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1.
BMJ Open Ophthalmol ; 9(1)2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981710

ABSTRACT

Lesions of incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) are associated with disease progression in age-related macular degeneration. However, the corresponding functional impact of these precursor lesions is unknown.We present a cross-sectional study of four patients employing clinical-grade MAIA (stimulus size: 0.43°, ~125 µm) and adaptive optics scanning light ophthalmoscope (AOSLO, stimulus size 0.07°, ~20 µm) based microperimetry (MP) to assess the specific impact of iRORA lesions on retinal sensitivity.AOSLO imaging showed overall reduced photoreceptor reflectivity and patches of hyporeflective regions at drusen with interspersed hyper-reflective foci in iRORA regions. MAIA-MP yielded an average retinal sensitivity loss of -7.3±3.1 dB at iRORA lesions compared with the in-eye control. With AOSLO-MP, the corresponding sensitivity loss was 20.1±4.8 dB.We demonstrated that iRORA lesions are associated with a severe impairment in retinal sensitivity. Larger cohort studies will be necessary to validate our findings.


Subject(s)
Macular Degeneration , Retinal Pigment Epithelium , Tomography, Optical Coherence , Visual Field Tests , Humans , Retinal Pigment Epithelium/pathology , Retinal Pigment Epithelium/diagnostic imaging , Cross-Sectional Studies , Macular Degeneration/pathology , Macular Degeneration/diagnosis , Macular Degeneration/physiopathology , Female , Male , Aged , Tomography, Optical Coherence/methods , Visual Field Tests/methods , Visual Acuity/physiology , Aged, 80 and over , Visual Fields/physiology , Ophthalmoscopy/methods , Atrophy/pathology
2.
Clin Exp Immunol ; 217(3): 279-290, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-38700066

ABSTRACT

Natural killer (NK) cells include different subsets with diverse effector capacities that are poorly understood in the context of parasitic diseases. Here, we investigated inhibitory and activating receptor expression on NK cells in patients with cutaneous leishmaniasis (CL) and explored their phenotypic and functional heterogeneity based on CD57 and NKG2C expression. The expression of CD57 identified NK cells that accumulated in CL patients and exhibited features of senescence. The CD57+ cells exhibited heightened levels of the activating receptor NKG2C and diminished expression of the inhibitory receptor NKG2A. RNA sequencing analyses based on NKG2C transcriptome have revealed two distinct profiles among CL patients associated with cytotoxic and functional genes. The CD57+NKG2C+ subset accumulated in the blood of patients and presented conspicuous features of senescence, including the expression of markers such as p16, yH2ax, and p38, as well as reduced proliferative capacity. In addition, they positively correlated with the number of days until lesion resolution. This study provides a broad understanding of the NK cell biology during Leishmania infection and reinforces the role of senescent cells in the adverse clinical outcomes of CL.


Subject(s)
CD57 Antigens , Cellular Senescence , Killer Cells, Natural , Leishmaniasis, Cutaneous , NK Cell Lectin-Like Receptor Subfamily C , Humans , Leishmaniasis, Cutaneous/immunology , Killer Cells, Natural/immunology , CD57 Antigens/metabolism , CD57 Antigens/immunology , NK Cell Lectin-Like Receptor Subfamily C/metabolism , NK Cell Lectin-Like Receptor Subfamily C/immunology , Cellular Senescence/immunology , Male , Female , Adult , Middle Aged , Young Adult
3.
Acta Trop ; 252: 107125, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38280636

ABSTRACT

There are no approved vaccines yet for human visceral leishmaniasis (VL), the most severe form of the leishmaniasis clinical manifestations that is fatal in over 95 % of untreated cases. It is well-accepted that immunological changes during aging have deleterious impact on the efficacy of vaccines and response to infections. In this work, we compared the response of young and aged mice to intranasal vaccination with killed Leishmania amazonensis promastigote antigens (LaAg) that were then challenged with L. infantum infection, a species that causes visceral leishmaniasis. Intranasal vaccination with LaAg induced a similar reduction in parasitism and hepatosplenomegaly in both young and aged mice compared to their unvaccinated counterparts. Following infection, there was also a less prominent inflammatory profile particularly in the vaccinated aged group, with lower production of TNF-α and nitrite compared to the respective unvaccinated group. Interestingly, the LaAg intranasal vaccination promoted increased production of IFN-γ that was observed in both young- and aged vaccinated groups. Additionally, CD4+ and CD8+T cells from both vaccinated groups presented decreased expression of the inhibitory receptors PD-1 and KLRG1 compared to their unvaccinated controls. Interestingly, a strong positive correlation was observed between the expression of both inhibitory receptors PD-1 and KLRG1 and parasitism, which was more conspicuous in the unvaccinated-aged mice than in the others. Overall, this study helps define new strategies to improve vaccine effectiveness and provides a perspective for prophylactic alternatives against leishmaniasis.


Subject(s)
Leishmania infantum , Leishmania mexicana , Leishmaniasis Vaccines , Leishmaniasis, Visceral , Leishmaniasis , Protozoan Vaccines , Humans , Animals , Mice , Aged , Leishmaniasis, Visceral/prevention & control , Programmed Cell Death 1 Receptor , Antigens, Protozoan , Mice, Inbred BALB C , Cytokines
4.
Eye (Lond) ; 38(3): 514-519, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37684375

ABSTRACT

BACKGROUND/OBJECTIVES: To investigate outcomes of referrals for suspected angle closure and explore whether anterior segment optical coherence tomography (AS-OCT) can be used to tighten triaging criteria in a glaucoma virtual clinic. SUBJECTS/METHODS: Retrospectively collected data. The first audit (04/2018-03/2019) identified referrals for suspected angle closure without other glaucoma-related findings (primary angle closure suspect (PACS) referrals). All patients underwent gonioscopy. The second audit (04-08/2019) identified patients with suspected angle closure in a virtual clinic. Management outcomes were assessed, using gonioscopy as reference standard. The outcomes of the second audit were re-audited after changing the triaging criterion from angle width <10° to iridotrabecular contact (ITC) in ≥1 quadrants on AS-OCT. RESULTS: Out of 1754 glaucoma referrals (first audit), 24.6% (431/1754) were PACS referrals. Of these, only 10.7% (42/393) had an occludable angle on gonioscopy, with 97.6% (41/42) being PACS. Of these, 78% (32/41) underwent laser peripheral iridotomy. Out of 137 referrals in the virtual clinic (second audit), 66.4% (91/137) were triaged to the face-to-face clinic. Of these, 31.9% (29/91) were discharged. AS-OCT had positive and negative predictive value of 74.3% (95% confidence intervals (CI) 57.8-86.0) and 82.1% (95% CI 70.0-90.2%), respectively, in detecting ITC in ≥1 quadrants. In the re-audit 45.9% (45/98) of those with suspected angle closure were triaged for gonioscopy, with 24.4% (11/45) of them being discharged. CONCLUSION: PACS referrals represent a substantial burden to hospital-based services and their accuracy is low. ITC in ≥1 quadrants on AS-OCT can be useful in triaging those who need further evaluation with gonioscopy.


Subject(s)
Glaucoma, Angle-Closure , Glaucoma , Humans , Critical Pathways , Retrospective Studies , Intraocular Pressure , Glaucoma, Angle-Closure/diagnosis , Prospective Studies , Tomography, Optical Coherence/methods , Gonioscopy , Anterior Eye Segment , Iris
5.
Rev. bras. geriatr. gerontol. (Online) ; 27: e240007, 2024. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1565324

ABSTRACT

Resumo Objetivo Verificar o impacto da participação de programas de exercícios físicos em pessoas idosas com doença de Alzheimer (DA) e os fatores que comprometem a sua prática. Método Trata-se de uma revisão sistemática nas bases de dados United States National Library of Medicine (PubMed), Web of Science, Scopus, Biblioteca Scientific Electronic Library Online (SciELO); LILACS e Embase, a partir de 2014. Utilizaram-se as diretrizes do PRISMA - 2020 e a análise de risco de viés com o apoio da ferramenta Cochrane (RoB2). Resultados Foram incluídos onze estudos para análise qualitativa. O comprometimento da memória episódica ocasiona um declínio na DA e envolve uma complexidade de processos cognitivos contendo múltiplos aspectos do sistema neural Conclusão A depressão, a ansiedade e a dificuldade de compreensão são os principais fatores que comprometem a participação da pessoa idosa com Alzheimer aos exercícios com o propósito de estímulo físico, e são os principais preditores que dificultam o desenvolvimento perceptivo-motor. Os protocolos com exercícios combinados parecem favorecer melhor a função executiva no paciente com DA. A conscientização do exercício físico é fundamental desde o início dos tratamentos, com a sugestão de se priorizar melhorias na atenção das pessoas idosas com DA. As particularidades da relação entre as atividades da vida diária e a capacidade funcional do paciente com Alzheimer ainda correspondem a uma lacuna a ser explorada, assim como a prescrição de exercícios específicos que considerem tanto o grau de atenção quanto o nível da doença.


Abstract Objective To assess the impact of participation in physical exercise programs among older adults with Alzheimer's disease (AD) and the factors that compromise its practice. Method This study constitutes a systematic review conducted across the databases of the United States National Library of Medicine (PubMed), Web of Science, Scopus, Scientific Electronic Library Online (SciELO), LILACS, and Embase, starting from 2014. The PRISMA - 2020 guidelines were employed, alongside bias risk analysis supported by the Cochrane (RoB2) tool. Results Eleven studies were included for qualitative analysis. The impairment of episodic memory leads to a decline in AD and involves a complexity of cognitive processes encompassing multiple aspects of the neural system. Conclusion Depression, anxiety, and difficulty in comprehension are the primary factors that compromise the participation of older adults with Alzheimer's in exercises aimed at physical stimulation, and they are the main predictors hindering perceptual-motor development. Protocols involving combined exercises appear to better promote executive function in patients with AD. Awareness of physical exercise is fundamental from the outset of treatments, with the suggestion to prioritize improvements in attention for older adults with AD. The particularities of the relationship between activities of daily living and the functional capacity of Alzheimer's patients still represent a gap to be explored, as well as the prescription of specific exercises that consider both the level of attention and the stage of the disease.

6.
Transl Vis Sci Technol ; 12(11): 16, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37962539

ABSTRACT

Purpose: Adaptive optics scanning laser ophthalmoscopy (AOSLO) enables the visualization and measurement of the retinal microvasculature structure in humans. We investigated the hypothesis that diabetes mellitus (DM) induces remodeling to the wall structure in small retinal arterioles. These alterations may allow better understanding of vascular remodeling in DM. Methods: We imaged retinal arterioles in one eye of 48 participants (26 with DM and 22 healthy controls) with an AOSLO. Structural metrics of 274 arteriole segments (203 with DM and 71 healthy controls) ≤ 50 µm in outer diameter (OD) were quantified and we compared differences in wall thickness (WT), wall-to-lumen ratio (WLR), inner diameter (ID), OD, and arteriolar index ratio (AIR) between controls and participants with DM. We also compared the individual AIR (iAIR) in groups of individuals. Results: The WLR, WT, and AIRs were significantly different in the arteriole segments of DM participants (P < 0.001). The iAIR was significantly deviated in the DM group (P < 0.001) and further division of the participants with DM into groups revealed that there was an effect of the presence of diabetic retinopathy (DR) on the iAIR (P < 0.001). Conclusions: DM induces remodeling of wall structure in small retinal arterioles and in groups of individuals. The use of AIR allows us to assess remodeling independently of vessel size in the retina and to compute an index for each individual subject. Translational Relevance: High-resolution retinal imaging allows noninvasive assessment of small retinal vessel remodeling in DM that can improve our understanding of DM and DR in living humans.


Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Humans , Arterioles/diagnostic imaging , Retina , Retinal Vessels/diagnostic imaging , Diabetic Retinopathy/diagnostic imaging , Ophthalmoscopy
7.
Biomed Opt Express ; 14(10): 5267-5281, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37854570

ABSTRACT

The trabecular meshwork (TM), located within the iridocorneal angle, is a target for many glaucoma treatments aimed at controlling intraocular pressure. However, structural variations between individuals are poorly understood. We propose a newly designed gonioscopic lens optimized for high-resolution imaging to image fine structures of the human TM in vivo. The body of the new lens is index-matched to the human cornea and includes a choice of two gonioscopic mirrors (59° and 63°) and matching air-spaced doublets placed on the anterior surface of the goniolens. The new design allows a diffraction-limited image plane at the iridocorneal angle structures. The goniolens design was built and then placed on the subjects eyes coupled to the cornea with goniogel and a 3D adjustable mount. Images were obtained using a commercially available OCT device (Heidelberg Spectralis). The optical resolution was measured in a model eye as 40.32 and 45.25 cy/mm respectively for each mirror angle. In humans, dense OCT scans with minimum spacing oriented tangential to the iris and ICA were performed on 7 healthy subjects (23-73 yrs). The TM was successfully imaged in all subjects. The custom goniolens improved the contrast of the uveoscleral meshwork structures and corneoscleral meshwork revealing limbus parallel striations, not visible with previous goniolens designs. Transverse OCT images were constructed along the segmentation line, providing an enface image of the TM structures including corneoscleral beams, previously only imaged in vivo using custom adaptive optics systems.

8.
Rev. cir. traumatol. buco-maxilo-fac ; 23(3): 6-13, jul.-set. 2023. graf
Article in Portuguese | LILACS, BBO - Dentistry | ID: biblio-1551440

ABSTRACT

O objetivo deste estudo quantitativo, transversal, retrospectivo e descritivo é conhecer a prevalência e a distribuição de traumatismo dentário (TD) em dois hospitais escola do Paraná, entre 2013 e 2021. Os dados (variáveis sociodemográficas; Classificação Internacional de Doenças; tipo e motivo do TD; número de dentes envolvidos e momento da ocorrência do trauma) foram extraídos dos prontuários eletrônicos dos pacientes com TD, por dois pesquisadores utilizando ficha padronizada, e descritos por frequências absolutas e relativas. Dentre 1.216 prontuários analisados, apenas 51 evidenciaram TD. Os homens (n=41/80,4%) representaram a maior parte dos pacientes. A fratura de coroa foi o tipo de TD mais encontrado (n=13/25,5%) e a queda, a maior motivação para os eventos (n=18/35,3%). A maior parte dos TD ocorreu antes da internação (n=46/90,2%) e 33 pacientes (64,7%) apresentaram até dois dentes acometidos por TD. Em razão do número reduzido de prontuários encontrados, sugere-se que estejam ocorrendo subnotificações dos casos de TD nos hospitais pesquisados. A inserção recente do cirurgião-dentista no ambiente hospitalar, associada à carência técnica de profissionais da equipe para a identificação de TD, e a análise específica de traumas dentários, sem a inclusão de eventos faciais, podem estar atreladas a essa subnotificação... (AU)


The objective of this quantitative, cross-sectional, retrospective and descriptive study is to know the prevalence and distribution of dental trauma (DT) in two teaching hospitals in Paraná, between 2013 and 2021. Data (sociodemographic variables; International Classification of Diseases; type and reason of the DT; number of teeth involved and time of trauma occurrence) were extracted from the electronic medical records of patients with DT, by two researchers using a standardized form, and described by absolute and relative frequencies. Among 1,216 medical records analyzed, only 51 showed DT. Men (n=41/80.4%) represented the majority of patients. Crown fracture was the most common type of DT (n=13/25.5%) and falls were the greatest motivation for the events (n=18/35.3%). Most DTs occurred before admission (n=46/90.2%) and 33 patients (64.7%) had up to two teeth affected by DTs. Due to the small number of medical records found, it is suggested that there are underreporting of DT cases in the surveyed hospitals. The recent insertion of dentists in the hospital environment, associated with the technical lack of team professionals to identify DT, and the specific analysis of dental trauma, without the inclusion of facial events, may be linked to this underreporting... (AU)


El objetivo de este estudio cuantitativo, transversal, retrospectivo y descriptivo es conocer la prevalencia y distribución del trauma dental (TD) en dos hospitales docentes de Paraná, entre 2013 y 2021. Datos (variables sociodemográficas; Clasificación Internacional de Enfermedades; tipo y motivo de la TD; número de dientes involucrados y tiempo de ocurrencia del trauma) fueron extraídas de las historias clínicas electrónicas de pacientes con TD, por dos investigadores utilizando un formulario estandarizado, y descritas por frecuencias absolutas y relativas. De las 1.216 historias clínicas analizadas, solo 51 presentaban TD. Los hombres (n = 41/80,4%) representaron la mayoría de los pacientes. La fractura de corona fue el tipo más común de TD (n = 13/25,5%) y las caídas fueron la mayor motivación para los eventos (n = 18/35,3%). La mayoría de TD ocurrieron antes del ingreso (n = 46/90.2%) y 33 pacientes (64.7%) tenían hasta dos dientes afectados por TD. Debido a la pequeña cantidad de historias clínicas encontradas, se sugiere que hay subregistro de casos de TD en los hospitales encuestados. La reciente inserción de odontólogos en el ámbito hospitalario, asociada a la falta técnica de equipo de profesionales para identificar TD, y el análisis específico del trauma dental, sin la inclusión de eventos faciales, pueden estar vinculados a este subregistro... (AU)


Subject(s)
Humans , Male , Female , Tooth Avulsion , Accidental Falls , Emergencies , Facial Bones/injuries , Electronic Health Records , Mandibular Injuries
9.
Rev. bras. ciênc. esporte ; 45: e20230012, 2023. tab, graf
Article in Portuguese | LILACS-Express | LILACS | ID: biblio-1521688

ABSTRACT

RESUMO Objetivou-se correlacionar a satisfação no trabalho e a qualidade de vida de 297 docentes de Educação Física. Os instrumentos utilizados foram os questionários sociodemográfico, QVT-PEF e WHOQOL-bref, empregando-se os testes Friedman e correlação de Spearman. Os resultados indicaram correlação positiva e significativa na comparação interna, tanto da satisfação no trabalho quanto da qualidade de vida. Contudo, a correlação entre os construtos foi considerada insuficiente para indicar relação entre eles. Em conclusão, os docentes de Educação Física apresentaram-se satisfeitos no trabalho e avaliaram positivamente os domínios da qualidade de vida, apesar de se constatar que a satisfação no trabalho não influenciou a percepção da qualidade de vida destes docentes.


ABSTRACT The objective was to correlate job satisfaction and quality of life of 297 Physical Education teachers. The instruments used were the sociodemographic, QVT-PEF and WHOQOL-bref questionnaires, using the Friedman and Spearman correlation tests. The results indicated a positive and significant correlation in the internal comparison, both for job satisfaction and quality of life. However, the correlation between the constructs was considered insufficient to indicate a relationship between them. In conclusion, Physical Education teachers were satisfied at work and positively evaluated the domains of quality of life, despite the fact that job satisfaction did not influence the perception of quality of life by these teachers.


RESUMEN El objetivo fue correlacionar la satisfacción en el trabajo y la calidad de vida de 297 maestros de Educación Física. Los instrumentos utilizados fueron los cuestionarios sociodemográficos, QVT-PEF y WHOQOL-bref, utilizando las pruebas de correlación de Friedman y Spearman. Los resultados indicaron una correlación positiva y significativa en la comparación interna, tanto para la satisfacción laboral como para la calidad de vida. Sin embargo, la correlación entre los constructos se consideró insuficiente para indicar una relación entre ellos. En conclusión, los maestros se mostraron satisfechos en el trabajo y evaluaron positivamente los dominios de calidad de vida, aunque se constató que la satisfacción laboral no influyó en la percepción de calidad de vida.

10.
Biomed Opt Express ; 13(9): 4652-4667, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-36187241

ABSTRACT

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma progression, and many treatments target the trabecular meshwork (TM). Imaging this region in vivo is challenging due to optical limitations of imaging through the cornea at high angles. We propose a gonioscopic OCT approach using a custom goniolens and a commercially available OCT device to improve imaging of the TM, Schlemm's canal (SC) and adjacent structures within the iridocorneal angle (ICA). The goniolens is modified with a plano-convex focusing lens and placed on the eye optically mated with goniogel and aided by a 3D adjustable mount. Gonioscopic OCT volume scans are acquired to image SC. Transverse enface images allowed measurements of SC over a 45° section of the ICA for the first time and revealed locations of SC narrowing. The band of extracanalicular limbal lamina and corneoscleral bands were imaged in most subjects and these bands were confirmed using exterior OCT imaging. The polarization dependence of the visibility of these structures is studied by polarization rotation the OCT beam with a half-wave plate, allowing increased contrast of SC. Gonioscopic OCT has successfully been used to image the human ICA in 3D in vivo. This approach provides more detailed characterization of the TM and SC, enhancing their contrast against their birefringent backgrounds.

11.
Vaccines (Basel) ; 10(8)2022 Aug 12.
Article in English | MEDLINE | ID: mdl-36016193

ABSTRACT

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

12.
Front Immunol ; 13: 884760, 2022.
Article in English | MEDLINE | ID: mdl-35844561

ABSTRACT

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.


Subject(s)
COVID-19 , Viral Vaccines , Adjuvants, Immunologic , Alum Compounds , Animals , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , Humans , Immunoglobulin G , Mice , Poly I-C , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
13.
Curr Issues Mol Biol ; 44(5): 2089-2106, 2022 May 09.
Article in English | MEDLINE | ID: mdl-35678670

ABSTRACT

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC50 values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC50 = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets.

14.
J. Phys. Educ. (Maringá) ; 33: e3346, 2022. tab, graf
Article in English | LILACS | ID: biblio-1421871

ABSTRACT

ABSTRACT Teaching in Higher Education requires involvement in several roles that can affect perceived quality of life within this class of workers. This study sought to determine the quality of life profiles of Physical Education professors and to associate them with their personal and professional characteristics. A total of 93 professors from the Greater Florianópolis mesoregion participated. A profiling questionnaire and the Whoqol-bref were used, in addition to Cluster analysis, the Ward method, and the Kruskal-Wallis, Friedman's and Chi-Square tests. Three groups of professors were identified: Group I had a more negative perception and lower scores in the whole quality of life construct (no involvement in extension); Group II had a more positive perception and higher quality of life scores (extension program coordinators); Group III had a regular perception of the overall assessment and of the physical and psychological domains, and intermediate scores compared to the other Groups (university extension collaborators).


RESUMO A docência no Ensino Superior exige o envolvimento em diversas funções que podem afetar a percepção de qualidade de vida desta classe de trabalhadores. O estudo buscou determinar os perfis de qualidade de vida de professores de Educação Física do Ensino Superior e associá-los às suas características pessoais e profissionais. Participaram 93 professores da mesorregião da Grande Florianópolis. Utilizou-se um questionário de caracterização e o Whoqol-bref e empregou-se análise de Clusters, método Ward e testes Kruskal Wallis, Friedman e Qui-Quadrado. Identificou-se três grupos de professores: Grupo I apresentou percepção mais negativa e escores menores em todo constructo da qualidade de vida (sem vínculos com a extensão); Grupo II revelou percepção mais positiva e escores mais elevados da qualidade de vida (coordenadores de ações extensionistas); Grupo III apresentou percepção regular da avaliação geral e dos domínios físico e psicológico e escores intermediários quando comparados aos demais Grupos (colaboradores da extensão universitária).


Subject(s)
Humans , Male , Female , Physical Education and Training , Quality of Life , Faculty/education , Perception , Teaching/education , Universities , Health Profile , Occupational Groups
15.
J Dent Child (Chic) ; 88(3): 196-201, 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34937630

ABSTRACT

Purpose: To evaluate the prevalence of periodontal disease and alveolar bone loss in overweight/obese Brazilian adolescents.
Methods: Participants included 12- to 18-year-old adolescents who were allocated into two groups: (1) normal weight; or (2) overweight/obese. Body mass index (BMI) and waist circumference (WC) were evaluated to classify overweight/obesity. Clinical measurements included the visible plaque index (VPI) and community periodontal index (CPI). Alveolar bone loss (ABL) was also evaluated by bitewing radiographs.
Results: There were 109 subjects. There were no significant differences between the groups for VPI and CPI code two (P >0.05). CPI code zero was more prevalent in normal weight subjects than in overweight/obese subjects (P <0.05). CPI codes one and three were significantly more frequent in the overweight/obese group (P <0.05). The normal weight subjects revealed a higher percentage of sites with no ABL (P <0.05), while the overweight/obese group had a higher prevalence of incipient ABL with the number of sites greater than one and less than three (P <0.05).
Conclusion: Overweight/obesity may affect the progression of early periodontitis in the presence of poor biofilm control in adolescents, as this group presents more bleeding on probing and pathological periodontal pockets greater than four mm as well as a higher prevalence of sites with incipient alveolar bone loss.


Subject(s)
Alveolar Bone Loss , Periodontal Diseases , Adolescent , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/epidemiology , Body Mass Index , Child , Humans , Obesity/complications , Obesity/epidemiology , Overweight/complications , Overweight/epidemiology , Prevalence
16.
Invest Ophthalmol Vis Sci ; 62(14): 29, 2021 11 01.
Article in English | MEDLINE | ID: mdl-34846516

ABSTRACT

Purpose: The retinal circulation regulates blood flow through various internal and external factors; however, it is unclear how locally these factors act within the retinal microcirculation. We measured the temporal and spatial variability of blood velocity in small retinal vessels using a dual-beam adaptive optics scanning laser ophthalmoscope. Methods: In young healthy subjects (n = 3), temporal blood velocity variability was measured in a local vascular region consisting of an arteriole, capillary, and venule repeatedly over 2 days. Data consisted of 10 imaging periods separated into two sessions: (1) five 6-minute image acquisition periods with 30-minute breaks, and (2) five 6-minute image acquisition periods with 10-minute breaks. In another group of young healthy subjects (n = 5), spatial distribution of velocity variability was measured by imaging three capillary segments during three 2-minute conditions: (1) baseline imaging condition (no flicker), (2) full-field flicker, and (3) no flicker condition again. Results: Blood velocities were measurable in all subjects with a reliability of about 2%. The coefficient of variation (CV) was used as an estimate of the physiological variability of each vessel. Over 2 days, the average CV in arterioles was 7% (±2%); in capillaries, it was 19% (±6%); and, in venules, it was 8% (±2%). During flicker stimulation, the average capillary CV was 16% during baseline, 15% during flicker stimulation, and 18% after flicker stimulation. Conclusions: Capillaries in the human retina exhibit spatial and temporal variations in blood velocity. This inherent variation in blood velocity places limits on studying the vascular regulation of individual capillaries, and the study presented here serves as a foundation for future endeavors.


Subject(s)
Blood Flow Velocity/physiology , Erythrocytes/physiology , Retinal Vessels/physiology , Adult , Arterioles/physiology , Capillaries/physiology , Female , Hemodynamics , Humans , Laser-Doppler Flowmetry , Male , Microcirculation , Ophthalmoscopy , Regional Blood Flow , Venules/physiology , Visual Acuity/physiology
17.
Sci Total Environ ; 801: 149599, 2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34467925

ABSTRACT

The effectiveness of advanced technologies on eliminating antibiotic resistant bacteria (ARB) and resistance genes (ARGs) from wastewaters have been recently investigated. Solar photo-Fenton has been proven effective in combating ARB and ARGs from Municipal Wastewater Treatment Plant effluent (MWWTPE). However, most of these studies have relied solely on cultivable methods to assess ARB removal. This is the first study to investigate the effect of solar photo-Fenton upon ARB and ARGs in MWWTPE by high throughput metagenomic analysis (16S rDNA sequencing and Whole Genome Sequencing). Treatment efficiency upon priority pathogens and resistome profile were also investigated. Solar photo-Fenton (30 mg L-1 of Fe2+ intermittent additions and 50 mg L-1 of H2O2) reached 76-86% removal of main phyla present in MWWTPE. An increase in Proteobacteria abundance was observed after solar photo-Fenton and controls in which H2O2 was present as an oxidant (Fenton, H2O2 only, solar/H2O2). Hence, tolerance mechanisms presented by this group should be further assessed. Solar photo-Fenton achieved complete removal of high priority Staphylococcus and Enterococcus, as well as Klebsiella pneumoniae and Pseudomonas aeruginosa. Substantial reduction of intrinsically multi-drug resistant bacteria was detected. Solar photo-Fenton removed nearly 60% of ARGs associated with sulfonamides, macrolides, and tetracyclines, and complete removal of ARGs related to ß-lactams and fluoroquinolones. These results indicate the potential of using solar-enhanced photo-Fenton to limit the spread of antimicrobial resistance, especially in developing tropical countries.


Subject(s)
Hydrogen Peroxide , Microbiota , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , Anti-Bacterial Agents/pharmacology , Drug Resistance, Microbial/genetics , Hydrogen-Ion Concentration , Wastewater
18.
Microorganisms ; 9(6)2021 Jun 11.
Article in English | MEDLINE | ID: mdl-34207948

ABSTRACT

There is so far no vaccine approved for human leishmaniasis, mainly because of the lack of appropriate adjuvants. This study aimed to evaluate in mice the capacity of a mixture of monophosphoryl lipid A (MPLA) and AddaVax® adjuvants in enhancing the efficacy of a Leishvacin®-like vaccine comprised of Leishmania amazonensis whole antigens (LaAg). For that, mice were immunized with LaAg plus MPLA/AddaVax® by the intramuscular route (i.m.) prior to challenge with 2 × 105 and 2 × 106 living parasites. Immunization with LaAg alone reduced the lesion growth of the 2 × 105-challenged mice only in the peak of infection, but that was not accompanied by reduced parasite load, and thus not considered protective. Mice given a 2 × 106 -challenge were not protected by LaAg. The association of LaAg with MPLA/AddaVax® was able to enhance the cutaneous hypersensitivity response compared with LaAg alone. Despite this, there was no difference in proliferative cell response to antigen ex vivo. Moreover, regardless of the parasite challenge, association of LaAg with MPL/AddaVax® did not significantly enhance protection in comparison with LaAg alone. This work demonstrated that MPL/AddaVax® is not effective in improving the efficacy of i.m. LaAg vaccine against cutaneous leishmaniasis.

19.
Front Immunol ; 12: 598943, 2021.
Article in English | MEDLINE | ID: mdl-34211455

ABSTRACT

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response.


Subject(s)
B7-H1 Antigen/metabolism , Leishmania braziliensis/physiology , Leishmaniasis/immunology , Neutrophils/immunology , T-Lymphocytes/immunology , Animals , B7-H1 Antigen/genetics , Cells, Cultured , Disease Models, Animal , Female , Humans , Immunosuppression Therapy , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Programmed Cell Death 1 Receptor/metabolism
20.
Cell Immunol ; 363: 104316, 2021 05.
Article in English | MEDLINE | ID: mdl-33713902

ABSTRACT

Clinical and experimental studies have described eosinophil infiltration in Leishmania amazonensis infection sites, positioning eosinophils strategically adjacent to the protozoan-infected macrophages in cutaneous leishmaniasis. Here, by co-culturing mouse eosinophils with L. amazonensis-infected macrophages, we studied the impact of eosinophils on macrophage ability to regulate intracellular L. amazonensis infection. Eosinophils prevented the increase in amastigote numbers within macrophages by a mechanism dependent on a paracrine activity mediated by eosinophil-derived prostaglandin (PG) D2 acting on DP2 receptors. Exogenous PGD2 mimicked eosinophil-mediated effect on managing L. amazonensis intracellular infection by macrophages and therefore may function as a complementary tool for therapeutic intervention in L. amazonensis-driven cutaneous leishmaniasis.


Subject(s)
Eosinophils/immunology , Leishmaniasis/immunology , Macrophages/immunology , Prostaglandin D2/immunology , Animals , Eosinophils/metabolism , Female , Leishmania/immunology , Leishmaniasis/metabolism , Macrophages/metabolism , Mice , Mice, Inbred BALB C , Paracrine Communication/immunology , Prostaglandin D2/metabolism , Receptors, Prostaglandin/metabolism
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