SMAD3 promotes expression and activity of the androgen receptor in prostate cancer.

Overexpression of androgen receptor (AR) is the primary cause of castration-resistant prostate cancer, although mechanisms upregulating AR transcription in this context are not well understood. Our RNA-seq studies revealed that SMAD3 knockdown decreased levels of AR and AR target genes, whereas SMAD4 or SMAD2 knockdown had little or no effect. ChIP-seq analysis showed that SMAD3 knockdown decreased global binding of AR to chromatin. Mechanistically, we show that SMAD3 binds to intron 3 of the AR gene to promote AR expression. Targeting these binding sites by CRISPRi reduced transcript levels of AR and AR targets. In addition, ∼50% of AR and SMAD3 ChIP-seq peaks overlapped, and SMAD3 may also cooperate with or co-activate AR for AR target expression. Functionally, AR re-expression in SMAD3-knockdown cells partially rescued AR target expression and cell growth defects. The SMAD3 peak in AR intron 3 overlapped with H3K27ac ChIP-seq and ATAC-seq peaks in datasets of prostate cancer. AR and SMAD3 mRNAs were upregulated in datasets of metastatic prostate cancer and CRPC compared with primary prostate cancer. A SMAD3 PROTAC inhibitor reduced levels of AR, AR-V7 and AR targets in prostate cancer cells. This study suggests that SMAD3 could be targeted to inhibit AR in prostate cancer.

Morphology Control of Mixed Metallic Organic Framework for High-Performance Hybrid Supercapacitors.

The study presents the binder-free synthesis of mixed metallic organic frameworks (MMOFs) supported on a ternary metal oxide (TMO) core as an innovative three-dimensional (3D) approach to enhance electron transport and mass transfer during the electrochemical charge-discharge process, resulting in high-performance hybrid supercapacitors. The research demonstrates that the choice of organic linkers can be used to tailor the morphology of these MMOFs, thus optimizing their electrochemical efficiency. Specifically, a NiCo-MOF@NiCoO2@Ni electrode, based on terephthalic linkers, exhibits highly ordered porosity and a vast internal surface area, achieving a maximum specific capacity of 2320 mC cm-2, while maintaining excellent rate capability and cycle stability. With these performances, the hybrid supercapacitor (HSC) achieves a maximum specific capacitance of 424.6 mF cm-2 (specific capacity 653.8 mC cm-2) and 30.7 F cm-3 with energy density values of 10.1 mWh cm-3 at 167.4 mW cm-3 (139.8 µWh cm-2 at 2310 µW cm-2), which are higher than those of previously reported MMOFs based electrodes. This research introduces a novel approach for metal organic framework based HSC electrodes, diverging from the traditional emphasis on metal ions, in order to achieve the desired electrochemical performance.

Epicardial HDAC3 Promotes Myocardial Growth Through a Novel MicroRNA Pathway.

BACKGROUND: Establishment of the myocardial wall requires proper growth cues from nonmyocardial tissues. During heart development, the epicardium and epicardium-derived cells instruct myocardial growth by secreting essential factors including FGF (fibroblast growth factor) 9 and IGF (insulin-like growth factor) 2. However, it is poorly understood how the epicardial secreted factors are regulated, in particular by chromatin modifications for myocardial formation. The current study is to investigate whether and how HDAC (histone deacetylase) 3 in the developing epicardium regulates myocardial growth. METHODS: Various cellular and mouse models in conjunction with biochemical and molecular tools were employed to study the role of HDAC3 in the developing epicardium. RESULTS: We deleted Hdac3 in the developing murine epicardium, and mutant hearts showed ventricular myocardial wall hypoplasia with reduction of epicardium-derived cells. The cultured embryonic cardiomyocytes with supernatants from Hdac3 knockout (KO) mouse epicardial cells also showed decreased proliferation. Genome-wide transcriptomic analysis revealed that Fgf9 and Igf2 were significantly downregulated in Hdac3 KO mouse epicardial cells. We further found that Fgf9 and Igf2 expression is dependent on HDAC3 deacetylase activity. The supplementation of FGF9 or IGF2 can rescue the myocardial proliferation defects treated by Hdac3 KO supernatant. Mechanistically, we identified that microRNA (miR)-322 and miR-503 were upregulated in Hdac3 KO mouse epicardial cells and Hdac3 epicardial KO hearts. Overexpression of miR-322 or miR-503 repressed FGF9 and IGF2 expression, while knockdown of miR-322 or miR-503 restored FGF9 and IGF2 expression in Hdac3 KO mouse epicardial cells. CONCLUSIONS: Our findings reveal a critical signaling pathway in which epicardial HDAC3 promotes compact myocardial growth by stimulating FGF9 and IGF2 through repressing miR-322 or miR-503, providing novel insights in elucidating the etiology of congenital heart defects and conceptual strategies to promote myocardial regeneration.

Graphene-Encapsulated Bifunctional Catalysts with High Activity and Durability for Zn-Air Battery.

Carbon-based electrocatalysts with both high activity and high stability are desirable for use in Zn-air batteries. However, the carbon corrosion reaction (CCR) is a critical obstacle in rechargeable Zn-air batteries. In this study, a cost-effective carbon-based novel material is reported with a high catalytic effect and good durability for the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), prepared via a simple graphitization process. In situ growth of graphene is utilized in a 3D-metal-coordinated hydrogel by introducing a catalytic lattice of transition metal alloys. Due to the direct growth of few-layer graphene on the metal alloy decorated 3d-carbon network, greatly reduced CCR is observed in a repetitive OER test. As a result, an efficient bifunctional electrocatalytic performance is achieved with a low ΔE value of 0.63 V and good electrochemical durability for 83 h at a current density of 10 mA cm-2 in an alkaline media. Moreover, graphene-encapsulated transition metal alloys on the nitrogen-doped carbon supporter exhibit an excellent catalytic effect and good durability in a Zn-air battery system. This study suggests a straightforward way to overcome the CCR of carbon-based materials for an electrochemical catalyst with wide application in energy conversion and energy storage devices.

Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study.

OBJECTIVE: Surgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. METHODS: This is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. RESULTS: 956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%). Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). CONCLUSION: Surgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

Concentration Gradient Induced Delithiation Failure of MoO3 for Li-Ion Batteries.

Electric vehicle manufacturers worldwide are demanding superior lithium-ion batteries, with high energy and power densities, compared to gasoline engines. Although conversion-type metal oxides are promising candidates for high-capacity anodes, low initial Coulombic efficiency (ICE) and poor capacity retention have hindered research on their applications. In this study, the ICE of conversion-type MoO3 is investigated, with a particular focus on the delithiation failure. A computational modeling predicts the concentration gradient of Li+ in MoO3 particles. The highly delithiated outer region of the particle forms a layer with low electronic conductivity, which impedes further delithiation. A comparative study using various sizes of MoO3 particles demonstrated that the electrode failure during delithiation is governed by the concentration gradient and the subsequent formation of a resistive shell. The proposed failure mechanism provides critical guidance for the development of conversion-type anode materials with improved electrochemical reversibility.

Screw-in force, torque generation, and performance of glide-path files with three rotation kinetics.

We aimed to evaluate the screw-in force, torque generation, and performance of three nickel-titanium (NiTi) glide-path files with different rotational kinetics. ProTaper Ultimate Slider (PULS) and HyFlex EDM Glide-path (HEDG) files were used for canal shaping with constant rotation (CON) or the alternative rotation technique (ART). In the ART mode, the NiTi file was periodically rotated at a speed of 1.5 times faster than that in the CON mode. WaveOne Gold Glider was used with reciprocating motion (WOGG_RCP). Sixty J-shaped resin blocks were assigned to five groups: PULS_CON, PULS_ART, HEDG_CON, HEDG_ART, and WOGG_RCP (n = 12). Glide-path preparation was performed using an automated pecking device. During glide-path preparation, the screw-in force and clockwise and counterclockwise torques were recorded and the number of pecking motions required to reach the working length was determined. The centering ratio was calculated after glide-path preparation using stereomicroscopic images. Data were analyzed using one-way analysis of variance with the Games-Howell post hoc test and the Kruskal-Wallis test with Bonferroni correction. PULS_ART generated a lower maximum screw-in force than PULS_CON. The average number of pecking motions required to reach the working length by HEDG_ART was lower than that by HEDG_CON. The mean centering ratios of PULS_CON and HEDG_CON were - 0.04 and - 0.06, respectively, while those of PULS_ART, HEDG_ART, and WOGG_RCP were 0.09, 0.01, and 0.08, respectively. The ART mode reduced the screw-in force of PULS and enabled faster glide-path preparation with the HEDG file.

Comparison of outcomes between abdominal, minimally invasive and combined vaginal-laparoscopic hysterectomy in patients with stage IAI/IA2 cervical cancer: 4C (Canadian Cervical Cancer Collaborative) study.

OBJECTIVE: Although minimally invasive hysterectomy (MIS-H) has been associated with worse survival compared to abdominal hysterectomy (AH) for cervical cancer, only 8% of patients in the LACC trial had microinvasive disease (Stage IA1/IA2). We sought to determine differences in outcome among patients undergoing MIS-H, AH or combined vaginal-laparoscopic hysterectomy (CVLH) for microinvasive cervical cancer. METHODS: A retrospective cohort study of all patients undergoing hysterectomy (radical and non radical) for FIGO 2018, microinvasive cervical cancer across 10 Canadian centers between 2007 and 2019 was performed. Recurrence free survival (RFS) was estimated using Kaplan Meier Survival analysis. Chi-square and log-rank tests were used to compare outcomes. RESULTS: 423 patients with microinvasive cervical cancer were included; 259 (61.2%) Stage IA1 (22/8.5% with LVSI) and 164(38.8%) IA2. The median age was 44 years (range 24-81). The most frequent histology was squamous (59.4%). Surgical approach was: 50.1% MIS-H (robotic or laparoscopic), 35.0% AH and 14.9% CVLH. Overall, 70.9% underwent radical hysterectomy and 76.5% had pelvic lymph node assessment. There were 16 recurrences (MIS-H:4, AH:9, CVLH: 3). No significant difference in 5-year RFS was found (96.7% MIS-H, 93.7% AH, 90.0% CVLH, p = 0.34). In a sub-analysis of patients with IA1 LVSI+/IA2(n = 186), survival results were similar. Further, there was no significant difference in peri-operative complications (p = 0.19). Patients undergoing MIS-H had a shorter median length of stay(0 days vs 3 (AH) vs. 1.5 (CVLH), p < 0.001), but had more ER visits (16.0% vs 3.6% (AH), 3.5% (CVLH), p = 0.036). CONCLUSION: In this cohort, including only patients with microinvasive cervical cancer, no difference in recurrence was found by surgical approach. This may be due to the low rate of recurrence making differences hard to detect or due to a true lack of difference. Hence, this patient population may benefit from MIS without compromising oncologic outcomes.

Uterine Sarcoma With FGFR1-TACC1 Gene Fusion: A Case Report and Review of the Literature.

With the growing availability of RNA sequencing technology in the pathology laboratory, new gene fusion-associated malignancies are increasingly being characterized. In this article, we describe the second ever reported case of a uterine sarcoma harboring a FGFR1-TACC1 gene fusion. The patient, a 53-yr-old perimenopausal woman, was found to have a 6 cm mass spanning the lower uterine segment and endocervix. Histologically, this was a spindle cell neoplasm with coagulative necrosis, moderate cytologic atypia, and increased mitotic activity. By immunohistochemistry, the neoplastic cells coexpressed CD34 and S100, and lacked smooth muscle marker expression. RNA sequencing revealed the presence of a FGFR1-TACC1 gene fusion. This report provides further evidence to suggest that FGFR1-TACC1 may be a recurrent fusion in a subset of uterine sarcomas. RNA sequencing using a panel that includes FGFR-TACC family fusions should be considered for uterine sarcomas that do not fit conventional diagnostic criteria, particularly as tumors with these fusions may be amenable to targeted therapy.

The relationship between changes in the korean fertility rate and policies to encourage fertility.

BACKGROUND: Korean government has established various policies to counter the low fertility rate since the mid-2000s, but it still has the lowest fertility rate among OECD member countries. This study investigated the relationship between changes in the Korean fertility rate and policies to encourage fertility. METHODS: This study utilized data of the total fertility rate of 250 local governments between 2014 and 2018, and a casebook of local government birth promotion policies. The dependent variable was fertility rate, and the independent variable was fertility promotion policy. Using SPSS 25.0 and M-plus 8.0 programs, descriptive statistical analysis and latent growth modeling were conducted. An unconditional quadratic function change model was selected as a final model of this study. RESULTS: The average of the initial fertility rate and the linear rate of change in the Korean fertility rate, and the rate of change of the quadratic function were all statistically significant, meaning that the fertility rate of decline increases over time. Also, the linear rate of change and the quadratic function change rate were significant, showing significant differences in the initial level and rate of change of the fertility rate between local governments. Among fertility policies, only the in-kind policy had a significant effect on the initial value of the fertility rate, meaning that the higher the number of in-kind policies, the higher the fertility rate. CONCLUSION: This study is crucial as it examined the changes in the fertility rate of Korean local governments as well as the policy factors affecting the fertility rate at a quantitative level.

Evaluation of design, mechanical properties, and torque/force generation of heat-treated NiTi glide path instruments.

BACKGROUND: Recently, various kinds of heat-treated nickel-titanium (NiTi) glide path instruments have been manufactured. This study aimed to investigate design, phase transformation behavior, mechanical properties of TruNatomy Glider (#17/02), V Taper 2H (#14/03), and HyFlex EDM (#15/03) and compare torque/force generated during simulated glide path preparation with them. METHODS: The designs and phase-transformation behaviors of the instruments were examined via scanning electron microscopy (n = 3) and differential scanning calorimetry (n = 2). Their bending (n = 15), torsional (n = 15), and cyclic fatigue resistances (n = 15) were tested. The ultimate strength and distortion angle were obtained from torsional resistance test. The number of cycles to failure (NCF) was calculated from cyclic fatigue resistance test. The preparation of the glide path was simulated using a double-curved artificial canal (n = 15), and the maximum torque and screw-in forces were measured. Data except NCF was compared between brands with one-way ANOVA with Tukey's honestly significant difference test. NCF was analyzed via Kruskal-Wallis and Mann-Whitney U tests. RESULTS: TruNatomy Glider had the greatest number of threads. TruNatomy Glider showed progressive taper, while V Taper 2H and HyFlex EDM had constant taper. The austenitic transformation-finish temperatures of all the instruments were above body temperature. V Taper 2H demonstrated significantly lower ultimate strength, higher distortion angle, and a higher number of cycles to failure compared with HyFlex EDM and TruNatomy Glider (p < 0.05). The maximum torque generated during preparing glide path was lowest for V Taper 2H, and the maximum screw-in force was lowest for HyFlex EDM (p < 0.05). TruNatomy Glider generated the highest torque and screw-in force during the apical preparation. CONCLUSIONS: V Taper 2H #14/03 showed superior cyclic fatigue resistance and lower ultimate strength. TruNatomy Glider generated greater clockwise torque and screw-in force during apical preparation. The mechanical properties, torque, and screw-force was affected by design of heat-treated glide path instruments. Cervical pre-flaring prior to glide path instrument is recommended.

Directive clinique no 408 : Prise en charge des maladies gestationnelles trophoblastiques.

OBJECTIF: Cette directive passe en revue l'évaluation clinique et la prise en charge des maladies gestationnelles trophoblastiques, notamment les traitements chirurgicaux et médicamenteux des tumeurs bénignes, prémalignes et malignes. L'objectif de la présente directive clinique est d'aider les fournisseurs de soins de santé à rapidement diagnostiquer les maladies gestationnelles trophoblastiques, à normaliser les traitements et le suivi et à assurer des soins spécialisés précoces aux patientes dont l'atteinte est maligne ou métastatique. PROFESSIONNELS CONCERNéS: Gynécologues généralistes, obstétriciens, médecins de famille, sages-femmes, urgentologues, anesthésistes, radiologistes, anatomopathologistes, infirmières autorisées, infirmières praticiennes, résidents, gynécologues-oncologues, oncologues médicaux, radio-oncologues, chirurgiens, omnipraticiens en oncologie, infirmières en oncologie, pharmaciens, auxiliaires médicaux et autres professionnels de la santé qui traitent des patientes atteintes d'une maladie gestationnelle trophoblastique. La présente directive vise également à fournir des renseignements aux parties intéressées qui prodiguent des soins de suivi à ces patientes après le traitement. POPULATION CIBLE: Femmes en âge de procréer atteintes d'une maladie gestationnelle trophoblastique. OPTIONS: Les femmes ayant reçu un diagnostic de maladie gestationnelle trophoblastique doivent être orientées vers un gynécologue afin qu'il réalise une évaluation initiale, envisage une intervention chirurgicale primaire (évacuation ou hystérectomie) et effectue un suivi. Il y a lieu d'orienter les femmes ayant reçu un diagnostic de tumeur trophoblastique gestationnelle vers un gynécologue-oncologue afin qu'il effectue la stadification tumorale, établisse le score de risque et envisage l'intervention chirurgicale primaire ou un traitement systémique (mono- ou polychimiothérapie) et la nécessité d'éventuels traitements supplémentaires. Il est recommandé de discuter de chaque cas de néoplasie gestationnelle trophoblastique lors d'une réunion multidisciplinaire de cas oncologiques et de l'inscrire dans une base de données centralisée (régionale et/ou nationale). DONNéES PROBANTES: Des recherches ont été effectuées au moyen des bases de données Embase et MEDLINE, du Cochrane Central Register of Controlled Trials et de la Cochrane Database of Systematic Reviews afin de trouver les études publiées depuis 2002 utilisant un ou plusieurs des mots clés suivants : trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome et remission. La recherche initiale a été effectuée en avril 2017; une mise à jour a été faite en mai 2019. Les données probantes pertinentes ont été sélectionnées aux fins d'inclusion selon l'ordre suivant : méta-analyses, revues systématiques, directives cliniques, essais cliniques randomisés, études de cohortes prospectives, études observationnelles, revues non systématiques, études de séries de cas et rapports. D'autres articles pertinents ont été trouvés en recoupant les revues répertoriées. Le nombre total d'études relevées était de 673, dont 79 études sont citées dans la présente revue. MéTHODES DE VALIDATION: Le contenu et les recommandations ont été rédigés et acceptés par les auteurs. La direction et le conseil d'administration de la Société de gynéco-oncologie du Canada ont passé en revue le contenu de la version préliminaire et ont soumis des commentaires à prendre en considération. Le conseil d'administration de la Société des obstétriciens et gynécologues du Canada a approuvé la version définitive aux fins de publication. La qualité des données probantes a été évaluée au moyen des critères de l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). Consulter les tableaux dans l'annexe en ligne pour connaître les critères de notation et d'interprétation des recommandations. BéNéFICES, RISQUES, COûTS: Les présentes recommandations aideront les médecins à diagnostiquer rapidement les maladies gestationnelles trophoblastiques et à orienter de façon urgente les patientes ayant reçu un diagnostic de maladie gestationnelle trophoblastique en gynécologie oncologique pour une prise en charge spécialisée. Le traitement des néoplasies gestationnelles trophoblastiques en centre spécialisé combiné à l'utilisation de bases de données centralisées permet de recueillir et de comparer des données sur les résultats thérapeutiques des patientes atteintes de ces tumeurs rares et d'optimiser les soins aux patientes. DÉCLARATIONS SOMMAIRES (CLASSEMENT GRADE ENTRE PARENTHèSES): RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).

Guideline No. 408: Management of Gestational Trophoblastic Diseases.

OBJECTIVE: This guideline reviews the clinical evaluation and management of gestational trophoblastic diseases, including surgical and medical management of benign, premalignant, and malignant entities. The objective of this guideline is to assist health care providers in promptly diagnosing gestational trophoblastic diseases, to standardize treatment and follow-up, and to ensure early specialized care of patients with malignant or metastatic disease. INTENDED USERS: General gynaecologists, obstetricians, family physicians, midwives, emergency department physicians, anaesthesiologists, radiologists, pathologists, registered nurses, nurse practitioners, residents, gynaecologic oncologists, medical oncologists, radiation oncologists, surgeons, general practitioners in oncology, oncology nurses, pharmacists, physician assistants, and other health care providers who treat patients with gestational trophoblastic diseases. This guideline is also intended to provide information for interested parties who provide follow-up care for these patients following treatment. TARGET POPULATION: Women of reproductive age with gestational trophoblastic diseases. OPTIONS: Women diagnosed with a gestational trophoblastic disease should be referred to a gynaecologist for initial evaluation and consideration for primary surgery (uterine evacuation or hysterectomy) and follow-up. Women diagnosed with gestational trophoblastic neoplasia should be referred to a gynaecologic oncologist for staging, risk scoring, and consideration for primary surgery or systemic therapy (single- or multi-agent chemotherapy) with the potential need for additional therapies. All cases of gestational trophoblastic neoplasia should be discussed at a multidisciplinary cancer case conference and registered in a centralized (regional and/or national) database. EVIDENCE: Relevant studies from 2002 onwards were searched in Embase, MEDLINE, the Cochrane Central Register of Controlled Trials, and Cochrane Systematic Reviews using the following terms, either alone or in combination: trophoblastic neoplasms, choriocarcinoma, trophoblastic tumor, placental site, gestational trophoblastic disease, hydatidiform mole, drug therapy, surgical therapy, radiotherapy, cure, complications, recurrence, survival, prognosis, pregnancy outcome, disease outcome, treatment outcome, and remission. The initial search was performed in April 2017 and updated in May 2019. Relevant evidence was selected for inclusion in the following order: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional significant articles were identified through cross-referencing the identified reviews. The total number of studies identified was 673, with 79 studies cited in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of Directors of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration, and the Board of Directors for the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. See the online appendix tables for key to grading and interpretation of recommendations. BENEFITS: These guidelines will assist physicians in promptly diagnosing gestational trophoblastic diseases and urgently referring patients diagnosed with gestational trophoblastic neoplasia to gynaecologic oncology for specialized management. Treating gestational trophoblastic neoplasia in specialized centres with the use of centralized databases allows for capturing and comparing data on treatment outcomes of patients with these rare tumours and for optimizing patient care. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Hormone Therapy Use After Premature Surgical Menopause Based on Prescription Records: A Population-Based Study.

OBJECTIVE: Premature surgical menopause (PSM) without subsequent hormone replacement therapy (HRT) can lead to morbidity and mortality. Our objective was to describe the use of HRT following PSM and identify variables associated with HRT use based on prescription records from a population-based cohort. METHODS: A population-based retrospective cohort of women in British Columbia, Canada who underwent PSM between the ages of 19 and 49 years. Women were identified using surgical data from the Discharge Abstract Database and linked to HRT prescription histories from the BC PharmaNet database for the period of 2004 to 2014. HRT prescription rates were calculated, and factors associated with postoperative HRT use were identified. RESULTS: A total of 12 837 women were included, with a median age of 43 years. They had undergone BSO with concurrent hysterectomy (49.9%). bilateral salpingo-oophorectomy (BSO) alone (42.1%), or bilateral oophorectomy (BO) (8%). The most common indications for surgery were endometriosis (17.9%), benign adnexal neoplasm (17.2%), and abnormal bleeding (14.0%). Only 55.3% of women ever used HRT, and 47.9% of these women used HRT for less than 1 year. HRT use was higher among women who underwent concurrent hysterectomy (60.7% vs. 50%, P < 0.001). This association remained significant after multivariate adjustment (aOR 1.64; 95% CI 1.50-1.79). Women with a known BRCA mutation were also more likely to use HRT postoperatively (aOR 3.73; 95% CI 2.14-6.81). CONCLUSION: In this large population-based study, HRT use after PSM was 50%. Our study highlights the need for education of both health care providers and patients, and for ongoing follow-up in this young population.

Guideline No. 403: Initial Investigation and Management of Adnexal Masses.

OBJECTIVES: To aid primary care physicians, emergency medicine physicians, and gynaecologists in the initial investigation of adnexal masses, defined as lumps that appear near the uterus or in or around ovaries, fallopian tubes, or surrounding connective tissue, and to outline recommendations for identifying women who would benefit from a referral to a gynaecologic oncologist for further management. INTENDED USERS: Gynaecologists, obstetricians, family physicians, general surgeons, emergency medicine specialists, radiologists, sonographers, nurses, medical learners, residents, and fellows. TARGET POPULATION: Adult women 18 years of age and older presenting for the evaluation of an adnexal mass. OPTIONS: Women with adnexal masses should be assessed for personal risk factors, history, and physical findings. Initial evaluation should also include imaging and laboratory testing to triage women for management of their care either by a gynaecologic oncologist or as per SOGC guideline no. 404 on the initial investigation and management of benign ovarian masses. EVIDENCE: A search of PubMed, Cochrane Wiley, and the Cochrane systematic reviews was conducted in January 2018 for English-language materials involving human subjects published since 2000 using three sets of terms: (i) ovarian cancer, ovarian carcinoma, adnexal disease, ovarian neoplasm, adnexal mass, fallopian tube disease, fallopian tube neoplasm, ovarian cyst, and ovarian tumour; (ii) the above terms in combination with predict neoplasm staging, follow-up, and staging; and (iii) the above two sets of terms in combination with ultrasound, tumour marker, CA 125, CEA, CA19-9, HE4, multivariable-index-assay, risk-of-ovarian-malignancy-algorithm, risk-of-malignancy-index, diagnostic imaging, CT, MRI, and PET. Relevant evidence was selected for inclusion in descending order of quality of evidence as follows: meta-analyses, systematic reviews, guidelines, randomized controlled trials, prospective cohort studies, observational studies, non-systematic reviews, case series, and reports. Additional articles were identified through cross-referencing the identified reviews. The total number of studies identified was 2350, with 59 being included in this review. VALIDATION METHODS: The content and recommendations were drafted and agreed upon by the authors. The Executive and Board of the Society of Gynecologic Oncology of Canada reviewed the content and submitted comments for consideration. The Board of Directors of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework (Table A1 of Online Appendix A). See Table A2 of Online Appendix A for the interpretation of strong and weak recommendations. The summary of findings is available upon request. BENEFITS, HARMS, COSTS: Adnexal masses are common, and guidelines on how to triage them and manage the care of patients presenting with adnexal masses will continue to guide the practice of primary care providers and gynaecologists. Ovarian cancer outcomes are improved when initial surgery is performed by a gynaecologic oncologist, likely as a result of complete surgical staging and optimal cytoreduction. Given these superior outcomes, guidelines to assist in the triage of adnexal masses and the referral and management of the care of patients with an adnexal mass are critical. SUMMARY STATEMENTS (GRADE RATINGS IN PARENTHESES): RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

Effect of autoclave sterilization on cyclic fatigue and torsional fracture resistance of NiTi rotary instruments.

The purpose of this study is to assess the effect of autoclave sterilization on the cyclic fatigue and torsional fracture resistance of ProTaper Universal (PTU), K3XF, HyFlex EDM (EDM), and TF adaptive (TFA). Sixty instruments from each file type were divided into two categories for cyclic fatigue group (CGr) and torsional fracture group (TGr). CGr and TGr were divided into three subgroups, respectively, consisting of ten instruments from each file type. Cyclic fatigue fracture test was performed using artificial canal made of stainless steel, and the mean number of cycles to failure (NCF) were determined. CGr1, the files were tested to establish baseline for NCF; CGr2, the files were tested cyclic fatigue after 10 cycles of autoclave; CGr3, instruments were autoclaved after being cycled to 25, 50, and 75% of corresponding NCF determined in CGr1, followed by cyclic fatigue test. The torsional fracture test was performed without autoclave (TGr1), after 3-cycle autoclave (TGr2), and 7-cycle autoclave (TGr3), respectively, which evaluated maximum torque and angular deflection. NCF, maximum torque and angular deflection were compared using one-way ANOVA with Bonferroni test. Two-way ANOVA was performed to determine the interaction between 'autoclave treatment' and 'type of NiTi file'. EDM showed highest NCF within the same autoclave treatment. TFA presented the lowest maximum torque and the highest angular deflection, and PTU presented the lowest angular deflection. Within the same NiTi file systems, most of NCF, maximum torque and angular deflection of tested files were not significantly influenced by autoclave condition.

Ultrathin nickel hydroxide on carbon coated 3D-porous copper structures for high performance supercapacitors.

An ultrathin nickel hydroxide layer electrodeposited on a carbon-coated three-dimensional porous copper structure (3D-C/Cu) is suggested as an additive and binder-free conductive electrode with short electron path distances, large electrochemical active sites, and improved structural stability, for high performance supercapacitors. The 3D-porous copper structure (3D-Cu) provides high electrical conductivity and facilitates electron transport between the Ni(OH)2 active materials and the current collector of the Ni-plate. A carbon coating was applied to the 3D-Cu to prevent the oxidation of Cu, without degrading the electron transport behavior of the 3D-Cu. The 3D-Ni(OH)2/C/Cu exhibited a high specific capacitance of 1860 F g-1 at 1 A g-1, and good cycling performance, with an 86.5% capacitance retention after 10 000 cycles. When tested in a two-electrode system, an asymmetric supercapacitor exhibited an energy density of 147.9 W h kg-1 and a power density of 37.0 kW kg-1. These results open a new area of ultrahigh-performance supercapacitors, supported by 3D-Cu electrodes.

A Titanium-Doped SiOx Passivation Layer for Greatly Enhanced Performance of a Hematite-Based Photoelectrochemical System.

This study introduces an in situ fabrication of nanoporous hematite with a Ti-doped SiOx passivation layer for a high-performance water-splitting system. The nanoporous hematite with a Ti-doped SiOx layer (Ti-(SiOx /np-Fe2 O3 )) has a photocurrent density of 2.44 mA cm(-2) at 1.23 VRHE and 3.70 mA cm(-2) at 1.50 VRHE . When a cobalt phosphate co-catalyst was applied to Ti-(SiOx /np-Fe2 O3 ), the photocurrent density reached 3.19 mA cm(-2) at 1.23 VRHE with stability, which shows great potential of the use of the Ti-doped SiOx layer with a synergistic effect of decreased charge recombination, the increased number of active sites, and the reduced hole-diffusion pathway from the hematite to the electrolyte.

An Overview of Pathogen Recognition Receptors for Innate Immunity in Dental Pulp.

Pathogen recognition receptors (PRRs) are a class of germ line-encoded receptors that recognize pathogen-associated molecular patterns (PAMPs). The activation of PRRs is crucial for the initiation of innate immunity, which plays a key role in first-line defense until more specific adaptive immunity is developed. PRRs differ in the signaling cascades and host responses activated by their engagement and in their tissue distribution. Currently identified PRR families are the Toll-like receptors (TLRs), the C-type lectin receptors (CLRs), the nucleotide-binding oligomerization domain-like receptors (NLRs), the retinoic acid-inducible gene-I-like receptors (RLRs), and the AIM2-like receptor (ALR). The environment of the dental pulp is substantially different from that of other tissues of the body. Dental pulp resides in a low compliance root canal system that limits the expansion of pulpal tissues during inflammatory processes. An understanding of the PRRs in dental pulp is important for immunomodulation and hence for developing therapeutic targets in the field of endodontics. Here we comprehensively review recent finding on the PRRs and the mechanisms by which innate immunity is activated. We focus on the PRRs expressed on dental pulp and periapical tissues and their role in dental pulp inflammation.

Quantum confinement and its related effects on the critical size of GeO2 nanoparticles anodes for lithium batteries.

This work has been performed to determine the critical size of the GeO2 nanoparticle for lithium battery anode applications and identify its quantum confinement and its related effects on the electrochemical performance. GeO2 nanoparticles with different sizes of ∼ 2, ∼ 6, ∼ 10, and ∼ 35 nm were prepared by adjusting the reaction rate, controlling the reaction temperature and reactant concentration, and using different solvents. Among the different sizes of the GeO2 nanoparticles, the ∼ 6 nm sized GeO2 showed the best electrochemical performance. Unexpectedly smaller particles of the ∼ 2 nm sized GeO2 showed the inferior electrochemical performances compared to those of the ∼ 6 nm sized one. This was due to the low electrical conductivity of the ∼ 2 nm sized GeO2 caused by its quantum confinement effect, which is also related to the increase in the charge transfer resistance. Those characteristics of the smaller nanoparticles led to poor electrochemical performances, and their relationships were discussed.