Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 76
Filtrar
1.
BMC Pediatr ; 24(1): 177, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38481225

RESUMO

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.


Assuntos
Anti-Infecciosos , Lactente , Criança , Humanos , Brasil , Hospitais , Hospitalização , Criança Hospitalizada , Antibacterianos/uso terapêutico , Hospitais Pediátricos
2.
Nat Commun ; 15(1): 14, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38167882

RESUMO

Cyclic high-dose testosterone administration, known as bipolar androgen therapy (BAT), is a treatment strategy for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we report the results of a multicenter, single arm Phase 2 study (NCT03554317) enrolling 45 patients with heavily pretreated mCRPC who received BAT (testosterone cypionate, 400 mg intramuscularly every 28 days) with the addition of nivolumab (480 mg intravenously every 28 days) following three cycles of BAT monotherapy. The primary endpoint of a confirmed PSA50 response rate was met and estimated at 40% (N = 18/45, 95% CI: 25.7-55.7%, P = 0.02 one-sided against the 25% null hypothesis). Sixteen of the PSA50 responses were achieved before the addition of nivolumab. Secondary endpoints included objective response rate (ORR), median PSA progression-free survival, radiographic progression-free survival (rPFS), overall survival (OS), and safety/tolerability. The ORR was 24% (N = 10/42). Three of the objective responses occurred following the addition of nivolumab. After a median follow-up of 17.9 months, the median rPFS was 5.6 (95% CI: 5.4-6.8) months, and median OS was 24.4 (95% CI: 17.6-31.1) months. BAT/nivolumab was well tolerated, resulting in only five (11%) drug related, grade-3 adverse events. In a predefined exploratory analysis, clinical response rates correlated with increased baseline levels of intratumoral PD-1 + T cells. In paired metastatic tumor biopsies, BAT induced pro-inflammatory gene expression changes that were restricted to patients achieving a clinical response. These data suggest that BAT may augment antitumor immune responses that are further potentiated by immune checkpoint blockade.


Assuntos
Nivolumabe , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Nivolumabe/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Androgênios , Antígeno Prostático Específico , Intervalo Livre de Progressão , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Prostate ; 84(2): 148-157, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37849074

RESUMO

BACKGROUND: Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. METHODS: A robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). RESULTS: This new assay (telomere chromogenic in situ hybridization ["Telo-CISH"]) produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. CONCLUSIONS: In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.


Assuntos
Lesões Pré-Cancerosas , Próstata , Masculino , Humanos , Hibridização in Situ Fluorescente/métodos , Hibridização In Situ , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/genética , Telômero
4.
BMC Gastroenterol ; 23(1): 419, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030984

RESUMO

BACKGROUND: Demonstration of access to the bile duct through Enlarged Papillary Fistulotomy, a method different from conventional fistulotomy. AIMS: Demonstration of the EFP technique with dissection in layers of the papilla for accessing the common bile duct, its efficiency and safety, rescue of cases of failure in cannulation and cases of access failure by EFP in the first attempt, facilitating cannulation in the second attempt. METHODS: Cross-sectional study, with retrospective data collection from 2233 ERCP exams with 528 EFP procedures, analysis of success and complications. RESULTS: 528 patients underwent EFP on the first attempt, with success in 465 cases (88.06%) and 63 failures (11.94%). Of these failures, 33 patients (52.38%) returned for a second EFP attempt, with success in 30 cases (90.9%) and failure in 3 cases (9.1%). Deep bile duct cannulation was achieved in 93.75% of EFP procedures, and cannulation failure occurred in 33 cases (6.25%). CONCLUSION: EFP showed efficiency in CBD cannulation, did not induce post-ERCP pancreatitis, no cases of perforation or false tract, but resulted in higher rates of minor bleeding, rescued cases of access failure by EFP, facilitated the posterior approach on the second attempt, it is safe, effective, low risk and associated with few comorbidities.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Esfinterotomia Endoscópica , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Esfinterotomia Endoscópica/efeitos adversos , Esfinterotomia Endoscópica/métodos , Estudos Retrospectivos , Estudos Transversais , Ducto Colédoco/diagnóstico por imagem , Ducto Colédoco/cirurgia
5.
Int J Biol Macromol ; 252: 126529, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-37633557

RESUMO

Although latex fluids are found in >20,000 plant species, the biochemical composition and biological function of their proteins are still poorly explored. Thus, this work aimed to conduct a proteomic analysis of Cryptostegia grandiflora latex (CgLP) for subsequent purification and characterization of an antifungal protein. After 2D-SDS-PAGE and mass spectrometry, 27 proteins were identified in CgLP, including a polygalacturonase inhibitor, cysteine peptidases, pathogenesis-related proteins (PR-4), and osmotins. Then, two osmotin isoforms (CgOsm) were purified, and a unique N-terminal sequence was determined (1ATFDIRSNCPYTVWAAAVPGGGRRLDRGQTWTINVAPGTA40). The PCR products revealed a cDNA sequence of 609 nucleotides for CgOsm, which encoded a polypeptide with 203 amino acid residues. The structure of CgOsm has features of typical osmotin or thaumatin-like proteins (TLPs), such as 16 conserved Cys residues, REDDD and FF motifs, an acidic cleft, and three main domains. Atomic force microscopy (AFM) and bioinformatics suggested that CgOsm is associated with three chain units. This result was interesting since the literature describes osmotins and TLPs as monomers. AFM also showed that Fusarium falciforme spores treated with CgOsm were drastically damaged. Therefore, it is speculated that CgOsm forms pores in the membrane of these cells, causing the leakage of cytoplasmic content.


Assuntos
Apocynaceae , Látex , Látex/química , Proteômica , Proteínas de Plantas/química , Isoformas de Proteínas/genética , Apocynaceae/química
6.
J. coloproctol. (Rio J., Impr.) ; 43(2): 75-81, Apr.-June 2023. graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1514427

RESUMO

Introduction: Anal examination and videoanoscopy (VA) are rarely performed during colonoscopies. In recent years, there has been a considerable increase in lesions of sexually transmitted anal and rectal infections, but these conditions are not noticed or reported during routine colonoscopy. Objective: To raise awareness regarding the fortuitous findings of lesions and sexually transmitted infections (STIs) in colonoscopy exams and to demonstrate that anal examination and VA provide important information and should be routinely performed. Methods: We conducted a descriptive retrospective study in 16,132 patients screened by colonoscopy and VA between 2006 and 2018. Among numerous other findings, the presence of anal condylomata and sexually transmitted retitis or perianal dermatitis was observed. The rates of each finding were calculated, and the patients were subdivided by sex and into age groups by blocks of ten years. Results: Among the 16,132 colonoscopies performed, 26 cases of condyloma (0.16%) and 50 cases of proctitis or perianal dermatitis suspicious for STI (0.33%) were found. Conclusion: Performing anal examination and VA systematically in all routine colonoscopies enabled the identification of numerous anal conditions, including several fortuitous cases of STIs. The study proposes that anal examination and VA should be performed in all routine colonoscopies and, in suspected cases, complementary tests for STIs. (AU)


Assuntos
Canal Anal/lesões , Neoplasias do Ânus/diagnóstico , Colonoscopia , Infecções por Papillomavirus/diagnóstico , Carcinoma in Situ/diagnóstico , Infecções por Papillomavirus/terapia , Dermatite de Contato/diagnóstico
7.
Anal Chem ; 95(16): 6507-6513, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37058365

RESUMO

The quantification of non-basic nitrogen-containing compounds (NCCs) in petroleum-derived samples has become a critical issue due to the undesirable effects of these compounds on the petroleum industry. In addition, there is a lack of analytical methods that allow the direct quantification of NCCs in these matrices. This paper provides strategies for obtaining quantitative information of NCCs in petroleum-derived samples using direct flow injection electrospray ionization (ESI) (-) Orbitrap mass spectrometry without fractionation steps. Benzocarbazole (BC) quantification was performed using the standard addition method. The method was validated, and all analytical parameters demonstrated satisfactory results in the matrix-mix. Paired Student's t-test exhibited the matrix effect (95% confidence level, p < 0.05). Limits of detection ranged from 2.94 to 14.91 µg L-1, and the limits of quantification ranged from 9.81 to 49.69 µg L-1. Intraday and interday accuracy and precision were not above 15%. Quantification of non-basic NCCs was carried out based on two approaches. In approach 1, the non-basic NCCs' total content in petroleum-derived samples was determined by the BC concentration and the total abundance correction. The method presented good performance with the average error of 21, 8.3, and 28% for crude oil, gas oil, and diesel samples, respectively. Approach 2 was based on the multiple linear regression model with regression significant at a 0.05 significance level within average relative errors of 16, 7.8, and 17% for the crude oil, gas oil, and diesel samples, respectively. Then, both approaches successfully predicted the quantification of non-basic NCCs by ESI direct flow injection.

8.
bioRxiv ; 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37066381

RESUMO

Telomeres are terminal chromosomal elements that are essential for the maintenance of genomic integrity. The measurement of telomere content provides useful diagnostic and prognostic information, and fluorescent methods have been developed for this purpose. However, fluorescent-based tissue assays are cumbersome for investigators to undertake, both in research and clinical settings. Here, a robust chromogenic in situ hybridization (CISH) approach was developed to visualize and quantify telomere content at single cell resolution in human prostate tissues, both frozen and formalin-fixed, paraffin-embedded (FFPE). This new assay ("Telo-CISH") produces permanently stained slides that are viewable with a standard light microscope, thus avoiding the need for specialized equipment and storage. The assay is compatible with standard immunohistochemistry, thereby allowing simultaneous assessment of histomorphology, identification of specific cell types, and assessment of telomere status. In addition, Telo-CISH eliminates the problem of autofluorescent interference that frequently occurs with fluorescent-based methods. Using this new assay, we demonstrate successful application of Telo-CISH to help identify precancerous lesions in the prostate by the presence of markedly short telomeres specifically in the luminal epithelial cells. In summary, with fewer restrictions on the types of tissues that can be tested, and increased histologic information provided, the advantages presented by this novel chromogenic assay should extend the applicability of tissue-based telomere length assessment in research and clinical settings.

9.
J Pediatric Infect Dis Soc ; 12(2): 76-82, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36461778

RESUMO

INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.


Assuntos
Anti-Infecciosos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Criança , Humanos , Brasil , Criança Hospitalizada , Estudos Prospectivos , Sistemas de Notificação de Reações Adversas a Medicamentos
10.
J Clin Invest ; 132(23)2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36194476

RESUMO

Testosterone is the canonical growth factor of prostate cancer but can paradoxically suppress its growth when present at supraphysiological levels. We have previously demonstrated that the cyclical administration of supraphysiological androgen (SPA), termed bipolar androgen therapy (BAT), can result in tumor regression and clinical benefit for patients with castration-resistant prostate cancer. However, predictors and mechanisms of response and resistance have been ill defined. Here, we show that growth inhibition of prostate cancer models by SPA required high androgen receptor (AR) activity and were driven in part by downregulation of MYC. Using matched sequential patient biopsies, we show that high pretreatment AR activity predicted downregulation of MYC, improved clinical response, and prolonged progression-free and overall survival for patients on BAT. BAT induced strong downregulation of AR in all patients, which is shown to be a primary mechanism of acquired resistance to SPA. Acquired resistance was overcome by alternating SPA with the AR inhibitor enzalutamide, which induced adaptive upregulation of AR and resensitized prostate cancer to SPA. This work identifies high AR activity as a predictive biomarker of response to BAT and supports a treatment paradigm for prostate cancer involving alternating between AR inhibition and activation.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Masculino , Humanos , Receptores Androgênicos/metabolismo , Androgênios/farmacologia , Neoplasias de Próstata Resistentes à Castração/metabolismo , Antagonistas de Receptores de Andrógenos/farmacologia , Antagonistas de Receptores de Andrógenos/uso terapêutico , Nitrilas , Testosterona/farmacologia , Resistencia a Medicamentos Antineoplásicos , Linhagem Celular Tumoral
11.
Mol Cell Endocrinol ; 558: 111775, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36096380

RESUMO

Gender-bias in COVID-19 severity has been suggested by clinical data. Experimental data in cell and animal models have demonstrated the role of sex hormones, particularly estrogens, in viral infections such as in COVID-19. SARS-CoV-2 uses ACE2 as a receptor to recognize host cells, and the protease TMPRSS2 for priming the Spike protein, facilitating virus entry into cells. However, the involvement of estrogenic receptors in SARS-CoV-2 infection are still being explored. Thus, in order to investigate the role of estrogen and its receptors in COVID-19, the estrogen receptors ERα, ERß and GPER1 were overexpressed in bronchial BEAS-2B cell, and then infected with SARS-CoV-2. Interestingly, the levels of ACE2 and TMPRSS2 mRNA were higher in SARS-CoV-2-infected cells, but no difference was observed in cells with estrogen receptors overexpression. GPER1 can be involved in virus infection or replication, since its higher levels reduces SARS-CoV-2 load. On the other hand, pharmacological antagonism of GPER1 enhanced viral load. Those data suggest that GPER1 has an important role in SARS-CoV-2 infection.


Assuntos
COVID-19 , Animais , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Receptores de Estrogênio , Receptor beta de Estrogênio , Receptor alfa de Estrogênio , Peptidil Dipeptidase A/metabolismo , RNA Mensageiro/genética , Estrogênios
12.
Psiquiatr. biol. (Internet) ; 29(3)septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-213242

RESUMO

Cotard syndrome is a mysterious and severe disorder. Many therapeutic interventions are reported as potentially efficacious mostly when an underlying psychotic depression or melancholia is diagnosed. However, the classification of depression has long been a contentious issue. Even though the major guide for therapeutic choice is severity, the binary model between endogenous and reactive depression is still widely employed in clinical practice. These considerations impact most clearly in in-between presentations. The authors present the case of R., a 64 year old woman, who was admitted with a major depressive episode with psychotic features, captured as a Cotard-like syndrome. After a two-months inpatient period and apparent clinical remission with high dose antidepressants and antipsychotic combination, she displayed an acute worsening leading to a re-admission just a day after discharge. The management in this second admission was tortuous, due to SARS-CoV2 related contingencies, the refractoriness of the presentation and iatrogenic intercurrences. The authors expose the course and treatment options employed, while reflecting on the question endogenous v. reactive, concluding that even seemingly clear clinical presentations may resist our different conceptualizations. (AU)


El síndrome de Cotard es un trastorno misterioso y grave. Muchas intervenciones terapéuticas son reportadas como potencialmente eficaces, perincipalmente cuando se diagnostica depresión psicótica o melancolía subyacentes. Sin embargo, la clasificación de la depresión ha sido una cuestión contenciosa durante mucho tiempo. Aun cuando la mayor guía para la elección terapéutica es la gravedad, el modelo binario entre depresión endógena y reactiva sigue siendo ampliamente utilizado en la práctica clínica. Estas consideraciones repercuten claramente en las presentaciones intermedias. Los autores presentan el caso de R., una mujer de 64 años, que fue ingresada con episodio depresivo mayor con características psicóticas, plasmado como síndrome de tipo Cotard. Tras dos meses de periodo hospitalario, y remisión clínica aparente con altas dosis de antidepresivos y combinación antipsicótica, mostró empeoramiento agudo conducente a reingreso transcurrido un solo día desde el alta. El manejo en este segundo ingreso fue tortuoso, debido a las contingencias relacionadas con el SARS-CoV2, la refractariedad de la presentación y las intercurrencias iatrogénicas. Los autores exponen el curso y las opciones de tratamiento utilizadas, a la vez que reflexionan sobre la cuestión endógena frente a reactiva, concluyendo que incluso las presentaciones clínicas aparentemente claras pueden resistirse a nuestras diferentes conceptualizaciones. (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Depressão , Transtorno Depressivo , Gravitação , Antidepressivos
13.
J Mol Model ; 28(9): 259, 2022 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-35978224

RESUMO

Phosphorus is a key and vital element for a diverse set of important biological molecules, being indispensable for life as we know. A deeper comprehension of its role in astrochemistry and atmospheric chemistry may aid in finding answers to how this element became available on Earth. The PO molecule is one of the main reservoirs of phosphorus in the interstellar medium (ISM), and a better understanding of the mechanisms and rate coefficients for its formation in the ISM is important for modelling its abundances. In this work, we perform multireference configuration interaction calculations on the formation of PO via the [Formula: see text] reaction, analyzing its potential energy surface and rate coefficients for the global reaction on both doublet and quartet states. We also perform DFT (M06-2X) and CCSD(T) calculations, in order to compare the results. We found that the OPO system possesses a high multiconfigurational character, making DFT and CCSD methodologies not suitable for its potential energy landscape calculation. The rate coefficients have been calculated using the master equation system solver (MESS) package, and the results compared to recent experimental data. It is shown that the quartet state contributes for temperatures higher than 700K. The computed rate coefficient can be described by a modified Arrhenius equation [[Formula: see text]] with [Formula: see text], [Formula: see text] and [Formula: see text] K.


Assuntos
Fósforo
14.
Phys Ther Sport ; 55: 146-154, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35421834

RESUMO

OBJECTIVE: To provide consensus on how to plan, organize and implement exercise-based injury prevention program (IPP) in sports. DESIGN: Delphi. SETTING: LimeSurvey platform. PARTICIPANTS: Experienced sports physical therapists from the International Federation of Sports Physical Therapy member countries. MAIN OUTCOME MEASURES: Factors related to sports IPP planning, organization and implementation. RESULTS: We included 305 participants from 32 countries. IPP planning should be based on an athlete's injury history, on pre-season screening results, and on injury rates (respectively, 98%, 92%, 89% agreement). In total 97% participants agreed that IPP organization should depend on the athlete's age, 93% on the competition level, and 93% on the availability of low-cost materials. It was agreed that IPP should mainly be implemented in warm-up sessions delivered by the head or strength/conditioning coach, with physical training sessions and individual physical therapy sessions (respectively, 94%, 92%, 90% agreement). CONCLUSION: Strong consensus was reached on (1) IPP based on the athlete's injury history, pre-season screening and evidence-based sports-specific injury rates; (2) IPP organization based on the athlete's age, competition level, and the availability of low-cost materials and (3) IPP implementation focussing on warm-up sessions implemented by the strength/conditioning coach, and/or individual prevention sessions by the physical therapist.


Assuntos
Traumatismos em Atletas , Fisioterapeutas , Esportes , Exercício de Aquecimento , Traumatismos em Atletas/prevenção & controle , Humanos
15.
Proc Natl Acad Sci U S A ; 119(8)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35131899

RESUMO

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.


Assuntos
Vacinas contra COVID-19/provisão & distribuição , COVID-19/prevenção & controle , Imunização Secundária/métodos , Modelos Estatísticos , Vacinação/métodos , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/economia , Países Desenvolvidos , Países em Desenvolvimento , Esquema de Medicação , Humanos , Imunização Secundária/economia , Uso Off-Label , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Análise de Sobrevida , Vacinação/economia
16.
Prostate ; 82(6): 706-722, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35188986

RESUMO

BACKGROUND: Most prostate cancers are "immune cold" and poorly responsive to immune checkpoint inhibitors. However, the mechanisms responsible for the lack of a robust antitumor adaptive immune response in the prostate are poorly understood, which hinders the development of novel immunotherapeutic approaches. AIMS: Most inflammatory infiltrates in the prostate are centered around benign glands and stroma, which can confound the molecular characterization of the antitumor immune response. We sought to analytically validate a chromogenic-based multiplex immunohistochemistry (IHC) approach applicable to whole slide digital image analysis to quantify T cell subsets from the tumor microenvironment of primary prostatic adenocarcinomas. As an initial application, we tested the hypothesis that PTEN loss leads to an altered antitumor immune response by comparing matched regions of tumors within the same individual with and without PTEN loss. MATERIALS & METHODS: Using the HALO Image Analysis Platform (Indica Labs), we trained a classifier to quantify the densities of eight T cell phenotypes separately in the tumor epithelial and stromal subcompartments. RESULTS: The iterative chromogenic approach using 7 different antibodies on the same slide provides highly similar findings to results using individually stained slides with single antibodies. Our main findings in carcinomas (benign removed) include the following: i) CD4+ T cells are present at higher density than CD8+ T cells; ii) all T cell subsets are present at higher densities in the stromal compartment compared to the epithelial tumor compartment; iii) most CD4+ and CD8+ T cells are PD1+; iv) cancer foci with PTEN loss harbored increased numbers of T cells compared to regions without PTEN loss, in both stromal and epithelial compartments; and v) the increases in T cells in PTEN loss regions were associated with ERG gene fusion status. DISCUSSION: This modular approach can apply to any IHC-validated antibody combination and sets the groundwork for more detailed spatial analyses. CONCLUSION: Iterative chromogenic IHC can be used for whole slide analysis of prostate tissue samples and can complement transcriptomic results including those using single cell and spatial genomic approaches.


Assuntos
Neoplasias da Próstata , Microambiente Tumoral , Humanos , Imuno-Histoquímica , Contagem de Linfócitos , Masculino , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/patologia
18.
Saúde Soc ; 31(4): e220437pt, 2022.
Artigo em Português | LILACS | ID: biblio-1424462

RESUMO

Resumo Nos primeiros meses da pandemia de covid-19, em 2020, os movimentos e organizações indígenas da região Nordeste do Brasil estabeleceram uma extensa rede de apoio e parcerias com grupos de pesquisadores e entidades da sociedade civil para a organização de campanhas de solidariedade aos povos indígenas. A produção de informações gerais e dados empíricos sobre como a doença atingiu os territórios e populações indígenas constituiu uma das principais estratégias de ação. Essa mobilização foi a base para a constituição de redes colaborativas que investigaram como ocorreu o enfrentamento dos povos diante da pandemia, por meio de um viés antropológico e aplicando métodos que poderíamos definir como uma pesquisa colaborativa virtual. Este artigo, portanto, discute o potencial desse tipo de parceria para a reflexão sobre o Subsistema de Atenção à Saúde Indígena, argumentando que esse modelo pode constituir uma forma de apoio ao controle social exercido por parte das comunidades.


Abstract In the first months of the covid-19 pandemic, in 2020, indigenous movements and organizations in the Northeast region of Brazil established an extensive network of support and partnerships with groups of researchers and civil society entities to organize campaigns of solidarity with the indigenous peoples. The production of general information and empirical data on how the disease reached indigenous territories and populations constituted one of the main strategies for action. This mobilization was the basis for establishing collaborative networks that investigated how the indigenous peoples faced the pandemic, from an anthropological bias and applying methods that we could define as virtual collaborative research. The article, thus, discusses the potential of this type of partnership for reflection on the Indigenous Health Care Subsystem, arguing that this model can constitute a kind of support for social control exercised by the communities.


Assuntos
Humanos , Masculino , Feminino , Controle Social Formal , Pesquisa Interdisciplinar , Saúde de Populações Indígenas , Monitoramento Epidemiológico , Povos Indígenas , COVID-19
19.
Vet Parasitol Reg Stud Reports ; 23: 100522, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33678377

RESUMO

The protozoan Neospora caninum is an important cause of abortion in cattle worldwide, with domestic dogs serving as the definitive hosts. Although hunting activities have been indicated as a potential risk factor for N. caninum infection in dogs, no serological evidence has so far been reported in hunting dogs, wild boars (Sus scrofa), and hunters. A total of 98 wild boars, 168 hunting dogs, and 15 hunters from three Brazilian regions were sampled and tested for anti-N. caninum antibodies by indirect immunofluorescence antibody test, resulting in 15/168 (9%) seropositive hunting dogs, and 0/98 wild boars, and 0/15 hunters seropositive. The absence of N. caninum antibodies in wild boars may suggest low exposure to oocysts shed by hunting dogs and wild canids in three different Brazilian regions. Finally, the absence of hunter seropositivity supports the current lack of evidence that N. caninum is a zoonotic parasite.


Assuntos
Anticorpos Antiprotozoários/sangue , Neospora , Sus scrofa/sangue , Cães Trabalhadores , Animais , Brasil/epidemiologia , Cães , Estudos Soroepidemiológicos , Sus scrofa/imunologia , Cães Trabalhadores/sangue , Cães Trabalhadores/imunologia
20.
J Nurs Meas ; 29(1): 80-93, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334844

RESUMO

BACKGROUND AND PURPOSE: Mobilization of critical patients should be precocious and the inclusion of nursing in this task can be decisive in paradigm shift. The purpose of this study was to validate the Portuguese version of the intensive care unit Mobility Scale for nursing use. METHODS: Prospective multicenter observational study. Patients' mobility was evaluated by rehabilitation nurses in order to determine interobserver agreement. The validation criteria was tested by determining the correlation between the evaluation results of mobility, strength, and functionality levels at discharge. RESULTS: Good interobserver agreement (R = 0.98; K = 0.76). Positive correlation with muscle strength (R = 0.77) and functionality (R = 0.85) levels at discharge. CONCLUSIONS: Based on the correlations observed the scale is a valid instrument for nurses and could be a useful tool for routine use. More research is recommended to make the results more robust.


Assuntos
Enfermagem de Cuidados Críticos/normas , Limitação da Mobilidade , Alta do Paciente/estatística & dados numéricos , Alta do Paciente/normas , Enfermagem em Reabilitação/estatística & dados numéricos , Enfermagem em Reabilitação/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Enfermagem de Cuidados Críticos/estatística & dados numéricos , Feminino , Humanos , Unidades de Terapia Intensiva/normas , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Portugal , Estudos Prospectivos , Reprodutibilidade dos Testes , Traduções
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...