Extracellular Vesicles From Liver Progenitor Cells Downregulates Fibroblast Metabolic Activity and Increase the Expression of Immune-Response Related Molecules

Extracellular vesicles (EVs) mediate cell-to-cell crosstalk whose content can induce changes in acceptor cells and their microenvironment. MLP29 cells are mouse liver progenitor cells that release EVs loaded with signaling cues that could affect cell fate. In the current work, we incubated 3T3-L1 mouse fibroblasts with MLP29-derived EVs, and then analyzed changes by proteomics and transcriptomics. Results showed a general downregulation of protein and transcript expression related to proliferative and metabolic routes dependent on TGF-beta. We also observed an increase in the ERBB2 interacting protein (ERBIN) and Cxcl2, together with an induction of ribosome biogenesis and interferon-related response molecules, suggesting the activation of immune system signaling

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true

PEGylated systems in pharmaceutics

This review addresses the use of poly(ethylene glycol) (PEG) and PEG conjugation for the design of novel dosage forms and the modification of biomolecules. The peculiarities of PEGylated nanoparticles, liposomes, proteins, enzymes, and small drug and polyelectrolyte molecules and their influence on systemic drug delivery, including overcoming of various biological barriers and adhesion to mucosal tissues (mucoadhesion), are considered

The roles played by the British Chiefs of Staff Committee in the evolution of Britain's nuclear weapon planning and policy-making, 1945-55

SIGLEAvailable from British Library Document Supply Centre- DSC:DX84631 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Evaluación del Diklason® ampollas en el dolor agudo

Antecedentes: El dolor agudo es definido como dolor de reciente comienzo y probablemente de duración limitada que se relaciona de manera causal y temporal con un daño o enfermedad.Los antiinflamatorios no esteroideos modulan el dolor periférico por reducción de la producción de prostaglandinas y de los neuropéptidos. Ejemplos típicos de dolor agudo son: el dolor post-operatorio, lumbago, dolor por injuria de partes blandas o hueso y cólico nefrítico. Este tipo de dolor es incrementado por la ansiedad, el catastrofismo, neuroticismo y la depresión. El diclofenac potásico ha demostrado ser un fármaco seguro y efectivo en el manejo del dolor agudo.Material y Método: Se realizó un estudio abierto, prospectivo y multicéntrico en 220 pacientes con diagnóstico de dolor agudo, de intensidad severa y moderada a los cuales se les suministró una dosis IM o IV de diclofenac potásico (Diklason®) de 75 mg y se midió la intensidad del dolor mediante las siguientes escalas: VAS 0-100, PID, SPID, Pain Relief y TOTPAR, medicación de rescate y escala clínica de cambio.La inocuidad se evaluó por interrogatorio directo de efectos adversos.Las evaluaciones se realizaron al inicio, a las 0.5, 1, 2, 4, 6, 8 y 12 h de la administración de la dosis.Resultados: Se produjo un descenso importante en los niveles de VAS desde los 30 min. de tratamiento y este descenso fue significativo entre los períodos de evaluación hasta las 8 horas, el efecto persistió hasta las 12 horas. El 90,45% de los pacientes comenzaron a sentir alivio del dolor a los 30 min. Todas las escalas evaluadas mostraron cambios significativos en los períodos evaluados desde los primeros 30 min. hasta las 8 horas (SPID), 12 h (SPID, PR, y TOTPAR).En el 92,72% de los pacientes los resultados fueron adecuados: excelentes (56,3%) y buenos (36,36%). Se presentaron 6 efectos adversos leves.Conclusiones: El diclofenac potásico (Diklason®) resulta rápido, efectivo y duradero en el manejo del dolor agudo de diferentes etiologías.Background: Acute pain is defined as a pain of recent onset and probably limited duration which is associated with a causal and temporal damage or disease.NSAIDs modulate peripheral pain by reducing prostaglandin and neuropeptides production. Typical examples of acute pain include post operatory, lumbago, bone or soft tissue injuries and, renal colic. This type of pain is increased by anxiety, catastropic events, neuroticism and depression. Diclofenac potassium is proved to be safe and effective in management acute pain.Materials and methods: We conducted a multicenter; prospective, open study in 220 patients with acute pain (moderate to severe intensity) which supply with IM or IV dose of diclofenac potassium (Diklason®) 75 mg, the pain intensity was measured by the following scales: VAS 0-100, PID, SPID, Pain Relief and TOTPAR, rescue medication and clinical scale changes.The safety was assessed by direct questioning side effects.Evaluations were performed at baseline at 30 minutes, 1, 2, 4, 6, 8, and 12 hours after dosage.Results: There was a significant decrease in VAS levels from 30 minutes of treatment and this decrease was significant between the evaluation periods up to 8 hours, the effect persisted for 12 hours. In 90.45% of patients began to feel pain relief within 30 minutes. All scales evaluated showed significant changes in the periods evaluated from the first 30 minutes up to 8 hours (SPID), 12 h (SPID, PR, and TOTPAR).In 92.72% of results were suitable: excellent (56.3%) and good (36.36%). We found 6 mild adverse effects.Conclusions: Diclofenac potassium (Diklason®) is quick, effective and durable in the management of acute pain of various etiologies

REMS: the environmental sensor suite for the Mars Science Laboratory rover

The Rover Environmental Monitoring Station (REMS) will investigate environ- mental factors directly tied to current habitability at the Martian surface during the Mars Sci- ence Laboratory (MSL) mission. Three major habitability factors are addressed by REMS: the thermal environment, ultraviolet irradiation, and water cycling. The thermal environment is determined by a mixture of processes, chief amongst these being the meteorological. Ac- cordingly, the REMS sensors have been designed to record air and ground temperatures, pressure, relative humidity, wind speed in the horizontal and vertical directions, as well as ultraviolet radiation in different bands. These sensors are distributed over the rover in four places: two booms located on the MSL Remote Sensing Mast, the ultraviolet sensor on the rover deck, and the pressure sensor inside the rover body. Typical daily REMS observa- tions will collect 180 minutes of data from all sensors simultaneously (arranged in 5 minute hourly samples plus 60 additional minutes taken at times to be decided during the course of the mission). REMS will add significantly to the environmental record collected by prior missions through the range of simultaneous observations including water vapor; the ability to take measurements routinely through the night; the intended minimum of one Martian year of observations; and the first measurement of surface UV irradiation. In this paper, we describe the scientific potential of REMS measurements and describe in detail the sensors that constitute REMS and the calibration proceduresPeer Reviewe