Fabrication of low cost and low impact RH and temperature sensors for the Internet of Environmental-Friendly Things

Given the increasing number of connected devices as a consequence of the Internet of Things (IoT) revolution, the issue of the removal and recycling of electronics is becoming more and more urgent. In this context, biodegradable electronics is expected to be one of the biggest technological revolutions to tackle this problem. Following this direction, in this work we present the fabrication and characterization of temperature and humidity sensors based on biodegradable materials with the goal of making their removal easier as well as reducing their environmental impact. In particular, these multi-sensing devices were fabricated following a screen-printing process using a carbon-based paste and a conjugated polymer, both on paper and on a water soluble substrate. The results are more than promising and show how with our biodegradable sensors it is possible to obtain a sensitivity of 1 dec/20%RH to moisture content and around 0.04%/°C sensitivity to temperature. It is demonstrated that the simplicity and flexibility of the fabrication approach followed in this work paves the way to a set of new “green” IoT nodes that could be extended to wide range of sensing applications

Overexpression of Cannabinoid CB2 Receptor in the Brain Induces Hyperglycaemia and a Lean Phenotype in Adult Mice

t is well known that the endocannabinoid system, through cannabinoid CB1 receptor activation,has an important role in the main aspects of energy balance (i.e. food intake, energy expenditureand glucose and fat metabolism), orchestrating all the machinery involved in body weight con-trol and energy homeostasis. A number of studies have revealed a crucial role of brain CB1receptors in these processes. However, functional cannabinoid CB2 receptors have also beendescribed in the brain, with no studies addressing their putative role in body weight control andglucose homeostasis. We have tested this hypothesis by analysing fasting-induced feeding, bodyweight, some hypothalamic neuropeptides, glucose tolerance and plasma hormones in an animalmodel specifically overexpressing CB2 receptors in the central nervous system. We found thatspecific overexpression of CB2 receptors in the brain promoted higher basal glucose levels,decreased fasting-induced feeding and, eventually, led to a lean phenotype and glucose intoler-ance. These findings could not be attributed to decreased locomotor activity, increased anxietyor depressive-like behaviours. The expression of relevant neuropeptides such as pro-opiomelano-cortin and galanin in the arcuate nucleus of the hypothalamus was altered but not those of theCB1 receptor. Indeed, no changes in CB1 expression were found in the liver, skeletal muscle andadipose tissue. However, cannabinoid CB1 and CB2 receptor expression in the endocrine pan-creas and glucagon plasma levels were decreased. No changes in plasma adiponectin, leptin,insulin and somatostatin were found. Taken together, these results suggest a role for centralcannabinoid CB2 receptors in body weight control and glucose homeostasis

Cardiac Safety of TGF-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study

Transforming growth factor-beta (TGF-β) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-β signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-β inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ≥6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-β inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials

The effect of seasoning with herbs on the nutritional, safety and sensory properties of reduced-sodium fermented Cobrançosa cv. table olives

This study aimed at evaluating the effectiveness of seasoning Cobrancosa table olives in a brine with aromatic ingredients, in order to mask the bitter taste given by KCl when added to reduced-sodium fermentation brines. Olives were fermented in two different salt combinations: Brine A, containing 8% NaCl and, Brine B, a reduced-sodium brine, containing 4% NaCl + 4% KCl. After the fermentation the olives were immersed in seasoning brines with NaCl (2%) and the aromatic herbs (thyme, oregano and calamintha), garlic and lemon. At the end of the fermentation and two weeks after seasoning, the physicochemical, nutritional, organoleptic, and microbiological parameters, were determined. The olives fermented in the reduced-sodium brines had half the sodium concentration, higher potassium and calcium content, a lower caloric level, but were considered, by a sensorial panel, more bitter than olives fermented in NaCl brine. Seasoned table olives, previously fermented in Brine A and Brine B, had no significant differences in the amounts of protein (1.23% or 1.11%), carbohydrates (1.0% or 0.66%), fat (20.0% or 20.5%) and dietary fiber (3.4% or 3.6%). Regarding mineral contents, the sodium-reduced fermented olives, presented one third of sodium, seven times more potassium and three times more calcium than the traditional olives fermented in 8% NaCl. Additionally, according to the panelists' evaluation, seasoning the olives fermented in 4% NaCl + 4% KCl, resulted in a decrease in bitterness and an improvement in the overall evaluation and flavor. Escherichia coli and Salmonella were not found in the olives produced.info:eu-repo/semantics/publishedVersio

Thymidylate synthase gene variants as predictors of clinical response and toxicity to fluoropyrimidine-based chemotherapy for colorectal cancer

Abstract Background: Fluoropyrimidines form the chemotherapy backbone of advanced and metastatic colorectal cancer (CRC). These drugs are frequently associated with toxicity events that result in dose adjustments and even suspension of the treatment. The thymidylate synthase (TYMS) gene is a potential marker of response and toxicity to fluoropyirimidines as this enzyme is the molecular target of these drugs. Our aim was to assess the association between variants of TYMS with response and toxicity to fluoropyrimidines in patients with CRC in independent retrospective and prospective studies. Methods: Variants namely rs45445694, rs183205964, rs2853542 and rs151264360 of TYMS were genotyped in 105 CRC patients and were evaluated to define their association with clinical response and toxicity to fluoropyrimidines. Additionally, the relationship between genotypes and tumor gene expression was analyzed by quantitative polymerase chain reaction. Results: The 2R/2R (rs45445694) was associated with clinical response (p = 0.05, odds ratio (OR) = 3.45) and severe toxicity (p = 0.0014, OR = 5.21, from pooled data). Expression analysis in tumor tissues suggested a correlation between the 2R/2R genotype and low TYMS expression. Conclusions: The allele 2R (rs45445694) predicts severe toxicity and objective response in advanced CRC patients. In addition, the alleles G(rs2853542) and 6bp-(rs151264360) are independent predictors of response failure to chemotherapy. This is the first study made on a Latin American population that points out TYMS gene variants have predictive values for response and toxicity in patients with CRC treated with fluoropyrimidine-based chemotherapy

Human Mas-related G protein-coupled receptors-X1 induce chemokine receptor 2 expression in rat dorsal root ganglia neurons and release of chemokine ligand 2 from the human LAD-2 mast cell line

Primate-specific Mas-related G protein-coupled receptors-X1 (MRGPR-X1) are highly enriched in dorsal root ganglia (DRG) neurons and induce acute pain. Herein, we analyzed effects of MRGPR-X1 on serum response factors (SRF) or nuclear factors of activated T cells (NFAT), which control expression of various markers of chronic pain. Using HEK293, DRG neuron-derived F11 cells and cultured rat DRG neurons recombinantly expressing human MRGPR-X1, we found activation of a SRF reporter gene construct and induction of the early growth response protein-1 via extracellular signal-regulated kinases-1/2 known to play a significant role in the development of inflammatory pain. Furthermore, we observed MRGPR-X1-induced up-regulation of the chemokine receptor 2 (CCR2) via NFAT, which is considered as a key event in the onset of neuropathic pain and, so far, has not yet been described for any endogenous neuropeptide. Up-regulation of CCR2 is often associated with increased release of its endogenous agonist chemokine ligand 2 (CCL2). We also found MRGPR-X1-promoted release of CCL2 in a human connective tissue mast cell line endogenously expressing MRGPR-X1. Thus, we provide first evidence to suggest that MRGPR-X1 induce expression of chronic pain markers in DRG neurons and propose a so far unidentified signaling circuit that enhances chemokine signaling by acting on two distinct yet functionally co-operating cell types. Given the important role of chemokine signaling in pain chronification, we propose that interruption of this signaling circuit might be a promising new strategy to alleviate chemokine-promoted pain

Variables hormonales y bioquímicas de la densidad mineral ósea y su correlación con hombres jóvenes obesos y no obesos sin diabetes

Introducción: la obesidad se ha asociado con mayor densidad mineral ósea (DMO), sin embargo, recientes estudios reportan que pudiese conllevar incremento de la resorción ósea y, por ende, mayor riesgo de fractura. Metodología: estudio de corte transversal analítico en donde se incluyeron hombres entre 18 y 30 años en quienes se realizaron diversas mediciones hormonales (insulina, testosterona libre y total, IGF-1, estradiol, leptina y adiponectina), bioquímicas (PTOG-glucosa, colesterol total, cHDL, cLDL, proteína C reactiva y HOMA-IR), antropométricas y otras, como composición grasa corporal, DMO y composición mineral ósea. Se evaluaron las diferencias de las variables cuantitativas entre obesos y no obesos mediante una prueba T-student o prueba de Wilcoxon. Para evaluar la correlación de DMO con las demás variables se usó la correlación de Spearman. Finalmente, se realizó un modelo de regresión lineal para predecir la DMO. Resultados: se incluyen 34 obesos y 35 no obesos. En el grupo de no obesos se obtuvo una media de 1,159 +/- 0,08 g/ cm2 de DMO comparado con el grupo de hombres obesos, con una media de 1,311 +/- 0,1 g/cm2 (p = 0,001). Se encontró que la DMO tiene una correlación fuerte con el contenido mineral óseo en los obesos respecto a los no obesos 3412,37 g (+/- 454,01) vs. 2575,96 g (+/-388,04), respectivamente, p <0,001. La adiponectina se correlacionó de forma negativa, aunque sin significancia en los obesos respecto a la densidad mineral ósea (r: -0,1913 y p = 0,27) y de forma débil y no significativa con los no obesos (r: 0,0074 y p = 0,96). Finalmente, se encontró que la presencia de obesidad, grasa total, contenido mineral óseo, insulina basal y HOMA-IR predicen de forma significativa la DMO en un modelo de regresión lineal. Conclusión: la DMO y el contenido mineral óseo son más altos en individuos obesos comparados con individuos no obesos, el índice de masa corporal y variables como insulina predicen la densidad mineral ósea

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials.

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT

Perturbation of the Dimer Interface of Triosephosphate Isomerase and its Effect on Trypanosoma cruzi

Most of the enzymes of parasites have their counterpart in the host. Throughout evolution, the three-dimensional architecture of enzymes and their catalytic sites are highly conserved. Thus, identifying molecules that act exclusively on the active sites of the enzymes from parasites is a difficult task. However, it is documented that the majority of enzymes consist of various subunits, and that conservation in the interface of the subunits is lower than in the catalytic site. Indeed, we found that there are significant differences in the interface between the two subunits of triosephosphate isomerase from Homo sapiens and Trypanosoma cruzi (TcTIM), which causes Chagas disease in the American continent. In the search for agents that specifically inhibit TcTIM, we found that 2,2′-dithioaniline (DTDA) is far more effective in inactivating TcTIM than the human enzyme, and that its detrimental effect is due to perturbation of the dimer interface. Remarkably, DTDA prevented the growth of Escherichia coli cells that had TcTIM instead of their own TIM and killed T. cruzi epimastigotes in culture. Thus, this study highlights a new approach base of targeting molecular interfaces of dimers