Barriers and misconceptions hindering reduction of intestinal schistosomiasis in Mbita Sub-County, Western Kenya.

BACKGROUND: Community and individual participation are crucial for the success of schistosomiasis control. The World Health Organization (WHO) has highlighted the importance of enhanced sanitation, health education, and Mass Drug Administration (MDA) in the fight against schistosomiasis. These approaches rely on the knowledge and practices of the community to be successful; however, where the community knowledge is low and inappropriate, it hinders intervention efforts. Hence, it is essential to identify barriers and misconceptions related to awareness of schistosomiasis, sources of infection, mode of transmission, symptoms, and control measures. METHODS: This was a mixed-method cross-sectional study involving 1200 pre-school children randomly selected and examined for Schistosoma mansoni infection using the Kato-Katz technique. All parents/guardians of selected children were enrolled for a pre-tested questionnaire survey, while 42 were engaged in focus group discussions (FGDs). The level of knowledge and awareness among parents/guardians about schistosomiasis was evaluated in relation to the infection status of their pre-school children. RESULTS: Among pre-school children, the prevalence of intestinal schistosomiasis was 45.1% (95% CI 41.7-48.5). A majority of parents/guardians (85.5%) had heard about schistosomiasis, and this awareness was associated with the participant's level of education (OR = 0.16, 95% CI 0.08, 0.34). In addition, a positive association was observed between higher educational attainment and knowledge of the causative agent (OR = 0.69, 95% CI 0.49, 0.96). Low education level was significantly associated with limited knowledge of transmission through lake water contact (OR = 0.71, 95% CI 0.52, 0.97) and infection from the lake (OR = 0.33, 95% CI 0.19, 0.57). Notably, parents/guardians who have heard of schistosomiasis could not recognize symptoms of S. mansoni infection, such as abdominal pain (91.8%, 815/888) and blood in the stool (85.1%, 756/888). Surprisingly, 49.8% (442/888) incorrectly identified hematuria (blood in urine), a key sign of S. haematobium, but not S. mansoni, in an endemic area for S. mansoni infection. The majority (82.6%, 734/888) of parents/guardians were unaware that dams are potential infection sites, despite 53.9% (479/888) of their pre-school-aged children testing positive for schistosome infection. CONCLUSIONS: Despite the high level of awareness of intestinal schistosomiasis in the study area, we identified a low level of knowledge regarding its causes, modes of transmission, signs and symptoms and potential sites of transmission within the community. This study emphasizes the need for targeted educational interventions to address the misconceptions and knowledge gaps surrounding intestinal schistosomiasis through tailored community-based programs.

Lack of information on gender differences in the package inserts of prescription drugs in Japan.

The package inserts of prescription drugs provide essential information for the proper administration of pharmacotherapy. The incidence of adverse reactions for several drugs is known to be higher in women than in men. However, no studies have examined whether information on gender differences is included in Japanese package inserts. Therefore, this study investigated information on gender differences in the package inserts of Japanese prescription drugs, using the drug information database JAMES provided by the Medical Information System Development Center and the Japan Pharmaceutical Information Center. Non-proprietary names of prescription drugs were yielded 1,679 in Japan. Of the 1,679 ingredients in package inserts of prescription drugs, 76 (4.5%) included information on gender differences. The number of inserts that contained information on gender differences in the "DOSAGE AND ADMINISTRATION," "ADVERSE REACTIONS," and "PHARMACOKINETICS" sections was 3, 16, and 62, respectively. Furthermore, in the "ADVERSE REACTIONS" section, 15 of the 16 inserts mentioned a higher frequency of adverse reactions in women compared with men. Importantly, most of the inserts with information on gender differences in the "PHARMACOKINETICS" section mentioned a higher area under the curve for women than for men. Most of the package inserts of prescription drugs with information on gender differences provide useful information aimed at preventing risks in women. However, there is an extreme lack of information on gender differences in the package inserts of prescription drugs in Japan, and we consider enhancing information on gender difference as an urgent issue.

Integrated multi-omics analyses and functional validation reveal TTK as a novel EMT activator for endometrial cancer.

BACKGROUND: Cancer-testis antigens (CTAs) are often expressed in tumor and testicular tissues but not in other normal tissues. To date, there has been no comprehensive study of the expression and clinical significance of CTA genes associated with endometrial cancer (EC) development. Additionally, the clinical relevance, biological role, and molecular mechanisms of the CTA gene TTK protein kinase (TTK) in EC are yet to be fully understood. METHODS: Using bioinformatics methods, we comprehensively investigated the genomic, transcriptomic, and epigenetic changes associated with aberrant TTK overexpression in EC samples from the TCGA database. We further investigated the mechanisms of the lower survival associated with TTK dysregulation using single-cell data of EC samples from the GEO database. Cell functional assays were used to confirm the biological roles of TTK in EC cells. RESULTS: We identified 80 CTA genes that were more abundant in EC than in normal tissues, and high expression of TTK was significantly linked with lower survival in EC patients. Furthermore, ROC analysis revealed that TTK could accurately distinguish stage I EC tissues from benign endometrial samples, suggesting that TTK has the potential to be a biomarker for early EC detection. We found TTK overexpression was more prevalent in EC patients with high-grade, advanced tumors, serous carcinoma, and TP53 alterations. Furthermore, in EC tissue, TTK expression showed a strong positive correlation with EMT-related genes. With single-cell transcriptome data, we identified a proliferative cell subpopulation with high expression of TTK and known epithelial-mesenchymal transition (EMT)-related genes and transcription factors. When proliferative cells were grouped according to TTK expression levels, the overexpressed genes in the TTKhigh group were shown to be functionally involved in the control of chemoresistance. Utilizing shRNA to repress TTK expression in EC cells resulted in substantial decreases in cell proliferation, invasion, EMT, and chemoresistance. Further research identified microRNA-21 (miR-21) as a key downstream regulator of TTK-induced EMT and chemoresistance. Finally, the TTK inhibitor AZ3146 was effective in reducing EC cell growth and invasion and enhancing the apoptosis of EC cells generated by paclitaxel. CONCLUSION: Our findings establish the clinical significance of TTK as a new biomarker for EC and an as-yet-unknown carcinogenic function. This present study proposes that the therapeutic targeting of TTK might provide a viable approach for the treatment of EC.

Most dentists approve of oral health check-ups for local residents at community pharmacies and desire collaboration with community pharmacists.

Community pharmacies are required to play a role in maintaining the health of local residents. Since September 2015, a national policy in Japan has allowed saliva tests to be used for oral health check-ups at community pharmacies. In the present study, we aimed to reveal dentists' perceptions and expectations for oral health check-ups provided at community pharmacies. A questionnaire survey was administered to dentists at 1,000 randomly selected dental clinics in Tokyo, Japan; 257 responses (25.7%) were included in the analysis and 85.2% of respondents approved of oral health check-ups at community pharmacies. Most respondents who approved of oral health check-ups expected that community pharmacists would recommend that local residents visit a dental clinic (85.8%) and provide a report to dentists (60.3%) after the check-up. Furthermore, 79.0% of respondents desired collaboration with community pharmacies. These findings suggested the potential for oral health check-ups to facilitate collaboration between community pharmacies and dental clinics aimed at maintaining and improving oral health of local residents.

Spontaneously implemented spatial coherence in vertical-cavity surface-emitting laser dot array.

We report a self-induced spatially-coherent dot array consisting of fourteen units of vertical-cavity surface-emitting modes that exhibit spatially uniform spectra. A 47.5 µm total beam width and 0.5° narrow emission are achieved using an oblong cavity enclosed with a flat top mirror, cylindrically curved bottom mirror, and side facet. Notably, terminating the side of the cavity with a perpendicular facet enhances the horizontal propagation, which couples with the vertical resonance in each dot, similar to the case of master lasers in injection-locked lasers that delocalize the modes. Conventional semiconductor lasers, edge-emitting lasers, and vertical-cavity surface-emitting lasers have a Fabry-Pérot cavity; furthermore, emission and resonance are in identical directions, limiting the beam width to micrometers. Though the present structure has the same scheme of propagation, the right-angled facet synchronizes the modes and drastically expands the beam width.

Long Non-Coding RNA TMPO-AS1 Promotes GLUT1-Mediated Glycolysis and Paclitaxel Resistance in Endometrial Cancer Cells by Interacting With miR-140 and miR-143.

Increased glycolysis in tumor cells is frequently associated with drug resistance. Overexpression of glucose transporter-1 (GLUT1) promotes the Warburg effect and mediates chemoresistance in various cancers. Aberrant GLUT1 expression is considered as an essential early step in the development of endometrial cancer (EC). However, its role in EC glycolysis and chemoresistance and the upstream mechanisms underlying GLUT1 overexpression, remain undefined. Here, we demonstrated that GLUT1 was highly expressed in EC tissues and cell lines and that high GLUT1 expression was associated with poor prognosis in EC patients. Both gain-of-function and loss-of-function studies showed that GLUT1 increased EC cell proliferation, invasion, and glycolysis, while also making them resistant to paclitaxel. The long non-coding RNA TMPO-AS1 was found to be overexpressed in EC tissues and to be negatively associated with EC patient outcomes. RNA-immunoprecipitation and luciferase reporter assays confirmed that TMPO-AS1 elevated GLUT1 expression by directly binding to two critical tumor suppressor microRNAs (miR-140 and miR-143). Downregulation of TMPO-AS1 remarkably reduced EC cell proliferation, invasion, glycolysis, and paclitaxel resistance in EC cells. This study established that dysregulation of the TMPO-AS1-miR-140/miR-143 axis contributes to glycolysis and drug resistance in EC cells by up-regulating GLUT1 expression. Thus, inhibiting TMPO-AS1 and GLUT1 may prove beneficial in overcoming glycolysis-induced paclitaxel resistance in patients with EC.

Long non-coding RNA DLEU2 drives EMT and glycolysis in endometrial cancer through HK2 by competitively binding with miR-455 and by modulating the EZH2/miR-181a pathway.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) and aerobic glycolysis are fundamental processes implicated in cancer metastasis. Although increasing evidence demonstrates an association between EMT induction and enhanced aerobic glycolysis in human cancer, the mechanisms linking these two conditions in endometrial cancer (EC) cells remain poorly defined. METHODS: We characterized the role and molecular mechanism of the glycolytic enzyme hexokinase 2 (HK2) in mediating EMT and glycolysis and investigated how long noncoding RNA DLEU2 contributes to the stimulation of EMT and glycolysis via upregulation of HK2 expression. RESULTS: HK2 was highly expressed in EC tissues, and its expression was associated with poor overall survival. Overexpression of HK2 effectively promoted EMT phenotypes and enhanced aerobic glycolysis in EC cells via activating FAK and its downstream ERK1/2 signaling. Moreover, microRNA-455 (miR-455) served as a tumor suppressor by directly interacting with HK2 mRNA and inhibiting its expression. Furthermore, DLEU2 displayed a significantly higher expression in EC tissues, and increased DLEU2 expression was correlated with worse overall survival. DLEU2 acted as an upstream activator for HK2-induced EMT and glycolysis in EC cells through two distinct mechanisms: (i) DLEU2 induced HK2 expression by competitively binding with miR-455, and (ii) DLEU2 also interacted with EZH2 to silence a direct inhibitor of HK2, miR-181a. CONCLUSIONS: This study identified DLEU2 as an upstream activator of HK2-driven EMT and glycolysis in EC cells and provided significant mechanistic insights for the potential treatment of EC.

Critical Roles of PIWIL1 in Human Tumors: Expression, Functions, Mechanisms, and Potential Clinical Implications.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a class of small non-coding RNA molecules that are 24-31 nucleotides in length. PiRNAs are thought to bind to PIWI proteins (PIWL1-4, a subfamily of Argonaute proteins), forming piRNA/PIWI complexes that influence gene expression at the transcriptional or post-transcriptional levels. However, it has been recently reported that the interaction of PIWI proteins with piRNAs does not encompass the entire function of PIWI proteins in human tumor cells. PIWIL1 (also called HIWI) is specifically expressed in the testis but not in other normal tissues. In tumor tissues, PIWIL1 is frequently overexpressed in tumor tissues compared with normal tissues. Its high expression is closely correlated with adverse clinicopathological features and shorter patient survival. Upregulation of PIWIL1 drastically induces tumor cell proliferation, epithelial-mesenchymal transition (EMT), invasion, cancer stem-like properties, tumorigenesis, metastasis and chemoresistance, probably via piRNA-independent mechanisms. In this article, we summarize the current existing literature on PIWIL1 in human tumors, including its expression, biological functions and regulatory mechanisms, providing new insights into how the dysregulation of PIWIL1 contributes to tumor initiation, development and chemoresistance through diverse signaling pathways. We also discuss the most recent findings on the potential clinical applications of PIWIL1 in cancer diagnosis and treatment.

Patient satisfaction with oral health check-ups at a community pharmacy and their effect on oral self-care habits and dental consultation behavior.

Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.

Tailored radical hysterectomy for locally advanced cervical cancer.

OBJECTIVE: The survival and prognostic factors for locally advanced cervical cancer treated with nerve-sparing Okabayashi-Kobayashi radical hysterectomy have not been elucidated. We aimed to evaluate the oncological outcomes of those patients after radical hysterectomy with adjuvant chemotherapy. METHODS: This retrospective cohort study was conducted from January 2002 to December 2011. Treatment was conducted at a single tertiary center in northern Japan. We used the Okabayashi-Kobayashi radical hysterectomy with lymphadenectomy. We applied unilateral nerve preservation for stage IIA/IIB cancer if there was a one-sided extension of the disease outside the cervix. Indication for adjuvant therapy was based on Sedlis criteria. High-risk was defined as evidence of lymph node metastasis, pathological parametrial invasion, and a positive/close surgical margin. The choice of adjuvant therapy was chemotherapy which consisted of paclitaxel and cisplatin. RESULTS: The study included 76 early-stage IB1 (≤4 cm) and IIA1 cervical cancer and 45 locally advanced stage IB2 (>4 cm), IIA2, and IIB disease treated consecutively. The median follow-up was 106 (range: 6-203) months. There were 18 (15%) patients with recurrence, with five of 76 in the early-stage (7%) and 13 of 45 in the locally advanced disease (29%) (P<0.001). For locally advanced cervical cancer, pT classification (P<0.001), lymph node metastasis (P=0.007), and histology (P=0.05) were associated with locoregional recurrence. The five-year locoregional recurrence rate in the locally advanced disease was 20% and 5% in the early-stage disease (P=0.01). The five-year disease-free survival in the locally advanced cervical cancer was 71% and 93% in the early-stage disease (P<0.001). The overall survival in locally advanced disease depended on the adeno-type histology and lymph node metastasis. CONCLUSION: The tailored use of nerve-sparing Okabayashi-Kobayashi radical hysterectomy with adjuvant chemotherapy based on tumor histology and lymph node metastasis may be a possible option as a treatment of locally advanced cervical cancer in selected patients.

Comparison of ThinPrep Integrated Imager-Assisted Screening versus Manual Screening of ThinPrep Liquid-Based Cytology Specimens.

OBJECTIVE: The aim of this study was to find out whether ThinPrep Integrated Imager (Hologic Inc.) screening is non-inferior to manual screening in the detection of cervical lesion. STUDY DESIGN: For a total of 4,011 ThinPrep Pap test specimens stained by ThinPrep staining, manual screening (Manual arm) and ThinPrep Integrated Imager screening (Imager arm) were performed so as not to be screened by the same cytotechnologist, and the sensitivity and specificity in the detection of cervical lesion were compared using McNemar's test. RESULTS: The sensitivity to detect CIN1 or more squamous cell abnormalities or glandular abnormalities was 91.67% (= 374/408, 95% confidence interval [CI]: 88.44-94.08%) for the Manual arm and 92.40% (= 377/408, 95% CI: 89.28-94.70%) for the Imager arm, and the specificity was 88.87% (= 3,113/3,503, 95% CI: 87.77-89.88%) for the Manual arm and 89.55% (= 3,137/3,503, 95% CI: 88.48-90.54%) for the Imager arm. The differences in sensitivity and in specificity, respectively, were 0.74% (95% CI: -3.14-4.61%, McNemar's test, p = 0.8041) and 0.69% (95% CI: -0.13-1.50%, McNemar's test, p = 0.1125). About the equality of sensitivity and specificity between the 2 methods, 95% CIs of the difference between sensitivity and specificity are in the clinical equivalence range of ±5%, so the Imager arm is non-inferior to the Manual arm. CONCLUSION: The Imager arm was confirmed to have an equivalent and non-inferior capacity in the detection of cervical lesions compared with the Manual arm, suggesting that its practical application in cervical cytology tests is highly possible.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study.

OBJECTIVE: This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. METHODS: A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient's background differences were assessed with inverse probability of treatment weighting using propensity score. RESULTS: Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3-4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51-10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. CONCLUSION: This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

MicroRNA-361-Mediated Inhibition of HSP90 Expression and EMT in Cervical Cancer Is Counteracted by Oncogenic lncRNA NEAT1.

Epithelial-mesenchymal transition (EMT) is a key process contributing to cervical cancer (CC) metastasis, and microRNAs (miRNAs) modulate the expression of genes implicated in EMT. However, the accurate role of miR-361 in CC-associated EMT and the mechanisms underlying its function in CC remains largely unknown. The functional roles of miR-361 in CC cells were explored by a series of cell functional assays. Luciferase reporter assays were used to demonstrate the potential interaction between miR-361, HSP90, and long non-coding RNA (lncRNA) NEAT1. We detected a reduction of miR-361 expression in CC tissues compared with normal tissues, and miR-361 overexpression inhibited invasion and EMT phenotypes of CC cells by directly targeting a key EMT activator HSP90. Additionally, we detected significantly higher levels of HSP90 in CC tissues compared with normal tissues, and high expression of HSP90 predicted a poorer prognosis. We further identified NEAT1 as a significantly upregulated lncRNA in CC tissues and high expression of NEAT1 was associated with worse survival in CC patients. NEAT1 directly repressed miR-361 expression and played an oncogenic role in CC cell invasion and sphere formation. Conclusions: These results demonstrated that miR-361 directly targets HSP90 to inhibit the invasion and EMT features, and NEAT1 functions as an oncogenic lncRNA that suppresses miR-361 expression and induces EMT and sphere formation in CC cells, thus providing critical insights into the molecular pathways operating in this malignancy.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

BACKGROUND: L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. METHODS: We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. RESULTS: Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. CONCLUSION: L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

MicroRNA-361: A Multifaceted Player Regulating Tumor Aggressiveness and Tumor Microenvironment Formation.

MicroRNA-361-5p (miR-361) expression frequently decreases or is lost in different types of cancers, and contributes to tumor suppression by repressing the expression of its target genes implicated in tumor growth, epithelial-to-mesenchymal transition (EMT), metastasis, drug resistance, glycolysis, angiogenesis, and inflammation. Here, we review the expression pattern of miR-361 in human tumors, describe the mechanisms responsible for its dysregulation, and discuss how miR-361 modulates the aggressive properties of tumor cells and alter the tumor microenvironment by acting as a novel tumor suppressor. Furthermore, we describe its potentials as a promising diagnostic or prognostic biomarker for cancers and a promising target for therapeutic development.

Expression of precipitating factors of pruritus found in humans in an imiquimod-induced psoriasis mouse model.

AIMS: To use a mouse model of imiquimod-induced psoriasis to investigate the relationship between pruritus and mast cells, nerve growth factor (NGF) and endogenous pruritogenic peptides, which are highly expressed in the skin of psoriasis patients. MAIN METHODS: We developed a mouse model of imiquimod-induced psoriasis and measured the frequency and duration of the model animals' self-scratching behavior using the SCLABA®-Real real-time scratch counting system. We then harvested the ears and subjected them to toluidine blue staining and real-time PCR. KEY FINDINGS: Topical application of imiquimod increased the Psoriasis Area and Severity Index score as well as the frequency and duration of self-scratching. Regarding internal factors, increases in mast cells number and mRNA expression of NGF and endogenous pruritogenic peptide precursor were confirmed. SIGNIFICANCE: Self-scratching behavior is accompanied by increased number of mast cells and expression of NGF and endogenous pruritogenic peptides in our imiquimod-induced psoriasis model. The expression of these factors was consistent with the features in patients with pruritic psoriasis, suggesting that our model reflects at least some of the precipitating factors of pruritus found in humans.

Long noncoding RNA NEAT1 drives aggressive endometrial cancer progression via miR-361-regulated networks involving STAT3 and tumor microenvironment-related genes.

BACKGROUND: High-grade endometrioid and serous endometrial cancers (ECs) are an aggressive subtype of ECs without effective therapies. The reciprocal communication between tumor cells and their surrounding microenvironment drives tumor progression. Long noncoding RNAs (lncRNAs) are key mediators of tumorigenesis and metastasis. However, little is known about the role of lncRNAs in aggressive EC progression and tumor microenvironment remodeling. METHODS: We performed an array-based lncRNA analysis of a parental HEC-50 EC cell population and derivatives with highly invasive, sphere-forming, and paclitaxel (TX)-resistant characteristics. We characterized the roles of the lncRNA NEAT1 in mediating aggressive EC progression in vitro and in vivo and explored the molecular events downstream of NEAT1. RESULTS: We identified 10 lncRNAs with upregulated expression (NEAT1, H19, PVT1, UCA1, MIR7-3HG, SNHG16, HULC, RMST, BCAR4 and LINC00152) and 10 lncRNAs with downregulated expression (MEG3, GAS5, DIO3OS, MIR155HG, LINC00261, FENDRR, MIAT, TMEM161B-AS1, HAND2-AS1 and NBR2) in the highly invasive, sphere-forming and TX-resistant derivatives. NEAT1 expression was markedly upregulated in early-stage EC tissue samples, and high NEAT1 expression predicted a poor prognosis. Inhibiting NEAT1 expression with small hairpin RNAs (shRNAs) diminished cellular proliferation, invasion, sphere formation, and xenograft tumor growth and improved TX response in aggressive EC cells. We showed that NEAT1 functions as an oncogenic sponge for the tumor suppressor microRNA-361 (miR-361), which suppresses proliferation, invasion, sphere formation and TX resistance by directly targeting the oncogene STAT3. Furthermore, miR-361 also suppressed the expression of multiple prometastatic genes and tumor microenvironment-related genes, including MEF2D, ROCK1, WNT7A, VEGF-A, PDE4B, and KPNA4. CONCLUSIONS: NEAT1 initiates a miR-361-mediated network to drive aggressive EC progression. These data support a rationale for inhibiting NEAT1 signaling as a potential therapeutic strategy for overcoming aggressive EC progression and chemoresistance.

Appendicular muscle mass and exercise/sports participation history in young Japanese women.

Background: It remains unclear how past exercise habits can affect the skeletal muscle mass in adulthood in Japanese populations. Aim: The purpose of the present investigation was to examine the association of appendicular muscle mass (AMM) and skeletal muscle mass index (SMI) with the history of exercise and/or physical activity participation in Japanese women. Subjects and methods: One hundred and twenty females, aged between 18 and 28 years old, participated in the present investigation. Using a dual-energy X-ray absorptiometry scanner, the appendicular lean soft tissue, which is considered as a measure of AMM, was evaluated. Skeletal muscle mass index (SMI) was also assessed. Furthermore, all subjects answered a physical activity questionnaire. Results: Exercise habits at 7 years of age or older positively affected the AMM and SMI. The results of the multiple regression analysis showed that exercise history at 16-18 years of age as well as the current status of exercise and/or physical activity participation was a significant predictor of SMI and AMM. Conclusions: These results indicate that not only the past history of participation in physical and/or sports activities but also the current status of daily physical activity and sports activity play an important role in maintaining appropriate SMI and AMM in young women.

A survey on awareness of the "finger-tip unit" and medication guidance for the use of topical steroids among community pharmacists.

Atopic dermatitis (AD) is a common chronic, pruritic inflammatory skin condition. AD is most commonly treated with topical corticosteroids, and the finger-tip unit (FTU) should be used as a guideline for the amount to be used per application. In this study, we investigated the adequacy of pharmacists' instructions on the amount of topical steroids to be applied and the way in which they enhance the effect of pharmaceutical interventions. A self- administered anonymous questionnaire was distributed using QLifePro to 300 pharmacists working in insurance pharmacies that filled at least one dermatologist's prescription per month on average in Japan. Out of 300 pharmacists, 196 (65.3%) recognized the Japanese Dermatological Association's 2016 guidelines for the treatment AD, 107 (35.6%) gave instructions using the FTU as an index of external dose of topical steroids, 157 (52.3%) explained the amount of steroid application using an index other than FTU, and 61 (38.9% of 157) had inadequately instructed AD patients to apply steroids as a thin layer. Pharmacists who had read the guidelines for AD tended to give an appropriate instruction using FTU as an index of external dose of topical steroids (p < 0.001). We found that many pharmacists in pharmacies gave inadequate instructions on the amount of topical steroid application and deviated from the guidelines for AD, mainly because of inadequate knowledge of the guidelines.

The Prevalence and Functional Impact of Chronic Edema and Lymphedema in Japan: LIMPRINT Study.

Background: This was a part of LIMPRINT (Lymphoedema IMpact and PRevalence-INTernational), an international study aimed at capturing the size and impact of lymphedema and chronic edema in different countries and health services across the world. The purpose of this study was to clarify the prevalence and the impact of chronic edema in Japan. Methods and Results: This was a two-phase facility-based study to determine the prevalence and functional impact of chronic edema in the adult population in Japan between 2014 and 2015. The prevalence study involved a university hospital, an acute community hospital, and a long-term medical facility. The impact study involved six facilities, including two outpatient clinics in acute care hospitals (one led by a physician and the other led by a nurse), inpatient wards in two acute care hospitals, and two nursing home/long-term care facilities. Various questionnaires and clinical assessments were used to gather patient demographic data and assess the functional impact of chronic edema. The results showed that chronic edema was much more prevalent in the long-term care facility than in acute care hospitals; cellulitis episodes occurred in ∼50% of cases in the gynecologist-led outpatient clinic, even though >80.0% of patients received standard management for edema; edema was found in the trunk region, including the buttock, abdomen, and chest-breast areas, in addition to the upper and lower limbs; and subjective satisfaction with edema control was low, even though the quality-of-life scores were good. Conclusions: The prevalence of chronic edema varied according to the facility type, ranging from 5.0% to 66.1%. The edema was located in all body parts, including the trunk region. Subjective satisfaction with control of edema was poor, while general quality of life was good. This large health care issue needs more attention.