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BACKGROUND: Penile cancer (PeCa) is a rare disease, but its incidence has increased worldwide, mostly in HPV+ patients. Nevertheless, there is still no targeted treatment for this carcinoma. OBJECTIVE: To predict the main signaling pathways involved in penile tumorigenesis and its potential drug targets. METHODS: Genome-wide copy number profiling was performed in 28 PeCa. Integration analysis of CNAs and miRNAs and mRNA targets was performed by DIANA-TarBase v.8. The potential impact of the miRNAs/target genes on biological pathways was assessed by DIANA-miRPath v.3.0. For each miRNA, KEGG pathways were generated based on the tarbase and microT-CDS algorithms. Pharmaco-miR was used to identify associations between miRNAs and their target genes to predict druggable targets. RESULTS: 269 miRNAs and 2,395 genes were mapped in cytobands with CNAs. The comparison of the miRNAs mapped at these cytobands and the miRNAs that were predicted to regulate the genes also mapped in these regions, resulted in a set of common 35 miRNAs and 292 genes. Enrichment pathway revealed their involvement in five top signaling pathways. EGFR and COX2 were identified as potential druggable targets. CONCLUSION: Our data indicate the potential use of EGFR and COX2 inhibitors as a target treatment for PeCa patients.

Holt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. The individual with the c.905delA variant has a severe cardiac phenotype but mild skeletal defects, unlike the individual with the c.246_249delGATG variant who has no cardiac problems but severe upper limbs malformations, including phocomelia. Both frameshift variants, c.246_249delGATG and c.905delA, generate mRNAs harbouring premature stop codons which, if not degraded by nonsense mediated decay, will lead to the production of shorter TBX5 proteins, p.Gln302Argfs*92 and p.Met83Phefs*6, respectively. Immunocytochemistry results suggest that both mutated proteins are produced and furthermore, like the wild-type protein, p.Gln302Argfs*92 mutant appears to be mainly localized in the nucleus, in contrast with p.Met83Phefs*6 mutant that displays a higher level of cytoplasmic localization. In addition, luciferase activity analysis revealed that none of the TBX5 mutants are capable of transactivating the NPPA promoter. In conclusion, our results provide evidence that both pathogenic variants cause a severe TBX5 loss-of-function, dramatically reducing its biological activity. The absence of cardiac problems in the individual with the p.Met83Phefs*6 variant supports the existence of other mechanisms/genes underlying the pathogenesis of HOS and/or the existence of an age-related delay in the development of a more serious cardiac phenotype. Further studies are required to understand the differential effects observed in the phenotypes of both individuals. Foundation for Science and Technology (FCT)Portuguese Foundation for Science and TechnologyEuropean Commission [UIDB/04326/2020]; FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BD/141918/2018, SFRH/BD/144230/2019]

Introduction: Dementia is a globally relevant health problem, which places a great burden on patients and their families. This study aimed to estimate the burden associated with Alzheimer's disease (AD) and other dementias in Brazil. Methods: In this descriptive study, we investigated the estimates obtained by the Global Burden of Disease study. We described the prevalence of AD and other dementias, years lived with disability (YLDs), age-standardized mortality, years of life lost (YLLs), and disability-adjusted life years (DALYs) among individuals aged 60 years or older between 2000 and 2016, with their respective 95% uncertainty intervals (95%UI). Results: During this period, the age-standardized prevalence of AD and other dementias per 100,000 people increased by 7.8%, from 961.7 (95%UI 828.3–1,117.5) to 1,036.9 (95%UI 882.0–1,219.5), with approximately 1.5 million people living with dementia in Brazil. The incidence increased by 4.5%. Similarly, all age-standardized rates had an upward trend (mortality: 3.1%; YLLs: 5.8%; YLDs: 7.9%; and DALYs: 6.3%). Mortality profiles increased with age in both years. Dementias were ranked fourth among the leading causes of death in people aged ≥70 years in 2000, rising to second place in 2016. In 2016, it also represented the second and third leading causes of disability among older women and men, respectively. Conclusion: Population growth and aging have resulted in an increased burden of AD and other dementias in Brazil. Preventive and early diagnostic measures are essential to mitigate the burden associated with these diseases. RESUMO Introdução: A demência é um problema de saúde globalmente relevante, com grande carga para os pacientes e suas famílias. Este estudo teve como objetivo estimar a carga associada à doença de Alzheimer (DA) e outras demências no Brasil. Métodos: Neste estudo descritivo, foram avaliadas as estimativas obtidas pelo estudo de Carga Global de Doença (Global Burden Disease). Descrevemos a prevalência de DA e outras demências, anos vividos com incapacidade (AVIs), mortalidade padronizada por idade, anos de vida perdidos por morte prematura (AVPs) e anos de vida perdidos ajustados por incapacidade (AVAIs), com respectivos intervalos de incerteza de 95% (95%II), em idosos com 60+ anos, entre 2000 e 2016. Resultados: No período, a prevalência padronizada por idade de DA e de outros tipos de demência aumentou 7,8%, de 961,7 (95%II 828,3–1.117,5) para 1.036,9 (95%II 882,0–1.219,5) por 100.000 pessoas, com aproximadamente 1,5 milhão de pessoas vivendo com demência no Brasil. Houve um aumento de 4,5% na incidência. Todas as taxas padronizadas por idade apresentaram tendência de aumento (mortalidade: 3,1%; AVPs: 5,8%; AVIs: 7,9%; e AVAIs: 6,3%). Os perfis de mortalidade demonstraram aumento com o envelhecimento, em ambos os anos. As demências ocuparam o quarto lugar entre as principais causas de morte em pessoas com 70+ anos em 2000, subindo para a segunda posição em 2016. Em 2016, também representou a segunda e terceira principais causas de incapacidade entre mulheres e homens mais velhos, respectivamente. Conclusões: O crescimento e envelhecimento populacional resultaram em aumento da carga de DA e de outras demências no Brasil. Medidas preventivas e de diagnóstico precoce são essenciais para atenuar a carga associada a essas doenças.

Background Various strategies are needed to mitigate the negative impact on or to increase fruit quality. The effect of spraying kaolin (K), Ascophyllum nodosum (An) and salicylic acid (SA), in trees with and without irrigation, on quality and sensorial attributes of hazelnut (Grada de Viseu cultivar) was investigated during two consecutive years (2016 and 2017) in a commercial orchard located in Moimenta da Beira, Portugal. Results The treatments affected positively the biometric parameters nut and kernel weight, length, width, thickness and volume as well as the vitamin E level, antioxidant activity and content of some individual phenolics, such as protocatechuic acid, gallocatechin, catechin and epicatechin. The levels of amino acids in hazelnut kernels decreased in all the assayed treatments, while the kernel colour and sensorial attributes were not affected by the treatments. Hazelnut physical properties (nut and kernels), chemical and phytochemical composition and antioxidant activities were positively related. Conclusions The application of K, An and SA improved the hazelnut tree response to climate change, without compromising the hazelnut chemical and sensorial quality. Furthermore, due to the similar observations for the same treatments with and without irrigation, it can be stated that K, An and SA can be efficient and cost-effective tools to mitigate summer stress in rain-fed orchards. © 2020 Society of Chemical Industry.

Context The sirtuins (SIRT1 to SIRT7) constitute a family of highly conserved nicotinamide adenine dinucleotide–dependent proteins. When activated, sirtuins control essential cellular processes to maintain metabolic homeostasis, while lack of expression of sirtuins has been related to chronic disease. Objective The aim of this systematic review is to analyze the role of fat consumption as a modulator of human sirtuins. Data Sources This review was conducted according to PRISMA guidelines. Studies were identified by searches of the electronic databases PubMed/MEDLINE, Scopus, and Web of Science. Study Selection Randomized clinical trials assessing the effect of fatty acid consumption on sirtuin mRNA expression, sirtuin protein expression, or sirtuin protein activity were eligible for inclusion. Data Extraction Two authors screened and determined the quality of the studies; disagreements were resolved by the third author. All authors compared the compiled data. Results Seven clinical studies with 3 different types of interventions involving healthy and nonhealthy participants were selected. Only SIRT1 and SIRT3 were evaluated. Overall, the evidence from clinical studies to date is insufficient to understand how lipid consumption modulates sirtuins in humans. The best-characterized mechanism highlights oleic acid as a natural activator of SIRT1. Conclusion These results draw attention to a new field of interest in nutrition science. The possible activation of sirtuins by dietary fat manipulation may represent an important nutritional strategy for management of chronic and metabolic disease. Systematic Review Registration PROSPERO registration number CRD42018114456.

Recent studies argue that the use of virtual reality tasks depicting activities daily living may be effective means for cognitive rehabilitation. The aim of this study was to test an ecologically oriented approach in virtual reality resembling the demands of everyday life activities for cognitive rehabilitation following stroke.The sample comprised 30 sub-acute stroke patients recovering from stroke in a rehabilitation hospital. They were assessed in a single-arm pre-post intervention study on global cognition, executive functions, memory and attention abilities. The intervention consisted of virtual reality in a multidomain cognitive training approach depicting everyday life tasks (preparing food, choosing clothes, shopping, etc.).Improvements were found in the assessed cognitive domains at 6 to 10 post-treatment sessions. In-depth analysis through reliable change scores has suggested larger treatment effects on global cognition.Overall results suggest that the use of virtual reality-based exercises on everyday life activities may be a useful cognitive rehabilitation approach to provide short-term gains in cognition following stroke.Implications for rehabilitationVirtual reality-based cognitive rehabilitation resembling everyday life activities may provide short-term gains in cognition of stroke patients;Consistent improvements in executive functions may require higher treatment dosage than for improvements in global cognition.

Funda??o de Amparo ? Pesquisa e ao Desenvolvimento Cient?fico e Tecnol?gico do Maranh?o. Grant Numbers: 00971/17, 01352/16. Federal University of Maranh?o. Postgraduate Program in Health Science. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Department of Biology. Laboratory of Genetics and Molecular Biology. S?o Lu?s, MA, Brazil. Aldenora Bello Cancer Hospital. S?o Lu?s, MA, Brazil. Aldenora Bello Cancer Hospital. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Postgraduate Program in Health Science. S?o Lu?s, MA, Brazil / Federal University of Maranh?o. Department of Biology. Laboratory of Genetics and Molecular Biology. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Public Health Department. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Department of Pathology. Biology Undergraduate Course. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Postgraduate Program in Health Science. S?o Lu?s, MA, Brazil. Federal University of Maranh?o. Department of Pathology. Biology Undergraduate Course. S?o Lu?s, MA, Brazil. Federal University of Par?. Oncology Research Center. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Cultura de Tecido e citogen?tica. Ananindeua, PA, Brasil. Federal University of Maranh?o. Department of Physiological Sciences. S?o Lu?s, MA, Brazil. Faculdades Pequeno Pr?ncipe. Instituto de Pesquisa Pel? Pequeno Pr?ncipe. Curitiba, PR, Brazil / Georgetown Lombardi Comprehensive Cancer Center. Department of Oncology. Washington, District of Columbia, United States. Federal University of Maranh?o. Department of Biology. Laboratory of Genetics and Molecular Biology. S?o Lu?s, MA, Brazil. The incidence of penile cancer (PeCa) is increasing worldwide, however, the highest rates are reported in underdeveloped countries. The molecular mechanisms that underly the onset and progression of these tumors are still unclear. Therefore, our goal was to determine the genome?wide copy number alterations and the involvement of human papiloma virus (HPV) (TP53 and RB1), inflammatory (COX2 and EGFR), and PI3K/AKT pathway (AKT1, AKT2, EGFR, ERBB3, ERBB4, PIK3CA, and PTEN) associated genes in patients with PeCa from a high incidence region in Brazil (Maranh?o). HPV genotyping was performed by nest?PCR and genome sequencing, copy number alterations (CNAs) by array comparative genomic hybridization and gene copy number status, gene, and protein expression by quantitative polymerase chain reaction, reverse transcriptase?quantitative polymerase chain reaction, and immunohistochemistry, respectively. HPV genotyping revealed one of the highest frequencies of HPV reported in PeCa, affecting 96.4% of the cases. The most common CNAs observed were located at the HPV integration sites, such as 2p12?p11.2 and 14q32.33, where ADAM 6, KIAA0125, LINC00226, LINC00221, and miR7641?2, are mapped. Increased copy number of ERBB3 and EGFR genes were observed in association with COX2 and EGFR overexpression, reinforcing the role of the inflammatory pathway in PeCa, and suggesting anti?EGFR and anti?COX2 inhibitors as promising therapies for PeCa. Additionally, TP53 and RB1 messenger RNA downregulation was observed, suggesting the occurrence of other mechanisms for repression of these oncoproteins, in addition to the canonical HPV/TP53/RB1 signaling pathway. Our data reinforce the role of epigenetic events in abnormal gene expression in HPV?associated carcinomas and suggest the pivotal role of HPV driving CNAs and controlling gene expression in PeCa.

Postural control relies on three principal sensory systems: vision, vestibular and proprioceptive; that are affected by aging. When performing a cognitive task concomitantly with a motor task, those sensory impairments lead to even greater deleterious effects on balance. We aimed to study the effects of a sensory aid (a light touch) on a dual task paradigm and sought to understand the different responses on balance due to aging. Fifty healthy and highly physical active women were divided in two groups: young (N = 25, 24.2 ± 4.0 years) and older adults (N = 25, 67.3 ± 4.2 years). In a random and balanced order, all participants performed five tasks: Stroop test while seated (Seated); Stroop test while standing quiet (ST); Standing quiet (BL); Standing quiet with a haptic input (LT); and Stroop test with a haptic input while standing quiet (SL). In the Stroop test, older women committed more errors (50 vs 11 errors, p 0.001) and had higher reaction time (1.001 ± 0.191 vs 0.699 ± 0.081 s, p 0.001). The haptic input (LT) reduced all body sway parameters, in both groups, regardless the condition. This means that postural control under a dual task paradigm (ST) deleterious effect can be mitigated by a haptic input.

We describe 2 human cases of infection with a new Neisseria species (putatively N. brasiliensis), 1 of which involved bacteremia. Genomic analyses found that both isolates were distinct strains of the same species, were closely related to N. iguanae, and contained a capsule synthesis operon similar to N. meningitidis.

Portugal is one of the countries with the highest tuberculosis (TB) burden in the European Union. Patients who are receiving antitumor necrosis factor (TNF) treatment should be screened and treated for latent tuberculosis infection (LTBI). This study aimed to evaluate the prevalence of LTBI and the number of active TB cases in patients with inflammatory bowel disease (IBD) treated with anti-TNF agents.This was a retrospective study from a Portuguese center that included patients with IBD who started anti-TNF treatment between 2013 and 2017. LTBI screening was considered positive in case of positive tuberculin skin test, positive/indeterminate interferon gamma release test, or history of exposure to TB irrespective of the results of the screening.One hundred and seventeen patients were included, 56% female, mean age 40 years; 91% had Crohn's disease; infliximab was initiated in 79%, adalimumab in 21%, and golimumab in 1%. Of these, 37 (32%) presented LTBI - tuberculin skin test was positive in 18 (49%) patients; interferon gamma release test was positive in 14 (38%) patients and undetermined in seven (19%); and there was a history of exposure in 12 (32%) patients. All patients screened with LTBI were on isoniazid for 9 months. During follow-up (mean 21.6 months), one patient under infliximab developed pleural TB 5 years after receiving treatment with isoniazid. None of the patients with negative LTBI screening developed active TB.In this sample of patients with IBD, the prevalence of LTBI before starting anti-TNF treatment was significant (32%), but only one patient had active TB after LTBI treatment.

Objectives: Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers. Methods: Eighty-three patients fulfilling diagnostic criteria for HAM/TSP were submitted to a comprehensive clinical, cognitive and functional evaluation, brain magnetic resonance imaging and determination of levels of IL-1β, IL-6, TNF-α, immunoglobulins and HTLV-1 proviral load in blood and cerebrospinal fluid. The control group was composed of 88 cognitively healthy subjects, matched for age, sex and educational level. Results: Compared to healthy subjects, HAM/TSP patients displayed significant global cognitive impairment and executive function deficits. HAM/TSP cognitive impairment was significantly associated with altered levels of IgM, IgG, IL-6 and TNF-α in blood. There was no association between HAM/TSP cognitive impairment and HTLV-1 proviral load. Conclusions: This study suggests cognitive impairment may be a long-term clinical manifestation of HTLV-1 infection, which seems to be linked to the persistent inflammatory activity that is found in the disease. Keywords: HTLV-1, Cognitive assessment, Tropical spastic paraparesis, Inflammation

The consumption of ultra-processed foods (UPF) has been associated with cardiometabolic risk factors. However, there is scarce literature on the association between UPF consumption, cardiovascular events, and cardiometabolic risk factors in subjects undergoing secondary care for cardiovascular diseases (CVD). Thus, we aimed to evaluate the association between UPF consumption, CVD, and cardiometabolic risk factors in subjects with established CVD. Baseline data from 2,357 subjects participating in a Brazilian multicenter study were analysed finding a mean UPF consumption of 18.7% of their energy intake. Higher figures of UPF consumption were founded associated with an increased presence of high waist circumference, overweight, peripheral arterial disease, and with a decreased odds of the simultaneous presence of coronary arterial disease, peripheral arterial diseases, and stroke when comparing among tertiles of UPF contribution to energy intake. These associations were observed when analyzing the whole sample and women but not men. Thus, these findings should help improve strategies for CVD patients in secondary care.

Objective:To evaluate the association of dietary inflammatory index (DII®) with the occurrence of cardiovascular events, cardiometabolic risk factors and with the consumption of processed, ultra-processed, unprocessed or minimally processed foods and culinary ingredients.Design:This was a cross-sectional study that analysed the baseline data from 2359 cardiac patients. Data on socio-demographic, anthropometric, clinical and food consumption were collected. Energy-adjusted food intake data were used to calculate DII, and the foods were classified according to the NOVA classification. Furthermore, the patients were grouped according to the number (1, 2 or ≥ 3) of manifested cardiovascular events. The data were analysed using linear and multinomial logistic regression.Settings:Multicentre study from Brazil.Participants:Patients with established cardiovascular events from the Brazilian Cardioprotective Nutritional Program Trial evaluated at baseline.Results:Most of the patients were male (58·8 %), older adults (64·2 %) and were overweight (68·8 %). Patients in the third tertile of DII (DII > 0·91) had were more likely to have 2 (OR 1·27, 95 % CI: 1·01–1·61) and ≥ 3 (OR 1·39, 95 % CI: 1·07–1·79) cardiovascular events, with poor cardiometabolic profile. They also were more likely to consume a higher percentage of processed, ultra-processed and culinary ingredients foods consumption compared with the patients in the first DII tertile (DII ≤ 0·91).Conclusion:A more pro-inflammatory diet is associated with a greater chance of having 2 and ≥ 3 cardiovascular events and cardiometabolic risk factors and were more likely to consume processed, ultra-processed and culinary ingredients compared to those with a more anti-inflammatory diet.

International audience; Background: The multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains. Methods: A total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB. Results: Serogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%. Conclusion: This is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination.

Background Invasive meningococcal disease (IMD) is an acute, highly transmissible and potentially fatal disease caused by Neisseria meningitidis. Prompt antimicrobial therapy and prophylaxis are recommended, where penicillin or ciprofloxacin are the available choices. However, the emergence of resistant isolates of N. meningitidis poses a challenge for antimicrobial therapy. Objectives To describe the clinical, epidemiological and biological characteristics of six penicillin- and ciprofloxacin-resistant, culture-confirmed IMD cases reported in El Salvador, Central America, between 2017 and 2019. Methods Following the detection of six patients presenting with IMD in El Salvador, clinical data were collected and epidemiological action plans conducted. Isolates were subjected to antimicrobial susceptibility testing by broth microdilution and WGS for genotyping and molecular characterization analysis, including phylogeny comparison with global sequences available from public databases. Results A total of six IMD cases caused by N. meningitidis serogroup Y, resistant to both penicillin (MIC >8.0 mg/L) and ciprofloxacin (MIC 0.125 mg/L), were detected from 2017 to 2019. Genomic analysis showed that penicillin resistance was mediated by the production of β-lactamase ROB-1. Ciprofloxacin resistance was attributed to an amino acid substitution in DNA gyrase (T91I). All isolates were classified as ST3587, clonal complex 23, and were genetically highly similar, based on core-genome SNP analysis. Conclusions To the best of our knowledge, we report the first cases of MDR N. meningitidis causing IMD in Latin America. Our findings highlight the emergence of this potential public health threat, with a profound impact on the efficacy of IMD treatment and prophylaxis protocols.

This study is focused on the development of a nanodevice for loading and release of 5-Fluorouracil (5-FU) with a view to improving its therapeutic efficiency, using as strategy the fabrication of a nanoconjugate through drug anchorage on the surface of carbon quantum dots (CQD). Several physicochemical and analytical techniques were employed to obtain information about materials morphology, structure, and optical properties. The results indicated that the interactions between both entities resulted in good physicochemical properties and photostability. Acid pH favored drug release, indicating a tendency to release 5-FU from 5-FU-CQD into the tumor microenvironment. The cytotoxicity of CQD and 5-FU-CQD nanoconjugate was evaluated against normal human lung fibroblast (GM07492A) and human breast cancer (MCF-7) cell lines. The CQD was non-toxic, indicating that these materials are biocompatible and can be used as a nanocarrier for 5-FU in biological systems. For the 5-FU-CQD nanoconjugate, it was observed a reduction in toxicity for normal cells compared to free 5-FU, suggesting that drug anchoring in CQD reduced drug-associated toxicity, while for cancer cells exhibited an antitumor effect equivalent to that of the free drug, opening perspectives for the application of this material in anticancer therapy.

Background Brazil is the world’s fifth most populous nation, and is currently experimenting a fast demographic aging process in a context of scarce resources and social inequalities. To understand the health profile of older adults in Brazil is fundamental for planning public policies. Methods The estimates were derived from data obtained through the collaboration between the Brazilian Ministry of Health and the Institute of Health Metrics and Evaluation of the University of Washington. The Brazilian Institute of Geography and Statistics provided the population estimates. Data on causes of death came from the Mortality Information System. To calculate morbidity, population-based studies on the prevalence of diseases in Brazil were comprehensively searched, in addition to information obtained from national databases such as the Hospital Information System, the Outpatient Information System, and the Injury Information System. We presented the Global Burden of Disease (GBD) 2017 estimates among Brazilian older adults (60+ years old) for life expectancy at birth (LE), healthy life expectancy (HALE), cause-specific mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life years (DALYs), from 2000 to 2017. Results LE at birth significantly increased from 71.3 years (95% UI to 70.9-71.8) to 75.2 years (95% UI 74.7-75.7). There was a trend of increasing HALE, from 62.2 years (95% UI 59.54-64.5) to 65.5 years (95% UI 62.6-68.0). The proportion of DALYs among older adults increased from 7.3 to 10.3%. Chronic noncommunicable diseases are the leading cause of death among middle aged and older adults, while Alzheimer’s disease is a leading cause only among older adults. Mood disorders, musculoskeletal pain, and hearing or vision losses are among the leading causes of disability. Conclusions The increase in LE and the decrease of the DALYs rates are probably results of the improvement of social conditions and health policies. However, the smaller increase of HALE than LE means that despite living more, people spend a substantial time of their old age with disability and illness. Preventable or potentially controllable diseases are responsible for most of the burden of disease among Brazilian older adults. Health investments are necessary to obtain longevity with quality of life in Brazil.

As the most abundant neuropeptides in Central Nervous System, Substance P and Neuropeptide Y are arguably involved in the response to brain trauma. This study aims to characterize a new concept of multi-staged neuropeptide response to TBI. This study assessed Substance P, Neuropeptide Y, S100B, standard inflammatory parameters and ionic disturbance in TBI victims, with and without intracranial lesions, and healthy controls. In the group with intracranial lesions, blood samples were drawn until 6 h after initial trauma, at 48 h and 7 days post-TBI. An early increase in Substance P (mean 613.463 ± 49.055 SE 6 h post-TBI with brain contusions vs. 441.441 ± 22.572 SE pg/dL control group) is evident. Concerning TBI without intraparenchymatous lesions, an increase in substance P is also present (825.60 ± 23.690 SE pg/dL). Following an initial increase and subsequent fall in NPY levels (45.997 ± 4.96 SE 6 h post-TBI vs. 32.395 ± 4.056 SE 48 h post-TBI vs. 19.700 ± 1.462 SE pg/mL control group), a late increase in NPY is obvious (43.268 ± 6.260 SE pg/mL 7 day post-TBI). Post-traumatic hypomagnesemia (0.754 ± 0.015 SE 6 h post-TBI vs. 0.897 ± 0.021 SE mmol/L control group) and a peak in S100B (95.668 ± 14.102 SE 6 h post-TBI vs. 30.187 ± 3.347 SE pg/mL control group) are also present. A multi-staged neuropeptide response to TBI is obvious and represents a potential therapeutic strategy for the treatment of intraparenchymal lesions and cerebral edema following TBI.

International audience; Hazelnuts (Corylus avellanaL.) have an important role in human nutrition and health. However, they are a common cause of food allergy. Due to hazelnut varietal diversity, variety-dependent differences in the IgE-binding properties may be suspected, which could allow therapeutic strategies based on the use of hypoallergenic varieties to induce desensitization. In a proteogenomic approach, we aimed to evaluate the allergenic potential of a genetically diverse set of hazelnuts (n = 13 varieties). Minor differences were found at the level of genes encoding important allergens, namely Cor a 8, Cor a 9, and Cor a 14. Nevertheless, IgE-reactivity was similar for all varieties using sera from seven allergic individuals. The predominant IgE-reactive proteins were Cor a 9 (100%) and Cor a 1.04 (60%), with the former being the most frequently identified by a two-dimensional gel electrophoresis (2-DE)-based proteomic approach. Therefore, it seems that the conventional exclusion diet will hold its ground for the time being.

Evidence from epidemiological and clinical studies suggests that nut consumption provides satiety and may contribute to the management of obesity. However, the effect of acute intake of nuts on appetite responses remains unclear. The objective of this study was to evaluate the acute effect of a shake containing 30 g of cashew nuts (Anacardium occidentale L.) and 15 g of Brazil nuts (Bertholletia excelsa H.B.K) on appetite responses in overweight subjects. This was a clinical, randomized, controlled, single-blind, cross-over, pilot study. On two non-consecutive test days, 15 subjects received a shake containing nuts, and a shake absent of nuts matched for energy and macronutrient content. Subjective appetite sensation was evaluated by visual analogue scales (VAS). Food intake was measured by weighing the lunch served at the end of each morning-test, which subjects ate ad libitum. Total energy intake was estimated by food records. This study is registered on the Brazilian Registers of Clinical Trials—ReBEC (protocol: U1111-1203-9891). We observed no significant difference in subjective appetite sensations between the groups. Food intake at lunch, as well as energy intake throughout the day also did not differ between the treatments. Our results suggest that the acute intake of a shake containing nuts was not able to enhance satiety, compared to a shake matched for energy and macronutrient content. Further studies are warranted to elucidate the satiety mechanisms of nuts intake.

Background: Motor functional neurological disorder (mFND) is a common and disabling condition. There are no evidence-based guidelines for treatment. Long-term outcome is often poor. This study describes the epidemiological profile, symptom pattern and outcome of patients admitted to the Belo Horizonte unit of the SARAH Network of Rehabilitation Hospitals from 1997 to 2018 with functional motor symptoms resulting from functional neurological disorder. Methods: This retrospective study reviewed data from 185 patients who met inclusion criteria for mFND. Diagnoses were made by multiple professionals in the presence of positive signs and excluding other neurological and systemic conditions. Results: 75.1% were women; 48.3% were receiving social security benefits. The youngest was 3 years old, the oldest 69. 23.8% were in wheelchairs, 77.2% had psychiatric disorders, 69.7% participated in rehabilitation programs and, among them, 70% improved. Conclusion: Participation in rehabilitation is beneficial for patients with mFND. Symptoms lasting for less than 30 days and aged less than 18 years had better outcomes (p

As the most abundant neuropeptides in Central Nervous System, Substance P and Neuropeptide Y are arguably involved in the response to brain trauma. This study aims to characterize a new concept of multi-staged neuropeptide response to TBI.This study assessed Substance P, Neuropeptide Y, S100B, standard inflammatory parameters and ionic disturbance in TBI victims, with and without intracranial lesions, and healthy controls. In the group with intracranial lesions, blood samples were drawn until 6 h after initial trauma, at 48 h and 7 days post-TBI.An early increase in Substance P (mean 613.463 ± 49.055 SE 6 h post-TBI with brain contusions vs. 441.441 ± 22.572 SE pg/dL control group) is evident. Concerning TBI without intraparenchymatous lesions, an increase in substance P is also present (825.60 ± 23.690 SE pg/dL). Following an initial increase and subsequent fall in NPY levels (45.997 ± 4.96 SE 6 h post-TBI vs. 32.395 ± 4.056 SE 48 h post-TBI vs. 19.700 ± 1.462 SE pg/mL control group), a late increase in NPY is obvious (43.268 ± 6.260 SE pg/mL 7 day post-TBI). Post-traumatic hypomagnesemia (0.754 ± 0.015 SE 6 h post-TBI vs. 0.897 ± 0.021 SE mmol/L control group) and a peak in S100B (95.668 ± 14.102 SE 6 h post-TBI vs. 30.187 ± 3.347 SE pg/mL control group) are also present.A multi-staged neuropeptide response to TBI is obvious and represents a potential therapeutic strategy for the treatment of intraparenchymal lesions and cerebral edema following TBI.

Purpose. To describe the antimicrobial resistance profile of Neisseria meningitidis isolates causing invasive disease in Brazil from 2009 to 2016. Methodology. Among 3548 N. meningitidis isolates received, 2888 (81.4 %) were analysed for antimicrobial resistance using the broth microdilution technique, as recommended by the Clinical and Laboratory Standards Institute. Isolates were tested for ciprofloxacin, chloramphenicol, ceftriaxone, penicillin G, ampicillin and rifampin. Results. All the isolates tested were susceptible to ceftriaxone, while 953 (33.0 %), 1307 (45.3 %) and 2 (0.07 %) isolates were penicillin G-, ampicillin- and rifampin-intermediate, respectively. Resistance to rifampin, ciprofloxacin and chloramphenicol was shown by three isolates (0.1 %), two isolates (0.07 %) and one (0.03 %) isolate, respectively. Although no isolates were resistant to penicillin G in the period of 2009–2016, our results show an upward trend in minimum inhibitory concentrations (MICs) for this drug as of 2010 (P

Made available in DSpace on 2022-04-29T08:36:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 Objective: Patterns of cytokine levels and their association with stroke severity, infarct size, and muscle strength are obscure. We aimed to analyze the immune mediators linked to T helper (Th)1, Th2, Th17, and regulatory T cell patterns and their association with stroke severity, infarct size, and muscle strength. Materials and methods: We included patients with acute stroke (n = 15) and healthy non-disabled individuals (n = 20) aged > 18 years. The dependent variables were stroke severity according to the National Institute of Health Stroke Scale (NIHSS), infarct size on computed tomography, handgrip strength by dynamometry, and global muscle strength according to the Medical Research Council (MRC) scale. The independent variables were the circulating cytokine levels. The cytokine levels were compared between the groups, and correlations between the clinical data were verified. Results: The stroke group had higher interleukin (IL)-6 (p < 0.0001) and IL-10 (p < 0.0001) levels, but lower tumor necrosis factor (TNF)-α (p = 0.036) levels than the control group. IL-10 and soluble tumor necrosis factor receptor (sTNF-RII) levels were correlated with each other (r = 0.533; p = 0.042) and infarct size (r = 0.653; p = 0.033 and r = 0.689; p = 0.018, respectively). MRC scores were positively and negatively correlated with handgrip strength of the affected side (r = 0.78; p = 0.001) and NIHSS scores (r = -0.87; p < 0.0001), respectively. Conclusions: Plasma levels of some cytokines were associated with changes in the acute phase of stroke, and IL-10 and sTNF-RII levels are potential biomarkers of infarct size. Department of Applied Physical Therapy Federal University of Triângulo Mineiro Department of Microbiology Immunology and Parasitology Federal University of Triângulo Mineiro Department of Neurology Psychology and Psychiatry Botucatu Medical School Clinics Hospital of the Federal University of Triângulo Mineiro Department of Neurology Psychology and Psychiatry Botucatu Medical School

The metabolic effects of cranberry and blueberry consumption on glycemic control have been evaluated in vitro and in animal models as well as in human studies, although findings have not been syste...

Background/Aims: Peritoneal protein loss (PPL) is associated with cardiovascular disease and mortality in peritoneal dialysis (PD). Controversial results have been published about the effect of paricalcitol in PPL among PD patients. This study intends to analyze the relationship between paricalcitol and PPL in PD. Methods: In a retrospective study, prevalent PD patients were divided into 2 groups: “with paricalcitol” and “without paricalcitol”. X2-test, Student’s t test, Pearson correlation coefficient and Logistic Regression analysis were applied. Results: Eighty-two patients were included. PPL was lower among patients medicated with paricalcitol (5.17 ± 1.71 vs. 6.79 ± 2.10 g/24 h, p = 0.0001). In multivariate analysis, paricalcitol and dialysate/plasma ratio of creatinine (D/P creatinine) were independently related to PPL (OR 4.270 [1.437–12.684], p = 0.009 and OR 0.205 [0.064–0.659], p = 0.008, respectively), adjusted for diabetes. Conclusion: Paricalcitol and D/P creatinine were independently related to PPL. Paricalcitol may have an effect on PPL in PD patients

Objectives Dietary total antioxidant capacity (dTAC) has been introduced as a useful tool to quantify the antioxidant content of a diet. However, few studies have evaluated the association of dTAC with cardiovascular disease (CVD) occurrence and cardiometabolic risk factors in people with established CVD events. Thus, we aimed to investigate the presence of an association between dTAC values, cardiovascular events, and cardiometabolic risk factors in individuals with previous CVD in a Brazilian multicenter study. Methods This study has a cross-sectional design. We evaluated baseline data from the Brazilian Cardioprotective Nutritional Program Trial. Sociodemographic, anthropometric, clinical, and food-consumption data were collected in face-to-face interviews. We estimated dTAC from the mean of two 24-h dietary recalls by values of ferric-reducing antioxidant power. Results We evaluated 2346 participants, most of whom were men (58.4%), older adults (64.2%), and overweight (68.6%), and had coronary artery disease (92.4%). The mean dTAC was equal to 5.6 (interquartile range, 3.9-7.8) mmol/1000 kcal. Participants in the third dTAC tertile (9.2 mmol/1000 kcal) had a 22%, 59%, and 69% lower chance, respectively, of having hypertriglyceridemic waist phenotype, abdominal aortic aneurysm, and amputation due to arterial disease in comparison to the first tertile (3.4 mmol/1000 kcal). Conclusions The dTAC was inversely associated with hypertriglyceridemic waist phenotype, abdominal aortic aneurysm, and amputation due to arterial disease in individuals undergoing secondary care for CVD. Our results can guide strategies for the prevention of new CVD and its consequences.

Clinical and endoscopic remissions constitute the therapeutic goals in ulcerative colitis (UC). Histological healing is currently not a target in UC. This study aims to determine the impact of the definition of endoscopic remission (Mayo endoscopic subscore [MSe] 0-1) and histological activity in the recurrence of UC and recurrence-free survival time.Patients with UC in clinical remission (partial Mayo score ≤ 1) and endoscopic remission (MSe ≤ 1) who underwent colonoscopy with biopsies between March 2010 and December 2013 were included. The validated Nancy score was used to evaluate histological activity, which considers inactivity if 0 to 1 and activity if 2 to 4. The recurrence-free time was evaluated and recurrence was defined as partial Mayo score ≥ 2, therapy to induce remission, hospitalization, or colectomy. Predictive factors associated with recurrence and time to recurrence were determined.Sixty patients were included; 58.3% (n = 35) were women, with a mean age of 52.7 years. MSe = 1 was observed in 46.7% (n = 28) and histological activity in 38.3% (n = 23). Clinical recurrence occurred in 31.7% (n = 19) of patients, with a cumulative risk of 17.1%/24.5%/26.7%/40.1% at 12/24/36/48 months, respectively. MSe = 1 (P = 0.02) and histological activity (P = 0.007) were significantly associated with recurrence. Of these, only histological activity (P = 0.03) was an independent predictive factor of recurrence. Patients with MSe = 1 (P = 0.02) and with histological activity (P = 0.01) had a significantly shorter recurrence-free time in univariate analysis. In multivariate analysis, only histological activity (P = 0.02) was an independent predictive factor of lower recurrence-free time.The presence of histological activity represents an independent predictive factor of recurrence and time to recurrence, which was not verified with MSe 0 to 1.

The aim of the present study was to investigate the relationship between serum phosphate levels, clinical parameters, body composition, and mortality.Multicenter longitudinal observational study of a cohort of 3552 patients in hemodialysis (HD) from 34 Nephrocare dialysis units in Portugal with 24 months of follow-up. Patients were divided into three groups depending on their serum phosphorus (3.5; 3.5-5.5;5.5 mg/dL). Statistical tests were performed with SPSS, version 20.0. A p 0.05 was considered significant.On the one hand, hypophosphatemia was significantly associated with better dialysis adequacy, higher age and overhydration. On the other hand, it was associated with lower albumin, protein intake, creatinine, hemoglobin, calcium, potassium, magnesium, body mass index (BMI), body cell mass index, fat tissue index and lean tissue index. These patients had lower survival rates compared with those with normo- and hyperphosphatemia. Hypophosphatemia was a predictor of death when adjusted for age, diabetes, HD vintage, gender, and Kt/V. Comparing the mortality predictors in hypo- and hyperphosphatemia, we found that low albumin, BMI, and high overhydration increased the mortality risk in the hypophosphatemic group, whereas in hyperphosphatemic patients data were not statistically significant.Currently, a high prevalence of hypophosphatemia exists in Portuguese HD patients. This condition is associated with worst nutritional and body composition parameters. In the context of additional indices of malnutrition (low albumin, low BMI or severe overhydration), hypophosphatemic patients presented higher mortality risk.

Objective Our objective was to perform a systematic review and meta-analysis of cohort studies evaluating the triglyceride-glucose (TyG) index as a tool for type 2 diabetes (T2D) prediction in adults and older adults. Methods Studies were identified in PubMed, Cochrane, Scopus, and Lilacs. Studies with cohort design, which evaluated the T2D incidence through the hazard ratio (HR) or relative risk (RR) or odds ratio values were included. Were included both studies that evaluated the incidence of T2D from tertiles, quartiles, quintiles, or single TyG index values. First, a meta-analysis only for studies that reported data in HR values was performed. Additionally, given the different association measurements used, the number of T2D cases, non-T2D cases, and the total number of participants were extracted from exposed and non-exposed groups when available. Then the risk ratio was calculated. A meta-analysis using the inverse variance method and the random-effects model was performed. Heterogeneity was assessed by I2 statistics and by inspecting funnel plots. Results Thirteen cohort studies with a total of 70,380 subjects, both sexes, adults, and older adults were included in the meta-analysis. Ten studies showed a significant association of the TyG index with T2D risk through HR estimative (overall HR: 2.44, 95% CI: 2.17–2.76). After estimating RR for nine studies, we also observed a significant association of the TyG index with T2D risk (RR: 3.12, 95 CI: 2.31–4.21). For all analyses, high heterogeneity was verified by I2 and visual inspection of funnel plots. Conclusions TyG index has a positive and significant association with T2D risk, suggesting that the TyG index may become an applicable tool to identify subjects with T2D risk. However, due to the high heterogeneity observed in overall HR and RR analysis, more studies could be necessary to confirm these results.

The consumption of food with MUFA has been associated with improvement of inflammation and oxidative stress in overweight individuals. In the present study, we evaluate the effect of high-oleic peanut intake within a hypoenergetic diet on inflammatory and oxidative status markers in overweight men. Sixty-four overweight men (BMI 26–35 kg/m2, 18–50 years old) participated in this randomised controlled study for 4 weeks, allocated into three groups: control (CT,n22), conventional peanut (CVP,n21) and high-oleic peanut (HOP,n21). They followed a hypoenergetic diet (−250 kcal/d; −1045 kJ/d) with or without 56 g of high-oleic or conventional peanuts. After the intervention, the inflammatory markers did not show significant changes in fasting concentrations or postprandial response among the experimental groups (P> 0·05). The activity of oxidative status markers remained unchanged after the intervention. However, in the CT, malondialdehyde showed lower concentration in comparison with the baseline (P= 0·020) and among the groups (P= 0·002). In the present study, the daily intake of high-oleic peanuts within a hypoenergetic diet did not modify the inflammatory markers and oxidative status in overweight men. More studies are needed to better understand the effect of high-oleic peanut intake on health outcomes.

Background The triglyceride-glucose index (TyG index) is a tool for insulin resistance evaluation, however, little is known about its association with coronary artery disease (CAD), which is the major cardiovascular death cause, and what factors may be associated with TyG index. Objective To evaluate the association between the TyG index and the prevalence of CAD phases, as well as cardiovascular risk factors. Methods The baseline data of patients in secondary care in cardiology from Brazilian Cardioprotective Nutritional Program Trial (BALANCE Program Trial) were analyzed. Anthropometric, clinical, socio-demographic and food consumption data were collected by trained professionals. The TyG index was calculated by the formula: Ln (fasting triglycerides (mg/dl) × fasting blood glucose (mg/dl)/2) and regression models were used to evaluate the associations. Results We evaluated 2330 patients, which the majority was male (58.1%) and elderly (62.1%). The prevalence of symptomatic CAD was 1.16 times higher in patients classified in the last tertile of the TyG index (9.9 ± 0.5) compared to those in the first tertile (8.3 ± 0.3). Cardiometabolic risk factors were associated with TyG index, with the highlight for higher carbohydrate and lower lipid consumption in relation to recommendations that reduced the chance of being in the last TyG index tertile. Conclusion The TyG index was positively associated with a higher prevalence of symptomatic CAD, with metabolic and behavioral risk factors, and could be used as a marker for atherosclerosis. Trial registration ClinicalTrials.gov identifier: NCT01620398. Registered 15 June, 2012

The aim of the study was to investigate the effects of two pelvic floor exercise programs on lower urinary tract symptoms and quality of life in participants with multiple sclerosis.This is a prospective, single-blind, clinical trial.The study used a community rehabilitation program within a large metropolitan health service.Thirty women in moderate stage of multiple sclerosis were referred for outpatient rehabilitation.In a period of 6 mos, participants underwent a pelvic floor exercise program, associated or not with vaginal electrotherapy.The main outcomes are overactive bladder, perineal contraction, and quality of life.The findings showed benefits of both programs on overactive bladder and quality of life. Participants undergoing exercise plus electrotherapy presented greater improvement on contraction of the perineal musculature and quality of life.Six months of exercise provided benefits on lower urinary tract symptoms and quality of life in women with multiple sclerosis. Electrical stimulation potentiated the improvement on perineal musculature and quality of life. This trial was registered prospectively with the Clinical Trials Register, ID: BR-287q65 (http://www.ensaiosclinicos.gov.br/rg/RBR-287q65/).

Background: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. Methods: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2&ndash, 3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. Results: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications, eccentric hypertrophy (p = 0.050), concentric hypertrophy (p = 0.041), and serum phosphate &ge, 3.6 mg/dL (p = 0.025), FGF-23 &ge, 168 (p = 0.0149), &alpha, klotho &lt, 313 (p = 0.044). Conclusions: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.

Background: Appropriate dietary recommendations represent a key part of secondary prevention in cardiovascular disease (CVD). We evaluated the effectiveness of the implementation of a nutritional program on quality of diet, cardiovascular events, and death in patients with established CVD. Methods: In this open-label, multicenter trial conducted in 35 sites in Brazil, we randomly assigned (1:1) patients aged 45 years or older to receive either the BALANCE Program (experimental group) or conventional nutrition advice (control group). The BALANCE Program included a unique nutritional education strategy to implement recommendations from guidelines, adapted to the use of affordable and regional foods. Adherence to diet was evaluated by the modified Alternative Healthy Eating Index. The primary end point was a composite of all-cause mortality, cardiovascular death, cardiac arrest, myocardial infarction, stroke, myocardial revascularization, amputation, or hospitalization for unstable angina. Secondary end points included biochemical and anthropometric data, and blood pressure levels. Results: From March 5, 2013, to Abril 7, 2015, a total of 2534 eligible patients were randomly assigned to either the BALANCE Program group (n = 1,266) or the control group (n = 1,268) and were followed up for a median of 3.5 years. In total, 235 (9.3%) participants had been lost to follow-up. After 3 years of follow-up, mean modified Alternative Healthy Eating Index (scale 0-70) was only slightly higher in the BALANCE group versus the control group (26.2 ± 8.4 vs 24.7 ± 8.6, P

Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.

Neisseria meningitidis is an important cause of meningococcal disease globally. Sequence type (ST)-11 clonal complex (cc11) is a hypervirulent meningococcal lineage historically associated with serogroup C capsule and is believed to have acquired the W capsule through a C to W capsular switching event. We studied the sequence of capsule gene cluster (cps) and adjoining genomic regions of 524 invasive W cc11 strains isolated globally. We identified recombination breakpoints corresponding to two distinct recombination events within W cc11: A 8.4-kb recombinant region likely acquired from W cc22 including the sialic acid/glycosyl-transferase gene, csw resulted in a C→W change in capsular phenotype and a 13.7-kb recombinant segment likely acquired from Y cc23 lineage includes 4.5 kb of cps genes and 8.2 kb downstream of the cps cluster resulting in allelic changes in capsule translocation genes. A vast majority of W cc11 strains (497/524, 94.8%) retain both recombination events as evidenced by sharing identical or very closely related capsular allelic profiles. These data suggest that the W cc11 capsular switch involved two separate recombination events and that current global W cc11 meningococcal disease is caused by strains bearing this mosaic capsular switch.

International audience; Kitoza refers to a traditional way of preparing beef and pork in Madagascar. However, in order to improve some drawbacks previous identified, the product was submitted to a reengineering process. The acceptance and sensory profiling of improved Kitoza products among Portuguese consumers was investigated. A local smoked loin sausage was selected as basis for comparison. Firstly, a Focus Group study was performed to identify sensory descriptors for Kitoza products and explore product perception. Subsequently, a Flash Profile and a consumer sensory acceptance study were conducted. Flash Profile's results showed that beef-and pork-based Kitoza products investigated differed considerably in all sensory dimensions. The Portuguese sausage was characterized as having a more intense and lasting after taste, as well as displaying a higher degree of (meat) doneness. The acceptance study yielded higher overall liking ratings for pork-than for beef-based Kitoza, although the Portuguese sausage remained the most appreciated product.

Background Neisseria meningitidis serogroup B remains a prominent cause of invasive meningococcal disease (IMD) in Brazil. Because two novel protein-based vaccines against serogroup B are available, the main purpose of this study was to provide data on the diversity and distribution of meningococcal vaccine antigen types circulating in Brazil. Methodology Genetic lineages, vaccine antigen types, and allele types of antimicrobial-associated resistance genes based on whole-genome sequencing of a collection of 145 Neisseria meningitidis serogroup B invasive strains recovered in Brazil from 2016 to 2018 were collected. Results A total of 11 clonal complexes (ccs) were identified among the 145 isolates, four of which were predominant, namely, cc461, cc35, cc32, and cc213, accounting for 72.0% of isolates. The most prevalent fHbp peptides were 24 (subfamily A/variant 2), 47 (subfamily A/variant 3), 1 (subfamily B/variant 1) and 45 (subfamily A/variant 3), which were predominantly associated with cc35, cc461, cc32, and cc213, respectively. The NadA peptide was detected in only 26.2% of the isolates. The most frequent NadA peptide 1 was found almost exclusively in cc32. We found seven NHBA peptides that accounted for 74.5% of isolates, and the newly described peptide 1390 was the most prevalent peptide exclusively associated with cc461. Mutated penA alleles were detected in 56.5% of the isolates, whereas no rpoB and gyrA mutant alleles were found. Conclusion During the study period, changes in the clonal structure of circulating strains were observed, without a predominance of a single hyperinvasive lineage, indicating that an epidemiologic shift has occurred that led to a diversity of vaccine antigen types in recent years in Brazil.

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013.The carriage survey was conducted among 531 children, aged 12 months to24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only.No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8-1.8%) and 95.5% (19.8-0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6-44.8%) and 185% (19.6-55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2-0.6%, p 0.001) and increase in serotype 19A (1.8-6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values.After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.

Background: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. Methods: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. Results: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. Conclusions: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates. This work was supported by GlaxoSmithKline Biologicals SA,including all costs associated with the development and publishingof the manuscript. info:eu-repo/semantics/publishedVersion

Dendritic cells (DCs) are the most efficient antigen-presenting cells and link the innate immune sensing of the environment to the initiation of adaptive immune responses, which may be directed to either acceptance or elimination of the recognized antigen. In cancer patients, though DCs would be expected to present tumor antigens to T lymphocytes and induce tumor-eliminating responses, this is frequently not the case. The complex tumor microenvironment subverts the immune response, blocks some effector mechanisms, and drives others to support tumor growth. Chronic inflammation in a tumor microenvironment is believed to contribute to the induction of such regulatory/tolerogenic response. Among the various mediators of the modulatory switch in chronic inflammation is the “antidanger signal” chaperone, heat shock protein 27 (Hsp27), that has been described, interestingly, to be associated with cell migration and drug resistance of breast cancer cells. Thus, here, we investigated the expression of Hsp27 during the differentiation of monocyte-derived DCs (Mo-DCs) from healthy donors and breast cancer patients and evaluated their surface phenotype, cytokine secretion pattern, and lymphostimulatory activity. Surface phenotype and lymphocyte proliferation were evaluated by flow cytometry, interferon- (IFN-) γ, and interleukin- (IL-) 10 secretion, by ELISA and Hsp27 expression, by quantitative polymerase chain reaction (qPCR). Mo-DCs from cancer patients presented decreased expression of DC maturation markers, decreased ability to induce allogeneic lymphocyte proliferation, and increased IL-10 secretion. In coculture with breast cancer cell lines, healthy donors’ Mo-DCs showed phenotype changes similar to those found in patients’ cells. Interestingly, patients’ monocytes expressed less GM-CSF and IL-4 receptors than healthy donors’ monocytes and Hsp27 expression was significantly higher in patients’ Mo-DCs (and in tumor samples). Both phenomena could contribute to the phenotypic bias of breast cancer patients’ Mo-DCs and might prove potential targets for the development of new immunotherapeutic approaches for breast cancer.

We aimed to investigate the nasopharyngeal colonization (NPC) by Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in the elderly population and to assess the demographic factors associated with NPC. This was an observational cohort study in which outpatients aged ≥60 years were enrolled from April to August 2017, with a follow-up visit from September through December 2017. Nasopharyngeal (NP) swabs were collected, bacteria were detected and isolated, and isolates were subjected to phenotypic and molecular characterization using standard microbiological techniques. At enrolment, the rates of S. aureus, methicillin-resistant S. aureus (MRSA), H. influenzae, and S. pneumoniae among 776 elderly outpatients were 15.9%, 2.3%, 2.5%, and 2.2%, respectively. Toxin production was detected in 21.1% of methicillin-susceptible S. aureus, and three SCCmec types were identified: II/IIb, IVa, and VI. At the follow-up visit, all carriage rates were similar (p > 0.05) to the rates at enrolment. Most of S. pneumoniae serotypes were not included in pneumococcal conjugate vaccines (PCVs), except for 7F, 3, and 19A. All strains of H. influenzae were non-typeable. Previous use of antibiotics and 23-valent pneumococcal polysaccharide vaccination (p < 0.05) were risk factors for S. aureus and MRSA carriage; S. aureus colonization was also associated with chronic kidney disease (p = 0.021). S. pneumoniae carriage was associated with male gender (p = 0.032) and an absence of diabetes (p = 0.034), while not receiving an influenza vaccine (p = 0.049) and chronic obstructive pulmonary disease (p = 0.031) were risk factors for H. influenzae colonization. The frailty of study participants was not associated with colonization status. We found a higher S. aureus carriage rate compared with the S. pneumoniae- and H. influenzae-carriage rates in a well-attended population in a geriatric outpatient clinic. This is one of the few studies conducted in Brazil that can support future colonization studies among elderly individuals.

Monosodium l-glutamate (MSG)-induced obesity is a useful model for non-alcoholic fatty liver disease (NAFLD) studies. However, there is limited data on its initiation and progression. Thus, this study aimed to characterize the onset of metabolic and histopathological features of NAFLD and its progression to non-alcoholic steatohepatitis (NASH) in this model. To perform this study, Swiss mice pups were neonatally injected with MSG (4 g/kg/day, s.c.) or equiosmolar saline and followed up to 60, 120 or 180 days old. At each age, blood, liver, as well as periepididymal and retroperitoneal fat pads were collected for morphometric, biochemical and histological analyses, the later according to NAFLD activity score. MSG mice presented hypertriglyceridemia and central obesity at all ages, but peripheral insulin-resistance was verified only in 120- and 180-day-old mice. Hepatic total fat and triglycerides content were higher in MSG mice at all ages. Accordingly, histopathological analysis showed that 60-day-old MSG mice had microvesicular steatosis with occasional ballooning, which evolved into NASH from 120 days old. Retroperitoneal fat accumulation was the only variable to independently correlate with NAFLD activity total score upon multivariate analysis (R 2=71.45%). There were no differences in IL-6 and TNF-α serum levels among groups. Overall, this study shows that NAFLD is a precocious outcome in MSG-obese mice, whereas the period comprised between 60 and 120 days old seems to be a crucial metabolic window for comprehending pathophysiological events involved in NAFLD-to-NASH progression in this model.

Made available in DSpace on 2018-12-11T16:51:42Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-05-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) This work aims at evaluating shelf life of meat from Boer-Saanen cross goats fed on diets containing vitamin E. Thirty-five feedlot-fed goats with an initial body weight of 21.6 ± 2.8 kg were subjected to four treatments in a completely randomized design: a control treatment with vitamin E plus others containing 50, 150, and 450 mg DL-α-tocopherol acetate/kg DM. Longissimus lumborum (LL) muscle samples were stored at temperatures between 4 and 6 °C during 15 days, and evaluated for lipid peroxidation using the thiobarbituric acid reactive substances (TBARS) method and for visual acceptance by consumers by different survival analysis techniques. The addition, vitamin E in diets influenced shelf life of LL muscle, indicating longer meat preservation as the levels of the vitamin in diet increased, as the results obtained in chemical and subjective visual assessments showed. TBARS analysis showed to be more accurate in predicting shelf life of meat than subjective visual assessment by consumers, which reached a saturation threshold of 2 mg malonaldehyde/kg of meat earlier at all tested levels of vitamin E inclusion. Department of Animal Science State University of Maringá, Av. Colombo, 5790 Department of Food Engineering State University of Maringá Department of Agronomy Universidade do Estado de Mato Grosso-UNEMAT, Av. das Arapongas, 1384N Department of Statistics State University of Maringá Department of Animal Science UNESP – São Paulo State University FMVZ – Botucatu, P.O. box 560 Department of Veterinary Sciences University Center of Maringá, Av. Guedner, 1610 Department of Animal Science Federal University of Sergipe, Av Mar Rondon S/N Department of Animal Science UNESP – São Paulo State University FMVZ – Botucatu, P.O. box 560 CNPq: MCT/CNPq 14/2013

Objective— Inhibition of mineral crystal formation is a crucial step in ectopic calcification. Serum calciprotein particles (CPPs) have been linked to chronic kidney disease (CKD) calcification propensity, but additional knowledge is required to understand their function, assemblage, and composition. The role of other circulating nanostructures, such as extracellular vesicles (EVs) in vascular calcification is currently unknown. Here, we investigated the association of GRP (Gla-rich protein) with circulating CPP and EVs and the role of CKD CPPs and EVs in vascular calcification. Approach and Results— Biological CPPs and EVs were isolated from healthy and CKD patients and comparatively characterized using ultrastructural, analytic, molecular, and immuno-based techniques. Our results show that GRP is a constitutive component of circulating CPPs and EVs. CKD stage 5 serum CPPs and EVs are characterized by lower levels of fetuin-A and GRP, and CPPs CKD stage 5 have increased mineral maturation, resembling secondary CPP particles. Vascular smooth muscle cell calcification assays reveal that CPPs CKD stage 5 and EVs CKD stage 5 are taken up by vascular smooth muscle cells and induce vascular calcification by promoting cell osteochondrogenic differentiation and inflammation. These effects were rescued by incubation of CPPs CKD stage 5 with γ-carboxylated GRP. In vitro, formation and maturation of basic calcium phosphate crystals was highly reduced in the presence of γ-carboxylated GRP, fetuin-A, and MGP (matrix gla protein), and a similar antimineralization system was identified in vivo. Conclusions— Uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD. We propose a major role for cGRP as inhibitory factor to prevent calcification at systemic and tissue levels.

The objective of this study was to investigate the effects of two programs for strengthening the pelvic floor on the urinary incontinence of patients with multiple sclerosis (MS).This is a prospective study of the clinical trial type, monitored for 6 mos, in which 24 women in the moderate stage of MS participated in a program of exercises for strengthening the pelvic floor-associated (experimental group) or not (control group) with electrotherapy. The variables analyzed were as follows: quality-of-life, overactivity of the bladder, perineal contraction, and level of anxiety and depression. The statistical procedures involved multivariate analyses of repeated measurements, with a significance of 5%.Initial homogeneity being observed in the anthropometric and clinical variables, both protocols resulted in improvements in quality-of-life (P = 0.001), overactive bladder (P = 0.001), perineal contraction (P = 0.004), and level of anxiety (P = 0.001) and depression (P = 0.001), in relation to the initial comparison. The association of electrotherapy with strengthening exercises increased the improvement of the patients regarding overactive bladder (P = 0.039) and perineal contraction (P = 0.001), in comparison with the control group.The results reinforce the benefit of exercises for strengthening the musculature of the pelvic floor in women with overactive bladder in MS and demonstrate a potential of the action when associated with electrotherapy.Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Identify common dysfunctions of the lower urinary tract in women with multiple sclerosis; (2) Discuss the relationship between quality-of-life, level of anxiety and depression, degree of perineal contraction, and overactive bladder; and (3) Recognize the benefits promoted by physical therapy for strengthening the pelvic floor in patients with multiple sclerosis.Advanced: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students.A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11-19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed.The overall carriage prevalence was 9.9% (95% confidence interval, 8.3-11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains.The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil.

Background Cardiovascular disease (CVD) is the main risk factor of morbidity and mortality in chronic kidney disease (CKD) patients. Insulin resistance (IR) has been reported to be a strong risk factor for CVD. The purpose of this study was to examine the usefulness of IR as a predictor of cardiovascular morbidity and end-stage renal disease (ESRD). Methods We followed during a period of 56months 119 type 2 diabetic CKD patients (stages 2 to 4) without history of CVD at the beginning of the study. Several laboratory parameters and left ventricular mass index (LVMI) were analyzed. The degree of IR was estimated by the Homeostasis Model Assessment (HOMA-IR). Cardiovascular morbidity was assessed according to the presence of cardiovascular hospital admission during the study period, defined by admissions caused by coronary heart disease, congestive heart failure, peripheral vascular disease and cerebrovascular disease. The population was divided in two groups: G-1 with cardiovascular admission ( n =48) and G-2: without admission ( n =71). The multiple logistic regression was used to assess predictors of cardiovascular morbidity and ESRD. The renal survival was evaluated by the Kaplan–Meier and long-rank test. Results We found that G-1 patients showed significantly higher HOMA-IR (3.8 vs 0.77, p =0.0001) and that HOMA-IR upper tercile showed significantly higher age, eGFR, LVMI, phosphorus, iPTH and IL-6. In a multivariate logistic regression model HOMA-IR and IL-6 were independent risk factors of cardiovascular morbidity (OR=2.847 [95% CI 1.048–7.735, p =0.012] and OR=2.483 [95% CI 1.221–5.049, p =0.04], respectively). In a univariate logistic regression model patients in the upper tercile presented significantly more cardiovascular admissions that in the lower tercile. CKD progression to ESRD was observed in 24 patients and those in the upper HOMA-IR tercile showed a higher CKD progression to ESRD than the rest of study patients. A multivariate logistic regression model showed that HOMA-IR (OR=1.034, 95% CI (1.005-1.650) p =0.040) was an independent predictor of ESRD. Kaplan–Meier analysis showed a difference in renal survival in the HOMA-IR terciles (log rank=8.093; p =0.017). Conclusion In our study IR is an important risk factor for cardiovascular morbidity and ESRD in a diabetic CKD population.