Drug repurposing: tolfenamic acid inactivates PrbP, a transcriptional accessory protein in liberibacter asiaticus

CLIBASIA_01510, PrbP, is a predicted RNA polymerase binding protein in Liberibacter asiaticus. PrbP was found to regulate expression of a small subset of ribosomal genes through interactions with the β-subunit of the RNA polymerase and a short, specific sequence on the promoter region. Molecular screening assays were performed to identify small molecules that interact with PrbP in vitro. Chemical hits were analyzed for therapeutic efficacy against L. asiaticus via an infected leaf assay, where the transcriptional activity of L. asiaticus was found to decrease significantly after exposure to tolfenamic acid. Similarly, tolfenamic acid was found to inhibit L. asiaticus infection in highly symptomatic citrus seedlings. Our results indicate that PrbP is an important transcriptional regulator for survival of L. asiaticus in planta, and the chemicals identified by molecular screening assays could be used as a therapeutic treatment for huanglongbing disease.Fil: Gardner, Christopher L.. University of Florida; Estados UnidosFil: Pagliai, Fernando A.. University of Florida; Estados UnidosFil: Pan, Lei. University of Florida; Estados UnidosFil: Bojilova, Lora. University of Florida; Estados UnidosFil: Torino, Maria Ines. University of Florida; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; ArgentinaFil: Lorca, Graciela L.. University of Florida; Estados UnidosFil: Gonzalez, Claudio F.. University of Florida; Estados Unido

Planeamiento estratégico BAT Perú: 2016-2018

El estudio realizado concluye que la estrategia genérica debe estar orientada a un enfoque con bajo costo, ello sostenido por la ventaja competitiva de los canales de distribución. Asimismo, se requiere de estrategias específicas en marketing orientadas al consumidor y a los puntos de venta para lograr una fidelización de la marca, agregándole valor. La sostenibilidad en el tiempo de este planteamiento tiene como piedra angular la innovación a lo largo de toda la cadena de distribución, logrando optimizar los procesos y, por ende, reduciendo los costos. Asimismo, la administración y el uso eficiente de la información irán en ese sentido, alcanzando además un mejor conocimiento del comportamiento de los consumidores y puntos de venta, consiguiendo determinar el enfoque necesario hacia el cliente objetivo. Cabe resaltar que la estrategia planteada es acorde a las políticas empresariales que determinan: el crecimiento no se sostiene en incentivar a los consumidores a un consumo mayor ni atraer a nuevos clientes sino en aumentar valor a las marcas, esto de la mano con una reducción de costos es lo que logrará incrementar la rentabilidad. Este trabajo presenta el planeamiento estratégico para el trienio 2016-2018 y será la base que demarcará el camino para la siguiente década

In vitro assessment of a novel composite scaffold for articular cartilage restoration

Articular cartilage (AC) lesions are a particular challenge for regenerative medicine due to cartilage low self-ability repair in case of damage. Hence, a significant goal of musculoskeletal tissue engineering is the development of suitable structures in virtue of their matrix composition and biomechanical properties [1]. The objective of our study was to design in vitro a supporting structure for cartilage chondrocytes to treat focal articular joint defects. We realized a bio-hybrid composite scaffold combining decellularized Wharton’s jelly (W’s J) with the biomechanical properties of the synthetic hydrogel polyvinyl alcohol (PVA). The hydrogel itself and the more specific decellularized cartilage matrix were used as controls. Immunohistochemical analysis highlighted a similar histomorphology for W’s J and AC matrices. Human chondrocytes were isolated from articular cartilage by collagenase II digestion and then characterized by flow-cytometry and RT-PCR to assess the expression of specific markers. CD44+/CD73+/CD151+ chondrocytes were seeded on PVA, PVA/AC and PVA/W’s J scaffolds to test their ability to support cell colonization. According to SEM micrographs and MTT proliferation assay, PVA/W’s J revealed a singular attitude to sustain cell proliferation despite its aspecific origin. Our preliminary evidences highlighted the chance of using Wharton’s jelly in combination with PVA hydrogels as an innovative and easily available scaffold for cartilage restoration

The “Wireless Sensor Networks for City-Wide Ambient Intelligence (WISE-WAI)” Project

This paper gives a detailed technical overview of some of the activities carried out in the context of the “Wireless Sensor networks for city-Wide Ambient Intelligence (WISE-WAI)” project, funded by the Cassa di Risparmio di Padova e Rovigo Foundation, Italy. The main aim of the project is to demonstrate the feasibility of large-scale wireless sensor network deployments, whereby tiny objects integrating one or more environmental sensors (humidity, temperature, light intensity), a microcontroller and a wireless transceiver are deployed over a large area, which in this case involves the buildings of the Department of Information Engineering at the University of Padova. We will describe how the network is organized to provide full-scale automated functions, and which services and applications it is configured to provide. These applications include long-term environmental monitoring, alarm event detection and propagation, single-sensor interrogation, localization and tracking of objects, assisted navigation, as well as fast data dissemination services to be used, e.g., to rapidly re-program all sensors over-the-air. The organization of such a large testbed requires notable efforts in terms of communication protocols and strategies, whose design must pursue scalability, energy efficiency (while sensors are connected through USB cables for logging and debugging purposes, most of them will be battery-operated), as well as the capability to support applications with diverse requirements. These efforts, the description of a subset of the results obtained so far, and of the final objectives to be met are the scope of the present paper

Exploring a tissue engineering strategy as a novel approach for haemophilic arthropathy treatment

Among the most disabling complications of Haemophilia, repeated and sponta- neous intra-articular haemorrhages may cause irreversible damage to the joint. This leads to haemophilic arthropathy, a polyarticular disease characterized by joint stiff- ness, chronic pain and a severely limited range of motion. Occurrence of haemophilic arthropathy can be avoided by the prophylactic administration of clotting factors to prevent articular haemorrhages, but it can also be addressed using anti-inflammatory drugs and surgery to alleviate the effects of articular damage, up to arthroplasty as resolute option [1]. However, innovative strategies for the prevention and treatment of this common and serious complication are still required, due to some important limits of current therapies, first of all inhibitor development. In this work, we inves- tigated a tissue engineering approach to regenerate articular focal lesions in Haemo- philic patients by in vitro development of an autologous bio-hybrid prosthesis. For this purpose, we isolated articular chondrocytes from Haemophilic patients (HaeCs) and characterized them for the first time in literature, to verify whether they were altered by blood exposure. Using healthy chondrocytes as control, optical microscope morphological analysis, flow cytometry immunophenotype evaluation and gene expression study by qRT-PCR were performed. After that, an innovative compos- ite scaffold was obtained by combining decellularized Wharton’s Jelly (W’s J) from human umbilical cord with a novel biodegradable polyvinyl alcohol (PVA) hydrogel [2]. Finally, we assessed HaeCs capacity to re-populate biosynthetic scaffolds by Scan- ning Electron Microscopy and MTT assay on cells seeded on supports. Taken togeth- er, our results contributed to define HaeCs phenotype, highlighting the possibility to use these cells for autologous implant. What is more, HaeCs capacity to growth and proliferate on composite scaffolds set the stage for planning the development of autologous tissue substitutes for haemophilic cartilage regeneration

Correction to: Being active with a total hip or knee prosthesis: a systematic review into physical activity and sports recommendations and interventions to improve physical activity behavior

Objectives: Regular physical activity (PA) is considered important after total hip and knee arthroplasty (THA/TKA). Objective was to systematically assess literature on recommendations given by healthcare professionals to persons after THA and TKA and to provide an overview of existing interventions to stimulate PA and sports participation. Methods: A systematic review with a narrative synthesis including articles published between January 1995 and January 2021 reporting on recommendations and interventions. The PubMed, Embase, CINAHL and PsycInfo databases were systematically searched for original articles reporting on physical activity and sports recommendations given by healthcare professionals to persons after THA and TKA, and articles reporting on interventions/programs to stimulate a physically active lifestyle after rehabilitation or explicitly defined as part of the rehabilitation. Methodological quality was assessed with the Mixed Methods Appraisal Tool (MMAT). The review was registered in Prospero (PROSPERO:CRD42020178556). Results: Twenty-one articles reported on recommendations. Low-impact activities were allowed. Contact sports, most ball sports, and martial arts were not recommended. One study informed on whether health-enhancing PA recommendations were used to stimulate persons to become physically active. No studies included recommendations on sedentary behavior. Eleven studies reported on interventions. Interventions used guidance from a coach/physiotherapist; feedback on PA behavior from technology; and face-to-face, education, goal-setting, financial incentives and coaching/financial incentives combined, of which feedback and education seem to be most effective. For methodological quality, 18 out of 21 (86%) articles about recommendations and 7 out of 11 (64%) articles about interventions scored yes on more than half of the MMAT questions (0–5 score). Conclusion: There is general agreement on what kind of sports activities can be recommended by healthcare professionals like orthopedic surgeons and physiotherapists. No attention is given to amount of PA. The same is true for limiting sedentary behavior. The number of interventions is limited and diverse, so no conclusions can be drawn. Interventions including provision of feedback about PA, seem to be effective and feasible

Being active with a total hip or knee prosthesis: a systematic review into physical activity and sports recommendations and interventions to improve physical activity behavior

Objectives Regular physical activity (PA) is considered important after total hip and knee arthroplasty (THA/TKA). Objective was to systematically assess literature on recommendations given by healthcare professionals to persons after THA and TKA and to provide an overview of existing interventions to stimulate PA and sports participation. Methods A systematic review with a narrative synthesis including articles published between January 1995 and January 2021 reporting on recommendations and interventions. The PubMed, Embase, CINAHL and PsycInfo databases were systematically searched for original articles reporting on physical activity and sports recommendations given by healthcare professionals to persons after THA and TKA, and articles reporting on interventions/programs to stimulate a physically active lifestyle after rehabilitation or explicitly defined as part of the rehabilitation. Methodological quality was assessed with the Mixed Methods Appraisal Tool (MMAT). The review was registered in Prospero (PROSPERO:CRD42020178556). Results Twenty-one articles reported on recommendations. Low-impact activities were allowed. Contact sports, most ball sports, and martial arts were not recommended. One study informed on whether health-enhancing PA recommendations were used to stimulate persons to become physically active. No studies included recommendations on sedentary behavior. Eleven studies reported on interventions. Interventions used guidance from a coach/physiotherapist; feedback on PA behavior from technology; and face-to-face, education, goal-setting, financial incentives and coaching/financial incentives combined, of which feedback and education seem to be most effective. For methodological quality, 18 out of 21 (86%) articles about recommendations and 7 out of 11 (64%) articles about interventions scored yes on more than half of the MMAT questions (0-5 score). Conclusion There is general agreement on what kind of sports activities can be recommended by healthcare professionals like orthopedic surgeons and physiotherapists. No attention is given to amount of PA. The same is true for limiting sedentary behavior. The number of interventions is limited and diverse, so no conclusions can be drawn. Interventions including provision of feedback about PA, seem to be effective and feasible

Amount and type of physical activity and sports from one year forward after hip or knee arthroplasty—A systematic review

Introduction After rehabilitation following total hip or knee arthroplasty (THA/TKA), patients are advised to participate in physical activity (PA) and sports. However, profound insight into whether people adopt a physically active lifestyle is lacking. Aim is to gain insight into the performed amount and type of PA (including sports) and time spent sedentarily by persons after THA/ TKA. Methods A systematic review (PROSPERO: CRD42020178556). Pubmed, Cinahl, EMBASE and PsycInfo were systematically searched for articles reporting on amount of PA, and on the kind of activities performed between January 1995-January 2021. Quality of the articles was assessed with the adapted tool from Borghouts et al. Results The search retrieved 5029 articles, leading to inclusion of 125 articles reporting data of 123 groups; 53 articles reported on subjects post-THA, 16 on post-hip-resurfacing arthroplasty, 40 on post-TKA, 15 on post-unicompartimental knee arthroplasty and 12 on a mix of arthroplasty types. With respect to quality assessment, 14 articles (11%) met three or fewer criteria, 29 (24%) met four, 32 (26%) met five, 42 (34%) met six, and 6 (5%) met seven out of the eight criteria. PA levels were comparable for THA and TKA, showing a low to moderately active population. Time spent was mostly of low intensity. Roughly 50% of -subjects met health-enhancing PA guidelines. They spent the largest part of their day sedentarily. Sports participation was relatively high (rates above 70%). Most participation was in low-impact sports at a recreational level. Roughly speaking, participants were engaged in sports 3 hours/week, consisting of about three 1-hour sessions. Conclusion Activity levels seem to be low; less than half of them seemed to perform the advised amount of PA following health-enhancing guidelines Sports participation levels were high. However, many articles were unclear about the definition of sports participation, which could have led to overestimation

Italian Guidelines in diagnosis and treatment of alopecia areata

Alopecia areata (AA) is an organ-specific autoimmune disorder that targets anagen phase hair follicles. The course is unpredictable and current available treatments have variable efficacy. Nowadays, there is relatively little evidence on treatment of AA from well-designed clinical trials. Moreover, none of the treatments or devices commonly used to treat AA are specifically approved by the Food and Drug Administration. The Italian Study Group for Cutaneous Annexial Disease of the Italian Society of dermatology proposes these Italian guidelines for diagnosis and treatment of Alopecia Areata deeming useful for the daily management of the disease. This article summarizes evidence-based treatment associated with expert-based recommendations

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission