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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Alimentação Saudável, Agricultura Urbana e Familiar
(2023) DOMENE, SEMÍRAMIS MARTINS ÁLVARES; SAWAYA, ANA LYDIA; MAUAD, THAIS; FRANCO, MARIA DO CARMO PINHO; ALBUQUERQUE, MARIA PAULA DE; WANDERLEY, MARIANGELA BELFIORE; PEREIRA, CRISTIANE MATOS; KAZZE, MARCELLA CABRAL; PELIANO, ANNA MARIA MEDEIROS
ABSTRACT As a result of the debates held during the XI Seminar on Service, Research and Public Policy, on the theme “Urban Agriculture and Food and Nutrition Security: organic food in school meals”, this article summarizes the speeches of researchers, agricultural producers, representatives of civil society institutions and government agencies on urban food production. From the perspective of the of urban agriculture contribution to the quality of food, issues related to the scope and limits of the distribution of these foods through public facilities and destination to public policies, such as the school meal program, are addressed in light of experiences in the cities of São Paulo and Castro, in Paraná. Considering the supply of urban centers and the importance of organizational and food environments, debate took national and international guidelines on the social determinants of contemporary health and nutrition as a theoretical reference. The difficulties that mark the production of urban agriculture were addressed, and the actions of local initiatives that made it possible to advance towards a viable economic activity that promotes healthy eating and equity were presented. The role of public food policies, still limited in the field of urban agriculture, is evident to strengthen the work of farmers and public managers engaged in initiatives that already point to the potential for growth in this form of food production.
INTRAHEPATIC BILIARY PROLIFERATIONS: HISTOPATHOLOGY AND POTENTIAL IMMUNOHISTOCHEMICAL MARKERS
(2023) HIRAYAMA, André Bubna; MELLO, Evandro Sobroza de; ALVES, Venâncio Avancini Ferreira
ABSTRACT Intrahepatic biliary proliferations represent a spectrum from reactive (ductular reaction, some with atypical architecture), hamartomatous (von Meyenburg complex), benign (bile duct adenoma) and precursor/borderline entities (biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct) to fully malignant (cholangiocarcinoma) neoplasms. Clinical pictures and even imaging patterns may be similar, requiring refined studies aiming at histopathological and immunohistochemistry for more precise diagnosis, essential for correct patient management. This article discusses updated concepts and definitions of most relevant entities aiming more specifically at the differential diagnosis in practice, focusing on morphology and immunohistochemistry, with a discussion of potential markers to help distinguishing between benign and malignant lesions.
Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression
(2024) SAMORANO, Luciana Paula; MANFRERE, Kelly Cristina Gomes; PEREIRA, Naiura Vieira; TAKAOKA, Roberto; VALENTE, Neusa Yuriko Sakai; SOTTO, Mirian Nacagami; SILVA, Luiz Fernando Ferraz; SATO, Maria Notomi; AOKI, Valeria
Background: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). Objective: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. Methods: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-alpha, IFN-gamma, TARC, and CCL-22. Results: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. Study limitations: Small sample size and limited length of follow-up. Conclusions: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. (c) 2023 Published by Elsevier Espana, S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Association of pulmonary black carbon accumulation with cardiac fibrosis in residents of Sao Paulo, Brazil
(2024) TAKANO, Ana Paula Cremasco; ANDRE, Carmen Diva Saldiva de; ALMEIDA, Raquel de; WAKED, Dunia; VERAS, Mariana Matera; SALDIVA, Paulo Hilario Nascimento
Evidence suggests that myocardial interstitial fibrosis, resulting from cardiac remodeling, may possibly be influenced by mechanisms activated through the inhalation of airborne pollutants. However, limited studies have explored the relationship between lifetime exposure to carbon-based particles and cardiac fibrosis, specially using post -mortem samples. This study examined whether long -term exposure to air pollution (estimated by black carbon accumulated in the lungs) is associated with myocardial fibrosis in urban dwellers of megacity of Sao Paulo. Data collection included epidemiological and autopsy-based approaches. Information was obtained by interviewing the next of kin and through the pathologist's report. The individual index of exposure to carbonbased particles, which we designed as the fraction of black carbon (FBC), was estimated through quantification of particles on the macroscopic lung surface. Myocardium samples were collected for histopathological analysis to evaluate the fraction of cardiac fibrosis. The association between cardiac fibrosis and FBC, age, sex, smoking status and hypertension was assessed by means of multiple linear regression models. Our study demonstrated that the association of FBC with cardiac fibrosis is influenced by smoking status and hypertension. Among hypertensive individuals, the cardiac fibrosis fraction tended to increase with the increase of the FBC in both groups of smokers and non-smokers. In non-hypertensive individuals, the association between cardiac fibrosis fraction and FBC was observed primarily in smokers. Long -term exposure to tobacco smoke and environmental particles may contribute to the cardiac remodeling response in individuals with pre-existing hypertension. This highlights the importance of considering hypertension as an additional risk factor for the health effects of air pollution on the cardiovascular system. Moreover, the study endorses the role of autopsy to investigate the effects of urban environment and personal habits in determining human disease.
Tobacco exposure, but not aging, shifts the frequency of peripheral blood B cell subpopulations
(2024) PINTO, Thalyta Nery Carvalho; SILVA, Cibele Cristine Berto Marques da; PINTO, Regina Maria Carvalho; DUARTE, Alberto Jose da Silva; BENARD, Gil; FERNANDES, Juliana Ruiz
Several disturbances in T-cell mediated immunity have been described during aging, but immunosenescence of the B-cell compartment is less well elucidated. The peripheral blood B-cell compartment (CD19+) can be split into six main subpopulations according to the cell surface markers IgD, CD27, CD24, and CD38: Transitional, naive, unswitched, switched, double negative and plasmablasts. We thus aimed to verify whether shifts in these subsets occur during healthy and pathological aging. We recruited three groups of aged people (> 60 years old), healthy, COPD patients, and smokers without altered pulmonary function test, and a fourth group of individuals 18-40 years old (youngs). Total B-cells percentage and absolute number were similar among the healthy aged, COPD patients, and youngs, but the smokers showed significantly higher absolute numbers. While all six B-cell subset percentages were comparable among the healthy aged, COPD patients, and youngs, smokers showed significantly higher percentages of switched B-cells and reduced naive B-cells than the other three groups, resulting in an inverted naive:switched ratio. Analysis of the cell subset absolute numbers showed a similar trend. Overall, our results suggest that aging drives milder alterations in the distribution of peripheral blood B-cell subpopulations than in the T-cell compartment. We suggest that it is the T-cell immunosenescence that most contributes to the poor humoral immune responses in the elderly, vaccine responses included. Surprisingly it was the smokers who showed significant alterations when compared with the youngs, healthy aged, and aged COPD patients, probably as a result of the chronic immune stimulation described in active smoking subjects.
Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants (vol 15, 1307546, 2024)
(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire Tabosa
Enhanced immunogenicity and protective efficacy in mice following a Zika DNA vaccine designed by modulation of membrane-anchoring regions and its association to adjuvants
(2024) TEIXEIRA, Franciane Mouradian Emidio; OLIVEIRA, Luana de Mendonca; BRANCO, Anna Claudia Calvielli Castelo; ALBERCA, Ricardo Wesley; SOUSA, Emanuella Sarmento Alho de; LEITE, Bruno Henrique de Sousa; ADAN, Wenny Camilla dos Santos; DUARTE, Alberto Jose da Silva; LINS, Roberto Dias; SATO, Maria Notomi; VIANA, Isabelle Freire Tabosa
Zika virus (ZIKV) is a re-emerging pathogen with high morbidity associated to congenital infection. Despite the scientific advances since the last outbreak in the Americas, there are no approved specific treatment or vaccines. As the development of an effective prophylactic approach remains unaddressed, DNA vaccines surge as a powerful and attractive candidate due to the efficacy of sequence optimization in achieving strong immune response. In this study, we developed four DNA vaccine constructs encoding the ZIKV prM/M (pre-membrane/membrane) and E (envelope) proteins in conjunction with molecular adjuvants. The DNA vaccine candidate (called ZK_Delta STP), where the entire membrane-anchoring regions were completely removed, was far more immunogenic compared to their counterparts. Furthermore, inclusion of the tPA-SP leader sequence led to high expression and secretion of the target vaccine antigens, therefore contributing to adequate B cell stimulation. The ZK_Delta STP vaccine induced high cellular and humoral response in C57BL/6 adult mice, which included high neutralizing antibody titers and the generation of germinal center B cells. Administration of ZK-Delta STP incorporating aluminum hydroxide (Alum) adjuvant led to sustained neutralizing response. In consistency with the high and long-term protective response, ZK_Delta STP+Alum protected adult mice upon viral challenge. Collectively, the ZK_Delta STP+Alum vaccine formulation advances the understanding of the requirements for a successful and protective vaccine against flaviviruses and is worthy of further translational studies.
Outlining the skin-homing and circulating CLA⁺NK cells in patients with severe atopic dermatitis
(2024) LIMA, Josenilson Feitosa de; TEIXEIRA, Franciane Mouradian Emidio; RAMOS, Yasmim alefe Leuzzi; CARVALHO, Gabriel Costa de; BRANCO, Anna Claudia Calvielli Castelo; PEREIRA, Naiura Vieira; SOTTO, Mirian Nacagami; AOKI, Valeria; SATO, Maria Notomi; ORFALI, Raquel Leao
Atopic dermatitis (AD) is a complex, multifactorial skin disease, characterized by pruritus and predominant Th2 inflammation. Innate immune cells may play a role in AD development and are composed of granulocytes, macrophages, innate-like T cells, and innate lymphoid cells. This study investigates the phenotypic and functional profile of circulating CLA(+) natural killer (NK) cells and its role in the skin-homing to NK cells infiltrated in adults' skin with AD. We selected 44 AD patients and 27 non-AD volunteers for the study. The results showed increased frequencies of both CLA(+)CD56(bright) and CLA(+)CD56(dim) NK cell populations in the peripheral blood, mainly in severe AD patients. Upon SEB stimulation, we observed an augmented percentage of CLA(+)CD56(dim) NK cells expressing CD107a, IFN-gamma, IL-10, and TNF, reinforcing the role of staphylococcal enterotoxins in AD pathogenesis. Additionally, we demonstrated increased dermal expression of both NK cell markers NCAM-1/CD56 and pan-granzyme, corroborating the skin-homing, mostly in severe AD. Further studies are necessary to elucidate the potential role of NK cells in the chronification of the inflammatory process in AD skin, as well as their possible relationship with staphylococcal enterotoxins, and as practicable therapeutic targets.
Aberrant activation of TCL1A promotes stem cell expansion in clonal haematopoiesis
(2023) WEINSTOCK, Joshua S.; GOPAKUMAR, Jayakrishnan; BURUGULA, Bala Bharathi; UDDIN, Md Mesbah; JAHN, Nikolaus; BELK, Julia A.; BOUZID, Hind; DANIEL, Bence; MIAO, Zhuang; LY, Nghi; MACK, Taralynn M.; PULLINGER, Clive R.; SHOEMAKER, M. Benjamin; DARBAR, Dawood; RODEN, Dan M.; ALBERT, Christine; KOOPERBERG, Charles; ZHOU, Ying; MANSON, Joann E.; DESAI, Pinkal; JOHNSON, Andrew D.; BLACKWELL, Thomas W.; MATHIAS, Rasika A.; ABECASIS, Goncalo R.; SMITH, Albert V.; KANG, Hyun M.; SATPATHY, Ansuman T.; NATARAJAN, Pradeep; KITZMAN, Jacob O.; WHITSEL, Eric A.; REINER, Alexander P.; BICK, Alexander G.; LUNA, Sofia E.; JAISWAL, Siddhartha; PROTHRO, Katherine P.; MITCHELL, Shaneice R.; LAURIE, Cecelia A.; BROOME, Jai G.; TAYLOR, Kent D.; GUO, Xiuqing; SINNER, Moritz F.; FALKENHAUSEN, Aenne S. von; KAAB, Stefan; SHULDINER, Alan R.; O'CONNELL, Jeffrey R.; LEWIS, Joshua P.; BOERWINKLE, Eric; BARNES, Kathleen C.; CHAMI, Nathalie; KENNY, Eimear E.; LOOS, Ruth J. F.; FORNAGE, Myriam; HOU, Lifang; LLOYD-JONES, Donald M.; REDLINE, Susan; CADE, Brian E.; PSATY, Bruce M.; BIS, Joshua C.; BRODY, Jennifer A.; SILVERMAN, Edwin K.; YUN, Jeong H.; QIAO, Dandi; PALMER, Nicholette D.; FREEDMAN, Barry I.; BOWDEN, Donald W.; CHO, Michael H.; DEMEO, Dawn L.; VASAN, Ramachandran S.; YANEK, Lisa R.; BECKER, Lewis C.; KARDIA, Sharon L. R.; PEYSER, Patricia A.; HE, Jiang; RIENSTRA, Michiel; HARST, Pim Van der; KAPLAN, Robert; HECKBERT, Susan R.; SMITH, Nicholas L.; WIGGINS, Kerri L.; ARNETT, Donna K.; IRVIN, Marguerite R.; TIWARI, Hemant; CUTLER, Michael J.; KNIGHT, Stacey; MUHLESTEIN, J. Brent; CORREA, Adolfo; RAFFIELD, Laura M.; GAO, Yan; ANDRADE, Mariza de; ROTTER, Jerome I.; RICH, Stephen S.; TRACY, Russell P.; KONKLE, Barbara A.; JOHNSEN, Jill M.; WHEELER, Marsha M.; SMITH, J. Gustav; MELANDER, Olle; NILSSON, Peter M.; CUSTER, Brian S.; DUGGIRALA, Ravindranath; CURRAN, Joanne E.; BLANGERO, John; MCGARVEY, Stephen; WILLIAMS, L. Keoki; XIAO, Shujie; YANG, Mao; GU, C. Charles; CHEN, Yii-Der Ida; LEE, Wen-Jane; MARCUS, Gregory M.; KANE, John P.
Mutations in a diverse set of driver genes increase the fitness of haematopoietic stem cells (HSCs), leading to clonal haematopoiesis(1). These lesions are precursors for blood cancers(2-6), but the basis of their fitness advantage remains largely unknown, partly owing to a paucity of large cohorts in which the clonal expansion rate has been assessed by longitudinal sampling. Here, to circumvent this limitation, we developed a method to infer the expansion rate from data from a single time point. We applied this method to 5,071 people with clonal haematopoiesis. A genome-wide association study revealed that a common inherited polymorphism in the TCL1A promoter was associated with a slower expansion rate in clonal haematopoiesis overall, but the effect varied by driver gene. Those carrying this protective allele exhibited markedly reduced growth rates or prevalence of clones with driver mutations in TET2, ASXL1, SF3B1 and SRSF2, but this effect was not seen in clones with driver mutations in DNMT3A. TCL1A was not expressed in normal or DNMT3A-mutated HSCs, but the introduction of mutations in TET2 or ASXL1 led to the expression of TCL1A protein and the expansion of HSCs in vitro. The protective allele restricted TCL1A expression and expansion of mutant HSCs, as did experimental knockdown of TCL1A expression. Forced expression of TCL1A promoted the expansion of human HSCs in vitro and mouse HSCs in vivo. Our results indicate that the fitness advantage of several commonly mutated driver genes in clonal haematopoiesis may be mediated by TCL1A activation.
Synaptic Oligomers and Glial Cells in Alzheimer Disease
(2023) GRINBERG, Lea Tenenholz
Small biopsies for pancreatic lesions: Is there still room for fine needle aspiration?
(2024) BUENO, Adriana; FELIPE-SILVA, Aloisio; SAIEG, Mauro
Pancreatic carcinoma is an aggressive tumour with increasing incidence in both sexes worldwide. Early detection is, therefore, essential for patient management. A recent advancement involves the utilization of larger, thicker gauge needles, which enable the collection of core-type biopsies (FNB). Here, we investigated the role of fine needle aspiration and cytopathology in the diagnostic workflow of pancreatic lesions. A search query was designed to search for articles in the PubMed database comparing FNA and FNB for biopsy of pancreatic lesions, and detailed data were extracted from selected studies. Statistical analyses were performed using the R package meta version 6.2. Twenty-one studies made the final cut for data extraction. Overall, median age was 64.3 years (+/- 6.1; 47.6-71.5), male: female proportion 53.9 (+/- 11.3; 27.6-67.4), lesion size 3.1 cm (+/- 0.5; 1.9-4.2 cm) and percentage of malignant cases 78.3% (+/- 26.8; 2.1-100). FNA and FNB diagnostic yield was 85.8% (+/- 10.3; 70.0-100.0) and 89.2% (+/- 7.7; 70.0-98.6), respectively. Average accuracy was 89.5% (+/- 11.7; 63.0-100.0) for FNA and 90.8% (+/- 7.1; 77.0-100.0) for FNB. Adverse effects rate was 1.0% (+/- 1.3; 0-4.3) for FNA and 2.2% (+/- 4.4; 0-16.1) for FNB. None of the selected variables had a significant statistical difference between both methods. FNA and FNB perform similarly for diagnostic material acquisition in pancreatic lesions. The best outcome comes from the association of both techniques, emphasizing the value of combining cytological and histological morphology for the most accurate analysis. Much has been debated about the supposed advantages of FNB versus FNA sample acquisition for pancreatic lesions, with limited improvement in clinical parameters. According to our analysis, FNA and FNB perform similarly for diagnostic material acquisition in pancreatic lesions, with room for association of both techniques, emphasizing the value of combining cytological and histological morphology for the most accurate analysis.image
Obituary Euphrosyne Setsu Umezawa
(2024) ANDRADE JUNIOR, Heitor Franco de
Demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy: an international cohort study and individual participant data meta-analysis
(2024) CHAPLEAU, Marianne; JOIE, Renaud La; YONG, Keir; AGOSTA, Federica; ALLEN, Isabel Elaine; APOSTOLOVA, Liana; BEST, John; BOON, Baayla D. C.; CRUTCH, Sebastian; FILIPPI, Massimo; FUMAGALLI, Giorgio Giulio; GALIMBERTI, Daniela; GRAFF-RADFORD, Jonathan; GRINBERG, Lea; IRWIN, David J.; JOSEPHS, Keith A.; MENDEZ, Mario F.; MENDEZ, Patricio Chrem; MIGLIACCIO, Raffaella; MILLER, Zachary A.; MONTEMBEAULT, Maxime; MURRAY, Melissa E.; NEMES, Sara; PELAK, Victoria; PERANI, Daniela; PHILLIPS, Jeffrey; PIJNENBURG, Yolande; ROGALSKI, Emily; SCHOTT, Jonathan M.; SEELEY, William; SULLIVAN, A. Campbell; SPINA, Salvatore; TANNER, Jeremy; WALKER, Jamie; WHITWELL, Jennifer L.; WOLK, David A.; OSSENKOPPELE, Rik; RABINOVICI, Gil
Background Posterior cortical atrophy is a rare syndrome characterised by early, prominent, and progressive impairment in visuoperceptual and visuospatial processing. The disorder has been associated with underlying neuropathological features of Alzheimer's disease, but large-scale biomarker and neuropathological studies are scarce. We aimed to describe demographic, clinical, biomarker, and neuropathological correlates of posterior cortical atrophy in a large international cohort. Methods We searched PubMed between database inception and Aug 1, 2021, for all published research studies on posterior cortical atrophy and related terms. We identified research centres from these studies and requested deidentified, individual participant data (published and unpublished) that had been obtained at the first diagnostic visit from the corresponding authors of the studies or heads of the research centres. Inclusion criteria were a clinical diagnosis of posterior cortical atrophy as defined by the local centre and availability of Alzheimer's disease biomarkers (PET or CSF), or a diagnosis made at autopsy. Not all individuals with posterior cortical atrophy fulfilled consensus criteria, being diagnosed using centre-specific procedures or before development of consensus criteria. We obtained demographic, clinical, biofluid, neuroimaging, and neuropathological data. Mean values for continuous variables were combined using the inverse variance meta-analysis method; only research centres with more than one participant for a variable were included. Pooled proportions were calculated for binary variables using a restricted maximum likelihood model. Heterogeneity was quantified using I-2. Findings We identified 55 research centres from 1353 papers, with 29 centres responding to our request. An additional seven centres were recruited by advertising via the Alzheimer's Association. We obtained data for 1092 individuals who were evaluated at 36 research centres in 16 countries, the other sites having not responded to our initial invitation to participate to the study. Mean age at symptom onset was 594 years (95% CI 589-598; I-2=77%), 60% (56-64; I-2=35%) were women, and 80% (72-89; I-2=98%) presented with posterior cortical atrophy pure syndrome. Amyloid beta in CSF (536 participants from 28 centres) was positive in 81% (95% CI 75-87; I-2=78%), whereas phosphorylated tau in CSF (503 participants from 29 centres) was positive in 65% (56-75; I-2=87%). Amyloid-PET (299 participants from 24 centres) was positive in 94% (95% CI 90-97; I-2=15%), whereas tau-PET (170 participants from 13 centres) was positive in 97% (93-100; I-2=12%). At autopsy (145 participants from 13 centres), the most frequent neuropathological diagnosis was Alzheimer's disease (94%, 95% CI 90-97; I-2=0%), with common co-pathologies of cerebral amyloid angiopathy (71%, 54-88; I-2=89%), Lewy body disease (44%, 25-62; I-2=77%), and cerebrovascular injury (42%, 24-60; I-2=88%). Interpretation These data indicate that posterior cortical atrophy typically presents as a pure, young-onset dementia syndrome that is highly specific for underlying Alzheimer's disease pathology. Further work is needed to understand what drives cognitive vulnerability and progression rates by investigating the contribution of sex, genetics, premorbid cognitive strengths and weaknesses, and brain network integrity.
Alzheimer's disease brain-derived extracellular vesicles reveal altered synapse-related proteome and induce cognitive impairment in mice
(2023) BODART-SANTOS, Victor; PINHEIRO, Lisandra S.; SILVA-JUNIOR, Almir J. da; FROZA, Rudimar L.; AHRENS, Rosemary; GONCALVES, Rafaella A.; ANDRADE, Mayara M.; CHEN, Yan; ALCANTARA, Carolina de Lima; GRINBERG, Lea T.; LEITE, Renata E. P.; FERREIRA, Sergio T.; FRASER, Paul E.; FELICE, Fernanda G. De
INTRODUCTIONExtracellular vesicles (EVs) have been implicated in the spread of neuropathology in Alzheimer's disease (AD), but their involvement in behavioral outcomes linked to AD remains to be determined. METHODSEVs isolated from post mortem brain tissue from control, AD, or frontotemporal dementia (FTD) donors, as well as from APP/PS1 mice, were injected into the hippocampi of wild-type (WT) or a humanized Tau mouse model (hTau/mTauKO). Memory tests were carried out. Differentially expressed proteins in EVs were assessed by proteomics. RESULTSBoth AD-EVs and APP/PS1-EVs trigger memory impairment in WT mice. We further demonstrate that AD-EVs and FTD-EVs carry Tau protein, present altered protein composition associated with synapse regulation and transmission, and trigger memory impairment in hTau/mTauKO mice. DISCUSSIONResults demonstrate that AD-EVs and FTD-EVs have negative impacts on memory in mice and suggest that, in addition to spreading pathology, EVs may contribute to memory impairment in AD and FTD. HighlightsA beta was detected in EVs from post mortem AD brain tissue and APP/PS1 mice.Tau was enriched in EVs from post mortem AD, PSP and FTD brain tissue.AD-derived EVs and APP/PS1-EVs induce cognitive impairment in wild-type (WT) mice.AD- and FTD-derived EVs induce cognitive impairment in humanized Tau mice.Proteomics findings associate EVs with synapse dysregulation in tauopathies.
Spatiotemporal characteristics of neurophysiological changes in patients with four-repeat tauopathies
(2024) SAMUDRA, Niyatee; LERNER, Hannah; YACK, Leslie; WALSH, Christine M.; KIRSCH, Heidi E.; KUDO, Kiwamu; YBALLA, Claire; JOIE, Renaud La; GORNO-TEMPINI, Maria L.; SPINA, Salvatore; SEELEY, William W.; NEYLAN, Thomas C.; MILLER, Bruce L.; RABINOVICI, Gil D.; BOXER, Adam; GRINBERG, Lea T.; RANKIN, Katherine P.; NAGARAJAN, Srikantan S.; RANASINGHE, Kamalini G.
IntroductionProgressive supranuclear palsy (PSP) and corticobasal degeneration (CBD), are the most common four-repeat tauopathies (4RT), and both frequently occur with varying degree of Alzheimer's disease (AD) copathology. Intriguingly, patients with 4RT and patients with AD are at opposite ends of the wakefulness spectrum-AD showing reduced wakefulness and excessive sleepiness whereas 4RT showing decreased homeostatic sleep. The neural mechanisms underlying these distinct phenotypes in the comorbid condition of 4RT and AD are unknown. The objective of the current study was to define the alpha oscillatory spectrum, which is prominent in the awake resting-state in the human brain, in patients with primary 4RT, and how it is modified in comorbid AD-pathology.MethodIn an autopsy-confirmed case series of 4R-tauopathy patients (n = 10), whose primary neuropathological diagnosis was either PSP (n = 7) or CBD (n = 3), using high spatiotemporal resolution magnetoencephalography (MEG), we quantified the spectral power density within alpha-band (8-12 Hz) and examined how this pattern was modified in increasing AD-copathology. For each patient, their regional alpha power was compared to an age-matched normative control cohort (n = 35).ResultPatients with 4RT showed increased alpha power but in the presence of AD-copathology alpha power was reduced.ConclusionsAlpha power increase in PSP-tauopathy and reduction in the presence of AD-tauopathy is consistent with the observation that neurons activating wakefulness-promoting systems are preserved in PSP but degenerated in AD. These results highlight the selectively vulnerable impacts in 4RT versus AD-tauopathy that may have translational significance on disease-modifying therapies for specific proteinopathies.
Maternal greenness exposure and preterm birth in Brazil: A nationwide birth cohort study*
(2024) YE, Tingting; XU, Rongbin; ABRAMSON, Michael J.; GUO, Yuming; ZHANG, Yiwen; SALDIVA, Paulo H. N.; COELHO, Micheline S. Z. S.; LI, Shanshan
In the dynamic landscape of maternal and child health, understanding the intricate interplay between environmental factors and pregnancy outcomes is of paramount importance. This study investigates the relationship between maternal greenness exposure and preterm births in Brazil using data spanning from 2010 to 2019. Satellite-derived indices, including the Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), were employed to assess greenness exposure during whole pregnancy in maternal residential area. Employing Cox proportional hazard models, we calculated the hazard ratios (HRs) with 95% confidence intervals (CIs) for changes in NDVI, while adjusting for individual and area-level covariates. In total, 24,010,250 live births were included. Prevalence of preterm birth was 11.5%, with a modest but statistically significant decreasing trend (p = 0.013) observed across the nation over the study period. The findings reveal a significant association between greenness exposure and a reduced risk of preterm birth. Specifically, for every 0.1 increase in NDVI, there was a 2.0% decrease in the risk of preterm birth (95%CI: 1.9%-2.2%). Stratified analyses based on maternal education and ethnicity indicated potential effect modifications, with stronger protective effects observed among younger mothers and those with less years of education. Sensitivity analyses using EVI yielded consistent results. In conclusion, this study suggests that higher maternal greenness exposure is linked to a decreased risk of preterm birth in Brazil. These findings imply that enhancing residential greenspaces could be a valuable public health strategy to promote maternal and child health in Brazil.
Comprehensive Glycoprofiling of Oral Tumors Associates N-Glycosylation With Lymph Node Metastasis and Patient Survival
(2023) CARNIELLI, Carolina Moretto; MORAIS, Thayna Melo de Lima; PATRONI, Fabio Malta de Sa; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; SOBROZA, Evandro; MATOS, Leandro Luongo; KOWALSKI, Luiz Paulo; LEME, Adriana Franco Paes; KAWAHARA, Rebeca; THAYSEN-ANDERSEN, Morten
While altered protein glycosylation is regarded a trait of oral squamous cell carcinoma (OSCC), the heterogeneous and dynamic glycoproteome of tumor tissues from OSCC patients remain unmapped. To this end, we here employ an integrated multi-omics approach comprising unbiased and quantitative glycomics and glycoproteomics applied to a cohort of resected primary tumor tissues from OSCC patients with (n = 19) and without (n = 12) lymph node metastasis. While all tumor tissues displayed relatively uniform N-glycome profiles suggesting overall stable global N-glycosylation during disease progression, altered expression of six sialylated N-glycans was found to correlate with lymph node metastasis. Notably, glycoproteomics and advanced statistical analyses uncovered altered site -specific Nglycosylation revealing previously unknown associations with several clinicopathological features. Importantly, the glycomics and glycoproteomics data unveiled that comparatively high abundance of two core-fucosylated and sialylated N-glycans (Glycan 40a and Glycan 46a) and one N-glycopeptide from fibronectin were associated with low patient survival, while a relatively low abundance of N-glycopeptides from both afamin and CD59 were also associated with poor survival. This study provides insight into the complex OSCC tissue Nglycoproteome, thereby forming an important resource to further explore the underpinning disease mechanisms and uncover new prognostic glycomarkers for OSCC.
Fragrances as a trigger of immune responses in different environments
(2024) MACCHIONE, M.; YOSHIZAKI, K.; FRIAS, D. P.; MAIER, K.; SMELAN, J.; PRADO, C. M.; MAUAD, T.
Fragrances can cause allergic skin reactions, expressed as allergic contact dermatitis and reactions in the respiratory tract that range from acute temporary upper airway irritation to obstructive lung disease. These adverse health effects may result from the stimulation of a specific (adaptive) immune response. Th1 cells, which essentially produce interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), play a key role in allergic contact dermatitis and also on allergic sensitization to common allergens (e.g., nickel and fragrance). It has been shown that fragrance allergy leads to Th2/Th22 production of IL-4, IL-5 and IL-13, controlling the development of IgE and mediating hypersensitivity reactions in the lung, such as asthma. Cytokines released during immune response modulate the expression of cytochrome P450 (CYPs) proteins, which can result in alterations of the pharmacological effects of substances in inflammatory diseases. The mechanisms linking environment and immunity are still not completely understood but it is known that aryl hydrocarbon receptor (AhR) is a sensor with conserved ligand-activated transcription factor, highly expressed in cells that controls complex transcriptional programs which are ligand and cell type specific, with CYPs as targeted genes. This review focuses on these important aspects of immune responses of the skin and respiratory tract cells, describing some in vitro models applied to evaluate the mechanisms involved in fragrance-induced allergy.
Ultrastructural characterization of alveolar microvascular damage in severe COVID-19 respiratory failure
(2023) NEGRI, Elnara Marcia; BENCHIMOL, Marlene; MAUAD, Thais; DUARTE-NETO, Amaro Nunes; GOTTARDI, Maiara; SILVA, Luiz Fernando Ferraz da; SALDIVA, Paulo Hilario Nascimento; DOLHNIKOFF, Marisa; SOUZA, Wanderley de; CALDINI, Elia Garcia
Endothelial dysfunction is a key phenomenon in COVID-19, induced by direct viral endothelial infection and secondary inflammation, mainly affecting the microvascular circulation. However, few studies described the subcellular aspects of the lung microvasculature and the associated thrombotic phenomena, which are widely present in severe COVID-19 cases. To that end, in this transversal observational study we performed transmission and scanning electron microscopy in nine lung samples of patients who died due to COVID-19, obtained via minimally invasive autopsies in Sao Paulo, Brazil, in 2020. All patients died due to acute respiratory failure and had microvascular thrombosis at histology. Electron microscopy revealed areas of endothelial damage with basal lamina disruption and virus infection in endothelial cells. In the capillary lumens, the ultrastructure of the thrombi is depicted, with red blood cells stacking, dysmorphism and hemolysis, fibrin meshworks, and extracellular traps. Our description illustrates the complex pathophysiology of microvascular thrombosis at the cellular level, which leads to some of the peculiar characteristics of severe COVID-19.
Chikungunya: a decade of burden in the Americas
(2024) SOUZA, William M. de; RIBEIRO, Guilherme S.; LIMA, Shirlene T. S. de; JESUS, Ronaldo de; MOREIRA, Filipe R. R.; WHITTAKER, Charles; SALLUM, Maria Anice M.; CARRINGTON, Christine V. F.; SABINO, Ester C.; KITRON, Uriel; FARIA, Nuno R.; WEAVER, Scott C.
In the Americas, one decade following its emergence in 2013, chikungunya virus (CHIKV) continues to spread and cause epidemics across the region. To date, 3.7 million suspected and laboratory-confirmed chikungunya cases have been reported in 50 countries or territories in the Americas. Here, we outline the current status and epidemiological aspects of chikungunya in the Americas and discuss prospects for future research and public health strategies to combat CHIKV in the region.

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