5-FU) is a major obstacle in treating oral squamous cell carcinoma (OSCC). However, little is known about apoptosis resistance, which contributes to 5-FU resistance in OSCC. METHODS: We focussed on the cellular inhibitor of apoptosis protein 2 (cIAP2) on the basis of a DNA microarray data using parental and 5-FU-resistant OSCC cell lines. The effects of cIAP2 downregulation on 5-FU sensitivity and apoptosis were evaluated. An immunohistochemical analysis of cIAP2 and related proteins, cIAP1 and X-linked IAP, was performed in 54 OSCC patients who were treated with 5-FU-based chemoradiotherapy and surgery. RESULTS: The downregulation of cIAP2 significantly enhanced the sensitivity of the 5-FU-resistant cells to 5-FU, with a significant increase in apoptosis. The immunohistochemical analysis demonstrated a high cIAP2 tumour expression to significantly correlate with the pathological response to chemoradiotherapy. Furthermore, a Cox regression analysis revealed the cIAP2 expression status (hazard ratio, 4.91; P=0.037) and the pathological response to chemoradiotherapy (hazard ratio, 0.418; P=0.016) to be significant prognostic factors for OSCC patients. CONCLUSION: These novel findings demonstrate that cIAP2 may represent a potentially useful therapeutic target for improving the treatment and survival of OSCC patients, particularly in the setting of 5-FU resistance.

Social status-dependent nest choice of territorial males under reproductive parasitism in a Lake Tanganyika cichlid Telmatochromis vittatus.

Field and laboratory studies were conducted to examine how territorial males of a Lake Tanganyika cichlid Telmatochromis vittatus balance the conflicting demands on nest choice between occupying large nests with more females and avoiding reproductive parasitism (nest piracy, which is adopted by the largest males in the population). Pirates less frequently intruded the nests farther from neighbours, perhaps due to the costs associated with travelling between nests. The field experiment showed that territorial male T. vittatus sacrificed the fitness benefits that large nests offer and instead prioritized occupying the nests farther from neighbours on which fewer pirates intruded. The field observations suggested that they adopt different strategies for nest choice according to their relative competitive ability to pirates; the large territorial males, who are size-matched to pirates and can defend their nests against them, compete for larger nests among the more-isolated nests, whereas subordinate territorial males, which are smaller than pirates and thus inferior to them, compete for the more-isolated nests among the less-isolated nests. These findings suggest that the territorial male T. vittatus chooses the more-isolated nests to avoid pirate males at the expense of occupying large nests.

Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in pharyngeal and rectal specimens using the BD Probetec ET system, the Gen-Probe Aptima Combo 2 assay and culture.

OBJECTIVES: This study compared the sensitivity and specificity of culture and two nucleic acid amplification tests (NAATs): the BD Probetec ET system (PT) and the Aptima Combo 2 (AC2) in detecting Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT) in pharyngeal and rectal specimens. METHODS: Male subjects were prospectively recruited at an MSM clinic in Toronto, Canada. Pharyngeal and rectal specimens were obtained for GC and CT culture, PT and AC2. Urine was also obtained for PT. A true positive was defined as: (1) positive culture, (2) positive PT and AC2 at the same site or (3) a single positive NAAT and detection of the same organism by any method at another site. RESULTS: 248 subjects were recruited. The prevalence of pharyngeal GC was 8.1%, rectal GC 11.7%, pharyngeal CT 2.0% and rectal CT 7.7%. The sensitivity of culture for pharyngeal GC and CT was 0%; 41.4% for rectal GC and 21.1% for rectal CT. The sensitivity of PT for pharyngeal GC, rectal GC, pharyngeal CT and rectal CT was 95.0%, 93.1%, 80.0% and 94.7%, respectively. The sensitivity of AC2 was 95.0% for pharyngeal GC and 100% at all other sites. Specificity was consistently above 98%. CONCLUSIONS: PT and AC2 detected GC and CT with superior sensitivity compared to culture. They detected 73 pharyngeal or rectal GC and CT infections compared to 16 by culture, using a rigorous gold standard. NAATs should be the method of choice for the detection of GC and CT in extragenital sites in men who have sex with men.

Midkine as a prognostic biomarker in oral squamous cell carcinoma.

The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription-PCR analysis and immunohistochemistry with fresh tumour samples. To determine whether S-MK concentrations have prognostic value, we performed survival analyses with clinical information by using the log-rank test. Serum midkine concentrations were significantly higher in patients with OSCC than in healthy controls (P<0.001). Serum midkine concentrations were also significantly increased in early-stage OSCC compared with those of healthy individuals (P<0.001). In addition, immunohistochemistry allowed identification of overexpressed MK protein in OSCC tissues. MK mRNA showed higher expression in OSCC samples compared with normal mucosal samples. Patients in high S-MK groups showed a significantly lower 5-year survival rate compared with patients in low S-MK groups (P<0.05). The increased S-MK concentrations in early-stage OSCC were strongly associated with poor survival. Serum midkine concentrations may thus be a useful marker not only for cancer screening but also for predicting prognosis of OSCC patients.