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1.
Cell ; 177(3): 654-668.e15, 2019 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-30929900

RESUMO

New neurons arise from quiescent adult neural progenitors throughout life in specific regions of the mammalian brain. Little is known about the embryonic origin and establishment of adult neural progenitors. Here, we show that Hopx+ precursors in the mouse dentate neuroepithelium at embryonic day 11.5 give rise to proliferative Hopx+ neural progenitors in the primitive dentate region, and they, in turn, generate granule neurons, but not other neurons, throughout development and then transition into Hopx+ quiescent radial glial-like neural progenitors during an early postnatal period. RNA-seq and ATAC-seq analyses of Hopx+ embryonic, early postnatal, and adult dentate neural progenitors further reveal common molecular and epigenetic signatures and developmental dynamics. Together, our findings support a "continuous" model wherein a common neural progenitor population exclusively contributes to dentate neurogenesis throughout development and adulthood. Adult dentate neurogenesis may therefore represent a lifelong extension of development that maintains heightened plasticity in the mammalian hippocampus.


Assuntos
Células-Tronco Embrionárias/metabolismo , Neurogênese , Animais , Diferenciação Celular , Giro Denteado/metabolismo , Embrião de Mamíferos/metabolismo , Células-Tronco Embrionárias/citologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Hipocampo/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo
2.
Cell ; 165(5): 1238-1254, 2016 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-27118425

RESUMO

Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our brain-region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.


Assuntos
Encéfalo/citologia , Técnicas de Cultura de Células , Modelos Biológicos , Organoides , Zika virus/fisiologia , Reatores Biológicos , Técnicas de Cultura de Células/economia , Embrião de Mamíferos , Desenvolvimento Embrionário , Humanos , Células-Tronco Pluripotentes Induzidas , Neurogênese , Neurônios/citologia , Organoides/virologia , Infecção por Zika virus/fisiopatologia , Infecção por Zika virus/virologia
3.
HNO ; 71(6): 386-395, 2023 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-37129641

RESUMO

In the present study, the concept of a systematic automated screening of temporary soldiers was evaluated based on the example of the ENT Department of the Bundeswehr Central Hospital Koblenz. From 2014 to 2017, anonymized data of 169 individuals were collected from the setting of the Bundeswehr Central Hospital. Included in the data are results from measurements with automated pure-tone audiometry (APTA; e.g., [3]), from measurements with the digit triple test for determination of the speech discrimination threshold in noise (e.g., [20]), and from interviews with questionnaires (Hearing-Dependent Daily Activities [HDDA], e.g., [14]; HearCom questionnaire, e.g., [15]). There was an initial publication from this project evaluating the questionnaires in terms of their suitability for detecting hearing loss [14]. In the following (from March 2015), only the HDDA, which was described as more sensitive, was used for measurements at the hearing screening measurement station. A complete run with the three procedures took approximately 22 min. Approximately 17% of the examined participants had abnormal findings in at least one of the procedures at the screening station. The results of the respective methods taken together detect more than any method alone and can be assumed to be complementary. Deviations between APTA with level monitor and manual tone audiometry were within the measurement accuracy. In the range between 1 and 4 kHz, hearing thresholds are somewhat underestimated with APTA. The threshold for the HDDA questionnaire with an HDDA sum ≥ 19 was confirmed. Automated hearing screening offers a good opportunity to check hearing ability on a regular basis in a standardized and reliable manner, while keeping personnel requirements low.


Assuntos
Perda Auditiva , Militares , Humanos , Audição , Ruído , Testes Auditivos/métodos , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Audiometria de Tons Puros/métodos , Limiar Auditivo
4.
Expert Rev Mol Med ; 25: e3, 2022 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-36517884

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by gradual memory loss and declining cognitive and executive functions. AD is the most common cause of dementia, affecting more than 50 million people worldwide, and is a major health concern in society. Despite decades of research, the cause of AD is not well understood and there is no effective curative treatment so far. Therefore, there is an urgent need to increase understanding of AD pathophysiology in the hope of developing a much-needed cure. Dissecting the cellular and molecular mechanisms of AD pathogenesis has been challenging as the most commonly used model systems such as transgenic animals and two-dimensional neuronal culture do not fully recapitulate the pathological hallmarks of AD. The recent advent of three-dimensional human brain organoids confers unique opportunities to study AD in a humanised model system by encapsulating many aspects of AD pathology. In the present review, we summarise the studies of AD using human brain organoids that recapitulate the major pathological components of AD including amyloid-ß and tau aggregation, neuroinflammation, mitochondrial dysfunction, oxidative stress and synaptic and circuitry dysregulation. Additionally, the current challenges and future directions of the brain organoids modelling system are discussed.


Assuntos
Doença de Alzheimer , Animais , Humanos , Doença de Alzheimer/etiologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Neurônios/metabolismo , Neurônios/patologia , Organoides/metabolismo , Organoides/patologia
5.
BMC Health Serv Res ; 22(1): 210, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172814

RESUMO

BACKGROUND: Medical legal partnerships provide an opportunity to help address various social determinants of health; however, the traditional practice of screening patients during clinical encounters is limited by the capacity of busy clinicians. Our medical legal partnership utilized care coordinators trained by the legal service attorneys to screen patients outside of clinical encounters for health harming legal needs. The goal of our study was to demonstrate that our novel model could successfully identify and refer patients of a safety-net healthcare system to appropriate legal services. METHODS: We conducted a mixed methods evaluation of the program. Data was collected during the implementation period of the program from March 2017 to August 2018. Operational data collected included number of patients screened, number of referrals to the legal partner, source and reason for referrals. Return on investment was calculated by subtracting program costs from the total reimbursement to the health system from clients' insurance benefits secured through legal services. RESULTS: During the 18-month study, 29,268 patients were screened by care coordinators for health harming legal needs, with 492 patients (1.7%) referred for legal assistance. Of the 133 cases closed in 2017, all clients were invited to participate in a telephone interview; 63 pre-consented to contact, 33 were successfully contacted and 23 completed the interview. The majority (57%) reported a satisfactory resolution of their legal barrier to health. This was accompanied by an improvement in self-reported health with a decrease of patients reporting less than optimal health from 16 (89%) prior to intervention to 8 (44%) after intervention [risk ratio (95% confidence interval): 0.20 (0.04, 0.91)]. Patients also reported improvements in general well-being for themselves and their family. The healthcare system recorded a 263% return on investment. CONCLUSIONS: In our medical legal partnership, screening for health harming legal needs by care coordinators outside of a clinical encounter allowed for efficient screening in a high risk population. The legal services intervention was associated with improvements in self-reported health and family well-being when compared to previous models. The return on investment was substantial.


Assuntos
Atenção à Saúde , Serviços Jurídicos , Humanos , Advogados , Programas de Rastreamento , Encaminhamento e Consulta
6.
Int J Mol Sci ; 22(23)2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34884903

RESUMO

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.


Assuntos
Neointima/prevenção & controle , Resveratrol/administração & dosagem , Vasa Vasorum/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Angioplastia com Balão/efeitos adversos , Animais , Vasos Coronários/efeitos dos fármacos , Modelos Animais de Doenças , Stents Farmacológicos/efeitos adversos , Desenho de Equipamento , Estudos de Viabilidade , Fibrina/metabolismo , Resveratrol/farmacocinética , Suínos
7.
Transpl Int ; 32(12): 1268-1276, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31502728

RESUMO

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.


Assuntos
Técnica Delphi , Detecção Precoce de Câncer/métodos , Transplante de Órgãos/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Consenso , Feminino , Guias como Assunto , Humanos , Masculino , Medição de Risco , Neoplasias Cutâneas/epidemiologia , Transplantados , Estados Unidos
8.
J Am Chem Soc ; 139(41): 14399-14405, 2017 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-28931277

RESUMO

This study reports a method for correlating the radical recombination efficiencies (FcP) of geminate radical cage pairs to the properties of the solvent. Although bulk viscosity (macroviscosity) is typically used to predict or interpret radical recombination efficiencies, the work reported here shows that microviscosity is a much better parameter. The use of microviscosity is valid over a range of different solvent system types, including nonpolar, aromatic, polar, and hydrogen bonding solvents. In addition, the relationship of FcP to microviscosity holds for solvent systems containing mixtures of these solvent types. The microviscosities of the solvent systems were straightforwardly determined by measuring the diffusion coefficient of an appropriate probe by NMR DOSY spectroscopy. By using solvent mixtures, selective solvation was shown to not affect the correlation between FcP and microviscosity. In addition, neither solvent polarity nor radical rotation affects the correlation between FcP and the microviscosity.

9.
J Am Chem Soc ; 138(30): 9389-92, 2016 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-27430611

RESUMO

This study reports the results of experiments that probed how solvents affect the recombination efficiency (FcP) of geminate radical cage pairs. The macroviscosity of solvents has traditionally been used to make quantitative predictions about FcP, but experiments reported here show that FcP varies dramatically for solvent systems with identical macroviscosities. Experiments show that FcP correlates with the solvent microviscosity: five different solvent systems (consisting of a solvent and a structurally similar viscogen) were examined, and FcP was the same for all five solvent systems at any particular microviscosity. The translational diffusion coefficient of the radicals (measured by DOSY) in the solvent system was used to define the microviscosity of the solvent system.

10.
Development ; 140(12): 2548-61, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23715548

RESUMO

It was long thought that no new neurons are added to the adult brain. Similarly, neurotransmitter signaling was primarily associated with communication between differentiated neurons. Both of these ideas have been challenged, and a crosstalk between neurogenesis and neurotransmitter signaling is beginning to emerge. In this Review, we discuss neurotransmitter signaling as it functions at the intersection of stem cell research and regenerative medicine, exploring how it may regulate the formation of new functional neurons and outlining interactions with other signaling pathways. We consider evolutionary and cross-species comparative aspects, and integrate available results in the context of normal physiological versus pathological conditions. We also discuss the potential role of neurotransmitters in brain size regulation and implications for cell replacement therapies.


Assuntos
Encéfalo/metabolismo , Neurogênese , Transmissão Sináptica , Vertebrados/metabolismo , Animais , Evolução Biológica , Encéfalo/citologia , Encéfalo/fisiologia , Proliferação de Células , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neuropeptídeo Y/metabolismo , Óxido Nítrico/metabolismo , Tamanho do Órgão , Receptores de GABA-A/metabolismo , Regeneração , Vertebrados/fisiologia
11.
J Natl Compr Canc Netw ; 14(5): 574-97, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27160235

RESUMO

Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Humanos , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Estados Unidos
12.
Am J Dermatopathol ; 37(6): 495-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24999549

RESUMO

Cutaneous squamous cell carcinoma with perineural invasion (PNI) is an important inconspicuous finding. We report a case of a common tumor with an uncommon finding. A 57-year-old white man presented with paresthesias and a new lesion at the site of a previously resected squamous cell carcinoma. At the time of case review, present deep in the dermis, were large hyalinized tumor nodules. These nodules could have easily have been dismissed as sclerotic tumor nodules or fibrotic in-transit metastases. With the clinical history in mind, these nodules were further investigated by immunohistochemistry and reviewed in conjunction with the Mohs frozen section slides. These nodules were subsequently diagnosed as significant peri- and intraneural invasion. This extremely unusual presentation of PNI is a potential diagnostic pitfall that is potentially under-recognized by dermatopathologists but crucial for determining patient management.


Assuntos
Carcinoma de Células Escamosas/patologia , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Nervos Periféricos/patologia , Neoplasias Cutâneas/patologia , Humanos , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/patologia , Transplante de Órgãos
13.
J Natl Compr Canc Netw ; 12(3): 410-24, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24616545

RESUMO

Merkel cell carcinoma is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative nonmelanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The NCCN Guidelines for Merkel Cell Carcinoma provide recommendations on the diagnosis and management of this aggressive disease based on clinical evidence and expert consensus. This version includes revisions regarding the use of PET/CT imaging and the addition of a new section on the principles of pathology to provide guidance on the analysis, interpretation, and reporting of pathology results.


Assuntos
Carcinoma de Célula de Merkel/diagnóstico , Carcinoma de Célula de Merkel/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Humanos
14.
J Natl Compr Canc Netw ; 12(6): 863-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24925197

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft tissue tumor characterized by a relatively high risk of local recurrence and low risk of metastasis. The NCCN Guidelines for DFSP provide multidisciplinary recommendations on the management of patients with this rare disease. These NCCN Guidelines Insights highlight the addition of the Principles of Pathology section, which provides recommendations on the pathologic assessment of DFSP. Because DFSP can mimic other lesions, immunohistochemical studies are often required to establish diagnosis. Cytogenetic testing for the characteristic translocation t(17;22)(q22;q13) can also be valuable in the differential diagnosis of DFSP with other histologically similar tumors.


Assuntos
Dermatofibrossarcoma/genética , Diagnóstico Diferencial , Recidiva Local de Neoplasia/genética , Neoplasias Cutâneas/genética , Biomarcadores Tumorais , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/patologia , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Translocação Genética
15.
Development ; 137(24): 4127-34, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21068061

RESUMO

In contrast to mammals, salamanders and teleost fishes can efficiently repair the adult brain. It has been hypothesised that constitutively active neurogenic niches are a prerequisite for extensive neuronal regeneration capacity. Here, we show that the highly regenerative salamander, the red spotted newt, displays an unexpectedly similar distribution of active germinal niches with mammals under normal physiological conditions. Proliferation zones in the adult newt brain are restricted to the forebrain, whereas all other regions are essentially quiescent. However, ablation of midbrain dopamine neurons in newts induced ependymoglia cells in the normally quiescent midbrain to proliferate and to undertake full dopamine neuron regeneration. Using oligonucleotide microarrays, we have catalogued a set of differentially expressed genes in these activated ependymoglia cells. This strategy identified hedgehog signalling as a key component of adult dopamine neuron regeneration. These data show that brain regeneration can occur by activation of neurogenesis in quiescent brain regions.


Assuntos
Encéfalo/citologia , Encéfalo/metabolismo , Neurogênese/fisiologia , Vertebrados/metabolismo , Animais , Dopamina/metabolismo , Eletroporação , Imuno-Histoquímica , Mesencéfalo/citologia , Mesencéfalo/metabolismo , Neurogênese/genética , Neurônios/citologia , Neurônios/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Oxidopamina/metabolismo , Prosencéfalo/citologia , Prosencéfalo/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Urodelos/metabolismo
17.
Skin Therapy Lett ; 18(1): 1-3, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23474655

RESUMO

Skin cancer in organ transplant recipients is a serious problem that manifests as increased squamous cell carcinoma in longterm patients. In these patients, a combination of cumulative sun exposure as well as the immunosuppressive effects of transplant medications can cause cutaneous malignancy. Skin cancer can affect transplant patients in multiple ways. It can decrease quality of life by causing various separate skin cancers that require frequent and sometimes painful treatment, as well as possibly result in disfigurement. The more aggressive tumors pose a risk of metastasis and death. Clinical efforts aimed at reduction in skin cancers in this high-risk population include increased education and surveillance, aggressive treatment of skin cancers and pre-cancers, changes to immunosuppressive regimens, and retinoid chemoprevention.


Assuntos
Carcinoma de Células Escamosas/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Transplantes , Humanos , Imunossupressores/efeitos adversos , Transplante de Órgãos/efeitos adversos , Educação de Pacientes como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Retinoides/uso terapêutico , Fatores de Risco , Luz Solar/efeitos adversos
18.
Am J Obstet Gynecol ; 206(3): 199.e1-4, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22381600

RESUMO

OBJECTIVE: We assessed the screening and remediation of home lead hazards prenatally in a high-risk population, hypothesizing that average blood-lead level and the number of poisonings would drop by 25%. STUDY DESIGN: One hundred fifty-two women underwent prenatal home inspections by certified lead inspectors. The hazards that were identified were remediated. The blood-lead levels of children of participating women were compared with matched control subjects. RESULTS: Blood-lead levels were obtained from 60 children and compared with matched control subjects. The average blood-lead level of children in the treatment group was 2.70 µg/dL vs 3.73 µg/dL in control subjects (P = .019). The percentage of children with levels >10 µg/dL in the treatment group was 0% vs 4.2% in control subjects (P = .128). CONCLUSION: Screening and remediation of houses of pregnant women is effective to reduce the average blood-lead level and number of children that exceed the federal level of concern for lead poisoning in a high-risk population.


Assuntos
Habitação , Intoxicação por Chumbo/prevenção & controle , Exposição Ambiental/prevenção & controle , Feminino , Humanos , Lactente , Intoxicação por Chumbo/sangue , Masculino , Missouri/epidemiologia , Gravidez
19.
J Pediatr Gastroenterol Nutr ; 54(4): 471-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21873894

RESUMO

OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of pain, fever, and inflammation. Long-term use of these drugs is associated with significant gastric injury. Activated neutrophils and oxidative stress seem to play a significant role in NSAID-induced gastric mucosal damage. The objective of our study is to examine the protective effects of an antioxidant and anti-inflammatory enzyme, heme oxygenase-1 (HO-1), in NSAID-induced gastric injury. METHODS: Mice were intraperitoneally injected with indomethacin (10 mg/kg) or sham. A specific inducer of HO-1, cobalt protoporphyrin (5 mg/kg), was given 24 hours before indomethacin to allow for the expression of HO-1. Controls received sham treatment. Twenty-four hours after indomethacin injection, gastric tissue damage was examined with histology. HO-1 expression was measured with immunoblot; cytokine levels were measured with enzyme-linked immunosorbent assay. Neutrophil infiltration was quantified with myeloperoxidase assay. Using electron paramagnetic resonance and desferrioxamine, we measured the labile iron pool in the mouse stomach as a marker of oxidative stress. RESULTS: Indomethacin caused gastric inflammation and ulcers, neutrophil activation, and increased tissue expression of interleukin-6 and tumor necrosis factor-alpha in mice. Inducing HO-1 with cobalt protoporphyrin reduced gastric inflammation, number of stomach ulcers, tissue neutrophil activation, and proinflammatory cytokine expression caused by indomethacin. CONCLUSIONS: These findings suggest that the induction of an anti-inflammatory and cytoprotective enzyme HO-1 may be a strategy to overcome the gastrointestinal adverse effects limiting the use of NSAIDs.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Heme Oxigenase-1/metabolismo , Indometacina/efeitos adversos , Proteínas de Membrana/metabolismo , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Apoptose/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática/métodos , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Indometacina/farmacologia , Interleucina-6/genética , Interleucina-6/metabolismo , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
20.
J Patient Rep Outcomes ; 6(1): 63, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-35696006

RESUMO

BACKGROUND: The COVID-19 pandemic has impacted the mental health and well-being of health care workers (HCWs). This study examined mental health outcomes and COVID-related stress impacts among a diverse sample of ambulatory HCWs, including clinicians and support staff, as well as the associations between mental health outcomes and work impairments in this population. Detailing these results can help in designing interventions to alleviate this burden. METHODS: "The Health Care Worker Stress Survey" was administered to ambulatory care providers and support staff at three multispecialty care delivery organizations as part of an online, cross-sectional study conducted between June 8, 2020, and July 13, 2020. RESULTS: The greatest stress impact reported by HCWs was the uncertainty regarding when the COVID-19 outbreak would be under control, while the least reported concern was about self-dying from COVID-19. Differences in COVID-19 stress impacts were observed by age, gender, and occupational risk factors. Approximately 50% of participants reported more than a minimal level of anxiety, including 22.5% who indicated moderate to severe levels of anxiety. Higher levels of anxiety were observed with younger ages and female gender, while occupational roles with increased exposure risk did not report higher levels of anxiety. Roughly two-thirds of the sample reported less than good sleep quality and one-third to one-half of the sample reported other sleep related problems that differed by age and gender. Role limitations due to emotional health correlated with COVID-19 related stress, anxiety and sleep problems. CONCLUSIONS: Using established, validated measures, we quantified mental health outcomes within a diverse sample of ambulatory care HCWs during the pandemic. Younger and female HCWs reported greater anxiety burden; HCWs with higher occupational risk of COVID exposure did not report higher levels of anxiety. Notable proportions of HCWs reported sleep and work impairments. Due to the cross-sectional nature of the study, it is difficult to attribute these patterns to the pandemic. These results underscore the depth and extent of mental health outcomes in HCWs in ambulatory settings and raise important questions on new interventions to relieve that burden. Further research is needed to study specific interventions to support the mental health and wellbeing of HCWs.

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