Impact of Lactic Acid Bacteria Fermentation on (Poly)Phenolic Profile and In Vitro Antioxidant and Anti-Inflammatory Properties of Herbal Infusions.

Recently, the development of functional beverages has been enhanced to promote health and nutritional well-being. Thus, the fermentation of plant foods with lactic acid bacteria can enhance their antioxidant capacity and others like anti-inflammatory activity, which may depend on the variations in the total content and profile of (poly)phenols. The present study aimed to investigate the impact of fermentation with two strains of Lactiplantibacillus plantarum of several herbal infusions from thyme, rosemary, echinacea, and pomegranate peel on the (poly)phenolic composition and whether lacto-fermentation can contribute to enhance their in vitro antioxidant and anti-inflammatory effects on human colon myofibroblast CCD18-Co cells. HPLC-MS/MS analyses revealed that fermentation increased the content of the phenolics present in all herbal infusions. In vitro analyses indicated that pomegranate infusion showed higher antioxidant and anti-inflammatory effects, followed by thyme, echinacea, and rosemary, based on the total phenolic content. After fermentation, despite increasing the content of phenolics, the antioxidant and anti-inflammatory effects via reduction pro-inflammatory markers (IL-6, IL-8 and PGE2) were similar to those of their corresponding non-fermented infusions, with the exception of a greater reduction in lacto-fermented thyme. Overall, the findings suggest that the consumption of lacto-fermented herbal infusions could be beneficial in alleviating intestinal inflammatory disorders.

Urolithin A production drives the effects of pomegranate on the gut microbial metabolism of bile acids and cholesterol in mild dyslipidaemic overweight and obese individuals.

The metabolism of (poly)phenols and some host metabolites, including bile acids (BAs) and cholesterol, varies among individuals depending on their gut microbiota. The gut microbial metabolism of ellagitannins (ETs) and ellagic acid (EA) produces urolithins (Uros), yielding three metabotypes with quantitative and qualitative differences based on dissimilar Uro-producing profiles (UM-A, UM-B, and UM-0, i.e., non-producers). Previous animal studies demonstrated that polyphenols impact BAs and cholesterol microbial metabolism, but data on their effects in humans and data regarding the inter-individual variability of these metabolic conversions are scant. We evaluated whether UMs, as distinctive functional gut-microbiome signatures, could determine the potential effect of a pomegranate extract (PE) rich in ET-EA on the metabolism of BAs and cholesterol in mild dyslipidaemic overweight-obese individuals, with possible consequences on host-lipid homeostasis and gut health. At the baseline, UM-B presented the highest levels of faecal total and secondary BAs and coprostanol, suggesting that the lipid absorption capacity and gut cytotoxic risk could be augmented in UM-B. PE intake significantly reduced faecal coprostanol and BA production, especially secondary BAs, and modulated the gut microbiome, reducing the gut cytotoxic risk, especially in UM-B individuals. The lowering of faecal microbial coprostanol and BAs and some BA-metabolising bacteria was quantitatively correlated with Uro concentrations, mainly faecal Uro-A. This suggests that PE consumption could exert cardiovascular and gut protection through Uro-A production as a direct driver of the effects and indirectly by reducing the Coriobacteriaceae family and BA pool, known factors involved in the gut absorption of lipids.

Pathogenic NLRP3 mutants form constitutively active inflammasomes resulting in immune-metabolic limitation of IL-1ß production.

Cryopyrin-associated periodic syndrome (CAPS) is an autoinflammatory condition resulting from monoallelic NLRP3 variants that facilitate IL-1ß production. Although these are gain-of-function variants characterized by hypersensitivity to cell priming, patients with CAPS and animal models of the disease may present inflammatory flares without identifiable external triggers. Here we find that CAPS-associated NLRP3 variants are forming constitutively active inflammasome, which induce increased basal cleavage of gasdermin D, IL-18 release and pyroptosis, with a concurrent basal pro-inflammatory gene expression signature, including the induction of nuclear receptors 4 A. The constitutively active NLRP3-inflammasome of CAPS is responsive to the selective NLRP3 inhibitor MCC950 and its activation is regulated by deubiquitination. Despite their preactivated state, the CAPS inflammasomes are responsive to activation of the NF-κB pathway. NLRP3-inflammasomes with CAPS-associated variants affect the immunometabolism of the myeloid compartment, leading to disruptions in lipids and amino acid pathways and impaired glycolysis, limiting IL-1ß production. In summary, NLRP3 variants causing CAPS form a constitutively active inflammasome inducing pyroptosis and IL-18 release without cell priming, which enables the host's innate defence against pathogens while also limiting IL-1ß-dependent inflammatory episodes through immunometabolism modulation.

Percepciones y experiencias de adultos mayores sobre sexualidad y servicios de salud sexual en Colombia

Introducción: Aunque a nivel mundial se ha demostrado que la población adulta mayor mantiene una vida sexual activa, es limitada por estereotipos, cambios fisiológicos resultados del proceso de envejecimiento y la ausencia de estrategias de salud integral para la sexualidad. Objetivo: Documentar la experiencia sexual de los adultos mayores en el país y entender los motivos que promueven o limitan la búsqueda de atención en salud sexual. Metodología: Estudio cualitativo en el que se realizaron 39 entrevistas y 4 talleres virtuales con hombres y mujeres de 50 años y más en Barranquilla, Bogotá, Cali, Medellín, sin excluir personas de otras ciudades. Resultados: Entre los principales hallazgos se evidencia que la población adulta mayor tiene valoraciones positivas frente a la sexualidad y el sexo, pero su desarrollo se ve limitado, especialmente para las mujeres, por los roles de género. La sexualidad en las personas mayores está atravesada por la educación inicial, la transformación de ideas sobre la sexualidad a lo largo de sus trayectorias de vida, las transformaciones del cuerpo, el estado de salud, las prácticas y experiencias sexuales recientes y la manera en la que se aproximan a la dimensión salud sexual con profesionales de la salud. Conclusiones: La heterogeneidad de experiencias, prácticas y valores dados a la sexualidad y al sexo en la vejez requieren de la generación de políticas y programas de atención integral basadas en investigaciones empíricas que superen las concepciones edadistas de la sexualidad. Este estudio es una contribución a la literatura local sobre sexualidad y vejez, así como al diseño de servicios de atención de salud y bienestar de acuerdo con las necesidades, identidades y circunstancias específicas de la población adulta mayor en materia de sexualidad.

Introduction: Although worldwide has been demonstrated that the older adult population maintains an active sexual life, this is limited by stereotypes, physiological changes resulting from the aging process and the absence of comprehensive health strategies for sexuality. Objective: To document the sexual experience of older adults in the country and to understand the reasons that promote or limit the search for sexual healthcare. Methodology: Qualitative study. Thirty-nine interviews and four virtual workshops were conducted with men and women 50 years of age and older in Barranquilla, Bogotá, Cali, and Medellín, although people from other cities were not excluded. Results: Among the main findings, it is evident that this population has positive evaluations of sexuality and sex, but its development is limited, especially for women, by gender roles. Sexuality in the elderly is formed by their initial education, the transformation of ideas about sexuality throughout their life trajectories, the transformations of their bodies, their state of health, recent sexual practices and experiences, and the way in which they approach this topic with health professionals. Conclusions: The heterogeneity of experiences, practices and values given to sexuality and sex in old age require policies and programs based on empirical research that overcome the ageist conception of sexuality. This study is a contribution to the national literature on sexuality and aging, and to the design of health care and well-being services according to the specific needs, identities and circumstances of the older adult population in terms of sexuality.

Percepciones de proveedores de servicios de salud sobre la salud sexual de los adultos mayores en Colombia

Introducción: La sexualidad y la salud sexual de las personas adultas mayores es una dimensión invisible en la prestación de los servicios de salud. Debido a esto, es importante conocer las percepciones y dificultades del personal de salud para brindar esta atención. Objetivo: Identificar diferencias y similitudes en la percepción que tienen los proveedores de servicios de salud en Colombia sobre la sexualidad y la salud sexual en el adulto mayor. Metodología: Se realizaron 5 grupos focales en Bogotá, Barranquilla, Cali y Medellín donde participaron 19 profesionales de la salud de una institución prestadora de servicios de salud sexual y reproductiva. Resultados: Los profesionales de la salud reconocen la sexualidad como un aspecto importante en la prestación de los servicios de salud en las personas mayores, a pesar de la invisibilidad actual del tema en la atención médica. Reconocen la complejidad de hablar sobre sexualidad en la interacción médico-paciente, en parte por la falta de entrenamiento de los profesionales de la salud y por las propias inhibiciones de los pacientes. Discusión: Persisten obstáculos sociales y teóricos para abordar los temas de sexualidad en consulta, al igual que diferencias de género para el tratamiento de temas de sexualidad y salud sexual. Conclusiones: Los prestadores de servicios de salud son claves para remover barreras a la atención, acompañamiento y comprensión de la salud sexual y la sexualidad de las personas mayores.

Introduction: The sexuality and sexual health of older people is an invisible dimension in the provision of health services. Therefore, it is important to know the perceptions and difficulties of health personnel to provide this care. Objective: To identify differences and similarities in the perception that health service providers in Colombia have about sexuality and sexual health in the elderly. Methodology: A total of 5 focus groups were held in Bogotá, Barranquilla, Cali and Medellín with the participation of 19 health professionals from an institution that provides sexual and reproductive health services. Results: Health professionals recognize sexuality as an important aspect in the provision of health services in the elderly, despite the current invisibility of the issue in medical care. They recognize the complexity of talking about sexuality in the doctor-patient interaction, partly due to the lack of training of health professionals, and due to the patients' own inhibitions. Discussion: Social and theoretical obstacles persist to address sexuality issues in consultation, as well as gender differences for the treatment of sexuality and sexual health issues. Conclusions: Health service providers are key to removing barriers to care, accompaniment and understanding of the sexual health and sexuality of the elderly.

Uso de métodos anticonceptivos de alta eficacia posterior a la interrupción voluntaria del embarazo en Profamilia, 2015-2020

Objetivo: Describir los métodos anticonceptivos reportados por las usuarias de servicios de interrupción voluntaria del embarazo (IVE), antes y posterior a la consulta, y explorar la asociación entre las características sociodemográficas y los antecedentes ginecológicos con la elección de anticonceptivos de alta eficacia posterior a la IVE, con gestaciones menores de 15 semanas, en el departamento de Antioquia, Colombia, en la institución Profamilia, entre el 2015 y el 2020. Metodología: Estudio de corte transversal. Se analizaron los 13 067 registros de consultas de IVE realizadas en Profamilia de la regional Antioquia, del 2015 al 2020. Las variables cualitativas se midieron con frecuencias y porcentajes, y las cuantitativas, con la media y la desviación estándar. Se implementaron modelos de regresión logística para establecer la asociación de las variables independientes con la variable de interés. Resultados: La consulta de IVE contribuyó al incremento del uso de métodos anticonceptivos de alta eficacia. Antes de la IVE, el 53 % de las mujeres no usaban ningún método. Posterior a la interrupción, el 97 % empezó a utilizar métodos de alta eficacia. Además del uso de métodos poco eficaces o el uso de preservativo, obtuvieron una posibilidad 13 veces más alta de elegir un método de alta eficacia. Conclusiones: La educación en métodos anticonceptivos posterior a una IVE es fundamental para promover el uso de opciones muy efectivas, con el fin de disminuir la aparición de nuevos embarazos no deseados que puedan llevar a una IVE recurrente.

Objective: To describe the contraceptive methods reported by users of voluntary termination of pregnancy (VTP) services, before and after consultation, and to examine the association between sociodemographic characteristics and gynecological history with choosing highly effective contraceptive methods after VTP, in gestations shorter than 15 weeks, in the department of Antioquia, Colombia, at the Profamilia institution, from 2015 to 2020. Methodology: This is a cross-sectional study. We analyzed 13 067 records of VTP consultations performed in Profamilia in Antioquia from 2015 to 2020. Qualitative variables were measured with frequencies and percentages, and quantitative variables with the mean and standard deviation. Logistic regression models were implemented to establish the association of the independent variables with the variable of interest. Results: VTP consultation contributed to increased use of highly effective contraceptive methods. Before VTP, 53% of women were not using any method. After the termination, 97% started using highly effective methods. Likewise, those using low efficacy methods or condoms were 13 times more likely to choose a highly effective method. Conclusions: Post-VTP contraceptive education is essential for promoting the use of highly effective methods to reduce the occurrence of new unwanted pregnancies that may lead to repeated VTP

Objetivo: Descrever os métodos anticoncepcionais referidos pelas usuárias de serviços de interrupção voluntária da gravidez (IVG), antes e depois da consulta, e estudar a associação entre as características sociodemográficas e os antecedentes ginecológicos com a eleição de anticoncepcionais de alta eficiência depois da IVG, com gestações menores de 15 semanas, no departamento de Antioquia, Colômbia, na instituição Profamilia, entre 2015 e 2020. Metodologia: Estudo de corte transversal. Analisaram-se os 13067 registros de consultas de IVG realizadas em Profamilia na sede Antioquia, de 2015 a 2020. As variáveis qualitativas mediram-se com frequências e porcentagens, e as quantitativas com a média e o desvio padrão. Implementaram-se modelos de regressão logística para estabelecer a associação das variáveis independentes com a variável de interesse. Resultados: A consulta de IVG contribuiu ao incremento do uso de métodos anticoncepcionais de alta eficiência. Antes da IVG, o 53% das mulheres não usavam nenhum método. Depois da interrupção, o 97% começou a usar métodos de alta eficiência. Além do uso de métodos pouco eficientes ou o uso da camisinha, obtiveram uma possibilidade 13 vezes maior de escolher um método de alta eficiência. Conclusões: A educação em métodos anticoncepcionais posterior a uma IVG é fundamental para promover o uso de opções muito efetivas, com o fim de diminuir a aparição de novas gravidezes não desejadas que podem levar a uma IVG recorrente.

Effect of Resistant Dextrin on Intestinal Gas Homeostasis and Microbiota.

Previous studies have shown that a resistant dextrin soluble fibre has prebiotic properties with related health benefits on blood glucose management and satiety. Our aim was to demonstrate the effects of continuous administration of resistant dextrin on intestinal gas production, digestive sensations, and gut microbiota metabolism and composition. Healthy subjects (n = 20) were given resistant dextrin (14 g/d NUTRIOSE®, Roquette Frères, Lestrem, France) for four weeks. Outcomes were measured before, at the beginning, end, and two weeks after administration: anal evacuations of gas during daytime; digestive perception, girth, and gas production in response to a standard meal; sensory and digestive responses to a comfort meal; volume of colonic biomass by magnetic resonance; taxonomy and metabolic functions of fecal microbiota by shotgun sequencing; metabolomics in urine. Dextrin administration produced an initial increase in intestinal gas production and gas-related sensations, followed by a subsequent decrease, which magnified after discontinuation. Dextrin enlarged the volume of colonic biomass, inducing changes in microbial metabolism and composition with an increase in short chain fatty acids-producing species and modulation of bile acids and biotin metabolism. These data indicate that consumption of a soluble fibre induces an adaptative response of gut microbiota towards fermentative pathways with lower gas production.

Milk-Derived Exosomes as Nanocarriers to Deliver Curcumin and Resveratrol in Breast Tissue and Enhance Their Anticancer Activity.

Dietary (poly)phenols are extensively metabolized, limiting their anticancer activity. Exosomes (EXOs) are extracellular vesicles that could protect polyphenols from metabolism. Our objective was to compare the delivery to breast tissue and anticancer activity in breast cancer cell lines of free curcumin (CUR) and resveratrol (RSV) vs. their encapsulation in milk-derived EXOs (EXO-CUR and EXO-RSV). A kinetic breast tissue disposition was performed in rats. CUR and RSV were analyzed using UPLC-QTOF-MS and GC-MS, respectively. Antiproliferative activity was tested in MCF-7 and MDA-MB-231 breast cancer and MCF-10A non-tumorigenic cells. Cell cycle distribution, apoptosis, caspases activation, and endocytosis pathways were determined. CUR and RSV peaked in the mammary tissue (41 ± 15 and 300 ± 80 nM, respectively) 6 min after intravenous administration of EXO-CUR and EXO-RSV, but not with equivalent free polyphenol concentrations. Nanomolar EXO-CUR or EXO-RSV concentrations, but not free CUR or RSV, exerted a potent antiproliferative effect on cancer cells with no effect on normal cells. Significant (p < 0.05) cell cycle alteration and pro-apoptotic activity (via the mitochondrial pathway) were observed. EXO-CUR and EXO-RSV entered the cells primarily via clathrin-mediated endocytosis, avoiding ATP-binding cassette transporters (ABC). Milk EXOs protected CUR and RSV from metabolism and delivered both polyphenols to the mammary tissue at concentrations compatible with the fast and potent anticancer effects exerted in model cells. Milk EXOs enhanced the bioavailability and anticancer activity of CUR and RSV by acting as Trojan horses that escape from cancer cells' ABC-mediated chemoresistance.

First exploratory study on the metabolome from plasma exosomes in patients with paroxysmal nocturnal hemoglobinuria.

INTRODUCTION: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease in which patients are at increased risk of thrombosis. The mechanisms underlying the associated thrombosis risk are still poorly understood, although it is known that Eculizumab, the drug of choice for symptomatic patients, prevents thrombotic events. Exosomes are extracellular vesicles that can carry and disseminate genetic material, tumor biomarkers and inflammatory mediators. To date, the metabolite cargo of plasma exosomes from PNH patients has not yet been explored. In this pilot trial, we compared the metabolome of plasma exosomes from PNH patients with that of healthy subjects in order to provide further insights into this rare disease. RESULTS: We used a non-targeted metabolomics approach with UPLC-ESI-QTOF-MS/MS and GC-MS platforms. Multivariate analyses revealed the differential occurrence (p < .001) of 78 metabolites in plasma exosomes from PNH patients vs healthy control subjects. Remarkably, prostaglandin F2-alpha (6.1-fold), stearoyl arginine (5.3-fold) and 26-hydroxycholesterol-3-sulfate (11.2-fold) were higher in PNH patients vs healthy controls (p < .001). CONCLUSIONS: This is the first description on the differential metabolite cargo occurring in plasma exosomes from PNH patients. Our results could contribute to the search for possible prognostic biomarkers of thrombotic risk in patients with PNH. Further research in a larger cohort to validate these results is warranted.

A serum metabolomics-driven approach predicts orange juice consumption and its impact on oxidative stress and inflammation in subjects from the BIONAOS study.

SCOPE: To identify biomarkers of orange juice (OJ) consumption containing different doses of polyphenols and to determine its impact on oxidative stress and inflammation using an untargeted metabolomics analysis. METHODS AND RESULTS: Thirty subjects aged 22-63 years from the BIONAOS study consumed a normal-polyphenol OJ (NPJ) or a high-polyphenol OJ (HPJ) (299 or 745 mg/L, respectively) for 12 weeks in a randomized, parallel, double-blind study. UHPLC-MS, univariate and multivariate statistical analysis and ROC curves were used to design biomarkers of consumption in serum. We propose betonicine, stachydrine, methyl glucopyranoside (alpha+beta), dihydroferulic acid and galactonate as a new metabolic signature to distinguish the intake of OJ with a different polyphenol content. Changes in metabolites related to OJ, oxidative stress and inflammation were observed. After HPJ consumption, the serum levels of hydroxyoctadecadienoic acid (9-HODE+13-HODE) and dihydroxyoctadecanoic acid (12,13-DiHOME and 9,10-DiHOME) decreased, whereas levels of 12-hydroxyeicosatetraenoic acid (12-HETE) increased. 5-HETE increased after the NPJ intervention exclusively. CONCLUSION: We designed a new panel of biomarkers to differentiate the intake of OJs containing different doses of polyphenols. On the other hand, the consumption of an OJ with a high content of flavanones improved oxidative stress and inflammatory biomarkers.

Low HIV testing uptake following diagnosis of a sexually transmitted infection in Spain: implications for the implementation of efficient strategies to reduce the undiagnosed HIV epidemic.

Sexually transmitted infections (STIs) are recognized as one of the conditions in which HIV testing is most clearly indicated. We analyse whether people diagnosed with an STI are being tested for HIV according to the experience of participants in an outreach rapid testing programme in Spain. Between 2008 and 2010, 6293 individuals underwent rapid testing and completed a self-administered questionnaire. We calculated the percentage of individuals that were diagnosed with an STI in the last 5 years and identified the setting where the last episode occurred. We then determined the percentage not receiving an HIV test after the last STI diagnosis and estimated the associated factors. Overall, 17.3% (N = 959) of participants reported an STI diagnosis in the last 5 years, of which 81.5% occurred in general medical settings. Sixty-one percent reported not undergoing HIV testing after their last STI diagnosis, 2.2% of whom reported they had refused the test. Not receiving an HIV test after the last STI diagnosis was independently associated with not being a man who has sex with men (MSM), having had fewer sexual partners, being diagnosed in general medical settings and having received a diagnosis other than syphilis. An unacceptably large percentage of people diagnosed with STI are not being tested for HIV because healthcare providers frequently fail to offer the test. Offering routine HIV testing at general medical settings, regardless of the type of STI diagnosed and population group, should be a high priority and is probably a more efficient strategy than universal screening in general healthcare settings.

Hesperetin and its sulfate and glucuronide metabolites inhibit TNF-α induced human aortic endothelial cell migration and decrease plasminogen activator inhibitor-1 (PAI-1) levels.

Epidemiological, clinical and preclinical studies have reported the protection offered by citrus consumption, mainly orange, against cardiovascular diseases, which is primarily mediated by the antiatherogenic and vasculoprotective effects of the flavanone hesperetin-7-O-rutinoside (hesperidin). However, flavanone aglycones or glycosides are not present in the bloodstream but their derived phase-II metabolites could be the actual bioactive molecules. To date, only a few studies have explored the effects of circulating hesperetin-derived metabolites (glucuronides and sulfates) on endothelial cells. Herein, we describe for the first time the effects of hesperetin 3'-O-glucuronide, hesperetin 7-O-glucuronide, hesperetin 3'-O-sulfate, hesperetin 7-O-sulfate and hesperetin on human aortic endothelial cell (HAEC) migration upon pro-inflammatory stimuli as an essential step to angiogenesis. Hesperetin and its derived metabolites, at physiologically relevant concentrations (1-10 µM), significantly attenuated cell migration in the presence of the pro-inflammatory cytokine TNF-α (50 ng mL(-1)), which was accompanied and perhaps mediated by a significant decrease in the levels of the thrombogenic plasminogen activator inhibitor-1 (PAI-1). However, hesperetin metabolites did not counteract the TNF-α-induced production of pro-inflammatory interleukin-6 (IL-6) and IL-8. We also study here for the first time, the metabolism of hesperetin and its derived metabolites by HAEC with and without a pro-inflammatory stimulus. All these results reinforce the concept according to which circulating phase-II hesperetin metabolites are critical molecules contributing to the cardioprotective effects upon consumption of citrus fruits such as orange.

Area-level socioeconomic context, total mortality and cause-specific mortality in Spain: Heterogeneous findings depending on the level of geographic aggregation.

The objective of this study was to estimate the association between area-level socioeconomic context and mortality in Spain, using two different geographic aggregations. Nation-wide prospective study covering all persons living in Spain in 2001. Mortality was analysed in Spanish citizens by province of residence and in citizens of Madrid by neighbourhood of residence. Provinces and neighbourhoods were grouped into quartiles according to two socioeconomic indicators: percentage of the population with university education and unemployment rate. The measure of association was the rate ratio for total mortality and cause-specific mortality, by each socioeconomic indicator in two age groups, 25-64 years (adult population) and 65 years and over (elderly population). After adjustment for all individual socioeconomic variables, the rate ratio for total mortality among residents in the provinces with the worst versus best socioeconomic context was 0.92 (95% CI 0.88-0.97) when the indicator was percentage of university population and 0.89 (0.85-0.93) when it was unemployment rate in the adult population, and 1.05 (1.00-1.11) and 1.08 (1.03-1.13), respectively, in the elderly population. No significant differences in mortality were observed between adults residing in neighbourhoods with the worst versus best socioeconomic context, but in the elderly population the mortality rate ratios for the two socioeconomic indicators were 1.04 (1.01-1.07) and 1.06 (1.03-1.09), respectively. Residents in provinces with the worst socioeconomic context had the lowest mortality from cancer and external causes and the highest mortality from cardiovascular diseases, while residents in neighbourhoods with the worst socioeconomic context had the highest mortality from respiratory and digestive diseases. Further research should find out the reasons for the lower total mortality in adult population residing in the Spanish provinces with the most adverse socioeconomic context and the reasons for excess mortality from digestive diseases and respiratory diseases among residents in neighbourhoods with the worst socioeconomic context.

Normal or High Polyphenol Concentration in Orange Juice Affects Antioxidant Activity, Blood Pressure, and Body Weight in Obese or Overweight Adults.

BACKGROUND: The consumption of orange juice may lead to reduced oxidative stress and may enhance the antioxidant defense system. OBJECTIVE: The aim was to evaluate the effects of the intake of orange juice containing either normal (NPJ) or high (HPJ) concentrations of polyphenols (299 and 745 mg/d, respectively) on the antioxidant defense system, oxidative stress biomarkers, and clinical signs of metabolic syndrome in 100 nonsmoking subjects who were either overweight or obese. METHODS: A randomized, double-blind crossover study was conducted over two 12-wk periods with a 7-wk washout period. The effects on enzymatic and nonenzymatic blood antioxidant defense systems, urinary and plasma oxidative stress biomarkers, and clinical signs of metabolic syndrome were evaluated before and after an intervention with both of the orange juices. Paired t tests and linear mixed-effects models were used to evaluate the effects of juice, time, and interactions. RESULTS: The intake of either NPJ or HPJ led to a decrease in urinary 8-hydroxy-2'-deoxyguanosine (NPJ: 935 ± 134 to 298 ± 19 ng/mg creatinine; HPJ: 749 ± 84 to 285 ± 17 ng/mg creatinine), 8-iso-prostaglandin F2α (NPJ: 437 ± 68 to 156 ± 14 ng/mg creatinine; HPJ: 347 ± 43 to 154 ± 13 ng/mg creatinine), erythrocyte catalase, and glutathione reductase activities. A decrease was also observed in body mass index, waist circumference, and leptin (all P < 0.05). The NPJ intervention decreased systolic and diastolic blood pressures (systolic blood pressure: 128 ± 1 to 124 ± 2 mm Hg; diastolic blood pressure: 79 ± 1 to 76 ± 1 mm Hg), whereas the HPJ intervention increased erythrocyte superoxide dismutase (SOD) activity (17.7 ± 1.5 to 23.1 ± 1.7 U/mg hemoglobin). CONCLUSIONS: Our results show that the consumption of either NPJ or HPJ protected against DNA damage and lipid peroxidation, modified several antioxidant enzymes, and reduced body weight in overweight or obese nonsmoking adults. Only blood pressure and SOD activity were influenced differently by the different flavanone supplementations. This trial was registered at clinicaltrials.gov as NCT01290250.

Lethality of Opioid Overdose in a Community Cohort of Young Heroin Users.

BACKGROUND: The aim of the study was to estimate the lethality of opioid overdose among young heroin users. METHODS: A prospective community cohort study was conducted in Barcelona and Madrid, Spain. Participants included 791 heroin users aged 18-30 years who were followed up between 2001 and 2006. Fatal overdoses were identified by record linkage of the cohort with the general mortality register, while non-fatal overdoses were self-reported at baseline and follow-up interviews. The person-years (py) at risk were computed for each participant. Fatal and non-fatal overdose rates were estimated by city. Transition towards injection shortly before the overdose could not be measured. Overdose lethality (rate of fatal overdose in proportion to total overdose) and its 95% CI was estimated using Bayesian models. RESULTS: The adjusted rates of fatal and non-fatal opioid overdose were 0.7/100 py (95% CI: 0.4-1.1) and 15.8/100 py (95% CI: 14.3-17.6), respectively. The adjusted lethality was 4.2% (95% CI: 2.5-6.5). CONCLUSIONS: Four out of 100 opioid overdoses are fatal. These are preventable deaths that could be avoided before or after the overdose takes place. Resources are urgently needed to prevent fatal opioid overdose.

High hepatitis C virus prevalence and incidence in a community cohort of young heroin injectors in a context of extensive harm reduction programmes.

BACKGROUND: Cohort studies on hepatitis C virus (HCV) among drug injectors are scarcer than studies on HIV. Combined harm reduction interventions (HRIs) can prevent HCV infection. Spain has a medium-high coverage of HRIs. METHODS: 513 young heroin users who injected drugs in the past 12 months (recent injectors) were street-recruited in 2001-2003 and followed until 2006 in three Spanish cities; 137 were anti-HCV seronegative, 77 of whom had ≥1 follow-up visit. Dried blood spots were tested for anti-HCV. HCV incidence and predictors of infection were estimated using Poisson models. RESULTS: At baseline, 73% were anti-HCV positive. Overall incidence (n=77) of HCV seroconversion was 39.8/100 person-years (py) (95% CI 28.7 to 53.8). Excluding non-injectors during follow-up from the analysis (n=57), HCV incidence was 52.9/100 py (95% CI 37.4 to 72.5). Injecting at least weekly (incidence rate ratio (IRR)=5.2 (95% CI 2.5 to 11.1)) and having ≥2 sexual partners (IRR=2.2 (95% CI 1.1 to 4.7)) were independent predictors of HCV seroconversion; drug-injection history <2 years was marginally associated (IRR=2.4 (95% CI 0.9 to 4.7)). HCV incidence may have been underestimated due to differential attrition. CONCLUSIONS: Despite fairly high HRI coverage among Spanish drug injectors, a distressingly high incidence of HCV in a context of high HCV prevalence was found among young heroin injectors.

Low mortality in the poorest areas of Spain: adults residing in provinces with lower per capita income have the lowest mortality.

The objective of this study is to ascertain whether income inequality and per capita income of area of residence show a relationship with mortality in Spain. Data are from a nation-wide prospective study with a 7-year mortality follow-up covering all persons living in Spain's 50 provinces in 2001. In total 28,944,854 subjects aged 25 years or over at baseline were studied. Rate ratio for total mortality and cause-specific mortality, according to provincial income inequality and per capita income in two age groups, 25-64 years (adult population) and 65 years and over (elderly population). Provincial income inequality was not related to total mortality or cause-specific mortality. Total mortality rate ratios among residents of the poorest versus the richest provinces were 0.89 (95% CI 0.95-0.93) in men and 0.91 (0.87-0.96) in women, among the adult population; and 1.02 (0.97-1.08) in men and 1.08 (1.02-1.16) in women, among the elderly population. With the exception of cardiovascular-disease mortality for which no association with per capita income was observed, adult residents of the poorest provinces registered the lowest mortality rate ratio for other causes of death. Elderly residents of the poorest provinces registered the highest mortality rate ratio for cardiovascular disease and the lowest mortality rate ratio for cancer and external causes. Aside from cardiovascular-disease mortality, the lowest mortality for most causes of death was registered by residents of the poorest provinces. Nevertheless, these findings need to be confirmed by similar studies using smaller areas as the unit of analysis.

A dietary resveratrol-rich grape extract prevents the developing of atherosclerotic lesions in the aorta of pigs fed an atherogenic diet.

The presence of grape and wine polyphenol resveratrol (RES) in the diet is negligible. Therefore, the cardiovascular benefits of this molecule, in a dietary context, remain to be established. We aimed to investigate, through dietary intervention, the effects of a resveratrol-rich grape extract (GE-RES) on the prevention of early aortic lesions in pigs fed an atherogenic diet (AD). These effects were compared with those produced by a grape extract lacking RES (GE) or RES alone. Pigs fed the AD for 4 months showed early atherosclerotic lesions in the thoracic aorta: degeneration and fragmentation of elastic fibers, increase of intima thickness, subendothelial fibrosis, and accumulation of fatty cells and anion superoxide radicals. GE-RES was the most effective treatment and prevented the disruption of aortic elastic fibers, decreased their alteration (57%), and reduced the intima thickness (33%) and the accumulation of fatty cells (42%) and O(2)(•-) (38%) in aortic tissue. In addition, GE-RES moderately downregulated the expression of the suppressors of cytokine signaling 1 (SOCS1) and 3 (SOCS3), key regulators of vascular cell responses, in peripheral mononuclear blood cells. Our results suggest that the consumption of this GE-RES nutraceutical, in a dietary prevention context, could prevent early atherosclerotic events. The presence of RES in the grape extract strengthened these effects.

HCV seroconversion among never-injecting heroin users at baseline: no predictors identified other than starting injection.

BACKGROUND: Heroin users who do not inject constitute a large pool of drug users with a potentially important impact on public health. We aimed to estimate the incidence of hepatitis C virus (HCV) among heroin users who had never injected (NIDUS) at baseline, and the effect of starting injecting during follow-up, other percutaneous exposures, sharing snorting paraphernalia, cocaine/crack use, and risky sexual behaviour on HCV-seroconversion. METHODS: Prospective cohort of 305 HCV-negative NIDUs at baseline, aged 18-30 and street-recruited in three Spanish cities in 2001-2003. Computer-assisted personal interviews were conducted and dried blood-spot samples were collected. Bivariate and multivariable Poisson models were used. RESULTS: Among the 305 never-injectors who were HCV-negative at baseline, 197 (64.6%) were followed-up and 21 seroconverted [HCV-incidence rate=5.8/100 person-years at risk (pyar) (95% CI: 3.6-8.9)]. HCV incidence in new-injectors was 28.4/100 pyar [(95% CI, 14.7-49.7) vs. 2.8/100 pyar (95% CI, 1.3-5.4)] among NIDUs. Of the risk exposures considered, starting injecting was the only predictor of HCV-seroconversion [adjusted relative risk=10.1, 95% CI: 3.8-26.7]. CONCLUSION: The HCV-seroconversion rate was 10 times higher among new-injectors than never-injectors. No predictors other than starting injecting were found for HCV-seroconversion. Harm reduction interventions to prevent HCV infection should include prevention of drug injection.