Daily medication management and adherence in the polymedicated elderly: a cross-sectional study in Portugal

The presence of age-related comorbidities prone elderly patients to the phenomenon of polypharmacy and consequently to a higher risk of nonadherence. Thus, this paper aims to characterize the medication consumption profile and explore the relationship of beliefs and daily medication management on medication adherence by home-dwelling polymedicated elderly people. A questionnaire on adherence, managing, and beliefs of medicines was applied to polymedicated patients with ≥65 years old, in primary care centers of the central region of Portugal. Of the 1089 participants, 47.7% were considered nonadherent. Forgetfulness (38.8%), difficulties in managing medication (14.3%), concerns with side effects (10.7%), and the price of medication (9.2%) were pointed as relevant medication nonadherence-related factors. It was observed that patients who had difficulties managing medicines, common forgetfulness, concerns with side effects, doubting the need for the medication, considered prices expensive, and had a lack of trust for some medicines had a higher risk of being nonadherent. This study provides relevant information concerning the daily routine and management of medicines that can be useful to the development of educational strategies to promote health literacy and improve medication adherence in polymedicated home-dwelling elderly.publishe

Enhancing face validity of mouse models of Alzheimer\u27s disease with natural genetic variation.

Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer\u27s disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were characterized using metabolic, functional, neuropathological and transcriptional assays. Strain-, sex- and genotype-specific differences were observed in cognitive ability, neurodegeneration, plaque load, cerebrovascular health and cerebral amyloid angiopathy. Analyses of brain transcriptional data showed strain was the greatest driver of variation. We identified significant variation in myeloid cell numbers in wild type mice of different strains as well as significant differences in plaque-associated myeloid responses in APP/PS1 mice between the strains. Collectively, these data support the use of wild-derived strains to better model the complexity of human AD

Enhancing face validity of mouse models of Alzheimer\u27s disease with natural genetic variation.

Classical laboratory strains show limited genetic diversity and do not harness natural genetic variation. Mouse models relevant to Alzheimer\u27s disease (AD) have largely been developed using these classical laboratory strains, such as C57BL/6J (B6), and this has likely contributed to the failure of translation of findings from mice to the clinic. Therefore, here we test the potential for natural genetic variation to enhance the translatability of AD mouse models. Two widely used AD-relevant transgenes, APPswe and PS1de9 (APP/PS1), were backcrossed from B6 to three wild-derived strains CAST/EiJ, WSB/EiJ, PWK/PhJ, representative of three Mus musculus subspecies. These new AD strains were characterized using metabolic, functional, neuropathological and transcriptional assays. Strain-, sex- and genotype-specific differences were observed in cognitive ability, neurodegeneration, plaque load, cerebrovascular health and cerebral amyloid angiopathy. Analyses of brain transcriptional data showed strain was the greatest driver of variation. We identified significant variation in myeloid cell numbers in wild type mice of different strains as well as significant differences in plaque-associated myeloid responses in APP/PS1 mice between the strains. Collectively, these data support the use of wild-derived strains to better model the complexity of human AD

Detection of exon skipping events in BRCA1 RNA using MLPA kit P002

A rapid and easy method to screen for aberrant cDNA would be a very useful diagnostic tool in genetics since a fraction of the DNA variants found affect RNA splicing. The currently used RT-PCR methods require new primer combinations to study each variant that might affect splicing. Since MLPA is routinely used to detect large genomic deletions and successfully detected exon skipping events in Duchenne muscular dystrophy in cDNA, we performed a pilot study to evaluate its value for BRCA1 cDNA. The effect of puromycin, DNase I and two different DNA cleaning protocols were tested in the RNA analysis of lymphocyte cultures. We used two samples from unrelated families with two different BRCA1 exon deletion events, two healthy unrelated controls and six samples from hereditary breast/ovarian cancer syndrome (HBOC) patients without BRCA1/2 mutations. Using RNA treated with DNase I and cleaned in a column system from puromycin-treated fractions, we were able to identify the two BRCA1 deletions. Additional HBOC patients did not show additional splice events. However, we were not able to get reproducible results. Therefore, the cDNA-MLPA technique using kit BRCA1 P002 is in our hands currently not reliable enough for routine RNA analysis and needs further optimization

Ancient coins: cluster analysis applied to find a correlation between corrosion process and burial soil characteristics

Although it is well known that any material degrades faster when exposed to an aggressive environment as well as that "aggressive" cannot be univocally defined as depending also on the chemical-physical characteristics of material, few researches on the identification of the most significant parameters influencing the corrosion of metallic object are available

Uncovering Disease Mechanisms in a Novel Mouse Model Expressing Humanized APOEε4 and Trem2*R47H.

Late-onset Alzheimer\u27s disease (AD; LOAD) is the most common human neurodegenerative disease, however, the availability and efficacy of disease-modifying interventions is severely lacking. Despite exceptional efforts to understand disease progression via legacy amyloidogenic transgene mouse models, focus on disease translation with innovative mouse strains that better model the complexity of human AD is required to accelerate the development of future treatment modalities. LOAD within the human population is a polygenic and environmentally influenced disease with many risk factors acting in concert to produce disease processes parallel to those often muted by the early and aggressive aggregate formation in popular mouse strains. In addition to extracellular deposits of amyloid plaques and inclusions of the microtubule-associated protein tau, AD is also defined by synaptic/neuronal loss, vascular deficits, and neuroinflammation. These underlying processes need to be better defined, how the disease progresses with age, and compared to human-relevant outcomes. To create more translatable mouse models, MODEL-AD (Model Organism Development and Evaluation for Late-onset AD) groups are identifying and integrating disease-relevant, humanized gene sequences from public databases beginning with APOEε4 and Trem2*R47H, two of the most powerful risk factors present in human LOAD populations. Mice expressing endogenous, humanized APOEε4 and Trem2*R47H gene sequences were extensively aged and assayed using a multi-disciplined phenotyping approach associated with and relative to human AD pathology. Robust analytical pipelines measured behavioral, transcriptomic, metabolic, and neuropathological phenotypes in cross-sectional cohorts for progression of disease hallmarks at all life stages. In vivo PET/MRI neuroimaging revealed regional alterations in glycolytic metabolism and vascular perfusion. Transcriptional profiling by RNA-Seq of brain hemispheres identified sex and age as the main sources of variation between genotypes including age-specific enrichment of AD-related processes. Similarly, age was the strongest determinant of behavioral change. In the absence of mouse amyloid plaque formation, many of the hallmarks of AD were not observed in this strain. However, as a sensitized baseline model with many additional alleles and environmental modifications already appended, the dataset from this initial MODEL-AD strain serves an important role in establishing the individual effects and interaction between two strong genetic risk factors for LOAD in a mouse host

Comprehensive Evaluation of the 5XFAD Mouse Model for Preclinical Testing Applications: A MODEL-AD Study.

The ability to investigate therapeutic interventions in animal models of neurodegenerative diseases depends on extensive characterization of the model(s) being used. There are numerous models that have been generated to study Alzheimer\u27s disease (AD) and the underlying pathogenesis of the disease. While transgenic models have been instrumental in understanding AD mechanisms and risk factors, they are limited in the degree of characteristics displayed in comparison with AD in humans, and the full spectrum of AD effects has yet to be recapitulated in a single mouse model. The Model Organism Development and Evaluation for Late-Onset Alzheimer\u27s Disease (MODEL-AD) consortium was assembled by the National Institute on Aging (NIA) to develop more robust animal models of AD with increased relevance to human disease, standardize the characterization of AD mouse models, improve preclinical testing in animals, and establish clinically relevant AD biomarkers, among other aims toward enhancing the translational value of AD models in clinical drug design and treatment development. Here we have conducted a detailed characterization of the 5XFAD mouse, including transcriptomics, electroencephalogram

Teachers' and pupils' definitions of bullying.

BACKGROUND: Comparison of teachers' and pupils' definitions of bullying is important for considering the implications for reports of its incidence in schools, for the study of developmental trends in children's and adolescents' perceptions of the phenomenon and for evaluating the effectiveness of interventions designed to combat bullying. AIMS: To investigate the effects of gender, teacher/pupil status and, for pupils, bullied/non-bullied (target/non-target) status and age on the definition of bullying. SAMPLES: Teachers (N=225: 158 women, 67 men) and pupils (N=1,820: 466 boys, 460 girls were 11-12 years old, year 7, and 415 boys, 479 girls were 13-14 years, year 9) in 51 UK secondary schools participated in a questionnaire survey. A total of 557 of the pupils (117 girls and 117 boys aged 11-12 years, and 197 girls and 126 boys aged 13-14 years) reported that they had been bullied at some time in their present school. METHODS: Written questionnaire responses to the question, 'Say what you think bullying is' have been content analysed to derive two sets of categories, one of bullying behaviour and the other of effects of bullying on the target. RESULTS: Regarding both bullying behaviour and the effects of bullying on the target, teachers - by comparison with pupils - have been found to express more comprehensive ideas in their definitions. Specifically, pupils compared with teachers are more likely to restrict their definitions to direct bullying (verbal and/or physical abuse) and are less likely to refer to social exclusion, a power imbalance in the bully's favour and the bully's intention to cause the target hurt or harm and to feel threatened. Analysis of definitions on the bases of sex, pupil age and target/non-target status show that: targets are more likely than non-targets are to refer to the bully's physically and verbally abusive behaviour, and for Year 7 compared with Year 9 pupils, to suggest that bullies socially exclude targets; girls are more likely than boys are to mention verbal abuse and the effects on the target of 'Feels hurt/harm', but boys are more likely than girls are to construe bullying as involving repetition; older pupils are more likely than younger ones are to refer to a power imbalance in the bully's favour but, for bully targets, younger ones compared with older ones are more likely to invoke the idea of social exclusion in their definitions. CONCLUSIONS: The most important implication of the findings of this study that there are important differences between teachers' and pupils' definitions of bullying is that teachers need to listen carefully to what pupils have to say about bullying and work with and help them to develop their conceptions of the phenomenon. Some teachers, too, need to develop their conceptions of bullying