Kombucha analogs from maqui juice: Consortium age and sugar concentration effects on anthocyanin stability and its relationship with antioxidant activity and digestive enzyme inhibition.

The fermentation of maqui juice (MJ), by incorporating kombucha as a starter culture, produces beverages with variable and stable anthocyanin contents. The metabolic effect of kombucha starter cultures obtained at different fermentation times was explored on the anthocyanin stability of maqui (Aristotelia chilensis (Mol.) Stuntz) juice supplemented at different concentrations of sucrose and fermented at different times. The stability of anthocyanins was associated with the levels of catechin detected in the fermentation system. This study concludes that the fermentation of MJ with sucrose (10%) and kombucha consortium of 7-days old, promotes the release and accumulation of phenolic compounds that act as co-pigments, with the best response in quality parameters of beverages such as color intensity, tone, hyperchromic effect, and a significant bathochromic shift. Finally, the additive effect of phenolic constituents with stable anthocyanins, confers to kombucha analogs an outstanding antioxidant quality and inhibitory effects on key enzymes in digestive processes.

Juvenile zebrafish (Danio rerio) are able to recover from lordosis.

Haemal lordosis, a frequent skeletal deformity in teleost fish, has long been correlated with increased mechanical loads induced by swimming activity. In the present study, we examine whether juvenile zebrafish can recover from haemal lordosis and explore the musculoskeletal mechanisms involved. Juveniles were subjected to a swimming challenge test (SCT) that induced severe haemal lordosis in 49% of the animals and then immediately transferred them to 0.0 total body lengths (TL) per second of water velocity for a week. The recovery from lordosis was examined by means of whole mount staining, histology and gene expression analysis. Results demonstrate that 80% of the lordotic zebrafish are capable of internal and external recovery within a week after the SCT. Recovered individuals presented normal shape of the vertebral centra, maintaining though distorted internal tissue organization. Through the transcriptomic analysis of the affected haemal regions, several processes related to chromosome organization, DNA replication, circadian clock and transcription regulation were enriched within genes significantly regulated behind this musculoskeletal recovery procedure. Genes especially involved in adipogenesis, bone remodeling and muscular regeneration were regulated. A remodeling tissue-repair hypothesis behind haemal lordosis recovery is raised. Limitations and future possibilities for zebrafish as a model organism to clarify mechanically driven musculoskeletal changes are discussed.

Valor pronóstico de los criterios PERCIST y los parámetros metabólicos de la PET/TC en pacientes con cáncer de esófago tras tratamiento neoadyuvante / Prognostic value of PERCIST and PET/CT metabolic parameters in patients with esophageal cancer after neoadjuvant treatment

Objetivo Valorar la utilidad clínica de los criterios PERCIST y de los cambios en los parámetros cuantitativos de la PET/TC con [18F]FDG como factores pronósticos para la supervivencia libre de progresión y la supervivencia cáncer-específica en pacientes con cáncer de esófago tratados mediante quimiorradioterapia. Material y métodos Se valoraron retrospectivamente 50 pacientes (48 hombres) diagnosticados de cáncer de esófago durante un intervalo de 7,5 años. Se utilizaron los criterios PERCIST para valorar la respuesta a la neoadyuvancia. Asimismo, se determinaron las variaciones del SUV máximo, volumen metabólico tumoral y glucólisis tumoral total entre los estudios PET/TC pre- y postratamiento. Las curvas ROC, el método de Kaplan-Meier y el modelo de regresión de Cox se aplicaron para el análisis de factores pronósticos y curvas de supervivencia. Resultados El seguimiento medio fue de 26,8 meses, produciéndose 40 recurrencias-progresiones y 41 muertes. El análisis de supervivencia mostró curvas de supervivencia cáncer-específica con diferencias estadísticamente significativas en relación con los criterios PERCIST y la variación del volumen metabólico tumoral y la glucólisis tumoral total. Los criterios PERCIST fueron el único factor predictivo independiente en el análisis multivariante. Ni el SUV máximo ni el tamaño tumoral fueron predictores para ninguno de los criterios de evaluación. Conclusión La aplicación de los criterios PERCIST, así como el cambio de volumen metabólico tumoral y glucólisis tumoral total de los estudios PET/TC demostraron ser factores pronósticos para la supervivencia cáncer-específica en pacientes de nuestro entorno tratados por cáncer de esófago. Los resultados podrían ayudar a personalizar el tratamiento (AU)

Aim To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival in patients with esophageal cancer treated by chemoradiotherapy. Material and methods Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV, metabolic tumor volume and total lesion glycolysis between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. Results The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in cancer-specific survival curves for PERCIST criteria and variation of metabolic tumor volume and total lesion glycolysis. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither maximum SUV nor tumor size were predictors for any of the assessment criteria Conclusion Application of PERCIST criteria as well as change in metabolic tumor volume and total lesion glycolysis from PET/CT studies proved to be prognostic factors for cancer-specific survival in patients in our setting treated for esophageal cancer. The results could help to personalize treatment (AU)

Changes in electromyographic activity of latent trigger points after a dry needling intervention: a randomised controlled trial.

OBJECTIVE: To analyse the effects of dry needling (DN) in upper trapezius latent trigger points (LTrPs) on pressure pain threshold (PPT) and surface electromyography (sEMG). DESIGN: Randomized, double-blind, placebo controlled clinical trial. SETTINGS: Sports Rehabilitation Laboratory, University of Castilla-La Mancha. PARTICIPANTS: Forty-six participants (18-35 years old) with LTrP in the upper trapezius were divided into two groups: DN-group and Sham-DN-group. INTERVENTIONS: In the DN-group, the needle was inserted 10-times through the skin, and it was manipulated up and down using a "fast in and out" technique. In the Sham-DN-group, non-penetrating needles were used. MAIN OUTCOME MEASURES: PPT, sEMG at rest, and sEMG in isometric contraction of the LTrP of the upper trapezius muscle were evaluated at baseline, 30 min after treatment, and after 24 h, and 72 h of follow-up. RESULTS: The mean change in sEMG at rest between baseline and 30 min was - 0.38 (0.38) %refRMS for the DN group and - 0.05 (0.31) %refRMS for the Sham-DN group (mean difference -0.34, 95% confidence interval (CI) of the difference: - 0.54 to - 0.13), and between baseline and 24 h was - 0.35 (0.35) %refRMS for the DN group and - 0.06 (0.58) %refRMS for the Sham-DN group (mean difference -0.29, 95% CI: -0.57 to -0.01). In addition, the DN-group showed higher values of PPT than the Sham-DN group at 72 h (5.22 (1.23) to 4.65 (1.03) kg/cm2; p < 0.05). CONCLUSIONS: A single session of DN intervention was effective in reducing the electromyographic activity, muscle fatigue and pain of the upper trapezius muscle in LTrP. CONTRIBUTION OF PAPER: In healthy volunteers dry needling is effective.

Prognostic value of PERCIST and PET/CT metabolic parameters after neoadjuvant treatment in patients with esophageal cancer.

AIM: To assess the clinical utility of PERCIST criteria and changes in [18F]FDG PET/CT quantitative parameters as prognostic factors for progression-free survival and cancer-specific survival (CSS) in patients with esophageal cancer treated by chemoradiotherapy. MATERIAL AND METHODS: Fifty patients (48 men) diagnosed with esophageal cancer were retrospectively evaluated over a 7.5-year interval. PERCIST criteria were used to assess response to neoadjuvant therapy. Variations in the metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) between pre- and post-treatment PET/CT studies were also determined. ROC curves, Kaplan-Meier method and Cox regression model were used for the analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 26.8 months, with 40 recurrences-progressions and 41 deaths. Survival analysis showed statistically significant differences in CSS curves for PERCIST criteria and variation of MTV and TLG. PERCIST criteria were the only independent predictor in the multivariate analysis. Neither SUVmax nor tumor size were predictors for any of the assessment criteria. CONCLUSION: Application of PERCIST criteria as well as change in MTV and TLG from PET/CT studies proved to be prognostic factors for CSS in patients in our setting treated for esophageal cancer. The results could help to personalize treatment.

Utilidad de la gammagrafía de tránsito gastrointestinal en la valoración del estreñimiento crónico / Utility of gastrointestinal transit scintigraphy in chronic constipation evaluation

Objetivo El estreñimiento crónico es una patología frecuente en la práctica clínica. Ante la falta de respuesta al tratamiento se recomienda evaluar la función gastrointestinal. Para ello puede ser útil la gammagrafía, aunque su uso no es generalizado. El objetivo del estudio fue valorar la utilidad de la gammagrafía de tránsito gastrointestinal en pacientes con estreñimiento crónico. Material y métodos Se valoraron 20 pacientes (13 niños) remitidos para estudio gammagráfico por estreñimiento crónico refractario al tratamiento, siringomielia, rectocele o migraña abdominal. Todos fueron sometidos a valoración clínica, determinación analítica, estudio de imagen radiológica y/o biopsia rectal. Se realizó un protocolo de estudio completo, incluyendo gammagrafía de vaciamiento gástrico, tránsito de intestino delgado y colónico. Para ello, se administró una dosis de [111In]In-DTPA diluida en agua (37MBq) junto con comida estandarizada. Siguiendo las guías internacionales, se definieron áreas de interés en el estómago, en el íleon terminal y en diferentes regiones del intestino grueso para calcular el centro geométrico como medida de progresión. Resultados De los 13 pacientes en edad pediátrica, 10 presentaron patrones gammagráficos anormales, modificando el tratamiento en 8 de ellos. La mayoría de los niños no mostraron alteraciones en las exploraciones radiológicas. En pacientes adultos, el resultado de la prueba conllevó el cambio del manejo terapéutico en todos ellos, Conclusiones El estudio gammagráfico proporcionó información útil en el estudio del estreñimiento crónico, influyendo en el diagnóstico y en el manejo terapéutico del paciente. La información fisiológica y cuantitativa que proporciona permite la determinación global y regional del tránsito gastrointestinal (AU)

Aim Chronic constipation is a common pathology in clinical practice. In the absence of response to treatment, assessment of gastrointestinal function is recommended. This can be performed by scintigraphy, although its use is not widespread. The aim of this paper was to assess the utility of gastrointestinal transits scintigraphy in patients with chronic constipation. Material and methods Twenty patients (13 children) sent for scintigraphy for chronic constipation refractory to treatment, syringomyelia, rectocele or abdominal migraine were evaluated. All underwent clinical assessment, analytical determination, radiological imaging and/or rectal biopsy. A complete study protocol was performed, including gastric emptying, small bowel and colonic transits scintigraphy. For this, a dose of [111In]In-DTPA diluted in water (37MBq) was administered together with standardized food. Following international guidelines, regions of interest were defined in the stomach, terminal ileum and different regions of the large intestine to calculate the geometric center as a measure of progression. Results Of the 13 pediatric patients, 10 had abnormal gammagraphic patterns, with treatment being modified in 8 of them. Most of the children showed no alterations on radiological explorations. In adult patients, the results of the test changed the therapeutic management in all of them. Conclusions Scintigraphic study provided useful information in the study of chronic constipation, influencing the diagnosis and therapeutic management of the patient. The physiological and quantitative information it provides allows both global and regional of gastrointestinal transit time determination (AU)

Utility of gastrointestinal transit scintigraphy in the evaluation of chronic constipation.

AIM: Chronic constipation is a common pathology in clinical practice. In the absence of response to treatment, assessment of gastrointestinal function is recommended. This can be performed by scintigraphy, although its use is not widespread. The aim of this paper was to assess the utility of gastrointestinal transits scintigraphy in patients with chronic constipation. MATERIAL AND METHODS: Twenty patients (13 children) sent for scintigraphy for chronic constipation refractory to treatment, syringomyelia, rectocele or abdominal migraine were evaluated. All underwent clinical assessment, analytical determination, radiological imaging and/or rectal biopsy. A complete study protocol was performed, including gastric emptying, small bowel and colonic transits scintigraphy. For this, a dose of [111In]In-DTPA diluted in water (37MBq) was administered together with standardized food. Following international guidelines, regions of interest were defined in the stomach, terminal ileum and different regions of the large intestine to calculate the geometric center as a measure of progression. RESULTS: Of the 13 pediatric patients, 10 had abnormal gammagraphic patterns, with treatment being modified in 8 of them. Most of the children showed no alterations on radiological explorations. In adult patients, the results of the test changed the therapeutic management in all of them. CONCLUSIONS: Scintigraphic study provided useful information in the study of chronic constipation, influencing the diagnosis and therapeutic management of the patient. The physiological and quantitative information it provides allows both global and regional of gastrointestinal transit time determination.

Experimental evidence that polystyrene nanoplastics cross the intestinal barrier of European seabass.

Plastic pollution in marine ecosystems constitutes an important threat to marine life. For vertebrates, macro/microplastics can obstruct and/or transit into the airways and digestive tract whereas nanoplastics (NPs; < 1000 nm) have been observed in non-digestive tissues such as the liver and brain. Whether NPs cross the intestinal epithelium to gain access to the blood and internal organs remains controversial, however. Here, we show directly NP translocation across the intestinal barrier of a fish, the European seabass, Dicentrarchus labrax, ex vivo. The luminal side of median and distal segments of intestine were exposed to fluorescent polystyrene NPs (PS-NPs) of 50 nm diameter. PS-NPs that translocated to the serosal side were then detected quantitatively by fluorimetry, and qualitatively by scanning electron microscopy (SEM) and pyrolysis coupled to gas chromatography and high-resolution mass spectrometry (Py-GC-HRMS). Fluorescence intensity on the serosal side increased 15-90 min after PS-NP addition into the luminal side, suggesting that PS-NPs crossed the intestinal barrier; this was confirmed by both SEM and Py-GC-HRMS. This study thus evidenced conclusively that NPs beads translocate across the intestinal epithelium in this marine vertebrate.

Parámetros cuantitativos de la PET/TC basal con 18F-FDG como factores pronósticos en el carcinoma de células escamosas de esófago / Baseline 18F-FDG PET/CT quantitative parameters as prognostic factors in esophageal squamous cell cancer

Objetivo: Determinar la utilidad de los parámetros cuantitativos de la PET/TC con 18F-FDG como factores pronósticos para la respuesta al tratamiento neoadyuvante, la supervivencia libre de progresión (SLP) y la supervivencia cáncer específica (SCE) en pacientes con carcinoma de células escamosas de esófago (CCE). Material y métodos: Se valoraron retrospectivamente 30 pacientes (29 hombres) diagnosticados de CCE durante un intervalo de 6años. Se determinaron los parámetros metabólicos SUV máximo (SUVmax), SUV medio (SUVmed), volumen metabólico tumoral (MTV) y glucólisis tumoral total (TLG) del estudio PET/TC al diagnóstico. Tras tratamiento con quimioterapia y/o radioterapia, se valoró la respuesta al tratamiento y la supervivencia de los pacientes. La comparación de parámetros entre grupos de respondedores y no respondedores se realizó mediante la prueba U de Mann-Whitney. Las curvas ROC y el método de Kaplan-Meier se utilizaron para el análisis de factores pronósticos y curvas de supervivencia. Resultados: El seguimiento medio fue de 22,4meses, produciéndose 22 recurrencias-progresiones y 25 fallecimientos. Se demostraron diferencias significativas entre respondedores y no respondedores con respecto al tamaño tumoral, el MTV y la TLG. El análisis de supervivencia halló diferencias significativas para SCE y SLP dependiendo de estos tres parámetros. Conclusión: Los parámetros metabólicos MTV y TLG, así como el tamaño tumoral, fueron factores pronósticos para la respuesta al tratamiento neoadyuvante, la SLP y la SCE en pacientes diagnosticados de CCE. Ni el SUVmax ni el SUVmed fueron predictores para ninguno de los criterios de evaluación. Los resultados permitirían personalizar el tratamiento de los pacientes (AU)

Aim: To determine the utility of 18F-FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). Material and methods: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test. ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. Results: The average follow-up was 22.4months, with 22 recurrence-progressions and 25 deads. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. Conclusion: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment (AU)

Baseline 18F-FDG PET/CT quantitative parameters as prognostic factors in esophageal squamous cell cancer.

AIM: To determine the utility of [18F]FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4 months, with 22 recurrence-progressions and 25 deaths. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.

Effects of dry needling on mechanical and contractile properties of the upper trapezius with latent myofascial trigger points: A randomized controlled trial.

BACKGROUND: Latent trigger point (LTrP) can cause motor dysfunction and disturb normal patterns of motor recruitment. OBJECTIVE: To analyze the effects of DN in the upper trapezius (UT) LTrP on pain and the mechanical and contractile properties of the muscle. DESIGN: A randomized, double-blinded, parallel-group-trial. METHODS: Fifty healthy volunteers with LTrPs in the UT were randomly divided into a DN-group (n = 26) and a Sham-DN-group (n = 24) and received one session of DN or placebo treatment. Mechanical and contractile properties of the muscle and pressure pain perception (PPP) were evaluated before treatment and in a 30min, 24 h and 72 h follow-up after treatment. RESULTS: In the mechanical properties, the DN-group showed lower values than the Sham-DN-group for dynamic stiffness at 72 h (p = 0.04). The DN-group showed lower values for dynamic stiffness at 72 h from baseline (278.74 ± 38.40 to 261.54 ± 33.64 N/m; p = 0.01) and for tone at 72 h from 30min (16.62 ± 1.27 to 15.88 ± 1.31 Hz; p = 0.01). In the contractile properties, the DN-group showed higher values for maximal radial displacement (Dm) of the muscle belly at 72 h from baseline (5.38 ± 1.67 to 6.13 ± 1.70 mm; p = 0.04), higher values for contraction time at 30min (28.53 ± 8.80 s; p = 0.03) and lower ones at 72 h (24.74 ± 4.36 s; p = 0.04) from baseline (26.97 ± 6.63 s). The DN-group showed a decrease of PPP from baseline to 72 h after treatment (5.16 ± 1.33 to 4.02 ± 0.97 mm; p < 0.01). CONCLUSION: The application of DN in healthy volunteers over LTrPs in the UT decreased dynamic stiffness, tone and contraction time and increased Dm at 72 h after treatment. Additionally, the PPP showed a decrease at 72 h after needling. CLINICALTRIALS.GOV: NCT04466813.

Baseline 18F-FDG PET/CT quantitative parameters as prognostic factors in esophageal squamous cell cancer. / Parámetros cuantitativos de la PET/TC basal con 18F-FDG como factores pronósticos en el carcinoma de células escamosas de esófago.

AIM: To determine the utility of 18F-FDG PET/CT quantitative parameters as prognostic factors for the response to neoadjuvant treatment, progression-free survival (PFS) and cancer-specific survival (CSS) in patients with esophageal squamous cell carcinoma (SCC). MATERIAL AND METHODS: Thirty patients (29 men) diagnosed with SCC were retrospectively evaluated over a 6-year interval. Metabolic parameters were determined: maximum SUV (SUVmax), mean SUV (SUVmed), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) from baseline PET/CT study. After treatment with chemotherapy and/or radiotherapy, response to treatment and patient survival were assessed. The comparison of parameters between groups of responders and non-responders was carried out using a Mann-Whitney U test. ROC curves and the Kaplan-Meier method were used for analysis of prognostic factors and survival curves. RESULTS: The average follow-up was 22.4months, with 22 recurrence-progressions and 25 deads. Significant differences were demonstrated between responders and non-responders with respect to tumor size, MTV and TLG. Survival analysis found significant differences for SCE and CSS depending on these three parameters. CONCLUSION: Metabolic parameters MTV and TLG, and tumor size were prognostic factors for neoadjuvant treatment response, PFS, and CSS in patients diagnosed with SCC. Neither SUVmax nor SUVmed were predictive for any of the evaluation criteria. Results could help to personalize patient treatment.

Rheological properties of ethyl cellulose-monoglyceride-candelilla wax oleogel vis-a-vis edible shortenings.

The gelation process, elasticity, and mechanical recovery after shear were studied in mixed oleogels of ethylcellulose (EC), monoglycerides (MG), and candelilla wax (CW). EC oleogels produced without MG showed grainy texture due to incomplete dissolution of crystalline fractions of raw EC in the vegetable oil (150 °C). These fractions were eliminated by dissolving the raw EC/MG mixture in ethanol, evaporating the solvent, dispersing, and dissolving the solid residue in the vegetable oil (150 °C) prior gelation. The EC polymeric network, and MG, and CW crystals had a positive interaction on the elasticity of mixed oleogels. Mixed oleogels produced under static conditions showed a 100 % of elasticity recovery after shearing, a phenomenon associated with an EC interchain hydrogen bonding mediated by hydroxyl groups of MGs. This tentatively resulted from the formation of junction zones of the type EC-[MG]n-EC. The rheological behavior of these olegels was remarkably close to that of commercial shortenings.

18F-FDG PET/CT quantitative parameters as prognostic factor in localized and inoperable lung cancer. / Parámetros cuantitativos de la PET/TC con 18F-FDG como factores pronósticos en el cáncer de pulmón localizado e inoperable.

AIM: To assess the utility of 18F-FDG PET/CT quantitative parameters as prognostic factor in patients diagnosed with localized and inoperable lung cancer treated by stereotactic body radiotherapy (SBRT). MATERIAL AND METHODS: Fifty patients (42 men) diagnosed in the last 7years with early-stage lung cancer and treated with SBRT alone were assessed by a prospective study. After PET/CT study, metabolic parameters maximum SUV (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were determined at different thresholds. The prognostic factors for overall survival (OS), cause-specific survival (CS) and disease-free survival (DFS) were analysed by Cox proportional hazards model and the survival analysis by Kaplan-Meier method. RESULTS: The average follow-up was 39.6months, with 21 recurrences and 24 dead. Univariate analysis determined MTV30 and MTV40 as predictors for OS; MTV30, MTV40, TLG30 and TLG40 for CS, and MTV2, MTV30, MTV40, TLG2, TLG30 and TLG40 for DFS. Survival analysis found statistically significant differences for CS and DFS depending on tumor size and for DFS considering the cut-off values of MTV2 and TLG2 (threshold SUVmax=2). SUVmax, age and sex were not shown to be significant factors. CONCLUSION: Pre-treatment quantitative assessment using metabolic parameters MTV2 and TLG2 as well as tumor size proved to be prognostic factors in patients diagnosed with localized and inoperable lung cancer treated by SBRT. Results could help to personalize treatment.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

Water-in-oil organogel based emulsions as a tool for increasing bioaccessibility and cell permeability of poorly water-soluble nutraceuticals.

The use of organogels in food and pharmaceutical sciences has several technical problems related with restricted diffusion of the drugs and lack of a proper gelator molecule. These features are important into the new product design. An alternative to improve technological properties in organogels is the use of emulsions. However, there is a lack of knowledge about the behavior on bioaccessibility and permeability of bioactives loaded into organogel-based emulsions. The objective of the present experimental work was to study the physical properties of organogel-based emulsions made with vegetable oil loaded with three different bioactives (betulin, curcumin and quercetin) and the influence on their bioaccessibility. Organogels were made of canola or coconut oils and myverol as gelator (10% w/w). Water-in-oil emulsions (at 5, 10 and 12.5 wt% of water content) were prepared by mixing the melted proper organogel and water (80 °C) under high shear conditions (20,000 rpm). Micrographs, rheological tests (amplitude, frequency, temperature sweeps and creep-compliance measurements), DSC and particle size analysis were performed to samples. In vitro digestion (oral, gastric and intestinal phase), lipolysis assays, bioaccessibility and permeability tests by cell culture of Caco-2 were made. Organogels of coconut oil have shown poor emulsification properties.

Longitudinal monitoring of anti-saliva antibodies as markers of repellent efficacy against Phlebotomus perniciosus and Phlebotomus papatasi in dogs.

A 2-year longitudinal study of enzyme-linked immunosorbent assay (ELISA) antibodies against Phlebotomus perniciosus and Phlebotomus papatasi (Diptera: Psychodidae) sandfly saliva was performed in 32 Beagle dogs treated preventively with an imidacloprid-permethrin topical insecticide in an endemic area in Spain. Dogs were grouped into three sandfly exposure groups according to the time of inclusion in the study. Assays analysed immunoglobulin G (IgG) against salivary gland homogenates (SGH) of both species and recombinant P. papatasi rSP32 and P. perniciosus rSP03B proteins in serum. The dogs were participating in a Leishmania infantum (Kinetoplastida: Trypanosomatidae) vaccine trial and were experimentally infected with the parasite in the second year. No dog acquired natural L. infantum infections during the first year, but most developed anti-saliva antibodies, and median log-transformed optical densities (LODs) were seasonal, mimicking those of local sandflies. This indicates that the repellent efficacy of the insecticide used is below 100%. Multi-level modelling of LODs revealed variability among dogs, autocorrelation and differences according to the salivary antigen and the dog's age. However, dog seroprevalence, estimated using pre-exposure LODs as cut-offs, was relatively low. This, and the fact that dogs did not become naturally infected with L. infantum, would support the efficacy and usefulness of this imidacloprid-permethrin topical insecticide in canine leishmaniasis control.

Meningoencefalitis recurrente por alopurinol / Recurrent meningoencephalitis due to allopurinol

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Simvastatin interferes with cancer 'stem-cell' plasticity reducing metastasis in ovarian cancer.

Cell plasticity of 'stem-like' cancer-initiating cells (CICs) is a hallmark of cancer, allowing metastasis and cancer progression. Here, we studied whether simvastatin, a lipophilic statin, could impair the metastatic potential of CICs in high-grade serous ovarian cancer (HGS-ovC), the most lethal among the gynecologic malignancies. qPCR, immunoblotting and immunohistochemistry were used to assess simvastatin effects on proteins involved in stemness and epithelial-mesenchymal cell plasticity (EMT). Its effects on tumor growth and metastasis were evaluated using different models (e.g., spheroid formation and migration assays, matrigel invasion assays, 3D-mesomimetic models and cancer xenografts). We explored also the clinical benefit of statins by comparing survival outcomes among statin users vs non-users. Herein, we demonstrated that simvastatin modifies the stemness and EMT marker expression patterns (both in mRNA and protein levels) and severely impairs the spheroid assembly of CICs. Consequently, CICs become less metastatic in 3D-mesomimetic models and show fewer ascites/tumor burden in HGS-ovC xenografts. The principal mechanism behind statin-mediated effects involves the inactivation of the Hippo/YAP/RhoA pathway in a mevalonate synthesis-dependent manner. From a clinical perspective, statin users seem to experience better survival and quality of life when compared with non-users. Considering the high cost and the low response rates obtained with many of the current therapies, the use of orally or intraperitoneally administered simvastatin offers a cost/effective and safe alternative to treat and potentially prevent recurrent HGS-ovCs.