Evaluation of the impact, treatment patterns, and patient and physician perceptions of vasomotor symptoms associated with menopause in Europe and the United States.

OBJECTIVES This study elicited the views of physicians and patients with vasomotor symptoms (VMS) associated with menopause on the impact of VMS and treatment patterns/perceptions. STUDY DESIGN Data from the Adelphi VMS Disease Specific Programme, a point-in-time survey conducted in 5 European countries and the United States in 2020, were used. Primary care providers (PCPs) and gynecologists seeing ≥3 patients/week with VMS associated with menopause completed a survey and chart review; their patients were invited to complete a survey and questionnaires. MAIN OUTCOME MEASURES Physicians reported treatment patterns and patient-specific symptoms and treatment preferences. Patients described symptoms, impact of VMS, and treatment satisfaction. RESULTS Participants included 115 PCPs and 118 gynecologists. Physicians reviewed the charts of 1816 patients, 854 of whom completed surveys. Moderate/severe impact of VMS on sleep, mood, quality of life, and work/study was reported by 35.8 %, 31.6 %, 23.6 %, and 15.4 % of women, respectively. Based on chart review, 64.8 % of women were currently prescribed treatment for VMS, most commonly hormone therapy (HT; 73.1 %), followed by selective serotonin or serotonin-norepinephrine reuptake inhibitors (31.3 %). Most women (57.3 %) with VMS were eligible for HT but averse to using it. Despite 91.4 % of physicians finding HT to be effective, 62.7 % agreed (slightly-strongly) that their patients are generally reluctant to use it. One-third of women were dissatisfied with VMS control. CONCLUSIONS VMS can considerably impact daily life. Effective treatment options that are better accepted could potentially improve management of VMS and lead to better quality of life for women with VMS associated with menopause. CLINICAL TRIAL REGISTRATION None

Economic outcomes in patients with chemotherapy-naive metastatic castration-resistant prostate cancer treated with enzalutamide or abiraterone acetate plus prednisone

Introduction: Prostate cancer (PC) is the second leading cause of cancer death among US men and accounts for considerable healthcare expenditures. We evaluated economic outcomes in men with chemotherapy-naı¨ve metastatic castration-resistant PC (mCRPC) treated with enzalutamide or abiraterone acetate plus prednisone (abiraterone). Methods: We performed a retrospective analysis on 3174 men (18 years or older) utilizing the Veterans Health Administration (VHA) database from 1 April 2014 to 31 March 2018. Men with mCRPC were included if they had at least one pharmacy claim for enzalutamide or abiraterone (first claim date = index date) following surgical or medical castration, had no chemotherapy treatment within 12 months prior to the index date, and had continuous VHA enrollment for at least 12 months pre- and post-index date. Men were followed until death, disenrollment, or end of study and were 1:1 propensity score matched (PSM). All-cause and PC-related resource use and costs per patient per month (PPPM) in the 12 months post index were compared between matched cohorts. Results: We identified 1229 men with mCRPC prescribed enzalutamide and 1945 prescribed abiraterone with mean ages of 74 and 73 years, respectively. After PSM, each cohort had 1160 patients. The enzalutamide cohort had fewer all-cause (2.51 vs 2.86; p\0.0001) and PC-related outpatient visits (0.86 vs 1.03; p\0.0001), with corresponding lower all-cause ($2588 vs$3115; p\0.0001) and PC-related ($1356 vs$1775; p\0.0001) PPPM outpatient costs compared with the abiraterone cohort. Allcause total costs (medical and pharmacy) PPPM ($8085 vs$9092; p = 0.0002) and PC-related total costs PPPM ($6321 vs$7280; p\0.0001) were significantly lower in the enzalutamide cohort compared with the abiraterone cohort. Conclusions: Enzalutamide-treated men with chemotherapy-naı ¨ve mCRPC had significantly lower resource utilization and healthcare costs compared with abiraterone-treated men. Plain Language Summary: Plain language summary available for this article.WOS:000516999800002Scopus - Affiliation ID: 60105072PMID: 32112280Science Citation Index ExpandedQ1 - Q2ArticleUluslararası işbirliği ile yapılan - EVETMayıs2020YÖK - 2019-2

Titanite Mineralization of Microbial Bioalteration Textures in Jurassic Volcanic Glass, Coast Range Ophiolite, California

Volcanic glasses are rarely preserved in the rock record, and the quality of preservation generally declines with increasing age. Records preserved in ancient basaltic glasses therefore provide important links between processes operating in the distant past, and those that are active on the Earth today. Microbial colonization has been linked to the formation of characteristic structures in basaltic glass, including tubules and granule-filled tubules, which are thought to be produced by microbially mediated glass dissolution. Structures of similar occurrence and morphology but filled almost entirely with fine-grained titanite have been documented in some ancient metabasalts. It has been suggested that the ancient titanite-mineralized structures are mineralized equivalents of hollow tubules in modern glassy basaltic rocks, but a direct link has not been firmly established. We report the discovery of tubular bioalteration structures in fresh and minimally altered basaltic glasses of middle Jurassic (164 Ma) age from the Stonyford Volcanic Complex (SFVC), Coast Range Ophiolite, California. Tubular structures hosted in unaltered basaltic glass are typically hollow, whilst those in zones of zeolitic alteration are mineralized by titanite. Tubules are continuous across zeolite-glass interfaces, which mark an abrupt change from titanite-filled to hollow tubules, demonstrating that titanite growth occurs preferentially within pre-existing tubular structures. Titanite mineralization in the SFVC represent a link between tubular structures in modern basaltic glass and titanite-mineralized features of similar morphology and spatial distribution in ancient metabasalts. Our observations support a link between textures in modern glassy basaltic rocks and some of the oldest-known putative ichnofossils

Maternal but Not Paternal Association of Ambulatory Blood Pressure With Albumin Excretion in Young Offspring With Type 1 Diabetes

OBJECTIVE: Familial predisposition to hypertension has been associated with the development of diabetic nephropathy in adults, but there are limited data in adolescents. Our aim was to assess whether parental ambulatory blood pressure (ABP) was associated with ABP and albumin excretion in young offspring with type 1 diabetes. RESEARCH DESIGN AND METHODS: Twenty-four-hour ABP monitoring was performed in 509 young offspring (mean +/- SD age 15.8 +/- 2.3 years) with type 1 diabetes, 311 fathers, and 444 mothers. Systolic (SBP) and diastolic blood pressure (DBP) measurements during 24 h, daytime, and nighttime were calculated. Three early morning urinary albumin-to-creatinine ratios (ACRs), A1C, and anthropometric parameters were available for the offspring. RESULTS: All paternal ABP parameters, except for nighttime SBP, were independently related to the offspring's ABP (24-h SBP beta = 0.18, 24-h DBP beta = 0.22, daytime SBP beta = 0.25, daytime DBP beta = 0.23, and nighttime DBP beta = 0.18; all P < 0.01). Maternal 24-h DBP (beta = 0.19, P = 0.004), daytime DBP (beta = 0.09, P = 0.04), and nighttime SBP (beta = 0.24 P = 0.001) were related to the corresponding ABP parameter in the offspring. Significant associations were found between the offspring's logACR and maternal ABP. The association with 24-h DBP (beta = 0.16, P = 0.02), daytime DBP (beta = 0.16 P = 0.02), and nighttime DBP (beta = 0.15 P = 0.03) persisted even after adjustment for the offspring's ABP. Mothers of offspring with microalbuminuria had higher ABP than mothers of offspring without microalbuminuria (all P < 0.05). CONCLUSIONS: In this cohort, parental ABP significantly influenced offspring blood pressure, therefore confirming familial influences on this trait. In addition, maternal ABP, particularly DBP, was closely related to ACR in the offspring, suggesting a dominant effect of maternal genes or an effect of the intrauterine environment on microalbuminuria risk

Single-Neuron Level One-Photon Voltage Imaging With Sparsely Targeted Genetically Encoded Voltage Indicators

Voltage imaging of many neurons simultaneously at single-cell resolution is hampered by the difficulty of detecting small voltage signals from overlapping neuronal processes in neural tissue. Recent advances in genetically encoded voltage indicator (GEVI) imaging have shown single-cell resolution optical voltage recordings in intact tissue through imaging naturally sparse cell classes, sparse viral expression, soma restricted expression, advanced optical systems, or a combination of these. Widespread sparse and strong transgenic GEVI expression would enable straightforward optical access to a densely occurring cell type, such as cortical pyramidal cells. Here we demonstrate that a recently described sparse transgenic expression strategy can enable single-cell resolution voltage imaging of cortical pyramidal cells in intact brain tissue without restricting expression to the soma. We also quantify the functional crosstalk in brain tissue and discuss optimal imaging rates to inform future GEVI experimental design

Prevalence of Abnormal Lipid Profiles and the Relationship With the Development of Microalbuminuria in Adolescents With Type 1 Diabetes

OBJECTIVE: To explore the prevalence of lipid abnormalities and their relationship with albumin excretion and microalbuminuria in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: The study population comprised 895 young subjects with type 1 diabetes (490 males); median age at the baseline assessment was 14.5 years (range 10-21.1), and median diabetes duration was 4.8 years (0.2-17). A total of 2,194 nonfasting blood samples were collected longitudinally for determination of total cholesterol, LDL cholesterol, HDL cholesterol, TG, and non-HDL cholesterol. Additional annually collected data on anthropometric parameters, A1C, and albumin-to-creatinine ratio (ACR) were available. RESULTS: Total cholesterol, LDL cholesterol, HDL cholesterol, and non-HDL cholesterol were higher in females than in males (all P 5.2 mmol/l (18.6%), non-HDL cholesterol >3.4 mmol/l (25.9%), TG >1.7 mmol/l (20.1%), and LDL cholesterol >3.4 mmol/l (9.6%). Age and duration were significantly related to all lipid parameters (P < 0.001); A1C was independently related to all parameters (P < 0.001) except HDL cholesterol, whereas BMI SD scores were related to all parameters (P < 0.05) except total cholesterol. Total cholesterol and non-HDL cholesterol were independently related to longitudinal changes in ACR (B coefficient +/- SE): 0.03 +/- 0.01/1 mmol/l, P = 0.009, and 0.32 +/- 0.014/1 mmol/l, P = 0.02, respectively. Overall mean total cholesterol and non-HDL cholesterol were higher in microalbuminuria positive (n = 115) than in normoalbuminuric subjects (n = 780): total cholesterol 4.7 +/- 1.2 vs. 4.5 +/- 0.8 mmol/l (P = 0.04) and non-HDL cholesterol 3.2 +/- 1.2 vs. 2.9 +/- 0.8 mmol/l (P = 0.03). CONCLUSIONS: In this longitudinal study of adolescents with type 1 diabetes, sustained lipid abnormalities were related to age, duration, BMI, and A1C. Furthermore, ACR was related to both total cholesterol and non-HDL cholesterol, indicating a potential role in the pathogenesis of diabetic nephropathy

Integrated Analyses of microRNAs Demonstrate Their Widespread Influence on Gene Expression in High-Grade Serous Ovarian Carcinoma

The Cancer Genome Atlas (TCGA) Network recently comprehensively catalogued the molecular aberrations in 487 high-grade serous ovarian cancers, with much remaining to be elucidated regarding the microRNAs (miRNAs). Here, using TCGA ovarian data, we surveyed the miRNAs, in the context of their predicted gene targets.Integration of miRNA and gene patterns yielded evidence that proximal pairs of miRNAs are processed from polycistronic primary transcripts, and that intronic miRNAs and their host gene mRNAs derive from common transcripts. Patterns of miRNA expression revealed multiple tumor subtypes and a set of 34 miRNAs predictive of overall patient survival. In a global analysis, miRNA:mRNA pairs anti-correlated in expression across tumors showed a higher frequency of in silico predicted target sites in the mRNA 3'-untranslated region (with less frequency observed for coding sequence and 5'-untranslated regions). The miR-29 family and predicted target genes were among the most strongly anti-correlated miRNA:mRNA pairs; over-expression of miR-29a in vitro repressed several anti-correlated genes (including DNMT3A and DNMT3B) and substantially decreased ovarian cancer cell viability.This study establishes miRNAs as having a widespread impact on gene expression programs in ovarian cancer, further strengthening our understanding of miRNA biology as it applies to human cancer. As with gene transcripts, miRNAs exhibit high diversity reflecting the genomic heterogeneity within a clinically homogeneous disease population. Putative miRNA:mRNA interactions, as identified using integrative analysis, can be validated. TCGA data are a valuable resource for the identification of novel tumor suppressive miRNAs in ovarian as well as other cancers

PRC1-mediated epigenetic programming is required to generate the ovarian reserve

10 p.-4 fig.The ovarian reserve defines the female reproductive lifespan, which in humans spans decades due to robust maintenance of meiotic arrest in oocytes residing in primordial follicles. Epigenetic reprogramming, including DNA demethylation, accompanies meiotic entry, but the chromatin changes that underpin the generation and preservation of ovarian reserves are poorly defined. We report that the Polycomb Repressive Complex 1 (PRC1) establishes repressive chromatin states in perinatal mouse oocytes that directly suppress the gene expression program of meiotic prophase-I and thereby enable the transition to dictyate arrest. PRC1 dysfuction causes depletion of the ovarian reserve and leads to premature ovarian failure. Our study demonstrates a fundamental role for PRC1-mediated gene silencing in female reproductive lifespan, and reveals a critical window of epigenetic programming required to establish ovarian reserve.Funding sources: National Institutes of Health grants R01GM122776 and R35GM141085 to S.H.N.Peer reviewe