Search

Summary: Despite extensive global research into genetic predisposition for severe COVID-19, knowledge on the role of rare host genetic variants and their relation to other risk factors remains limited. Here, 52 genes with prior etiological evidence were sequenced in 1,772 severe COVID-19 cases and 5,347 population-based controls from Spain/Italy. Rare deleterious TLR7 variants were present in 2.4% of young (

Summary: Background: We evaluated the association of hepatitis B virus (HBV) treatment with all-cause, and liver-related mortality among individuals with HBV and cirrhosis in British Columbia (BC), Canada. Methods: This analysis included people diagnosed with HBV and had cirrhosis in the BC Hepatitis Testers Cohort, including data on all individuals diagnosed with HBV from 1990 to 2015 in BC and integrated with healthcare administrative data. We followed people with cirrhosis from the first cirrhosis diagnosis date until death or December 31, 2020. We compared all-cause and liver related mortality between those who received treatment and those who did not. HBV treatment was considered a time-varying variable. We performed multivariable Cox proportional hazards model and competing risk regression models to assess the association of HBV treatment with all causes, and liver-related mortality respectively using inverse probability of treatment weighted population. Findings: Among 4962 individuals with HBV and cirrhosis, 48.1% received HBV treatment. Treated individuals had a median follow-up of 2.97 years, compared to 2.87 years for untreated individuals. The treated group was older (median age 57 vs 54 years), had higher proportion of treated of males [1802 (75.50%) vs 1766 (68.8%)], from urban area [2318 (97.2%) vs 2355 (91.8%)], and from East and South Asian ethnicity [1506 (63.1%) vs 709 (27.5%)] compared to untreated group. Untreated people experienced higher all-cause mortality (115.47 vs. 35.72 per 1000 person-years) and liver-related mortality (49.86 vs. 11.39 per 1000 person-years). Multivariable models showed that HBV treatment significantly lowered the risk of all-cause mortality (adjusted hazard ratio (aHR) 0.74; 95% CI: 0.65, 0.84) and liver-related mortality (adjusted subdistribution hazard ratio (asHR) 0.72; 95% CI: 0.58, 0.89) compared to untreated individuals. Among untreated individuals with HBV, those with HCV coinfection had a higher risk of both all-cause and liver-related mortality (aHR 1.57; 95% CI: 1.22, 2.04, and asHR 1.60; 95% CI: 1.25, 2.05, respectively). Interpretation: HBV treatment was associated with a significant reduction in all-cause and liver-related mortality among individuals with cirrhosis. The findings highlight the need for treatment among individuals with HBV related cirrhosis especially those with coinfection with hepatitis C virus. Funding: This work was supported by the BC Centre for Disease Control and the Canadian Institutes of Health Research (CIHR) [Grant # NHC-142832, PJT-156066, and SC1 -178736]. JDM has received doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). DJ has received Doctoral Research Award (#201910DF1-435705-64343) from the Canadian Institutes of Health Research (CIHR) and doctoral fellowship from the CanHepC. CanHepC is funded by a joint initiative of the Canadian Institutes of Health Research (CIHR) (NHC-142832) and the Public Health Agency of Canada (PHAC).

Summary: Actinomycetota (Actinobacteria) is an ecologically and industrially important phylum which is challenging to extract pure high-molecular-weight (HMW) DNA from. This protocol provides a parallelized, cost-effective, and straightforward approach for consistently extracting pure HMW DNA using modified non-toxic commercial kits suitable for higher throughput applications. We further provide a workflow for sequencing and assembly of complete genomes using an optimized Oxford Nanopore rapid barcoding protocol and Illumina data error correction. : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Objectives: Addressing the needs of ethnic minorities will be key to finding undiagnosed individuals living with hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV). To inform screening initiatives in British Columbia (BC), Canada, the factors associated with HBV and/or HCV and/or HIV infection among different ethnic groups within a large population-based cohort were assessed. Methods: Persons diagnosed with HBV, HCV, or HIV in BC between 1990 and 2015 were grouped as East Asian, South Asian, Other Visible Minority (African, Central Asian, Latin American, Pacific Islander, West Asian, unknown ethnicity), and Not a Visible Minority, using a validated name-recognition software. Factors associated with infection within each ethnic group were assessed with multivariable multinomial logistic regression models. Results: Participants included 202 521 East Asians, 126 070 South Asians, 65 210 Other Visible Minorities, and 1 291 561 people who were Not a Visible Minority, 14.4%, 3.3%, 4.5%, and 6.3% of whom had HBV and/or HCV and/or HIV infections, respectively. Injection drug use was most prevalent among infection-positive people who were Not a Visible Minority (22.1%), and was strongly associated with HCV monoinfection, HBV/HCV coinfection, and HCV/HIV coinfection, but not with HBV monoinfection among visible ethnic minorities. Extreme material deprivation and social deprivation were more prevalent than injection drug use or problematic alcohol use among visible ethnic minorities. Conclusions: Risk factor distributions varied among persons diagnosed with HBV and/or HCV and/or HIV of differing ethnic backgrounds, with lower substance use prevalence among visible minority populations. This highlights the need for tailored approaches to infection screening among different ethnic groups.

Background: Hepatitis C (HCV) affects diverse populations such as people who inject drugs (PWID), 'baby boomers,’ gay/bisexual men who have sex with men (gbMSM), and people from HCV endemic regions. Assessing HCV syndemics (i.e.relationships with mental health/chronic diseases) among subpopulations using Latent Class Analysis (LCA) may facilitate targeted program planning. Methods: The BC Hepatitis Testers Cohort(BC-HTC) includes all HCV cases identified in BC between 1990 and 2015, integrated with medical administrative data. LCA grouped all BC-HTC HCV diagnosed people(n = 73,665) by socio-demographic/clinical indicators previously determined to be relevant for HCV outcomes. The final model was chosen based on fit statistics, epidemiological meaningfulness, and posterior probability. Classes were named by most defining characteristics. Results: The six-class model was the best fit and had the following names and characteristics:‘Younger PWID’ (n =11,563): recent IDU (67%), people born >1974 (48%), mental illness (62%), material deprivation (59%).‘Older PWID’ (n =15,266): past IDU (78%), HIV (17%), HBV (17%) coinfections, alcohol misuse(68%).‘Other Middle-Aged People’ (n = 9019): gbMSM (26%), material privilege (31%), people born between 1965−1974 (47%).‘People of Asian backgrounds’ (n = 4718): East/South Asians (92%), no alcohol misuse (97%) or mental illness (93%), people born

Background: Costa Rica has undergone significant changes to its forest ecosystems due, in part, to the proliferation of palm oil and other industrial agriculture operations. However, the country also boasts conservation programmes that are among the most robust in the neotropics. Consequently, gradients of anthropogenic to intact ecosystems are found throughout the country. Forest ecosystems may decrease vector-borne disease (VBD) risk by maintaining insect populations in a state of relative equilibrium; however, evidence suggests that intact forests foster biodiversity and may also amplify VBD risk in some circumstances. As a result, focal points of human-vector contact are likely idiosyncratic. This may be particularly true in indigenous territories, which have been shown to play a vital role in maintaining the ecological integrity of conservation areas. Here, we investigate the relationships between anthropogenic landscapes, indigenous territories, protected areas, and risk of VBD. Methods: We quantified spatial dynamics of risk across three distinct categories of VBD in Costa Rica: emerging flaviviruses (Zika virus disease and dengue); neglected tropical diseases (cutaneous leishmaniasis and Chagas disease); and a disease nearing eradication (malaria). We collected district-level incidence data from between 2006 and 2017 and used spatial statistics to identify hotspots of elevated risk. We then quantified the associations between anthropogenic landscapes, intact forest ecosystems, and indigenous territories with both the presence and persistence of elevated transmission risk over time using multivariate hurdle models. Findings: We detected clear patterns of non-random disease risk across each of the three categories of VBD. Compared with protected areas, districts with higher proportions of human-altered landscapes, particularly agricultural intensification, were at higher risk for VBD across all categories. Districts with the highest proportion of crop cover, compared with the lowest proportion, were significantly associated with the presence of hotspots for Zika virus disease (OR 15·19 [95% CI 6·19–37·26]), dengue (13·00 [7·24–23·35]), leishmaniasis (4·46 [1·18–16·84]), Chagas disease (3·09 [1·47–6·49]), and malaria (8·40 [3·56–19·83]). Interpretation: A set of spatial epidemiology tools within a planetary health framework allowed for a refined understanding of the risk of VBD of global public health significance in a biodiversity hotspot. Our findings may be used to better guide targeted public health disease surveillance, control, and prevention programmes. Additional research to understand the role that socioeconomic factors play in the variating VBD risk would contribute additional context to these findings, as these factors are often also spatially associated. Funding: None.

Background: Limited data are available on HBV, HCV, and HIV co-infections and triple infection. We characterized co-occurrence of HIV, HBV, and HCV infections at the population level in British Columbia (BC) to identify patterns of predisposing factors unique to co-infection subgroups. Methods: We analyzed data from the BC Hepatitis Testers Cohort, which includes all individuals tested for HCV or HIV in BC between 1992 and 2013, or included in provincial public health registries of HIV, HCV, HBV, and active tuberculosis. Individuals were classified as negative, mono-, and co-infection groups based on HIV, HBV, and HCV status. We evaluated associations between risk factors (injection drug use, sexual orientation etc.) and co-infection groups using multivariate multinomial logistic regression. Findings: Of a total of 1,376,989 individuals included in the analysis, 1,276,290 were negative and 100,699 were positive for HIV, HBV, and/or HCV. Most cases (91,399, 90.8%) were mono-infected, while 3991 (4.0%) had HBV/HCV, 670 HBV/HIV (0.7%), 3459 HCV/HIV (3.4%), and 1180 HBV/HCV/HIV (1.2%) co-infection. Risk factor and demographic distribution varied across co-infection categories. MSM classification was associated with higher odds of all HIV co-infection groups, particularly HBV/HIV (OR 6.8; 95% CI: 5.6, 8.27), while injection drug use was most strongly associated with triple infection (OR 64.19; 95% CI: 55.11, 74.77) and HIV/HCV (OR 23.23; 95% CI: 21.32, 25.31). Interpretation: Syndemics of substance use, sexual practices, mental illness, socioeconomic marginalization, and co-infections differ among population groups, highlighting avenues for optimal composition and context for health services to meet each population's unique needs. Funding: BC Centre for Disease Control and Canadian Institutes of Health Research. Keywords: Hepatitis B, Hepatitis C, HIV, Substance use, Syndemics, Co-infection

Rice bran is an excellent nutritional source of bioactive compounds, including phytochemicals such as ferulic acid, γ-oryzanol, phytosterols and tocols. These bioactive molecules have shown cardiometabolic protection, such as anti-diabetic and anti-hypertensive effects, but more importantly, lipid lowering effects due to cholesterol synthesis downregulation and increased faecal excretion. Moreover, rice bran phytochemicals have been described to mitigate oxidative stress by increasing antioxidant enzymes and by reducing oxygen radical production, and to possess anti-inflammatory activity due to downregulation of NF-κβ activation and reduction of pro-inflammatory cytokines production. This review aims to update and summarize clinical and animal studies, describing the multifactorial activities of rice bran and the individual contribution of its main bioactive compounds, namely, γ-oryzanol, ferulic acid, phytosterols, triterpenic alcohols and tocotrienols. Technological factors affecting biological activities of the different rice bran-derived preparations are also discussed.

Rice bran has long been considered as a nutritional supplement in the prevention of cardiovascular diseases. ApoE−/− mice were fed high fat diet supplemented with 1 or 5% rice bran enzymatic extract (RBEE). In parallel, 100 ng/ml LPS induced human monocytes were treated with 20 µg/ml RBEE, ferulic acid (FA) or γ-oryzanol (γ-Ory). RBEE diet supplements reduced NF-κβ activation, TNF-α, COX-2 and iNOS expression and serum NO-derived metabolites. Additionally, NADPH oxidase subunits were downregulated, resulting in lower superoxide production, as evidenced by lower dihydroethidium fluorescence and oxLDL deposition in the aorta. RBEE, FA and γ-Ory reduced pro-inflammatory monocyte (CD14++ CD16+) phenotype and increased non-classical monocytes (CD14− CD16++). A shift towards M2 polarised macrophages was observed, leading to reduced IL-6 and TNF-α mRNA expressions. RBEE chronic consumption ameliorates atherosclerosis-related oxidative stress and inflammation showing its potential as nutritional supplement. FA moiety of γ-Ory was identified as the main responsible for the actions observed.

Background: Population-level monitoring of hepatitis C virus (HCV) infected people across the cascade of care identifies gaps in access and engagement in care and treatment. We characterized a population-level cascade of care for HCV in British Columbia (BC), Canada and identified factors associated with leakage at each stage. Methods: The BC Hepatitis Testers Cohort (BC-HTC) includes 1.5 million individuals tested for HCV, HIV, reported cases of hepatitis B, and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalizations, cancers, prescription drugs and mortality data. We defined six HCV cascade of care stages: 1) estimated population prevalence; 2) HCV diagnosed; 3) HCV RNA tested; 4) genotyped; 5) initiated treatment; and 6) achieved sustained virologic response (SVR). Results: We estimated that 73,203 people were HCV antibody positive in BC in 2012 (undiagnosed: 18,301, 25%; diagnosed: 54,902, 75%). Of these, 56%(40,656) had HCV RNA testing; 34%(26,300) were genotyped; 12%( 8532 ) had received interferon-based therapy and 7%(5197) had SVR. Males, older birth cohorts, and HBV coinfected were less likely to undergo HCV RNA testing. Among those with chronic HCV infection, 32% had received liver-related care. Retention in liver care was more likely in those with HIV, cirrhosis, and drug/alcohol use and less likely in males and HBV coinfected. Conclusions: Although there are gaps in HCV RNA testing and genotyping after HCV diagnosis, the major gap in the cascade of care was low treatment initiation. People with comorbidities progressed through the cascade of testing and care but few received treatment.

Background: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet β cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. Methods: In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient's lymphocytes with CB-SCs in vitro and returns the “educated” lymphocytes (but not the CB-SCs) into the patient's blood circulation. This study is registered with ClinicalTrials.gov, NCT01350219. Findings: Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naïve CD4+ T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4+ central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4+ effector memory T cells (TEM) and CD8+ TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C–C chemokine receptor 7 (CCR7) expressions on naïve T, TCM, and TEM cells. Following two treatments with SCE therapy, islet β-cell function was improved and maintained in individuals with residual β-cell function, but not in those without residual β-cell function. Interpretation: Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet β-cell function in Caucasian subjects. Funding: Obra Social “La Caixa”, Instituto de Salud Carlos III, Red de Investigación Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation.

Grape pomace enzymatic extract (GP-EE) exhibits a potent antioxidant and vasodilator activity, although the mechanisms underlying this action are not completely understood. Our aim was to evaluate its vasoactive mechanisms, focusing on vascular NADPH oxidase and superoxide dismutase (SOD)-dependent pathways. GP-EE effectively restored vascular impairment induced by the NADPH oxidase activator endothelin-1 through downregulation of its Nox-1 and p47phox subunits. GP-EE partially prevented endothelial dysfunction elicited by the SOD inhibitor, DETCA, preserving EC-SOD and Mn-SOD isoenzymes protein expression. Although many of these vasoactive effects could be attributed to the presence of catechin, GP-EE was able to exert additional protection against the vascular deleterious effects evoked by NADPHox activation and SOD inhibition. This additional vasoprotection could be related to the enzymatic extraction process, providing polyphenols from winemaking residue with a potent activity against vascular dysfunction by preventing NADPHox activation and maintaining SOD defense, making GP-EE as an ideal nutritional supplement.

Resumen: Introducción: La diabetes mellitus 1 es la segunda enfermedad crónica y el trastorno endocrino-metabólico más frecuente en la infancia. Se estima una prevalencia entre 1,1 y 1,4/1000 menores de 15 años. En Andalucía la prevalencia es mayor (1,7 por mil).El objetivo del estudio es analizar la calidad de vida y adherencia al tratamiento, centrándonos en la población pediátrica de Andalucía. Métodos: Estudio analítico observacional transversal multicéntrico. La muestra fue de 178 pacientes de seis hospitales con Endocrinología Pediátrica. A cada paciente se le entregaron dos cuestionarios; la encuesta de calidad de vida (PedsQL versión 3.0) y adherencia al tratamiento SCI-R. Además, se recogieron datos demográficos, clínicos, del control metabólico, y complicaciones. Resultados: Se obtuvieron niveles altos tanto en la adherencia como en la calidad de vida. La primera se relacionó de forma inversa con la edad y la HbA1c, aunque el coeficiente fue tan bajo que no permite sacar conclusiones significativas. La calidad de vida se asoció con el uso de sistema de monitorización continua de glucosa en tiempo real (MCG-TR) integrado con ISCI, así como con menos hipoglucemias graves y complicaciones renales.La HbA1c media fue 7,1%. El 12,9% de los pacientes usaban ISCI. El 83,2% empleaban exclusivamente la glucemia capilar, mientras que el 16,8% usaba algún dispositivo de monitorización de glucosa intersticial. Conclusiones: Se trata del primer estudio realizado en Andalucía que analiza la calidad de vida en pacientes pediátricos. Los resultados muestran niveles altos de adherencia y de calidad de vida, además de un buen control metabólico. Abstract: Introduction: Diabetes mellitus 1 is the second most frequent chronic disease, and the most frequent endocrine-metabolic disorder in childhood. The estimated prevalence is between 1.1 and 1.4 / 1000 children under 15 years years-old. In Andalusia the prevalence is higher (1.7 per thousand).The objective of the study is to evaluate health-related quality of life (HRQoL) and adherence to treatment, specifically in the paediatric population of Andalusia. Methods: A multicentre cross-sectional observational analytical study was conducted on a sample of 178 patients from six hospitals with a Paediatric Endocrinology Unit. Each patient received two questionnaires; quality of life (PedsQL version 3.0) and adherence to the self-care recommendations (SCI-R) treatment. The demographic, clinical, metabolic control data, and possible complications were also collected. Results: High levels were obtained in both adherence and health-related quality of life (HRQoL). Adherence was inversely related to age and HbA1c. The health-related quality of life (HRQoL) was associated with the use of a continuous real-time glucose monitoring system (MCG-TR) combined with continuous subcutaneous insulin infusion (CSII), as well as with a lower number of severe hypoglycaemia and renal complications. The mean HbA1c was 7.1%. 12,9% of patients used ISCI. 83.2% used capillary glycemia exclusively, while 16.8% used some interstitial glucose monitoring device. Conclusions: This is the first study in Andalusia that analyzes the health-related quality of life (HRQoL) of pediatric patients. The results show high levels of adherence and health-related quality of life (HRQoL), as well as good metabolic control.

Introduction: Diabetes Mellitus 1 (DM1) is the second most frequent chronic disease, and the most frequent endocrine-metabolic disorder in childhood. The estimated prevalence is between 1.1 and 1.4 / 1000 children under 15 years years-old. In Andalusia the prevalence is higher (1.7 per thousand).The objective of the study is to evaluate health-related quality of life (HRQoL) and adherence to treatment, specifically in the paediatric population of Andalusia. Methods: A multicentre cross-sectional observational analytical study was conducted on a sample of 178 patients from six hospitals with a Paediatric Endocrinology Unit. Each patient received two questionnaires; quality of life (PedsQL version 3.0) and adherence to the self-care recommendations (SCI-R) treatment. The demographic, clinical, metabolic control data, and possible complications were also collected. Results: High levels were obtained in both adherence and health-related quality of life (HRQoL). Adherence was inversely related to age and HbA1c. The health-related quality of life (HRQoL) was associated with the use of a continuous real-time glucose monitoring system (MCG-TR) combined with continuous subcutaneous insulin infusion (CSII), as well as with a lower number of severe hypoglycaemia and renal complications. The mean HbA1c was 7.1%. 12,9% of patients used ISCI. 83.2% used capillary glycemia exclusively, while 16.8% used some interstitial glucose monitoring device. Conclusions: This is the first study in Andalusia that analyzes the health-related quality of life (HRQoL) of pediatric patients. The results show high levels of adherence and health-related quality of life (HRQoL), as well as good metabolic control. Resumen: Introducción: La Diabetes Mellitus 1 (DM1) es la segunda enfermedad crónica y el trastorno endocrino-metabólico más frecuente en la infancia. Se estima una prevalencia entre 1.1 y 1.4/1000 menores de 15 años. En Andalucía la prevalencia es mayor (1,7 por mil).El objetivo del estudio es analizar la calidad de vida y adherencia al tratamiento, centrándonos en la población pediátrica de Andalucía. Métodos: Estudio analítico observacional transversal multicéntrico. La muestra fue de 178 pacientes de seis hospitales con Endocrinología Pediátrica. A cada paciente se le entregaron dos cuestionarios; la encuesta de calidad de vida (PedsQL versión 3.0) y adherencia al tratamiento SCI-R. Además, se recogieron datos demográficos, clínicos, del control metabólico, y complicaciones. Resultados: Se obtuvieron niveles altos tanto en la adherencia como en la calidad de vida. La primera se relacionó de forma inversa con la edad y la HbA1c, aunque el coeficiente fue tan bajo que no permite sacar conclusiones significativas. La calidad de vida, se asoció con el uso de sistema de monitorización continua de glucosa en tiempo real (MCG-TR) integrado con ISCI, así como con menos hipoglucemias graves y complicaciones renales.La HbA1c media fue 7,1%. El 12,9% de los pacientes usaban ISCI. El 83,2% empleaban exclusivamente la glucemia capilar, mientras que el 16,8% usaba algún dispositivo de monitorización de glucosa intersticial. Conclusiones: Se trata del primer estudio realizado en Andalucía que analiza la calidad de vida en pacientes pediátricos. Los resultados muestran niveles altos de adherencia y de calidad de vida, además de un buen control metabólico.

Resumen: Objetivo: Validar la escala Rowland Dementia Assessment Scale (RUDAS) como instrumento de cribado de deterioro cognitivo y demencia en atención primaria (AP). Es un test breve, válido para población con bajo nivel educativo formal y fácilmente traducible en entornos multiculturales. Diseño: Se realizó un estudio epidemiológico descriptivo, de corte transversal, con seguimiento a los 5 años. Emplazamiento: Centro de salud de atención primaria de O Grove, que atiende a una población de 10.650 habitantes en Pontevedra. Participantes: Ciento cincuenta personas aleatoriamente seleccionadas, con una edad media de 76,35 ± 7,12 años, bajo nivel educativo, origen predominantemente rural y semirrural y nivel socioeconómico bajo. Intervención: Se analizó la viabilidad, la aceptabilidad, la validez y la fiabilidad de la escala. Mediciones principales: RUDAS, Mini Mental State Examination, Clinical Dementia Rating, Índice de Katz, Índice de Barthel, Índice de Lawton y Escala de Depresión Geriátrica de Yesavage. Resultados: El test fue bien acogido por los pacientes y rápido de aplicar (7,58 ± 2,10 min). El área bajo la curva COR para el diagnóstico de demencia fue 0,983 (IC 95%: 0,97-1,00). Para un punto de corte óptimo de 22,5 presentó una sensibilidad del 89,3% y una especificidad del 100%. El área bajo la curva COR para discriminar personas con DCL de personas con demencia fue 0,965 (IC 95%: 0,91-1,00). Conclusiones: El RUDAS ha demostrado ser un instrumento viable y eficiente para cribar demencias en AP, libre de influencias educativas y socioculturales. Es especialmente sensible para discriminar población con deterioro cognitivo leve de población con demencia. Abstract: Objective: To validate Rowland Dementia Assessment Scale (RUDAS), as an instrument for the screening of people with dementia and cognitive impairment in Primary Health Care (PHC). RUDAS is a brief cognitive test, appropriate for people with minimum completed level of education and easily adaptable to multicultural contexts. For these reason it could be a good instrument for dementia screening in PHC. Design: Cross-sectional descriptive epidemiological study with a five-year follow up. Location: O Grove PHC centre, Galicia, Spain (covering a population of 10,650 individuals). Outcome measures: RUDAS; Mini Mental State Examination; Clinical Dementia Rating; Katz, Barthel and Lawton Indexes; MMSE and Yesavage Geriatric Depression Scale. Participants: A total of 150 older adults (mean age 76.35 ± 7.12 years) randomly selected, from a low sociocultural and economical background and mainly rural and semirural origin. Intervention: RUDAS viability in PHC was checked, and its psychometric properties assessed: reliability, sensitivity, specificity, positive and negative predictive values. Results: RUDAS application was brief (7.58 ± 2.10 min) and well accepted. RUDAS area under receiver operating characteristic (ROC) curve for the detection of dementia was 0.983 (95% confidence interval (CI): 0.97-1.00) for an optimal cut-off point of 22.5, with sensitivity of 89.3%, and a specificity of 100%. Area under ROC curve for discriminating dementia from mild cognitive impairment was 0.965 (95% CI: 0.91-1.00). Conclusions: RUDAS test is fit for dementia screening in PHC and it is especially sensitive to discriminate PWD from people with MCI.

Background: Little is known about atopic dermatitis (AD) among children in Puerto Rico. Objective: To examine risk factors and identify approaches to better diagnose AD in Puerto Rican children. Methods: Case-control study of AD among 540 children aged 6–14 years in San Juan, Puerto Rico. AD was defined as: 1) physician-diagnosed AD, 2) RAST-AD: AD symptoms plus ≥1 positive IgE to allergens, and 3) STR-AD: AD-symptoms and skin test reactivity to ≥1 allergen. Logistic regression was used for the multivariable analysis. We also evaluated the diagnostic performance of various approaches by comparing their sensitivity, specificity, positive predicted value [PPV], negative predictive value [NPV], and area under curve [AUC]). Results: Of the 70 children with STR-AD, only 5 (7.1%) had PD-AD. In children without asthma, a positive IgE to Dermatophagoides (D.) pteronyssinus and signs of mold/mildew at home were significantly associated with 3.3 and 5 times increased odds of STR-AD, respectively. Among children with asthma, private/employer-based health insurance and a positive IgE to D. pteronyssinus were each significantly associated with approximately twofold increased odds of STR-AD. A combination of current eczema symptoms and a positive IgE to D. pteronyssinus yielded a sensitivity ≥70%, specificity and NPV ≥95%, PPV ≥88%, and an AUC ≥0.85 for STR-AD. Replacing a positive IgE to D. pteronyssinus with a positive IgE to ≥1 allergen slightly increased sensitivity without affecting other parameters. Conclusions: AD is markedly under-diagnosed by physicians in Puerto Rico. This could be improved by assessing eczema symptoms and measuring IgEs to common allergens. Keywords: Atopic dermatitis, Under-diagnosis, Puerto Rico, Children

Kawasaki disease is a self-limiting acute vasculitis that affects small and medium-sized vessels, and is the most common cause of acquired heart disease in children in our environment. Up to 25% of untreated patients develop coronary aneurysms. It is suspected that an infectious agent may be the trigger of the disease, but the causative agent is still unknown. Based on the previous evidence, recommendations are proposed for the diagnosis, treatment of acute disease, and the long-term management of these patients, in order to unify criteria. The diagnosis must be quick, based on easy-to-use algorithms and with the support of complementary tests. This document includes the indication of available imaging techniques, as well as the planning of cardiological examinations based on the initial involvement. Intravenous immunoglobulin is the basis of the initial treatment. The role of corticosteroids is still controversial, but there are studies that support its use as adjuvant treatment. A multidisciplinary working group has developed a scheme with different treatment guidelines depending on the risk factors at diagnosis, the patient's clinical situation, and response to previous treatment, including indications for thromboprophylaxis in patients with coronary involvement. The stratification of risk for long-term treatment is essential, as well as the recommendations on the procedures based on the initial cardiological involvement and its progression. Patients with coronary aneurysms require continuous and uninterrupted cardiological monitoring for life. Resumen: La enfermedad de Kawasaki es una vasculitis aguda autolimitada que afecta a vasos de pequeño y mediano calibre y es la causa más común de enfermedad cardiaca adquirida en niños en nuestro medio. Hasta un 25% de pacientes no tratados desarrollan aneurismas coronarios. Se sospecha que un agente infeccioso puede ser el desencadenante de la enfermedad, pero aún se desconoce el agente causal. En base a la evidencia previa, se proponen recomendaciones para el diagnóstico, tratamiento de la enfermedad aguda y manejo a largo plazo de estos pacientes, con el fin de unificar criterios. El diagnóstico debe ser rápido, basado en algoritmos de fácil manejo y con el apoyo de pruebas complementarias. Este documento recoge la indicación de las técnicas de imagen disponibles, así como la planificación de las revisiones cardiológicas en función de la afectación inicial. La inmunoglobulina intravenosa es la base del tratamiento inicial. El papel de los corticoides aún es controvertido, pero cada vez hay más estudios que avalan su uso como tratamiento adyuvante. Un equipo multidisciplinar ha elaborado un esquema con diferentes pautas de tratamiento en función de los factores de riesgo al diagnóstico, situación clínica del paciente y respuesta al tratamiento previo, incluyendo indicaciones sobre tromboprofilaxis en pacientes con afectación coronaria. La estratificación del riesgo para el tratamiento a largo plazo es esencial, así como las recomendaciones acerca del proceder en función de la afectación cardiológica inicial y su evolución. Los pacientes con aneurismas coronarios requieren un seguimiento cardiológico continuo e ininterrumpido de por vida.

Extra Virgin Olive Oil (EVOO) contains monounsaturated fatty acids and multiple minor components with biological properties and health benefits. We evaluate whether a diet supplemented on Oleaster®(OT), an EVOO obtained by a new process aimed to increase phenolic composition, provided additional benefits to those observed in the animals fed a diet rich in traditional EVOO on atherosclerosis development and vasomotor function in aortic vessel of ApoE−/− mice. Results were compared with those obtained in mice fed an EVOO, a standard diet (SD) or a high fat diet (HFD) rich in saturated fatty acids. Both extra-virgin olive oils reduced macrophage accumulation and protein expression of iNOS, ICAM-1 and VCAM-1, TNF-α and NF-κB, independently of its phenolic content toward values found in SD. Superoxide anion production was also reduced to the same extent in Apo E−/− mice fed EVOO or OT. Endothelial function assessed by ACh-induced vasodilatation, and lipid accumulation within the atherosclerotic plaque were restored in OT- but not in EVOO-fed mice. We conclude that EVOO contribute to prevent the inflammatory markers of atherosclerosis plaque progression but the polyphenolic content is not responsible for this effect. However, those compounds are able to restore endothelial function and to reduce lipid accumulation within the atherosclerotic lesion.

A series of simulated reactivity-initiated accident (RIA) tests on irradiated fully recrystallized boiling water reactor Zircaloy-2 cladding has been performed by means of the expansion-due-to-compression (EDC) test method. The EDC method reproduces fuel pellet–clad mechanical interaction (PCMI) conditions for the cladding during RIA transients with respect to temperature and loading rates by out-of-pile mechanical testing. The tested materials had a large variation in burnup and hydrogen content (up to 907 wppm). The results of the EDC tests showed variation in the PCMI resistance of claddings with similar burnup and hydrogen content, making it difficult to clearly identify ductile-to-brittle transition temperatures. The EDC-tested samples of the present and previous work were investigated by light optical and scanning electron microscopy to study the influence of factors such as azimuthal variation of the Zr-hydrides and the presence of hydride rims and radially oriented hydrides. Two main characteristics were identified in samples with low ductility with respect to hydrogen content and test temperature: hydride rims and radial hydrides at the cladding outer surface. Crack propagation and failure modes were also studied, showing two general modes of crack propagation depending on distribution and amount of radially oriented hydrides. It was concluded that the PCMI resistance of irradiated cladding under normal conditions with homogenously distributed circumferential hydrides is high, with good margin to the RIA failure limits. To further improve safety, focus should be on conditions causing nonfavorable hydride distribution, such as hydride reorientation and formation of hydride blisters at the cladding outer surface. Keywords: Failure, Hydrides, Hydrogen Content, Pellet–Clad Mechanical Interaction, Reactivity-Initiated Accident, Transient

A headspace solid phase microextraction (SPME) method has been developed to determine metabolites of dimethylformamide, N-hydroxymethyl-N-methylformamide, and N-methylformamide (NMF) as NMF in urine by gas chromatography with nitrogen-phosphorus detector (GC-NPD). An SPME holder with a 65-microm PDMS/DVB fiber coating was used. Optimal desorption conditions were 250 degrees C for 1 min, adsorption at 80 degrees C for 15 min, and 3.00 mL of sample in the headspace vial. The method presented good resolution, repeatability, recovery, detection limit, ruggedness and response linearity.