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1.
ACS Omega ; 9(27): 29282-29289, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39005823

RESUMO

A new selective synthetic approach to indole derivatives bearing a tetrazole moiety has been developed. Arynes, generated in situ from o-(trimethylsilyl)aryl triflates and KF, reacted smoothly with 2-(2-benzyl-2H-tetrazol-5-yl)-2H-azirines to give 3-(2-benzyl-2H-tetrazol-5-yl)-indole derivatives with high selectivity. Deprotection of the tetrazole moiety gave 3-(1H-tetrazol-5-yl)-indole derivatives.

2.
JBI Evid Synth ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973380

RESUMO

OBJECTIVE: This review aims to assess the effectiveness of eHealth early intervention programs in supporting premature infants and their parents transition from neonatal intensive care units (NICUs) to home and the impact of such programs on parental and infant outcomes. INTRODUCTION: The literature has shown the benefits of eHealth early intervention programs to support premature infants and their parents after discharge from NICUs. Parents have reported benefits such as enhanced user-friendliness, increased confidence in infant care, satisfaction, and knowledge acquisition. However, the effectiveness of these programs on parental and infant outcomes remains unclear. INCLUSION CRITERIA: This review will consider studies that assess any early intervention program using eHealth to support premature infants and their parents after discharge from NICU. The programs may be initiated during hospitalization or within the first month of discharge. The programs will include interventions that use eHealth components (eg, teleconsultation), either alone or in combination with face-to-face interventions (eg, home visits). This review will consider parental outcomes, including stress, anxiety, competence, and satisfaction, as well as infant outcomes, including health service utilization and cognitive, motor, and social development. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. The search strategy will aim to find both published and unpublished quantitative studies in English, Spanish, and Portuguese, without any geographical or cultural limitations. Two reviewers will independently perform study selection, critical appraisal, and data extraction. The results will be accompanied by a narrative synthesis. If possible, a meta-analysis will be conducted and the Summary of Findings will be presented using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42023444721.

3.
Nat Microbiol ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858594

RESUMO

Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.

4.
Oncol Ther ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829416

RESUMO

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

5.
Oncol Ther ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836997

RESUMO

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

6.
Ultrasound Med Biol ; 50(8): 1071-1087, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38762390

RESUMO

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Fígado , Técnicas de Imagem por Elasticidade/métodos , Humanos , Hepatopatias/diagnóstico por imagem , Fígado/diagnóstico por imagem , Guias de Prática Clínica como Assunto
7.
Foods ; 13(9)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38731699

RESUMO

White crowberries (Corema album) are a fruit from an endemic shrub found in Southern European Atlantic costal dunes. Although this shrub and its fruits never became a formal commercial crop for a number of reasons, it has a long-lasting relevance and tradition, much associated with summer, beach and holidays. The main goal of this study was to conduct a thematic analysis of the words and small expressions people associate with white crowberries. For that, a questionnaire was used, and the participants were asked to indicate in an open-ended question which top-of-mind words/small expressions they associate with white crowberries. A total of 501 people participated in this study, of which only 394 knew about white crowberries, and from those, only 229 answered the open-ended question of interest to this purpose. The results showed that the words/small expressions given by the participants were distributed between five categories (1-Memories of places, people and times, 2-Emotions and experiences, 3-Sensorial perception, 4-Properties and uses, and 5-Natural resources' valuation). Additionally, 18 subcategories were also identified. The most representative of the categories was sensorial perception and the most relevant of the subcategories was habitats (a subcategory from category 1). The most frequent words mentioned by the participants were beach, berry and summer. In addition, the effect of sociodemographic groups was investigated and some variations were observed in the categories of the words mentioned by the participants according to sex, living environment or region. This work allowed for the identification of a high variability in the words or expressions that account for a rich patrimony of tacit knowledge, memories, emotions and perceptions of the population towards white crowberries, thus confirming their social as well as nutritional relevance.

8.
Ultrasound Med Biol ; 50(8): 1088-1098, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38658207

RESUMO

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.


Assuntos
Fígado Gorduroso , Fígado , Ultrassonografia , Humanos , Tecido Adiposo/diagnóstico por imagem , Fígado Gorduroso/diagnóstico por imagem , Fígado/diagnóstico por imagem , Ultrassonografia/métodos
9.
Biometals ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647983

RESUMO

Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC-CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC50) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.

10.
Science ; 384(6694): 428-437, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662827

RESUMO

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.


Assuntos
Bacteroides fragilis , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico , Neoplasias , Vitamina D , Animais , Feminino , Humanos , Masculino , Camundongos , Bacteroides fragilis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia , Mucosa Intestinal/imunologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/metabolismo , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Neoplasias/microbiologia , Neoplasias/terapia , Vitamina D/administração & dosagem , Vitamina D/metabolismo , Dieta , Linhagem Celular Tumoral , Calcifediol/administração & dosagem , Calcifediol/metabolismo , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo
11.
J Cancer Res Clin Oncol ; 150(4): 183, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594593

RESUMO

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , América Latina , Consenso , Sunitinibe
12.
Front Cardiovasc Med ; 11: 1342832, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38450375

RESUMO

Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).

13.
Reprod Domest Anim ; 59(3): e14548, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38459830

RESUMO

The in vivo fertilization process occurs in the presence of follicular fluid (FF). The aim of this study was to evaluate the effect of in vitro fertilization medium supplementation with 5% or 10% bovine follicular fluid (BFF) on the production of in vitro bovine embryos. FF was collected from ovarian follicles with a diameter of 8-10 mm, and cumulus-oocyte complexes (COCs) were co-incubated with sperm for 24 h in the commercial medium BotuFIV® (BotuPharma©), being distributed among the experimental groups: oocytes fertilized in a control medium; oocytes fertilized in a medium supplemented with 5% BFF; and oocytes fertilized in a medium supplemented with 10% BFF. After fertilization, the zygotes were cultured in vitro for 8 days. Embryo development was assessed through cleavage rates (day 2) and blastocyst formation rates (day 8). The relative expression of the genes OCT4, IFNT2, BAX, HSP70 and SOD2 was measured using the real-time polymerase chain reaction method. There was no difference (p > .05) among the different experimental groups in terms of cleavage rates and blastocyst formation rates. Regarding the gene expression results, only the blastocysts from oocytes fertilized with 10% BFF showed significantly lower expression of IFNT2 (p = .003) and SOD2 (p = .01) genes compared to blastocysts from oocytes fertilized in control medium alone, while there was no difference between blastocyst from oocytes fertilized in control medium and the ones from oocytes fertilized with 5% BFF. In addition to this, the blastocysts from oocytes fertilized with 5% BFF showed significantly reduced levels of expression of the heat shock protein HSP70 (p < .001) and the pro-apoptotic protein BAX (p = .015) compared to blastocysts from oocytes fertilized with control medium. This may indicate that lower supplementation of BFF to the IVF medium creates a more suitable environment for fertilization and is less stressful for the zygote.


Assuntos
Fertilização in vitro , Líquido Folicular , Feminino , Masculino , Bovinos , Animais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Fertilização in vitro/veterinária , Sêmen , Oócitos , Desenvolvimento Embrionário , Blastocisto/metabolismo , Proteínas de Choque Térmico HSP70/genética , Fertilização
14.
Animals (Basel) ; 14(6)2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38539981

RESUMO

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.

15.
Ann Hepatol ; 29(4): 101477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38360269

RESUMO

INTRODUCTION AND OBJECTIVES: A high prevalence of steatotic liver disease has been described in psoriasis. However, the influence of genetic polymorphisms has yet to be investigated in this scenario. This study aims to determine the frequency of steatosis, advanced liver fibrosis and PNPLA3/TM6SF2 genotypes in individuals with psoriasis and to evaluate the impact of genetic polymorphisms, metabolic parameters and cumulative methotrexate dose on steatosis and fibrosis. MATERIALS AND METHODS: Cross-sectional study that prospectively included psoriasis outpatients, submitted to clinical and laboratory analysis, transient elastography (FibroScan®, Fr) and PNPLA3/TM6SF2 genotyping. Steatosis was defined by CAP ≥275 dB/m and advanced liver fibrosis as transient elastography ≥10 kPa. Logistic regression analysis evaluated the independent variables related to steatosis and fibrosis; p-value< 0.05 was considered significant. RESULTS: One hundred and ninety-nine patients were enrolled (age 54.6 ± 12.6 years, 57.3% female). Metabolic syndrome (MetS), steatosis and advanced liver fibrosis prevalence were 55.8%, 54.8% and 9%, respectively. PNPLA3 and TM6SF2 genotypes frequencies were CC 42.3%/CG 49.5%/GG 8.2% and CC 88.7%/ CT 11.3%/ TT 0%. MetS (OR3.01 95%CI 1.51-5.98; p = 0.002) and body mass index (OR1.17 95%CI 1.08-1.26; p < 0.01) were independently associated with steatosis. Diabetes Mellitus (T2DM) (OR10.76 95%CI 2.42-47.87; p = 0.002) and harboring at least one PNPLA3 G allele (OR5.66 95%CI 1.08-29.52; p = 0.039) were associated with advanced fibrosis, but not TM6SF2 polymorphism or cumulative MTX dose. CONCLUSIONS: MetS and T2DM confer higher odds for steatosis and advanced fibrosis in individuals with psoriasis. PNPLA3 G allele, but not TM6SF2 polymorphism, impacts a 5-fold odds of advanced liver fibrosis.


Assuntos
Técnicas de Imagem por Elasticidade , Lipase , Cirrose Hepática , Proteínas de Membrana , Psoríase , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Lipase/genética , Proteínas de Membrana/genética , Estudos Transversais , Cirrose Hepática/genética , Psoríase/genética , Adulto , Idoso , Estudos Prospectivos , Fígado Gorduroso/genética , Prevalência , Predisposição Genética para Doença , Fatores de Risco , Síndrome Metabólica/genética , Síndrome Metabólica/complicações , Polimorfismo Genético , Genótipo , Aciltransferases , Fosfolipases A2 Independentes de Cálcio
16.
Nat Immunol ; 25(3): 448-461, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38351322

RESUMO

Conventional dendritic cells (cDCs) include functionally and phenotypically diverse populations, such as cDC1s and cDC2s. The latter population has been variously subdivided into Notch-dependent cDC2s, KLF4-dependent cDC2s, T-bet+ cDC2As and T-bet- cDC2Bs, but it is unclear how all these subtypes are interrelated and to what degree they represent cell states or cell subsets. All cDCs are derived from bone marrow progenitors called pre-cDCs, which circulate through the blood to colonize peripheral tissues. Here, we identified distinct mouse pre-cDC2 subsets biased to give rise to cDC2As or cDC2Bs. We showed that a Siglec-H+ pre-cDC2A population in the bone marrow preferentially gave rise to Siglec-H- CD8α+ pre-cDC2As in tissues, which differentiated into T-bet+ cDC2As. In contrast, a Siglec-H- fraction of pre-cDCs in the bone marrow and periphery mostly generated T-bet- cDC2Bs, a lineage marked by the expression of LysM. Our results showed that cDC2A versus cDC2B fate specification starts in the bone marrow and suggest that cDC2 subsets are ontogenetically determined lineages, rather than cell states imposed by the peripheral tissue environment.


Assuntos
Células Dendríticas , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Animais , Camundongos , Diferenciação Celular
17.
Environ Toxicol Pharmacol ; 107: 104398, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403142

RESUMO

Ubiquitin Proteasomal System (UPS) and autophagy dysregulation initiate cancer. These pathways are regulated by zinc finger proteins. Trivalent inorganic arsenic (iAs) displaces zinc from zinc finger proteins disrupting functions of important cellular proteins. The effect of chronic environmental iAs exposure (100 nM) on UPS has not been studied. We tested the hypothesis that environmental iAs exposure suppresses UPS, activating autophagy as a compensatory mechanism. We exposed skin (HaCaT and Ker-CT; independent quadruplicates) and lung (BEAS-2B; independent triplicates) cell cultures to 0 or 100 nM iAs for 7 or 8 weeks. We quantified ER stress (XBP1 splicing employing Reverse Transcriptase -Polymerase Chain Reaction), proteasomal degradation (immunoblots), and initiation and completion of autophagy (immunoblots). We demonstrate that chronic iAs exposure suppresses UPS, initiates autophagy, but suppresses autophagic protein degradation in skin and lung cell lines. Our data suggest that chronic iAs exposure inhibits autophagy which subsequently suppresses UPS.


Assuntos
Arsênio , Arsenicais , Arsênio/toxicidade , Proteólise , Complexo de Endopeptidases do Proteassoma , Autofagia
18.
Animals (Basel) ; 14(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38275783

RESUMO

This prospective observational cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore responses to an early intensive neurorehabilitation protocol in a clinical setting. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the potential structural and protective role of proteins and the release of neurotrophic factors. Furthermore, FES was parametrized according to the presence or absence of deep pain. Following treatment, 72.6% of the cats achieved ambulation: 9 cats within 15 days, 2 cats within 30 days and 5 cats within 60 days. During the four-year follow-up, there was evidence of improvement in both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats showed improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied in the first weeks after injury and accurate parametrization according to the presence or absence of deep pain, may help in functional recovery and ambulation, reducing the probability of amputation.

19.
Cad. Bras. Ter. Ocup ; 32: e3590, 2024. tab
Artigo em Português | LILACS-Express | LILACS, Index Psicologia - Periódicos | ID: biblio-1557380

RESUMO

Resumo Introdução Crianças com Transtorno do Espectro Autista (TEA) podem apresentar questões comportamentais, no processamento sensorial, na cognição e na linguagem, que afetam seu desempenho ocupacional, necessitando de acesso a serviços escolares, terapêuticos e de saúde. O acesso a esses serviços esteve restrito durante a pandemia de COVID-19, tornando essa população particularmente ainda mais vulnerável às restrições sociais impostas à época. Objetivo Descrever a percepção dos pais cuidadores de pré-escolares com TEA acerca do comportamento e desempenho ocupacional de seus filhos durante a pandemia da COVID-19. Método Estudo transversal, descritivo, quantitativo e qualitativo baseado em entrevistas com 60 cuidadores de pré-escolares com TEA. Os participantes responderam à seguinte pergunta: Você está notando alguma diferença no comportamento e desempenho da criança durante a pandemia? Para caracterização das crianças, foram utilizados o Sistema de Classificação de Funcionalidade no Autismo: Comunicação Social (ACSF:SC), o Inventário de Avaliação Pediátrica de Incapacidade - Teste Adaptativo de Computador (PEDI-CAT) e o Perfil Sensorial 2 (SP-2). Todas as entrevistas foram anotadas e 15 delas foram gravadas e transcritas. O material foi submetido à análise temática de conteúdo. Resultados Foram entrevistadas 43 mães, 15 casais e dois pais de crianças com TEA. Das 60 crianças, 46 (76,7%) eram meninos, com idade de 3 a 5 anos (53,6 ±10,18 meses). Os cuidadores perceberam mudanças no comportamento e desempenho ocupacional, com prevalência de relatos de piora. Houve aumento nas estereotipias, rigidez e hiperfoco, bem como menor engajamento nas atividades cotidianas. A presença dos cuidadores beneficiou algumas crianças, mas há relato de estresse, especialmente por parte das mães. Conclusão Houve variação nos relatos, com maior tendência à piora no comportamento e desempenho ocupacional das crianças com TEA.


Abstract Introduction Children with Autism Spectrum Disorder (ASD) face behavioral, sensory processing, cognitive, and language challenges that affect their ability to perform activities of daily living (ADL) and necessitate access to educational, therapeutic, and health services. The COVID-19 pandemic limited access to these essential services, exacerbating the challenges faced by this vulnerable population due to imposed social distancing measures. Objective To explore the perceptions of parent caregivers of preschoolers with ASD regarding their children's behavior and performance in ADL during the COVID-19 pandemic. Method This cross-sectional, descriptive study utilized both quantitative and qualitative approaches, interviewing 60 caregivers of preschoolers with ASD. Participants were asked about any observed changes in their child's behavior and ability to engage in ADL during the pandemic. Child characterization involved the Autism Classification System of Functioning: Social Communication (ACSF:SC), the Pediatric Evaluation of Disability Inventory - Computer Adaptive Test (PEDI-CAT), and the Sensory Profile 2 (SP-2). Interviews were documented, with 15 recorded and transcribed for thematic content analysis. Results Participants included 43 mothers, 15 couples, and two fathers, totaling 60 children, of whom 46 (76.7%) were boys aged between 3 and 5 years (mean age 53.6 ±10.18 months). Caregivers reported changes in behavior and performance in ADL, predominantly noting deterioration. Increases in stereotypic behaviors, rigidity, and hyperfocus were observed, along with decreased participation in ADL. While the presence of caregivers benefited some children, it also led to reported stress, particularly among mothers. Conclusion The study found a predominant trend of deteriorating behavior and performance in ADL among children with ASD during the pandemic, based on caregiver reports.

20.
Arq. ciências saúde UNIPAR ; 27(2): 948-966, Maio-Ago. 2023.
Artigo em Português | LILACS | ID: biblio-1425160

RESUMO

A pandemia causada pelo SARS-CoV-2 (COVID-19) trouxe inúmeros impactos na vida cotidiana, tanto nos aspectos econômicos, como nos emocionais, psicológicos e sociais. Em situações difíceis, as pessoas, muitas vezes, recorrem à espiritualidade ou à religiosidade. O objetivo deste estudo foi investigar a presença da religiosidade/espiritualidade entre a população brasileira diante da pandemia da COVID- 19, correlacionado com a qualidade de vida. É um estudo quantitativo, descritivo e transversal, realizado nos últimos meses de 2020. Os dados foram coletados por meio de respostas aos instrumentos WHOQOL-Bref e o WHOQOL-SRPB, de forma online, por meio do Google Forms®. Utilizou-se o método de amostragem não probabilístico do tipo snowball sampling, totalizando 948 respostas. Os dados foram tabulados por meio do software Microsoft Excel (2019) e analisados estatisticamente, considerando significativo p<0,05. Os dados apresentados mostram de forma enfática como os participantes que pertencem a alguma religião, apresentaram melhor relação nos domínios saúde psicológica, independência, meio ambiente e espiritualidade/religião/crenças pessoais em comparação àqueles que declaram não pertencer a uma religião. No entanto, não houve diferença estatisticamente significativa para os domínios saúde física e relações sociais. Conclui-se que o pertencimento a uma religião pode contribuir para a melhoria da qualidade de vida e auxiliar o enfrentamento das situações desfavoráveis durante a pandemia COVID-19. Diante disso, destaca-se a importância do desenvolvimento de novos estudos sobre o tema, para compreender com mais veemência e detalhamento, a relação dessas variáveis em contextos de crise que possam alterar a rotina de vida das pessoas.


The pandemic caused by SARS-CoV-2 (COVID-19) has brought numerous impacts on daily life, both in economic, emotional, psychological, and social aspects. In difficult situations, people often turn to spirituality or religiosity. The objective of this study was to investigate the presence of religiosity/spirituality among the Brazilian population facing the pandemic of COVID-19, correlated with quality of life. Quantitative, descriptive, cross-sectional study conducted in the last months of 2020. Data were collected by means of responses to the WHOQOL-Bref and the WHOQOL-SRPB instruments, online, through Google Forms®. The non-probabilistic snowball sampling method was used, totaling 948 answers. Data were tabulated using Microsoft Excel software (2019) and statistically analyzed, considering p<0.05 significant. The data presented emphatically show how the participants, who belong to some religion, presented a better relationship in the domains psychological health, independence, and environment and spirituality/religion/personal beliefs compared to those who do not have a religion. However, there was no statistically significant difference for the physical health and social relationships domains. It is concluded that belonging to a religion can contribute to improved quality of life and assist in coping with unfavorable situations during the COVID-19 pandemic. Therefore, the importance of developing new studies on the subject is highlighted, in order to understand more vehemently the relationship of these variables in crisis contexts that can change the routine of people's lives.


La pandemia causada por el SARS-CoV-2 (COVID-19) ha traído numerosos impactos en la vida cotidiana, tanto en los aspectos económicos, emocionales, psicológicos y sociales. En situaciones difíciles, las personas suelen recurrir a la espiritualidad o la religiosidad. El objetivo de este estudio fue investigar la presencia de religiosidad/espiritualidad en la población brasileña que enfrenta la pandemia de COVID- 19, correlacionada con la calidad de vida. Estudio cuantitativo, descriptivo, transversal, realizado en los últimos meses de 2020. Los datos fueron recolectados por medio de respuestas a los instrumentos WHOQOL-Bref y WHOQOL-SRPB, en línea, a través de Google Forms®. Se utilizó el método de muestreo no probabilístico de bola de nieve, totalizando 948 respuestas. Los datos fueron tabulados utilizando el software Microsoft Excel (2019) y analizados estadísticamente, considerando p<0,05 significativa. Los datos presentados muestran enfáticamente cómo los participantes, que pertenecen a alguna religión, presentaron una mejor relación en los dominios salud psicológica, independencia y entorno y espiritualidad/religión/creencias personales en comparación con aquellos que no tienen religión. Sin embargo, no hubo diferencias estadísticamente significativas para los dominios salud física y relaciones sociales. Se concluye que la pertenencia a una religión puede contribuir a mejorar la calidad de vida y ayudar a afrontar situaciones desfavorables durante la pandemia de COVID-19. Por lo tanto, se destaca la importancia de desarrollar nuevos estudios sobre el tema, para comprender con más vehemencia la relación de estas variables en contextos de crisis que pueden cambiar la rutina de vida de las personas.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Religião , Espiritualidade , COVID-19/diagnóstico , População , Estudos Transversais/métodos , Pandemias
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