Inflammation, dysregulated metabolism and aromatase in obesity and breast cancer.

Obesity is associated with an increased risk of estrogen-dependent breast cancer after menopause. Adipose tissue undergoes important changes in obesity due to excess storage of lipids, leading to adipocyte cell death and the recruitment of macrophages. The resultant state of chronic low-grade inflammation is associated with the activation of NFkB signaling and elevated levels of aromatase, the rate-limiting enzyme in estrogen biosynthesis.

Effect of body position and ventilation on umbilical artery and venous blood flows during delayed umbilical cord clamping in preterm lambs.

Objective: While delayed umbilical cord clamping (UCC) is thought to facilitate placental to infant blood transfusion, the physiological factors regulating flow in the umbilical arteries and veins during delayed UCC is unknown. We investigated the effects of gravity, by changing fetal height relative to the placenta, and ventilation on umbilical blood flows and the cardiovascular transition during delayed UCC at birth.

Methods: Catheters and flow probes were implanted into preterm lambs (128 days) prior to delivery to measure pulmonary, carotid, umbilical artery (UaBF) and umbilical venous (UvBF) blood flows.

Axitinib Has Antiangiogenic and Antitumorigenic Activity in Myxoid Liposarcoma.

Myxoid liposarcoma is a rare form of soft-tissue sarcoma. Although most patients initially respond well to treatment, approximately 21% relapse, highlighting the need for alternative treatments. To identify novel treatment regimens and gain a better understanding of myxoid liposarcoma tumor biology, we screened various candidate and approved targeted therapeutics and chemotherapeutics against myxoid liposarcoma cell lines.

DNA methylation mediated up-regulation of TERRA non-coding RNA is coincident with elongated telomeres in the human placenta.

Study Question: What factors regulate elongated telomere length in the human placenta?

Summary Answer: Hypomethylation of TERRA promoters in the human placenta is associated with high TERRA expression, however, no clear mechanistic link between these phenomena and elongated telomere length in the human placenta was found.

What Is Known Already: Human placenta tissue and trophoblasts show longer telomere lengths compared to gestational age-matched somatic cells. However, telomerase (hTERT) expression and activity in the placenta is low, suggesting a role for an alternative lengthening of telomeres (ALT).

Bacterial membrane vesicles: Biogenesis, immune regulation and pathogenesis.

Outer membrane vesicles were first described approximately 50 years ago and for many years were considered to be an artifact of bacterial growth. Since that initial discovery, it has become evident that outer membrane vesicles are produced by almost all Gram-negative bacteria as part of their normal growth in addition to driving pathogenesis within the host. More recently, the identification of membrane vesicle (MV) production by some Gram-positive bacteria, parasites, fungi, mycobacteria and infected host cells has significantly broadened the field of MV research and emphasized their importance to pathogenesis.

Effect of betamethasone, surfactant, and positive end-expiratory pressures on lung aeration at birth in preterm rabbits.

Antenatal glucocorticoids, exogenous surfactant, and positive end-expiratory pressure (PEEP) ventilation are commonly provided to preterm infants to enhance respiratory function after birth. It is unclear how these treatments interact to improve the transition to air-breathing at birth. We investigated the relative contribution of antenatal betamethasone, prophylactic surfactant, and PEEP (3 cmHO) on functional residual capacity (FRC) and dynamic lung compliance (C) in preterm (28 day GA) rabbit kittens at birth.

Developmental origins of male subfertility: role of infection, inflammation, and environmental factors.

Male gamete development begins with the specification of primordial cells in the epiblast of the early embryo and is not complete until spermatozoa mature in the epididymis of adult males. This protracted developmental process involves extensive alteration of the paternal germline epigenome. Initially, epigenetic reprogramming in fetal germ cells results in removal of most DNA methylation, including parent-specific epigenetic information.

The timing of umbilical cord clamping at birth: physiological considerations.

While it is now recognized that umbilical cord clamping (UCC) at birth is not necessarily an innocuous act, there is still much confusion concerning the potential benefits and harms of this common procedure. It is most commonly assumed that delaying UCC will automatically result in a time-dependent net placental-to-infant blood transfusion, irrespective of the infant's physiological state. Whether or not this occurs, will likely depend on the infant's physiological state and not on the amount of time that has elapsed between birth and umbilical cord clamping (UCC).

Reliability of Single-Use PEEP-Valves Attached to Self-Inflating Bags during Manual Ventilation of Neonates--An In Vitro Study.

Introduction: International resuscitation guidelines suggest to use positive end-expiratory pressure (PEEP) during manual ventilation of neonates. Aim of our study was to test the reliability of self-inflating bags (SIB) with single-use PEEP valves regarding PEEP delivery and the effect of different peak inflation pressures (PIP) and ventilation rates (VR) on the delivered PEEP.

Methods: Ten new single-use PEEP valves from 5 manufacturers were tested by ventilating an intubated 1 kg neonatal manikin containing a lung model with a SIB that was actuated by an electromechanical plunger device.

Pluripotent stem cells progressing to the clinic.

Basic experimental stem cell research has opened up the possibility of many diverse clinical applications; however, translation to clinical trials has been restricted to only a few diseases. To broaden this clinical scope, pluripotent stem cell derivatives provide a uniquely scalable source of functional differentiated cells that can potentially repair damaged or diseased tissues to treat a wide spectrum of diseases and injuries. However, gathering sound data on their distribution, longevity, function and mechanisms of action in host tissues is imperative to realizing their clinical benefit.

Stem Cell Therapies in Clinical Trials: Progress and Challenges.

Clinical investigations using stem cell products in regenerative medicine are addressing a wide spectrum of conditions using a variety of stem cell types. To date, there have been few reports of safety issues arising from autologous or allogeneic transplants. Many cells administered show transient presence for a few days with trophic influences on immune or inflammatory responses.

Analysis of ER-mitochondria contacts using correlative fluorescence microscopy and soft X-ray tomography of mammalian cells.

Mitochondrial fission is important for organelle transport, quality control and apoptosis. Changes to the fission process can result in a wide variety of neurological diseases. In mammals, mitochondrial fission is executed by the GTPase dynamin-related protein 1 (Drp1; encoded by DNM1L), which oligomerizes around mitochondria and constricts the organelle.

Stem Cell Research.

Stem cells have great potential in basic research and are being slowly integrated into toxicological research. This symposium provided an overview of the state of the field, stem cell models, described allogenic stem cell treatments and issues of immunogenicity associated with protein therapeutics, and tehn concentrated on stem cell uses in regenerative medicine focusing on lung and testing strategies on engineered tissues from a pathologist's perspective.