Palbociclib in Combination with either Aromatase Inhibitors or Fulvestrant for Patients with Advanced HR+/HER2- Breast Cancer in Germany: Final Results of the Phase 2 Multicohort INGE-B Trial.

Introduction: The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, so far lacking evidence for efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated.

Methods: The prospective, multicenter, multicohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany.

Structural Requirements for the Outpatient Treatment of Benign Diseases of the Uterus.

In many cases, outpatient surgical treatment of benign diseases of the uterus has advantages over inpatient care. This has been demonstrated by the healthcare situation in other countries. However, the prerequisite for the provision of outpatient services is that this does not lead to any impairment in the quality of care or of patient safety.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole.

Background: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials.

Clinical Significance of the Immunohistochemical Expression of Histone Deacetylases (HDACs)-2, -4, and -5 in Ovarian Adenocarcinomas.

Background: Histone deacetylases (HDACs) are implicated in carcinogenesis, and HDAC inhibitors (HDACis) are explored as a therapeutic tool in several tumors. The aim of this study was to evaluate the clinical significance of HDAC-2, -4, and -5 expression in epithelial ovarian carcinoma (EOC).

Methods: HDAC-2, -4, and -5 immunohistochemical expression was examined in 92 EOC tissue specimens and was correlated with clinicopathological characteristics.

Immunometric and functional measurement of endogenous vasoinhibin in human sera.

Introduction: Circulating levels of the antiangiogenic protein vasoinhibin, a fragment of prolactin, are of interest in vasoproliferative retinopathies, preeclampsia, and peripartum cardiomyopathy; however, it is difficult to determine the circulating levels of vasoinhibin due to the lack of quantitative assays.

Methods: This study used human serum samples to assess the concentration and bioactivity of vasoinhibin using a novel enzyme-linked immunosorbent assay (ELISA) for human vasoinhibin, which employs an anti-vasoinhibin monoclonal antibody, a human umbilical vein endothelial cell (HUVEC) proliferation assay, and a chick chorioallantoic membrane (CAM) angiogenesis assay.

Results: Serum samples from 17 pregnant women without (one group) and with preeclampsia and pregnancy induced hypertension (another group) demonstrated endogenous vasoinhibin concentrations in the range of 5-340 ng/ml.

Interaction of barn owl leading edge serrations with freestream turbulence.

The silent flight of barn owls is associated with wing and feather specialisations. Three special features are known: a serrated leading edge that is formed by free-standing barb tips which appears as a comb-like structure, a soft dorsal surface, and a fringed trailing edge. We used a model of the leading edge comb with 3D-curved serrations that was designed based on 3D micro-scans of rows of barbs from selected barn-owl feathers.

Total Pelvic Floor Lifting: A New Approach for the Anatomic Repair of Pelvic Floor Hypermobility and Vaginal Laxity in Parous Women.

Recent years have seen a steady increase in the information available regarding pelvic floor changes after childbirth. Obstetric trauma, to which all structures of the urogenital sphere are subjected, can affect different anatomical areas, including the vagina, perineum, deep pelvic floor muscles, and sphincter. Main complaints of parous women with regard to their pelvic floor are vaginal laxity, a wide introitus, and increased mobility of the uterus.

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice.

Retrospective analysis of apical prolapse correction by unilateral pectineal suspension: perioperative and short-term results.

Introduction And Hypothesis: We have previously published the novel method of unilateral pectineal suspension (UPS) for apical prolapse correction. UPS provides mesh-free midline uterus suspension using a single non-absorbable suture to attach the anterior cervix to the lateral part of the iliopectineal ligament. The purpose of this retrospective cohort study was to analyze the short-term efficacy, perioperative complication rate, and overall patient acceptance of the new UPS surgical concept.

The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis.

Misalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery.

Sea lions could use multilateration localization for object tracking as tested with bio-inspired whisker arrays.

Previous behavioural research on live sea lions has shown that they are able to detect the direction of oncoming vortices, even when impacting contralaterally. These experiments showed that the whisker system and the animal's neural processing is seemingly able to detect the Direction of Arrival (DoA) from just one side of the heads vibrissal pads. Therefore, temporal differences between whisker stimulation is a likely method for determining the angle.

A review of simulation experiment techniques used to analyze wildfire effects on water quality and supply.

This review addresses the critical knowledge gap of techniques simulating combustion and heating characteristics present in natural wildfires and their use in assessing postfire impacts on water quality and quantity. Our assessment includes both laboratory and plot-scale techniques with burn and rainfall simulation components. Studies included focus on advancing understanding of changes in chemical and physical properties of soil, as well as subsequent runoff changes.

Unilateral pectineal suspension - A new surgical approach for apical correction of pelvic organ prolapse.

Background And Objectives: There are numerous vaginal and abdominal surgical approaches for the treatment of pelvic organ prolapse (POP). Even the standard techniques show great variability due to modifications depending on anatomy, available instruments and materials. Recently, the role of hysterectomy in prolapse surgery as well as the use of synthetic meshes have been questioned.

HS in Critical Illness-A New Horizon for Sodium Thiosulfate?

Ever since the discovery of endogenous HS and the identification of its cytoprotective properties, efforts have been made to develop strategies to use HS as a therapeutic agent. The ability of HS to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous HS, nor the administration of inorganic HS-releasing salts or slow-releasing HS-donors are feasible for clinical use.

An organoid model derived from human adipose stem/progenitor cells to study adipose tissue physiology.

We established a functional adipose organoid model system for human adipose stem/progenitor cells (ASCs) isolated from white adipose tissue (WAT). ASCs were forced to self-aggregate by a hanging-drop technique. Afterwards, spheroids were transferred into agar-coated cell culture dishes to avoid plastic-adherence and dis-aggregation.

Human Placental Tissue Contains A Placental Lactogen-Derived Vasoinhibin.

Hormonal factors affecting the vascular adaptions of the uteroplacental unit in noncomplicated and complicated pregnancies are of interest. Here, 4 human placentas from women with and without preeclampsia (PE) were investigated for the presence of placental lactogen (PL)-derived, antiangiogenic vasoinhibin. Western blotting and mass spectrometry of placental tissue revealed the presence of a 9-kDa PL-derived vasoinhibin, the normal 22-kDa full-length PL, and a 28-kDa immunoreactive protein of undetermined nature.

Robotic mesh-supported pectopexy for pelvic organ prolapse: expanding the options of pelvic floor repair.

Pelvic organ prolapse affects 30-50% of the female population. For definitive treatment surgery is unavoidable. Sacrocolpopexy has been the gold standard for anatomical correction of pelvic organ prolapse since the 1990s.

Quiescence, Stemness and Adipogenic Differentiation Capacity in Human DLK1/CD34/CD24 Adipose Stem/Progenitor Cells.

We explore the status of quiescence, stemness and adipogenic differentiation capacity in adipose stem/progenitor cells (ASCs) ex vivo, immediately after isolation from human subcutaneous white adipose tissue, by sorting the stromal vascular fraction into cell-surface DLK1/CD34, DLK1/CD34 and DLK1/CD34 cells. We demonstrate that DLK1/CD34 cells, the only population exhibiting proliferative and adipogenic capacity, express ex vivo the bonafide quiescence markers p21, p27 and p57 but neither proliferation markers nor the senescence marker p16. The pluripotency markers NANOG, SOX2 and OCT4 are barely detectable in ex vivo ASCs while the somatic stemness factors, c-MYC and KLF4 and the early adipogenic factor C/EBPβ are highly expressed.

Survival benefit of tamoxifen in male breast cancer: prospective cohort analysis.

Background: Due to the lack of prospective data, current treatment of male breast cancer (MBC) is based on information obtained from retrospective analysis or by extrapolation from studies on female patients. In this prospectively enrolled cohort study, we retrospectively examined the survival effect of tamoxifen in MBC patients.

Methods: In this prospectively enrolled cohort study, 448 patients with MBC were treated between May 2009 and June 2018.

High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia.

Safe and efficacious pan-genotypic direct-acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF + DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016.

Sprouty1 Prevents Cellular Senescence Maintaining Proliferation and Differentiation Capacity of Human Adipose Stem/Progenitor Cells.

The role of Ras-Mitogen-activated protein kinase (MAPK) signaling in cellular aging is not precisely understood. Recently, we identified Sprouty1 (SPRY1) as a weight-loss target gene in human adipose stem/progenitor cells (ASCs) and showed that Sprouty1 is important for proper regulation of adipogenesis. In the present study, we show that loss-of-function of Sprouty1 by CRISPR/Cas9-mediated genome editing in human ASCs leads to hyper-activation of MAPK signaling and a senescence phenotype.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

Background: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole.