Field trial for assessment of avian influenza vaccination effectiveness in Indonesia

The aim of this field study was to determine the efficacy of vaccination against highly pathogenic avian influenza (HPAI) virus strain H5N1 in Indonesia. A limited, prototype clinical trial was performed using a standardised treatment group, in which poultry flocks were vaccinated at least twice with a selected H5N1 vaccine, and a control group comprising flocks treated with nonstandardised procedures chosen by the farmer. Each group consisted of six flocks comprising either layers or native chickens. Haemagglutination inhibition (HI) antibody levels were determined by regular serum sampling, and outbreak surveillance relied on non-Al-vaccinated sentinel birds. After three vaccinations high antibody titres were produced in the treatment group, and the percentage of layers with an HI titre > 40 was approximately 90%. Although no conclusions can be drawn regarding reduction of virus transmission, this study demonstrated that 11 farms remained free from Al during the observation period, and that a surveillance programme based on differentiating infected from vaccinated animals (DIVA) can be implemented

Complete sequencing of TP53 predicts poor response to systemic therapy of advanced breast cancer

TP53 has been implicated in regulation of the cell cycle, DNA repair, and apoptosis. We studied, in primary breast tumors through direct cDNA sequencing of exons 2-11, whether TP53 gene mutations can predict response in patients with advanced disease to either first-line tamoxifen therapy (202 patients, of whom 55% responded) or up-front (poly)chemotherapy (41 patients, of whom 46% responded). TP53 mutations were detected in 90 of 243 (37%) tumors, and one-fourth of these mutations resulted in a premature termination of the protein. The mutations were observed in 32% (65 of 202) of the primary tumors of tamoxifen-treated patients and in 61% (25 of 41) of the primary tumors of the chemotherapy patients. TP53 mutation was significantly associated with a poor response to tamoxifen [31% versu

Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study

OBJECTIVE: Several lines of evidence suggest that estrogens influence the development of osteoarthritis (OA). The aim of this study was to explore the association of two common polymorphisms within the aromatase (CYP19A1) and estrogen receptor (ER) alpha (ESR1) genes with severe OA of the lower limbs. METHODS: The rs1062033 (CYP19A1) and rs2234693 (ESR1) single nucleotide polymorphisms were genotyped in 5528 individuals (3147 patients with severe hip or knee OA, and 2381 controls) from four centres in Spain and the United Kingdom. Gene expression was measured in femoral bone samples from a group of patients. RESULTS: In the global analysis, both polymorphisms were associated with OA, but there was a significant sex interaction. The GG genotype at rs1062033 was associated with an increased risk of knee OA in women [odds ratio (OR) 1.23; P=0.04]. The CC genotype at rs2234693 tended to be associated with reduced OA risk in women (OR 0.76, P=0.028, for knee OA; OR=0.84, P=0.076 for hip OA), but with increased risk of hip OA in men (OR 1.28; P=0.029). Women with unfavourable genotypes at both loci had an OR of 1.61 for knee OA (P=0.006). The rs1062033 genotype associated with higher OA risk was also associated with reduced expression of the aromatase gene in bone. CONCLUSIONS: Common genetic variations of the aromatase and ER genes are associated with the risk of severe OA of the large joints of the lower limb in a sex-specific manner. These results are consistent with the hypothesis that estrogen activity may influence the development of large-joint OA

Objectively measured physical activity in european adults: cross-sectional findings from the Food4Me study

Introduction Physical inactivity has been estimated to be responsible for more than 5.3 million deaths worldwide [1]. Moreover, among European men and women, approximately 7.3% of all deaths in 2008 might be attributable to inactivity compared with 3.7% to obesity [2] and there is strong evidence to suggest that even small increases in physical activity (PA) would lower the risk for many non-communicable diseases [1–3]. Yet, levels of PA across populations remain low [4]. To tackle this public health issue, the US Centers for Disease Control and Prevention and the American College of Sports Medicine produced standardized PA guidelines 20 years ago [5]. Since then, the World Health Organization (WHO), the European Union, and most countries around the world, have included PA guidelines in their health policies. Guidelines for Americans and Europeans have been updated to include recommendations for adolescents and for older adults [6–9]. For adults aged 18–64 years old, the WHO recommends a minimum of 150 min of moderate intensity PA per week, 75 min of vigorous intensity PA or an equivalent amount of moderate and vigorous PA (MVPA) [9]. In 2008, 34.8% of adults 15 years or older were insufficiently active in Europe [4]. Regular surveillance is needed to update these prevalence estimates and to evaluate the effectiveness of PA policies and promotion programs in European countries. In this context, the objective assessment of PA is a key issue. Prevalence of physical inactivity has been mainly derived from self-reported measures such as the Baecke questionnaire [10] or the International Physical Activity Questionnaire (IPAQ) [11]. These questionnaires have been, and still are, widely used due to their simple administration and low cost [12]. However, PA is frequently misreported, which leads to considerable measurement error [13–15]. Accelerometers offer a potential solution because they measure PA objectively. Given that they are small and easy to wear, store data up to several weeks and are acceptable in terms of reliability, these devices are now used increasingly in large studies to assess PA in children, adolescents and adults [16]. Although some European countries have reported adherence to PA guidelines using accelerometers in large cohorts [17–19], comparisons between European countries measured according to the same standardized protocols and concurrently are lacking. Between 2012 and 2014, PA was assessed objectively by accelerometry in the participants of the Food4Me Proof-of-Principle (PoP) study. The Food4Me Study was a web-based randomized controlled trial on personalized nutrition, across seven European countries: Germany, Greece, Ireland, The Netherlands, Poland, Spain and the United Kingdom. The aim of the current paper is to describe and compare PA in adults from these countries, and evaluate adherence to PA guidelines, using baseline data from the Food4Me PoP study

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Prevalence of Frailty in European Emergency Departments (FEED): an international flash mob study

Introduction Current emergency care systems are not optimized to respond to multiple and complex problems associated with frailty. Services may require reconfiguration to effectively deliver comprehensive frailty care, yet its prevalence and variation are poorly understood. This study primarily determined the prevalence of frailty among older people attending emergency care. Methods This cross-sectional study used a flash mob approach to collect observational European emergency care data over a 24-h period (04 July 2023). Sites were identified through the European Task Force for Geriatric Emergency Medicine collaboration and social media. Data were collected for all individuals aged 65 + who attended emergency care, and for all adults aged 18 + at a subset of sites. Variables included demographics, Clinical Frailty Scale (CFS), vital signs, and disposition. European and national frailty prevalence was determined with proportions with each CFS level and with dichotomized CFS 5 + (mild or more severe frailty). Results Sixty-two sites in fourteen European countries recruited five thousand seven hundred eighty-five individuals. 40% of 3479 older people had at least mild frailty, with countries ranging from 26 to 51%. They had median age 77 (IQR, 13) years and 53% were female. Across 22 sites observing all adult attenders, older people living with frailty comprised 14%. Conclusion 40% of older people using European emergency care had CFS 5 + . Frailty prevalence varied widely among European care systems. These differences likely reflected entrance selection and provide windows of opportunity for system configuration and workforce planning