Potential use for chronic pain: Poly(Ethylene Glycol)-Poly(Lactic-Co-Glycolic Acid) nanoparticles enhance the effects of Cannabis-Based terpenes on calcium influx in TRPV1-Expressing cells

The objective of these in vitro studies was to investigate the impact of the encapsulation of three cannabis-based terpenes, namely β-myrcene (MC), β-caryophyllene (CPh), and nerolidol (NL), on their potential efficacy in pain management. Terpene-encapsulated poly(ethylene glycol)-poly(lactic-co-glycolic acid) nanoparticles (PEG-PLGA NPs) were prepared by an emulsion-solvent evaporation method. The terpene-loaded NPs were examined in HEK293 cells that express the nociceptive transient receptor potential vanilloid- 1 (TRPV1), an ion channel involved in pain perception. TRPV1 activation was assessed by monitoring calcium influx kinetics over 1 h in cells pre-treated with the fluorescent indicator Fluo-4. In addition, the fluorescence intensity changes induced by the NPs in living cells were also explored by a fluorescence microscope. Furthermore, the cytotoxicity of the terpene-loaded NPs was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-3,5-diphenyl tetrazolium bromide (MTT) proliferation assay. The terpene-loaded NPs had a diameter in the range of 250–350 nm and a zeta potential of approximately −20 mV. The encapsulation efficiency was 18.5%, 51.3%, and 60.3% for MC, NL, and CPh NPs, respectively. The nano-formulations significantly increased the fluorescence intensity in comparison with free terpenes. Furthermore, combinations of terpene-loaded NPs produced significantly higher calcium responses when compared to combinations of free terpenes. Similar findings were shown by the fluorescence images. In conclusion, the terpene-PLGA NPs can be promising therapeutics for more effective pain management

Postoperative Analgesia in Plastic Surgery Procedures

Advances in the knowledge of the secondary effects of acute postoperative pain have motivated anesthesiologists and surgeons to pay special attention to its prevention and correct management. Surgical procedures in plastic surgery are very varied and produce postoperative pain in direct relation to the site, type, and extent of surgery, with facial interventions being the least painful (with the exception of rhinoplasty) and the most painful being breast surgery, abdominoplasty, and extensive liposuctions due to the possibility of trauma to peripheral nerves and greater secondary inflammation. The combination of surgeries produces more intense post-surgical pain. There is insufficient data on the frequency and severity of pain after plastic surgery, be it reconstructive or cosmetic. Although opioids have been considered to be the cornerstone in the treatment of postsurgical pain, their use in plastic surgery patients must be carefully evaluated for various reasons that interfere with the results of this type of surgery. Similar to other surgical specialties, multimodal analgesia is now the most appropriate way to prevent and treat pain in these patients. This chapter is a comprehensive review of the management of acute postoperative pain in certain plastic surgery procedures, with emphasis on the multimodal approach

High-fat diet alters stress behavior, inflammatory parameters and gut microbiota in Tg APP mice in a sex-specific manner

Long-term high-fat diet (HFD) consumption commonly leads to obesity, a major health concern of western societies and a risk factor for Alzheimer's disease (AD). Both conditions present glial activation and inflammation and show sex differences in their incidence, clinical manifestation, and disease course. HFD intake has an important impact on gut microbiota, the bacteria present in the gut, and microbiota dysbiosis is associated with inflammation and certain mental disorders such as anxiety. In this study, we have analyzed the effects of a prolonged (18 weeks, starting at 7 months of age) HFD on male and female mice, both wild type (WT) and TgAPP mice, a model for AD, investigating the behavioral profile, gut microbiota composition and inflammatory/phagocytosis-related gene expression in hippocampus. In the open-field test, no overt differences in motor activity were observed between male and female or WT and TgAPP mice on a low-fat diet (LFD). However, HFD induced anxiety, as judged by decreased motor activity and increased time in the margins in the open-field, and a trend towards increased immobility time in the tail suspension test, with increased defecation. Intriguingly, female TgAPP mice on HFD showed less immobility and defecation compared to female WT mice on HFD. HFD induced dysbiosis of gut microbiota, resulting in reduced microbiota diversity and abundance compared with LFD fed mice, with some significant differences due to sex and little effect of genotype. Gene expression of pro-inflammatory/phagocytic markers in the hippocampus were not different between male and female WT mice, and in TgAPP mice of both sexes, some cytokines (IL-6 and IFN¿) were higher than in WT mice on LFD, more so in female TgAPP (IL-6). HFD induced few alterations in mRNA expression of inflammatory/phagocytosis-related genes in male mice, whether WT (IL-1ß, MHCII), or TgAPP (IL-6). However, in female TgAPP, altered gene expression returned towards control levels following prolonged HFD (IL-6, IL-12ß, TNF¿, CD36, IRAK4, PYRY6). In summary, we demonstrate that HFD induces anxiogenic symptoms, marked alterations in gut microbiota, and increased expression of inflammatory genes, except for female TgAPP that appear to be resistant to the diet effects. Lifestyle interventions should be introduced to prevent AD onset or exacerbation by reducing inflammation and its associated symptoms; however, our results suggest that the eventual goal of developing prevention and treatment strategies should take sex into consideration.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO), Grant Numbers BFU2014-51836-C2-1-R to LMGS and MAA, BFU2014-51836-C2-2-R and BFU2017-82565-C21-R2 to JAC; Madrid Council S2010/BMD-2349 to MLC; Centre for Biomedical Network Research for Physiopathology of Obesity and Nutrition (CIBEROBN) to JAC, Centre for Biomedical Network Research for Frailty and Healthy Ageing (CIBERFES) to LMGS and MAA, and Centre for Biomedical Network Research for Neurodegenerative Diseases (CIBERNED) to MLC. AC-C was granted with a FPI fellowship by the MINECO (BES-2015-072980)

Comparación de la fibra detergente neutra en gramíneas, calculada mediante algoritmo de análisis de imágenes rojo, verde y azul vs espectroscopia del infrarrojo cercano

The aim of this study to the evaluate the precision of the Red, Green, Blue (RGB) image analysis algorithm included in the TaurusWebs V2017® software for calculating the percentage of neutral detergent fiber (NDF) in the dry matter of grasses, from images of the grasslands taken by a drone with RGB camera. The results were compared with NDF values calculated with near infrared spectroscopy (NIRS). Forty-two samples were taken for NIRS: 18 from grasses from the high tropics in Cundinamarca: kikuyu (Pennisetum clandestinum), velvet grass (Holcus lanatus) and reed canarian grass (Phalaris arundinacea) and 24 from the lower tropics in Tolima, Colombia: pangola (Digitaria decumbens), para (Brachiaria mutica), Bermuda grass (Cynodon dactylon) and silver grass (Bothriochloa pertusa). The results were compared against 180 evaluations made with the algorithm of the images of the same grasses where the samples were taken for NIRS. The Kendall and Spearman correlation tests were significant (p<0.05), with an association of rho = 0.81 for the Kruskal Wallis hypothesis test (p>0.05). There were no significant differences in NDF values under the two methodologies and according to the Wilcoxon test, the medians of DNF calculated by NIRS vs. those of the algorithm are the same. In conclusion, the information generated with the algorithm can be used for NDF analysis work in grasses.El trabajo estuvo orientado a evaluar la precisión del algoritmo de análisis de imágenes Red, Green, Blue (RGB) incluido en el software TaurusWebs V2017® para el cálculo del porcentaje de fibra detergente neutra (FDN) en la materia seca de gramíneas, a partir de imágenes de las praderas tomadas por un dron con cámara RGB. Los resultados fueron comparados con los valores de FDN calculados con espectroscopia del infrarrojo cercano (NIRS). Se tomaron 42 muestras para NIRS: 18 de gramíneas de trópico alto en Cundinamarca: kikuyo (Pennisetum clandestinum), falsa poa (Holcus lanatus) y pasto brasilero (Phalaris arundinacea) y 24 de trópico bajo en Tolima, Colombia: pangola (Digitaria decumbens), pará (Brachiaria mutica), bermuda (Cynodon dactylon) y colosuana (Bothriochloa pertusa). Los resultados se compararon contra 180 evaluaciones hechas con el algoritmo de las imágenes de las mismas gramíneas donde se tomaron las muestras para NIRS. Las pruebas de correlación de Kendall y de Spearman fueron significativas (p<0.05), con una asociación de rho=0.81 para la prueba de hipótesis de Kruskal Wallis (p> 0.05). No hubo diferencias significativas en los valores de FDN bajo las dos metodologías y según la prueba de Wilcoxon las medianas de la FDN calculada por NIRS vs. las del algoritmo son iguales. En conclusión, la información generada con el algoritmo se puede utilizar para trabajos de análisis del FDN en gramíneas

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A bicyclic α-iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration

I2 receptors (I2-IR) are widely distributed in the central nervous system. I2-IR ligands are associated with a neuroprotective effect but, as I2-IR structure remains unknown, the discovery of better and more selective ligands is necessary to understand the pharmacological and molecular implications of I2-IR. Recently, we described a new imidazoline-structure family which showed high affinity and selectivity for I2-IR. In vivo studies in mice indicated a neuroprotective role and revealed beneficial effects in behaviour and cognition with a murine model of neurodegeneration, senescence-accelerated prone mouse (SAMP8). Herein, we report a novel non-imidazoline-structure of bicyclic α-iminophosphonates family with high affinities for I2-IR. In vivo studies in 5X-FAD mice (a transgenic representative model of AD) and SAMP8 mice (a model of neurodegeneration linked to aging) showed an improvement in behaviour and cognition, a reduction of AD hallmarks and of neuroinflammation markers for the mice treated with the lead compound B06. After evaluating several pathways associated with neurodegeneration, we demonstrated that CaN pathway plays a critical role on the neuroprotective effects of I2-IR ligands on SAMP8 mice model. To rule out warnings of the novel family, we calculated DMPK and physicochemical properties for the novel bicyclic α-iminophosphonates. As well, we carried out drug metabolism, safety studies and in vivo pharmacokinetics for lead compound B06. In summary, we present a novel family of I2-IR ligands, its effectiveness in in vivo models and the possible neuroprotective molecular mechanism mediated by them. This highlights that the modulation of I2-IR by bicyclic α-iminophosphonates may open a new therapeutic venue for unmet neurodegenerative conditions

Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease

Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and 3D-QSAR studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased the FADD protein in the hippocampus, a key marker in neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions

COVID-19 outbreaks in a transmission control scenario: challenges posed by social and leisure activities, and for workers in vulnerable conditions, Spain, early summer 2020

Severe acute respiratory syndrome coronavirus 2 community-wide transmission declined in Spain by early May 2020, being replaced by outbreaks and sporadic cases. From mid-June to 2 August, excluding single household outbreaks, 673 outbreaks were notified nationally, 551 active (>6,200 cases) at the time. More than half of these outbreaks and cases coincided with: (i) social (family/friends’ gatherings or leisure venues) and (ii) occupational (mainly involving workers in vulnerable conditions) settings. Control measures were accordingly applied

Multiwavelength behaviour of the blazar OJ 248 from radio to γ-rays

We present an analysis of the multiwavelength behaviour of the blazar OJ 248 at z = 0.939 in the period 2006-2013. We use low-energy data (optical, near-infrared, and radio) obtained by 21 observatories participating in the Gamma-Ray Large Area Space Telescope (GLAST)-AGILE Support Program of the Whole Earth Blazar Telescope, as well as data from the Swift (optical-UV and X-rays) and Fermi (γ-rays) satellites, to study flux and spectral variability and correlations among emissions in different bands. We take into account the effect of absorption by the Damped Lyman α intervening system at z = 0.525. Two major outbursts were observed in 2006-2007 and in 2012-2013 at optical and near-IR wavelengths, while in the high-frequency radio light curves prominent radio outbursts are visible peaking at the end of 2010 and beginning of 2013, revealing a complex radio-optical correlation. Cross-correlation analysis suggests a delay of the optical variations after the γ-ray ones of about a month, which is a peculiar behaviour in blazars. We also analyse optical polarimetric and spectroscopic data. The average polarization percentage P is less than 3 per cent, but it reaches ∼19 per cent during the early stage of the 2012-2013 outburst. A vague correlation of P with brightness is observed. There is no preferred electric vector polarization angle and during the outburst the linear polarization vector shows wide rotations in both directions, suggesting a complex behaviour/structure of the jet and possible turbulence. The analysis of 140 optical spectra acquired at the Steward Observatory reveals a strong Mg II broad emission line with an essentially stable flux of 6.2 × 10- 15 erg cm- 2 s- 1 and a full width at half-maximum of 2053 km s- 1