Graphene-coated Rayleigh SAW resonators for NO2detection

This paper describes the development of a novel low-cost Rayleigh Surface Acoustic Wave Resonator (SAWR) device coated with a graphene layer that is capable of detecting PPM levels of NO2 in air. The sensor comprises two 262 MHz ST-cut quartz based Rayleigh SAWRs arranged in a dual oscillator configuration; where one resonator is coated with gas-sensitive graphene, and the other left uncoated to act as a reference. An array of NMP-dispersed exfoliated reduced graphene oxide dots was deposited in the active area inside the SAWR IDTs by a non-contacting, micro ink-jet printing system. An automated Mass Flow Controller system has been developed that delivers gases to the SAWR sensors with circuitry for excitation, amplification, buffering and signal read-out. This SAW-based graphene sensor has sensitivity to NO2 of ca. 25 Hz/ppm and could be implemented in a low-power low-cost gas sensor

A study to assess the unmet medical needs associated with the use of basal insulin in patients with type 2 diabetes

Aim: To describe in a real-world setting, the proportion of patients with a symptomatic hypoglycaemic event and the proportion of individuals with type 2 diabetes, who newly or recently initiated with basal insulin, achieving individual or general HbA1c target. Materials and Method: DINAS-AR was a national prospective observational study to assess the unmet needs in patients with type 2 diabetes treated with basal insulin with or without oral antihyperglycaemic drugs and/or GLP-1 receptor agonist. The study was conducted at 19 hospitals. Results: A total of 385 uncontrolled patients (≥18 years) who recently initiated basal insulin or who initiated treatment within a year prior to study enrolment entered the study. Outcomes were follow-up incidence of hypoglycaemic events, change of HbA1C and achievement of HBA1c <7% or individual target. A total of 44 patients (11.9%) reported the occurrence of ≥1 symptomatic hypoglycaemia event(s). HbA1c reductions were greater in patients who had recently initiated treatment with basal insulin (between 15 and 90 days prior to study entry) vs patients who initiated treatment within 1 year. A total of 80 patients (31.6%) achieved individual HbA1c target (or target <7.0%) at Week 24. Furthermore, the proportion of patients achieving this target without symptomatic hypoglycaemia was 26.1% (n = 66). A lower percentage of glycemia target achievement was observed in patients reporting hypoglycaemia (n = 14), 20.6% of all patients reporting hypoglycaemia event(s) vs (n = 66) 35.7% of all patients without hypoglycaemia event reported. Conclusion: In this real-world study, although the hypoglycaemia rate was not high in adults with type 2 diabetes treated with insulin, there was a lower percentage of patients that achieved glycemic target among those reporting hypoglycaemia events vs patients who did not report them.Fil: Frechtel, Gustavo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Forti, Lujan. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: Faingold, María Cristina. Unidad Asistencial "Dr. César Milstein"; ArgentinaFil: Perez Mangui, Federico. Centro de Investigaciones Metabólicas; ArgentinaFil: Orio, Silvia. No especifíca;Fil: Issa, Claudia. Sanatorio Guemes Sociedad Anonima.; ArgentinaFil: Guaita, María Silvina. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: Vivas, Norma. Sanofi Aventis Argentina Sociedad Anonima.; ArgentinaFil: De Luca, Julian A.. Sanofi Aventis Argentina Sociedad Anonima.; Argentin

Three-Dimensional Shapes of Spinning Helium Nanodroplets

A significant fraction of superfluid helium nanodroplets produced in a free-jet expansion have been observed to gain high angular momentum resulting in large centrifugal deformation. We measured single-shot diffraction patterns of individual rotating helium nanodroplets up to large scattering angles using intense extreme ultraviolet light pulses from the FERMI free-electron laser. Distinct asymmetric features in the wide-angle diffraction patterns enable the unique and systematic identification of the three-dimensional droplet shapes. The analysis of a large dataset allows us to follow the evolution from axisymmetric oblate to triaxial prolate and two-lobed droplets. We find that the shapes of spinning superfluid helium droplets exhibit the same stages as classical rotating droplets while the previously reported metastable, oblate shapes of quantum droplets are not observed. Our three-dimensional analysis represents a valuable landmark for clarifying the interrelation between morphology and superfluidity on the nanometer scale

GLI1 inactivation is associated with developmental phenotypes overlapping with Ellis–van Creveld syndrome

Peer reviewe

Structure of nanoparticles embedded in micellar polycrystals

We investigate by scattering techniques the structure of water-based soft composite materials comprising a crystal made of Pluronic block-copolymer micelles arranged in a face-centered cubic lattice and a small amount (at most 2% by volume) of silica nanoparticles, of size comparable to that of the micelles. The copolymer is thermosensitive: it is hydrophilic and fully dissolved in water at low temperature (T ~ 0{\deg}C), and self-assembles into micelles at room temperature, where the block-copolymer is amphiphilic. We use contrast matching small-angle neuron scattering experiments to probe independently the structure of the nanoparticles and that of the polymer. We find that the nanoparticles do not perturb the crystalline order. In addition, a structure peak is measured for the silica nanoparticles dispersed in the polycrystalline samples. This implies that the samples are spatially heterogeneous and comprise, without macroscopic phase separation, silica-poor and silica-rich regions. We show that the nanoparticle concentration in the silica-rich regions is about tenfold the average concentration. These regions are grain boundaries between crystallites, where nanoparticles concentrate, as shown by static light scattering and by light microscopy imaging of the samples. We show that the temperature rate at which the sample is prepared strongly influence the segregation of the nanoparticles in the grain-boundaries.Comment: accepted for publication in Langmui

Development and validation of a novel risk score for primary percutaneous coronary intervention for ST elevation myocardial infarction

Background Primary percutaneous coronary intervention (PPCI) is the default treatment for patients with ST elevation myocardial infarction (STEMI) and carries a higher risk of adverse outcomes when compared with elective and urgent PCI. Conventional PCI risk scores tend to be complex and may underestimate the risk associated with PPCI due to under-representation of patients with STEMI in their datasets. This study aimed to develop a simple, practical and contemporary risk model to provide risk stratification in PPCI. Methods Demographic, clinical and outcome data were collected for all patients who underwent PPCI between January 2009 and October 2013 at the Northern General Hospital, Sheffield. Multiple regression analysis was used to identify independent predictors of mortality and to construct a risk model. This model was then separately validated on an internal and external dataset. Results The derivation cohort included 2870 patients with a 30-day mortality of 5.1% (145 patients). Only four variables were required to predict 30-day mortality: age [OR:1.047, 95% CI:1.031–1.063], call-to-balloon (CTB) time [OR:1.829, 95% CI:1.198–2.791], cardiogenic shock [OR:13.886, 95% CI:8.284–23.275] and congestive heart failure [OR:3.169, 95% CI:1.420–7.072]. Internal validation was performed in 693 patients and external validation in 660 patients undergoing PPCI. Our model showed excellent discrimination on ROC-curve analysis (C-Stat = 0.87 internal and 0.86, external), and excellent calibration on Hosmer-Lemeshow testing (p = 0.37 internal, 0.55 external). Conclusions We have developed a bedside risk model which can predict 30-day mortality after PPCI using only four variables: age, CTB time, congestive heart failure and shock

Mutations in SCNM1 cause orofaciodigital syndrome due to minor intron splicing defects affecting primary cilia

Orofaciodigital syndrome (OFD) is a genetically heterogeneous ciliopathy characterized by anomalies of the oral cavity, face, and digits. We describe individuals with OFD from three unrelated families having bi-allelic loss-of-function variants in SCNM1 as the cause of their condition. SCNM1 encodes a protein recently shown to be a component of the human minor spliceosome. However, so far the effect of loss of SCNM1 function on human cells had not been assessed. Using a comparative transcriptome analysis between fibroblasts derived from an OFD-affected individual harboring SCNM1 mutations and control fibroblasts, we identified a set of genes with defective minor intron (U12) processing in the fibroblasts of the affected subject. These results were reproduced in SCNM1 knockout hTERT RPE-1 (RPE-1) cells engineered by CRISPR-Cas9-mediated editing and in SCNM1 siRNA-treated RPE-1 cultures. Notably, expression of TMEM107 and FAM92A encoding primary cilia and basal body proteins, respectively, and that of DERL2, ZC3H8, and C17orf75, were severely reduced in SCNM1-deficient cells. Primary fibroblasts containing SCNM1 mutations, as well as SCNM1 knockout and SCNM1 knockdown RPE-1 cells, were also found with abnormally elongated cilia. Conversely, cilia length and expression of SCNM1-regulated genes were restored in SCNM1-deficient fibroblasts following reintroduction of SCNM1 via retroviral delivery. Additionally, functional analysis in SCNM1-retrotransduced fibroblasts showed that SCNM1 is a positive mediator of Hedgehog (Hh) signaling. Our findings demonstrate that defective U12 intron splicing can lead to a typical ciliopathy such as OFD and reveal that primary cilia length and Hh signaling are regulated by the minor spliceosome through SCNM1 activity.This work was supported by a grant from the Spanish Ministry of Science and Innovation (PID2019-105620RB-I00/AEI/10.13039/501100011033)

Prevalence of buccal micronuclei in farm workers from fraile pintado, Jujuy, Argentine

El conocimiento sobre las medidas de bioseguridad y los efectos tóxicos durante la aplicación de pesticidas en la provincia de Jujuy, Argentina, es escaso, particularmente en relación con las medidas de protección y la mezcla de pesticidas utilizados por los trabajadores rurales. Este estudio se realizó para determinar la prevalencia de la actividad de acetilcolinesterasa de glóbulos rojos (AChE) y micronúcleos bucales (MN). Se realizó un estudio observacional de 209 trabajadores agrícolas (106 individuos expuestos y103 controles) de Fraile Pintado, Jujuy, Argentina. Se recogieron muestras de sangre completa (2 ml) en tubos Vacutainer heparinizados. La actividad de AChE se determinó de acuerdo con el método de Ellman. Las células de la mucosa bucal exfoliada se recogieron usando un cepillo de dientes. Los resultados citogenéticos mostraron un aumento significativo de MN en individuos expuestos a pesticidas en comparación con los controles (10.08y 2.15; p <0.0001), mientras que la actividad AChE fue significativamente menor en individuos expuestos en comparación con los controles (4093.44y 9132.25; p <0.0001). Los resultados actuales sugieren la necesidad del biomonitoreo periódico de MN bucal y AChE junto con educación y capacitación de trabajadores ocupacionales sobre la aplicación segura de pesticidas potencialmente dañinos.Knowledge about biosafety measures and toxic effects during pesticide application in the province of Jujuy, Argentine, is scarce, particularly concerning protective measures and the mixing of pesticides used by rural workers. This study was conducted to determine the prevalence of buccal micronuclei (MN) and red blood cell acetylcholinesterase (AChE) activity. An observational study of 209 agricultural workers (106 exposed individuals and 103 controls) from Fraile Pintado, Jujuy, Argentine, was carried out. Blood samples (2 mL) were collected in heparinized Vacutainer tubes. AChE activity was determined according to Ellman’s method. Exfoliated buccal mucosa cells were collected using a toothbrush. Cytogenetic results showed a significant MN increase in pesticide-exposed individuals as compared with controls (10.08 and 2.15; p < 0.0001), whereas AChE activity was significantly lower in exposed ones compared with control individuals (4093.44 and 9132.25; p < 0.0001). The present results suggest the need for the periodic biomonitoring of buccal MN and AChE together with education and training of occupational workers on the safe application of potentially harmful pesticides.Fil: Bianco Sadir, Graciela Eugenia. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: Julian, Rocio Florencia. Universidad Nacional de Jujuy. Instituto de Ecorregiones Andinas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Ecorregiones Andinas; Argentina. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: Rivera Funes, María del Carmen. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: Cazon, Lauro Nicolas. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: González Poma, Emanuel Celestino. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; ArgentinaFil: Borsetti, Hugo Mario. Universidad Nacional de Jujuy. Facultad de Ciencias Agrarias; Argentina. Universidad Nacional de Jujuy. Instituto de Estudios Celulares, Genéticos y Moleculares; ArgentinaFil: de Luca, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; Argentin

Association Between Response to Etrolizumab and Expression of Integrin αE and Granzyme A in Colon Biopsies of Patients With Ulcerative Colitis

Background & AimsEtrolizumab is a humanized monoclonal antibody against the β7 integrin subunit that has shown efficacy vs placebo in patients with moderate to severely active ulcerative colitis (UC). Patients with colon tissues that expressed high levels of the integrin αE gene (ITGAE) appeared to have the best response. We compared differences in colonic expression of ITGAE and other genes between patients who achieved clinical remission with etrolizumab vs those who did.MethodsWe performed a retrospective analysis of data collected from 110 patients with UC who participated in a phase 2 placebo-controlled trial of etrolizumab, as well as from 21 patients with UC or without inflammatory bowel disease (controls) enrolled in an observational study at a separate site. Colon biopsies were collected from patients in both studies and analyzed by immunohistochemistry and gene expression profiling. Mononuclear cells were isolated and analyzed by flow cytometry. We identified biomarkers associated with response to etrolizumab. In the placebo-controlled trial, clinical remission was defined as total Mayo Clinic Score ≤2, with no individual subscore >1, and mucosal healing was defined as endoscopic score ≤1.ResultsColon tissues collected at baseline from patients who had a clinical response to etrolizumab expressed higher levels of T-cell−associated genes than patients who did not respond (P < .05). Colonic CD4+ integrin αE+ cells from patients with UC expressed higher levels of granzyme A messenger RNA (GZMA mRNA) than CD4+ αE− cells (P < .0001); granzyme A and integrin αE protein were detected in the same cells. Of patients receiving 100 mg etrolizumab, a higher proportion of those with high levels of GZMA mRNA (41%) or ITGAE mRNA (38%) than those with low levels of GZMA (6%) or ITGAE mRNA (13%) achieved clinical remission (P < .05) and mucosal healing (41% GZMAhigh vs 19% GZMAlow and 44% ITGAEhigh vs 19% ITGAElow). Compared with ITGAElow and GZMAlow patients, patients with ITGAEhigh and GZMAhigh had higher baseline numbers of epithelial crypt-associated integrin αE+ cells (P < .01 for both), but a smaller number of crypt-associated integrin αE+ cells after etrolizumab treatment (P < .05 for both). After 10 weeks of etrolizumab treatment, expression of genes associated with T-cell activation and genes encoding inflammatory cytokines decreased by 40%−80% from baseline (P < .05) in patients with colon tissues expressing high levels of GZMA at baseline.ConclusionsLevels of GZMA and ITGAE mRNAs in colon tissues can identify patients with UC who are most likely to benefit from etrolizumab; expression levels decrease with etrolizumab administration in biomarkerhigh patients. Larger, prospective studies of markers are needed to assess their clinical value