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1.
Cell Death Differ ; 31(3): 360-377, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38365970

RESUMO

Phenotypic plasticity, defined as the ability of individual cells with stable genotypes to exert different phenotypes upon exposure to specific environmental cues, represent the quintessential hallmark of the cancer cell en route from the primary lesion to distant organ sites where metastatic colonization will occur. Phenotypic plasticity is driven by a broad spectrum of epigenetic mechanisms that allow for the reversibility of epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions (EMT/MET). By taking advantage of the co-existence of epithelial and quasi-mesenchymal cells within immortalized cancer cell lines, we have analyzed the role of EMT-related gene isoforms in the regulation of epithelial mesenchymal plasticity (EMP) in high grade serous ovarian cancer. When compared with colon cancer, a distinct spectrum of downstream targets characterizes quasi-mesenchymal ovarian cancer cells, likely to reflect the different modalities of metastasis formation between these two types of malignancy, i.e. hematogenous in colon and transcoelomic in ovarian cancer. Moreover, upstream RNA-binding proteins differentially expressed between epithelial and quasi-mesenchymal subpopulations of ovarian cancer cells were identified that underlie differential regulation of EMT-related isoforms. In particular, the up- and down-regulation of RBM24 and ESRP1, respectively, represent a main regulator of EMT in ovarian cancer cells. To validate the functional and clinical relevance of our approach, we selected and functionally analyzed the Tropomyosin 1 gene (TPM1), encoding for a protein that specifies the functional characteristics of individual actin filaments in contractile cells, among the ovarian-specific downstream AS targets. The low-molecular weight Tpm1.8/9 isoforms are specifically expressed in patient-derived ascites and promote invasion through activation of EMT and Wnt signaling, together with a broad spectrum of inflammation-related pathways. Moreover, Tpm1.8/9 expression confers resistance to taxane- and platinum-based chemotherapy. Small molecule inhibitors that target the Tpm1 isoforms support targeting Tpm1.8/9 as therapeutic targets for the development of future tailor-made clinical interventions.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Movimento Celular , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Via de Sinalização Wnt , Transição Epitelial-Mesenquimal , Proteínas de Ligação a RNA/metabolismo
2.
Naturwissenschaften ; 110(2): 13, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36971882

RESUMO

Several sawfly species (Hymenoptera: Symphyta) possess larval stages with oesophageal diverticula in which plant compounds are sequestered and used for defence against predators. These organs are present in the larvae of Susana (Tenthredinidae) but remain poorly studied. Here, the aim was to analyse the diverticula extract of Susana cupressi by gas chromatography-mass spectrometry to better understand the ecology of this species. The foliage of the hostplant (Cupressus sempervirens), as well as the larval foregut, midgut, and haemolymph were also analysed. Complementary data were gathered by morphological observations, bioassays using ants, and genetic analyses to identify the studied Susana species. Altogether, 48 terpenes were identified, 30 being sesquiterpenes. The terpenes were generally detected in the foliage, but also in the diverticula, foregut, and midgut, whereas none of them in the haemolymph. The main compounds were alpha-cedrene, alpha-fenchene, alpha-pinene, alpha-terpinyl acetate, beta-myrcene, beta-pinene, cedrol, delta 3-carene, epi-bicyclosesquiphellandrene, germacrene D, limonene, sabinene, and terpinolene. The chemical profiles of these 13 compounds were significantly correlated between foliage-diverticula, diverticula-foregut and foregut-midgut, but not correlated for the three remaining possible comparisons. Alpha-pinene decreased and germacrene D increased from the foliage to the diverticula, which may reflect a specific sequestration of the latter terpene and its known deleterious effects on insects. We conclude that larvae of S. cupressi, similarly to those of diprionids, are well defended against predatory attacks by sequestering and regurgitating hostplant terpenes, including germacrene D.


Assuntos
Formigas , Cupressus , Divertículo , Himenópteros , Animais , Cupressus/química , Larva , Terpenos/análise
3.
Catal Sci Technol ; 12(13): 4243-4254, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35873718

RESUMO

Alumina (Al2O3) is one of the most used supports in the chemical industry due to its exceptional thermal stability, surface area, and acidic properties. Mesoscopic structured alumina with adequate acidic properties is important in catalysis to enhance the selectivity and conversion of certain reactions and processes. This study introduces a synthetic method based on electrospinning to produce Al2O3 nanofibers (ANFs) with zeolite mordenite (MOR) nanocrystals (hereafter, hybrid ANFs) to tune the textural and surface acidity properties. The hybrid ANFs with electrospinning form a non-woven network with macropores. ANF-HMOR, i.e., ANFs containing protonated mordenite (HMOR), shows the highest total acidity of ca. 276 µmol g-1 as determined with infrared spectroscopy using pyridine as a molecular probe (IR-Py). IR-Py results reveal that Lewis acid sites are prominently present in the hybrid ANFs. Brønsted acid sites are also observed in the hybrid ANFs and are associated with the HMOR presence. The functionality of hybrid ANFs is evaluated during methanol dehydration to dimethyl ether (DME). The proof of concept reaction reveals that ANF-HMOR is the more active and selective catalyst with 87% conversion and nearly 100% selectivity to DME at 573 K. The results demonstrate that the textural properties and the acid site type and content can be modulated in hybrid ANF structures, synergistically improving the selectivity and conversion during the methanol dehydration reaction. From a broader perspective, our results promote the utilization of hybrid structural materials as a means to tune chemical reactions selectively.

4.
Eur J Pain ; 26(5): 1123-1134, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35263480

RESUMO

BACKGROUND: The objective of this study was to develop prediction models and explore the external validity of the models in a large sample of patients with chronic widespread pain (CWP) and fibromyalgia (FM). METHODS: Patients with CWP and FM referred to rehabilitation services in Norway (n = 986) self-reported data on potential predictors prior to entering rehabilitation, and self-reported outcomes at one-year follow-up. Logistic regression models of improvement, worsening and work status, and a linear regression model of health-related quality of life (HRQoL), were developed using lasso regression. Externally validated estimates of model performance were obtained from the validation set. RESULTS: The number of participants in the development and the validation sets was 771 and 215 respectively; only participants with outcome data (n = 519-532 and 185, respectively) were included in the analyses. On average, HRQoL and work status changed little over one year. The prediction models included 10-11 predictors. Discrimination (AUC statistic) for prediction of outcome at follow-up was 0.71 for improvement, 0.67 for worsening, and 0.87 for working. The median absolute error of predictions of HRQoL was 0.36 (0.22-0.51). Reasonably good predictions of working at follow-up and HRQoL could be obtained using only the baseline scores as predictors. CONCLUSIONS: Moderately complex prediction models (10-11 predictors) generated poor to excellent predictions of patient-relevant outcomes. Simple prediction models of working and HRQoL at follow-up may be nearly as accurate and more practical. SIGNIFICANCE: Prediction modelling of outcome in rehabilitation has been sparsely explored. Such models may guide clinical decision-making. This study developed and externally validated prediction models for outcomes of people with chronic widespread pain and fibromyalgia in a rehabilitation setting. Multivariable prediction models generated poor to excellent predictions of patient-relevant outcomes, but the complexity of these models may reduce their clinical utility. Simple univariable prediction models were nearly as accurate and may have more potential for use in clinical practice.


Assuntos
Dor Crônica , Fibromialgia , Humanos , Modelos Logísticos , Qualidade de Vida , Resultado do Tratamento
5.
Int J Mol Sci ; 22(3)2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33525681

RESUMO

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1ß and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1ß expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Polidesoxirribonucleotídeos/administração & dosagem , Selenometionina/administração & dosagem , Varicocele/tratamento farmacológico , Animais , Caspase 1/genética , Modelos Animais de Doenças , Quimioterapia Combinada , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-1beta/genética , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Polidesoxirribonucleotídeos/farmacologia , Ratos , Selenometionina/farmacologia , Testosterona/metabolismo , Varicocele/genética , Varicocele/metabolismo
6.
BMC Public Health ; 20(1): 1353, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32887600

RESUMO

BACKGROUND: The population prevalence of many diseases is known. However, little is known of the population prevalence of motor impairments. METHODS: The aim of this study was to determine the point prevalence of specific motor impairments (weakness, fatigue, contracture, impaired balance and impaired coordination) in the population aged 55 years and older resident in New South Wales, Australia in 2018. 55,210 members of the 45 and Up cohort were invited to participate in a follow-up survey that included questions on motor impairment. Responses were received from 20,141 people (36%). Calibrated estimates of prevalence of specific motor impairments, and of having at least one motor impairment, were obtained using survey weights based on the known multivariate distributions of age, gender and geographical location (28 regions) in the population. RESULTS: More than one-third of adults aged over 55 residing in New South Wales have difficulty using their hands, arms or legs. The prevalence of each motor impairment (muscle weakness, fatigue, contracture, impaired balance or impaired coordination) in this population is between 4 and 12%. The prevalence of at least one of these impairments is 21%. The prevalence of at least one impairment in people aged 85 and over is 42%. Women consistently had more difficulty using hands, arms and legs, and more motor impairment, than men. Difficulty using hands, arms and legs and the prevalence of all motor impairments, especially poor balance, greatly increased with age. CONCLUSION: The prevalence of specific motor impairments in older Australian adults is high - comparable to that of the most prevalent diseases. There may be merit in considering motor impairment as a significant public health problem in its own right.


Assuntos
Transtornos Motores/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Contratura/epidemiologia , Estudos Transversais , Fadiga/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/epidemiologia , New South Wales/epidemiologia , Prevalência
8.
An Acad Bras Cienc ; 92(2): e20200800, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638868

RESUMO

In the second part of the review on electrochemical energy storage, the devolvement of batteries is explored. First, fundamental aspects of battery operation will be given, then, different materials and chemistry of rechargeable batteries will be explored, including each component of the cell. In negative electrodes, metallic, intercalation and transformation materials will be addressed. Examples are Li or Na metal batteries, graphite and other carbonaceous materials (such as graphene) for intercalation of metal-ions and transition metal oxides and silicon for transformation. In the positive electrode section, materials for intercalation and transformation will be reviewed. The state-of-the-art on intercalation as lithium cobalt oxide and nickel containing oxides will be approached for intercalation materials, whereas sulfur and metal-air will also be explored for transformation. Alongside, the role of electrolyte will be discussed concerning performance and safety, with examples for the next generation devices. Finally, a general future perspective will address both electrochemical capacitors and batteries.

9.
An Acad Bras Cienc ; 92(2): e20200796, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32638869

RESUMO

The Nobel Prize in Chemistry 2019 recognized the importance of Li-ion batteries and the revolution they allowed to happen during the past three decades. They are part of a broader class of electrochemical energy storage devices, which are employed where electrical energy is needed on demand and so, the electrochemical energy is converted into electrical energy as required by the application. This opens a variety of possibilities on the utilization of energy storage devices, beyond the well-known mobile applications, assisting on the decarbonization of energy production and distribution. In this series of reviews in two parts, two main types of energy storage devices will be explored: electrochemical capacitors (part I) and rechargeable batteries (part II). More specifically, we will discuss about the materials used in each type of device, their main role in the energy storage process, their advantages and drawbacks and, especially, strategies to improve their performance. In the present part, electrochemical capacitors will be addressed. Their fundamental difference to batteries is explained considering the process at the electrode/electrolyte surface and the impact in performance. Materials used in electrochemical capacitors, including double layer capacitors and pseudocapacitive materials will be reviewed, highlighting the importance of electrolytes. As an important part of these strategies, synthetic routes for the production of nanoparticles will also be approached (part I).

10.
Clin Ther ; 42(6): 1034-1046, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32482490

RESUMO

PURPOSE: Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur unpredictably, partly due to the pharmacokinetic (PK) variability of oral LD, resulting from gastrointestinal dysfunction and from the effects of food on absorption. CVT-301 is a levodopa inhalation powder for the treatment of OFF period symptoms in patients on oral dopa-decarboxylase inhibitor/LD. PK and safety profiles of single dose CVT-301, administered with oral carbidopa (CD) and oral CD/LD, were examined in patients with Parkinson's disease in the fed state. METHODS: Eligible patients were aged 30-85 years, with a clinical diagnosis of Parkinson's disease and a body mass index of 18-32 kg/m2, and were receiving treatment with a stable regimen that included oral CD/LD (25/100 mg) (total LD, ≤800 mg/d). A high-fat/protein meal was eaten 4-5 h after the administration of the morning oral CD/LD dose. Blood samples for predose PK analysis were obtained after the meal, followed by a single inhaled dose of CVT-301 84 mg (+25 mg of oral CD) or oral CD/LD (25/100 mg) or vice versa in 2 dosing periods in a crossover design. Blood was sampled at 0, 5, 10, 15, 30, and 45 min and at 1, 1.5, 2, 3, and 4 h postdose. Tolerability assessments included treatment-emergent adverse events. FINDINGS: Twenty-three patients were enrolled (65.2% male; 87.0% white; mean age, 69.3 years; mean body mass index, 26.9 kg/m2; mean Parkinson's disease duration, 8.2 years; mean baseline LD dosage, 460.9 mg/d; 73.9% at Hoehn and Yahr stage <2.5). PK analyses were based on LD concentrations without baseline adjustment. Median Tmax values with CVT-301 and oral CD/LD were 15 and 120 min (P < 0.001). Cmax with CVT-301 was lower than with oral CD/LD (590.3 vs 844.3 ng/mL). C10min and C30min values with CVT-301 were approximately twice those with CD/LD (522.9 and 531.5 ng/mL vs 247.3 and 300.9 ng/mL, respectively). %CV for C5min to Cmax with CVT-301 was lower than that with oral CD/LD. The most common treatment-emergent adverse event was cough (CVT-301, 7 patients [30.4%]; oral CD/LD, 1 patient [4.5%]). IMPLICATIONS: PK properties showed that CVT-301 was more rapidly absorbed, with higher plasma LD concentrations in the first 45 min, and demonstrated lower interpatient variability, than was oral CD/LD in the fed condition. The study findings suggest that CVT-301 can be used without regard to food intake. ClinicalTrials.gov identifier: NCT03887884.


Assuntos
Antiparkinsonianos/farmacocinética , Carbidopa/administração & dosagem , Levodopa/farmacocinética , Doença de Parkinson/tratamento farmacológico , Administração por Inalação , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/sangue , Carbidopa/efeitos adversos , Estudos Cross-Over , Feminino , Interações Alimento-Droga , Humanos , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Levodopa/sangue , Masculino , Pessoa de Meia-Idade
11.
Nutrients ; 12(5)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357526

RESUMO

Cadmium (Cd) damages the thyroid gland. We evaluated the effects of myo-inositol (MI), seleno-L-methionine (Se) or their combination on the thyroids of mice simultaneously administered with Cd chloride (CdCl2). Eighty-four male mice were divided into 12 groups (seven mice each). Six groups (controls) were treated with 0.9% NaCl (vehicle), Se (0.2 mg/kg/day), Se (0.4 mg/kg/day), MI (360 mg/kg/day), MI+Se (0.2 mg/kg) and MI+Se (0.4 mg/kg). The other six groups were treated with CdCl2 (2 mg/kg), CdCl2+MI, CdCl2+Se (0.2 mg/kg), CdCl2+Se (0.4 mg/kg), CdCl2+MI+Se (0.2 mg/kg) and CdCl2+MI+Se (0.4 mg/kg). An additional group of CdCl2-challenged animals (n= 7) was treated with resveratrol (20 mg/kg), an effective and potent antioxidant. All treatments lasted 14 days. After sacrifice, the thyroids were evaluated histologically and immunohistochemically. CdCl2 reduced the follicular area, increased the epithelial height, stroma, and cells expressing monocyte chemoattractant protein-1 (MCP-1) and C-X-C motif chemokine 10 (CXCL10). CdCl2+Se at 0.2/0.4 mg/kg insignificantly reversed the follicular and stromal structure, and significantly decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI significantly reversed the thyroid structure and further decreased the number of MCP-1 and CXCL10-positive cells. CdCl2+MI+Se, at both doses, brought all indices to those of CdCl2-untreated mice. MI, particularly in association with Se, defends mice from Cd-induced damage. The efficacy of this combination was greater than that of resveratrol, at least when using the follicular structure as a read-out for a comparison. We suggest that the use of these nutraceuticals, more specifically the combination of MI plus SE, can protect the thyroid of Cd-exposed subjects.


Assuntos
Cloreto de Cádmio/toxicidade , Suplementos Nutricionais , Inositol/administração & dosagem , Inositol/farmacologia , Selênio/administração & dosagem , Selênio/farmacologia , Glândula Tireoide/efeitos dos fármacos , Glândula Tireoide/metabolismo , Animais , Antioxidantes , Quimiocina CCL2/metabolismo , Quimiocina CXCL10/metabolismo , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos C57BL , Resveratrol/administração & dosagem , Resveratrol/farmacologia , Glândula Tireoide/patologia
12.
Nutrients ; 12(5)2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32466161

RESUMO

Varicocele is one of the main causes of infertility in men. Oxidative stress and consequently apoptosis activation contribute to varicocele pathogenesis, worsening its prognosis. Natural products, such as lycopene, showed antioxidant and anti-inflammatory effects in several experimental models, also in testes. In this study we investigated lycopene effects in an experimental model of varicocele. Male rats (n = 14) underwent sham operations and were administered with vehicle (n = 7) or with lycopene (n = 7; 1 mg/kg i.p., daily). Another group of animals (n = 14) underwent surgical varicocele. After 28 days, the sham and 7 varicocele animals were euthanized, and both operated and contralateral testes were weighted and processed. The remaining rats were treated with lycopene (1 mg/kg i.p., daily) for 30 days. Varicocele rats showed reduced testosterone levels, testes weight, Bcl-2 mRNA expression, changes in testes structure and increased malondialdehyde levels and BAX gene expression. TUNEL (Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling) assay showed an increased number of apoptotic cells. Treatment with lycopene significantly increased testosterone levels, testes weight, and Bcl-2 mRNA expression, improved tubular structure and decreased malondialdehyde levels, BAX mRNA expression and TUNEL-positive cells. The present results show that lycopene exerts beneficial effects in testes, and suggest that supplementation with the tomato-derived carotenoid might be considered a novel nutraceutical strategy for the treatment of varicocele and male infertility.


Assuntos
Suplementos Nutricionais , Infertilidade Masculina/tratamento farmacológico , Licopeno/farmacologia , Varicocele/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Carotenoides/farmacologia , Marcação In Situ das Extremidades Cortadas , Masculino , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Testículo/efeitos dos fármacos , Testosterona/sangue , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
13.
Food Chem Toxicol ; 132: 110675, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31306689

RESUMO

Cadmium (Cd) induces functional and morphological changes in kidney. Therefore, the effects of a natural nutraceutical antioxidant, myo-inositol (MI), were evaluated in mice kidneys after Cd challenge. Twenty-eight C57 BL/6 J mice were divided into these groups: 0.9% NaCl; MI (360 mg/kg/day); CdCl2 (2 mg/kg/day) plus vehicle; CdCl2 (2 mg/kg/day) plus MI (360 mg/kg/day). After 14 days, kidneys were processed for structural, biochemical and morphometric evaluation. Treatment with CdCl2 increased urea nitrogen and creatinine in serum and augmented tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression. Furthermore, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1) and myo-inositol oxygenase (MIOX) immunoreactivity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells number were significantly higher than control and MI groups. Glutathione (GSH) content and glutathione peroxidase (GPx) activity were reduced and structural changes were evident. The treatment with MI significantly lowered urea nitrogen and creatinine levels, TNF-α and iNOS expression, MCP-1, KIM-1 and MIOX immunoreactivity and TUNEL positive cells number, increased GSH content and GPx activity and preserved kidney morphology. A protection of MI against Cd-induced damages in mice kidney was demonstrated, suggesting a strong antioxidant role of this nutraceutical against environmental Cd harmful effects on kidney lesions.


Assuntos
Cloreto de Cádmio/toxicidade , Suplementos Nutricionais , Inositol/farmacologia , Rim/efeitos dos fármacos , Animais , Antioxidantes/administração & dosagem , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
14.
J Hosp Infect ; 103(4): 388-394, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31220480

RESUMO

BACKGROUND: Certain Clostridium difficile ribotypes have been associated with complex disease phenotypes including recurrence and increased severity, especially the well-described hypervirulent RT027. This study aimed to determine the pattern of ribotypes causing infection and the association, if any, with severity. METHODS: All faecal samples submitted to a large diagnostic laboratory for C. difficile testing between 2011 and 2013 were subject to routine testing and culture. All C. difficile isolates were ribotyped, and associated clinical and demographic patient data were retrieved and linked to ribotyping data. RESULTS: In total, 86 distinct ribotypes were identified from 705 isolates of C. difficile. RT002 and RT015 were the most prevalent (22.5%, N=159). Only five isolates (0.7%) were hypervirulent RT027. Ninety of 450 (20%) patients with clinical information available died within 30 days of C. difficile isolation. RT220, one of the 10 most common ribotypes, was associated with elevated median C-reactive protein and significantly increased 30-day all-cause mortality compared with RT002 and RT015, and with all other ribotypes found in the study. CONCLUSIONS: A wide range of C. difficile ribotypes were responsible for C. difficile infection presentations. Although C. difficile-associated mortality has reduced in recent years, expansion of lineages associated with increased severity could herald increases in future mortality. Enhanced surveillance for emerging lineages such as RT220 that are associated with more severe disease is required, with genomic approaches to dissect pathogenicity.


Assuntos
Clostridioides difficile/classificação , Clostridioides difficile/genética , Infecções por Clostridium/microbiologia , Infecções por Clostridium/patologia , Ribotipagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Clostridioides difficile/isolamento & purificação , Clostridioides difficile/patogenicidade , Fezes/microbiologia , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
15.
J Appl Physiol (1985) ; 126(5): 1445-1453, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30571291

RESUMO

This review, the first in a series of minireviews on the passive mechanical properties of skeletal muscles, seeks to summarize what is known about the muscle deformations that allow relaxed muscles to lengthen and shorten. Most obviously, when a muscle lengthens, muscle fascicles elongate, but this is not the only mechanism by which muscles change their length. In pennate muscles, elongation of muscle fascicles is accompanied by changes in pennation and changes in fascicle curvature, both of which may contribute to changes in muscle length. The contributions of these mechanisms to change in muscle length are usually small under passive conditions. In very pennate muscles with long aponeuroses, fascicle shear could contribute substantially to changes in muscle length. Tendons experience moderate axial strains even under passive loads, and, because tendons are often much longer than muscle fibers, even moderate tendon strains may contribute substantially to changes in muscle length. Data obtained with new imaging techniques suggest that muscle fascicle and aponeurosis strains are highly nonuniform, but this is yet to be confirmed. The development, validation, and interpretation of continuum muscle models informed by rigorous measurements of muscle architecture and material properties should provide further insights into the mechanisms that allow relaxed muscles to lengthen and shorten.


Assuntos
Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Aponeurose/fisiologia , Humanos , Tendões/fisiologia
17.
Oxid Med Cell Longev ; 2018: 4285694, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30228855

RESUMO

Cadmium (Cd) is a harmful heavy metal, which causes severe brain damage and neurotoxic effects. Polydeoxyribonucleotide (PDRN) stimulates adenosine A2A receptor, thus contrasting several deleterious mechanisms in course of tissue damages. We aimed to investigate the possible neuroprotective effect of PDRN in a murine model of Cd-induced brain toxicity. Male C57 BL/6J mice were treated as follows: vehicle (0.9% NaCl, 1 ml/kg/day), PDRN (8 mg/kg/day), CdCl2 (2 mg/kg/day), and CdCl2 + PDRN. Animals were tested with the Morris water maze test to assess spatial memory and learning. After 14 days of treatment, brains were processed to evaluate the presence of edema in the cerebral tissue, the expression of mammalian target of rapamycin kinase (mTOR) and brain-derived neurotrophic factor (BDNF), and the morphological behavior of the hippocampal structures. After CdCl2 administration, the escape latency was high, protein expression of BDNF was significantly decreased if compared to controls, mTOR levels were higher than normal controls, and brain edema and neuronal damages were evident. The coadministration of CdCl2 and PDRN significantly diminished the escape latency, increased BDNF levels, and decreased protein expression of mTOR. Furthermore, brain edema was reduced and the structural organization and the number of neurons, particularly in the CA1 and CA3 hippocampal areas, were improved. In conclusion, a functional, biochemical, and morphological protective effect of PDRN against Cd induced toxicity was demonstrated in mouse brain.


Assuntos
Cádmio/toxicidade , Fármacos Neuroprotetores/farmacologia , Polidesoxirribonucleotídeos/farmacologia , Animais , Edema Encefálico/patologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Hipocampo/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Polidesoxirribonucleotídeos/administração & dosagem , Tempo de Reação/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
18.
Am J Mens Health ; 12(4): 751-759, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29658371

RESUMO

African American (AA)/Black men are more likely to develop aggressive prostate cancer (PCa), yet less likely to be screened despite guidelines espousing shared decision-making regarding PCa screening and prostate-specific antigen (PSA) testing. Given the documented racial disparities in PCa incidence and mortality, engaging interactions with physicians are especially important for AA/Black men. Thus, this study evaluated occurrence of physician-patient conversations among AA/Black men, and whether such conversations were associated with PCa knowledge. We also quantified the serum PSA values of participants who had, and had not, discussed testing with their physicians. Self-identified AA/Black men living in California and New York, ages 21-85, donated blood and completed a comprehensive sociodemographic and health survey ( n = 414). Less than half (45.2%) of participants had discussed PCa screening with their physicians. Multivariate analyses were used to assess whether physician-patient conversations predicted PCa knowledge after adjusting for key sociodemographic/economic and health-care variables. Increased PCa knowledge was correlated with younger age, higher income and education, and having discussed the pros and cons of PCa testing with a physician. Serum PSA values were measured by ELISA. Higher-than-normal PSA values were found in 38.5% of men who had discussed PCa screening with a physician and 29.1% who had not discussed PCa screening. Our results suggest that physician-AA/Black patient conversations regarding PCa risk need improvement. Encouraging more effective communication between physicians and AA/Black men concerning PCa screening and PSA testing has the potential to reduce PCa health disparities.


Assuntos
Negro ou Afro-Americano , Tomada de Decisões , Detecção Precoce de Câncer , Programas de Rastreamento , Antígeno Prostático Específico/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Relações Médico-Paciente , Neoplasias da Próstata/diagnóstico , Encaminhamento e Consulta , Inquéritos e Questionários , Estados Unidos , Adulto Jovem
20.
Antibodies (Basel) ; 8(1)2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31544808

RESUMO

In this work, we have used a new method to predict the epitopes of HA1 protein of influenza virus to several antibodies HC19, CR9114, BH151 and 4F5. While our results reproduced the binding epitopes of H3N2 or H5N1 for the neutralizing antibodies HC19, CR9114, and BH151 as revealed from the available crystal structures, additional epitopes for these antibodies were also suggested. Moreover, the predicted epitopes of H5N1 HA1 for the newly developed antibody 4F5 are located at the receptor binding domain, while previous study identified a region 76-WLLGNP-81 as the epitope. The possibility of antibody recognition of influenza virus via different mechanism by binding to different epitopes of an antigen is also discussed.

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