AAV-mediated neuronal expression of an scFv antibody selective for Aß oligomers protects synapses and rescues memory in Alzheimer models.

The accumulation of soluble oligomers of the amyloid-ß peptide (AßOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AßOs and shows minimal reactivity to Aß monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AßOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AßO binding to neurons and AßO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AßOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AßO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.

Effect of Adding Guava (Psidium guajava) Epicarp Extract Flour on the Physicochemical, Textural, Colour and Sensory Properties of Frankfurters.

RESEARCH BACKGROUND: The industrial transformation of tropical fruits, and in particular guava, generates a large quantity of by-products that are generally disposed of as organic waste. In these by-products a large quantity of bioactive substances is concentrated, such as carotenoids, which can be used for the partial substitution of nitrites in meat sausages without affecting their physicochemical, colour and conservation characteristics. Although there are some studies in this regard, there is still a lack of research, especially on guava residues, to verify this hypothesis. Therefore, the aim of this study is to investigate the influence of the components of the guava epicarp extract on the physicochemical, textural, colour and sensory properties of frankfurters. EXPERIMENTAL APPROACH: There treatments were investigated (25, 50 and 75% nitrite replacement with guava epicarp flour extract), along with a control treatment without the extract. The physicochemical properties, colour coordinates, and texture parameters were analysed, and a sensory evaluation was also carried out. The treatment that gave the best results was subjected to stability analysis over 30 days. RESULTS AND CONCLUSIONS: The addition of 25% guava epicarp flour extract gave the best results, since it did not affect the colouration of the sausages or their physicochemical and textural properties. Likewise, during the stability analysis over time, the parameters related to fat oxidation were not affected, and final products had a residual nitrite load of (23.6±0.2) mg/kg, lower than the maximum allowed (150 mg/kg). NOVELTY AND SCIENTIFIC CONTRIBUTION: The partial substitution of the nitrites in frankfurters with the carotenoids from the guava epicarp flour added in a mass fraction up to 25% can be a viable alternative to produce sausages with lower content of nitrites, without affecting their colouration or shelf life. This is important for the meat industry, which favours the development of new products using substances of natural origin.

Müller Cells Derived from Adult Chicken and Mouse Retina Neurospheres Acquire the Dopaminergic Phenotype.

Neurospheres prepared from multipotent progenitors in the retina obtained from postnatal mice differentiate into neurons and Müller glia (De Melo Reis et al., in Cell Mol Neurobiol 31:835-846, 2011). Here, we investigated whether neurospheres prepared from adult chickens (ciliary marginal zone, CMZ) or (ciliary body) retina could also lead to differentiated neurons and glia. Neurospheres were prepared from post-hatched chickens or from adult mice after 7 days in the presence of mitogenic factors (FGFb, insulin, and EGF), generating neurons and glial cells. In addition, Müller (2M6 or glutamine synthetase positive cells) derived from post-hatch chicken CMZ neurospheres displayed the dopaminergic phenotype. Furthermore, we observed that Müller cells derived from adult chickens and mice retina neurospheres released significant amounts of dopamine as well as of its metabolites. Taken together, our data lead us to conclude that as for embryonic (chick) or newborn (mouse), the dopaminergic phenotype is a default condition of Müller glial cells obtained from neurospheres prepared from mature retina. Our data raise the possibility that Müller cells from differentiated tissue could be used to ameliorate neurodegenerative diseases involving dopaminergic dysfunction as in Parkinson's disease as shown previously (Stutz et al., in J Neurochem 128:829-840, 2014).

Microglial dysfunction connects depression and Alzheimer's disease.

Alzheimer's disease (AD) and major depressive disorder (MDD) are highly prevalent neuropsychiatric conditions with intriguing epidemiological overlaps. Depressed patients are at increased risk of developing late-onset AD, and around one in four AD patients are co-diagnosed with MDD. Microglia are the main cellular effectors of innate immunity in the brain, and their activation is central to neuroinflammation - a ubiquitous process in brain pathology, thought to be a causal factor of both AD and MDD. Microglia serve several physiological functions, including roles in synaptic plasticity and neurogenesis, which may be disrupted in neuroinflammation. Following early work on the 'sickness behavior' of humans and other animals, microglia-derived inflammatory cytokines have been shown to produce depressive-like symptoms when administered exogenously or released in response to infection. MDD patients consistently show increased circulating levels of pro-inflammatory cytokines, and anti-inflammatory drugs show promise for treating depression. Activated microglia are abundant in the AD brain, and concentrate around senile plaques, hallmark lesions composed of aggregated amyloid-ß peptide (Aß). The Aß burden in affected brains is regulated largely by microglial clearance, and the complex activation state of microglia may be crucial for AD progression. Intriguingly, recent reports have linked soluble Aß oligomers, toxins that accumulate in AD brains and are thought to cause memory impairment, to increased brain cytokine production and depressive-like behavior in mice. Here, we review recent findings supporting the inflammatory hypotheses of AD and MDD, focusing on microglia as a common player and therapeutic target linking these devastating disorders.

Murine dopaminergic Müller cells restore motor function in a model of Parkinson's disease.

Müller cells constitute the main glial cell type in the retina where it interacts with virtually all cells displaying relevant functions to retinal physiology. Under appropriate stimuli, Müller cells may undergo dedifferentiation, being able to generate other neural cell types. Here, we show that purified mouse Müller cells in culture express a group of proteins related to the dopaminergic phenotype, including the nuclear receptor-related 1 protein, required for dopaminergic differentiation, as well the enzyme tyrosine hydroxylase. These dopaminergic components are active, since Müller cells are able to synthesize and release dopamine to the extracellular medium. Moreover, Müller-derived tyrosine hydroxylase can be regulated, increasing its activity because of phosphorylation of serine residues in response to agents that increase intracellular cAMP levels. These observations were extended to glial cells obtained from adult monkey retinas with essentially the same results. To address the potential use of dopaminergic Müller cells as a source of dopamine in cell therapy procedures, we used a mouse model of Parkinson's disease, in which mouse Müller cells with the dopaminergic phenotype were transplanted into the striatum of hemi-parkinsonian mice generated by unilateral injection of 6-hydroxydopamine. These cells fully decreased the apomorphine-induced rotational behavior and restored motor functions in these animals, as measured by the rotarod and the forelimb-use asymmetry (cylinder) tests. The data indicate local restoration of dopaminergic signaling in hemi-parkinsonian mice confirmed by measurement of striatal dopamine after Müller cell grafting.

Composition and activity against oral pathogens of the essential oil of Melampodium divaricatum (Rich.) DC.

The chemical composition of the essential oil isolated from the aerial parts of Melampodium divaricatum (Rich.) DC. (Asteraceae) was characterized by GC-FID and GC/MS analyses. (E)-Caryophyllene (56.0%), germacrene D (12.7%), and bicyclogermacrene (9.2%) were identified as the major oil components. The antimicrobial activity of the oil against seven standard strains of oral pathogens from the American Type Culture Collection (ATCC) was evaluated by determining minimum inhibitory concentrations (MICs) using the microdilution method. MIC Values below 100 µg/ml were obtained against Streptococcus sobrinus (90 µg/ml), Lactobacillus casei (30 µg/ml), S. mutans (20 µg/ml), and S. mitis (18 µg/ml). In contrast, the MIC values of the major oil compound (E)-caryophyllene were higher than 400 µg/ml against all pathogens, suggesting that the activity of the oil might depend on minor oil components and/or on synergistic effects. The M. divaricatum essential oil is a promising agent to include in anticariogenic oral rinse formulations for the control of oral pathogens.

Peach Palm Fruit (Bactris gasipaes) Peel: A Source of Provitamin A Carotenoids to Develop Emulsion-Based Delivery Systems.

The peach palm fruit (Bactris gasipaes) peel is a byproduct after fruit consumption. The peel flour of two varieties (yellow and red) was separately obtained by hot air drying and was subsequently milled. The proximate analysis showed that the red variety exhibited higher protein, fat, and fiber contents than the yellow one. A higher carotenoid (836.5 ± 24.5 µg/g), phenolic compounds (83.17 ± 1.76 mg GAE/100 g), and provitamin A activity (33.10 ± 0.83 µg retinol/g) were found in the cooked red variety. The carotenoid and phenolic compositions were analyzed by HPLC-PDA-MS, finding ß-carotene and γ-carotene to be major compounds. The effect of thermal treatment increased the amount of these provitamin A carotenoids and lycopene, which were detected only in the red variety. Among phenolic compounds, procyanidin dimer (isomer I), feruloyl quinic acid, and several apigenin C-hexosides were identified as major constituents of peach palm epicarp. A carotenoid-rich emulsion-based delivery system was obtained after the optimization (RSM model) of carotenoid extraction with ultraturrax and sunflower oil and further development of an ultrasound-assisted emulsion. The best conditions for a stable emulsion were 73.75% water, 25% carotenoid-rich oil extract, 1.25% emulsifiers, and 480 W of ultrasonic power for 5 min. The optimized emulsion had a total carotenoid content of 67.61 µg/g, Provitamin A activity of 3.23 ± 0.56 µg RAE/g, droplet size of 502.23 nm, polydispersity index of 0.170, and zeta potential of -32.26 mV. This emulsion was chemically and physically stable for 35 days at 30 ± 2 °C, showing potential as a food additive with biofunctional properties. The strategy here developed is an economical and environmentally friendly process that allows the reuse of the byproduct of B. gasipaes.

Inhibition of choline acetyltransferase as a mechanism for cholinergic dysfunction induced by amyloid-ß peptide oligomers.

Dysregulated cholinergic signaling is an early hallmark of Alzheimer disease (AD), usually ascribed to degeneration of cholinergic neurons induced by the amyloid-ß peptide (Aß). It is now generally accepted that neuronal dysfunction and memory deficits in the early stages of AD are caused by the neuronal impact of soluble Aß oligomers (AßOs). AßOs build up in AD brain and specifically attach to excitatory synapses, leading to synapse dysfunction. Here, we have investigated the possibility that AßOs could impact cholinergic signaling. The activity of choline acetyltransferase (ChAT, the enzyme that carries out ACh production) was inhibited by ~50% in cultured cholinergic neurons exposed to low nanomolar concentrations of AßOs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction, lactate dehydrogenase release, and [(3)H]choline uptake assays showed no evidence of neuronal damage or loss of viability that could account for reduced ChAT activity under these conditions. Glutamate receptor antagonists fully blocked ChAT inhibition and oxidative stress induced by AßOs. Antioxidant polyunsaturated fatty acids had similar effects, indicating that oxidative damage may be involved in ChAT inhibition. Treatment with insulin, previously shown to down-regulate neuronal AßO binding sites, fully prevented AßO-induced inhibition of ChAT. Interestingly, we found that AßOs selectively bind to ~50% of cultured cholinergic neurons, suggesting that ChAT is fully inhibited in AßO-targeted neurons. Reduction in ChAT activity instigated by AßOs may thus be a relevant event in early stage AD pathology, preceding the loss of cholinergic neurons commonly observed in AD brains.

Effect of temperature and particle size on physicochemical and techno-functional properties of peach palm peel flour (Bactris gasipaes, red and yellow ecotypes).

In this study, the effect of temperature and particle size on the techno-functional properties of the flour from peach palm fruit peels (Bactris gasipaes, red and yellow ecotype) were evaluated. The flour from peach palm epicarp obtained by natural convective drying was physicochemically characterized, including the assessment of total dietary fiber determined under the gravimetric enzymatic method. The results obtained showed that temperature and particle size present a significant effect (p < 0.001) on techno-functional properties except for swelling capacity. The flour from the red ecotype presented better nutritional: total dietary fiber 47.93 ± 1.72%, protein 6.87 ± 0.15% and techno-functional properties: water retention capacity (WRC) 7.13 ± 0.29 g/g, oil retention capacity (ORC) 6.24 ± 0.08 g/g, emulsifier activity (EA) 56.84 ± 0.28%, emulsifier stability (ES) 50.33 ± 0.31% than the yellow one water absorption capacity (WAC) 5.31 ± 0.03 g/g and water solubility (WS) 59.58 ± 0.04% at 60 °C and 0.25 mm. Therefore, this study showed that the flour obtained from peach palm fruit peels contains high fiber and protein values and could be used as a promising natural additive (source of dietary fiber or emulsifier) for the food industry.

ARTHROSCOPIC FOOT AND ANKLE SURGERY: BRAZILIAN SURGEON PROFILE.

Objective: To study the profile of the practice of arthroscopy among ankle and foot surgeons in Brazil and its evolution in recent years. Methods: Observational, cross-sectional study, using a survey sent to all members of the Associação Brasileira de Medicina e Cirurgia do Tornozelo e Pé (ABTPé) in 2017 and 2019. Results: In total, 75 surgeons participated in 2017 and 82 in 2019 and most had over 10 years of experience. Of these, 56 participants in 2017 (75%) and 68 in 2019 (82%) used arthroscopy. The number of specialists with no to five years of experience (p = 0.027) and who learned the technique during fellowship (p = 0.007) increased. The use of the 4.0 mm optics and 30° optics (p = 0.040) increased whereas the routine use of traction (p = 0.049) and radiofrequency (p = 0.002) decreased. The main pathology treated with anterior ankle arthroscopy was bone injury. The most frequent complication was neuropraxia. Conclusion: Most of the foot and ankle surgeons who use arthroscopy have more than 10 years of experience, performed anterior access, and are concentrated in the Southeast region of the country. The number of younger surgeons who learned the technique during fellowship increased. Level of Evidence III, Cross-Sectional Comparative Study.

Objetivo: Mostrar o perfil da prática da artroscopia entre cirurgiões de tornozelo e pé no Brasil e sua evolução nos últimos anos. Métodos: Estudo observacional, transversal, realizado por meio de questionário eletrônico enviado para todos os membros da Associação Brasileira de Medicina e Cirurgia do Tornozelo e Pé (ABTPé) em 2017 e 2019. Resultados: Obtivemos 75 respondentes em 2017 e 82 em 2019; a maioria tinha mais de 10 anos de experiência. Dos respondentes, 56 realizavam artroscopia em 2017 (75%) e 68 em 2019 (82%). Foi observado aumento no número de especialistas com até 5 anos de experiência (p = 0,027) e que aprenderam a técnica durante o estágio de especialização (p = 0,007). Houve aumento no uso da ótica de 4,0 mm e 30° de angulação (p = 0,040), e diminuição do uso rotineiro de tração (p = 0,049) e de radiofrequência (p = 0,002). A principal patologia tratada com artroscopia anterior do tornozelo foi o impacto ósseo, e a complicação mais frequente foi a neuropraxia. Conclusão: A maioria dos cirurgiões de pé e tornozelo que utiliza artroscopia tem mais de 10 anos de experiência, usa o acesso anterior e concentra-se na região Sudeste do país. Foi observado aumento no número de cirurgiões mais novos e que aprenderam a técnica durante o estágio de especialização. Nível de Evidência III, Estudo Transversal Comparativo.

Relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers. / Relação entre maturação sexual e indicadores antropométricos e pressóricos em adolescentes.

This study aimed to investigate the relationship between sexual maturation and anthropometric and blood pressure indicators in teenagers. This was a population-based cross-sectional study, conducted with 345 teenagers, aged 10 to 19 years, between 2018 and 2020. In this study, data referent to sociodemographic and anthropometric variables, blood pressure, and sexual maturation were collected. The data analysis was performed by applying the Principle Component Analysis (PCA), which generated three components and then tested the correlation between sexual maturation and the generated components. Most of the teenagers were female (53%), normotensive (66.1%), and with a normal weight (73%). A positive correlation was found between breast development and component 1 and component 2, as well as a negative correlation between the breasts and component 3. In the boys, the development of genitals and pubic hair was positively correlated with component 2 and inversely correlated with component 3. It could therefore be concluded that there is a relationship between sexual maturation and the anthropometric and blood pressure indicators, which proved to be representative variables for cardiovascular risk in teenagers, even if not in their entirety.

Objetivou-se investigar a relação entre a maturação sexual com indicadores antropométricos e pressóricos de adolescentes. Estudo transversal de base populacional, realizado entre 2018 e 2020, com 345 adolescentes de 10 a 19 anos. Coletou-se variáveis sociodemográficas e antropométricas, pressão arterial e maturação sexual. A análise dos dados foi feita por meio da Análise de Componentes Principais, que gerou três componentes e, posteriormente, testou-se a correlação entre a maturação sexual e os componentes gerados. A maioria dos adolescentes eram do sexo feminino (53%), normotensos (66,1%) e com peso normal (73%). Houve correlação positiva entre o desenvolvimento das mamas com o componente 1 e o componente 2, e correlação negativa entre mamas e o componente 3. Nos meninos, o desenvolvimento dos genitais e pelos pubianos estiveram positivamente correlacionados com o componente 2 e inversamente correlacionados com o componente 3. Conclui-se que existe relação entre a maturação sexual e os indicadores antropométricos e pressóricos, sendo variáveis representativas de risco cardiovascular em adolescentes, mesmo que não em sua totalidade.

Body dissatisfaction, drug use, and associated factors among adolescents in three Brazilian cities. / Insatisfação com a imagem corporal, uso de drogas e fatores associados entre adolescentes em três cidades brasileiras.

OBJECTIVE: analyze the association between drug use and body dissatisfaction among adolescents in three Brazilian cities. METHOD: cross-sectional study, using a nested randomized controlled trial to evaluate the drug use prevention program #TamoJunto2.0 of the Ministry of Health in Brazilian schools. The sample consisted of 5,213 students from 73 schools in three Brazilian cities. The outcome body satisfaction was analyzed using the Stunkard scale and the explanatory variables were drug use and sociodemographic data. RESULTS: the adolescents were between 12 and 14 years old; about 69.9% of them reported body dissatisfaction, and 35.67% used alcohol in the previous year. Dissatisfaction due to overweight was higher among girls (41.5%) and dissatisfaction due to underweight was higher among boys (33.1%). Adolescents who used marijuana were 39% (OR=1.39) more likely to feel dissatisfied due to underweight and being a girl increased the chances of feeling dissatisfied due to overweight by 24% (OR=1.24). CONCLUSION: the levels of body dissatisfaction deserve attention in hebiatric nursing care and reinforce the importance of educational strategies addressing body image and drug use, relating them to the various subjective attributes that can affect the health of adolescents, whether in the community or at school.(1) High prevalence of body dissatisfaction related to overweight. (2) Girls presented 24% more chances of feeling body dissatisfaction due to overweight. (3) Marijuana use in adolescence can increase by 39% body dissatisfaction due to underweight. (4) Last year, about 35.7% of adolescents had already consumed alcohol. (5) Health promotion and stimulation of positive perceptions of self-image.

Nitrite reduction in beef burger using papaya (Carica papaya L.) epicarp.

Current pressure on the need to reduce nitrite content in meat products without affecting sensory properties such as color requires research for the development of healthy foods and the improvement of the quality of life of human beings. Fruit by-products are an important source of bioactive compounds, which can be used as natural additives in food processing. The objective of this study was to evaluate papaya epicarp flour as a natural ingredient in nitrite reduction of beef burger. Papaya epicarp samples after lyophilized were ground. A composite central design and a response surface methodology were used in order to analyze the process variables (nitrite and papaya epicarp flour concentrations) on the color of the beef burger. Response variables were carotenoid fractions and CIEL*a*b*. The optimal color-maximizing nitrite/flour ratio in beef burger was found corresponding to 150 mg/kg nitrite/40 mg/kg flour, where the maximum values for ß-cryptoxanthin, zeaxanthin, and lycopene were 0.451, 0.447, and 0.251 mg/100 g of sample, respectively, together with the lower value of L* (64.38). This study showed the agro-industrial potential of papaya epicarp flour to reduce nitrite concentrations in this food, in addition, the valuation of this by-product could bring economic and environmental benefits.

Rapid size-exclusion high performance liquid chromatography method for the quality control of amyloid-ß oligomers.

Amyloid-ß (Aß) dysmetabolism is thought to be the main trigger for neurodegenerative events in Alzheimer's disease (AD). In particular, soluble Aß oligomers (AßOs) are proposed as key mediators of synaptic and cognitive dysfunction in AD. Over the past few decades, AßOs prepared from synthetic Aß have been widely applied in vitro and in vivo, the so-called chemical models of AD, uncovering their multiple neurotoxic mechanisms. However, the lack of a reliable quality control (QC) for synthetic AßOs may reflect poor experimental reproducibility. In keeping with this, we optimized and validated a rapid and reproducible SECHPLC method using fluorescence detection for the QC of synthetic AßOs. Our analytical method offers an unprecedent alternative to improve the reproducibility of AD chemical models.

Access to the Unified Health System in the perspective of male homosexuals.

OBJECTIVES: To analyze the perception of male homosexuals regarding the access to the Unified Health System. METHODS: A qualitative study with male homosexuals in a city in the Northeast Brazil. Eight subjects participated, a socioeconomic questionnaire was used for data collection and a focal group was carried out, in which the narratives were recorded and later transcribed. For the analysis of the speeches, the analysis of thematic content was used. RESULTS: The analysis revealed five thematic categories that express the limitations on humanization and reception, as well as in the quality of health care offered to subjects, disregarding the psychosocial and lifestyle-related demands. FINAL CONSIDERATIONS: It was emphasized that the focus group technique contributed to the approach of the research with the perception of male homosexuals marked by prejudice and discrimination, reflecting the subjects' dissatisfaction with the care received in the health services.

Diet-Derived Fatty Acids, Brain Inflammation, and Mental Health.

Western societies experienced drastic changes in eating habits during the past century. The modern nutritional profile, typically rich in saturated fats and refined sugars, is recognized as a major contributing factor, along with reduced physical activity, to the current epidemics of metabolic disorders, notably obesity and diabetes. Alongside these conditions, recent years have witnessed a gradual and significant increase in prevalence of brain diseases, particularly mood disorders. While substantial clinical/epidemiological evidence supports a correlation between metabolic and neuropsychiatric disorders, the mechanisms of pathogenesis in the latter are often multifactorial and causal links have been hard to establish. Neuroinflammation stands out as a hallmark feature of brain disorders that may be linked to peripheral metabolic dyshomeostasis caused by an unhealthy diet. Dietary fatty acids are of particular interest, as they may play a dual role, both as a component of high-calorie obesogenic diets and as signaling molecules involved in inflammatory responses. Here, we review current literature connecting diet-related nutritional imbalance and neuropsychiatric disorders, focusing on the role of dietary fatty acids as signaling molecules directly relevant to inflammatory processes and to neuronal function.

Natural pigment extraction optimization from coffee exocarp and its use as a natural dye in French meringue.

This study aimed to optimize the pigment extraction process for coffee exocarp and to evaluate its coloring effect on French meringue. The anthocyanins were determined with the differential pH method and the process was optimized with the response surface methodology. The solvent concentration (SC) and solid solvent ratio (SSR) had a significant effect on the anthocyanin content and surface color of the coffee cherry extracts. The optimal extraction conditions 60% SC and 25% SSR resulted in the highest concentration of anthocyanins (0.145 mg cyanidin 3-glucoside/g of coffee fresh exocarp). For the French meringue, the 3% extract concentration had the smallest total color difference (ΔE), as compared to the control, evidencing the potential of coffee exocarp dyes in place of synthetic dyes in the manufacture of French meringue.