MICA-129 dimorphism and soluble MICA are associated with the progression of multiple myeloma

Natural killer (NK) cells are immune innate effectors playing a pivotal role in the immunosurveillance of multiple myeloma (MM) since they are able to directly recognize and kill MM cells. In this regard, among activating receptors expressed by NK cells, NKG2D represents an important receptor for the recognition of MM cells, being its ligands expressed by tumor cells, and being able to trigger NK cell cytotoxicity. The MHC class I-related molecule A (MICA) is one of the NKG2D ligands; it is encoded by highly polymorphic genes and exists as membrane-bound and soluble isoforms. Soluble MICA (sMICA) is overexpressed in the serum of MM patients, and its levels correlate with tumor progression. Interestingly, a methionine (Met) to valine (Val) substitution at position 129 of the α2 heavy chain domain classifies the MICA alleles into strong (MICA-129Met) and weak (MICA-129Val) binders to NKG2D receptor. We addressed whether the genetic polymorphisms in the MICA-129 alleles could affect MICA release during MM progression. The frequencies of Val/Val, Val/Met, and Met/Met MICA-129 genotypes in a cohort of 137 MM patients were 36, 43, and 22%, respectively. Interestingly, patients characterized by a Val/Val genotype exhibited the highest levels of sMICA in the sera. In addition, analysis of the frequencies of MICA-129 genotypes among different MM disease states revealed that Val/Val patients had a significant higher frequency of relapse. Interestingly, NKG2D was downmodulated in NK cells derived from MICA-129Met/Met MM patients. Results obtained by structural modeling analysis suggested that the Met to Val dimorphism could affect the capacity of MICA to form an optimal template for NKG2D recognition. In conclusion, our findings indicate that the MICA-129Val/Val variant is associated with significantly higher levels of sMICA and the progression of MM, strongly suggesting that the usage of soluble MICA as prognostic marker has to be definitely combined with the patient MICA genotype

Multicomponent Antibiofilm Lipid Nanoparticles as Novel Platform to Ameliorate Resveratrol Properties: Preliminary Outcomes on Fibroblast Proliferation and Migration

: The well-being of skin and mucous membranes is fundamental for the homeostasis of the body and thus it is imperative to treat any lesion quickly and correctly. In this view, polyphenols might assist and enhance a successful wound healing process by reducing the inflammatory cascade and the production of free radicals. However, they suffer from disadvantageous physico-chemical properties, leading to restricted clinical use. In this work, a complex mixture of PEGylated lipid, Glyceryl monoester, 18-β-Glycyrrhetinic Acid and Menthol was designed to entrap Resveratrol (RSV) as the active ingredient and further produce lipid nanoparticles (LNPs) by homogenization followed by high-frequency sonication. The nanosystem was properly characterized in terms of particle size (DLS, SEM), zeta potential, drug loading, antioxidant power (DPPH), release behaviour, cytocompatibility, wound healing and antibiofilm properties. The optimized lipid mixture was homogeneous, melted at 57-61 °C and encapsulated amorphous RSV (4.56 ± 0.04% w/w). The RSV-loaded LNPs were almost monodispersed (PDI: 0.267 ± 0.010), with nanometric size (162.86 ± 3.12 nm), scavenger properties and suitable DR% and LE% values (96.82 ± 1.34% and 95.17 ± 0.25%, respectively). The release studies were performed to simulate the wound conditions: 1-octanol to mimic the lipophilic domains of biological tissues (where the First Order kinetic was observed) and citrate buffer pH 5.5 according to the inflammatory wound exudate (where the Korsmeyer-Peppas kinetic was followed). The biological and microbiological evaluations highlighted fibroblast proliferation and migration effects as well as antibiofilm properties at extremely low doses (LNPs: 22 μg/mL, corresponding to RSV 5 µM). Thus, the proposed multicomponent LNPs could represent a valuable RSV delivery platform for wound healing purposes

Fulminant septic shock caused by Capnocytophaga canimorsus in Italy: Case report

Capnocytophaga canimorsus infection was recently recognized as a zoonosis. We report the first case of fulminant septic shock in Italy caused by this pathogen. The patient, with a history of splenectomy, died at the main hospital in Brescia with a presumptive diagnosis of sepsis. PCR and sequencing on post mortem samples confirmed C. canimorsus as a causative organism. Our purpose is to alert medical professionals to the virulence of C. canimorsus in asplenic and immunocompromised patients. Keywords: Capnocytophaga canimorsus, septic shock, PCR, sequencin

Manual de Indicadores para Monitoreo de Planes Prediales de Manejo de Bosque con Ganadería Integrada – MBGI Región Patagónica

El presente informe presenta los indicadores MBGI a una escala predial para la región Patagónica, y propone una metodología para la toma de información y posterior análisis de los indicadores. En un proceso participativo, entendido como una consulta amplia a expertos y trabajo de taller para la redefinición y priorización de indicadores, y por indicación de la Mesa Nacional MBGI, se generaron los siguientes indicadores de monitoreo a escala predial. El trabajo se llevó adelante con la participación de un grupo diversificado de expertos especialmente seleccionados (ej. INTA, Universidades, CONICET, Direcciones de Bosques, MAyDS, MAGyP). Los indicadores que a continuación se detallan son una guía orientativa y facilitadora para los productores, técnicos y organismos del Estado en el manejo adaptativo de las prácticas MBGI en la región Patagónica. Es decir, los indicadores han sido diseñados como una herramienta para la determinación de las líneas de base a nivel predial, así como para asistir al monitoreo de los planes de manejo, brindando elementos básicos para la interpretación, reflexión y ajuste de las prácticas de manejo implementadas en el campo. La sustentabilidad per se, puede ser un objetivo móvil dados los cambios ambientales y sociales que se producen temporalmente. Sin embargo, es importante resaltar, que existen umbrales que, al ser traspasados impiden el logro de la misma. Este es uno de los principales objetivos del empleo de indicadores, aunque uno de los aspectos más complejos. Tanto evaluar la evolución de los indicadores a través del tiempo, como referir el estado de los mismos a dichos umbrales son las principales funciones de su medición, ya que subrayan las alertas más necesarias a la hora de implementar un manejo adaptativo. Otro aspecto central a tener en cuenta es que el predio debe contar con un área bajo pastoreo, un área de conservación y un área conectora, las que deben estar claramente especificadas, en el espacio. Cada una de ellas posee un objetivo diferente. Por ello, los indicadores deberían reflejar la situación real en cada una en forma independiente, considerando que el valor “deseado” o esperado dependerá del objetivo que esa área deba cumplir.EEA Santa CruzFil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Rusch, Verónica Elena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área Forestal. Grupo de Ecología Forestal; Argentina.Fil: Von Müller, Axel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Esquel; Argentina.Fil: Varela, Santiago Agustin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; ArgentinaFil: Quinteros, Claudia Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro científico tecnológico Conicet - Patagonia norte; Argentina.Fil: Quinteros, Claudia Pamela. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de investigación Esquel de montaña y estepa patagonica; Argentina.Fil: Martínez Pastur, Guillermo José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas (CADIC); Argentina

Herramienta para analizar la relación entre la toma de decisiones y el mantenimiento de los servicios ecosistémicos: Estudio de caso en bosque nativo de ñire de patagonia norte.

La toma de decisiones sobre el manejo de los sistemas socio-ecológicos que producen Servicios Ecosistémicos (SE) son complejas por los plazos, las interacciones de los factores intervinientes, y las percepciones de los actores. Este trabajo tiene como objetivo proponer una metodología que permita integrar los conocimientos sobre los procesos de cambio de los ecosistemas y los de toma de decisión, resaltando el rol de los SE. Mediante un taller de expertos, y basándonos en información preexistente y cálculos ad hoc, se integraron tres propuestas metodológicas: (1) los Modelos de Estados y Transiciones, que modelan el comportamiento del ecosistema, sus caminos de degradación y recuperación; (2) la definición y cuantificación de los SE provistos por cada uno de los estados del ecosistema, considerando los SE finales, los beneficios y el valor monetario de los mismos y (3) los modelos de Toma de Decisiones basado en estadística bayesiana, que considera los objetivos finales mediante una matriz de valoración; los objetivos intermedios, y las decisiones de manejo posibles que impactan sobre estos. La propuesta se ejemplifica con bosques de Nothofagus antárctica de Patagonia norte.Decision making about the management of socio-ecological systems that produce Ecosystem Services (ES) are complicated by the terms, number of factors involved in the processes and their interactions, and perceptions of the actors. This paper aims to propose a methodology to integrate knowledge about the processes of ecosystem change and decision making, highlighting the role of SE. Through a workshop of experts, and based on existing information and calculations ad hoc three methodological proposals were integrated: (1) Models States and Transitions, modelling ecosystem behaviour, its ways of degradation and recovery; (2) the definition and quantification of the ES provided by each of the states of the ecosystem, considering the final ES end, benefits and monetary value and (3) A Decision Making Models, based on Bayesian networks which considers the final objectives through a matrix of values; intermediate objectives and possible management decisions that impact on them. The proposal is exemplified by Nothofagus antarctica forests of northern Patagonia.EEA Santa CruzFil: Rusch, Verónica Elena. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Área Forestal. Grupo de Ecología Forestal; Argentina.Fil: Goijman, Andrea Paula. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentina.Fil: Peri, Pablo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santa Cruz; Argentina.Fil: Peri, Pablo Luis. Universidad Nacional de la Patagonia Austral; Argentina.Fil: Peri, Pablo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Lopez, Dardo Ruben. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Manfredi. Campo Anexo Villa Dolores; Argentina.Fil: Lopez, Dardo Ruben. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Claps, Leonardo Luis. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; Argentina.Fil: Sarasola, Mauro Miguel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche; Argentina.Fil: Cardozo, Andrea. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Bariloche. Agencia de Extensión Rural El Bolsón; Argentina.Fil: Rusch, Graciela Mónica. Norwegian Institute for Nature Research (NINA). Trondheim; Norueg

Antimicrobial Prophylaxis in Neonates and Children Undergoing Dental, Maxillo-Facial or Ear-Nose-Throat (ENT) Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication in surgical procedures, mainly because clean/contaminated surgery involves organs that are normally colonized by bacteria. Dental, maxillo-facial and ear-nose-throat (ENT) surgeries are among those that carry a risk of SSIs because the mouth and the first respiratory tracts are normally colonized by a bacterial flora. The aim of this consensus document was to provide clinicians with recommendations on surgical antimicrobial prophylaxis in neonates (<28 days of chronological age) and pediatric patients (within the age range of 29 days-18 years) undergoing dental, maxillo-facial or ENT surgical procedures. These included: (1) dental surgery; (2) maxilla-facial surgery following trauma with fracture; (3) temporo-mandibular surgery; (4) cleft palate and cleft lip repair; (5) ear surgery; (6) endoscopic paranasal cavity surgery and septoplasty; (7) clean head and neck surgery; (8) clean/contaminated head and neck surgery and (9) tonsillectomy and adenoidectomy. Due to the lack of pediatric data for the majority of dental, maxillo-facial and ENT surgeries and the fact that the recommendations for adults are currently used, there is a need for ad hoc studies to be rapidly planned for the most deficient areas. This seems even more urgent for interventions such as those involving the first airways since the different composition of the respiratory microbiota in children compared to adults implies the possibility that surgical antibiotic prophylaxis schemes that are ideal for adults may not be equally effective in children

Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Undergoing Orthopedic and Hand Surgery: A RAND/UCLA Appropriateness Method Consensus Study

Surgical site infections (SSIs) represent a potential complication in any type of surgery and can occur up to one year after the procedure in the case of implant placement. In the field of orthopedic and hand surgery, the rate of SSIs is a relevant issue, considering the need for the placement of synthesis devices and the type of some interventions (e.g., exposed fractures). This work aims to provide guidance on the management of peri-operative antibiotic prophylaxis for the pediatric and neonatal population undergoing orthopedic and hand surgery in order to standardize the management of patients and to reduce, on the one hand, the risk of SSI and, on the other, the development of antimicrobial resistance. The following scenarios were considered: (1) bloodless fracture reduction; (2) reduction of unexposed fracture and grade I and II exposed fracture; (3) reduction of grade III exposed fracture or traumatic amputation; (4) cruel fracture reduction with percutaneous synthesis; (5) non-traumatic amputation; (6) emergency intact skin trauma surgery and elective surgery without synthetic media placement; (7) elective orthopedic surgery with prosthetic and/or synthetic media placement and spinal surgery; (8) clean elective hand surgery with and without bone involvement, without use of synthetic means; (9) surgery of the hand on an elective basis with bone involvement and/or with use of synthetic means. This manuscript has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding the behavior to be adopted in the peri-operative setting in neonatal and pediatric orthopedic and hand surgery. The specific scenarios developed are aimed at guiding the healthcare professional in practice to ensure the better and standardized management of neonatal and pediatric patients, together with an easy consultation