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1.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998227

RESUMO

The possibility of directly growing carbon nanofibers (CNFs) and carbon nanotubes (CNTs) on half-Heusler alloys by Chemical Vapour Deposition (CVD) is investigated for the first time, without using additional catalysts, since the half-Heusler alloys per se may function as catalytic substrates, according to the findings of the current study. As a carbon source, acetylene is used in the temperature range of 700-750 °C. The n-type half-Heusler compound Zr0.4Ti0.60.33Ni0.33Sn0.98Sb0.020.33 is utilized as the catalytic substrate. At first, a computational model is developed for the CVD reactor, aiming to optimize the experimental process design and setup. The experimental process conditions are simulated to investigate the reactive species concentrations within the reactor chamber and the activation of certain reactions. SEM analysis confirms the growth of CNFs with diameters ranging from 450 nm to 1 µm. Raman spectroscopy implies that the formed carbon structures resemble CNFs rather than CNTs, and that amorphous carbon also co-exists in the deposited samples. From the characterization results, it may be concluded that a short reaction time and a low acetylene flow rate lead to the formation of a uniform CNF coating on the surface of half-Heusler alloys. The purpose of depositing carbon nanostructures onto half-Heusler alloys is to improve the current transfer, generated from these thermoelectric compounds, by forming a conductive coating on their surface.

2.
Int J Surg Case Rep ; 120: 109834, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823227

RESUMO

INTRODUCTION: Wandering spleen (WS) is a rare clinical condition found in less than 0.5 % of splenectomies and is characterized by ectopic location of the spleen within the abdomen or pelvis. It is always caused by excessive mobility brought on by the ligamentous laxity of its peritoneal attachments. Abdominal ultrasonography and computed tomography are the key imaging modalities for inquiry of WS. CASE PRESENTATION: We report the case of a 47-year-old woman who presented with painless abdominal swelling since the age of 6 years. An abdominal examination revealed a palpable, firm, mobile mass in the right lower abdomen approximately 15 × 15 cm in dimensions. A contrast CT scan of the abdomen revealed the absence of the spleen in the left upper quadrant. The patient was managed conservatively and followed for five years with favourable outcome. DISCUSSION: Failure of the dorsal mesogastrium to merge with the posterior abdominal wall in the second month of embryonic development is one of the reasons for WS. The nonsurgical conservative approach is limited to patients who are high-risk surgical candidates and have minimal symptoms and no complications. CONCLUSION: The good clinical outcome of our patient suggests that conservative non-surgical approach may be a reasonable alternative to unwarranted surgical intervention in selected clinically stable patients who have no evidence of splenic torsion or infarction, avoiding the possible complications of surgery.

3.
medRxiv ; 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38746281

RESUMO

Background: Dengue cases can progress to severe ant life-threating forms particularly in subsequent heterologous infections. However, recent studies had explored additional risk factors, including underlying health conditions, even in individuals without prior exposure to dengue, notably, in patients with endothelial dysfunction and chronic inflammation. This study examines the link between diabetes and the development of severe dengue disease in dengue-naive patients during the 2019 dengue outbreak in São Jose do Rio Preto, Brazil. Methodology: We enrolled 529 laboratory-confirmed dengue cases, identified through DENV RT-PCR or NS1 antigen assays in a hospital cohort of acute febrile illness. Subsequently, we investigated the presence of anti-dengue and anti-Zika IgG antibodies. Samples testing positive for Zika were excluded from the analyses. Two groups were analyzed: naïve (DV-), and dengue history (DV+). Results: Initially, presence of diabetes and kidney disease, as well as being dengue-naive, were associated with a higher frequency of severe and potentially severe clinical outcomes. Multivariate analysis identified diabetes as a risk factor, while the presence of anti-dengue antibodies was considered protective. Analysis of dengue naïve samples, highlighted diabetes as an independent risk factor to severe forms of dengue disease. In DV+ patients, no condition was highlighted as a risk factor by univariate analysis or multivariate analysis. Conclusions: We investigated and confirmed diabetes as a risk factor for severe dengue disease in individuals without prior dengue or Zika exposure. Our conclusions raise significant concerns given diabetes' ever increasing global prevalence and its potential impact on patients with or previous dengue exposure.

4.
J Exp Med ; 221(8)2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38819409

RESUMO

Th17 cell plasticity is crucial for development of autoinflammatory disease pathology. Periodontitis is a prevalent inflammatory disease where Th17 cells mediate key pathological roles, yet whether they exhibit any functional plasticity remains unexplored. We found that during periodontitis, gingival IL-17 fate-mapped T cells still predominantly produce IL-17A, with little diversification of cytokine production. However, plasticity of IL-17 fate-mapped cells did occur during periodontitis, but in the gingiva draining lymph node. Here, some Th17 cells acquired features of Tfh cells, a functional plasticity that was dependent on IL-6. Notably, Th17-to-Tfh diversification was important to limit periodontitis pathology. Preventing Th17-to-Tfh plasticity resulted in elevated periodontal bone loss that was not simply due to increased proportions of conventional Th17 cells. Instead, loss of Th17-to-Tfh cells resulted in reduced IgG levels within the oral cavity and a failure to restrict the biomass of the oral commensal community. Thus, our data identify a novel protective function for a subset of otherwise pathogenic Th17 cells during periodontitis.


Assuntos
Plasticidade Celular , Interleucina-17 , Periodontite , Células Th17 , Células Th17/imunologia , Animais , Periodontite/imunologia , Periodontite/patologia , Plasticidade Celular/imunologia , Interleucina-17/metabolismo , Interleucina-17/imunologia , Camundongos , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , Células T Auxiliares Foliculares/imunologia , Gengiva/imunologia , Gengiva/patologia , Imunoglobulina G/imunologia , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/patologia
5.
Magn Reson Med ; 92(2): 836-852, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38502108

RESUMO

PURPOSE: Arterial spin labeling (ASL) is a widely used contrast-free MRI method for assessing cerebral blood flow (CBF). Despite the generally adopted ASL acquisition guidelines, there is still wide variability in ASL analysis. We explored this variability through the ISMRM-OSIPI ASL-MRI Challenge, aiming to establish best practices for more reproducible ASL analysis. METHODS: Eight teams analyzed the challenge data, which included a high-resolution T1-weighted anatomical image and 10 pseudo-continuous ASL datasets simulated using a digital reference object to generate ground-truth CBF values in normal and pathological states. We compared the accuracy of CBF quantification from each team's analysis to the ground truth across all voxels and within predefined brain regions. Reproducibility of CBF across analysis pipelines was assessed using the intra-class correlation coefficient (ICC), limits of agreement (LOA), and replicability of generating similar CBF estimates from different processing approaches. RESULTS: Absolute errors in CBF estimates compared to ground-truth synthetic data ranged from 18.36 to 48.12 mL/100 g/min. Realistic motion incorporated into three datasets produced the largest absolute error and variability between teams, with the least agreement (ICC and LOA) with ground-truth results. Fifty percent of the submissions were replicated, and one produced three times larger CBF errors (46.59 mL/100 g/min) compared to submitted results. CONCLUSIONS: Variability in CBF measurements, influenced by differences in image processing, especially to compensate for motion, highlights the significance of standardizing ASL analysis workflows. We provide a recommendation for ASL processing based on top-performing approaches as a step toward ASL standardization.


Assuntos
Encéfalo , Circulação Cerebrovascular , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Marcadores de Spin , Humanos , Circulação Cerebrovascular/fisiologia , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Imagem de Perfusão/métodos , Masculino , Feminino , Adulto , Algoritmos
6.
Pharmacogenomics J ; 24(2): 6, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438359

RESUMO

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10-8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.


Assuntos
Farmacogenética , Neoplasias da Próstata , Masculino , Humanos , Bevacizumab/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/genética , Fatores de Risco
7.
Matrix Biol ; 127: 23-37, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331051

RESUMO

BACKGROUND: The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. METHODS: Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5-/- (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. RESULTS: In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5-/- (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. CONCLUSIONS: We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.


Assuntos
Nefropatias , Macrófagos , Camundongos , Animais , Receptor 1 de Quimiocina CX3C/genética , Receptor 1 de Quimiocina CX3C/metabolismo , Macrófagos/metabolismo , Rim/metabolismo , Inflamação/metabolismo , Nefropatias/metabolismo , RNA/metabolismo
8.
Exp Dermatol ; 33(1): e14894, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37522746

RESUMO

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell-associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell-associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.


Assuntos
Hidradenite Supurativa , Humanos , Quimases , Mastócitos/metabolismo , Quinase Syk , Triptases
9.
PLoS Negl Trop Dis ; 17(11): e0011710, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37943879

RESUMO

BACKGROUND: The co-circulation of flaviviruses in tropical regions has led to the hypothesis that immunity generated by a previous dengue infection could promote severe disease outcomes in subsequent infections by heterologous serotypes. This study investigated the influence of antibodies generated by previous Zika infection on the clinical outcomes of dengue infection. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 1,043 laboratory confirmed dengue patients and investigated their prior infection to Zika or dengue. Severe forms of dengue disease were more frequent in patients with previous Zika infection, but not in those previously exposed to dengue. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that previous Zika infection may represent a risk factor for subsequent severe dengue disease, but we did not find evidence of antibody-dependent enhancement (higher viral titer or pro-inflammatory cytokine overexpression) contributing to exacerbation of the subsequent dengue infection.


Assuntos
Vírus da Dengue , Dengue , Infecção por Zika virus , Zika virus , Humanos , Anticorpos Antivirais , Reações Cruzadas
10.
Viruses ; 15(9)2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37766255

RESUMO

Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.


Assuntos
COVID-19 , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Criança , Idoso , Adulto , Humanos , Pessoa de Meia-Idade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Doenças Negligenciadas , Influenza Humana/epidemiologia , SARS-CoV-2
11.
Braz J Microbiol ; 54(3): 1827-1834, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37589928

RESUMO

Acute respiratory infections are a constant public health problem causing childhood morbidity and mortality worldwide. Reported cases of major respiratory infections decreased in 2020 after restrictive measures were adopted to contain the COVID-19 pandemic, but there is little data on the impact after these measures were relaxed in the subsequent years. This study conducted molecular analysis to identify rhinovirus, respiratory syncytial virus, influenza A virus, and adenovirus in SARS-CoV-2-negative samples taken from symptomatic pediatric patients during 2021 and 2022 to ascertain the impact of pandemic response measures within the broader epidemiological scenario. The positivity rates found were 28.3% and 50.8%, in 2021 and 2022, respectively, representing a significant increase (1.8 times) in the circulation of non-SARS-CoV-2 viruses after the reduction of non-pharmacological measures to contain the COVID-19 pandemic. Within the positive samples, rhinovirus and respiratory syncytial virus were most frequent (44.4 and 18% in 2021; 44.5 and 22.5% in 2022), whereas influenza A and adenovirus were found in lower frequency (12.5 and 5.5% in 2021; 13.4 and 4.9% in 2022, respectively). Because these different respiratory virus diseases produce similar symptoms, diagnosis based on clinical condition alone can be inaccurate, and more reliable testing is required to select the best therapeutic approach for each case. The loosening of restrictive measures to contain the COVID-19 pandemic led to higher numbers of other respiratory infections in pediatric patients. Ongoing surveillance and differential diagnosis of respiratory viruses are required to better understand their seasonal patterns after the COVID-19 pandemic to guide prevention and control strategies.


Assuntos
COVID-19 , Infecções por Enterovirus , Infecções Respiratórias , Humanos , Criança , Pandemias , Brasil/epidemiologia , COVID-19/epidemiologia , Estações do Ano , SARS-CoV-2 , Vírus Sinciciais Respiratórios , Rhinovirus , Infecções Respiratórias/epidemiologia
12.
Exp Dermatol ; 32(6): 869-877, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36933897

RESUMO

Hidradenitis suppurativa is a complex inflammatory disease in which predicting therapeutic response remains challenging. IL-23 interacts with sex hormones but the relationships between the two in HS remains uninvestigated. To assess whether baseline clinical, hormonal or molecular markers are associated with clinical response to IL-23 antagonism with risankizumab in hidradenitis suppurativa. Twenty six individuals with Hurley stage 2/3 disease were administered risankizumab 150 mg Week 0, 4, 12. Baseline sex hormones and skin biopsies were taken. Clinical response at Week 16 assessed by the HiSCR, and differences between responders and non-responders assessed. Eighteen of 26 participants achieved HiSCR50 at week 16 (69.2%). Clinical response to IL-23 antagonism was associated with male gender, elevated total serum testosterone and decreased levels of FSH. Stratification by clinical responders/nonresponders identified differentially expressed genes including PLPP4 and MAPK10. Immunohistochemistry identified elevated numbers of CD11c, IL-17A and IL-17F positive cells compared to nonresponders. CD11c + cells significantly correlated with serum levels of total testosterone and inversely correlated with serum FSH. Clinical response to IL-23 antagonism in HS is associated with serum sex hormones, Th17 polarized inflammation in lesional tissue and CD11c + cells. These potential therapeutic biomarkers require further validation in larger cohorts but may suggest potential targeted HS therapy.


Assuntos
Hidradenite Supurativa , Humanos , Masculino , Estudos Prospectivos , Biomarcadores , Interleucina-23 , Hormônio Foliculoestimulante/uso terapêutico
13.
Eur Respir J ; 61(5)2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36922030

RESUMO

BACKGROUND: COVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID). METHODS: We assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury. RESULTS: Monocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6-CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence. CONCLUSIONS: Our data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.


Assuntos
COVID-19 , Influenza Humana , Lesão Pulmonar , Humanos , Monócitos/metabolismo , Quimiocinas CXC/metabolismo , Receptores Virais/metabolismo , Receptores CXCR6 , Receptores de Quimiocinas/metabolismo , Síndrome de COVID-19 Pós-Aguda , Ligantes , Convalescença , Receptores Depuradores/metabolismo , Quimiocina CXCL16 , Gravidade do Paciente
14.
BJS Open ; 7(1)2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36633418

RESUMO

INTRODUCTION: Acutely symptomatic abdominal wall and groin hernias (ASH) are a common acute surgical presentation. There are limited data to guide decisions related to surgical repair technique and use of antibiotics, which can be driven by increased risk of surgical site infection (SSI) in this group. This study aims to report rates of SSI following ASH repair and explore the use of patient-reported outcome measure reporting in this setting. METHODS: An 18-week, UK-based, multicentre prospective cohort study (NCT04197271) recruited adults with ASH. This study reports operatively managed patients. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing (Bluebelle score) were collected. Descriptive analyses were performed to estimate event rates of SSI and regression analysis explored the relationship between Bluebelle scores and SSI. The 30 and 90-day follow-up visits assessed complications and quality of life. RESULTS: The MASH study recruited 273 patients, of whom 218 were eligible for this study, 87.2 per cent who underwent open repair. Mesh was used in 123 patients (50.8 per cent). Pre- and postoperative antibiotics were given in 163 (67.4 per cent) and 28 (11.5 per cent) patients respectively. There were 26 reported SSIs (11.9 per cent). Increased BMI, incisional, femoral, and umbilical hernia were associated with higher rates of SSI (P = 0.006). In 238 patients, there was a difference in healthy utility values at 90 days between patients with and without SSI (P = 0.025). Also, when analysing 191 patients with Bluebelle scores, those who developed an SSI had higher Bluebelle values (P < 0.001). CONCLUSION: SSI is frequent in repair of acutely symptomatic hernia and correlates with BMI and site of hernia.


Assuntos
Serviços Médicos de Emergência , Herniorrafia , Infecção da Ferida Cirúrgica , Adulto , Humanos , Antibacterianos/uso terapêutico , Herniorrafia/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Infecção da Ferida Cirúrgica/epidemiologia , Medidas de Resultados Relatados pelo Paciente , Reino Unido/epidemiologia , Fatores de Risco
15.
Environ Res ; 220: 115156, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36574796

RESUMO

Multi-walled carbon nanotubes (MWCNTs) are tubular-shaped carbon allotropes, composed of multiple concentric graphene cylinders. The extended systems of conjugated double bonds, that MWCNTs are constituted by, provide them with high electron affinities, enabling them to act as electron donors or acceptors. Consequently, their potential biomedical applications, as synthetic antioxidant agents, are of particular interest. Based on the above, the purpose of the present study was to evaluate the intrinsic antioxidant properties of pristine and carboxylated MWCNTs, as well as of novel hybrid nanocomposites of MWCNTs and inorganic nanoparticles. To this end, after the synthesis and characterization of MWCNTs, their antiradical, reducing, and antigenotoxic properties were assessed in cell-free assays, using a methodological approach that has been recently proposed by our research group. According to our results, most of the tested MWCNTs exhibited strong antioxidant activities. More elaborately, the hybrid material of MWCNTs and ferrous oxide nanoparticles, i.e., CNTs@Fe3O4, showed robust scavenging capacities in all free-radical scavenging assays examined. As regards reducing properties, the pristine MWCNTs, i.e., CNTs-Ref, exhibited the greater electron donating capacity. Finally, in terms of antigenotoxic properties, the hybrid material of MWCNTs and silicon carbide nanoparticles, i.e., CNTs@SiC, exhibited potent ability to inhibit the formation of peroxyl radicals, thus preventing from the oxidative DNA damage. Conclusively, our findings suggest that the MWCNTs of the study could be considered as promising broad-spectrum antioxidants, however, further investigations are required to evaluate their toxicological profile in cell-based and in vivo systems.


Assuntos
Antioxidantes , Nanotubos de Carbono , Antioxidantes/farmacologia , Nanotubos de Carbono/toxicidade , Nanotubos de Carbono/química , Sistema Livre de Células , Estresse Oxidativo , Ácidos Carboxílicos
16.
PLoS One ; 17(10): e0275639, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36201503

RESUMO

BACKGROUND: Women with breast cancer in sub-Saharan Africa are commonly diagnosed at advanced stages. In Tanzania, more than 80% of women are diagnosed with stage III or IV disease, and mortality rates are high. This study explored factors contributing to delayed diagnostic evaluation among women with breast cancer in Tanzania. METHODS: A qualitative study was performed at Muhimbili National Hospital in Dar es Salaam, Tanzania. Twelve women with symptomatic pathologically proven breast cancer were recruited. In-depth, semi-structured interviews were conducted in Swahili. Interviews explored the women's journey from symptom recognition to diagnosis, including the influence of breast cancer knowledge and pre-conceptions, health seeking behaviors, psychosocial factors, preference for alternative treatments, and the contribution of culture and norms. Audio-recorded interviews were transcribed and translated into English. Thematic analysis was facilitated by a cloud-based qualitative analysis software. RESULTS: All women reported that their first breast symptom was a self-identified lump or swelling. Major themes for factors contributing to delayed diagnostic presentation of breast cancer included lack of basic knowledge and awareness of breast cancer and misconceptions about the disease. Participants faced barriers with their local primary healthcare providers, including symptom mismanagement and delayed referrals for diagnostic evaluation. Other barriers included financial hardships, fear and stigma of cancer, and use of traditional medicine. The advice and influence of family members and friends played key roles in healthcare-seeking behaviors, serving as both facilitators and barriers. CONCLUSION: Lack of basic knowledge and awareness of breast cancer, stigma, financial barriers, and local healthcare system barriers were common factors contributing to delayed diagnostic presentation of breast cancer. The influence of friends and family also played key roles as both facilitators and barriers. This information will inform the development of educational intervention strategies to address these barriers and improve earlier diagnosis of symptomatic breast cancer in Tanzania.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/psicologia , Feminino , Humanos , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Pesquisa Qualitativa , Estigma Social , Tanzânia
17.
Elife ; 112022 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-35900198

RESUMO

Mimivirus is the prototype of the Mimiviridae family of giant dsDNA viruses. Little is known about the organization of the 1.2 Mb genome inside the membrane-limited nucleoid filling the ~0.5 µm icosahedral capsids. Cryo-electron microscopy, cryo-electron tomography, and proteomics revealed that it is encased into a ~30-nm diameter helical protein shell surprisingly composed of two GMC-type oxidoreductases, which also form the glycosylated fibrils decorating the capsid. The genome is arranged in 5- or 6-start left-handed super-helices, with each DNA-strand lining the central channel. This luminal channel of the nucleoprotein fiber is wide enough to accommodate oxidative stress proteins and RNA polymerase subunits identified by proteomics. Such elegant supramolecular organization would represent a remarkable evolutionary strategy for packaging and protecting the genome, in a state ready for immediate transcription upon unwinding in the host cytoplasm. The parsimonious use of the same protein in two unrelated substructures of the virion is unexpected for a giant virus with thousand genes at its disposal.


Assuntos
Vírus Gigantes , Mimiviridae , Capsídeo/metabolismo , Microscopia Crioeletrônica/métodos , Genoma Viral , Vírus Gigantes/genética , Mimiviridae/genética , Nucleoproteínas/genética , Nucleoproteínas/metabolismo , Oxirredutases/metabolismo
18.
Br J Surg ; 109(8): 754-762, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35608216

RESUMO

BACKGROUND: Acutely symptomatic abdominal wall and groin hernias are a common reason for acute surgical hospital admissions. There are limited data to guide the treatment of these patients. This study aimed to assess outcomes of emergency hernia surgery and identify common management strategies, to improve care for these high-risk patients. METHODS: A 20-week, national multicentre, collaborative, prospective cohort study (NCT04197271) recruited adults with acutely symptomatic abdominal wall and groin hernias across the UK. Data on patient characteristics, inpatient management, quality of life, complications, and wound healing were collected. Follow-up telephone calls at 30 and 90 days were used to assessed complications and quality of life. Descriptive analyses were undertaken to describe the population and outcomes. RESULTS: Twenty-three hospitals recruited 272 eligible patients. Inguinal (37.8 per cent) and umbilical (37.1 per cent) hernias were the most common. Some 13.9 per cent were awaiting elective surgery and 12.8 per cent had previously declined intervention. CT was performed in 47.1 per cent and 81.3 per cent underwent surgical management. Open repairs were carried out in 93.5 per cent, and 92.5 per cent of these were performed under general anaesthesia. Four of 13 laparoscopic procedures were converted to open surgery. Mesh was used in 55.1 per cent of repairs, typically synthetic non-absorbable (87.4 per cent). Complications were infrequent; surgical-site infection (9.4 per cent), delirium (3.2 per cent), and pneumonia (2.3 per cent) were the most common. The 90-day mortality rate was 4.9 per cent. Immediate surgical management was associated with a significant improvement in quality of life at 30 days (median score 0.73-0.82). CONCLUSION: There is variation in the investigation, management, and surgical technique used to treat acutely symptomatic abdominal wall and groin hernias in the UK. The optimal management strategy for specific acute presentations remains to be established. Presented to the Association of Surgeons in Training Conference, Birmingham, UK, March 2021, the Association of Surgeons of Great Britain and Ireland Congress, May 2021, the World Society of Emergency Surgery, Edinburgh, UK, September 2021, and the European Hernia Society Congress, Copenhagen, Denmark, October 2021.


Assuntos
Hérnia Inguinal , Herniorrafia , Adulto , Hérnia Inguinal/diagnóstico , Hérnia Inguinal/cirurgia , Herniorrafia/métodos , Humanos , Estudos Prospectivos , Qualidade de Vida , Telas Cirúrgicas
19.
Front Neurol ; 12: 753284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777224

RESUMO

SARS-CoV-2 infection has been shown to damage multiple organs, including the brain. Multiorgan MRI can provide further insight on the repercussions of COVID-19 on organ health but requires a balance between richness and quality of data acquisition and total scan duration. We adapted the UK Biobank brain MRI protocol to produce high-quality images while being suitable as part of a post-COVID-19 multiorgan MRI exam. The analysis pipeline, also adapted from UK Biobank, includes new imaging-derived phenotypes (IDPs) designed to assess the possible effects of COVID-19. A first application of the protocol and pipeline was performed in 51 COVID-19 patients post-hospital discharge and 25 controls participating in the Oxford C-MORE study. The protocol acquires high resolution T1, T2-FLAIR, diffusion weighted images, susceptibility weighted images, and arterial spin labelling data in 17 min. The automated imaging pipeline derives 1,575 IDPs, assessing brain anatomy (including olfactory bulb volume and intensity) and tissue perfusion, hyperintensities, diffusivity, and susceptibility. In the C-MORE data, IDPs related to atrophy, small vessel disease and olfactory bulbs were consistent with clinical radiology reports. Our exploratory analysis tentatively revealed some group differences between recovered COVID-19 patients and controls, across severity groups, but not across anosmia groups. Follow-up imaging in the C-MORE study is currently ongoing, and this protocol is now being used in other large-scale studies. The protocol, pipeline code and data are openly available and will further contribute to the understanding of the medium to long-term effects of COVID-19.

20.
Neuroimage ; 238: 118236, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34091034

RESUMO

The mismatch in the spatial resolution of Arterial Spin Labeling (ASL) MRI perfusion images and the anatomy of functionally distinct tissues in the brain leads to a partial volume effect (PVE), which in turn confounds the estimation of perfusion into a specific tissue of interest such as gray or white matter. This confound occurs because the image voxels contain a mixture of tissues with disparate perfusion properties, leading to estimated perfusion values that reflect primarily the volume proportions of tissues in the voxel rather than the perfusion of any particular tissue of interest within that volume. It is already recognized that PVE influences studies of brain perfusion, and that its effect might be even more evident in studies where changes in perfusion are co-incident with alterations in brain structure, such as studies involving a comparison between an atrophic patient population vs control subjects, or studies comparing subjects over a wide range of ages. However, the application of PVE correction (PVEc) is currently limited and the employed methodologies remain inconsistent. In this article, we outline the influence of PVE in ASL measurements of perfusion, explain the main principles of PVEc, and provide a critique of the current state of the art for the use of such methods. Furthermore, we examine the current use of PVEc in perfusion studies and whether there is evidence to support its wider adoption. We conclude that there is sound theoretical motivation for the use of PVEc alongside conventional, 'uncorrected', images, and encourage such combined reporting. Methods for PVEc are now available within standard neuroimaging toolboxes, which makes our recommendation straightforward to implement. However, there is still more work to be done to establish the value of PVEc as well as the efficacy and robustness of existing PVEc methods.


Assuntos
Algoritmos , Doença de Alzheimer/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/análise , Compostos de Anilina , Encéfalo/patologia , Encéfalo/fisiopatologia , Radioisótopos de Carbono , Artérias Cerebrais , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Córtex Entorrinal/diagnóstico por imagem , Córtex Entorrinal/patologia , Córtex Entorrinal/fisiopatologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Hipocampo/fisiopatologia , Processamento de Imagem Assistida por Computador/métodos , Glicoproteínas de Membrana/análise , Proteínas do Tecido Nervoso/análise , Tamanho do Órgão , Perfusão , Tomografia por Emissão de Pósitrons , Piridinas , Pirrolidinonas , Compostos Radiofarmacêuticos , Marcadores de Spin , Vesículas Sinápticas/química , Tiazóis
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