Initial experience of 980-nm diode laser treatment for recurrent non-muscle-invasive bladder cancer.

Introduction: Laser ablation using a 980-nm wavelength diode laser, which is a new-generation laser, for recurrent bladder cancer is known to have a lower incidence of complications and recurrence than conventional transurethral resection of bladder tumor surgery. This is the first study to report the use of 980-nm diode laser ablation for recurrent non-muscle-invasive bladder cancer in Japan.

Case Presentation: A 73-year-old man underwent transurethral laser ablation for the treatment of recurrent non-muscle-invasive bladder cancer.

Canine induced pluripotent stem cells can be successfully maintained in weekend-free culture systems.

Canine induced pluripotent stem cells (ciPSCs) can provide useful insights into novel therapies in both veterinary and medical fields. However, limited accessibility to the present culture medium and requirement of considerable time, effort, and cost for routine ciPSC maintenance restrict advancement in ciPSC research. In addition, it is unknown whether ciPSC culture conditions influence differentiation propensity.

Effect of the spatial-temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse.

Background: In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women.

FOXO1 mitigates the SMAD3/FOXL2 transcriptomic effect in a model of human adult granulosa cell tumor.

Background: Adult granulosa cell tumor (aGCT) is a rare type of stromal cell malignant cancer of the ovary characterized by elevated estrogen levels. aGCTs ubiquitously harbor a somatic mutation in FOXL2 gene, Cys134Trp (c.402C < G); however, the general molecular effect of this mutation and its putative pathogenic role in aGCT tumorigenesis is not completely understood.

Safety and Efficacy of the Sirolimus Gel for TSC Patients With Facial Skin Lesions in a Long-Term, Open-Label, Extension, Uncontrolled Clinical Trial.

Introduction: Our previous clinical studies have demonstrated the short-term efficacy and safety of the sirolimus gel for patients with tuberous sclerosis complex (TSC). However, long-term clinical evidence is lacking. Our objective was to assess the safety and efficacy of long-term treatment with the sirolimus gel for the skin lesions of TSC patients.

FOXO1 Negates the Cooperative Action of FOXL2 and SMAD3 in CYP19 Expression in HGrC1 Cells by Sequestering SMAD3.

Adult granulosa cell tumor (aGCT) is a rare type of ovarian cancer characterized by estrogen excess. Interestingly, only the single somatic mutation was found across virtually all aGCTs. We previously reported that FOXL2 stimulates CYP19 transcription synergistically with SMAD3, leading to elevated estradiol synthesis in a human granulosa cell line (HGrC1).

-(Carboxymethyl)arginine Is One of the Dominant Advanced Glycation End Products in Glycated Collagens and Mouse Tissues.

Advanced glycation end products (AGEs) accumulate in proteins during aging in humans. In particular, the AGE structure -(carboxymethyl)arginine (CMA) is produced by oxidation in glycated collagen, accounting for one of the major proteins detected in biological samples. In this study, we investigated the mechanism by which CMA is generated in collagen and detected CMA in collagen-rich tissues.

A School Nurse Application of the ECHO Model.

Type I diabetes (T1D) is one of the most common childhood diseases and Type 2 diabetes (T2D) is increasing at alarming rates. Given that children spend a great percentage of their time in school, this setting is a critical environment for models of care that lead to better management of this and other health conditions. The School Nurses Managing Diabetes Care ECHO was offered to Colorado school nurses to build their capacity in providing evidence-based management of T1D.

Characteristics of effective collaboration: A study of Nurse-Family Partnership and child welfare.

Background: In February 2018, President Trump signed into law the Family First Prevention Act, legislation in the United States aimed at providing prevention services for families at risk of entering the child welfare system. The effectiveness of these prevention efforts is dependent on the formation of collaborative relationships between prevention-programs and child welfare.

Objective: To identify factors that influence the ability of the Nurse-Family Partnership (NFP) and Child Protective Services (CPS) to collaborate in serving high-risk mothers and their children.

Risk assessment practices among home visiting nurses and child protection caseworkers in Colorado, United States: A qualitative investigation.

Nurses and caseworkers engage in assessments with the families they serve. Nurse home visitors from Nurse-Family Partnership (NFP) improve maternal-child health outcomes with first-time low-income mothers through care, education and support. In the United States, Child Protective Services (CPS) are state-level governmental agencies that protect children, including responding to reports of child maltreatment.

Strengthening the Health Workforce through the ECHO Stages of Participation: Participants' Perspectives on Key Facilitators and Barriers.

Introduction: Project Extension for Community Health Outcomes (ECHO) was originally developed by the University of New Mexico's Health Science Center (UNMHSC) to build the capacities of primary-care providers and to increase specialty-care access to rural and underserved populations. ECHO Colorado, a replication site at the University of Colorado Anschutz Medical Campus (CUAMC), was developed with the same purpose and to help build the health workforce of Colorado. The CUAMC and its community-based partners recognized that by reducing unnecessary referrals to the medical campus and building primary-care capacity in communities, both would increase their scope and expand overall capacity.

Molecular Aspects and Clinical Relevance of GDF9 and BMP15 in Ovarian Function.

Growth and differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) are oocyte-secreted factors with a leading role in the control of ovarian function in female reproduction, modulating both the cell fate of the somatic granulosa cells and the quality and developmental competence of the egg. This short review aims to consolidate the molecular aspects of GDF9 and BMP15 and their integral actions in female fertility to understand particularly their effects on oocyte quality and fetal growth. The significant consequences of mutations in the GDF9 and BMP15 genes in women with dizygotic twins as well as the clinical relevance of these oocyte factors in the pathogenesis of primary ovarian insufficiency and polycystic ovary syndrome are also addressed.

FOXL2C134W-Induced CYP19 Expression via Cooperation With SMAD3 in HGrC1 Cells.

Germline knockout studies in female mice demonstrated an essential role for forkhead box L2 (FOXL2) in early follicle development, whereas an inducible granulosa cell (GC)-specific deletion of Foxl2 in adults has shown ovary-to-testis somatic sex reprogramming. In women, over 120 different germline mutations in the FOXL2 gene have been shown to cause blepharophimosis/ptosis/epicantus inversus syndrome associated with or without primary ovarian insufficiency. By contrast, a single somatic mutation (FOXL2C134W) accounts for almost all adult-type GC tumors (aGCTs).

Activation of Endoplasmic Reticulum Stress in Granulosa Cells from Patients with Polycystic Ovary Syndrome Contributes to Ovarian Fibrosis.

Recent studies report the involvement of intra-ovarian factors, such as inflammation and oxidative stress, in the pathophysiology of polycystic ovary syndrome (PCOS), the most common endocrine disorder of reproductive age women. Endoplasmic reticulum (ER) stress is a local factor that affects various cellular events during a broad spectrum of physiological and pathological conditions. It may also be an important determinant of pro-fibrotic remodeling during tissue fibrosis.

PAI-1 in granulosa cells is suppressed directly by statin and indirectly by suppressing TGF-β and TNF-α in mononuclear cells by insulin-sensitizing drugs.

Problem: Plasminogen activator inhibitor-1 (PAI-1) is elevated in women with polycystic ovary syndrome (PCOS), but the regulation in granulosa cells (GCs) is unclear.

Method Of Study: PAI-1 expression in PCOS ovaries was investigated immunohistologically. PAI-1 expressions in HGrC1, a human GC cell line, were investigated at mRNA and activity levels.

Growth and differentiation factor 9 promotes oocyte growth at the primary but not the early secondary stage in three-dimensional follicle culture.

Purpose: Factors that differentially regulate oocyte and granulosa cell growth within the early preantral follicle and how these factors differ at each stage of follicle growth remain poorly understood. The aim of this study was to isolate and evaluate the effect of recombinant growth and differentiation factor 9 (GDF9) on oocyte and granulosa cell growth at the primary and early secondary stages of preantral follicle growth during in vitro culture.

Methods: Primary stage follicles (diameters of 50-89 μm) and early secondary stage follicles (diameters of 90-120 μm) were isolated from immature mice, and individual, intact follicles were cultured in vitro in the presence and absence of recombinant GDF9.

Knowledge, Attitudes, and Risk for Sudden Unexpected Infant Death in Children of Adolescent Mothers: A Qualitative Study.

Objective: To investigate practices, knowledge, attitudes, and beliefs regarding infant sleep among adolescent mothers, a demographic at high risk for sudden unexpected infant death, and to identify novel public health interventions targeting the particular reasons of this population.

Study Design: Seven targeted focus groups including 43 adolescent mothers were conducted at high school daycare centers throughout Colorado. Focus groups were recorded, transcribed, validated, and then analyzed in NVivo 10.

Endoplasmic Reticulum (ER) Stress Induces Sirtuin 1 (SIRT1) Expression via the PI3K-Akt-GSK3β Signaling Pathway and Promotes Hepatocellular Injury.

Sirtuin 1 (SIRT1), an NAD(+)-dependent histone deacetylase, plays crucial roles in various biological processes including longevity, stress response, and cell survival. Endoplasmic reticulum (ER) stress is caused by dysfunction of ER homeostasis and exacerbates various diseases including diabetes, fatty liver, and chronic obstructive pulmonary disease. Although several reports have shown that SIRT1 negatively regulates ER stress and ER stress-induced responses in vitro and in vivo, the effect of ER stress on SIRT1 is less explored.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice.

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice.

Decreased inhibin B responses following recombinant human chorionic gonadotropin administration in normal women and women with polycystic ovary syndrome.

Objective: To determine whether granulosa cells contribute to excess androgen production, by assessing inhibin B (Inh B) responses to hCG in women with polycystic ovary syndrome (PCOS) and in normal women.

Design: Prospective study.

Setting: Academic medical center.

Paracrine regulation of theca androgen production by granulosa cells in the ovary.

Objective: To test whether and to what extent inhibin mediates Cyp17 messenger RNA (mRNA) expression in theca cells (TCs) in response to FSH stimulation of granulosa cells (GCs).

Design: Ex vivo and in vitro experimental study.

Setting: University.

GRK-6 mediates FSH action synergistically enhanced by estrogen and the oocyte in rat granulosa cells.

Estrogen is known to play a pivotal role in granulosa cell responses to follicle-stimulating hormone (FSH) that is critical for the establishment of dominant follicles and subsequent ovulation in mammals. Thus, elucidating the cellular and molecular mechanisms that regulate FSH activity is important to understand female fertility. We previously discovered that the oocyte is required for estrogen to exert its positive effects on FSH activity in rat granulosa cells.

Granulosa cell tumor mutant FOXL2C134W suppresses GDF-9 and activin A-induced follistatin transcription in primary granulosa cells.

A single somatic FOXL2 mutation (FOXL2(C134W)) was identified in almost all granulosa cell tumor (GCT) patients. In the pituitary, FOXL2 and Smad3 coordinately regulate activin stimulation of follistatin transcription. We explored whether a similar regulation occurs in the ovary, and whether FOXL2(C134W) has altered activity.

Essential but differential role of FOXL2wt and FOXL2C134W in GDF-9 stimulation of follistatin transcription in co-operation with Smad3 in the human granulosa cell line COV434.

The FOXL2(C134W) mutation has been identified in virtually all adult granulosa cell tumors (GCTs). Here we show that the exogenous FOXL2 expression is necessary for GDF-9 stimulation of follistatin transcription in the human GCT cell line, COV434 that lacks endogenous FOXL2 expression. Interestingly, in the presence of Smad3 co-expression, FOXL2(C134W) negated GDF-9 stimulation of follistatin transcription.