On metastability and Markov state models for non-stationary molecular dynamics.

Unlike for systems in equilibrium, a straightforward definition of a metastable set in the non-stationary, non-equilibrium case may only be given case-by-case-and therefore it is not directly useful any more, in particular in cases where the slowest relaxation time scales are comparable to the time scales at which the external field driving the system varies. We generalize the concept of metastability by relying on the theory of coherent sets. A pair of sets A and B is called coherent with respect to the time interval [t, t] if (a) most of the trajectories starting in A at t end up in B at t and (b) most of the trajectories arriving in B at t actually started from A at t.

Predictive model of limestone scaling in ammonia stripping towers and its experimental validation on a treatment plant fed by MSW leachate-polluted groundwater.

Groundwater pollution by municipal solid waste (MSW) landfill leachate is a global concern. Stripping towers are one of the most implemented techniques for the removal of ammonia pollution. This study presents a predictive computational model to estimate calcium carbonate precipitation in ammonia stripping towers.

Multifocality in Sporadic Medullary Thyroid Carcinoma: An International Multicenter Study.

Background: Current surgical standard of care in sporadic medullary thyroid carcinoma (sMTC) consists of a minimum of total thyroidectomy with central neck dissection. Some have suggested thyroid lobectomy with isthmusectomy and central neck dissection for patients with sMTC, given their lower frequency of bilateral disease, although this topic has not been thoroughly studied. This study assessed the prevalence of multifocality in sMTC via a large international multi-institutional retrospective review to quantify this prevalence, including the impact of geography, to assess more accurately the risks associated with alternative surgical approaches.

ECG is an inefficient screening-tool for left ventricular hypertrophy in normotensive African children population.

Background: Left ventricular hypertrophy (LVH) is a marker of pediatric hypertension and predicts development of cardiovascular events. Electrocardiography (ECG) screening is used in pediatrics to detect LVH thanks to major accessibility, reproducibility and easy to use compared to transthoracic echocardiography (TTE), that remains the standard technique. Several diseases were previously investigated, but no data exists regarding our study population.

PML/RARa inhibits PTEN expression in hematopoietic cells by competing with PU.1 transcriptional activity.

Acute promyelocitic leukemia (APL) is characterized by the pathognomonic presence in leukemic blasts of the hybrid protein PML/RARA, that acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid differentiation. Here, we show that primary blasts from APL patients express lower levels of the oncosuppressor protein PTEN, as compared to blast cells from other AML subtypes or normal bone marrow, and demonstrate that PML-RARA directly inhibits PTEN expression. We show that All-Trans Retinoic Acid (ATRA) triggers in APL cells an active chromatin status at the core regulatory region of the PTEN promoter, that allows the binding of the myeloid-regulating transcription factor PU.

Prevalence of Cardiovascular Disease and Osteoporosis During Androgen Deprivation Therapy Prescription Discordant to EAU Guidelines: Results From a Multicenter, Cross-sectional Analysis From the CHOsIng Treatment for Prostate canCEr (CHOICE) Study.

Objective: To analyze the prevalence of cardiovascular disease (CVD) and osteoporosis in patients treated with androgen deprivation therapy (ADT) for prostate cancer (PCa) but not adherent to European Association of Urology (EAU) guidelines.

Materials And Methods: The CHOosIng Treatment for Prostate CanCEr (CHOICE) study was an Italian multicenter, cross-sectional study conducted from December 2010 to January 2012. A total of 1386 patients treated with ADT for PCa (first prescription or renewal of ADT) were selected.

The aurora kinase inhibitor VX-680 shows anti-cancer effects in primary metastatic cells and the SW13 cell line.

New therapeutic targets are needed to fight cancer. Aurora kinases (AK) were recently identified as vital key regulators of cell mitosis and have consequently been investigated as therapeutic targets in preclinical and clinical studies. Aurora kinase inhibitors (AKI) have been studied in many cancer types, but their potential capacity to limit or delay metastases has rarely been considered, and never in adrenal tissue.

Patient-reported impact of spondyloarthritis on work disability and working life: the ATLANTIS survey.

Background: The aim was to establish how patients experience the impact of spondyloarthritis (SpA) on work disability and working life.

Methods: The survey was performed in 17/20 regions in Italy (1 January to 31 March 2013). A multiple-choice questionnaire was published on the official website of the sponsor - the National Association of Rheumatic Patients (ANMAR) - and hard-copies were distributed at outpatient clinics for rheumatic patients.

The novel R347g pathogenic mutation of aromatic amino acid decarboxylase provides additional molecular insights into enzyme catalysis and deficiency.

We report here a clinical case of a patient with a novel mutation (Arg347→Gly) in the gene encoding aromatic amino acid decarboxylase (AADC) that is associated with AADC deficiency. The variant R347G in the purified recombinant form exhibits, similarly to the pathogenic mutation R347Q previously studied, a 475-fold drop of kcat compared to the wild-type enzyme. In attempting to unravel the reason(s) for this catalytic defect, we have carried out bioinformatics analyses of the crystal structure of AADC-carbidopa complex with the modelled catalytic loop (residues 328-339).

Targeting nuclear transporters in cancer: Diagnostic, prognostic and therapeutic potential.

The Karyopherin superfamily is a major class of soluble transport receptors consisting of both import and export proteins. The trafficking of proteins involved in transcription, cell signalling and cell cycle regulation among other functions across the nuclear membrane is essential for normal cellular functioning. However, in cancer cells, the altered expression or localization of nuclear transporters as well as the disruption of endogenous nuclear transport inhibitors are some ways in which the Karyopherin proteins are dysregulated.

Airborne toluene removal for minimizing occupational health exposure by means of a trickle-bed biofilter.

The paper presents the experimental results on a biotrickling pilot plant, with a water scrubber as pre-treatment, finalized to the treatment of an airborne toluene stream in a working place. The air stream was characterized by a very high variability of the inlet concentrations of toluene (range: 4.35-68.

Probabilistic Derivation of Spatiotemporal Correlation Functions in the Hydrodynamic Limit.

In this paper, we use probability theory to prove in suitable conditions the equivalence of equilibrium time correlation functions of microscopic density fields with the time correlation functions of local macroscopic density fields evolved by hydrodynamics in (approximate) phenomenological continuum theories of matter. We further discuss a useful and rigorous numerical algorithm, derived from this framework, to compute macroscopic space- and time-dependent behaviors (such as the hydrodynamical one) via molecular dynamics simulations.

The Challenging Intrauterine Contraceptive: In-office Hysteroscopic Approach.

Study Object: To describe 3 cases of misplaced or retained Intrauterine Contraceptive (IUC) that were successfully resolved by hysteroscopy performed in an ambulatory setting using miniaturized electrosurgical and mechanical operative instruments.

Design: Step-by-step description of the technique using slides, pictures, and video (educative video) (Canadian Task Force classification III).

Setting: Misplaced or retained IUC may be related to several causes; incorrect insertion is the leading cause.

Novel PPARγ Modulator GED-0507-34 Levo Ameliorates Inflammation-driven Intestinal Fibrosis.

Background: Intestinal fibrosis is mainly associated with Crohn's disease and is defined as a progressive and excessive deposition of extracellular matrix components. No specific antifibrotic therapies are available. In this study, we evaluate the antifibrotic effect of a novel 5-ASA analog able to activate the peroxisome proliferator-activated receptor γ, named GED-0507-34 Levo.

A Structural Model of the Human α7 Nicotinic Receptor in an Open Conformation.

Nicotinic acetylcholine receptors (nAchRs) are ligand-gated ion channels that regulate chemical transmission at the neuromuscular junction. Structural information is available at low resolution from open and closed forms of an eukaryotic receptor, and at high resolution from other members of the same structural family, two prokaryotic orthologs and an eukaryotic GluCl channel. Structures of human channels however are still lacking.

Importance of perforating vessels in nipple-sparing mastectomy: an anatomical description.

Background: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered.

Influence of denitrification reactor retention time distribution (RTD) on dissolved oxygen control and nitrogen removal efficiency.

Low concentrations of dissolved oxygen (DO) are usually found in biological anoxic pre-denitrification reactors, causing a reduction in nitrogen removal efficiency. Therefore, the reduction of DO in such reactors is fundamental for achieving good nutrient removal. The article shows the results of an experimental study carried out to evaluate the effect of the anoxic reactor hydrodynamic model on both residual DO concentration and nitrogen removal efficiency.

Mapping forest fuels through vegetation phenology: the role of coarse-resolution satellite time-series.

Traditionally fuel maps are built in terms of 'fuel types', thus considering the structural characteristics of vegetation only. The aim of this work is to derive a phenological fuel map based on the functional attributes of coarse-scale vegetation phenology, such as seasonality and productivity. MODIS NDVI 250 m images of Sardinia (Italy), a large Mediterranean island with high frequency of fire incidence, were acquired for the period 2000-2012 to construct a mean annual NDVI profile of the vegetation at the pixel-level.

Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line.

Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated.

Retinoic acid receptors: from molecular mechanisms to cancer therapy.

Retinoic acid (RA), the major bioactive metabolite of retinol or vitamin A, induces a spectrum of pleiotropic effects in cell growth and differentiation that are relevant for embryonic development and adult physiology. The RA activity is mediated primarily by members of the retinoic acid receptor (RAR) subfamily, namely RARα, RARβ and RARγ, which belong to the nuclear receptor (NR) superfamily of transcription factors. RARs form heterodimers with members of the retinoid X receptor (RXR) subfamily and act as ligand-regulated transcription factors through binding specific RA response elements (RAREs) located in target genes promoters.

HFE gene variants and iron-induced oxygen radical generation in idiopathic pulmonary fibrosis.

In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage. The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL).

Neutralization of TNFSF10 ameliorates functional outcome in a murine model of Alzheimer's disease.

Alzheimer's disease is one of the most common causes of death worldwide, with poor treatment options. A tissue landmark of Alzheimer's disease is accumulation of the anomalous protein amyloid-β in specific brain areas. Whether inflammation is an effect of amyloid-β on the Alzheimer's disease brain, or rather it represents a cause for formation of amyloid plaques and intracellular tangles remains a subject of debate.