CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells.

Tetraspanins are often used as Extracellular Vesicle (EV) detection markers because of their abundance on these secreted vesicles. However, data on their function on EV biogenesis are controversial and compensatory mechanisms often occur upon gene deletion. To overcome this handicap, we have compared the effects of tetraspanin CD9 gene deletion with those elicited by cytopermeable peptides with blocking properties against tetraspanin CD9. Both CD9 peptide or gene deletion reduced the number of early endosomes. CD9 peptide induced an increase in lysosome numbers, while CD9 deletion augmented the number of MVB and EV secretion, probably because of compensatory CD63 expression upregulation. In vivo, CD9 peptide delayed primary tumour cell growth and reduced metastasis size. These effects on cell proliferation were shown to be concomitant with an impairment in mitochondrial quality control. CD9 KO cells were able to compensate the mitochondrial malfunction by increasing total mitochondrial mass reducing mitophagy. Our data thus provide the first evidence for a functional connection of tetraspanin CD9 with mitophagy in melanoma cells.

Análisis de la cobertura vacunal frente a tétanos en adolescentes: evolución y situación actual en Extremadura (España) / Analysis of tetanus vaccination coverage in adolescents: evolution and current state in Extremadura

INTRODUCCIÓN: el tétanos es una enfermedad aguda grave cuyo tratamiento es difícil y, por tanto, es fundamental su prevención. La administración de cinco dosis de vacuna antitetánica es suficiente para conferir una protección a largo plazo. En los últimos años se ha observado cierta disminución en las coberturas, lo que supone la existencia de población no suficientemente inmunizada. El objetivo de este estudio es analizar la cobertura vacunal de la dosis de recuerdo frente al tétanos en adolescentes en la localidad de Santa Amalia, provincia de Badajoz (España), durante los últimos 20 años (1996-2016). MATERIAL Y MÉTODOS: estudio observacional transversal. Se revisaron las tarjetas de vacunación y los registros de las dosis administradas en los documentos manuscritos y registro informático en el entorno JARA Atención Sanitaria (JARA-AS). Entre 1996 y 2001, la vacunación se hacía en el centro escolar, con registro manual. Desde 2002, se administró la vacuna en el centro de salud, con registro manual (2002-2007) e informático (2008-2016). RESULTADOS: analizada la cobertura de forma agrupada, los peores resultados de vacunación se apreciaron en centro de salud utilizando registro manual (35,6%), mientras que las mejores cifras de vacunación se encontraron en centro de salud con registro informático (100%), seguido por el grupo de centro escolar (83,0%). CONCLUSIONES: este estudio pone de manifiesto una alta cobertura de vacunación frente a tétanos en la dosis de recuerdo en adolescentes de 14 años en Santa Amalia, similar a la cobertura nacional, a diferencia de la baja cobertura existente en el resto de Extremadura

INTRODUCTION: tetanus is a severe acute disease that is difficult to treat, and therefore its prevention is essential. The administration of 5 doses of tetanus vaccine suffices to confer long-term protection. In recent years, there has been evidence of a decrease in vaccination coverage, which entails that immunization in the population is insufficient. The aim of this study was to analyse the vaccination coverage rate for the booster dose of tetanus vaccine in adolescents residing in the town of Santa Amalia in the province of Badajoz (Spain) in the past 20 years (1996-2016). MATERIALS AND METHODS: the study had a cross-sectional and observational design and involved the review of vaccination cards and records of the administered doses of vaccine, both manual and electronic (JARA Primary Care system). Between 1996 and 2001, vaccination was performed in the school setting and documented manually. Since 2002, vaccination was performed in the primary care centre, and documented manually between 2002 and 2007 and in the electronic health records system between 2008 and 2016. RESULTS: the analysis of vaccination coverage by groups found the poorest results in the period that vaccination was performed in the primary care centre and documented manually (35.6%), while the best results corresponded to the period when vaccination was made in the primary care centre and documented in the electronic health records (100%), followed by the period of vaccination in the school with manual documentation (83.0%). CONCLUSIONS: the study found a high vaccination coverage for the booster dose of tetanus vaccine in adolescents aged 14 years residing in Santa Amalia, similar to the national average coverage, despite the low coverage rates documented in the rest of Extremadura

Calidad de vida en personas portadoras de una ostomía digestiva / Quality of life in people carrying a digestive ostomy / Qualidade de vida nas pessoas portadoras de estomas digestivas

Introducción: Las personas ostomizadas experimentan problemáticas clínicas, per-sonales, familiares y sociales que repercuten en su calidad de vida. Objetivo: Rea-lizar una revisión bibliométrica y exploratoria relacionada con la calidad de vida en personas portadoras de ostomías digestivas. Metodología: Se realizó búsqueda en Scopus, utilizando los descriptores: "Quality of life" y "Surgical stomas". Se selec-cionaron artículos publicados a partir del año 2014, en cualquier idioma, derivados de investigación y revisiones, escritos por enfermería exclusivamente o en cooperación con otras áreas de salud; se excluyeron las publicaciones de ostomías urológicas y respiratorias. Resultados: La muestra total fue de 39 manuscritos. El año de mayor publicación fue 2016; el 66,7 % de las investigaciones correspondía a nivel de eviden-cia baja y el 56,4 % correspondía a investigaciones descriptivas. A nivel exploratorio, el 31,4 % de los estudios utilizó cuestionarios relacionados con la calidad de vida, en el 14,2 % se indagó la calidad de vida a través de estudios cualitativos y en el 54,2 % se evaluaron otras temáticas que interfieren en la calidad de vida. Conclusión: La bibliometría muestra publicaciones con nivel de evidencia baja. Los resultados ex-ploratorios muestran alteración del bienestar en la dimensión física primordialmente, generando situaciones de afrontamiento que afectan la calidad de vida

Introduction: Ostomate patients experiment clinical, personal, social, and family issues which have an impact in their quality of life. Objective: To perform a bi-bliometric and exploratory review related to the quality of life in people carrying digestive ostomies. Methodology: The descriptors "Quality of life" and "Surgical stomas" were used to perform a search in Scopus. Published papers from the year 2014, derived from research and reviews written by nurses exclusively or in collaboration with other areas of health and published in different languages were chosen. The publications of urological and respiratory ostomies were excluded. Results: There was a total sample of 39 manuscripts. The year of highest publications was 2016; the 66.7 % of the research corresponded to a level of low evidence and the 56.4 % corresponded to descriptive research. An exploratory level of 31.4 % of the studies used questionnaires related to the quality of life; in the 14.2 % the quality of life was inquired through qualitative studies, and in the 54.2 % other topics that interfere in the quality of life, were evaluated. Conclusion: The Bibliometrics shows publications with a low level of evidence. The ex-ploratory results show mainly, an alteration of the well-being in the physical dimension, generating coping situations that affect the quality of life.

Introdução: As pessoas com estomas experimentam problemáticas clinicas, pessoais, familiares e sociais que repercutem na sua qualidade de vida Objetivo: Realizar uma revisão bibliográfica exploratória relacionada com a qualidade de vida de pessoas portadoras de estomas digestivas. Mé-todos: Realizou-se a pesquisa no Scopus, utilizando os descritores: "Quality of life" e "Surgical sto-mas". Selecionaram-se artigos publicados desde 2014 em qualquer língua, derivados de pesquisas e revisões, escritos por enfermagem exclusivamente ou em cooperação com outras áreas da saúde, excluíram-se artigos de estomas urológicas e respiratórias. Resultados: Obtiveram-se 39 artigos. O ano de maior publicação foi 2016, o 66,7% dos estudos tinha nível de evidência baixoe o 56,4% correspondeu a estudos descritivos. No nível exploratório, o 31,4% dos estudos empregou escalas relacionadas com qualidade de vida, o 14,2% indagou a qualidade de vida desenvolvendo pesquisas qualitativase o 54,2% avaliaram outras temáticas que interferem na qualidade de vida. Conclusão: A literatura científica mostrou resultados com nível de evidencia baixo. Os resultados exploratórios evidenciaram alteração do bem-estar na dimensão física primordialmente, gerando situações de afrontamento que afetam a qualidade de vida.

Retro-Auricular Thyroidectomy: An Open Approach.

Distant access robot-assisted thyroidectomy has gained popularity in recent years. Adoption of distant access procedures has been limited by cost, need for specialized training and expertise. We report our preliminary clinical experience with our modification of the retro-auricular thyroidectomy approach that allows adequate exposure for thyroid lobectomy without robotic or endoscopic assistance. This is a retrospective chart review of ten patients who have undergone retro-auricular thyroidectomies in the absence of robotic or endoscopic assistance. Ten patients were identified to have undergone this procedure over an 18-month period. All patients were female with average age 36 years (range 27-52). Six were right sided and 4 were left sided procedures. The average gland size was 4.2 cm (range 3.7-6 cm). The average nodule size was 2.1 cm (range 1.1-3.5 cm). The average operative time was 91 min (range 76-114 min). All patients had benign pathology on final histopathology. There were no conversions to open cervical thyroidectomy. Two patients had vocal cord paresis that resolved spontaneously. The average postoperative follow up was 3 months (range 1-7 months). Our technique for retro-auricular thyroidectomy is a safe, reproducible, and cost effective option for remote access thyroidectomy.

Iron deficiency is associated with Hypothyroxinemia and Hypotriiodothyroninemia in the Spanish general adult population: Di@bet.es study.

Previous studies have suggested that iron deficiency (ID) may impair thyroid hormone metabolism, however replication in wide samples of the general adult population has not been performed. We studied 3846 individuals free of thyroid disease, participants in a national, cross sectional, population based study representative of the Spanish adult population. Thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) were analyzed by electrochemiluminescence (E170, Roche Diagnostics). Serum ferritin was analyzed by immunochemiluminescence (Architect I2000, Abbott Laboratories). As ferritin levels decreased (>100, 30-100, 15-30, <15 µg/L) the adjusted mean concentrations of FT4 (p < 0.001) and FT3 (p < 0.001) descended, whereas TSH levels remained unchanged (p = 0.451). In multivariate logistic regression models adjusted for age, sex, UI, BMI and smoking status, subjects with ferritin levels <30 µg/L were more likely to present hypothyroxinemia (FT4 < 12.0 pmol/L p5): OR 1.5 [1.1-2.2] p = 0.024, and hypotriiodothyroninemia (FT3 < 3.9 pmol/L p5): OR 1.8 [1.3-2.6] p = 0.001 than the reference category with ferritin ≥30 µg/L. There was no significant heterogeneity of the results between men, pre-menopausal and post-menopausal women or according to the iodine nutrition status. Our results confirm an association between ID and hypothyroxinemia and hypotriiodothyroninemia in the general adult population without changes in TSH.

Comparison of the Effects of Goat Dairy and Cow Dairy Based Breakfasts on Satiety, Appetite Hormones, and Metabolic Profile.

The satiating effects of cow dairy have been thoroughly investigated; however, the effects of goat dairy on appetite have not been reported so far. Our study investigates the satiating effect of two breakfasts based on goat or cow dairy and their association with appetite related hormones and metabolic profile. Healthy adults consumed two breakfasts based on goat (G-Breakfast) or cow (C-Breakfast) dairy products. Blood samples were taken and VAS tests were performed at different time points. Blood metabolites were measured and Combined Satiety Index (CSI) and areas under the curves (AUC) were calculated. Desire to eat rating was significantly lower (breakfast & time interaction p < 0.01) and hunger rating tended to be lower (breakfast & time interaction p = 0.06) after the G-breakfast. None of the blood parameters studied were different between breakfasts; however, AUCGLP-1 was inversely associated with the AUChunger and AUCdesire-to-eat after the G-Breakfast, whereas triglyceride levels were directly associated with AUCCSI after the C-Breakfast. Our results suggest a slightly higher satiating effect of goat dairy when compared to cow dairy products, and pointed to a potential association of GLP-1 and triglyceride levels with the mechanisms by which dairy products might affect satiety after the G-Breakfast and C-Breakfast, respectively.

Reference values for TSH may be inadequate to define hypothyroidism in persons with morbid obesity: Di@bet.es study.

OBJECTIVE: To analyze the reference range of thyroid-stimulating hormone (TSH) in different BMI categories and its impact on the classification of hypothyroidism. METHODS: The study included 3,928 individuals free of thyroid disease (without previous thyroid disease, no interfering medications, TSH <10 µUI/mL and thyroid peroxidase antibodies [TPO Abs] <50 IU/mL) who participated in a national, cross-sectional, population-based study and were representative of the adult population of Spain. Data gathered included clinical and demographic characteristics, physical examination, and blood and urine sampling. TSH, free thyroxine, free triiodothyronine, and TPO Ab were analyzed by electrochemiluminescence (E170, Roche Diagnostics, Basel, Switzerland). RESULTS: The reference range (p2.5-97.5) for TSH was estimated as 0.6 to 4.8 µUI/mL in the underweight category (BMI<20 kg/m2 ), 0.6 to 5.5 µUI/mL in the normal-weight category (BMI 20-24.9 kg/m2 ), 0.6 to 5.5 µUI/mL in the overweight category (BMI 25-29.9 kg/m2 ), 0.5 to 5.9 µUI/mL in the obesity category (BMI 30-39.9 kg/m2 ), and 0.7 to 7.5 µUI/mL in the morbid obesity category (BMI ≥40). By using the reference criteria for the normal-weight population, the prevalence of high TSH levels increased threefold in the morbid obesity category (P < 0.01). CONCLUSIONS: Persons with morbid obesity might be inappropriately classified if the standard ranges of normality of TSH for the normal-weight population are applied to them.

Population-Based National Prevalence of Thyroid Dysfunction in Spain and Associated Factors: Di@bet.es Study.

BACKGROUND: The aim of this study was to investigate the national prevalence of thyroid dysfunction in Spain and its association with various clinical, environmental, and demographic variables. METHODS: The study included 4554 subjects (42.4% men) with a mean age of 50 years (range 18-93 years), who were participants in a national, cross-sectional, population-based survey conducted in 2009-2010. Data gathered included clinical and demographic characteristics, physical examination, and blood sampling. Thyrotropin, free thyroxine, free triiodothyronine, and thyroid peroxidase antibody (TPOAb) concentrations were analyzed by electrochemiluminescence. Urinary iodine (UI) levels were measured in an isolated urine sample. RESULTS: The prevalence of treated hypothyroidism, untreated subclinical hypothyroidism, and untreated clinical hypothyroidism was 4.2% [confidence interval (CI) 3.6-4.9%], 4.6% [CI 4.0-5.2%], and 0.3% [CI 0.1-0.5%], respectively. The prevalence of total hypothyroidism (including all fractions) was 9.1% [CI 8.2-10.0%]. The prevalence of total hyperthyroidism was 0.8% [CI 0.6-1.1]. A total of 7.5% [CI 6.7-8.3%] of the population tested positive for TPOAbs (≥50 IU/mL). In multivariate logistic regression models, TPOAbs were strongly associated with both hypothyroidism (p < 0.001) and hyperthyroidism (p = 0.005), whereas high UI levels (>200 µg/g creatinine) were associated with hypothyroidism (p < 0.001). The positive association between UI and hypothyroidism remained for both treated (p < 0.001) and untreated (p < 0.05) hypothyroidism, whereas it was especially significant for non-autoimmune (TPOAbs negative) forms (p < 0.001). At UI levels ≥200 µg/g, there was a positive correlation between UI and thyrotropin levels (ß = 0.152, p < 0.001) and a negative correlation between UI and free triiodothyronine levels (ß = -0.134, p = 0.001). CONCLUSION: According to the data, a large proportion (10%) of the Spanish population has some evidence of thyroid dysfunction. High TPOAb concentrations were associated with both hypo- and hyperthyroidism, whereas high UI concentrations were associated with hypothyroidism.

Functionalized lipid nanoparticles-cellophane hybrid films for molecular delivery: preparation, physicochemical characterization, and stability.

Lipid nanoparticles functionalized with the sunscreen 2,4-dihydroxybenzophenone (FLNPs) have been prepared by the ultrasound method and embedded in highly hydrophilic cellophane supports (regenerated cellulose, RC), creating biocompatible hybrid films (RC-FLNPs samples). The morphology of the FLNPs was studied with transmission microscopy, whereas the surface and interior chemical composition was analyzed by micro-Raman spectroscopy. RC-FLNPs hybrid films were prepared from the immersion of two cellophane supports with different thicknesses and water uptake properties (RC-3 and RC-6) in an aqueous dispersion of FLNPs. The structure of this hybrid material was visualized with bright-field microscopy, which clearly showed the inclusion of the FLNPs in the cellophane matrix. The stability of the RC-FLNPs films with respect to both aqueous environments and time was demonstrated by NaCl diffusion measurements. The reduction in the diffusion coefficient through the nanoparticle-modified films compared with the original supports confirms the presence of nanoparticles for concentration gradients of up to 0.4 M (osmotic pressure around 10 bar), indicating the stability of the hybrid hydrophilic material, even in aqueous environments and under matter flow conditions for a period of 21 days.

Non-invasive evaluation of bilateral renal regional blood flow and tubular dynamics during acute unilateral ureteral obstruction.

BACKGROUND: Global renal haemodynamic responses to acute unilateral ureteral obstruction (AUUO) have been studied extensively in animals, yet little is known about the concurrent changes in haemodynamics and tubular fluid dynamics that occur within the distinct regions of the kidney during AUUO. The advent of electron beam computerized tomography (EBCT) now allows us to evaluate non-invasively intrarenal haemodynamics and tubular fluid dynamics in vivo. METHODS: Using EBCT, we quantified total, cortical and medullary renal blood flow (RBF, C-RBF and M-RBF), and the concurrent intratubular fluid contrast concentration (ITCC) from contrast media dilution curves, prior to, and at 30 and 90 min after the onset of AUUO in five pigs. RESULTS: At 30 min after AUUO, there was a small 17+/-7% fall in C-RBF that did not quite reach significance (P = 0.076), whereas RBF, M-RBF, glomerular filtration rate (GFR) and ITCC were preserved. At 90 min, both C-RBF and RBF had fallen by 54+/-8 and 45+/-5%, respectively (P<0.05). GFR also tended to decrease (by 49+/-8%, P<0.06), whereas there was preservation of M-RBF. ITCC increased in the proximal and distal tubules, and tended to increase in Henle's loop. In the contralateral kidney, AUUO did not alter the haemodynamics, but transiently decreased ITCC in all tubular segments. CONCLUSION: EBCT allows evaluation of AUUO-induced changes in intrarenal haemodynamics and tubular fluid dynamics. AUUO decreased cortical, but not medullary perfusion of the ipsilateral kidney, and increased the ITCC in most tubular segments, suggesting increased tubular reabsorption that may have helped maintain GFR and tubular fluid flow.

Low-dose angiotensin II enhances pressor responses without causing sustained hypertension.

Subpressor doses of angiotensin II (SP-Ang II) cause a slow increase in blood pressure in rats as assessed by tail cuff plethysmography (TCP), reflecting either sustained hypertension or an exaggerated pressor response to diverse stimuli. We examined whether subpressor doses of Ang II enhance blood pressure responses to simple stress (handling of trained rats for TCP). We implanted telemetry in Sprague-Dawley rats. After 10 days of recovery and TCP training, we implanted osmotic minipumps with either SP-Ang II (50 ng/kg per minute) or vehicle, and then measured systolic blood pressure continuously in unrestrained rats for 13 days. We also recorded telemetry readings while obtaining TCP measurements every 2 days. SP-Ang II increased blood pressure from 134+/-19 to 159+/-22 mm Hg by TCP, which matched the simultaneous telemetry readings of 131+/-20 to 154+/-25 mm Hg. In contrast, SP-Ang II did not change the blood pressure in the unrestrained rats (measured with continuous telemetry: 124+/-2 versus 127+/-1 mm Hg). The blood pressure in the control rats did not change in the unrestrained state (125+/-3 versus 128+/-5 mm Hg on days 0 and 12, respectively), and only slightly increased during TCP (11+/-5 and 6+/-4 mm Hg by TCP and simultaneous telemetry, respectively; P=NS). In summary, SP-Ang II, although unable to provoke sustained hypertension, nonetheless magnifies the pressor response to otherwise trivial stimuli. We speculate that even modestly elevated Ang II levels may contribute to hypertensive complications because such levels promote the punctuation of an apparent normotensive state by episodic hypertension occasioned by seemingly innocuous stimuli.

Enhanced renal cortical vascularization in experimental hypercholesterolemia.

BACKGROUND: Experimental hypercholesterolemia is associated with pro-inflammatory changes and impaired regulation of tissue perfusion, which may lead to neovascularization. However, it is yet unknown whether such changes take place in the kidney. In this study, using a novel three-dimensional (3-D) micro computed-tomography technique we tested the hypothesis that hypercholesterolemia was associated with increased microvascular density in the renal cortex. METHODS: Kidneys were excised from pigs after 12 weeks of either a normal (N = 6) or high cholesterol (HC; N = 5) diet, histology slides processed, and a segmental renal artery injected with a radio-opaque intravascular silicone polymer. Renal samples were scanned with micro computed-tomography, transverse and three-dimensional images were reconstructed, and microvessels (80 to 360 microm in diameter) counted in situ. RESULTS: Serum cholesterol levels were significantly higher in hypercholesterolemic compared to normal pigs (383 +/- 76 vs. 81 +/- 7 mg/dL, P < 0.01), and microvascular spatial density was significantly higher in their inner and middle renal cortex (189 +/- 7 vs. 126 +/- 6 microvessels/cm2, P < 0.0001). Hypercholesterolemic kidneys also showed mild interstitial mononuclear infiltration and heavier immunostaining of vascular endothelial growth factor, but no other signs of morphological damage. CONCLUSIONS: These results demonstrate that early diet-induced hypercholesterolemia is associated with increased microvascular density in the renal cortex, which precedes signs of overt renal morphological damage. These alterations may potentially affect regulation and/or spatial distribution of intrarenal blood flow in hypercholesterolemia, and may participate in renal disease progression.