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Lamina-associated polypeptide 1 (LAP1), a ubiquitously expressed nuclear envelope protein, appears to be essential for the maintenance of cell homeostasis. Although rare, mutations in the human LAP1-encoding TOR1AIP1 gene cause severe diseases and can culminate in the premature death of affected individuals. Despite there is increasing evidence of the pathogenicity of TOR1AIP1 mutations, the current knowledge on LAP1's physiological roles in humans is limited; hence, investigation is required to elucidate the critical functions of this protein, which can be achieved by uncovering the molecular consequences of LAP1 depletion, a topic that remains largely unexplored. In this work, the proteome of patient-derived LAP1-deficient fibroblasts carrying a pathological TOR1AIP1 mutation (LAP1 E482A) was quantitatively analyzed to identify global changes in protein abundance levels relatively to control fibroblasts. An in silico functional enrichment analysis of the mass spectrometry-identified differentially expressed proteins was also performed, along with additional in vitro functional assays, to unveil the biological processes that are potentially dysfunctional in LAP1 E482A fibroblasts. Collectively, our findings suggest that LAP1 deficiency may induce significant alterations in various cellular activities, including DNA repair, messenger RNA degradation/translation, proteostasis and glutathione metabolism/antioxidant response. This study sheds light on possible new functions of human LAP1 and could set the basis for subsequent in-depth mechanistic investigations. Moreover, by identifying deregulated signaling pathways in LAP1-deficient cells, our work may offer valuable molecular targets for future disease-modifying therapies for TOR1AIP1-associated nuclear envelopathies.

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Background: Alzheimer's disease (AD) diagnosis is difficult, and new accurate tools based on peripheral biofluids are urgently needed. Extracellular vesicles (EVs) emerged as a valuable source of biomarker profiles for AD, since their cargo is disease-specific and these can be easily isolated from easily accessible biofluids, as blood. Fourier Transform Infrared (FTIR) spectroscopy can be employed to analyze EVs and obtain the spectroscopic profiles from different regions of the spectra, simultaneously characterizing carbohydrates, nucleic acids, proteins, and lipids. Objective: The aim of this study was to identify blood-derived EVs (bdEVs) spectroscopic signatures with AD discriminatory potential. Methods: Herein, FTIR spectra of bdEVs from two biofluids (serum and plasma) and distinct sets of Controls and AD cases were acquired, and EVs' spectra analyzed. Results: Analysis of bdEVs second derivative peaks area revealed differences between Controls and AD cases in distinct spectra regions, assigned to carbohydrates and nucleic acids, amides, and lipids. Conclusions: EVs' spectroscopic profiles presented AD discriminatory value, supporting the use of bdEVs combined with FTIR as a screening or complementary tool for AD diagnosis.

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Phosphorylation plays a key role in Alzheimer's disease (AD) pathogenesis, impacting distinct processes such as amyloid-beta (Aß) peptide production and tau phosphorylation. Impaired phosphorylation events contribute to senile plaques and neurofibrillary tangles' formation, two major histopathological hallmarks of AD. Blood-derived extracellular particles (bdEP) can represent a disease-related source of phosphobiomarker candidates, and hence, in this pilot study, bdEP of Control and AD cases were analyzed by a targeted phosphoproteomics approach using a high-density microarray that featured at least 1145 pan-specific and 913 phosphosite-specific antibodies. This approach, innovatively applied to bdEP, allowed the identification of 150 proteins whose expression levels and/or phosphorylation patterns were significantly altered across AD cases. Gene Ontology enrichment and Reactome pathway analysis unraveled potentially relevant molecular targets and disease-associated pathways, and protein-protein interaction networks were constructed to highlight key targets. The discriminatory value of both the total proteome and the phosphoproteome was evaluated by univariate and multivariate approaches. This pilot experiment supports that bdEP are enriched in phosphotargets relevant in an AD context, holding value as peripheral biomarker candidates for disease diagnosis.

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The complex mitochondrial network makes it very challenging to segment, follow, and analyze live cells. MATLAB tools allow the analysis of mitochondria in timelapse files, considerably simplifying and speeding up the process of image processing. Nonetheless, existing tools produce a large output volume, requiring individual manual attention, and basic experimental setups have an output of thousands of files, each requiring extensive and time-consuming handling. To address these issues, a routine optimization was developed, in both MATLAB code and live-script forms, allowing for swift file analysis and significantly reducing document reading and data processing. With a speed of 100 files/min, the optimization allows an overall rapid analysis. The optimization achieves the results output by averaging frame-specific data for individual mitochondria throughout time frames, analyzing data in a defined manner, consistent with those output from existing tools. Live confocal imaging was performed using the dye tetramethylrhodamine methyl ester, and the routine optimization was validated by treating neuronal cells with retinoic acid receptor (RAR) agonists, whose effects on neuronal mitochondria are established in the literature. The results were consistent with the literature and allowed further characterization of mitochondrial network behavior in response to isoform-specific RAR modulation. This new methodology allowed rapid and validated characterization of whole-neuron mitochondria network, but it also allows for differentiation between axon and cell body mitochondria, an essential feature to apply in the neuroscience field. Moreover, this protocol can be applied to experiments using fast-acting treatments, allowing the imaging of the same cells before and after treatments, transcending the field of neuroscience.

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Objective: Clusterin is involved in a variety of physiological processes, including proteostasis. Several clusterin polymorphisms were associated with an increased risk of developing Alzheimer's disease, the world-leading cause of dementia. Herein, the effect of a clusterin polymorphism, aging and dementia in the levels of clusterin in human plasma were analysed in a primary care-based cohort, and the association of this chaperone with fibrillar structures discussed. Methods: 64 individuals with dementia (CDR≥1) and 64 age- and sex-matched Controls from a Portuguese cohort were genotyped for CLU rs1136000 polymorphism, and the plasma levels of clusterin and fibrils were assessed. Results: An increased prevalence of the CC genotype was observed for the dementia group, although no significant robustness was achieved. CLU rs11136000 SNP did not significantly change plasma clusterin levels in demented individuals. Instead, clusterin levels decreased with aging and even more in individuals with dementia. Importantly, plasma clusterin levels correlated with the presence of fibrillar structures in Control individuals, but not in those with dementia. Conclusion: This study reveals a significant decrease in plasma clusterin in demented individuals with aging, which related to altered clusterin-fibrils dynamics. Potentially, plasma clusterin and its association with fibrillar structures can be used to monitor dementia progression along aging.

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Aging is the main risk factor for the appearance of age-related neurodegenerative diseases, including Alzheimer's disease (AD). AD is the most common form of dementia, characterized by the presence of senile plaques (SPs) and neurofibrillary tangles (NFTs), the main histopathological hallmarks in AD brains. The core of these deposits are predominantly amyloid fibrils in SPs and hyperphosphorylated Tau protein in NFTs, but other molecular components can be found associated with these pathological lesions. Herein, an extensive literature review was carried out to obtain the SPs and NFTs proteomes, followed by a bioinformatic analysis and further putative biomarker validation. For SPs, 857 proteins were recovered, and, for NFTs, 627 proteins of which 375 occur in both groups and represent the common proteome. Gene Ontology (GO) enrichment analysis permitted the identification of biological processes and the molecular functions most associated with these lesions. Analysis of the SPs and NFTs common proteins unraveled pathways and molecular targets linking both histopathological events. Further, validation of a putative phosphotarget arising from the in silico analysis was performed in serum-derived extracellular vesicles from AD patients. This bioinformatic approach contributed to the identification of putative molecular targets, valuable for AD diagnostic or therapeutic intervention.

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The plastic architecture of the mitochondrial network and its dynamic structure play crucial roles ensuring that varying energetic demands are rapidly met. Given the brain's high energy demand, mitochondria play a particularly critical role in neuronal and axonal energy homeostasis. With ageing physiological properties of the organism deteriorate, and are associated with loss of cellular homeostasis, accumulation of dysfunctional organelles and damaged macromolecules. Thus, mitochondrial loss of efficiency is likely to be both a cause and a consequence of ageing. Additionally distinct cellular events can contribute to oxidative stress, disruption of metabolism and mitochondria homeostasis, resulting in neuropathology. However, although the correlation between ageing and mitochondria disfunction is well established, the response to oxidative stress, particularly proteostasis, remains to be fully elucidated. The work here described explores the degradation of mitochondria oxidative stress-response mechanisms with ageing in human cells, addressing the physiological effects on proteostasis, focused on its role in differentiating between healthy and pathological ageing. Increased protein aggregation appears to be tightly related to impairment of ageing mitochondria response to oxidative stress, and antioxidative agents are shown to have a progressive protective effect with age; cells from old individuals show higher susceptibility to oxidative stress, in terms of protein aggregation, cell viability, or mitochondria homeostasis. These results support the antioxidant properties of flavonoids as a good therapeutic strategy for age-related diseases. Given their protective effect, this family of compounds can be of strategic therapeutic value for protein-aggregation related diseases.

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In recent years, multiple disciplines have focused on mitochondrial biology and contributed to understanding its relevance towards adult-onset neurodegenerative disorders. These are complex dynamic organelles that have a variety of functions in ensuring cellular health and homeostasis. The plethora of mitochondrial functionalities confers them an intrinsic susceptibility to internal and external stressors (such as mutation accumulation or environmental toxins), particularly so in long-lived postmitotic cells such as neurons. Thus, it is reasonable to postulate an involvement of mitochondria in aging-associated neurological disorders, notably neurodegenerative pathologies including Alzheimer's disease and Parkinson's disease. On the other hand, biological effects resulting from neurodegeneration can in turn affect mitochondrial health and function, promoting a feedback loop further contributing to the progression of neuronal dysfunction and cellular death. This review examines state-of-the-art knowledge, focus on current research exploring mitochondrial health as a contributing factor to neuroregeneration, and the development of therapeutic approaches aimed at restoring mitochondrial homeostasis in a pathological setting.

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OBJECTIVE: To assess the association between the presence of public outlets selling fruits and vegetables and the regular intake of these foods by adolescents from public schools in the city of Curitiba, Paraná, Brazil. METHODS: Data collection was carried out by a questionnaire answered by the adolescents. Regular intake was defined as eating fruits and vegetables five or more times a week. Environmental data were obtained by assessing the availability and prices of fruits and vegetables traded in public outlets within a 1.6-km radius from 30 randomly selected public schools. RESULTS: A total of 1,232 students from 30 public schools participated in the study. 43.4% of the adolescents reported a regular intake of fruits; 67.0% of them reported a regular intake of vegetables. In the schools, fruit intake ranged from 26.8 to 68.0%, and the vegetables intake ranged from 54.8 to 82.2%. A total of 22 schools had fruit and vegetables being traded in their surroundings. Regular intake of vegetables was positively correlated with their variety (r=0.82; p=0.007). The Moran's local index indicated low fruit intake in a high-supply region; in other three regions with low supply, there was a high intake of fruits; and there was a high consumption of vegetables in a high-supply region. CONCLUSIONS: There are differences in the supply of fruits and vegetables of public outlets in the school's surroundings as well as in the distribution of regular intake among regions. The density of public outlets and the variety were both associated with greater intake of fruits and vegetables among adolescents of public school.

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PURPOSE: Transcriptome analysis of pancreatic ductal adenocarcinoma (PDAC) has been useful to identify gene expression changes that sustain malignant phenotypes. Yet, most studies examined only tumor tissues and focused on protein-coding genes, leaving long non-coding RNAs (lncRNAs) largely underexplored. METHODS: We generated total RNA-Seq data from patient-matched tumor and nonmalignant pancreatic tissues and implemented a computational pipeline to survey known and novel lncRNAs. siRNA-mediated knockdown in tumor cell lines was performed to assess the contribution of PDAC-associated lncRNAs to malignant phenotypes. Gene co-expression network and functional enrichment analyses were used to assign deregulated lncRNAs to biological processes and molecular pathways. RESULTS: We detected 9,032 GENCODE lncRNAs as well as 523 unannotated lncRNAs, including transcripts significantly associated with patient outcome. Aberrant expression of a subset of novel and known lncRNAs was confirmed in patient samples and cell lines. siRNA-mediated knockdown of a subset of these lncRNAs (LINC01559, LINC01133, CCAT1, LINC00920 and UCA1) reduced cell proliferation, migration and invasion. Gene co-expression network analysis associated PDAC-deregulated lncRNAs with diverse biological processes, such as cell adhesion, protein glycosylation and DNA repair. Furthermore, UCA1 knockdown was shown to specifically deregulate co-expressed genes involved in DNA repair and to negatively impact DNA repair following damage induced by ionizing radiation. CONCLUSIONS: Our study expands the repertoire of lncRNAs deregulated in PDAC, thereby revealing novel candidate biomarkers for patient risk stratification. It also provides a roadmap for functional assays aimed to characterize novel mechanisms of action of lncRNAs in pancreatic cancer, which could be explored for therapeutic development.

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BACKGROUND: Increasing evidence links impaired brain insulin signaling and insulin resistance to the development of Alzheimer's disease (AD). OBJECTIVE: This evidence prompted a search for molecular players common to AD and diabetes mellitus (DM). METHODS: The work incorporated studies based on a primary care-based cohort (pcb-Cohort) and a bioinformatics analysis to identify central nodes, that are key players in AD and insulin signaling (IS) pathways. The interactome for each of these key proteins was retrieved and network maps were developed for AD and IS. Synaptic enrichment was performed to reveal synaptic common hubs. RESULTS: Cohort analysis showed that individuals with DM exhibited a correlation with poor performance in the Mini-Mental State Examination (MMSE) cognitive test. Additionally, APOE ɛ2 allele carriers appear to potentially be relatively more protected against both DM and cognitive deficits. Ten clusters were identified in this network and 32 key synaptic proteins were common to AD and IS. Given the relevance of signaling pathways, another network was constructed focusing on protein kinases and protein phosphatases, and the top 6 kinase nodes (LRRK2, GSK3B, AKT1, EGFR, MAPK1, and FYN) were further analyzed. CONCLUSION: This allowed the elaboration of signaling cascades directly impacting AßPP and tau, whereby distinct signaling pathway play a major role and strengthen an AD-IS link at a molecular level.

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Exosomes are small extracellular vesicles (EVs) present in human biofluids that can transport specific disease-associated molecules. Consequently blood-derived exosomes have emerged as important peripheral biomarker sources for a wide range of diseases, among them Alzheimer's disease (AD). Although there is no effective cure for AD, an accurate diagnosis, relying on easily accessible peripheral biofluids, is still necessary to discriminate this disease from other dementias, test potential therapies and even monitor rate of disease progression. The ultimate goal is to produce a cost-effective and widely available alternative, which can also be employed as a first clinical screen. In this study, EVs with exosome-like characteristics were isolated from serum of Controls and AD cases through precipitation- and column-based methods, followed by mass spectrometry analysis. The resulting proteomes were characterized by Gene Ontology (GO) and multivariate analyses. Although GO terms were similar for exosomes' proteomes of Controls and ADs, using both methodologies, a clear segregation of disease cases was obtained when using the precipitation-based method. Nine significantly different abundant proteins were identified between Controls and AD cases, representing putative biomarker candidate targets. Among them are AACT and C4BPα, two Aß-binding proteins, whose exosome levels were further validated in individuals from independent cohorts using antibody-based approaches. The findings discussed represent an important contribution to the identification of novel exosomal biomarker candidates useful as potential blood-based tools for AD diagnosis.

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Myotonic dystrophy type 1 (DM1) is a hereditary and multisystemic disease characterized by myotonia, progressive distal muscle weakness and atrophy. The molecular mechanisms underlying this disease are still poorly characterized, although there are some hypotheses that envisage to explain the multisystemic features observed in DM1. An emergent hypothesis is that nuclear envelope (NE) dysfunction may contribute to muscular dystrophies, particularly to DM1. Therefore, the main objective of the present study was to evaluate the nuclear profile of DM1 patient-derived and control fibroblasts and to determine the protein levels and subcellular distribution of relevant NE proteins in these cell lines. Our results demonstrated that DM1 patient-derived fibroblasts exhibited altered intracellular protein levels of lamin A/C, LAP1, SUN1, nesprin-1 and nesprin-2 when compared with the control fibroblasts. In addition, the results showed an altered location of these NE proteins accompanied by the presence of nuclear deformations (blebs, lobes and/or invaginations) and an increased number of nuclear inclusions. Regarding the nuclear profile, DM1 patient-derived fibroblasts had a larger nuclear area and a higher number of deformed nuclei and micronuclei than control-derived fibroblasts. These results reinforce the evidence that NE dysfunction is a highly relevant pathological characteristic observed in DM1.

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Alzheimer's disease (AD) is the leading cause of dementia worldwide and is characterized by the accumulation of the ß-amyloid peptide (Aß) in the brain, along with profound alterations in phosphorylation-related events and regulatory pathways. The production of the neurotoxic Aß peptide via amyloid precursor protein (APP) proteolysis is a crucial step in AD development. APP is highly expressed in the brain and is complexly metabolized by a series of sequential secretases, commonly denoted the α-, ß-, and γ-cleavages. The toxicity of resulting fragments is a direct consequence of the first cleaving event. ß-secretase (BACE1) induces amyloidogenic cleavages, while α-secretases (ADAM10 and ADAM17) result in less pathological peptides. Hence this first cleavage event is a prime therapeutic target for preventing or reverting initial biochemical events involved in AD. The subsequent cleavage by γ-secretase has a reduced impact on Aß formation but affects the peptides' aggregating capacity. An array of therapeutic strategies are being explored, among them targeting Retinoic Acid (RA) signalling, which has long been associated with neuronal health. Additionally, several studies have described altered RA levels in AD patients, reinforcing RA Receptor (RAR) signalling as a promising therapeutic strategy. In this review we provide a holistic approach focussing on the effects of isoform-specific RAR modulation with respect to APP secretases and discuss its advantages and drawbacks in subcellular AD related events.

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Mitochondria are associated with various cellular activities critical to homeostasis, particularly in the nervous system. The plastic architecture of the mitochondrial network and its dynamic structure play crucial roles in ensuring that varying energetic demands are rapidly met to maintain neuronal and axonal energy homeostasis. Recent evidence associates aging and neurodegeneration with anomalous neuronal metabolism as age-dependent alterations of neuronal metabolism are now believed to occur prior to neurodegeneration. The brain has a high energy demand, which makes it particularly sensitive to mitochondrial dysfunction. Distinct cellular events causing oxidative stress or disruption of metabolism and mitochondrial homeostasis can trigger a neuropathology. This review explores the bioenergetic hypothesis for the neurodegenerative pathomechanisms, discussing factors leading to age-related brain hypometabolism and its contribution to cognitive decline. Recent research on the mitochondrial network in healthy nervous system cells, its response to stress, and how it is affected by pathology, as well as current contributions to novel therapeutic approaches will be highlighted.

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ABSTRACT Objective: To assess the association between the presence of public outlets selling fruits and vegetables and the regular intake of these foods by adolescents from public schools in the city of Curitiba, Paraná, Brazil. Methods: Data collection was carried out by a questionnaire answered by the adolescents. Regular intake was defined as eating fruits and vegetables five or more times a week. Environmental data were obtained by assessing the availability and prices of fruits and vegetables traded in public outlets within a 1.6-km radius from 30 randomly selected public schools. Results: A total of 1,232 students from 30 public schools participated in the study. 43.4% of the adolescents reported a regular intake of fruits; 67.0% of them reported a regular intake of vegetables. In the schools, fruit intake ranged from 26.8 to 68.0%, and the vegetables intake ranged from 54.8 to 82.2%. A total of 22 schools had fruit and vegetables being traded in their surroundings. Regular intake of vegetables was positively correlated with their variety (r=0.82; p=0.007). The Moran's local index indicated low fruit intake in a high-supply region; in other three regions with low supply, there was a high intake of fruits; and there was a high consumption of vegetables in a high-supply region. Conclusions: There are differences in the supply of fruits and vegetables of public outlets in the school's surroundings as well as in the distribution of regular intake among regions. The density of public outlets and the variety were both associated with greater intake of fruits and vegetables among adolescents of public school.

RESUMO Objetivo: Avaliar a associação entre presença de equipamentos públicos de comércio de frutas e hortaliças com seu consumo regular por adolescentes de escolas públicas de Curitiba, Paraná. Métodos: Informações dos adolescentes foram coletadas por meio de questionário. Considerou-se como regular o consumo de frutas e hortaliças cinco ou mais vezes na semana. Foram incluídos dados do ambiente obtidos por auditagem de equipamentos públicos de venda de frutas e hortaliças no raio de 1,6 km do entorno de 30 escolas estaduais aleatoriamente sorteadas, no qual foram avaliados a disponibilidade e os preços desses alimentos. Resultados: Participaram do estudo 1.232 alunos de 30 escolas estaduais. O consumo regular de frutas foi referido por 43,4% e de hortaliças por 67,0% dos adolescentes. Nas escolas, o consumo de frutas variou entre 26,8 e 68,0% e o de hortaliças entre 54,8 e 82,2%; 22 escolas contavam com oferta de frutas e hortaliças no entorno. O consumo regular de hortaliças esteve correlacionado positivamente com a sua variedade (r=0,82; p=0,007). O índice de Moran local indicou baixo consumo de frutas em uma regional de alta oferta e, em outras três, alto consumo de frutas e hortaliças para baixa oferta e alto consumo de hortaliças em uma regional de alta oferta. Conclusões: Existem diferenças na oferta de frutas e hortaliças dos equipamentos públicos no entorno escolar e na distribuição do consumo regular entre as regionais. Características relacionadas à densidade de equipamentos de comércio e à variedade estiveram associadas ao maior consumo de frutas e hortaliças entre os adolescentes de escolas públicas.

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O estudo analisou fatores socioeconômicos associados à aquisição de insumos para manejo da glicemia por pessoas com Diabetes Mellitus tipo 1 durante o distanciamento social pela Pandemia de COVID-19 no Brasil. Pesquisa transversal com coleta de dados realizada durante 21 dias do mês de julho de 2020, com um formulário online sobre dados socioeconômicos e aquisição de insumos para monitorização glicêmica. Foi aplicado o teste Qui-Quadrado de Pearson com análise de resíduos ajustados (p<0,05). Participaram 472 adultos de ambos os sexos. Foram encontradas associações entre o tipo de aparelho utilizado para monitorização glicêmica (glicosímetro ou sistema Flash) e renda (p<0,000), escolaridade (p=0,007), macrorregiões (p=0,049) e tipo de cidade (p=0,043); entre aquisição de insulinas e renda (p<0,000), macrorregião (p=0,027) e tipo de bairro (p=0,003); entre aquisição de fitas reagentes e renda (p<0,000); entre aquisição de lancetas e renda (p=0,001), tipo de cidade (p=0,035) e de bairro (p=0,010); entre o uso de Sistema Flash e renda (p<0,000) e tipo de bairro (p=0,006). Os resultados expõem as desigualdades sociais na aquisição de insumos para manejo da glicemia por pessoas com Diabetes Tipo 1 durante a Pandemia no Brasil.

This study analyzed socioeconomic factors related with the acquisition of supplies for blood glucose management by people with Type 1 Diabetes Mellitus during social distancing due to the COVID-19 Pandemic in Brazil. This was a cross-sectional study with data collected during 21 days in July 2020, by an online form on socioeconomic data and acquisition of supplies for glycemic monitoring. This research applied Pearson's Chi-Squared test with adjusted residual analysis (p<0.05). 472 adults of both sexes participated. Relationships were found between the type of device used for blood glucose monitoring (glucometer or Flash system) and income (p<0.000), education (p=0.007), macro-regions (p=0.049), and type of city (p=0.043); between insulin acquisition and income (p<0.000), macro-region (p=0.027) and type of neighborhood (p=0.003); between acquisition of reagent strips and income (p<0.000); between acquisition of lancets and income (p=0.001), type of city (p=0.035) and neighborhood (p=0.010); between the use of Flash System and income (p<0.000) and type of neighborhood (p=0.006). The results expose the social inequalities in the acquisition of supplies for blood glucose management by people with Type 1 Diabetes during the Pandemic in Brazil.

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APOE ε4 and BIN1 are the two main genetic risk factors for sporadic Alzheimer's Disease (AD). Among several BIN1 variants, the rs744373 is frequently associated with AD risk by contributing to tau pathology and poor cognitive performance. This study addressed the association of APOE and BIN1 rs744373 to specific characteristics in a Portuguese primary care-based study group, denoted pcb-Cohort. The study included 590 participants from five primary care health centers in the Aveiro district of Portugal. Individuals were evaluated and scored for cognitive and clinical characteristics, and blood samples were collected from the volunteers meeting the inclusion and exclusion criteria (N = 505). APOE and BIN1 genotypes were determined, and their association with cognitive characteristics and other diseases that might contribute to cognitive deficits, namely depression, hypertension, type 2 diabetes, dyslipidemia, osteoarticular diseases, gastrointestinal diseases, cardiovascular and respiratory diseases, was assessed. The diseases attributed to the study group were those previously diagnosed and confirmed by specialists. The results generated through multivariate analysis show that APOE ε4 carriers significantly associated with poorer cognitive performance (OR = 2.527; p = 0.031). Additionally, there was a significant risk of dyslipidemia for APOE ε4 carriers (OR = 1.804; p = 0.036), whereas BIN1 rs744373 risk-allele carriers were at a significantly lower risk of having dyslipidemia (OR = 0.558; p = 0.006). Correlations were evident for respiratory diseases in which APOE ε4 showed a protective tendency (OR = 0.515; p = 0.088), and BIN1 had a significative protective profile (OR = 0.556; p = 0.026). Not of statistical significance, APOE ε2 showed a trend to protect against type 2 diabetes (OR = 0.342; p = 0.093), in contrast BIN1 rs744373 risk-allele carriers were more likely to exhibit the disease (OR = 1.491; p = 0.099). The data here presented clearly show, for the first time, that the two top genetic risk factors for sporadic AD impact a similar group of common diseases, namely dyslipidemia, respiratory diseases, and type 2 diabetes.

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Este estudo comparou a existência de pontos de comercialização de frutas e hortaliças provenientes de sistemas de produção convencional e orgânicos, verificando diferenças nos preços desses alimentos em Curitiba (PR). A coleta de dados aconteceu em 2018, mapeando os pontos de venda cadastrados na Secretaria Municipal de Abastecimento de Curitiba, registrando os alimentos ofertados (convencional e orgânico), e os preços de frutas, legumes e verduras, listados no instrumento de avaliação de estabelecimentos de comercialização dos alimentos para consumo em domicílio (ESAO-s Feiras Livres). Realizou-se o cálculo da razão de preços do dia, registrado conforme os preços praticados na central de abastecimento de Curitiba. Os alimentos convencionais foram encontrados em mais pontos (n =74) em relação aos alimentos orgânicos (n = 15). A oferta dos orgânicos ficou limitada a áreas mais centrais e regiões com maior renda. A maioria dos orgânicos apresentaram preços mais altos que os convencionais. Foi demonstrado que existem desigualdades na distribuição espacial e no preço entre frutas e hortaliças orgânicas e convencionais, indicando que a população do município não tem qualidade no acesso a estes alimentos, dispendendo valores maiores, caso queira optar por escolhas orgânicas.

The study compared the existence of points of commercialization of fruits and vegetables from conventional and organic production systems and verifying differences in the prices of these foods in Curitiba, Paraná. Data collection took place in 2018, mapping the points of sale registered with the Curitiba Municipal Secretariat of Supply, registering the foods offered (conventional / organic), and the prices of fruits and vegetables, listed in the Instrument of Evaluation of establishments in marketing of food for consumption at home (ESAO-s Feiras Livres). The price ratio of the day was calculated, recorded according to the prices practiced at the Central de Abastecimento of Curitiba. Conventional foods were found in more points (n = 74) in relation to organic foods (n = 15). The supply of organics was limited to more central areas, a region with higher income. Most organic products had higher prices than conventional ones. It has been shown that there are inequalities in the spatial distribution and in the price between organic and conventional fruits and vegetables, indicating that the population of the municipality does not have quality access to these foods and may have higher values if they want to choose organic choices.

El estudio comparó la existencia de puntos de comercialización de frutas y verduras de sistemas de producción convencionales y orgánicos, y verificó diferencias en los precios de estos alimentos en Curitiba, Paraná. La recolección de datos se llevó a cabo en 2018, mapeando los puntos de venta registrados en la Secretaría de Abastecimiento Municipal de Curitiba, registrando los alimentos ofertados (convencionales / orgánicos), y los precios de frutas y verduras, enumerados en el Instrumento de Evaluación de Establecimientos de comercialización de alimentos para consumo en el hogar (ESAO-s Feiras Livres). Se calculó la ratio de precios del día, registrado de acuerdo con los precios practicados en la Central de Abastecimento de Curitiba. Los alimentos convencionales se encontraron en más puntos (n = 74) con relación a los alimentos orgánicos (n = 15). La oferta de productos orgánicos se limitó a áreas más centrales, una región con mayores ingresos. La mayoría de los orgánicos tenían precios más altos que los convencionales. Se ha demostrado que existen desigualdades en la distribución espacial y en el precio entre frutas y verduras orgánicas y convencionales, lo que indica que la población del municipio no tiene acceso de calidad a estos alimentos y puede tener valores más altos si así lo desea elija opciones orgánicas.

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