Scattering of a plasmonic nanoantenna embedded in a silicon waveguide

Plasmonic antennas integrated on silicon devices have large and yet unexplored potential for controlling and routing light signals. Here, we present theoretical calculations of a hybrid silicon-metallic system in which a single gold nanoantenna embedded in a single-mode silicon waveguide acts as a resonance-driven filter. As a consequence of scattering and interference, when the resonance condition of the antenna is met, the transmission drops by 85% in the resonant frequency band. Firstly, we study analytically the interaction between the propagating mode and the antenna by including radiative corrections to the scattering process and the polarization of the waveguide walls. Secondly, we find the configuration of maximum interaction and numerically simulate a realistic nanoantenna in a silicon waveguide. The numerical calculations show a large suppression of transmission and three times more scattering than absorption, consequent with the analytical model. The system we propose can be easily fabricated by standard silicon and plasmonic lithographic methods, making it promising as real component in future optoelectronic circuits.Comment: 10 pages, 5 figure

3D bioprinted functional skeletal muscle models have potential applications for studies of muscle wasting in cancer cachexia

Acquired muscle diseases such as cancer cachexia are responsible for the poor prognosis of many patients suffering from cancer. In vitro models are needed to study the underlying mechanisms of those pathologies. Extrusion bioprinting is an emerging tool to emulate the aligned architecture of fibers while implementing ad- ditive manufacturing techniques in tissue engineering. However, designing bioinks that reconcile the rheological needs of bioprinting and the biological requirements of muscle tissue is a challenging matter. Here we formulate a biomaterial with dual crosslinking to modulate the physical properties of bioprinted models. We design 3D bioprinted muscle models that resemble the mechanical properties of native tissue and show improved prolif- eration and high maturation of differentiated myotubes suggesting that the GelMA-AlgMA-Fibrin biomaterial possesses myogenic properties. The electrical stimulation of the 3D model confirmed the contractile capability of the tissue and enhanced the formation of sarcomeres. Regarding the functionality of the models, they served as platforms to recapitulate skeletal muscle diseases such as muscle wasting produced by cancer cachexia. The genetic expression of 3D models demonstrated a better resemblance to the muscular biopsies of cachectic mouse models. Altogether, this biomaterial is aimed to fabricate manipulable skeletal muscle in vitro models in a non- costly, fast and feasible manne

Canagliflozin: A New Therapeutic Option in Patients That Present Postprandial Hyperinsulinemic Hypoglycemia after Roux-en-Y Gastric Bypass: A Pilot Study

Cirurgia bariàtrica; Teràpia farmacològica; Hipoglucèmia postprandialCirugía bariátrica; Terapia farmacológica; Hipoglucemia posprandialBariatric surgery; Pharmacological therapy; Postprandial hypoglycemiaIntroduction: Roux-en-Y gastric bypass (RYGB) is the most common surgical procedure for morbid obesity. However, it can present serious late complications, like postprandial hyperinsulinemic hypoglycemia (PHH). Recent data suggested an increase in intestinal SGLT-1 after RYGB. However, there is no data on the inhibition of SGLT-1 to prevent PHH in patients with prior RYBG. On this basis, we aimed to evaluate (a) the effect of canagliflozin 300 mg on the response to 100 g glucose overload (oral glucose tolerance test [OGTT]); (b) the pancreatic response after intra-arterial calcium stimulation in the context of PHH after RYGB. Materials and Methods: This is a prospective pilot study including patients (n = 21) with PHH after RYGB, matched by age and gender with healthy controls (n = 5). Basal OGTT and after 2 weeks of daily 300 mg of canagliflozin was performed in all cases. In addition, venous sampling after intra-arterial calcium stimulation of the pancreas was performed in 10 cases. Results: OGTT after canagliflozin showed a significant reduction of plasma glucose levels (minute 30: 161.5 ± 36.22 vs. 215.9 ± 58.11 mg/dL; minute 60: 187.46 ± 65.88 vs. 225.9 ± 85.60 mg/dL, p < 0.01) and insulinemia (minute 30: 95.6 ± 27.31 vs. 216.35 ± 94.86 mg/dL, p = 0.03; minute 60: 120.85 ± 94.86 vs. 342.64 ± 113.32 mIU/L, p < 0.001). At minute 180, a significant reduction (85.7%) of the rate of hypoglycemia was observed after treatment with canagliflozin (p < 0.00001). All cases presented normal pancreatic response after intra-arterial calcium administration. Conclusion: Canagliflozin (300 mg) significantly decreased glucose absorption and prevented PHH after 100 g OGTT in patients with RYGB. Our results suggest that canagliflozin could be a new therapeutic option for patients that present PHH after RYGB.There were no funding sources

A micellar formulation of quercetin prevents cisplatin nephrotoxicity

Producción CientíficaThe antioxidant flavonoid quercetin has been shown to prevent nephrotoxicity in animal models and in a clinical study and is thus a very promising prophylactic candidate under development. Quercetin solubility is very low, which handicaps clinical application. The aim of this work was to study, in rats, the bioavailability and nephroprotective efficacy of a micellar formulation of Pluronic F127-encapsulated quercetin (P-quercetin), with improved hydrosolubility. Intraperitoneal administration of P-quercetin leads to an increased plasma concentration and bioavailability of quercetin compared to the equimolar administration of natural quercetin. Moreover, P-quercetin retains overall nephroprotective properties, and even slightly improves some renal function parameters, when compared to natural quercetin. Specifically, P-quercetin reduced the increment in plasma creatinine (from 3.4 ± 0.5 to 1.2 ± 0.3 mg/dL) and urea (from 490.9 ± 43.8 to 184.1 ± 50.1 mg/dL) and the decrease in creatinine clearance (from 0.08 ± 0.02 to 0.58 ± 0.19 mL/min) induced by the nephrotoxic chemotherapeutic drug cisplatin, and it ameliorated histological evidence of tubular damage. This new formulation with enhanced kinetic and biopharmaceutical properties will allow for further exploration of quercetin as a candidate nephroprotector at lower dosages and by administration routes oriented towards its clinical use.Fundación de Universidades y Enseñanzas Superiores de Castilla y León (FUESCyL) y Banco de Santander - (grant: Ed. 2014– 2015 Desafío UNIV-EMP)Fundación General de la Universidad de Salamanca, Fondo Europeo de Desarrollo Regional (FEDER) y Junta de Castilla y León - (grant: Ed. 2015 Lanzadera TC)Junta de Castilla y León - (grant: VA225U14

Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

Background. Community-associated methicillin-resistant Staphylococcus aureus(CAMRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective. Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Material and Methods. Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires)between March 2010 and October 2011. Patients were included if they were ≥ 14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results. A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions. CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina.Fil: Lopez Furst, Maria Jose. Sanatorio Municipal Dr. Julio Méndez, Ciudad Autónoma de Buenos Aires; Argentina;Fil: de Vedia, Lautaro. Gobierno de la Ciudad de Buenos Aires. Htal.de Infecciosas F.j. Muñiz; Argentina;Fil: Fernandez, Silvina. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Gardella, Noella Mariel. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Ganaha, Cristina. Pcia. de Buenos Aires. Hospital Vicente López y Planes, Gral. Rodríguez; Argentina;Fil: Prieto, Sergio. Provincia de Buenos Aires. Hospital Nuestra Señora de Luján; Argentina;Fil: Carbone, Edith. Hospital Aeronautico Central; Argentina;Fil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Htal.de Infecciosas F.j. Muñiz; Argentina;Fil: Rotryng, Flavio. Universidad Abierta Interamericana; Argentina;Fil: Morera, Graciana I.. Hospital Dr. Jose Cullen; Argentina;Fil: Mollerach, Marta Eugenia. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Biologica. Cat.de Microbiologia; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina;Fil: Stryjewski, Martin E.. Centro de Educaciones Medicas E Investig.Clinica "Norberto Quirno"; Argentina

Selective activity over a constitutively active RET-variant of the oral multikinase inhibitor dovitinib: results of the CNIO-BR002 phase I-trial

Background: given our preclinical data showing synergy between dovitinib and paclitaxel in preclinical models we conducted this phase I trial aiming to define the recommended phase II-dose (RP2D) on the basis of toxicity and pharmacodynamic criteria while searching for genetic variants that could sensitize patients to the regimen under study. Patients and methods: a 3+3 escalation schedule was adopted. Seriated FGF23 and dovitinib and paclitaxel pharmacokinetic profiles were determined along a single-agent dovitinib 'priming-phase' followed by a dovitinib + paclitaxel combination phase. RECIST 1.1 criteria and NCI CTCAE V.4.0 were used. In fresh pre-treatment tumor biopsy samples, FGFR1, 2 and 3 amplifications were revealed by FISH probes; 32 missense variants were genotyped in tumors and peripheral blood mononuclear cells with Taqman genotyping assays (FGFR1-3 and RET). Constructs encoding for wild-type and variant genes associated with clinical benefit were transfected into HEK-293 cells for preclinical experiments checking constitutive activation and dovitinib sensitivity of the variants. Results: twelve patients were recruited in three dose-levels. At level 1B (200 mg dovitinib 5-days-on/2-days-off plus 60 mg/m 2-week of paclitaxel) more than 50% FGF23 upregulation was observed and no dose-limiting-toxicities (DLTs) occurred. The most frequent toxicities were asthenia, neutropenia, nausea/vomiting and transaminitis. Two patients with progressive disease prior to trial inclusion achieved prolonged disease stabilization. Both had the germline variant G2071A in the RET gene, which led to constitutive activation of the protein product and Y-905 phosphorylation, both in transfectants and in patients with the alteration. This variant was sensitive to dovitinib; in addition both patients experienced progression upon medication withdrawal. Conclusions: level 1B was the RP2D as it provided adequate pharmacodynamic exposure to dovitinib. The G2071A germline variant act as a genetic modifier that renders different tumors sensitive to dovitinib

Urinary exosomes reveal protein signatures in hypertensive patients with albuminuria

Albuminuria is an indicator of cardiovascular risk and renal damage in hypertensive individuals. Chronic renin-angiotensin system (RAS) suppression facilitates blood pressure control and prevents development of new-onset-albuminuria. A significant number of patients, however, develop albuminuria despite chronic RAS blockade, and the physiopathological mechanisms are underexplored. Urinary exosomes reflect pathological changes taking place in the kidney. The objective of this work was to examine exosomal protein alterations in hypertensive patients with albuminuria in the presence of chronic RAS suppression, to find novel clues underlying its development. Patients were followed-up for three years and were classified as: a) patients with persistent normoalbuminuria; b) patients developing de novo albuminuria; and c) patients with maintained albuminuria. Exosomal protein alterations between groups were identified by isobaric tag quantitation (iTRAQ). Confirmation was approached by target analysis (SRM). In total, 487 proteins were identified with high confidence. Specifically, 48 proteins showed an altered pattern in response to hypertension and/or albuminuria. Out of them, 21 proteins interact together in three main functional clusters: glycosaminoglycan degradation, coagulation and complement system, and oxidative stress. The identified proteins constitute potential targets for drug development and may help to define therapeutic strategies to evade albuminuria progression in hypertensive patients chronically treated.Instituto de Salud Carlos III, fondos FEDER/FSE (PI11/01401, PI13/01873, PI14/01841, IF08/3667-1, PI11-02239, PI 14/0917, PI11/02432, PI13/01746, PI14/01650, PI16/01334, PT13/0001/0013, CP09/00229, CP15/00129, CPII15/00027), Fundacion SENEFRO, Fundacion Conchita Rabago de Jimenez Diaz, and Redes Tematicas de Investigacion Cooperativa (fondos FEDER/FSE, RD12/0021/0001, RD12/0042/0071). These results are lined up with the Spanish initiative on the Human Proteome Project (SpHPP).S

Prevention of Chemotherapy-induced Peripheral Neuropathy with PRESIONA, a Therapeutic Exercise and Blood Flow Restriction Program: A Randomized Controlled Study Protocol

Objective This trial will analyze the acute and cumulative effects of a tailored program called PRESIONA that combines therapeutic exercise and blood flow restriction to prevent chemotherapy-induced peripheral neuropathy (CIPN) in individuals with early breast cancer undergoing neoadjuvant chemotherapy. Methods PRESIONA will be a physical therapist–led multimodal exercise program that uses blood flow restriction during low-load aerobic and strength exercises. For the acute study, only 1 session will be performed 1 day before the first taxane cycle, in which 72 women will be assessed before intervention and 24 hours post intervention. For the cumulative study, PRESIONA will consist of 24 to 36 sessions for 12 weeks following an undulatory prescription. At least 80 women will be randomized to the experimental group or control group. Feasibility will be quantified based on the participant recruitment to acceptance ratio; dropout, retention, and adherence rates; participant satisfaction; tolerance; and program security. In the efficacy study, the main outcomes will be CIPN symptoms assessed with a participant-reported questionnaire (EORTC QLQ-CIPN20). In addition, to determine the impact on other participant-reported health and sensorimotor and physical outcomes, the proportion of completed scheduled chemotherapy sessions will be examined at baseline (t0), after anthracycline completion (t1), after intervention (t2), and at the 2-month (t3) and 1-year follow-ups (t4). Conclusion The proposed innovative approach of this study could have a far-reaching impact on therapeutic options, and the physical therapist role could be essential in the oncology unit to improve quality of life in individuals with cancer and reduce side effects of cancer and its treatments. Impact Physical therapists in the health care system could be essential to achieve the planned doses of chemotherapy to improve survival and decrease the side effects of individuals with breast cancer. The prevention of CIPN would have an impact on the quality of life in these individuals, and this protocol potentially could provide an action guide that could be implemented in any health care system.This study is funded by Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (FI19/00230), the Spanish Ministry of Education Cultura y Deporte (FPU17/00939 and FPU18/03575), and Ilustre Colegio Profesional de Fisioterapeutas de Andalucía (AI-04/2020)

¿Puede el peletizado y el uso de hidrogel mejorar la implantación de Festuca pallescens en condiciones naturales? Comunicación

Publicado en: Revista Argentina de Producción Animal. Vol. 42 (Sup. 1) : 125 (2022). Mejoramiento Genético y Producción de Semillas ForrajerasLa alta presión de pastoreo, junto con el cambio climático, están provocando el retroceso de algunos pastizales en zonas productivas de la Patagonia. Esto es lo que ocurre con los pastizales dominados por Festuca pallescens (coirón blanco o coirón dulce), una especie clave debido a su gran distribución y su importancia como forrajera para el ganado (Siffredi et al 2014). Desde hace varios años se vienen realizando trabajos de domesticación y mejoramiento genético de F. pallescens en el INTA con el objetivo de llevarla al cultivo en zonas degradadas o altamente susceptibles a la degradación. De este modo se lograría incrementar la productividad de los pastizales, mitigar su degradación y promover su restauración (Marchelli et al 2021).Estación Experimental Agropecuaria BarilocheFil: Martin Albarracin, Valeria Leticia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Martin Albarracin, Valeria Leticia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Easdale, Marcos Horacio. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Easdale, Marcos Horacio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Avanzini, Germán. Barenbrug Argentina. Departamento de Investigación y Desarrollo en Biotecnología; ArgentinaFil: Azpilicueta, Maria Marta. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Azpilicueta, Maria Marta. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Guidalevich, Verónica. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Guidalevich, Verónica. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche IFAB); ArgentinaFil: Lopez, Aldana Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Lopez, Aldana Soledad. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Marchelli, Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); ArgentinaFil: Marchelli, Paula. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Instituto de Investigaciones Forestales y Agropecuarias Bariloche (IFAB); Argentin

p73 is required for appropriate BMP-induced mesenchymal-to-epithelial transition during somatic cell reprogramming

The generation of induced pluripotent stem cells (iPSCs) by somatic cell reprogramming holds great potential for modeling human diseases. However, the reprogramming process remains very inefficient and a better understanding of its basic biology is required. The mesenchymal-to-epithelial transition (MET) has been recognized as a crucial step for the successful reprogramming of fibroblasts into iPSCs. It has been reported that the p53 tumor suppressor gene acts as a barrier of this process, while its homolog p63 acts as an enabling factor. In this regard, the information concerning the role of the third homolog, p73, during cell reprogramming is limited. Here, we derive total Trp73 knockout mouse embryonic fibroblasts, with or without Trp53, and examine their reprogramming capacity. We show that p73 is required for effective reprogramming by the Yamanaka factors, even in the absence of p53. Lack of p73 affects the early stages of reprogramming, impairing the MET and resulting in altered maturation and stabilization phases. Accordingly, the obtained p73-deficient iPSCs have a defective epithelial phenotype and alterations in the expression of pluripotency markers. We demonstrate that p73 deficiency impairs the MET, at least in part, by hindering BMP pathway activation. We report that p73 is a positive modulator of the BMP circuit, enhancing its activation by DNp73 repression of the Smad6 promoter. Collectively, these findings provide mechanistic insight into the MET process, proposing p73 as an enhancer of MET during cellular reprogramming.Peer reviewe