Artigos e Materiais de Revistas Científicas - FM/MPT

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.


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  • article
    Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report
    (2024) GOMES, Luciana Beatriz Mendes; SANDOVAL, Renata Lazari; XAVIER, Camila Braganca; CORREA, Tatiana Strava; MATUDA, Raquel Midori Koga; SOUZA, Zenaide Silva de; LIMA, Luiz Guilherme Cernaglia Aureliano de; MACEDO, Mariana Petaccia de; CARVALHO, Filomena Marino; SUZUKI, Daniele Assad
    Malignant mixed mullerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease's molecular features and possible therapeutic approaches.
  • article 0 Citação(ões) na Scopus
    Temporal patterns of bacterial communities in the Billings Reservoir system
    (2024) MARCONDES, Marta Angela; PESSOA, Rodrigo; DUARTE, Alberto Jose da Silva; CLISSA, Patricia Bianca; SANABANI, Sabri Saeed
    In this study, high-throughput sequencing of 16S rRNA amplicons and predictive PICRUSt functional profiles were used to perform a comprehensive analysis of the temporal bacterial distribution and metabolic functions of 19 bimonthly samples collected from July 2019 to January 2020 in the surface water of Billings Reservoir, S & atilde;o Paulo. The results revealed that most of the bacterial 16S rRNA gene sequences belonged to Cyanobacteria and Proteobacteria, which accounted for more than 58% of the total bacterial abundance. Species richness and evenness indices were highest in surface water from summer samples (January 2020), followed by winter (July 2019) and spring samples (September and November 2019). Results also showed that the highest concentrations of sulfate (SO4-2), phosphate (P), ammonia (NH3), and nitrate (NO3-) were detected in November 2019 and January 2020 compared with samples collected in July and September 2019 (P < 0.05). Principal component analysis suggests that physicochemical factors such as pH, DO, temperature, and NH3 are the most important environmental factors influencing spatial and temporal variations in the community structure of bacterioplankton. At the genus level, 18.3% and 9.9% of OTUs in the July and September 2019 samples, respectively, were assigned to Planktothrix, while 14.4% and 20% of OTUs in the November 2019 and January 2020 samples, respectively, were assigned to Microcystis. In addition, PICRUSt metabolic analysis revealed increasing enrichment of genes in surface water associated with multiple metabolic processes rather than a single regulatory mechanism. This is the first study to examine the temporal dynamics of bacterioplankton and its function in Billings Reservoir during the winter, spring, and summer seasons. The study provides comprehensive reference information on the effects of an artificial habitat on the bacterioplankton community that can be used to interpret the results of studies to evaluate and set appropriate treatment targets.
  • article 0 Citação(ões) na Scopus
    The landscape of biomedical research funding in Brazil: a current overview
    (2024) GOMES, Cristiano M.; MARCHINI, Giovanni; JUNIOR, Jose de Bessa; CARVALHAL, Gustavo; CALDEIRA, Marina P. R.; SALDIVA, Paulo Hilario; KRIEGER, Jose Eduardo; AGENA, Fabiana; REIS, Sabrina; PASCHOAL, Candice; FROES, Milena; SROUGI, Miguel; NAHAS, William C.; FAVORITO, Luciano A.
    Objective: The objective of this narrative review is to discuss the current state of research funding in Brazil. Materials and Methods: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. Results: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. Conclusions: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry -sponsored studies, investigator -led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.
  • article 0 Citação(ões) na Scopus
    Machine learning for predicting Chagas disease infection in rural areas of Brazil
    (2024) GHILARDI, Fabio De Rose; SILVA, Gabriel; VIEIRA, Thallyta Maria; MOTA, Ariela; BIERRENBACH, Ana Luiza; DAMASCENO, Renata Fiuza; OLIVEIRA, Lea Campos de; CHIAVEGATTO FILHO, Alexandre Dias Porto; SABINO, Ester
    Introduction Chagas disease is a severe parasitic illness that is prevalent in Latin America and often goes unaddressed. Early detection and treatment are critical in preventing the progression of the illness and its associated life-threatening complications. In recent years, machine learning algorithms have emerged as powerful tools for disease prediction and diagnosis.Methods In this study, we developed machine learning algorithms to predict the risk of Chagas disease based on five general factors: age, gender, history of living in a mud or wooden house, history of being bitten by a triatomine bug, and family history of Chagas disease. We analyzed data from the Retrovirus Epidemiology Donor Study (REDS) to train five popular machine learning algorithms. The sample comprised 2,006 patients, divided into 75% for training and 25% for testing algorithm performance. We evaluated the model performance using precision, recall, and AUC-ROC metrics.Results The Adaboost algorithm yielded an AUC-ROC of 0.772, a precision of 0.199, and a recall of 0.612. We simulated the decision boundary using various thresholds and observed that in this dataset a threshold of 0.45 resulted in a 100% recall. This finding suggests that employing such a threshold could potentially save 22.5% of the cost associated with mass testing of Chagas disease.Conclusion Our findings highlight the potential of applying machine learning to improve the sensitivity and effectiveness of Chagas disease diagnosis and prevention. Furthermore, we emphasize the importance of integrating socio-demographic and environmental factors into neglected disease prediction models to enhance their performance. Chagas disease, a severe parasitic illness prevalent in Latin America, poses significant challenges due to delayed detection and treatment. Machine learning algorithms, advanced computer programs, have emerged as valuable tools for disease prediction and diagnosis. In our study, we utilized these algorithms to forecast Chagas disease risk based on factors such as age, gender, and living conditions. Drawing on data from the Retrovirus Epidemiology Donor Study (REDS), we trained five algorithms, with one showing promising results, achieving an impressive score of 0.772 out of 1. By establishing a specific threshold, we could potentially reduce testing costs while maintaining high detection rates. This research highlights the potential of machine learning in improving Chagas disease diagnosis and prevention by incorporating socio-demographic and environmental factors. Integrating these elements into predictive models has the potential to enhance their effectiveness and sensitivity, thereby improving disease management outcomes and ultimately reducing the burden of Chagas disease in affected regions.
  • article 0 Citação(ões) na Scopus
    Identification of Predictors of Metastatic Potential in Paragangliomas to Develop a Prognostic Score (PSPGL)
    (2024) IGUCHI, Daniela Yone Veiga; FILHO, Sebastiao Nunes Martins; SOARES, Ibere Cauduro; SIQUEIRA, Sheila Aparecida Coelho; ALVES, Venancio Avancini Ferreira; ASSATO, Aline Kawassaki; YANG, Ji Hoon; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida Barisson Villares; FAGUNDES, Gustavo Freitas Cardoso; MENDONCA, Berenice B.; JR, Delmar Muniz Lourenco; HOFF, Ana O.; CASTRONEVES, Luciana Audi; FERRAZ-DE-SOUZA, Bruno; GIANNELLA, Maria Lucia Cardillo Correa; PEREIRA, Maria Adelaide Albergaria
    Context Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5% to 35% of PGLs, and there are no reliable predictors of metastatic disease.Objective This work aimed to develop a prognostic score of metastatic potential in PGLs.Methods A retrospective analysis was conducted of clinical data from a cohort with PGLs and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and nonmetastatic PGL (absence of metastasis >= 96 months of follow-up) groups. Univariate and multivariable analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariable analysis. Kaplan-Meier curves were generated to estimate disease-specific survival (DSS).Results Out of 263 patients, 35 patients had metastatic PGL and 110 patients had nonmetastatic PGL. In multivariable analysis, 4 features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), more than 3 mitosis/10 high-power field (HPF) (28 points), extension into adipose tissue (20 points), and extra-adrenal location (19 points). A PSPGL of 24 or greater showed similar sensitivity with higher specificity than the Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL less than or equal to 20 was associated with a risk of metastasis of approximately 10%, whereas a PSPGL of 40 or greater was associated with approximately 80%. The presence of metastasis and Ki-67 of 3% or greater were related to lower DSS.Conclusion The PSPGL, composed of 4 easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimating metastasis risk.
  • article 0 Citação(ões) na Scopus
    Large-scale production of non-conventional edible plants for biodiverse school meals
    (2024) RANIERI, Guilherme Reis; MADEIRA, Nuno Rodrigo; SLATER, Betzabeth; MARCHESI, Mariana de Toledo; OLIVEIRA, Maria Angela Delgado de; BADUE, Ana Flavia Borges; MAUAD, Thais
    Introduction: School feeding programs are important for ensuring food security and promoting child health and development, particularly in low-income countries. In view of this importance, it is possible to increase the quality of these meals by diversifying the vegetables offered and incorporating underutilized plants to improve dietary diversity and nutritional quality into school meals. Methods: This study was carried out using the action research methodology following the implementation and development of the ""Inova na Horta"" project in the city of Jundia & iacute;, S & atilde;o Paulo, Brazil. The project was based on the existing and functioning physical and organizational structure of a municipal organic farm. Vegetables were selected from among 210 non-conventional species and varieties, which were further selected for continuous production based on 8 nutritional, culinary and cultivation criteria. Results: Thirty-four vegetables were selected for continuous cultivation and provisions to the school kitchens. Nine tons of vegetables were produced and provided to 90 municipal schools from 2020-2023. Leafy vegetables accounted for most the production, with a total weight of 6441 kg corresponding to 71.6% of the total harvest. Kitchen teams were trained throughout the project duration. Discussion: The feasibility of the production and culinary use of 34 biodiverse, nutrient-rich and underutilized food vegetables for school meals was demonstrated. The selected vegetables are nutrient-rich and contain higher amounts of minerals and proteins than the control vegetables (conventional vegetables), thus complementing several nutrients in school meals. This methodology can be replicated by municipalities of various sizes as a public policy of food and nutritional security associated with the valorization of local biodiversity.
  • article 2 Citação(ões) na Scopus
    Neuron-specific enolase at admission as a predictor for stroke volume, severity and outcome in ischemic stroke patients: a prognostic biomarker review
    (2024) MOCHETTI, Matheus Menao; SILVA, Estevao Garcia Porello; CORREA, Adriana Aparecida Feltrin; CABETTE, Marcela Rocha; PERISSINOTTI, Iago Navas; SILVA, Lucas Oliveira Junqueira; PESSOA, Adriano de Souza; OLIVEIRA, Rodrigo Cardoso de; SILVA, Luiz Fernando Ferraz da; SOUZA, Heraldo Possolo de; ALENCAR, Julio Cesar Garcia de
    An ideal blood biomarker for stroke should provide reliable results, enable fast diagnosis, and be readily accessible for practical use. Neuron-specific enolase (NSE), an enzyme released after neuronal damage, has been studied as a marker for brain injury, including cerebral infarction. However, different methodologies and limited sample sizes have restricted the applicability of any potential findings. This work aims to determine whether NSE levels at Emergency Department (ED) admission correlate with stroke severity, infarcted brain volume, functional outcome, and/or death rates. A systematic literature review was performed using PubMed, Embase, and Scopus databases. Each reviewer independently assessed all published studies identified as potentially relevant. All relevant original observational studies (cohort, case-control, and cross-sectional studies) were included. Eleven studies (1398 patients) met the inclusion criteria. Among these, six studies reported a significant correlation between NSE levels and stroke severity, while only one found no association. Four studies indicated a positive relationship between infarcted brain volume assessed by imaging and NSE levels, in contrast to the findings of only one study. Four studies identified an association related to functional outcome and death rates, while three others did not reach statistical significance in their findings. These data highlight that NSE levels at ED admissions proved to be a promising tool for predicting the outcome of ischemic stroke patients in most studies. However, they presented high discrepancies and low robustness. Therefore, further research is necessary to establish and define the role of NSE in clinical practice.
  • article 0 Citação(ões) na Scopus
    Exposure to urban ambient particles (PM2.5) before pregnancy affects the expression of endometrial receptive markers to embryo implantation in mice: Preliminary results
    (2024) CASTRO, Karla Ribeiro de; ALMEIDA, Gustavo Henrique Dona Rodrigues; MATSUDA, Monique; VIEIRA, Rodolfo de Paula; MARTINS, Marco Garcia; RICI, Rose Eli Grassi; SALDIVA, Paulo Hilario Nascimento; VERAS, Mariana Matera
    Air pollution (AP) is one of the main recent concerns in reproductive healthy due to its potential to promote negative outcomes during pregnancy and male and female fertility. Several studies have demonstrated that AP exposure has been linked to increased embryonic implantation failures, alterations in embryonic, fetal and placental development. For a well-succeeded implantation, both competent blastocyst and receptive endometrium are required. Based on the lack of data about the effect of AP in endometrial receptivity, this study aimed to evaluate he particulate matter (PM) exposure impact on uterine receptive markers in mice and associate the alterations to increased implantation failures due to AP. For this study, ten dams per group were exposed for 39 days to either filter (F) or polluted air (CAP). At fourth gestational day (GD4), females were euthanized. Morphological, ultrastructural, immunohistochemical and molecular analysis of uterine and ovarian samples were performed. CAP-exposed females presented a reduced number of corpus luteum; glands and epithelial cells were increased with pinopodes formation impairment. Immunohistochemistry analysis revealed decreased LIF protein levels. These preliminary data suggests that PM exposure may exert negative effects on endometrial receptivity by affecting crucial parameters to embryonic implantation as uterine morphological differentiation, corpus luteum quantity and LIF expression during implantation window.
  • article 0 Citação(ões) na Scopus
    Ambient PM2.5 and productivity-adjusted life years lost in Brazil: a national population-based study
    (2024) WEN, Bo; ADEMI, Zanfina; WU, Yao; XU, Rongbin; YU, Pei; YE, Tingting; COELHO, Micheline de Sousa Zanotti Stagliorio; SALDIVA, Paulo Hilario Nascimento; GUO, Yuming; LI, Shanshan
    Enormous health burden has been associated with air pollution and its effects continue to grow. However, the impact of air pollution on labour productivity at the population level is still unknown. This study assessed the association between premature death due to PM2.5 exposure and the loss of productivity-adjusted life years (PALYs), in Brazil. We applied a novel variant of the difference-in-difference (DID) approach to assess the association. Daily all-cause mortality data in Brazil were collected from 2000-2019. The PALYs lost increased by 5.11% (95% CI: 4.10-6.13%), for every 10 mu g/m3 increase in the 2-day moving average of PM2.5. A total of 9,219,995 (95% CI: 7,491,634-10,921,141) PALYs lost and US$ 268.05 (95% CI: 217.82-317.50) billion economic costs were attributed to PM2.5 exposure, corresponding to 7.37% (95% CI: 5.99-8.73%) of the total PALYs lost due to premature death. This study also found that 5,005,306 PALYs could be avoided if the World Health Organization (WHO) air quality guideline (AQG) level was met. In conclusion, this study demonstrates that ambient PM2.5 exposure is associated with a considerable labour productivity burden relating to premature death in Brazil, while over half of the burden could be prevented if the WHO AQG was met. The findings highlight the need to reduce ambient PM2.5 levels and provide strong evidence for the development of strategies to mitigate the economic impacts of air pollution.
  • article 0 Citação(ões) na Scopus
    Lung tissue expression of epithelial injury markers is associated with acute lung injury severity but does not discriminate sepsis from ARDS
    (2024) COSTA, Natalia de Souza Xavier; SIGRIST, Giovana da Costa; SCHALCH, Alexandre Santos; BELOTTI, Luciano; DOLHNIKOFF, Marisa; SILVA, Luiz Fernando Ferraz da
    BackgroundAcute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in critically ill patients, and diffuse alveolar damage (DAD) is considered its histological hallmark. Sepsis is one of the most common aetiology of ARDS with the highest case-fatality rate. Identifying ARDS patients and differentiate them from other causes of acute respiratory failure remains a challenge. To address this, many studies have focused on identifying biomarkers that can help assess lung epithelial injury. However, there is scarce information available regarding the tissue expression of these markers. Evaluating the expression of elafin, RAGE, and SP-D in lung tissue offers a potential bridge between serological markers and the underlying histopathological changes. Therefore, we hypothesize that the expression of epithelial injury markers varies between sepsis and ARDS as well as according to its severity.MethodsWe compared the post-mortem lung tissue expression of the epithelial injury markers RAGE, SP-D, and elafin of patients that died of sepsis, ARDS, and controls that died from non-pulmonary causes. Lung tissue was collected during routine autopsy and protein expression was assessed by immunohistochemistry. We also assessed the lung injury by a semi-quantitative analysis.ResultsWe observed that all features of DAD were milder in septic group compared to ARDS group. Elafin tissue expression was increased and SP-D was decreased in the sepsis and ARDS groups. Severe ARDS expressed higher levels of elafin and RAGE, and they were negatively correlated with PaO2/FiO2 ratio, and positively correlated with bronchopneumonia percentage and hyaline membrane score. RAGE tissue expression was negatively correlated with mechanical ventilation duration in both ARDS and septic groups. In septic patients, elafin was positively correlated with ICU admission length, SP-D was positively correlated with serum lactate and RAGE was correlated with C-reactive protein.ConclusionsLung tissue expression of elafin and RAGE, but not SP-D, is associated with ARDS severity, but does not discriminate sepsis patients from ARDS patients.
  • article 3 Citação(ões) na Scopus
    Long non-coding RNA SNHG8 drives stress granule formation in tauopathies
    (2023) BHAGAT, Reshma; MINAYA, Miguel A.; RENGANATHAN, Arun; MEHRA, Muneshwar; MARSH, Jacob; MARTINEZ, Rita; ETELEEB, Abdallah M.; NANA, Alissa L.; SPINA, Salvatore; SEELEY, William W.; GRINBERG, Lea T.; KARCH, Celeste M.
    Tauopathies are a heterogenous group of neurodegenerative disorders characterized by tau aggregation in the brain. In a subset of tauopathies, rare mutations in the MAPT gene, which encodes the tau protein, are sufficient to cause disease; however, the events downstream of MAPT mutations are poorly understood. Here, we investigate the role of long non-coding RNAs (lncRNAs), transcripts >200 nucleotides with low/no coding potential that regulate transcription and translation, and their role in tauopathy. Using stem cell derived neurons from patients carrying a MAPT p.P301L, IVS10 + 16, or p.R406W mutation and CRISPR-corrected isogenic controls, we identified transcriptomic changes that occur as a function of the MAPT mutant allele. We identified 15 lncRNAs that were commonly differentially expressed across the three MAPT mutations. The commonly differentially expressed lncRNAs interact with RNA-binding proteins that regulate stress granule formation. Among these lncRNAs, SNHG8 was significantly reduced in a mouse model of tauopathy and in FTLD-tau, progressive supranuclear palsy, and Alzheimer's disease brains. We show that SNHG8 interacts with tau and stress granule-associated RNA-binding protein TIA1. Overexpression of mutant tau in vitro is sufficient to reduce SNHG8 expression and induce stress granule formation. Rescuing SNHG8 expression leads to reduced stress granule formation and reduced TIA1 levels in immortalized cells and in MAPT mutant neurons, suggesting that dysregulation of this noncoding RNA is a causal factor driving stress granule formation via TIA1 in tauopathies.
  • article 0 Citação(ões) na Scopus
    Mutant tau and stress lead to downregulation of long noncoding RNA, SNHG8
    (2023) BHAGAT, Reshma; MINAYA, Miguel A.; RENGANATHAN, Arun; MEHRA, Muneshwar; MARSH, Jacob; MARTINEZ, Rita; ETELEEB, Abdallah M.; NANA, Alissa L.; SPINA, Salvatore; SEELEY, William W.; GRINBERG, Lea T.; KARCH, Celeste M.
  • article 0 Citação(ões) na Scopus
    Airway smooth muscle and long-term clinical efficacy following bronchial thermoplasty in severe asthma
    (2024) WIJSMAN, Pieta C.; GOORSENBERG, Annika W. M.; D'HOOGHE, Julia N. S.; HACKEN, Nick H. T. ten; ROELOFS, Joris J. T. H.; MAUAD, Thais; WEERSINK, Els J. M.; SHAH, Pallav; ANNEMA, Jouke T.; I, Peter Bonta
    The mechanism of action of bronchial thermoplasty (BT) treatment for patients with severe asthma is incompletely understood. This study investigated the 2.5-year impact of BT on airway smooth muscle (ASM) mass and clinical parameters by paired data analysis in 22 patients. Our findings demonstrate the persistence of ASM mass reduction of >50% after 2.5 years. Furthermore, sustained improvement in asthma control, quality of life and exacerbation rates was found, which is in line with previous reports. An association was found between the remaining ASM and both the exacerbation rate (r=0.61, p=0.04 for desmin, r=0.85, p<0.01 for alpha smooth muscle actin (SMA)) and post-bronchodilator forced expiratory volume in 1 s predicted percentage (r=-0.69, p=0.03 for desmin, r=-0.58, p=0.08 for alpha SMA). This study provides new insight into the long-term impact of BT.
  • article 4 Citação(ões) na Scopus
    Is Alzheimer disease a disease?
    (2024) KORCZYN, Amos D.; GRINBERG, Lea T.
    Dementia, a prevalent condition among older individuals, has profound societal implications. Extensive research has resulted in no cure for what is perceived as the most common dementing illness: Alzheimer disease (AD). AD is defined by specific brain abnormalities - amyloid-beta plaques and tau protein neurofibrillary tangles - that are proposed to actively influence the neurodegenerative process. However, conclusive evidence of amyloid-beta toxicity is lacking, the mechanisms leading to the accumulation of plaques and tangles are unknown, and removing amyloid-beta has not halted neurodegeneration. So, the question remains, are we making progress towards a solution? The complexity of AD is underscored by numerous genetic and environmental risk factors, and diverse clinical presentations, suggesting that AD is more akin to a syndrome than to a traditional disease, with its pathological manifestation representing a convergence of pathogenic pathways. Therefore, a solution requires a multifaceted approach over a single 'silver bullet'. Improved recognition and classification of conditions that converge in plaques and tangle accumulation and their treatment requires the use of multiple strategies simultaneously. Alzheimer disease is a complex and multifactorial condition. The authors of this Perspective suggest that its lack of a singular common pathogenesis prevents it from being regarded as a straightforward 'disease' and that treatment will therefore require a multifaceted approach.
  • article 0 Citação(ões) na Scopus
    Wildfire-related PM 2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil *
    (2024) GAO, Yuan; HUANG, Wenzhong; YU, Pei; XU, Rongbin; GASEVIC, Danijela; YUE, Xu; COELHO, Micheline de Sousa Zanotti Stagliorio; SALDIVA, Paulo Hilario Nascimento; GUO, Yuming; LI, Shanshan
    Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfirerelated fine particulate matter (PM 2.5 ) with cause -specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire -related PM 2.5 was defined as exposure to annual mean wildfirerelated PM 2.5 concentrations in the 1 -year prior to death. The variant difference -in -differences method was employed to explore the wildfire -related PM 2 . 5 -cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: <= 1.82 mu g/m 3 ) of wildfire -related PM 2.5 exposure, those in the fourth quartile (Q4: 4.22-17.12 mu g/m 3 ) of wildfire -related PM 2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013-1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014-1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002-1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424-49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12-24.38) per 100,000 population, were attributable to wildfire -related PM 2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfirerelated cardiovascular premature deaths.
  • article 0 Citação(ões) na Scopus
    Effects of land cover and air pollution on the risk of premature births
    (2024) MOREIRA, Tiana C. L.; POLIZEL, Jefferson L.; REQUIA, Weeberb J.; SALDIVA, Paulo Hilario Nascimento; FILHO, Demostenes F. da Silva; SALDIVA, Silvia Regina Dias Medici; MAUAD, Thais
  • article 0 Citação(ões) na Scopus
    Mapping the (un)healthy city: Proximity to urban facilities and chance of premature mortality from myocardial infarction in Sao Paulo city
    (2024) LEITE, Carlos; SALDIVA, Paulo; ANDRE, Carmen Diva Saldiva de; BARROZO, Ligia Vizeu; ALVIM, Angelica Benatti; HERLING, Tereza; CORREA, Eliene; ACOSTA, Claudia; ANDRE, Paulo Afonso de; SILVA, Luiz Fernando Ferraz da; PEREIRA, Ivan; MARQUES, Andresa Ledo
    Applied research in healthy cities is often based on empirical investigations of the association between the built environment and health outcomes using spatial analysis. We investigated the influence of proximity to urban facilities on the occurrence of early deaths from myocardial infarction (age <60 years) in the city of Sa similar to o Paulo, with cause of death determined by autopsy. The study data were extracted from interviews applied to relatives/ caregivers of 458 deceased autopsied at the Death Verification Service, collecting information on demographic characteristics, residential address, life habits and previous health conditions. After geocoding the residential addresses of the deceased, the distances to different urban facilities were calculated. The existence of an association between the odds of death from myocardial infarction aged <60 years versus >= 60 years and distance to urban facilities was assessed by fitting logistic regression models. The results showed a significant association between these distances and the odds of early death from infarction. More specifically, when distances to different facilities were halved, the odds of death at <60 years were reduced by a factor of 0.78 (-22 %) for community clubs; 0.73 (-27 %) for sports centers; and by 0.80 (20 %) for cycle paths). These results indicate the potential of interventions to benefit human health through the formulation of spatially-integrated public policies in cities.
  • article 0 Citação(ões) na Scopus
    Human movement and environmental barriers shape the emergence of dengue
    (2024) HARISH, Vinyas; COLON-GONZALEZ, Felipe J.; MOREIRA, Filipe R. R.; GIBB, Rory; KRAEMER, Moritz U. G.; DAVIS, Megan; REINER, Robert C.; PIGOTT, David M.; PERKINS, T. Alex; WEISS, Daniel J.; BOGOCH, Isaac I.; VAZQUEZ-PROKOPEC, Gonzalo; SAIDE, Pablo Manrique; BARBOSA, Gerson L.; SABINO, Ester C.; KHAN, Kamran; FARIA, Nuno R.; HAY, Simon I.; CORREA-MORALES, Fabian; CHIARAVALLOTI-NETO, Francisco; BRADY, Oliver J.
    Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens. Here, using a dynamic modelling approach, the authors find that the spread of dengue through Mexico and Brazil is shaped by specific interactions between human mobility, climate, and the environment. Their models can also be applied to predict future spread in these geographic areas.
  • article 1 Citação(ões) na Scopus
    Idiopathic collapsing glomerulopathy is associated with APOL1 high-risk genotypes or Mendelian variants in most affected individuals in a highly admixed population
    (2024) NEVES, Precil; WATANABE, Andreia; WATANABE, Elieser; NARCIZO, Amanda; NUNES, Kelly; LERARIO, Antonio; FERREIRA, Frederico; CAVALCANTE, Livia; WONGBOONSIN, Janewit; MALHEIROS, Denise; JORGE, Lecticia; SAMPSON, Matthew; NORONHA, Irene; ONUCHIC, Luiz
    Collapsing glomerulopathy (CG) is most often associated with fast progression to kidney failure with an incidence apparently higher in Brazil than in other countries. However, the reason for this occurrence is unknown. To better understand this, we performed an integrated analysis of clinical, histological, therapeutic, causative genetic and genetic ancestry data in a highly genetically admixed cohort of 70 children and adult patients with idiopathic CG (ICG). The disease onset occurred at 23 (interquartile range: 17-31) years and approximately half of patients progressed to chronic kidney disease requiring kidney replacement therapy (CKD-KRT) 36 months after diagnosis. Causative genetic bases, assessed by targeted-gene panel or wholeexome sequencing, were identified in 58.6% of patients. Among these cases, 80.5% harbored APOL1 high -risk genotypes (HRG) and 19.5% causative Mendelian variants (MV). Self-reported non -White patients more frequently had HRG. MV was an independent risk factor for progression to CKD-KRT by 36 months and the end of follow-up, while remission was an independent protective factor. All patients with HRG manifested CG at 9-44 years of age, whereas in those with APOL1 low-risk genotype, the disease arose throughout life. HRGs were associated with higher proportion of African genetic ancestry. Novel causative MVs were identified in COL4A5, COQ2 and PLCE1 and previously described causative MVs were identified in MYH9, TRPC6, COQ2, COL4A3 and TTC21B. Three patients displayed HRG combined with a variant of uncertain significance (ITGB4, LAMA5 or PTPRO). MVs were associated with worse kidney prognosis. Thus, our data reveal that the genetic status plays a major role in ICG pathogenesis, accounting for more than half of cases in a highly admixed Brazilian population. Kidney International (2024) 105, 593-607; j.kint.2023.11.028 Lay Summary Collapsing glomerulopathy is a severe kidney disease that often leads to chronic dialysis or kidney transplantation. To expand its understanding, we performed a broad clinical and genetic analysis of a highly admixed patient population with idiopathic collapsing glomerulopathy. Interestingly, we identified a genetic cause in more than half of the 70 evaluated patients. Moreover, in a significant majority of the cases with a genetic form, the disease was associated with the presence of risk variants in both alleles of the APOL1 gene, which are genetic variants associated with African ethnicity. These patients, in fact, displayed a higher proportion of African genetic ancestry. The other genetic cases occurred due to causative variants in other genes, being classified as Mendelian forms. Mendelian cases had a higher risk of progression to kidney failure, and all patients with 2 APOL1 risk alleles manifested collapsing glomerulopathy between 9 and 44 years of age.
  • article 0 Citação(ões) na Scopus
    Effect of Hypertonic Saline Solution on the Ventilatory Mechanics of Lungs Donated After Brain Death
    (2024) RUIZ, Liliane Moreira; BRAGA, Karina Andrighetti de Oliveira; NEPOMUCENO, Natalia Aparecida; CORREIA, Aristides Tadeu; CARVALHO, Guilherme Henrique Ribeiro de; VILELA, Vanessa Sana; DOLHNIKOFF, Marisa; PEGO-FERNANDES, Paulo Manuel
    Introduction: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD. Methods: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD. Results: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05). Conclusions: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue.