Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 72
Filtrar
1.
Pharmacol Res ; : 107284, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925462

RESUMO

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.

2.
Sci Total Environ ; 937: 173405, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38796020

RESUMO

A hydrological and hydrochemical database (produced by the M-TROPICS critical zone observatory) in the upper Nyong Basin from 1998 to 2017 was used to evaluate the river's response to climatic and anthropogenic forcing and examine chemical weathering processes. SiO2 and HCO3- constitute about 85 % of the Total dissolved solids (TDS) load, equivalent to 0.12 × 109 kg. y-1. Electrical conductivity (EC), Total dissolved solids (TDS), major cations, major anions (except F- and NO3-) and alkalinity (Alk) vary seasonally and follow a predictable model with discharge. Atlantic Meridional Mode oscillation controls the long-term water chemistry. Atmospheric input and silicate weathering are the main factors influencing the Nyong rivers chemistry. However, several indices supported the progressive water quality deterioration by human activities, namely: the excess of Cl- and SO42- after the substraction of atmospheric inputs, the basic pH observed for specific samples, long-term increase in the values of pH, EC, TDS, EC, Mg2+, Ca2+, F-, NO3-, HCO3-, Alk, SiO2 and Dissolved Organic Carbon. Runoff and physical erosion have an important control on chemical erosion in the upper Nyong Basin rivers. The chemical erosion rate (3.3 t.km-2.y-1) equals the silicate weathering rate. The CO2 consumption rate, in the Nyong rivers, is lower than the global average (98× 103 for silicate weathering and 246 × 103 mol.km-2.y-1 for chemical erosion) and estimated at 52.3 × 103 for silicate weathering and 54.1 × 103 mol.km-2.y-1 for chemical erosion. At Olama, the most downstream location of the monitoring setup, the Nyong River Basin consumed 1 × 109 mol.y-1 of CO2 by chemical erosion.

3.
iScience ; 27(2): 108808, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303713

RESUMO

Type I interferons (IFNs) increase the excitability of dorsal root ganglia (DRGs) neurons via MNK-eIF4E signaling to promote pain sensitization in mice. Activation of stimulator of interferon response cGAMP interactor 1 (STING) signaling is pivotal for type I IFN induction. We hypothesized that vinorelbine, a chemotherapeutic and activator of STING, would cause a neuropathic pain-like state in mice via STING signaling in DRG neurons associated with IFN production. Vinorelbine caused tactile allodynia and grimacing in wild-type (WT) mice and increased p-IRF3, type I IFNs, and p-eIF4E in peripheral nerves. Supporting our hypothesis, vinorelbine failed to induce IRF3-IFNs-MNK-eIF4E in StingGt/Gt mice and, subsequently, failed to cause pain. The vinorelbine-elicited increase of p-eIF4E was not observed in Mknk1-/- (MNK1 knockout) mice in peripheral nerves consistent with the attenuated pro-nociceptive effect of vinorelbine in these mice. Our findings show that activation of STING signaling in the periphery causes a neuropathic pain-like state through type I IFN signaling to DRG nociceptors.

4.
J Palliat Med ; 27(4): 572-575, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37870757

RESUMO

In this segment of the emergency palliative care case series, we present a patient who arrives at a small community emergency department with acute intracranial hemorrhage, aspiration, and respiratory failure. Usual care includes aggressive airway management with intubation and mechanical ventilation, and a recommendation from stroke neurologists and neurosurgeons at the tertiary care center to transfer the patient. The patient's wife has some understanding that the prognosis is likely to be poor, and asks that the patient not be transferred if he is unlikely to return to independent function. A general neurologist is consulted to provide a prognostic opinion, and goals-of-care discussions are facilitated by a palliative care consultant. After expedited evaluation, the neurologist provides a prognostic assessment, while the palliative care clinician explores potential next steps with the patient's wife, based upon his known goals and values, ultimately leading to high-value goal-concordant end-of-life care for the patient and his family.


Assuntos
Serviços Médicos de Emergência , Assistência Terminal , Masculino , Humanos , Cuidados Paliativos , Serviço Hospitalar de Emergência , Prognóstico
5.
Proc Natl Acad Sci U S A ; 120(52): e2306090120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38117854

RESUMO

The sigma 2 receptor (σ2R) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σ2R/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal antinociceptive effect is approximately 24 h following dosing. We sought to understand this unique antineuropathic pain effect by addressing two key questions: do these σ2R/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout mice for Tmem97, we find that a σ2R/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce antinociception in the spared nerve injury model in mice. Using primary mouse dorsal root ganglion neurons, we demonstrate that FEM-1689 inhibits the integrated stress response (ISR) and promotes neurite outgrowth via a σ2R/TMEM97-specific action. We extend the clinical translational value of these findings by showing that FEM-1689 reduces ISR and p-eIF2α levels in human sensory neurons and that it alleviates the pathogenic engagement of ISR by methylglyoxal. We also demonstrate that σ2R/TMEM97 is expressed in human nociceptors and satellite glial cells. These results validate σ2R/TMEM97 as a promising target for further development for the treatment of neuropathic pain.


Assuntos
Neuralgia , Masculino , Feminino , Humanos , Camundongos , Animais , Ligantes , Neuralgia/metabolismo , Nociceptores/metabolismo , Células Receptoras Sensoriais/metabolismo , Camundongos Knockout , Modelos Animais de Doenças , Gânglios Espinais/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
6.
OTA Int ; 6(2): e267, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37780184

RESUMO

Case: A 56-year-old woman with metastatic melanoma and femoral lesions with impending pathologic fracture was indicated for intramedullary brachytherapy (IMBT) and intramedullary nail. Conclusions: IMBT + intramedullary nail is a new technique for the treatment of long bone metastases. IMBT maximizes radiation to the tumor and minimizes radiation to surrounding tissues. It allows the patient to resume systemic treatment expediently. Our cadaver model and patient were both treated for femoral metastases; however, this technique allows for the treatment of any long bone. This is a safe technique that minimizes treatment time compared with other standard radiation regimens.

7.
bioRxiv ; 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37333411

RESUMO

Type I interferons (IFNs) increase the excitability of dorsal root ganglion (DRG) neurons via activation of MNK-eIF4E translation signaling to promote pain sensitization in mice. Activation of STING signaling is a key component of type I IFN induction. Manipulation of STING signaling is an active area of investigation in cancer and other therapeutic areas. Vinorelbine is a chemotherapeutic that activates STING and has been shown to cause pain and neuropathy in oncology clinical trials in patients. There are conflicting reports on whether STING signaling promotes or inhibits pain in mice. We hypothesized that vinorelbine would cause a neuropathic pain-like state in mice via STING and signaling pathways in DRG neurons associated with type I IFN induction. Vinorelbine (10 mg/kg, i.v.) induced tactile allodynia and grimacing in WT male and female mice and increased p-IRF3 and type I IFN protein in peripheral nerves. In support of our hypothesis, vinorelbine-mediated pain was absent in male and female StingGt/Gt mice. Vinorelbine also failed to induce IRF3 and type I IFN signaling in these mice. Since type I IFNs engage translational control via MNK1-eIF4E in DRG nociceptors, we assessed vinorelbine-mediated p-eIF4E changes. Vinorelbine increased p-eIF4E in DRG in WT animals but not in StingGt/Gt or Mknk1-/- (MNK1 KO) mice. Consistent with these biochemical findings, vinorelbine had an attenuated pro-nociceptive effect in male and female MNK1 KO mice. Our findings support the conclusion that activation of STING signaling in the peripheral nervous system causes a neuropathic pain-like state that is mediated by type I IFN signaling to DRG nociceptors.

8.
bioRxiv ; 2023 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-37090527

RESUMO

The Sigma 2 receptor (σ2R) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σ2R/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal anti-nociceptive effect is approximately 24 hours following dosing. We sought to understand this unique anti-neuropathic pain effect by addressing two key questions: do these σ2R/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout (KO) mice for Tmem97, we find that a new σ2R/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce anti-nociception in the spared nerve injury model in mice. Using primary mouse dorsal root ganglion (DRG) neurons, we demonstrate that FEM-1689 inhibits the integrated stress response (ISR) and promotes neurite outgrowth via a σ2R/TMEM97-specific action. We extend the clinical translational value of these findings by showing that FEM-1689 reduces ISR and p-eIF2α levels in human sensory neurons and that it alleviates the pathogenic engagement of ISR by methylglyoxal. We also demonstrate that σ2R/TMEM97 is expressed in human nociceptors and satellite glial cells. These results validate σ2R/TMEM97 as a promising target for further development for the treatment of neuropathic pain.

9.
Sci Total Environ ; 869: 161824, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36720396

RESUMO

The accumulation of nanoplastics (NPs) in the environment has raised concerns about their impact on human health and the biosphere. The main aim of this study is to understand the mechanism that governs the capture of NPs by jellyfish mucus extracted from the jellyfish Aurelia sp. (A.a.) and compare the capture/removal efficiency to that of conventional coagulants and mucus from other organisms. The efficacy of A.a mucus to capture polystyrene and acrylic NPs (∼100 nm) from spiked wastewater treatment plant (WWTP) effluent was evaluated. The mucus effect on capture kinetics and destabilization of NPs of different polymer compositions, sizes and concentrations was quantified by means of fluorescent NPs, dynamic light scattering and zeta potential measurements and visualized by scanning electron microscopy. A dosing of A.a. mucus equivalent to protein concentrations of ∼2-4 mg L-1 led to a rapid change in zeta potential from a baseline of -30 mV to values close to 0 mV, indicating a marked change from a stable to a non-stable dispersion leading to a rapid (<10 min) and significant removal of NPs (60 %-90 %) from a stable suspension. The A.a. mucus outperformed all other mucus types (0-37 %) and coagulants (0 %-32 % for ferric chloride; 23-40 % for poly aluminum chlorohydrate), highlighting the potential for jellyfish mucus to be used as bio-flocculant. The results indicate a mucus-particle interaction consisting of adsorption-bridging and "mesh" filtration. Further insight is provided by carbohydrate composition and protein disruption analysis. Total protein disruption resulted in a complete loss of the A.a. mucus capacity to capture NPs, while the breaking of disulfide bonds and protein unfolding resulted in improved capture capacity. The study demonstrates that natural jellyfish mucin can capture and remove NPs in water and wastewater treatment systems more efficiently than conventional coagulants, highlighting the potential for development of a new type of bio-flocculant.


Assuntos
Nanopartículas , Cifozoários , Purificação da Água , Animais , Humanos , Mucinas/metabolismo , Microplásticos , Adsorção , Purificação da Água/métodos , Nanopartículas/química
10.
J Extracell Vesicles ; 11(10): e12272, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36239715

RESUMO

Activating mutations in the receptor KIT promote the dysregulated proliferation of human mast cells (huMCs). The resulting neoplastic huMCs secrete extracellular vesicles (EVs) that can transfer oncogenic KIT among other cargo into recipient cells. Despite potential contributions to diseases, KIT-containing EVs have not been thoroughly investigated. Here, we isolated and characterized KIT-EV subpopulations released by neoplastic huMCs using an immunocapture approach that selectively isolates EVs containing KIT in its proper topology. Immunocapture of EVs on KIT antibody-coated electron microscopy (EM) affinity grids allowed to assess the morphology and size of KIT-EVs. Immunoblot analysis demonstrated KIT-EVs have a distinct protein profile from KIT-depleted EVs, contain exosome and microvesicle markers, and are separated into these subtypes by ultracentrifugation. Cell treatment with sphingomyelinase inhibitors shifted the protein content among KIT-EV subtypes, suggesting different biogenesis routes. Proteomic analysis revealed huMC KIT-EVs are enriched in proteins involved in signalling, immune responses, and cell migration, suggesting diverse biological functions, and indicated neoplastic huMCs disseminate KIT via shuttling in heterogeneous microvesicle- and exosome-like EVs. Further, selective KIT-immunocapture will enable the enrichment of specific huMC-derived EVs from complex human biosamples and facilitate an understanding of their in vivo functions and potential to serve as biomarkers of specific biological pathologies.


Assuntos
Exossomos , Vesículas Extracelulares , Biomarcadores/metabolismo , Exossomos/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Mastócitos/metabolismo , Proteômica , Esfingomielina Fosfodiesterase/metabolismo
11.
Sci Rep ; 12(1): 9607, 2022 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-35689084

RESUMO

Dysphagia is a serious stroke complication but lacks effective therapy. We investigated safety and preliminary efficacy of anodal transcranial direct current stimulation (atDCS) paired with swallowing exercises in improving post-stroke dysphagia from an acute unilateral hemispheric infarction (UHI). We conducted a double-blind, early phase-2 randomized controlled trial, in subjects (n = 42) with moderate-severe dysphagia [Penetration and Aspiration Scale (PAS) score ≥ 4], from an acute-subacute UHI. Subjects were randomized to Low-Dose, High-Dose atDCS or Sham stimulation for 5 consecutive days. Primary safety outcomes were incidence of seizures, neurological, motor, or swallowing function deterioration. Primary efficacy outcome was a change in PAS scores at day-5 of intervention. Main secondary outcome was dietary improvement at 1-month, assessed by Functional Oral Intake (FOIS) score. No differences in pre-defined safety outcomes or adjusted mean changes in PAS, FOIS scores, between groups, were observed. Post-hoc analysis demonstrated that 22 /24 subjects in the combined atDCS group had a clinically meaningful dietary improvement (FOIS score ≥ 5) compared to 8 /14 in Sham (p = 0.037, Fisher-exact). atDCS application in the acute-subacute stroke phase is safe but did not decrease risk of aspiration in this early phase trial. The observed dietary improvement is promising and merits further investigation.


Assuntos
Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Encéfalo , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Resultado do Tratamento
12.
J Neurosci ; 42(10): 1930-1944, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35058371

RESUMO

We aimed to investigate a sexually dimorphic role of calcitonin gene-related peptide (CGRP) in rodent models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 signaling, CGRP receptor antagonists olcegepant and CGRP8-37 both given intrathecally, blocked, and reversed hyperalgesic priming only in females. A monoclonal antibody against CGRP, given systemically, blocked priming specifically in female rodents but failed to reverse it. In the spared nerve injury model, there was a transient effect of both CGRP antagonists, given intrathecally, on mechanical hypersensitivity in female mice only. Consistent with these findings, intrathecally applied CGRP caused a long-lasting, dose-dependent mechanical hypersensitivity in female mice but more transient effects in males. This CGRP-induced mechanical hypersensitivity was reversed by olcegepant and the KCC2 enhancer CLP257, suggesting a role for anionic plasticity in the dorsal horn in the pain-promoting effects of CGRP in females. In spinal dorsal horn slices, CGRP shifted GABAA reversal potentials to significantly more positive values, but, again, only in female mice. Therefore, CGRP may regulate KCC2 expression and/or activity downstream of CGRP receptors specifically in females. However, KCC2 hypofunction promotes mechanical pain hypersensitivity in both sexes because CLP257 alleviated hyperalgesic priming in male and female mice. We conclude that CGRP promotes pain plasticity in female rodents but has a limited impact in males.SIGNIFICANCE STATEMENT The majority of patients impacted by chronic pain are women. Mechanistic studies in rodents are creating a clear picture that molecular events promoting chronic pain are different in male and female animals. We sought to build on evidence showing that CGRP is a more potent and efficacious promoter of headache in female than in male rodents. To test this, we used hyperalgesic priming and the spared nerve injury neuropathic pain models in mice. Our findings show a clear sex dimorphism wherein CGRP promotes pain in female but not male mice, likely via a centrally mediated mechanism of action. Our work suggests that CGRP receptor antagonists could be tested for efficacy in women for a broader variety of pain conditions.


Assuntos
Dor Crônica , Simportadores , Animais , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Feminino , Humanos , Hiperalgesia/metabolismo , Masculino , Camundongos , Ratos , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Roedores
13.
Polymers (Basel) ; 13(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34372170

RESUMO

Polyester nanocomposites reinforced with graphene nanoplatelets (GnPs) with two different lateral sizes are prepared by high shear mixing, followed by compression molding. The effects of the size and concentration of GnP, as well as of the processing method, on the electrical conductivity and electromagnetic interference (EMI) shielding behavior of these nanocomposites are experimentally investigated. The in-plane electrical conductivity of the nanocomposites with larger-size GnPs is approximately one order of magnitude higher than the cross-plane volume conductivity. According to the SEM images, the compression-induced alignments of GnPs is found to be responsible for this anisotropic behavior. The orientation of the small size GnPs in the composite is not influenced by the compression process as strongly, and consequently, the electrical conductivity of these nanocomposites exhibits only a slight anisotropy. The maximum EMI shielding effectiveness (SE) of 27 dB (reduction of 99.8% of the incident radiation) is achieved at 25 wt.% of the smaller-size GnP loading. Experimental results show that the EMI shielding mechanism of these composites has a strong dependency on the lateral dimension of GnPs. The non-aligned smaller-size GnPs are leveraged to obtain a relatively high absorption coefficient (≈40%). This absorption coefficient is superior to the existing single-filler bulk polymer composite with a similar thickness.

14.
Nanomaterials (Basel) ; 11(6)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34205535

RESUMO

The effect of the crystallization of polypropylene (PP) forming an immiscible polymer blend with polystyrene (PS) containing conductive multi-wall carbon nanotubes (MWCNTs) on its electrical conductivity and electrical percolation threshold (PT) was investigated in this work. PP/PS/MWCNTs composites with a co-continuous morphology and a concentration of MWCNTs ranging from 0 to 2 wt.% were obtained. The PT was greatly reduced by a two-step approach. First, a 50% reduction in the PT was achieved by using the effect of double percolation in the blend system compared to PP/MWCNTs. Second, with the additional thermal treatments, referred to as slow-cooling treatment (with the cooling rate 0.5 °C/min), and isothermal treatment (at 135 °C for 15 min), ultra-low PT values were achieved for the PP/PS/MWCNTs system. A 0.06 wt.% of MWCNTs was attained upon the use of the slow-cooling treatment and 0.08 wt.% of MWCNTs upon the isothermal treatment. This reduction is attributed to PP crystals' volume exclusion, with no alteration in the blend morphology.

15.
Polymers (Basel) ; 13(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33671111

RESUMO

High-voltage capacitors are key components for circuit breakers and monitoring and protection devices, and are important elements used to improve the efficiency and reliability of the grid. Different technologies are used in high-voltage capacitor manufacturing process, and at all stages of this process polymeric films must be used, along with an encapsulating material, which can be either liquid, solid or gaseous. These materials play major roles in the lifespan and reliability of components. In this paper, we present a review of the different technologies used to manufacture high-voltage capacitors, as well as the different materials used in fabricating high-voltage film capacitors, with a view to establishing a bibliographic database that will allow a comparison of the different technologies.

16.
Sci Signal ; 14(674)2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33727337

RESUMO

In the peripheral nervous system, ligand-receptor interactions between cells and neurons shape sensory experience, including pain. We set out to identify the potential interactions between sensory neurons and peripheral cell types implicated in disease-associated pain. Using mouse and human RNA sequencing datasets and computational analysis, we created interactome maps between dorsal root ganglion (DRG) sensory neurons and an array of normal cell types, as well as colitis-associated glial cells, rheumatoid arthritis-associated synovial macrophages, and pancreatic tumor tissue. These maps revealed a common correlation between the abundance of heparin-binding EGF-like growth factor (HBEGF) in peripheral cells with that of its receptor EGFR (a member of the ErbB family of receptors) in DRG neurons. Subsequently, we confirmed that increased abundance of HBEGF enhanced nociception in mice, likely acting on DRG neurons through ErbB family receptors. Collectively, these interactomes highlight ligand-receptor interactions that may lead to treatments for disease-associated pain and, furthermore, reflect the complexity of cell-to-neuron signaling in chronic pain states.


Assuntos
Gânglios Espinais , Nociceptividade , Animais , Ligantes , Camundongos , Dor/genética , Células Receptoras Sensoriais
17.
Clin Gastroenterol Hepatol ; 19(8): 1679-1687, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32693047

RESUMO

BACKGROUND & AIMS: We examined the frequency of and factors associated with delays in diagnosis of hepatocellular carcinoma (HCC) in a cohort of patients with cirrhosis in the Veterans Health Administration. METHODS: In a retrospective study, we collected and analyzed data from the Veterans Health Administration's electronic health records. We used a multivariate logistic regression model to identify factors associated with a delay in diagnosis of HCC of more than 60 days following a red flag (defined as the earliest date at which a diagnosis of HCC could have been made, based on American Association for the Study of Liver Disease 2005 guidelines). We used multivariate Cox proportional hazards model to evaluate the effects of delayed diagnosis on survival, adjusting for patient and provider characteristics. RESULTS: Among 655 patients with cirrhosis and a diagnosis of HCC from 2006 through 2011, 46.9% had a delay in diagnosis of more than 60 days following a red flag for HCC. Delays in diagnosis for more than 60 days were significantly associated with lack of provider adherence to the guidelines (adjusted odds ratio [OR], 4.82; 95% CI, 3.12-7.45), a diagnostic imaging evaluation instead of only measurement of alfa fetoprotein (adjusted OR, 2.63; 95% CI, 1.09-6.24), and diagnosis as an incidental finding during examination for an unrelated medical problem (compared with an HCC-related assessment) (adjusted OR, 2.26; 95% CI, 1.09-4.67). Diagnostic delays of 60 days or more were associated with lower mortality compared to patients without a delay in diagnosis (unadjusted hazard ratio, 0.57; 95% CI, 0.47-0.68 and adjusted hazard ratio, 0.63; 95% CI, 0.50-0.78). CONCLUSIONS: Nearly half of veterans with cirrhosis have delays in diagnosis of HCC of 60 days or more after a red flag, defined by guidelines. Interventions are needed to improve timely follow-up of red flags for HCC and adherence to guidelines, to increase early detection of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Neoplasias Hepáticas/diagnóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
18.
Sci Total Environ ; 752: 141880, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32892046

RESUMO

Wastewater treatment plants (WWTPs) serve as an important route of microplastics (MPs) to the environment. Therefore, more effective MPs sampling and detection methodologies, as well as a better understanding of their influence on MPs occurrence and distributions in WWTP effluents, are needed for better removal and control. In this work, the efficiency of a municipal WWTP to remove MPs was assessed by collecting samples from raw to tertiary effluent during a 12-month sampling campaign (season-based) using different sampling methods (containers, 24-h composite and large grab samples). MPs retrieved from different treatment units within the WWTP were identified and quantified using plastic/non-plastic staining followed by optical microscopy, SEM and µ-Raman microscopy. Overall, the mean removal efficiency of MPs in the WWTP was 97%, with most MPs removed by the secondary stage and a mean effluent concentration of 1.97 MPs L-1 after sand filtration. The relative abundance of particles was lower than fibers in treated effluent compared with the raw wastewater, with MP fibers constituting 74% of the total MPs in raw wastewater and 91% in treated effluent. Taking seasonal variations into account is important as total MPs concentration in the effluent was notably higher in winter compared with the other seasons. Increasing the sampled volume using large samples or 24-h composite samples significantly reduced the variability between replicates. However, MPs concentration post the tertiary stage was significantly lower using morning sampling (9 am) by large grab sampling method (1.2 MPs L-1) compared to 24-h composite sampling (3.2 MPs L-1) possibly due to intra-daily changes. Using a finer mesh size (0.45 µm) to capture MPs beyond the size range typically studied (≥20 µm) effectively doubled the number of MPs detected in the tertiary effluent and highlights the importance of standardizing sampling procedures.

19.
Polymers (Basel) ; 12(10)2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33066586

RESUMO

Production process was chosen in order to be readily scalable at the industrial level. The resin/graphene mixture was prepared through high shear mixing at six different weight concentrations between 0% and 10%. Samples were subsequently produced by compression molding. The electrical properties were measured both in-the-plane and across-the-plane using, respectively, a four-point probe and a two-electrode system. The two-electrode system was a dielectric spectrometer, and accordingly, the across-the-plane measurements were conducted in the frequency-domain. Mechanical measurements were conducted using conventional three-point bending and impact setups. The percolation threshold was found to be in the range of 3-5 wt.% concentration, for which the conductivity showed a 7 orders of magnitude increase. These results were quite similar to the samples containing around 50 wt.% of glass fibers. Surprisingly, the in-the-plane conductivity was found to be lower than the bulk conductivity, contrary to what was found with the same filler for thermoplastic composites prepared by melt compounding. No significant increase in mechanical properties as a function of filler loading was observed, except maybe a slight increase in the material toughness.

20.
J Environ Manage ; 266: 110642, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32392134

RESUMO

Wastewater treatment plants (WWTPs) are a focal point for the removal of microplastic (MP) particles before they are discharged into aquatic environments. WWTPs are capable of removing substantial quantities of larger MP particles but are inefficient in removing particles with any one dimension of less than 100 µm, with influents and effluents tending to have similar quantities of these smaller particles. As a single WWTP may release >100 billion MP particles annually, collectively WWTPs are significant contributors to the problem of MP pollution of global surface waters. Currently, there are no policies or regulations requiring the removal of MPs during wastewater treatment, but as concern about MP pollution grows, the potential for wastewater technologies to capture particles before they reach surface waters has begun to attract attention. There are promising technologies in various stages of development that may improve the removal of MP particles from wastewater. Better incentivization could speed up the research, development and adoption of innovative practices. This paper describes the current state of knowledge regarding MPs, wastewater and relevant policies that could influence the development and deployment of new technologies within WWTPs. We review existing technologies for capturing very small MP particles and examine new developments that may have the potential to overcome the shortcomings of existing methods. The types of collaborations needed to encourage and incentivize innovation within the wastewater sector are also discussed, specifically strong partnerships among scientific and engineering researchers, industry stakeholders, and policy decision makers.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Monitoramento Ambiental , Microplásticos , Plásticos , Eliminação de Resíduos Líquidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...