Climatic applicability of downdraught evaporative cooling in the United States of America

The potential for application of downdraught cooling in the United States of America (U.S.) depends on its climatic characteristics. However, due to the large geographic span of the country, it varies due to differences in latitude, and a range of geographic features influencing climate, including altitude, topography and terrain. This study describes the development of climatic applicability maps of downdraught cooling in the U.S., which can aid designers in the initial identification of the correct cooling strategy for the geographic area of interest. The proposed approach is based on a set of maps, which are derived from two related climatic indexes: dry bulb temperature to wet bulb temperature depression (DBT−WBT), representing the climatic opportunity, and 26ºC minus wet bulb temperature (26ºC−WBT), representing the climatic opportunity against the theoretical cooling requirement for each location. The downdraught cooling strategy and degree of applicability is classified in the map, based on the aforementioned climatic and cooling parameters. Finally, four representative buildings in four different regions with different climatic conditions were selected for climatic analysis. This resulted in the identification of some climate zones for downdraught cooling application in the U.S. and the suggestion of appropriate design strategies for each of them

Very long-term efficacy and safety of paclitaxel-eluting balloon after a bare-metal stent for the treatment of ST-elevation myocardial infarction: 8-year results of a randomized clinical trial (PEBSI study)

Drug-eluting stents; Drug-coated balloons; Myocardial infarctionStents alliberadors de fàrmacs; Globus recoberts de fàrmacs; Infart de miocardiStents liberadores de fármacos; Globos recubiertos de fármacos; Infarto de miocardioBackground: Drug-eluting stents (DES) are considered the therapy of choice in ST-segment elevation myocardial infarction (STEMI); however, a low persistent rate of revascularizations and stent thrombosis exist over the time. We have previously shown that a paclitaxel (PTX)-drug-coated balloon (DCB) after a bare-metal stent (BMS) implantation (DCB-combined strategy) yields superior angiographic and clinical results compared to BMS in the short term. However, the long-term safety and efficacy of this approach remain uncertain. Methods: An 8-year clinical follow-up was conducted on patients enrolled in the randomized PEBSI-1 trial (NCT01839890). The original trial included patients who suffered a STEMI, patients were randomly assigned to receive a DCB-combined strategy or BMS only and the primary endpoint was in-stent late luminal loss (LLL) at 9-month follow-up. After the completion of this study, death, myocardial re-infarction, ischemia-driven repeated revascularizations included target lesion revascularization (TLR) and target vessel revascularization (TVR), and stent thrombosis, were assessed by yearly contact by a clinical visit, telephone or by electronic records. These outcomes were adhered to ARC-2 criteria. Results: The rate of incomplete follow-up was very low, with only 3 out of 111 patients (2.7%) in the DCB-combined strategy group and 1 out of 112 patients (0.9%) in the BMS group. At 8 years there were a lower rate of TVR [3.7% vs. 14.3%; hazard ratio (HR): 0.243; 95% confidence interval (CI): 0.081–0.727; P=0.006], and a trend towards lower TLR (2.8% vs. 8.9%; HR: 0.300; 95% CI: 0.083–1.090; P=0.052) in the DCB-combined strategy group. No statistical difference between the DCB-combined strategy and BMS groups were found for all causes of death, deaths from cardiovascular disease, reinfarctions or stent thrombosis. Notably in the DCB-combined strategy group, no episode of stent thrombosis occurred after the first year. Similarly, there were no cardiovascular deaths, TVR and TLR in the DCB-combined strategy group after 5 years. In contrast, during the period from year 5 to 8, the BMS group experienced an additional cardiovascular death, as well as one case of TVR, one case of TLR, and one case of stent thrombosis. Conclusions: In STEMI patients, the DCB-combined strategy maintains its safety and clinical efficacy over time. Our rates of TVR, TLR, and very late stent thrombosis (VLST) at very long-term are the lowest ever found in a STEMI trial. Further studies are warranted to assess the potential superiority of this novel strategy as compared with new-generation DES to prevent very late events in these patients. Trial Registration: ClinicalTrials.gov; identifier: NCT01839890.This investigation has received the support of the Spanish Clinical Research Network (SCReN), financed by the ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, under the project PT13/0002/0005 (Plan Estatal de I+D+I 2013-2016) and co-funded by the European Regional Development Fund (FEDER). An unrestricted research grant was received from Biotronik

New strategies to find chromatin silencers in the pathogenic fungus Ustilago maydis

Ustilago maydis is a smut fungus that infects maize, causing tumors, stunted growth and consequently reduced yields leadingto economic losses [2]. A key aspect of the pathogenic development of U.maydis is the action of effectors, which are secretedvirulence factors with principal roles in plant defense suppression and host's metabolism alterations. Many genes encodingeffector proteins are grouped in silenced clusters in the genome highly induced during infection. It has been shown thatintroduction of resistance marker genes with high expression promoters in these clusters de-repress the surrounding region ofthe insertion point [3]. Consequently, it is suggested that these clusters are subjected to chromatin silencing. However, U. maydislacks the canonical factors involved in chromatin silencing. The main purpose of this project is to find regulators that control thesilencing state of these regions. To achieve this goal we are going to perform a screening in a U.maydis strain harboring anantibiotic resistant marker gene inside a silenced cluster. In order to do this strain, we decided to introduce in one of theseclusters an antibiotic marker that will be controlled by an endogenous promoter followed of a different resistance marker genewith a high expressed promoter that will disturb the silencing of the region of insertion. Once we obtained this strain, we restoredsilencing by removing the high expressed gene, which is flanked by two direct repeat sequences, expressing the flippaserecombinase [1]. We are currently performing the first steps of the mutagenesis assay using the recently generated strain

High-intensity high-volume swimming induces more robust signaling through PGC-1α and AMPK activation than sprint interval swimming in <i>m. triceps brachii</i>

We aimed to test whether high-intensity high-volume training (HIHVT) swimming would induce more robust signaling than sprint interval training (SIT) swimming within the m. triceps brachii due to lower metabolic and oxidation. Nine well-trained swimmers performed the two training procedures on separate randomized days. Muscle biopsies from m. triceps brachii and blood samples were collected at three different time points: a) before the intervention (pre), b) immediately after the swimming procedures (post) and c) after 3 h of rest (3 h). Hydroperoxides, creatine kinase (CK), and lactate dehydrogenase (LDH) were quantified from blood samples, and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and the AMPKpTHR172/AMPK ratio were quantified by Western blot analysis. PGC-1α, sirtuin 3 (SIRT3), superoxide-dismutase 2 (SOD2), and vascular endothelial growth factor (VEGF) mRNA levels were also quantified. SIT induced a higher release of LDH (

Mechanotransduction and growth factor signalling to engineer cellular microenvironments

Engineering cellular microenvironments involves biochemical factors, the extracellular matrix (ECM) and the interaction with neighbouring cells. This progress report provides a critical overview of key studies that incorporate growth factor (GF) signalling and mechanotransduction into the design of advanced microenvironments. Materials systems have been developed for surface-bound presentation of GFs, either covalently tethered or sequestered through physico-chemical affinity to the matrix, as an alternative to soluble GFs. Furthermore, some materials contain both GF and integrin binding regions and thereby enable synergistic signalling between the two. Mechanotransduction refers to the ability of the cells to sense physical properties of the ECM and to transduce them into biochemical signals. Various aspects of the physics of the ECM, i.e. stiffness, geometry and ligand spacing, as well as time-dependent properties, such as matrix stiffening, degradability, viscoelasticity, surface mobility as well as spatial patterns and gradients of physical cues are discussed. To conclude, various examples illustrate the potential for cooperative signalling of growth factors and the physical properties of the microenvironment for potential applications in regenerative medicine, cancer research and drug testing

Systematic review with meta-analysis: vasoactive drugs for the treatment of hepatorenal syndrome type 1

Background Hepatorenal syndrome type 1 (HRS1) is a functional, rapidly progressive, potentially reversible form of acute kidney injury occurring in patients with cirrhosis. Characterised by intense renal arterial vasoconstriction, it carries a very poor prognosis. There is a significant unmet need for a widely approved, safe and effective pharmacological treatment. Aim To re-evaluate efficacy and safety of pharmacological treatments for HRS1, in the light of recently published randomised controlled trials (RCTs). Methods MEDLINE (OvidSP), EMBASE, PubMed and Cochrane registers were searched for RCTs reporting efficacy and adverse events related to pharmacological treatment of HRS1. Search terms included: ‘hepatorenal syndrome’, ‘terlipressin’, ‘noradrenaline’, ‘octreotide’, ‘midodrine’, ‘vasopressin’, ‘dopamine’, ‘albumin’ and synonyms. Comparison of vasoactive drugs vs. placebo/no treatment, and two active drugs were included. Meta-analysis was performed for HRS1 reversal, creatinine improvement, mortality and adverse events. Results Twelve RCTs enrolling 700 HRS1 patients were included. Treatment with terlipressin and albumin led to HRS1 reversal more frequently than albumin alone or placebo (RR: 2.54, 95% CI: 1.51–4.26). Noradrenaline was effective in reversing HRS1, but trials were small and nonblinded. Overall, there was mortality benefit with terlipressin (RR: 0.79, 95% CI: 0.63–1.01), but sensitivity analysis including only trials with low risk of selection bias weakened this relationship (RR: 0.87, 95% CI: 0.71–1.06). Notably, there was a significant risk of adverse events with terlipressin therapy (RR: 4.32, 95% CI: 0.75–24.86). Conclusions Terlipressin treatment is superior to placebo for achieving HRS1 reversal, but mortality benefit is less clear. Terlipressin is associated with significant adverse events, but infusion regimens may be better tolerated. There is continued need for safe and effective treatment options for hepatorenal syndrome

T-cell-derived miRNA-214 mediates perivascular fibrosis in hypertension

RATIONALE: Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. OBJECTIVES: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. METHODS AND RESULTS: Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold, P=0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214-/- prevented Ang II-induced periaortic fibrosis, Col1a1, Col3a1, Col5a1, and Tgfib1 expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214-/- mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang II-induced recruitment of T cells into perivascular adipose tissue was abolished in miR-214-/- mice. Adoptive transfer of miR-214-/- T cells into RAG1-/- mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II nduced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214-/-. T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214-/- prevented Ang II-induction of profibrotic T cell cytokines (IL-17, TNF-a, IL-9, and IFN-y) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness. CONCLUSIONS: T-cell-derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release

Cirugía robótica en patología quirúrgica benigna y maligna (urología, cirugía general y digestiva, cirugía cardiotorácica, ginecología, endocrinología, oftalmología y cirugía de cabeza y cuello). Capítulo I: cirugía cardiotorácica, endocrina, oftalmológica y cirugía de cabeza y cuello

Cirurgia robòtica; Tècniques quirúrgiques; InnovacióCirugía robótica; Técnicas quirúrgicas; InnovaciónRobotic surgery; Surgical techniques; InnovationAquest estudi té l’objectiu de determinar si la cirurgia assistida per robot, quan aquesta és el tractament indicat en una sèrie de patologies benignes o malignes, ha de ser incorporada en la cartera comuna bàsica de serveis assistencials del SNS i, per tant, convertir-se en una tecnologia finançada a través de fons públics. Per fer-ho s’ha avaluat l’eficàcia o l’efectivitat, la seguretat i l’eficiència de la cirurgia assistida per robot en comparació amb la cirurgia oberta o endoscòpica en un grup d’indicacions de patologia benigna o maligna en les especialitats de cirurgia cardiotoràcica, endocrina, oftalmològica, de cap i coll.El estudio tiene el objetivo de determinar si la cirugía asistida por robot, cuando la cirugía es el tratamiento indicado en una serie de patologías benignas o malignas, debe ser incorporada en la cartera común básica de servicios asistenciales del SNS y, por tanto, convertirse en una tecnología financiada a través de fondos públicos. Para ello se ha evaluado la eficacia o la efectividad, la seguridad y la eficiencia de la cirugía asistida por robot en comparación con la cirugía abierta o endoscópica en un grupo de indicaciones de patología benigna o maligna en las especialidades de cirugía cardiotorácica, endocrina, oftalmológica y de cabeza y cuello.The aim of the report is to determine whether robot-assisted surgery —when surgery is the indicated treatment for a series of benign or malignant pathologies— should be included in the basic common portfolio of the SNS healthcare services and thus become a publicly funded technology. To this end, the efficacy or effectiveness, safety and efficiency of robot-assisted surgery has been evaluated in comparison with open or endoscopic surgery in a group of indications of benign or malignant pathology in the specialities of cardiothoracic surgery, endocrine surgery, ophthalmological surgery, head and neck surgery

Management and outcomes of patients with left atrial appendage thrombus prior to percutaneous closure

Altres ajuts: Fundación Interhospitalaria para la Investigación Cardiovascular (FIC Foundation); Abbott.Objective: Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus. Methods: This multicentre observational registry included 126 consecutive patients referred for LAAC with LAA thrombus on preprocedural imaging. Treatment strategies included intensification of antithrombotic therapy (IAT) or direct LAAC. The primary and secondary endpoints were a composite of bleeding, stroke and death at 18 months, and procedural success, respectively. Results: IAT was the preferred strategy in 57.9% of patients, with total thrombus resolution observed in 60.3% and 75.3% after initial and subsequent IAT, respectively. Bleeding complications and stroke during IAT occurred in 9.6% and 2.9%, respectively, compared with 3.8% bleeding and no embolic events in the direct LAAC group before the procedure. Procedural success was 90.5% (96.2% vs 86.3% in direct LAAC and IAT group, respectively, p=0.072), without cases of in-hospital thromboembolic complications. The primary endpoint occurred in 29.3% and device-related thrombosis was found in 12.8%, without significant difference according to treatment strategy. Bleeding complications at 18 months occurred in 22.5% vs 10.5% in the IAT and direct LAAC group, respectively (p=0.102). Conclusion: In the presence of LAA thrombus, IAT was the initial management strategy in half of our cohort, with initial thrombus resolution in 60% of these, but with a relatively high bleeding rate (∼10%). Direct LAAC was feasible, with high procedural success and absence of periprocedural embolic complications. However, a high rate of device-related thrombosis was detected during follow-up