Aspirin and the risk of colorectal and other digestive tract cancers: an updated meta-analysis through 2019

Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear

Bursts of activity in collective cell migration

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems

A diagnostic study comparing conventional and real-time PCR for Strongyloides stercoralis on urine and on faecal samples

Abstract Strongyloides stercoralis is a soil-transmitted helminth with a wide distribution in tropical and subtropical areas. The diagnosis of S. stercoralisinfection can be challenging, due to the low sensitivity of microscopic examination of stool samples and coproculture. In the last decade, different in-house molecular biology techniques for S. stercoralis have been implemented. They demonstrated good accuracy, although sensitivity does not seem sufficiently high yet. Recently, a novel PCR technique has been evaluated for the detection of S. stercoralis DNA in urine. Aim of this work was to compare the sensitivity of the real-time PCR (qPCR) on feces routinely used at the Centre for Tropical Disease (CTD) of Negrar, Verona, Italy, with that of the novel based PCR on urine. As secondary objective, we evaluated a Urine Conditioning Buffer ® (Zymoresearch) with the aim of improving nucleic acid stability in urine during sample storage/transport at ambient temperatures. Patients attending the CTD and resulting positive at routine screening with serology for S. stercoralis were invited, previous written consent, to supply stool and urine samples for molecular biology. A convenience sample of 30 patients was included. The sensitivity of qPCR on feces resulted 63%, and that of based PCR on urine was 17%. In all the samples treated with the Urine Conditioning Buffer ® there was no detectable DNA. In conclusion, the sensitivity of the novel technique resulted low, and needs further implementation before being considered as a valid alternative to the validated method

Experimentum corporis

El cuerpo no existe, esa es la intuición sobre la que se construye el artículo. El cuerpo no comparte el rango del ser ni del acto. No es un objeto en medio de otros objetos, tampoco un sujeto al lado de otros sujetos. El cuerpo no tiene consistencia, no es: insiste. Los cuerpos, cada cuerpo, es una potencia que insiste según grados diferentes. ¿Y cómo opera esa insistencia? Por imágenes; un cuerpo es una potencia de emanación de imágenes y producción del montaje abigarrado de las mismas. Esa doble operación carece de presupuestos y se hace cada vez. Un cuerpo es la experimentación de ese cada vez. El artículo intenta, por lo tanto, escribir un cuerpo, hacer un catálogo posible de sus imágenes, de sus insistencias; en ese sentido, no se trataría de un concepto ni un saber sobre el cuerpo sino, más bien, fragmentos de cuerpos, un auténtico experimentum corporisThe body does not exist; that’s the intuition in which this text is build. The body doesn’t share the rank of being or act. Is not an object among objects, neither a subject between subjects. Body doesn’t have a consistence: it insists. The body, each body, is a power that insists in different degrees. How does this insistence operate? By images; the body is a power of emanation of images and the process of mounting attached in it. That double operation lacks of specifications and is made each time. A body is the experimentation of that each time. The article tries, therefore, to write a body, to make a catalogue of it possible images, of it insistence; in this sense, it’s not about a concept or a knowledge of the body but rather fragments of bodies; an authentic experimentum corporis.Fil: Biset, Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Conforte, Juan Manuel. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; ArgentinaFil: Fioretti, Lorena Cintia. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Humanidades. Universidad Nacional de Córdoba. Instituto de Humanidades; ArgentinaFil: la Rocca, Paula. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Centro de Investigaciones María Saleme Burnichón; ArgentinaFil: Lorio, Natalia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Humanidades. Universidad Nacional de Córdoba. Instituto de Humanidades; ArgentinaFil: Maccioni, Franca. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Humanidades. Universidad Nacional de Córdoba. Instituto de Humanidades; ArgentinaFil: Martínez Ramacciotti, Javier Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad. Universidad Nacional de Córdoba. Centro de Investigaciones y Estudios sobre Cultura y Sociedad; ArgentinaFil: Milone, María Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Humanidades. Universidad Nacional de Córdoba. Instituto de Humanidades; ArgentinaFil: Neuburger, Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Humanidades. Universidad Nacional de Córdoba. Instituto de Humanidades; ArgentinaFil: Santucci, Silvana. Universidad Católica de Córdoba. Facultad de Filosofía y Humanidades; Argentina. Universidad Nacional de Tres de Febrero. Instituto de Investigaciones en Arte y Cultura "Dr. Norberto Griffa". Programa de Estudios Latinoamericanos Contemporáneos y Comparados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization

MSH5 is a MutS-homologous protein required for meiotic DNA recombination. In addition, recent studies suggest that the human MSH5 protein (hMSH5) participates to mitotic recombination and to the cellular response to DNA damage and thus raise the possibility that a tight control of hMSH5 function(s) may be important for genomic stability. With the aim to characterize mechanisms potentially involved in the regulation of hMSH5 activity, we investigated its intracellular trafficking properties. We demonstrate that hMSH5 possesses a CRM1-dependent nuclear export signal (NES) and a nuclear localization signal that participates to its nuclear targeting. Localization analysis of various mutated forms of hMSH5 by confocal microscopy indicates that hMSH5 shuttles between the nucleus and the cytoplasm. We also provide evidence suggesting that hMSH5 stability depends on its subcellular compartmentalization, hMSH5 being much less stable in the nucleus than in the cytoplasm. Together, these data suggest that hMSH5 activity may be regulated by nucleocytoplasmic shuttling and nuclear proteasomal degradation, both of these mechanisms contributing to the control of nuclear hMSH5 content. Moreover, data herein also support that in tissues where both hMSH5 and hMSH4 proteins are expressed, hMSH5 might be retained in the nucleus through masking of its NES by binding of hMSH4

A Multifaceted Analysis of Immune-Endocrine-Metabolic Alterations in Patients with Pulmonary Tuberculosis

Our study investigated the circulating levels of factors involved in immune-inflammatory-endocrine-metabolic responses in patients with tuberculosis with the aim of uncovering a relation between certain immune and hormonal patterns, their clinical status and in vitro immune response. The concentration of leptin, adiponectin, IL-6, IL-1β, ghrelin, C-reactive protein (CRP), cortisol and dehydroepiandrosterone (DHEA), and the in vitro immune response (lymphoproliferation and IFN-γ production) was evaluated in 53 patients with active untreated tuberculosis, 27 household contacts and 25 healthy controls, without significant age- or sex-related differences. Patients had a lower body mass index (BMI), reduced levels of leptin and DHEA, and increased concentrations of CRP, IL-6, cortisol, IL-1β and nearly significant adiponectin values than household contacts and controls. Within tuberculosis patients the BMI and leptin levels were positively correlated and decreased with increasing disease severity, whereas higher concentrations of IL-6, CRP, IL-1β, cortisol, and ghrelin were seen in cases with moderate to severe tuberculosis. Household contacts had lower DHEA and higher IL-6 levels than controls. Group classification by means of discriminant analysis and the k-nearest neighbor method showed that tuberculosis patients were clearly different from the other groups, having higher levels of CRP and lower DHEA concentration and BMI. Furthermore, plasma leptin levels were positively associated with the basal in vitro IFN-γ production and the ConA-driven proliferation of cells from tuberculosis patients. Present alterations in the communication between the neuro-endocrine and immune systems in tuberculosis may contribute to disease worsening

Galectin-4 Controls Intestinal Inflammation by Selective Regulation of Peripheral and Mucosal T Cell Apoptosis and Cell Cycle

Galectin-4 is a carbohydrate-binding protein belonging to the galectin family. Here we provide novel evidence that galectin-4 is selectively expressed and secreted by intestinal epithelial cells and binds potently to activated peripheral and mucosal lamina propria T-cells at the CD3 epitope. The carbohydrate-dependent binding of galectin-4 at the CD3 epitope is fully functional and inhibited T cell activation, cycling and expansion. Galectin-4 induced apoptosis of activated peripheral and mucosal lamina propria T cells via calpain-, but not caspase-dependent, pathways. Providing further evidence for its important role in regulating T cell function, galectin-4 blockade by antisense oligonucleotides reduced TNF-alpha inhibitor induced T cell death. Furthermore, in T cells, galectin-4 reduced pro-inflammatory cytokine secretion including IL-17. In a model of experimental colitis, galectin-4 ameliorated mucosal inflammation, induced apoptosis of mucosal T-cells and decreased the secretion of pro-inflammatory cytokines. Our results show that galectin-4 plays a unique role in the intestine and assign a novel role of this protein in controlling intestinal inflammation by a selective induction of T cell apoptosis and cell cycle restriction. Conclusively, after defining its biological role, we propose Galectin-4 is a novel anti-inflammatory agent that could be therapeutically effective in diseases with a disturbed T cell expansion and apoptosis such as inflammatory bowel disease

Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1): an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study to investigate the effect of once daily nitisinone on 24-h urinary homogentisic acid excretion in patients with alkaptonuria after 4 weeks of treatment.

BACKGROUND: Alkaptonuria (AKU) is a serious genetic disease characterised by premature spondyloarthropathy. Homogentisate-lowering therapy is being investigated for AKU. Nitisinone decreases homogentisic acid (HGA) in AKU but the dose-response relationship has not been previously studied. METHODS: Suitability Of Nitisinone In Alkaptonuria 1 (SONIA 1) was an international, multicentre, randomised, open-label, no-treatment controlled, parallel-group, dose-response study. The primary objective was to investigate the effect of different doses of nitisinone once daily on 24-h urinary HGA excretion (u-HGA24) in patients with AKU after 4 weeks of treatment. Forty patients were randomised into five groups of eight patients each, with groups receiving no treatment or 1 mg, 2 mg, 4 mg and 8 mg of nitisinone. FINDINGS: A clear dose-response relationship was observed between nitisinone and the urinary excretion of HGA. At 4 weeks, the adjusted geometric mean u-HGA24 was 31.53 mmol, 3.26 mmol, 1.44 mmol, 0.57 mmol and 0.15 mmol for the no treatment or 1 mg, 2 mg, 4 mg and 8 mg doses, respectively. For the most efficacious dose, 8 mg daily, this corresponds to a mean reduction of u-HGA24 of 98.8% compared with baseline. An increase in tyrosine levels was seen at all doses but the dose-response relationship was less clear than the effect on HGA. Despite tyrosinaemia, there were no safety concerns and no serious adverse events were reported over the 4 weeks of nitisinone therapy. CONCLUSIONS: In this study in patients with AKU, nitisinone therapy decreased urinary HGA excretion to low levels in a dose-dependent manner and was well tolerated within the studied dose range. TRIAL REGISTRATION NUMBER: EudraCT number: 2012-005340-24. Registered at ClinicalTrials.gov: NCTO1828463