Arterial Stiffness vs Sarcopenia in Portuguese Elderly Population

Aging often results in the appearance of sarcopenia, which is characterized by loss of muscle mass and strength. The incidence of sarcopenia in the elderly is a quite common and leads to weakness and disability, as well as a lower quality of life, also assuming a high social and economic impact. One previous study has shown an independent negative association between arterial stiffness and skeletal muscle mass decline [1], which suggest its relationship with sarcopenia. This work aims to evaluate the relation between sarcopenia and the arterial stiffness, in Portuguese elderly population A cohort of 38 elderly volunteers between 67 and 95 years, with and without Sarcopenia, were selected from nursing homes and day centers of Portuguese charity institution - Santa Casa da Misericórdia de Almada. All volunteers have the same living condition, meals and lifestyle routine, excepting the medications. The diagnosis and degree (severe or moderate) of sarcopenia were performed according to the European consensus on definition and diagnosis of sarcopenia [2] at the same day with arterial stiffnesses measurements assessed by carotid-femoral Pulse Wave Velocity (cfPWV). Our data show a positive correlation for cfPWV with the sarcopenia severity degree, which represents an increasing in arterial stiffness and might be explained by the fact that the loss of muscle mass is often associated with chronic inflammation [3]. Despite of the small cohort size, the male gender held a bigger mean value of cfPWV, with significant p-value (0.014), in comparison to the female gender, which estimates a higher CV risk for the male elders of the region of Almada and Greater Lisbon compared to the female gender. Further investigations would be desirable in order to obtain larger samples and ascertain the estimates for the respective groups.publishersversionpublishe

ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITIES OF METHANOL EXTRACTS AND ALKALOID FRACTIONS OF FOUR MEXICAN MEDICINAL PLANTS OF SOLANACEAE

Background: Methanol extracts and alkaloid fractions of different parts of four plant species belonging to Solanaceae family and used in Mexican traditional medicine were investigated for their total phenolic contents, anti-inflammatory and antioxidant properties. Materials and Methods: The total phenolic compounds of each extract was determined according to the Folin-Ciocalteu method, while the in vitro radical scavenging activities of the extracts were assessed using the DPPH and ABTS radicals. The in vivo anti-inflammatory activity was determined using the TPA-induced mouse ear edema model. Results: The methanol extracts contained the highest concentrations of phenolic compounds and also exhibited the best reducing power on the DPPH and ABTS radicals, in a concentration-dependent fashion. However, the anti-inflammatory activity did not follow the same trend, as some alkaloid fractions that showed low radical reducing power exhibited the strongest anti-inflammatory activity. Conclusion: The methanol extract obtained from the flowers of Nicotiana glauca presented the best overall performance with the largest amount of phenolic compounds (111 µg garlic acid equivalents/g of extract), the best antioxidant activity (94.80% inhibition of DPPH and 97.57% of ABTS) and the highest anti-inflammatory activity (81.93% inhibition of the inflammatio

Estructura de stock de sable negro (Aphanopus carbo Lowe, 1839) en el sur del Atlántico nordeste

Black scabbardfish stock structure is still unknown in European waters where, due to the scarcity of biological information, the ICES considers that there is a single stock unit. This study is the final outcome of a scientific project that applies a holistic approach to research on the population structure of the black scabbardfish and aims to define the most appropriate strategy for the conservation of this resource in southern NE Atlantic waters. The factors studied include life history parameters, otolith shape analysis, parasites, landings-and-effort data and contaminants. Sampling was conducted between 2005 and 2007 in three areas of the southern NE Atlantic: mainland Portugal, Madeira and the Azores. The mainland and the Azores have an established commercial fishery, whereas the Azores has only an exploratory fishery. The majority of results indicated the existence of different stocks of black scabbardfish in the study area. Of the 8 parameters, 6 were in agreement with separate stocks between the mainland and Madeira, 5 were in agreement with separate stocks between the mainland and the Azores, and 4 were in agreement with separate stocks between Madeira and the Azores.La estructura de la población de sable negro en las aguas europeas es todavía desconocida y, debido a la escasez de la información biológica disponible, ICES ha considerado una sola unidad de stock en la totalidad de dichas aguas. El proyecto que originó este estudio es un trabajo integrado para investigar la estructura poblacional de sable negro y pretende definir la estrategia más apropiada para la conservación de este recurso en aguas del sur del Atlántico nordeste. Para cumplir con el objetivo del proyecto se llevaron a cabo varios estudios: determinación de parámetros que definen el ciclo vital, análisis de forma del otolito, parásitos, datos de desembarques y esfuerzo pesquero, y contaminantes. El muestreo fue realizado entre 2005 y 2007 en tres áreas del sur del Atlántico nordeste: Portugal continental, aguas de Madeira y Azores. Las dos primeras áreas tienen una pesquería comercial establecida, mientras que en Azores existe una pesquería exploratoria. La mayoría de los resultados concluyeron la existencia de diferentes unidades poblacionales del sable negro en el área sur del Atlántico nordeste. Seis de los ocho parámetros confirman la separación entre los individuos del continente y Madeira, mientras que 5 parámetros corroboran la separación entre el continente y Azores. Solamente 4 técnicas corroboran la separación entre Madeira y Azores

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

BACKGROUND: Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. METHODS: We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. RESULTS: A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. CONCLUSION: The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean famil

Detection of Pathogenic Mycobacteria Based on Functionalized Quantum Dots Coupled with Immunomagnetic Separation

Mycobacteria have always proven difficult to identify due to their low growth rate and fastidious nature. Therefore molecular biology and more recently nanotechnology, have been exploited from early on for the detection of these pathogens. Here we present the first stage of development of an assay incorporating cadmium selenide quantum dots (QDs) for the detection of mycobacterial surface antigens. The principle of the assay is the separation of bacterial cells using magnetic beads coupled with genus-specific polyclonal antibodies and monoclonal antibodies for heparin-binding hemagglutinin. These complexes are then tagged with anti-mouse biotinylated antibody and finally streptavidin-conjugated QDs which leads to the detection of a fluorescent signal. For the evaluation of performance, the method under study was applied on Mycobacterium bovis BCG and Mycobacterium tuberculosis (positive controls), as well as E. coli and Salmonella spp. that constituted the negative controls. The direct observation of the latter category of samples did not reveal fluorescence as opposed to the mycobacteria mentioned above. The minimum detection limit of the assay was defined to 104 bacteria/ml, which could be further decreased by a 1 log when fluorescence was measured with a spectrofluorometer. The method described here can be easily adjusted for any other protein target of either the pathogen or the host, and once fully developed it will be directly applicable on clinical samples

Genetic parameters for somatic cell score according to udder infection status in Valle del Belice dairy sheep and impact of imperfect diagnosis of infection

<p>Abstract</p> <p>Background</p> <p>Somatic cell score (SCS) has been promoted as a selection criterion to improve mastitis resistance. However, SCS from healthy and infected animals may be considered as separate traits. Moreover, imperfect sensitivity and specificity could influence animals' classification and impact on estimated variance components. This study was aimed at: (1) estimating the heritability of bacteria negative SCS, bacteria positive SCS, and infection status, (2) estimating phenotypic and genetic correlations between bacteria negative and bacteria positive SCS, and the genetic correlation between bacteria negative SCS and infection status, and (3) evaluating the impact of imperfect diagnosis of infection on variance component estimates.</p> <p>Methods</p> <p>Data on SCS and udder infection status for 1,120 ewes were collected from four Valle del Belice flocks. The pedigree file included 1,603 animals. The SCS dataset was split according to whether animals were infected or not at the time of sampling. A repeatability test-day animal model was used to estimate genetic parameters for SCS traits and the heritability of infection status. The genetic correlation between bacteria negative SCS and infection status was estimated using an MCMC threshold model, implemented by Gibbs Sampling.</p> <p>Results</p> <p>The heritability was 0.10 for bacteria negative SCS, 0.03 for bacteria positive SCS, and 0.09 for infection status, on the liability scale. The genetic correlation between bacteria negative and bacteria positive SCS was 0.62, suggesting that they may be genetically different traits. The genetic correlation between bacteria negative SCS and infection status was 0.51. We demonstrate that imperfect diagnosis of infection leads to underestimation of differences between bacteria negative and bacteria positive SCS, and we derive formulae to predict impacts on estimated genetic parameters.</p> <p>Conclusions</p> <p>The results suggest that bacteria negative and bacteria positive SCS are genetically different traits. A positive genetic correlation between bacteria negative SCS and liability to infection was found, suggesting that the approach of selecting animals for decreased SCS should help to reduce mastitis prevalence. However, the results show that imperfect diagnosis of infection has an impact on estimated genetic parameters, which may reduce the efficiency of selection strategies aiming at distinguishing between bacteria negative and bacteria positive SCS.</p

Cancer health disparities in racial/ethnic minorities in the United States

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA—African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.Fil: Zavala, Valentina A.. University of California; Estados UnidosFil: Bracci, Paige M.. University of California; Estados UnidosFil: Carethers, John M.. University of Michigan; Estados UnidosFil: Carvajal Carmona, Luis. University of California at Davis; Estados UnidosFil: Coggins, Nicole B.. University of California at Davis; Estados UnidosFil: Cruz Correa, Marcia R.. Universidad de Puerto Rico; Puerto RicoFil: Davis, Melissa. No especifíca;Fil: de Smith, Adam J.. University of California; Estados UnidosFil: Dutil, Julie. Ponce Research Institute; Puerto RicoFil: Figueiredo, Jane C.. Cedars Sinai Medical Center; Estados UnidosFil: Fox, Rena. University of California; Estados UnidosFil: Graves, Kristi D.. University Of Georgetown; Estados UnidosFil: Gomez, Scarlett Lin. University of California; Estados UnidosFil: Llera, Andrea Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Neuhausen, Susan L.. No especifíca;Fil: Newman, Lisa. No especifíca;Fil: Nguyen, Tung. University of California; Estados UnidosFil: Palmer, Julie R.. National Institutes of Health; Estados UnidosFil: Palmer, Nynikka R.. University of California; Estados UnidosFil: Pérez Stable, Eliseo J.. National Institutes of Health; Estados UnidosFil: Piawah, Sorbarikor. University of California; Estados UnidosFil: Rodriquez, Erik J.. National Institutes of Health; Estados UnidosFil: Sanabria Salas, María Carolina. Instituto Nacional de Cancerología; ColombiaFil: Schmit, Stephanie L.. University of Southern California; Estados UnidosFil: Serrano Gomez, Silvia J.. Instituto Nacional de Cancerología; ColombiaFil: Stern, Mariana Carla. University of Southern California; Estados UnidosFil: Weitzel, Jeffrey. No especifíca;Fil: Yang, Jun J.. St. Jude Children’s Research Hospital; Estados UnidosFil: Zabaleta, Jovanny. No especifíca;Fil: Ziv, Elad. University of California; Estados UnidosFil: Fejerman, Laura. University of California; Estados Unido

Analysis of neurodegenerative disease-causing genes in dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a clinically heterogeneous disorder with a substantial burden on healthcare. Despite this, the genetic basis of the disorder is not well defined and its boundaries with other neurodegenerative diseases are unclear. Here, we performed whole exome sequencing of a cohort of 1118 Caucasian DLB patients, and focused on genes causative of monogenic neurodegenerative diseases. We analyzed variants in 60 genes implicated in DLB, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and atypical parkinsonian or dementia disorders, in order to determine their frequency in DLB. We focused on variants that have previously been reported as pathogenic, and also describe variants reported as pathogenic which remain of unknown clinical significance, as well as variants associated with strong risk. Rare missense variants of unknown significance were found in APP, CHCHD2, DCTN1, GRN, MAPT, NOTCH3, SQSTM1, TBK1 and TIA1. Additionally, we identified a pathogenic GRN p.Arg493* mutation, potentially adding to the diversity of phenotypes associated with this mutation. The rarity of previously reported pathogenic mutations in this cohort suggests that the genetic overlap of other neurodegenerative diseases with DLB is not substantial. Since it is now clear that genetics plays a role in DLB, these data suggest that other genetic loci play a role in this disease.Peer reviewe

Investigating the genetic architecture of dementia with Lewy bodies: a two-stage genome-wide association study

Background Dementia with Lewy bodies is the second most common form of dementia in elderly people but has been overshadowed in the research field, partly because of similarities between dementia with Lewy bodies, Parkinson’s disease, and Alzheimer’s disease. So far, to our knowledge, no large-scale genetic study of dementia with Lewy bodies has been done. To better understand the genetic basis of dementia with Lewy bodies, we have done a genome-wide association study with the aim of identifying genetic risk factors for this disorder. Methods In this two-stage genome-wide association study, we collected samples from white participants of European ancestry who had been diagnosed with dementia with Lewy bodies according to established clinical or pathological criteria. In the discovery stage (with the case cohort recruited from 22 centres in ten countries and the controls derived from two publicly available database of Genotypes and Phenotypes studies [phs000404.v1.p1 and phs000982.v1.p1] in the USA), we performed genotyping and exploited the recently established Haplotype Reference Consortium panel as the basis for imputation. Pathological samples were ascertained following autopsy in each individual brain bank, whereas clinical samples were collected by clinical teams after clinical examination. There was no specific timeframe for collection of samples. We did association analyses in all participants with dementia with Lewy bodies, and also in only participants with pathological diagnosis. In the replication stage, we performed genotyping of significant and suggestive results from the discovery stage. Lastly, we did a meta-analysis of both stages under a fixed-effects model and used logistic regression to test for association in each stage. Findings This study included 1743 patients with dementia with Lewy bodies (1324 with pathological diagnosis) and 4454 controls (1216 patients with dementia with Lewy bodies vs 3791 controls in the discovery stage; 527 vs 663 in the replication stage). Results confirm previously reported associations: APOE (rs429358; odds ratio [OR] 2·40, 95% CI 2·14–2·70; p=1·05 × 10–⁴⁸), SNCA (rs7681440; OR 0·73, 0·66–0·81; p=6·39 × 10–¹⁰), and GBA (rs35749011; OR 2·55, 1·88–3·46; p=1·78 × 10–⁹). They also provide some evidence for a novel candidate locus, namely CNTN1 (rs7314908; OR 1·51, 1·27–1·79; p=2·21 × 10–⁶); further replication will be important. Additionally, we estimate the heritable component of dementia with Lewy bodies to be about 36%. Interpretation Despite the small sample size for a genome-wide association study, and acknowledging the potential biases from ascertaining samples from multiple locations, we present the most comprehensive and well powered genetic study in dementia with Lewy bodies so far. These data show that common genetic variability has a role in the disease

A comprehensive screening of copy number variability in dementia with Lewy bodies

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk. (C) 2019 Elsevier Inc. All rights reserved.Peer reviewe