Artigos e Materiais de Revistas Científicas - LIM/03

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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 1 Citação(ões) na Scopus
    Immune Evasion of SARS-CoV-2 Omicron Subvariants XBB.1.5, XBB.1.16 and EG.5.1 in a Cohort of Older Adults after ChAdOx1-S Vaccination and BA.4/5 Bivalent Booster
    (2024) MACHADO, Rafael Rahal Guaragna; CANDIDO, erika Donizetti; AGUIAR, Andressa Simoes; CHALUP, Vanessa Nascimento; SANCHES, Patricia Romao; DORLASS, Erick Gustavo; AMGARTEN, Deyvid Emanuel; PINHO, Joao Renato Rebello; DURIGON, Edison Luiz; OLIVEIRA, Danielle Bruna Leal
    The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report the neutralizing activities of 177 sera samples from 59 older adults, aged 62-97 years, 1 and 4 months after vaccination with a 4th dose of ChAdOx1-S (Oxford/AstraZeneca) and 3 months after a 5th dose of Comirnaty Bivalent Original/Omicron BA.4/BA.5 vaccine (Pfizer-BioNTech). The ChAdOx1-S vaccination-induced antibodies neutralized efficiently the ancestral D614G and BA.4/5 variants, but to a much lesser extent the XBB.1.5, XBB.1.16, and EG.5.1 variants. The results showed similar neutralization titers between XBB.1.16 and EG.5.1 and were lower compared to XBB.1.5. Sera from the same individuals boosted with the bivalent mRNA vaccine contained higher neutralizing antibody titers, providing a better cross-protection against Omicron XBB.1.5, XBB.1.16 and EG.5.1 variants. Previous history of infection during the epidemiological waves of BA.1/BA.2 and BA.4/BA.5, poorly enhanced neutralization activity of serum samples against XBBs and EG.5.1 variants. Our data highlight the continued immune evasion of recent Omicron subvariants and support the booster administration of BA.4/5 bivalent vaccine, as a continuous strategy of updating future vaccine booster doses to match newly emerged SARS-CoV-2 variants.
  • article 1 Citação(ões) na Scopus
    Seroprevalence of hepatitis E virus in patients with chronic liver disease
    (2024) ARAUJO, Lilian Rose Maia Gomes de; BATISTA, Andrea Doria; COELHO, Maria Rosangela Cunha Duarte; SANTOS, Joelma Carvalho; CUNHA, Gabriel Galindo; LEAL, Gabriela Rodrigues Aguiar; PINHO, Joao Renato Rebello; DOMINGUES, Ana Lucia Coutinho; LOPES, Edmundo Pessoa
    IntroductionThe seroprevalence of hepatitis E virus (HEV) in patients with chronic liver disease (CLD) is little known in Brazil. Studies have suggested that HEV may harmfully influence the course of CLD, with a higher risk of progression to cirrhosis.ObjectiveTo estimate the prevalence of the anti-HEV antibody (IgG) in patients with CLD and to describe demographic data and risk factors, as well as clinical-laboratory and ultrasound parameters.Patients and methodsCross-sectional study that included 227 patients with CLD followed at a referral outpatient clinic from June 2022 to March 2023. The patients were investigated clinically and tested for liver functions, anti-HEV IgG and, in positive cases, for HEV-RNA. Ultrasonography of the upper abdomen was also carried out.ResultsInvestigation of 227 patients (50 with hepatitis B, 49 with nonalcoholic fatty liver disease, 33 with hepatitis C, 17 with alcoholic liver disease, 16 with schistosomiasis and 62 with mixed disease), 55.5% were female, with an average age of 57 +/- 13 years; 37.9% had liver cirrhosis. Seven patients (3.08%) presented anti-HEV positive and HEV-RNA negative. Ultrasound identified association between anti-HEV and contact with pigs, presence of gynecomastia or palmar erythema, lower platelet count, higher APRI and FIB-4 values, and splenomegaly.ConclusionAlthough the prevalence of anti-HEV in patients with CLD was low in this study, the antibody was observed more frequently in cases with a history of contact with pigs and with clinical-laboratory or imaging evidence of more advanced chronic liver disease.
  • article 0 Citação(ões) na Scopus
    Influenceofbloodphenylalaninelevelvariationsonthedevelopmentofexecutivefunctionsandsocialcognitioninchildrenwithphenylketonuria
    (2023) DUARTE, Cristiane Mendes de Almeida; PIAZZON, Flavia Balbo; ROCCO, Isadora Salvador; MELLO, Claudia Berlim de
    Toinvestigatetheperformanceof27childrenwithphenylketonuria(PKU) intestsofExecutiveFunctions( EF) andSocialCognition(SC), andtheirassociationswithmetaboliccontrolinferredbyphenylalanine( Phe) levels. Methods: ThePKUgroupwasdichotomizedaccordingtobaselinePhe-levelsinto;""classicalPKU""( n= 14), withPhe-levelsabove1200mmol/L(> 20mg/dL); and""mildPKU""(n= 13) withPhebetween360and1200mmol/L(6-20mg/dL). TheneuropsychologicalassessmentfocusedontheEFandSCsubtestsoftheNEPSYIIbatteryandintellectualperformance. Childrenwerecomparedtoagematchedhealthyparticipants. Results: ParticipantswithPKUpresentedsignificantlylowerIntellectualQuotient(IQ) comparedtocontrols( p= 0.001). RegardingEFanalysisadjustedbyageandIQ, significantdifferencesbetweengroupswereobservedonlyintheexecutiveattentionsubtests( p= 0.029). TheSCsetofvariableswassignificantlydifferentbetweengroups( p= 0.003), asintheaffectiverecognitiontask(p< 0.001). InthePKUgroup, therelativevariationofPhe-achieved32.1 +/- 21.0%. RelativePhe-variationwascorrelatedonlywithmeasuresofWorkingMemory(p< 0.001), VerbalFluency( p= 0.004), InhibitoryControl(p= 0.035) andTheoryofMind(p= 0.003). Conclusions: PhonologicalVerbalFluency, WorkingMemory, InhibitoryControl, andTheoryofMindwereshowntobemostvulnerablewhenthereisnonidealmetaboliccontrol. VariationsinthelevelofPhemayhaveaselectivenegativeeffectonExecutiveFunctionsandSocialCogni- tion, butnotonintellectualperformance.
  • article 0 Citação(ões) na Scopus
    Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service
    (2024) ADRIANO, Marcia Regina Gimenes; BORTOLAI, Adriana; MADIA, Fabricia Andreia Rosa; CARVALHO, Gleyson Francisco da Silva; NASCIMENTO, Amom Mendes; ZANARDO, Evelin Aline; WOLFF, Beatriz Martins; WAISBERG, Jaques; BOS-MIKICH, Adriana; KULIKOWSKI, Leslie Domenici; DIAS, Alexandre Torchio
    ObjectivesMale infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience.ResultsWe evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).
  • article 0 Citação(ões) na Scopus
    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.
  • article 0 Citação(ões) na Scopus
    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
  • article 0 Citação(ões) na Scopus
    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.
  • article 0 Citação(ões) na Scopus
    Incomplete recovery of the CD4+/CD8+ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection
    (2024) PRATES, Gabriela da Silva; MONTEIRO, Mariana Amelia; OLIVEIRA, Ericka Constantinov; NASCIMENTO, Najara Ataide de Lima; VEIGA, Ana Paula Rocha; FERREIRA, Mauricio Domingues; POLIS, Thales Jose Bueno; CAETANO, Gabriela Prandi; SOARES, Beatriz Rodrigues Pellegrina; MAGRI, Marcello Mihailenko Chaves; PEREIRA, Luisa Oliveira; FONSECA, Luiz Augusto Marcondes; ALVES, Wagner Silva; DUARTE, Alberto Jose da Silva; CASSEB, Jorge Simao do Rosario
    Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4(+)/CD8(+) ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4(+)/CD8(+) ratio was <= 1 for 70% of the patients in both groups. Older age, CD4(+) cell count at inclusion, Nadir CD8(+)T-cell count, and Initial CD4(+)/CD8(+) ratio <= 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4(+)/CD8(+) ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4(+)/CD8(+) ratio > 1. The nadir CD4(+)T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4(+)/CD8(+) ratio <= 1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.
  • article 1 Citação(ões) na Scopus
    Biallelic variants in DNA2 cause poikiloderma with congenital cataracts and severe growth failure reminiscent of Rothmund-Thomson syndrome
    (2023) LAZZARO FILHO, Ricardo Di; YAMAMOTO, Guilherme Lopes; SILVA, Tiago J.; ROCHA, Leticia A.; LINNENKAMP, Bianca D. W.; CASTRO, Matheus Augusto Araujo; BARTHOLDI, Deborah; SCHALLER, Andre; LEEB, Tosso; KELMANN, Samantha; UTAGAWA, Claudia Y.; STEINER, Carlos E.; STEINMETZ, Leandra; HONJO, Rachel Sayuri; KIM, Chong Ae; WANG, Lisa; ABOURJAILI-BILODEAU, Raphael; CAMPEAU, Philippe; WARMAN, Matthew; PASSOS-BUENO, Maria Rita; HOCH, Nicolas C.; BERTOLA, Debora Romeo
    Rothmund-Thomson syndrome (RTS) is a rare, heterogeneous autosomal recessive genodermatosis, with poikiloderma as its hallmark. It is classified into two types: type I, with biallelic variants in ANAPC1 and juvenile cataracts, and type II, with biallelic variants in RECQL4, increased cancer risk and no cataracts. We report on six Brazilian probands and two siblings of Swiss/Portuguese ancestry presenting with severe short stature, widespread poikiloderma and congenital ocular anomalies. Genomic and functional analysis revealed compound heterozygosis for a deep intronic splicing variant in trans with loss of function variants in DNA2, with reduction of the protein levels and impaired DNA double-strand break repair. The intronic variant is shared by all patients, as well as the Portuguese father of the European siblings, indicating a probable founder effect. Biallelic variants in DNA2 were previously associated with microcephalic osteodysplastic primordial dwarfism. Although the individuals reported here present a similar growth pattern, the presence of poikiloderma and ocular anomalies is unique. Thus, we have broadened the phenotypical spectrum of DNA2 mutations, incorporating clinical characteristics of RTS. Although a clear genotype-phenotype correlation cannot be definitively established at this moment, we speculate that the residual activity of the splicing variant allele could be responsible for the distinct manifestations of DNA2-related syndromes.
  • article 2 Citação(ões) na Scopus
    Burden of Rare Copy Number Variants in Microcephaly: A Brazilian Cohort of 185 Microcephalic Patients and Review of the Literature
    (2024) TOLEZANO, Giovanna Cantini; BASTOS, Giovanna Civitate; COSTA, Silvia Souza da; FREIRE, Bruna Lucheze; HOMMA, Thais Kataoka; HONJO, Rachel Sayuri; YAMAMOTO, Guilherme Lopes; PASSOS-BUENO, Maria Rita; KOIFFMANN, Celia Priszkulnik; KIM, Chong Ae; VIANNA-MORGANTE, Angela Maria; JORGE, Alexander Augusto de Lima; BERTOLA, Debora Romeo; ROSENBERG, Carla; KREPISCHI, Ana Cristina Victorino
    Microcephaly presents heterogeneous genetic etiology linked to several neurodevelopmental disorders (NDD). Copy number variants (CNVs) are a causal mechanism of microcephaly whose investigation is a crucial step for unraveling its molecular basis. Our purpose was to investigate the burden of rare CNVs in microcephalic individuals and to review genes and CNV syndromes associated with microcephaly. We performed chromosomal microarray analysis (CMA) in 185 Brazilian patients with microcephaly and evaluated microcephalic patients carrying < 200 kb CNVs documented in the DECIPHER database. Additionally, we reviewed known genes and CNV syndromes causally linked to microcephaly through the PubMed, OMIM, DECIPHER, and ClinGen databases. Rare clinically relevant CNVs were detected in 39 out of the 185 Brazilian patients investigated by CMA (21%). In 31 among the 60 DECIPHER patients carrying < 200 kb CNVs, at least one known microcephaly gene was observed. Overall, four gene sets implicated in microcephaly were disclosed: known microcephaly genes; genes with supporting evidence of association with microcephaly; known macrocephaly genes; and novel candidates, including OTUD7A, BBC3, CNTN6, and NAA15. In the review, we compiled 957 known microcephaly genes and 58 genomic CNV loci, comprising 13 duplications and 50 deletions, which have already been associated with clinical findings including microcephaly. We reviewed genes and CNV syndromes previously associated with microcephaly, reinforced the high CMA diagnostic yield for this condition, pinpointed novel candidate loci linked to microcephaly deserving further evaluation, and provided a useful resource for future research on the field of neurodevelopment.
  • article 0 Citação(ões) na Scopus
    Disease progression in Sanfilippo type B: Case series of Brazilian patients
    (2024) MONTENEGRO, Yorran Hardman Araujo; KUBASKI, Francyne; TRAPP, Franciele Barbosa; RIEGEL-GIUGLIANI, Mariluce; SOUZA, Carolina Fischinger Moura de; RIBEIRO, Erlane Marques; LOURENCO, Charles Marques; CARDOSO-DOS-SANTOS, Augusto Cesar; RIBEIRO, Marcia Goncalves; KIM, Chong Ae; CASTRO, Matheus Augusto Araujo; EMBIRUCU, Emilia Katiane; STEINER, Carlos Eduardo; VAIRO, Filippo Pinto e; BALDO, Guilherme; GIUGLIANI, Roberto; POSWAR, Fabiano de Oliveira
    Mucopolysaccharidosis type IIIB (MPS IIIB) is caused by deficiency of alpha-N-acetylglucosaminidase, leading to storage of heparan sulphate. The disease is characterized by intellectual disability and hyperactivity, among other neurological and somatic features. Here we studied retrospective data from a total of 19 MPS IIIB patients from Brazil, aiming to evaluate disease progression. Mean age at diagnosis was 7.2 years. Speech delay was one of the first symptoms to be identified, around 2-3 years of age. Behavioral alterations include hyperactivity and aggressiveness, starting around age four. By the end of the first decade, patients lost acquired abilities such as speech and ability to walk. Furthermore, as disease progresses, respiratory, cardiovascular and joint abnormalities were found in more than 50% of the patients, along with organomegaly. Most common cause of death was respiratory problems. The disease progression was characterized in multiple systems, and hopefully these data will help the design of appropriate clinical trials and clinical management guidelines.
  • article 0 Citação(ões) na Scopus
    Study of the peripheral and central auditory pathways in patients with mucopolysaccharidosis
    (2024) CHIMELO, Flavia Teixeira; SILVA, Liliane Aparecida Fagundes; NEVES-LOBO, Ivone Ferreira; KIM, Chong Ae; MATAS, Carla Gentile
    Objective: To investigate the peripheral and central auditory pathways in mucopolysaccharidosis (MPS) individuals. Method: The research sample comprised 15 individuals (one female and 14 males), aged 8 to 46 years. The following procedures were used: medical history survey, otoscopy, speech and puretone threshold audiometry, acoustic immittance measures, and central auditory pathway assessment with brainstem auditory evoked potentials (BAEP) and long-latency auditory evoked potentials (LLAEP). Results: The pure-tone audiometry identified hearing loss in 13 individuals, and more than 90 % of the hearing loss was sensorineural. The degree of hearing loss was between mild to moderately severe with descendent configuration. Type A tympanogram predominated, and acoustic reflexes were present according to the types and degrees of hearing loss. Among the individuals with abnormal BAEP, longer wave III and V absolute latencies were the main findings. In addition, the unilateral absence of wave I was observed in two cases. In the LLAEP, longer latencies were observed in 14 individuals, and the most impaired components were the P1 and P3 in children and adolescents and the P2, N2 and P3 in adult individuals. Conclusion: The peripheral auditory pathway assessment revealed a predominantly sensorineural hearing loss, affecting mainly high frequencies, and in the central pathway was observed abnormal brainstem and cortical auditory processing in individuals with MPS.
  • article 0 Citação(ões) na Scopus
    Itraconazole Serum Trough Concentrations Using Oral Capsules for the Treatment of Chronic Pulmonary Aspergillosis: What is the Target?
    (2023) OLIVEIRA, Vitor Falcao de; TABORDA, Mariane; ARCIERI, Vitor Ciampone; KRUSCHEWSKY, Wdson Luis Lima; COSTA, Andre Nathan; DUARTE, Nilo Jose Coelho; ROMANO, Paschoalina; EBNER, Persio de Almeida Rezende; MAGRI, Adriana Satie Goncalves Kono; ABDALA, Edson; LEVIN, Anna S. S.; MAGRI, Marcello Mihailenko Chaves
    BackgroundIn regions where there is only itraconazole capsule as a therapeutic option for treatment of chronic pulmonary aspergillosis (CPA), measuring the serum concentrations becomes even more important for therapeutic success.ObjectiveEvaluate the initial itraconazole serum trough concentrations after the administration of oral capsule of itraconazole for the treatment of CPA.MethodsThe measurement was performed at least 7-days after initiation of therapy. The standard treatment at our institution was a 200 mg capsule every 12 h. We defined that an adequate serum trough concentration of itraconazole during treatment was 1-4 mg/L.ResultsThis study recruited 28 patients. The median value was 0.30 mg/L (IQR 0.01-0.70). Only 11% (n = 3) had adequate serum concentrations based on guideline recommendation. All patients with clinical deterioration had itraconazole serum levels <= 0.8 mg/L.ConclusionThe initial serum concentrations of itraconazole after capsule formulation administration were low. Increasing the dose should be considered when the itraconazole concentration is low, especially if it is <= 0.8 mg/L, and the patient presents with clinical deterioration. Larger studies are needed to evaluate the adequate concentrations recommended for CPA.
  • article 0 Citação(ões) na Scopus
    Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
    (2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
    Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
  • article 0 Citação(ões) na Scopus
    Impacts of the first wave of the COVID-19 pandemic on leisure and transportation physical activity among healthcare workers
    (2024) GURGEL, Aline Rachel Bezerra; GUIMARAES, Jean Augusto Coelho; BRUM, Patricia Chakur; LIMA, Antonio Carlos Pedroso de; GIAVINA-BIANCHI, Pedro; PERES, Carlos Henrique Mesquita; FRANCISCO, Maria Cristina Peres Braido; SANTOS, Lanuse Garcia Neves dos; SANTOS, Rita de Cassia Cezar; SANTOS, Roseli Eliana Beseggio; CORA, Aline; DUARTE, Alberto Jose da Silva; LAZARI, Carolina dos Santos; PEREIRA, Antonio Jose; SABINO, Ester Cerdeira; CORCHS, Felipe; SEGURADO, Aluisio Cotrim; COSTA, Silvia Figueiredo; LEVIN, Anna S.
    Introduction: The COVID-19 pandemic may lead to reduced physical activity (PA) in health care workers (HCWs). Objective: To evaluate leisure and transport-related PA in HCW of a COVID-19-dedicated hospital during the first wave of the COVID-19 pandemic. Methods: This is a cross-sectional study with a sample of 1,527 HCWs. Socioeconomic aspects, occupational characteristics, and engagement in leisure and transport-related PA were investigated through an online survey administered in August of 2020. Results: More than 80 % HCWs performed < 150 min/week of leisure-related PA, and 85 % performed <= 30 min/ day transport-related PA. Being male was associated with more PA (OR: 1.93; 95 % CI:1.40-2.66) and transportrelated PA; working in nursing, physical therapy, and cleaning/housekeeping services was associated with low PA (OR: 0.70; 95 % CI:0.51-0.95). Physicians and administrative staff were less active in transport-related PA. Conclusions: HCWs working in a COVID-19 hospital had low levels of PA in the domains of leisure and transportation.
  • article 1 Citação(ões) na Scopus
    Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
    (2023) BRITO-ZERON, P.; FLORES-CHAVEZ, A.; NG, W. -F.; HORVATH, I. Fanny; RASMUSSEN, A.; PRIORI, R.; BALDINI, C.; ARMAGAN, B.; OZKIZILTAS, B.; PRAPROTNIK, S.; SUZUKI, Y.; QUARTUCCIO, L.; HERNANDEZ-MOLINA, G.; ABACAR, K.; BARTOLONI, E.; RISCHMUELLER, M.; OLIVEIRA, F. Reis-de; TREVISANI, V. Fernandes Moca; JURCUT, C.; FUGMANN, C.; CARUBBI, F.; HOFAUER, B.; VALIM, V.; PASOTO, S. G.; RETAMOZO, S.; ATZENI, F.; FONSECA-AIZPURU, E.; LOPEZ-DUPLA, M.; GIACOMELLI, R.; NAKAMURA, H.; AKASBI, M.; THOMPSON, K.; SZANTO, A.; FARRIS, A. D.; VILLA, M.; BOMBARDIERI, S.; KILIC, L.; TUFAN, A.; PIRKMAJER, K. Perdan; FUJISAWA, Y.; VITA, S. De; INANC, N.; RAMOS-CASALS, M.
    ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
  • article 1 Citação(ões) na Scopus
    Influence of exposure to climate-related hazards in the phenotypic expression of primary Sjögren's syndrome
    (2023) FLORES-CHAVEZ, A.; BRITO-ZERON, P.; NG, W. -f.; SZANTO, A.; RASMUSSEN, A.; PRIORI, R.; BALDINI, C.; ARMAGAN, B.; OEZKIZILTAS, B.; PRAPROTNIK, S.; SUZUKI, Y.; QUARTUCCIO, L.; HERNANDEZ-MOLINA, G.; INANC, N.; BARTOLONI, E.; RISCHMUELLER, M.; OLIVEIRA, F. Reis-de; TREVISANI, V. Fernandes Moca; JURCUT, C.; NORDMARK, G.; CARUBBI, F.; HOFAUER, B.; VALIM, V.; PASOTO, S. G.; RETAMOZO, S.; ATZENI, F.; FONSECA-AIZPURU, E.; LOPEZ-DUPLA, M.; GIACOMELLI, R.; NAKAMURA, H.; AKASBI, M.; THOMPSON, K.; HORVATH, I. Fanny; FARRIS, A. D.; SIMONCELLI, E.; BOMBARDIERI, S.; KILIC, L.; TUFAN, A.; PIRKMAJER, K. Perdan; FUJISAWA, Y.; VITA, S. De; ABACAR, K.; RAMOS-CASALS, M.
    Objective To analyse how the key components at the time of diagnosis of the Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease) can be influenced by the potential exposure to climate-related natural hazards. Methods For the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Climate-related hazards per country were defined according to the OECD and included seven climate-related hazard types: extreme temperature, extreme precipitation, drought, wildfire, wind threats, river flooding, and coastal flooding. Climatic variables were defined as dichotomous variables according to whether each country is ranked among the ten countries with the most significant exposure. Results After applying data-cleaning techniques and excluding people from countries not included in the OECD climate rankings, the database study analysed 16,042 patients from 23 countries. The disease was diagnosed between 1 and 3 years earlier in people living in countries included among the top 10 worst exposed to extreme precipitation, wildfire, wind threats, river flooding, and coastal flooding. A lower frequency of dry eyes was observed in people living in countries exposed to wind threats, river flooding, and coastal flooding, with a level of statistical association being classified as strong (p<0.0001 for the three variables). The frequency of dry mouth was significantly lower in people living in countries exposed to river flooding (p<0.0001) and coastal flooding (p<0.0001). People living in countries included in the worse climate scenarios for extreme temperature (p<0.0001) and river flooding (p<0.0001) showed a higher mean ESSDAI score in comparison with people living in no-risk countries. In contrast, those living in countries exposed to worse climate scenarios for wind threats (p<0.0001) and coastal flooding (p<0.0001) showed a lower mean ESSDAI score in comparison with people living in no-risk countries. Conclusion Local exposure to extreme climate-related hazards plays a role in modulating the presentation of Sjogren across countries concerning the age at which the disease is diagnosed, the frequency of dryness, and the degree of systemic activity.
  • article 0 Citação(ões) na Scopus
    Investigation of etiology of community-acquired pneumonia in hospitalized patients in a tertiary hospital of Sao Paulo City, Brazil
    (2023) JOELSONS, Daniel; ALENCAR, Cecilia Salete; PINHO, Joao Renato Rebello; HO, Yeh-Li
    Background: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations. Methods: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens. Results: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy. Conclusion: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics. (c) 2023 Sociedade Brasileira de Infectologia.
  • article 0 Citação(ões) na Scopus
    Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility
    (2023) MINUTENTAG, Iael Weissberg; SENEDA, Ana Laura; BARROS-FILHOS, Mateus C.; CARVALHO, Marcio de; SOUZA, Vanessa G. P.; HASIMOTO, Claudia N.; MORAES, Marcelo P. T.; MARCHI, Fabio A.; LAM, Wan L.; REIS, Patricia P.; DRIGO, Sandra A.
    Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment.
  • article 0 Citação(ões) na Scopus
    Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins
    (2023) PRIETO, T. G.; BALDAVIRA, C. M.; MACHADO-RUGOLO, J.; OLIVIERI, E. H. R.; SILVA, E. C. A. da; SILVA, V. G.; ABSABER, A. M.; TAKAGAKI, T. Y.; CAPELOZZI, V. L.
    Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete-scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/ NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.