Recent Consanguinity and Outbred Autozygosity Are Associated With Increased Risk of Late-Onset Alzheimer's Disease

Prior work in late-onset Alzheimer's disease (LOAD) has resulted in discrepant findings as to whether recent consanguinity and outbred autozygosity are associated with LOAD risk. In the current study, we tested the association between consanguinity and outbred autozygosity with LOAD in the largest such analysis to date, in which 20 LOAD GWAS datasets were retrieved through public databases. Our analyses were restricted to eight distinct ethnic groups: African-Caribbean, Ashkenazi-Jewish European, European-Caribbean, French-Canadian, Finnish European, North-Western European, South-Eastern European, and Yoruba African for a total of 21,492 unrelated subjects (11,196 LOAD and 10,296 controls). Recent consanguinity determination was performed using FSuite v1.0.3, according to subjects' ancestral background. The level of autozygosity in the outbred population was assessed by calculating inbreeding estimates based on the proportion (FROH) and the number (NROH) of runs of homozygosity (ROHs). We analyzed all eight ethnic groups using a fixed-effect meta-analysis, which showed a significant association of recent consanguinity with LOAD (N = 21,481; OR = 1.262, P = 3.6 × 10-4), independently of APOE∗4 (N = 21,468, OR = 1.237, P = 0.002), and years of education (N = 9,257; OR = 1.274, P = 0.020). Autozygosity in the outbred population was also associated with an increased risk of LOAD, both for FROH (N = 20,237; OR = 1.204, P = 0.030) and NROH metrics (N = 20,237; OR = 1.019, P = 0.006), independently of APOE∗4 [(FROH, N = 20,225; OR = 1.222, P = 0.029) (NROH, N = 20,225; OR = 1.019, P = 0.007)]. By leveraging the Alzheimer's Disease Sequencing Project (ADSP) whole-exome sequencing (WES) data, we determined that LOAD subjects do not show an enrichment of rare, risk-enhancing minor homozygote variants compared to the control population. A two-stage recessive GWAS using ADSP data from 201 consanguineous subjects in the discovery phase followed by validation in 10,469 subjects led to the identification of RPH3AL p.A303V (rs117190076) as a rare minor homozygote variant increasing the risk of LOAD [discovery: Genotype Relative Risk (GRR) = 46, P = 2.16 × 10-6; validation: GRR = 1.9, P = 8.0 × 10-4]. These results confirm that recent consanguinity and autozygosity in the outbred population increase risk for LOAD. Subsequent work, with increased samples sizes of consanguineous subjects, should accelerate the discovery of non-additive genetic effects in LOAD

A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses

Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it

Chiral Effective Lagrangian and Quark Masses

The status of lattice determinations of quark masses is reviewed (with the exception of m_b). Attempts to extract the low-energy constants in the effective chiral Lagrangian are discussed, with special emphasis on those couplings which are required to test the hypothesis of a massless up-quark. Furthermore, the issue of quenched chiral logarithms is addressed.Comment: Invited talk presented at Lattice2002(plenary), 12 pages, 3 figure

Therapeutic potential of marine macrolides: An overview from 1990 to 2022

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGThe sea is a vast ecosystem that has remained primarily unexploited and untapped, resulting in numerous organisms. Consequently, marine organisms have piqued the interest of scientists as an abundant source of natural resources with unique structural features and fascinating biological activities. Marine macrolide is a top-class natural product with a heavily oxygenated polyene backbone containing macrocyclic lactone. In the last few decades, significant efforts have been made to isolate and characterize macrolides’ chemical and biological properties. Numerous macrolides are extracted from different marine organisms such as marine microorganisms, sponges, zooplankton, molluscs, cnidarians, red algae, tunicates, and bryozoans. Notably, the prominent macrolide sources are fungi, dinoflagellates, and sponges. Marine macrolides have several bioactive characteristics such as antimicrobial (antibacterial, antifungal, antimalarial, antiviral), anti-inflammatory, antidiabetic, cytotoxic, and neuroprotective activities. In brief, marine organisms are plentiful in naturally occurring macrolides, which can become the source of efficient and effective therapeutics for many diseases. This current review summarizes these exciting and promising novel marine macrolides in biological activities and possible therapeutic applications

Generating natural language tags for video information management

This exploratory work is concerned with generation of natural language descriptions that can be used for video retrieval applications. It is a step ahead of keyword-based tagging as it captures relations between keywords associated with videos. Firstly, we prepare hand annotations consisting of descriptions for video segments crafted from a TREC Video dataset. Analysis of this data presents insights into human’s interests on video contents. Secondly, we develop a framework for creating smooth and coherent description of video streams. It builds on conventional image processing techniques that extract high-level features from individual video frames. Natural language description is then produced based on high-level features. Although feature extraction processes are erroneous at various levels, we explore approaches to putting them together to produce a coherent, smooth and well-phrased description by incorporating spatial and temporal information. Evaluation is made by calculating ROUGE scores between human-annotated and machine-generated descriptions. Further, we introduce a task-based evaluation by human subjects which provides qualitative evaluation of generated descriptions

Studies on dental erosion: An in vivo-in vitro model of endogenous dental erosion - its application to testing protection by fluoride gel application

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher’s copy is included.Background: The objective in this study was to develop an in vivo-in vitro model of endogenous erosion, with a view to exploring the potential for some degree of its control by the use of topical fluoride gel application to teeth. Methods: Six volunteers each wore a small clasp retained palatal acrylic appliance to which six sterilized enamel tiles were bonded. Three tiles on each appliance were coated extra-orally with either 1.23 per cent acidulated phosphate fluoride (APF) or 2.2 per cent sodium fluoride (NaF) neutral gel for four minutes prior to multiple periods of exposure to the simulated gastric acid, cumulating in 16, 36, 80 and 150 minutes of exposure. Impressions of the enamel tiles prior to and following acid exposure permitted dies to be prepared. These were sectioned through the exposed areas and examined under a stereomicroscope to assess maximum depths of erosion. Results: The depth of erosive demineralization of enamel was found to be greatly reduced with increased frequency of APF gel application. The reduction in enamel loss was less following topical application of NaF gel. Conclusions: It was concluded that fluoride gels significantly reduced enamel erosion using this in vivo-in vitro model and therefore, if prescribed appropriately, should help reduce tooth tissue loss from endogenous erosion.L Jones, D Lekkas, D Hunt, J McIntyre and W Rafi

Prevalence of physical inactivity and barriers to physical activity among obese attendants at a community health-care center in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are significant public health problems worldwide with serious health consequences. With increasing urbanization and modernization there has been an increase in prevalence of obesity that is attributed to reduced levels of physical activity (PA). However, little is known about the prevalence of physical inactivity and factors that prohibit physical activity among Pakistani population. This cross-sectional study is aimed at estimating the prevalence of physical inactivity, and determining associated barriers in obese attendants accompanying patients coming to a Community Health Center in Karachi, Pakistan.</p> <p>Findings</p> <p>PA was assessed by using international physical activity questionnaire (IPAQ). Barriers to PA were also assessed in inactive obese attendants. A pre-tested questionnaire was used to collect data from a total of 350 obese attendants. Among 350 study participants 254 (72.6%) were found to be physically inactive (95% CI: 68.0%, 77.2%). Multivariable logistic regression analysis indicated that age greater than 33 years, BMI greater than 33 kg/m²and family history of obesity were independently and significantly associated with physical inactivity. Moreover, there was a significant interaction between family structure and gender; females living in extended families were about twice more likely to be inactive, whereas males from extended families were six times more likely to be inactive relative to females from nuclear families. Lack of information, motivation and skills, spouse & family support, accessibility to places for physical activity, cost effective facilities and time were found to be important barriers to PA.</p> <p>Conclusions</p> <p>Considering the public health implications of physical inactivity it is essential to promote PA in context of an individual's health and environment. Findings highlight considerable barriers to PA among obese individuals that need to be addressed during counseling sessions with physicians.</p