Association between vitamin D status and age-related macular degeneration by genetic risk.

Importance: Deficient 25-hydroxyvitamin D (25[OH]D) concentrations have been associated with increased odds of age-related macular degeneration (AMD).

Objective: To examine whether this association is modified by genetic risk for AMD and whether there is an association between AMD and single-nucleotide polymorphisms of genes involved in vitamin D transport, metabolism, and genomic function.

Design, Setting, And Participants: Postmenopausal women (N = 913) who were participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS) (aged 54 to <75 years) with available serum 25(OH)D concentrations (assessed October 1, 1993, to December 31, 1998), genetic data, and measures of AMD (n = 142) assessed at CAREDS baseline from May 14, 2001, through January 31, 2004, were studied.

Managing Endometrial Cancer: The Role of Pelvic Lymphadenectomy and Secondary Surgery.

Purpose: In November 2010, the French National Cancer Institute published new guidelines for managing endometrial cancer. Pelvic lymphadenectomy is not indicated for preoperative low-intermediate risk type 1 endometrial cancer, and high-risk patients should undergo secondary surgery with para-aortic lymphadenectomy. This study evaluated these new guidelines with regard to overall survival (OS), relapse-free survival (RFS), and morbidity for patients with low-intermediate risk disease.

A Simple Laparoscopic Procedure to Restore a Normal Vaginal Length After Colpohysterectomy With Large Upper Colpectomy for Cervical and/or Vaginal Neoplasia.

Colpohysterectomy is sometimes associated with a large upper colpectomy resulting in a shortened vagina, potentially impacting sexual function. We report on a preliminary experience of a laparoscopic colpoplasty to restore a normal vaginal length. Patients with shortened vaginas after a laparoscopic colpohysterectomy were considered for a laparoscopic modified Davydov's procedure to create a new vaginal vault using the peritoneum of the rectum and bladder.

Extraperitoneal Para-aortic Lymphadenectomy by Robot-Assisted Laparoscopy in Gynecologic Oncology: Preliminary Experience and Advantages and Limitations.

Background: We are reporting the preliminary multicentric experience in extraperitoneal para-aortic lymphadenectomy by robot-assisted laparoscopy (EPLRL) in gynecologic oncology.

Materials And Methods: Two teams from the cancer centers performed EPLRL in 37 patients with gynecologic cancer.

Results: There were 30 patients with cervical cancer, 6 with endometrial cancer, and 1 with adnexal cancer.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

Background: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision.

Methods: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE).

Development of a technique to detect the activated form of the progesterone receptor and correlation with clinical and histopathological characteristics of endometrioid adenocarcinoma of the uterine corpus.

Objective: Hormonal therapy is generally reserved for patients with endometrial cancers that fail cytotoxic chemotherapy, but there is a lack of sufficiently sensitive diagnostics to identify potential responders. We sought to develop a diagnostic technique to detect activated progesterone receptors (APR) in endometrial cancers using routine immunohistochemistry (IHC) and to correlate the presence of APR with other histopathological features and clinical disease stage.

Methods: Seventy-two tumor block specimens from patients with endometrial cancer were processed with conventional IHC methods for estrogen receptor-α (ERα), progesterone receptor (PR) and Ki67, a marker of proliferation.

The Relationship Between Serum 25-Hydroxyvitamin D Levels and Nuclear Cataract in the Carotenoid Age-Related Eye Study (CAREDS), an Ancillary Study of the Women's Health Initiative.

Purpose: To investigate the relationship between serum 25-hydroxyvitamin D (25[OH]D) levels and nuclear cataract among participants of the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative (WHI) Observational Study (OS).

Methods: Nuclear cataract was assessed from slit lamp photographs (2001-2004) taken 6 years after collecting serum analyzed for 25(OH)D levels at WHI baseline (1994-1998) in 1278 CAREDS participants age 50 to 79 years. Multivariate (age, iris color, smoking, pulse pressure) odds ratios (ORs) for nuclear cataract (nuclear opacities > level 4 or cataract extraction) by quintiles of serum 25(OH)D were estimated using logistic regression.

Calcium and vitamin D supplementation do not influence menopause-related symptoms: Results of the Women's Health Initiative Trial.

Background: It is unknown whether supplementation with calcium and vitamin D has an impact on menopause-related symptoms.

Methods: As part of the Women's Health Initiative Calcium/Vitamin D Supplementation Trial (CaD), women were randomized at 40 clinical sites to elemental calcium carbonate 1000 mg with vitamin D 400 IU daily or placebo. At the CaD baseline visit (year 1 or year 2) and during a mean follow-up of 5.

Adolescent endogenous sex hormones and breast density in early adulthood.

Introduction: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer.

Methods: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25-29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997.

Impaired Skeletal Muscle Oxygenation and Exercise Tolerance in Pulmonary Hypertension.

Background: Limb muscle dysfunction is documented in pulmonary arterial hypertension (PAH), but little is known regarding muscle oxygen (O2) supply and its possible effects on exercise tolerance in PAH.

Methods: Ten patients with PAH and 10 matched controls underwent progressive maximal cardiopulmonary exercise test, voluntary and nonvolitional dominant quadriceps muscle strength measures, and nondominant quadriceps biopsy to assess maximal oxygen uptake, muscle function, and lower limb fiber type and capillarity, respectively. Both groups then performed normoxic and hyperoxic submaximal intensity exercise protocol at the same absolute workload during which muscle O2 supply was assessed by measuring changes in myoglobin-deoxyhemoglobin level (Δ[Mb-HHb]) and tissue oxygenation index in the dominant quadriceps using near-infrared spectroscopy.

In silico discovery and validation of potent small-molecule inhibitors targeting the activation function 2 site of human oestrogen receptor α.

Introduction: Current approaches to inhibit oestrogen receptor-alpha (ERα) are focused on targeting its hormone-binding pocket and have limitations. Thus, we propose that inhibitors that bind to a coactivator-binding pocket on ERα, called activation function 2 (AF2), might overcome some of these limitations.

Methods: In silico virtual screening was used to identify small-molecule ERα AF2 inhibitors.

What is the normal tissues morbidity following Helical Intensity Modulated Radiation Treatment for cervical cancer?

Background And Purpose: To report on normal tissues morbidity following IMRT for cervix cancer.

Material And Methods: The first 61 patients of a prospective series were included. 50 Gy to the PTV 1(pelvis) and 60 Gy to the PTV 2 (centro-pelvic disease and GTV nodes) were delivered concomitantly in 28 fractions, followed by a brachytherapy boost.

Provider beliefs about diabetes treatment have little impact on glycemic control of their patients with diabetes.

Objective: To improve the health of people with diabetes, it is essential to identify why patients experience extended periods of poor glycemic control before therapeutic intensification.

Research Design And Methods: We surveyed 252 primary care providers at Kaiser Permanente Northwest to determine their beliefs about the glycemic goals of their patients, treatment intensification behavior, and barriers to achieving optimal glycemic control. We linked the responses of 149 providers to the health records of their 18 346 patients with diabetes.

Women's attitudes towards a pre-conception healthy lifestyle programme.

Nearly half of US women begin pregnancy overweight or obese and more than half of overweight or obese pregnant women experience excessive gestational weight gain. Recent lifestyle intervention programmes have helped women avoid excessive weight gain during pregnancy, but helping women lose weight before pregnancy may be a more effective way to improve pregnancy outcomes. This study assessed women's attitudes towards pre-conception diet and weight management interventions.

Contribution of lymphoscintigraphy to intraoperative sentinel lymph node detection in early cervical cancer: Analysis of the prospective multicenter SENTICOL cohort.

Purpose: To evaluate the contribution of preoperative lymphoscintigraphy to intraoperative lymphatic mapping (ILM) in early cervical cancer

Methods: We conducted an ancillary analysis of the multicenter prospective SENTICOL study in early cervical cancer. Radiocolloid was injected intracervically on the day before (long protocol) or morning of (short protocol) surgery, lymphoscintigraphy was performed, and the results of a centralized image review were communicated to the surgeons. ILM was performed on combined radioactivity/patent blue detection.

Minimally invasive surgical management of early-stage cervical cancer: an analysis of the risk factors of surgical complications and of oncologic outcomes.

Objectives: The objective of this study was to evaluate the morbidity and the oncologic outcomes of laparoscopic radical hysterectomy in treating early-stage cervical cancer.

Methods: We included all patients with early-stage cervical cancer (IA, IB1, IIA1, and IIB), as assessed by the Federation International of Gynecology and Obstetrics staging criteria, undergoing laparoscopic radical hysterectomy from January 1999 to December 2013 in our center. Morbidity was classified according to the Clavien and Dindo classification.

Menopausal symptoms in women with chronic kidney disease.

Objective: This study aims to determine whether menopausal symptoms differed between women with chronic kidney disease (CKD) and women without CKD, and whether CKD modified associations of late vasomotor symptoms (VMS) with mortality and/or cardiovascular events.

Methods: CKD, defined as estimated glomerular filtration rate lower than 60 mL/minute/1.73 m (using the Chronic Kidney Disease Epidemiology Collaboration equation), was determined in 17,891 postmenopausal women, aged 50 to 79 years at baseline, in the multiethnic Women's Health Initiative cohort.

Birthweight, mediating biomarkers and the development of type 2 diabetes later in life: a prospective study of multi-ethnic women.

Aims/hypothesis: The aim of this work was to investigate the prospective relationship between low birthweight (LBW) and type 2 diabetes risk later in life and the mediation effects of type 2 diabetes biomarkers linking LBW to type 2 diabetes risk.

Methods: We measured baseline plasma concentrations of various type 2 diabetes biomarkers in 1,259 incident type 2 diabetes cases and 1,790 controls in the Women's Health Initiative-Observational Study. Self-report birthweights of the participants were recorded.

Associations of menopausal vasomotor symptoms with fracture incidence.

Context: Vasomotor symptoms (VMS) are common. Whether VMS are associated with fracture incidence or bone mineral density (BMD) levels is unknown.

Objective: This study aimed to examine associations of baseline VMS with fracture incidence and BMD.

Role of a double docking to improve lymph node dissection: when robotically assisted laparoscopy for para-aortic lymphadenectomy is associated to a pelvic procedure.

Objective: The objective of this study was to demonstrate that robotically assisted laparoscopy for aortic lymph node dissection was improved when double docking (DD) of the Da Vinci system is used for combined surgical procedures [defined by the combination of a pelvic procedure and a para-aortic lymphadenectomy (PAL)].

Methods: From February 2007 to February 2013, 41 patients underwent combined procedures including PAL up to the left renal vein in 2 cancer centers. We used 2 different approaches as follows: a single docking (SD) of the Da Vinci system (transperitoneal PAL and pelvic surgery) during the first period (22 patients) and a DD during the second period (19 patients).

Identification of a potent antiandrogen that targets the BF3 site of the androgen receptor and inhibits enzalutamide-resistant prostate cancer.

There has been a resurgence of interest in the development of androgen receptor (AR) inhibitors with alternative modes of action to overcome the development of resistance to current therapies. We demonstrated previously that one promising strategy for combatting mutation-driven drug resistance is to target the Binding Function 3 (BF3) pocket of the receptor. Here we report the development of a potent BF3 inhibitor, 3-(2,3-dihydro-1H-indol-2-yl)-1H-indole, which demonstrates excellent antiandrogen potency and anti-PSA activity and abrogates the androgen-induced proliferation of androgen-sensitive (LNCaP) and enzalutamide-resistant (MR49F) PCa cell lines.