Increased levels of extracellular ATP in glaucomatous retinas: Possible role of the vesicular nucleotide transporter during the development of the pathology.

Purpose: To study retinal extracellular ATP levels and to assess the changes in the vesicular nucleotide transporter (VNUT) expression in a murine model of glaucoma during the development of the disease.

Methods: Retinas were obtained from glaucomatous DBA/2J mice at 3, 9, 15, and 22 months together with C57BL/6J mice used as age-matched controls. To study retinal nucleotide release, the retinas were dissected and prepared as flattened whole mounts and stimulated in Ringer buffer with or without 59 mM KCl.

Neuroprotective Effect of Tauroursodeoxycholic Acid on N-Methyl-D-Aspartate-Induced Retinal Ganglion Cell Degeneration.

Retinal ganglion cell degeneration underlies the pathophysiology of diseases affecting the retina and optic nerve. Several studies have previously evidenced the anti-apoptotic properties of the bile constituent, tauroursodeoxycholic acid, in diverse models of photoreceptor degeneration. The aim of this study was to investigate the effects of systemic administration of tauroursodeoxycholic acid on N-methyl-D-aspartate (NMDA)-induced damage in the rat retina using a functional and morphological approach.

Impact of aromatase inhibitor treatment on vertebral morphology and bone mineral density in postmenopausal women with breast cancer.

Objective: The aim of this study was to evaluate the impact of aromatase inhibitor (AI) treatment on vertebral morphology by vertebral fracture assessment in postmenopausal women with early-stage breast cancer.

Methods: A clinical cross-sectional study was conducted. A group of 156 postmenopausal women with breast cancer (mean [SD] age, 60.

Chemical Library Screening and Structure-Function Relationship Studies Identify Bisacodyl as a Potent and Selective Cytotoxic Agent Towards Quiescent Human Glioblastoma Tumor Stem-Like Cells.

Cancer stem-like cells reside in hypoxic and slightly acidic tumor niches. Such microenvironments favor more aggressive undifferentiated phenotypes and a slow growing "quiescent state" which preserves them from chemotherapeutic agents that essentially target proliferating cells. Our objective was to identify compounds active on glioblastoma stem-like cells, including under conditions that mimick those found in vivo within this most severe and incurable form of brain malignancy.

The Still Bay and Howiesons Poort at Sibudu and Blombos: Understanding Middle Stone Age Technologies.

The classification of archaeological assemblages in the Middle Stone Age of South Africa in terms of diversity and temporal continuity has significant implications with respect to recent cultural evolutionary models which propose either gradual accumulation or discontinuous, episodic processes for the emergence and diffusion of cultural traits. We present the results of a systematic technological and typological analysis of the Still Bay assemblages from Sibudu and Blombos. A similar approach is used in the analysis of the Howiesons Poort (HP) assemblages from Sibudu seen in comparison with broadly contemporaneous assemblages from Rose Cottage and Klasies River Cave 1A.

A non-invasive prevention program model for the assessment of osteoporosis in the early postmenopausal period: a pilot study on FRAX(®) and QUS tools advantages.

Objective: The study analyses the performances of FRAX algorithm and quantitative ultrasound (QUS) tool in relationship to the dual-energy X-ray absorptiometry (DXA) categorization to identify patients at risk of osteoporosis during menopause and to reach new thresholds for recommending the first DXA examination.

Design: Retrospective cohort study.

Patients And Measurements: Two hundred eighty-two postmenopausal patients filled out a questionnaire which determined their FRAX index and performed a bone evaluation by QUS of the calcaneus to determine their stiffness index (SI).

A Milk and Ochre Paint Mixture Used 49,000 Years Ago at Sibudu, South Africa.

Gas chromatography/mass spectrometry, proteomic and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM/EDS) analyses of residue on a stone flake from a 49,000 year-old layer of Sibudu (South Africa) indicate a mixture of ochre and casein from milk, likely obtained by killing a lactating wild bovid. Ochre powder production and use are documented in Middle Stone Age South African sites but until now there has been no evidence of the use of milk as a binder. Our analyses show that this ochre-based mixture was neither a hafting adhesive nor a residue left after treating animal skins, but a liquid mixture consisting of a powdered pigment mixed with milk; in other words, a paint medium that could have been applied to a surface or to human skin.

Maternal depressive symptoms during pregnancy, placental expression of genes regulating glucocorticoid and serotonin function and infant regulatory behaviors.

Background: Glucocorticoids and serotonin may mediate the link between maternal environment, fetal brain development and 'programming' of offspring behaviors. The placenta regulates fetal exposure to maternal hormonal signals in animal studies, but few data address this in humans. We measured prospectively maternal depressive symptoms during pregnancy and mRNAs encoding key gene products determining glucocorticoid and serotonin function in term human placenta and explored associations with infant regulatory behaviors.

Anti-metastatic outcome of isoform-specific prolactin receptor targeting in breast cancer.

Controversy exists concerning the role of the long prolactin receptor (PRLR) in the progression of breast cancer. By targeting pre-mRNA splicing, we succeeded in knocking down only the long PRLR in vivo, leaving the short forms unaffected. Using two orthotopic and highly-metastatic models of breast cancer, one of which was syngeneic (mouse 4T1) to allow assessment of tumor-immune interactions and one of which was endocrinologically humanized (human BT-474) to activate human PRLRs, we examined the effect of long PRLR knockdown on disease progression.

Non-hormonal treatment of vulvo-vaginal atrophy-related symptoms in post-menopausal women.

In post-menopausal period vulvo-vaginal atrophy (VVA)-related symptoms may seriously affect women's quality of life. Hormonal replacement therapy effectively relieves these symptoms but it is not always safe or accepted, and a non-hormonal treatment is often needed instead. Over a period of 12 weeks, we tested the effect of a twice-a-week vulvo-vaginal application of a hyaluronic acid, AC collagen, isoflavones and vitamins-based cream (Perilei Pausa) on 35 women in post-menopausal period, reporting VVA-related symptoms.

Increased nocturnal heart rate and wave reflection are early markers of cardiovascular disease in Williams-Beuren syndrome children.

Objective: Williams-Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS.

Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.

Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer. Cell entry of HCV and other pathogens is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model, we show that a monoclonal antibody specific for the TJ protein claudin-1 (ref.

Antiplasmodial and anti-inflammatory effects of an antimalarial remedy from the Wayana Amerindians, French Guiana: takamalaimë (Psidium acutangulum Mart. ex DC., Myrtaceae).

Ethnopharmacological Relevance: Field investigations highlighted the use of Psidium acutangulum Mart. ex DC (syn. P.

Maternal depressive symptoms throughout pregnancy are associated with increased placental glucocorticoid sensitivity.

Background: Maternal prenatal depression predicts post-partum depression and increases risk of prematurity and low birth weight. These effects may be mediated by altered placental function. We hypothesized that placental function would be influenced by the gestational week of experiencing depressive symptoms and aimed to examine associations between maternal depressive symptoms during pregnancy and placental expression of genes involved in glucocorticoid and serotonin transfer between mother and fetus.

Squaraine as a bright, stable and environment-sensitive far-red label for receptor-specific cellular imaging.

Herein, we show that a far-red arylidene-squaraine dye is stable against nucleophiles, in contrast to arene-squaraines. Owing to the fluorescence enhancement in apolar media together with high brightness and photostability, this dye was successfully applied to detect the oxytocin G protein-coupled receptor and monitor its internalization in living cells.

Auditory temporal abilities in children with history of recurrent otitis media in the first years of life and persistent in preschool and school ages.

Purpose: To study the temporal auditory ordering and resolution abilities in children with and without a history of early OME and ROME, as well as to study the responses according to age.

Methods: A total of 59 children were evaluated, and all of them presented pure tone thresholds within the normal range at the time of the conduction of the hearing tests. The children were divided into two groups according to the occurrence of episodes of recurrent otitis media.

Fluorogenic squaraine dimers with polarity-sensitive folding as bright far-red probes for background-free bioimaging.

Polarity-sensitive fluorogenic dyes raised considerable attention because they can turn on their fluorescence after binding to biological targets, allowing background-free imaging. However, their brightness is limited, and they do not operate in the far-red region. Here, we present a new concept of fluorogenic dye based on a squaraine dimer that unfolds on changing environment from aqueous to organic and thus turns on its fluorescence.

Prognostic significance of left atrial enlargement in a general population: results of the PAMELA study.

We estimated the risk of cardiovascular events, cardiovascular mortality, and all-cause mortality associated with left atrium (LA) enlargement alone or combined with echocardiographic left ventricular hypertrophy (LVH) in 1785 representatives of the general population of Monza recruited for the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study. LA enlargement was assessed by measuring LA diameter via echocardiography. LA enlargement was defined as a LA diameter>2.

Cellular responses following retinal injuries and therapeutic approaches for neurodegenerative diseases.

Retinal neurodegenerative diseases like age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa each have a different etiology and pathogenesis. However, at the cellular and molecular level, the response to retinal injury is similar in all of them, and results in morphological and functional impairment of retinal cells. This retinal degeneration may be triggered by gene defects, increased intraocular pressure, high levels of blood glucose, other types of stress or aging, but they all frequently induce a set of cell signals that lead to well-established and similar morphological and functional changes, including controlled cell death and retinal remodeling.

Drivers for animal welfare policies in Europe.

The European region has been, and remains, a global leader in the development of animal welfare policies. The region has a great diversity of cultures and religions, different levels of socio-economic development, and varied legislation, policies and practices. Nevertheless, there are common drivers for animal welfare policy based on a history of animal welfare ethics and obligations to animal users and society in general.

Megalencephalic leukoencephalopathy with subcortical cysts protein 1 regulates glial surface localization of GLIALCAM from fish to humans.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by myelin vacuolization and caused by mutations in MLC1 or GLIALCAM. Patients with recessive mutations in either MLC1 or GLIALCAM show the same clinical phenotype. It has been shown that GLIALCAM is necessary for the correct targeting of MLC1 to the membrane at cell junctions, but its own localization was independent of MLC1 in vitro.

Neandertal demise: an archaeological analysis of the modern human superiority complex.

Neandertals are the best-studied of all extinct hominins, with a rich fossil record sampling hundreds of individuals, roughly dating from between 350,000 and 40,000 years ago. Their distinct fossil remains have been retrieved from Portugal in the west to the Altai area in central Asia in the east and from below the waters of the North Sea in the north to a series of caves in Israel in the south. Having thrived in Eurasia for more than 300,000 years, Neandertals vanished from the record around 40,000 years ago, when modern humans entered Europe.

[Acetylsalicylic acid and prevention of preeclampsia].

Two to six percent of all pregnant women develop preeclampsia. In the worst case its complications threaten the life of both the fetus and the mother. It seems that especially an early and severe preeclampsia diagnosed before 34 weeks of pregnancy can be prevented by using low-dose acetylsalicylic acid medication, which shall be started sufficiently early, not later than pregnancy week 16.

Assessment of inner retina dysfunction and progressive ganglion cell loss in a mouse model of glaucoma.

The DBA/2J mouse is a model of ocular hypertension and retinal ganglion cell (RGC) degeneration, the main features of which are iris pigment dispersion (IPD) and iris stromal atrophy (ISA). These animals also experience glaucomatous changes, including an increase in intraocular pressure (IOP) beginning at about 9-12 months of age and sectorial RGC death in the retina. The aim of this study was to determine the onset of functional changes exhibited by DBA/2J mice in the inner retina.