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1.
Environ Res ; 260: 119629, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39025349

RESUMO

From the beginning of May 2023 to the end of August 2023, the Northern Hemisphere experienced significant wildfire activity with the most widespread fires occurring in Canada. Forest fires in Canada destroyed more than 15.6 million hectares of forests. These wildfires worsened air quality across the region and other parts of the world. The smoke reached southern Europe by the end of June 2023. To better understand the consequences of such forest fires far from the site of origin, aerosol optical, microphysical and radiative properties were analyzed during this event for southern Europe using data from the Visible Infrared Imaging Radiometer Suite (VIIRS), TROPOspheric Monitoring Instrument (TROPOMI), and Aerosol Robotic Network (AERONET). TROPOMI aerosol index (AI) and the carbon monoxide (CO) product confirm that the smoke originated directly from these forest fires. AERONET data from the El Arenosillo site in southern Spain showed maximum aerosol optical depth (AOD) values on June 27 reached 2.36. Data on Angstrom Exponent (AE), aerosol volume size distribution (VSD), single scattering albedo (SSA), fine mode fraction (FMF), volume particle concentration, effective radius (REff), absorption AOD (AAOD), extinction AE (EAE) and absorption AE (AAE) showed that fine-mode particles with carbonaceous aerosols contribution predominated in the atmosphere above the El Arenosillo site. Direct aerosol radiative forcing (DARF) at the top (DARFTOA) and bottom of atmosphere (DARFBOA) were -103.1 and -198.93 Wm-2, respectively. The atmospheric aerosol radiative forcing (DARFATM) was found to be 95.83 Wm-2 and with a heating rate 2.69 K day-1, which indicates the resulting warming of the atmosphere.

2.
Radiology ; 306(2): e213198, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36165790

RESUMO

Background A new modality, phase-sensitive breast tomosynthesis (PBT), may have similar diagnostic performance to conventional breast tomosynthesis but with a reduced radiation dose. Purpose To perform a pilot study of the performance of a novel PBT system compared with conventional digital breast tomosynthesis (DBT) in patients undergoing additional diagnostic imaging workup for breast lesions. Materials and Methods In a prospective study from June 2020 to March 2021, participants with suspicious breast lesions detected at screening DBT or MRI were recruited for additional PBT imaging before additional diagnostic workup or biopsy. In this pilot study, nine radiologists independently evaluated image quality and assessed the likelihood of lesion malignancy by retrospectively evaluating DBT and PBT images in two separate reading sessions. Image quality was rated subjectively using a Likert scale from 1 to 5. Areas under the receiver operating characteristic curve (AUCs) were used to compare the lesion classification (malignant vs benign) performance of the radiologists. Results Images in 50 patients (mean age, 56 years ± 12 [SD]; 49 women) with 52 evaluable lesions (28 malignant) were assessed. For image appearance and general feature visibility, DBT images had a higher total mean image quality score (3.8) than PBT images (2.9), with P < .002 for each comparison. For classification of lesions as benign or malignant, the AUCs were 0.74 for both PBT and DBT. PBT images were acquired at a 24% mean radiation dose reduction (mean, 1.78 mGy vs 2.34 mGy for DBT; P < .001). Conclusion The phase-sensitive breast tomosynthesis system had a 24% lower mean radiation dose compared with digital breast tomosynthesis, although with lower image quality. Diagnostic performance of the system remains to be determined in larger studies. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Gao and Moy in this issue.


Assuntos
Neoplasias da Mama , Mama , Feminino , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Estudos Retrospectivos , Mama/diagnóstico por imagem , Mamografia/métodos , Neoplasias da Mama/patologia
3.
J Digit Imaging ; 36(1): 365-372, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36171520

RESUMO

We describe the curation, annotation methodology, and characteristics of the dataset used in an artificial intelligence challenge for detection and localization of COVID-19 on chest radiographs. The chest radiographs were annotated by an international group of radiologists into four mutually exclusive categories, including "typical," "indeterminate," and "atypical appearance" for COVID-19, or "negative for pneumonia," adapted from previously published guidelines, and bounding boxes were placed on airspace opacities. This dataset and respective annotations are available to researchers for academic and noncommercial use.


Assuntos
COVID-19 , Humanos , Inteligência Artificial , Radiografia , Aprendizado de Máquina , Radiologistas , Radiografia Torácica/métodos
4.
Optom Vis Sci ; 99(1): 9-17, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882607

RESUMO

SIGNIFICANCE: We know the prevalence of traumatic brain injury (TBI)-related vision impairment and ocular injury symptoms. Lacking is an understanding of health care utilization to treat these symptoms. Utilization knowledge is important to structuring access to treatment, identifying clinical training needs, and providing evidence of the effectiveness of treatment. PURPOSE: This article reports rehabilitation, glasses/contacts, and imaging/photography/video recommendations made by optometrists and ophthalmologists as part of the Department of Veterans Affairs-mandated Performance of Traumatic Brain Injury Specific Ocular Health and Visual Functioning Examination administered to veterans with TBI at Department of Veterans Affairs polytrauma specialty facilities. METHODS: Using a retrospective design, natural language processing, and descriptive and regression statistics, data were analyzed for 2458 Operation Enduring Freedom/Operation Iraqi Freedom veterans who were administered the mandated examination between 2008 and 2017. RESULTS: Of the 2458 veterans, vision rehabilitation was recommended for 24%, glasses/contacts were recommended for 57%, and further imaging/photography/video testing was recommended for 58%. Using key words in the referral, we determined that 37% of veterans were referred to blind rehabilitation, 16% to occupational therapy, and 3% to low-vision clinics. More than 50% of the referrals could have been treated by blind rehabilitation, occupational therapy, or low-vision clinics. Rehabilitation referrals were significantly associated with younger age, floaters, photosensitivity, double vision, visual field and balance deficits, dizziness, and difficulty reading. In comparison, prescriptions for glasses and contacts were associated with older age, photosensitivity, blurred vision, decreased visual field and night vision, difficulty reading, and dry eye. Imaging/photography/video testing was associated with floaters, photosensitivity, and headache. CONCLUSIONS: Findings delineate service delivery models available to veterans with TBI-related vision impairment. The challenge these data address is the lack of clear paths from diagnosis of TBI to identification of vision dysfunction deficits to specialized vision rehabilitation, and finally to community reintegration and community based-vision rehabilitation.


Assuntos
Lesões Encefálicas Traumáticas , Veteranos , Campanha Afegã de 2001- , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico , Humanos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Transtornos da Visão/diagnóstico , Transtornos da Visão/epidemiologia , Transtornos da Visão/etiologia
5.
Gene Ther ; 28(10-11): 646-658, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33558692

RESUMO

CRISPR-Cas systems have emerged as a powerful tool to generate genetic models for studying normal and diseased central nervous system (CNS). Targeted gene disruption at specific loci has been demonstrated successfully in non-dividing neurons. Despite its simplicity, high specificity and low cost, the efficiency of CRISPR-mediated knockout in vivo can be substantially impacted by many parameters. Here, we used CRISPR-Cas9 to disrupt the neuronal-specific gene, NeuN, and optimized key parameters to achieve effective gene knockout broadly in the CNS in postnatal mice. Three cell lines and two primary neuron cultures were used to validate the disruption of NeuN by single-guide RNAs (sgRNA) harboring distinct spacers and scaffold sequences. This triage identified an optimal sgRNA design with the highest NeuN disruption in in vitro and in vivo systems. To enhance CRISPR efficiency, AAV-PHP.B, a vector with superior neuronal transduction, was used to deliver this sgRNA in Cas9 mice via neonatal intracerebroventricular (ICV) injection. This approach resulted in 99.4% biallelic indels rate in the transduced cells, leading to greater than 70% reduction of total NeuN proteins in the cortex, hippocampus and spinal cord. This work contributes to the optimization of CRISPR-mediated knockout and will be beneficial for fundamental and preclinical research.


Assuntos
Sistemas CRISPR-Cas , RNA Guia de Cinetoplastídeos , Animais , Sistema Nervoso Central , Edição de Genes/métodos , Técnicas de Inativação de Genes , Camundongos , Neurônios/metabolismo , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo
6.
Inhal Toxicol ; 33(9-14): 295-307, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34788178

RESUMO

The United States Environmental Protection Agency (US EPA) is currently refining its approach for risk assessments conducted under the amended Toxic Substances Control Act (TSCA), largely based on recommendations from the National Academies of Sciences, Engineering, and Medicine (NASEM). We identified several issues with the current TSCA risk assessment approach that were not addressed by NASEM in its recommendations. Here, we demonstrate these issues with a case study of the 'Risk Evaluation for Asbestos, Part 1: Chrysotile Asbestos,' which US EPA released in December 2020. In this evaluation, US EPA found that occupational and some consumer uses of automotive brakes and clutches that contain asbestos result in unreasonable risks. These risks were calculated from estimated exposures during brake work and an inhalation unit risk (IUR) developed for chrysotile asbestos. We found that US EPA overestimated risk as a result of unrealistic inputs to both the exposure and toxicity components of the risk equation, and because the Agency did not fully consider relevant epidemiology and toxicity evidence in its systematic review. Our evaluation demonstrates areas in which the TSCA risk assessment approach could be improved to result in risk evaluations that are supported by the available scientific evidence.


Assuntos
Amianto , Exposição Ocupacional , Asbestos Serpentinas/análise , Medição de Risco , Estados Unidos
7.
J Am Acad Dermatol ; 82(5): 1158-1165, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31931085

RESUMO

OBJECTIVE: To provide a formal statistical comparison of the efficacy of melanoma detection among different clinical settings. METHODS: A systematic review and meta-analysis of all relevant observational studies on number needed to treat (NNT) in relation to melanoma was performed in MEDLINE. We performed a random-effects model meta-analysis and reported NNTs with 95% confidence intervals (CIs). The subgroup analysis was related to clinical setting. RESULTS: In all, 29 articles including a total of 398,549 biopsies/excisions were analyzed. The overall NNT was 9.71 (95% CI, 7.72-12.29): 22.62 (95% CI, 12.95-40.10) for primary care, 9.60 (95% CI, 6.97-13.41) for dermatology, and 5.85 (95% CI, 4.24-8.27) for pigmented lesion specialists. LIMITATIONS: There is heterogeneity in data reporting and the possibility of missing studies. In addition, the incidence of melanoma varies among clinical settings, which could affect NNT calculations. CONCLUSION: Pigmented lesion specialists have the lowest NNT, followed by dermatologists, suggesting that involving specialists in the diagnosis and treatment of pigmented skin lesions can likely improve patient outcomes.


Assuntos
Melanoma/epidemiologia , Melanoma/cirurgia , Cirurgia de Mohs/estatística & dados numéricos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/cirurgia , Centros Médicos Acadêmicos , Biópsia por Agulha , Procedimentos Cirúrgicos Dermatológicos/métodos , Procedimentos Cirúrgicos Dermatológicos/estatística & dados numéricos , Dermatologistas/estatística & dados numéricos , Feminino , Humanos , Imuno-Histoquímica , Incidência , Masculino , Melanoma/diagnóstico , Cirurgia de Mohs/métodos , Neoplasias Cutâneas/diagnóstico , Resultado do Tratamento , Estados Unidos
8.
Crit Care Med ; 47(9): 1184-1193, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31162200

RESUMO

OBJECTIVES: Optimistic expectations about prognosis by surrogate decision-makers in ICUs are common, but there are few data about the causes and clinical consequences. Our objective was to determine the causes of optimistic expectations about prognosis among surrogates and whether it is associated with more use of life support at the end of life. DESIGN: Prospective, multicenter cohort study from 2009 to 2012. SETTING: Twelve ICUs from multiple regions of the United States. SUBJECTS: The surrogates and physicians of 275 incapacitated ICU patients at high risk of death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Surrogates and physicians completed a validated instrument assessing their prognostic expectations for hospital survival. We determined the proportion of surrogates with optimistic expectations, defined as a prognostic estimate that was at least 20% more optimistic than the physician's, then determined how frequently this arose from surrogates miscomprehending the physicians' prognosis versus holding more hopeful beliefs compared with the physician. We used multivariable regression to examine whether optimistic expectations were associated with length of stay, stratified by survival status, and time to withdrawal of life support among nonsurvivors. Overall, 45% of surrogates (95% CI, 38-51%) held optimistic expectations about prognosis, which arose from a combination of misunderstanding the physician's prognostic expectations and from holding more hopeful beliefs compared with the physician. Optimistic expectations by surrogates were associated with significantly longer duration of ICU treatment among nonsurvivors before death (ß coefficient = 0.44; 95% CI, 0.05-0.83; p = 0.027), corresponding to a 56% longer ICU stay. This difference was associated with a significantly longer time to withdrawal of life support among dying patients whose surrogates had optimistic prognostic expectations compared with those who did not (ß coefficient = 0.61; 95% CI, 0.16-1.07; p = 0.009). CONCLUSIONS: The prevalent optimism about prognosis among surrogates in ICUs arises both from surrogates' miscomprehension of physicians' prognostications and from surrogates holding more hopeful beliefs. This optimism is associated with longer duration of life support at the end of life.


Assuntos
Comunicação , Tomada de Decisões , Otimismo , Médicos/psicologia , Procurador/psicologia , APACHE , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Relações Profissional-Família , Prognóstico , Estudos Prospectivos , Análise de Sobrevida , Estados Unidos , Suspensão de Tratamento/estatística & dados numéricos
9.
J Cardiovasc Electrophysiol ; 30(5): 792-799, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834611

RESUMO

BACKGROUND: Central sleep apnea (CSA) is a breathing disorder caused by the intermittent absence of central respiratory drive. Transvenous phrenic nerve stimulation is a new therapeutic option, recently approved by the FDA , for the treatment of CSA. OBJECTIVE: To describe the technique used to implant the transvenous phrenic nerve stimulation system (the remede System, Respicardia, Inc). METHODS: The remede System is placed in the pectoral region, typically on the right side. A single stimulation lead is placed in either the left pericardiophrenic vein (PPV) or the right brachiocephalic vein (RBC). A sensing lead is placed into the azygous vein to detect respiration. RESULTS: In the remede System Pivotal trial, 147 of 151 (97%) patients were successfully implanted with the system. Sixty-two percent of stimulation leads were placed in the PPV and 35% in the RBC. Mean procedure time was 2.7 ± 0.8 hours and 94% of patients were free from implant-related serious adverse events through 6 months. CONCLUSION: In patients with CSA, transvenous phrenic nerve stimulation is an effective and safe therapy with an implant procedure similar to that of cardiac implantable electronic devices.


Assuntos
Diafragma/inervação , Terapia por Estimulação Elétrica/instrumentação , Neuroestimuladores Implantáveis , Nervo Frênico/fisiopatologia , Implantação de Prótese , Respiração , Apneia do Sono Tipo Central/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Humanos , Duração da Cirurgia , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Apneia do Sono Tipo Central/diagnóstico , Apneia do Sono Tipo Central/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
10.
Crit Rev Toxicol ; 49(7): 597-613, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31965908

RESUMO

Esophageal cancers comprise about 1% of all cancers diagnosed in the US but are more prevalent in other regions of the world. Several regulatory agencies have classified asbestos as a known human carcinogen, and it is linked to multiple diseases and malignancies, including lung cancer and mesothelioma. In a 2006 review of the epidemiological literature, the Institute of Medicine (IOM) did not find sufficient evidence to demonstrate a causal relationship between asbestos exposure and esophageal cancer. To reevaluate this conclusion, we performed a critical review of the animal toxicological, epidemiological, and mechanism of action literature on esophageal cancer and asbestos, incorporating studies published since 2006. Although there is some evidence in the epidemiological literature for an increased risk of esophageal cancer in asbestos-exposed occupational cohorts, these studies generally did not control for critical esophageal cancer risk factors (e.g. smoking, alcohol consumption). Furthermore, data from animal toxicological studies do not indicate that asbestos exposure increases esophageal cancer risk. Based on our evaluation of the literature, and reaffirming the IOM's findings, we conclude that there is insufficient evidence to demonstrate a causal link between asbestos exposure and esophageal cancer.


Assuntos
Amianto , Exposição Ambiental/estatística & dados numéricos , Neoplasias Esofágicas/epidemiologia , Substâncias Perigosas , Animais , Humanos
11.
Med Mycol ; 57(6): 688-693, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30462288

RESUMO

Coccidioidomycosis, the fungal infection caused by dimorphic Coccidioides species, is typically diagnosed by histopathologic identification of spherules, by culture, or by serology. These tests are reliable but time-intensive, delaying diagnosis and treatment. Rapid real-time polymerase chain reaction (RT-PCR) can be performed and was validated to identify Coccidioides immitis using an in-house developed assay for the Becton Dickinson molecular instrument (BD MAXTM). These studies were performed using patient samples that had been shown to be positive on previously set up fungal cultures. To evaluate this new RT-PCR test in the clinical setting, we conducted a retrospective chart review of patients (N = 1160) who underwent Coccidioides PCR (Cocci PCR) on clinical samples between March 1, 2014, and Dec 31, 2016. We abstracted clinical, microbiologic, serologic, radiographic, treatment, and follow-up data. Specimens of cerebrospinal fluid (CSF), bronchioalveolar lavage fluid (BAL), lung tissue biopsy (LTB), sputum, and pleural fluid were evaluated to determine sensitivity and specificity. Of the 113 specimens that tested positive for Cocci PCR, all had clinical disease defined by traditional clinical criteria, yielding 100% specificity. Overall sensitivity was 74% versus 46% for fungal culture and was available in 4 hours rather than 1-2 weeks. Sensitivities varied by source material and clinical setting. CSF had a sensitivity of 59%, BAL for acute pneumonia 91%, sputum for acute pneumonia 94%, pleural fluid 86%, but LTB for lung nodules only 44%. Overall positive predictive value (PPV) was 100%, while negative predictive value (NPV) was 96%, but again this varied by specimen and clinical setting. Our experience with clinical testing of >1160 specimens over 2-3 years shows we can utilize this technology to improve our ability to diagnose disease but that the sensitivity varies by specimen source and clinical setting.


Assuntos
Coccidioides/isolamento & purificação , Coccidioidomicose/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Biópsia , Líquido da Lavagem Broncoalveolar/microbiologia , California , Coccidioidomicose/sangue , Humanos , Pulmão/microbiologia , Pulmão/patologia , Derrame Pleural/microbiologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Escarro/microbiologia
12.
J Environ Sci Health B ; 54(10): 866-874, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31258003

RESUMO

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.


Assuntos
Agricultura/métodos , Cumarínicos/metabolismo , Mikania/metabolismo , Extratos Vegetais/toxicidade , Plantas Medicinais/metabolismo , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Brasil , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Humanos , Mikania/química , Testes de Mutagenicidade , Agricultura Orgânica/métodos , Extratos Vegetais/análise , Extratos Vegetais/química
13.
Hum Mol Genet ; 25(14): 3011-3028, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27340223

RESUMO

Atrioventricular septal defects (AVSDs) are a common severe form of congenital heart disease (CHD). In this study we identified deleterious non-synonymous mutations in two cilia genes, Dnah11 and Mks1, in independent N-ethyl-N-nitrosourea-induced mouse mutant lines with heritable recessive AVSDs by whole-exome sequencing. Cilia are required for left/right body axis determination and second heart field (SHF) Hedgehog (Hh) signaling, and we find that cilia mutations affect these requirements differentially. Dnah11avc4 did not disrupt SHF Hh signaling and caused AVSDs only concurrently with heterotaxy, a left/right axis abnormality. In contrast, Mks1avc6 disrupted SHF Hh signaling and caused AVSDs without heterotaxy. We performed unbiased whole-genome SHF transcriptional profiling and found that cilia motility genes were not expressed in the SHF whereas cilia structural and signaling genes were highly expressed. SHF cilia gene expression predicted the phenotypic concordance between AVSDs and heterotaxy in mice and humans with cilia gene mutations. A two-step model of cilia action accurately predicted the AVSD/heterotaxyu phenotypic expression pattern caused by cilia gene mutations. We speculate that cilia gene mutations contribute to both syndromic and non-syndromic AVSDs in humans and provide a model that predicts the phenotypic consequences of specific cilia gene mutations.


Assuntos
Dineínas do Axonema/genética , Cílios/genética , Defeitos dos Septos Cardíacos/genética , Proteínas/genética , Animais , Dineínas do Axonema/biossíntese , Padronização Corporal/genética , Cílios/efeitos dos fármacos , Modelos Animais de Doenças , Etilnitrosoureia/toxicidade , Exoma/genética , Regulação da Expressão Gênica , Coração/fisiopatologia , Defeitos dos Septos Cardíacos/patologia , Proteínas Hedgehog/biossíntese , Proteínas Hedgehog/genética , Humanos , Camundongos , Mutação , Transdução de Sinais/genética
14.
Environ Res ; 160: 256-268, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29031215

RESUMO

BACKGROUND: Thousands of synthetic turf fields in the US are regularly used by millions of individuals (particularly children and adolescents). Although many safety assessments have concluded that there are low or negligible risks related to exposure to chemicals found in the recycled rubber used to make these fields, concerns remain about the safety of this product. Existing studies of recycled rubber's potential health risks have limitations such as small sample sizes and limited evaluation of relevant exposure pathways and scenarios. OBJECTIVE: Conduct a comprehensive multipathway human health risk assessment (HHRA) of exposure to chemicals found in recycled rubber. METHODS: All available North American data on the chemical composition of recycled rubber, as well as air sampling data collected on or near synthetic turf fields, were identified via a literature search. Ingestion, dermal contact, and inhalation pathways were evaluated according to US Environmental Protection Agency (US EPA) guidance, and exposure scenarios for adults, adolescents, and children were considered. RESULTS: Estimated non-cancer hazards and cancer risks for all the evaluated scenarios were within US EPA guidelines. In addition, cancer risk levels for users of synthetic turf field were comparable to or lower than those associated with natural soil fields. CONCLUSIONS: This HHRA's results add to the growing body of literature that suggests recycled rubber infill in synthetic turf poses negligible risks to human health. This comprehensive assessment provides data that allow stakeholders to make informed decisions about installing and using these fields.


Assuntos
Materiais de Construção/análise , Materiais de Construção/toxicidade , Exposição Ambiental/análise , Borracha/química , Adolescente , Adulto , Criança , Exposição Ambiental/efeitos adversos , Humanos , Neoplasias/induzido quimicamente , Reciclagem , Medição de Risco , Borracha/efeitos adversos
15.
Tetrahedron ; 74(15): 1951-1956, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30853725

RESUMO

The ß-subunit of human thyroid stimulating hormone (hTSH) has been synthesized as a single glycoform bearing a chitobiose disaccharide at the native glycosylation site. Key to the successful completion of this synthesis was the introduction of an arginine-tagged acetamidomethyl group, which served to greatly facilitate handling of a glycopeptide fragment with poor aqueous solubility. This general solution to the challenge of working with intractable peptides is expected to find wide use in protein synthesis.

16.
WMJ ; 117(2): 79-82, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30048577

RESUMO

BACKGROUND: Quality improvement (QI) education in residency training has become critical for numerous reasons, but little has been written about factors that lead to successful improvement projects within residency training. METHODS: A quality improvement curriculum for third-year psychiatry residents was developed. The percentage of resident projects that have been successfully implemented was calculated. Residents completed the QI Knowledge Application Tool adapted for psychiatry before and after the curriculum to assess knowledge and skills. RESULTS: Eighteen of 19 resident projects were successfully implemented. QI Knowledge Application Tool scores improved from 4.8 to 8.1 (P = 0.0053) after completion of the curriculum. CONCLUSIONS: Residents are able to implement successful projects and to increase their knowledge and skills in quality improvement when given appropriate resources and incentives.


Assuntos
Currículo , Educação de Pós-Graduação em Medicina , Internato e Residência , Psiquiatria/educação , Melhoria de Qualidade , Adulto , Avaliação Educacional , Feminino , Humanos , Masculino
17.
J Am Chem Soc ; 139(22): 7632-7639, 2017 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-28448128

RESUMO

The Ras proteins are essential GTPases involved in the regulation of cell proliferation and survival. Mutated oncogenic forms of Ras alter effector binding and innate GTPase activity, leading to deregulation of downstream signal transduction. Mutated forms of Ras are involved in approximately 30% of human cancers. Despite decades of effort to develop direct Ras inhibitors, Ras has long been considered "undruggable" due to its high affinity for GTP and its lack of hydrophobic binding pockets. Herein, we report a total chemical synthesis of all-l- and all-d-amino acid biotinylated variants of oncogenic mutant KRas(G12V). The protein is synthesized using Fmoc-based solid-phase peptide synthesis and assembled using combined native chemical ligation and isonitrile-mediated activation strategies. We demonstrate that both KRas(G12V) enantiomers can successfully fold and bind nucleotide substrates and binding partners with observable enantiodiscrimination. By demonstrating the functional competency of a mirror-image form of KRas bound to its corresponding enantiomeric nucleotide triphosphate, this study sets the stage for further biochemical studies with this material. In particular, this protein will enable mirror-image yeast surface display experiments to identify all-d peptide ligands for oncogenic KRas, providing a useful tool in the search for new therapeutics against this challenging disease target.


Assuntos
Proteínas Proto-Oncogênicas p21(ras)/síntese química , Sequência de Aminoácidos , Variação Genética , Humanos , Dobramento de Proteína , Proteínas Proto-Oncogênicas p21(ras)/genética
18.
J Immunol ; 194(6): 2551-60, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-25667416

RESUMO

The link between autoimmune diseases and primary immunodeficiency syndromes has been increasingly appreciated. Immunologic evaluation of a young man with autoimmune enterocolopathy and unexplained infections revealed evidence of immunodeficiency, including IgG subclass deficiency, impaired Ag-induced lymphocyte proliferation, reduced cytokine production by CD8(+) T lymphocytes, and decreased numbers of NK cells. Genetic evaluation identified haploinsufficiency of NFAT5, a transcription factor regulating immune cell function and cellular adaptation to hyperosmotic stress, as a possible cause of this syndrome. Inhibition or deletion of NFAT5 in normal human and murine cells recapitulated several of the immune deficits identified in the patient. These results provide evidence of a primary immunodeficiency disorder associated with organ-specific autoimmunity linked to NFAT5 deficiency.


Assuntos
Doenças Autoimunes/imunologia , Gastroenteropatias/imunologia , Haploinsuficiência/imunologia , Síndromes de Imunodeficiência/imunologia , Fatores de Transcrição/imunologia , Animais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/genética , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Análise Mutacional de DNA , Gastroenteropatias/diagnóstico , Gastroenteropatias/genética , Expressão Gênica/imunologia , Haploinsuficiência/genética , Humanos , Immunoblotting , Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/genética , Células Jurkat , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Masculino , Camundongos da Linhagem 129 , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Adulto Jovem
19.
Regul Toxicol Pharmacol ; 86: 312-318, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28377091

RESUMO

Bisphenol A (BPA) is a high production volume chemical that is used in plastics and epoxy coatings. In 2015, California's Office of Environmental Health Hazard Assessment (OEHHA) added BPA to the Proposition 65 list of chemicals "known to cause reproductive toxicity" based on its Developmental and Reproductive Toxicant Identification Committee's (DART-IC) conclusion that BPA has been shown to cause female reproductive toxicity. A critical factor in determining compliance with Proposition 65 is a Maximum Allowable Dose Level (MADL), which is the exposure level at which a chemical would have no observable reproductive effect even if a person were exposed to 1000 times that level. We performed a comprehensive review of the literature, including the studies reviewed by DART-IC, and derived an oral MADL. Of all the studies we identified, Delclos et al. (2014) is of sufficient quality, has the lowest no observed effect level (NOEL), and results in the most conservative MADL of 157 µg/d. This is generally supported by other studies, including those that were considered by DART-IC. Also, the oral MADL provides a similar margin of safety as OEHHA's dermal MADL and other regulatory guidelines. Taken together, the scientific data support an oral MADL of 157 µg/d.


Assuntos
Compostos Benzidrílicos/administração & dosagem , Fenóis/administração & dosagem , Reprodução/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , California , Feminino , Humanos , Legislação de Medicamentos , Concentração Máxima Permitida , Fenóis/toxicidade
20.
Lung ; 194(3): 379-85, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26980483

RESUMO

PURPOSE: Previous studies with small sample sizes have shown a wide range of complication rates and no study has investigated the yield of computed tomography-guided transthoracic core needle biopsies (CTTCB) for coccidioidomycosis. To better assess the safety, accuracy, and risk factors for complications of CTTCB of pulmonary nodules, we conducted a retrospective study at a high-volume academic center in an endemic coccidioidomycosis area. METHODS: We conducted a retrospective study of 203 patients who underwent CTTCB of pulmonary nodules between December 2010 and May 2013. We collected demographics, clinical, and radiographic data. Each case was reviewed for complications. Diagnostic accuracy was assessed by comparing CTTCB with final diagnoses. RESULTS: The overall complication rate was 25 %. Pneumothorax accounted for 24 % of complications with 7 % of pneumothoraces requiring chest tube. 1.5 % were complicated by hemoptysis but none required blood transfusions. There was an association between complications and age, presence of emphysema on CT, traversed lung length, and lesion depth. The overall sensitivity of the CTTCB for all types of lung cancer was 93 %, and specificity of 100 %. The positive predictive value of CTTCB for lung cancer was 100 %. The sensitivity and specificity of CTTCB for a coccidiomycosis lung nodule was 83 % with a specificity of 100 % with a PPV of 100 %. CONCLUSION: Our study demonstrates that CTTCB is a relatively safe method for evaluating lung nodules and highly accurate in evaluating lung nodules due to coccidioidomycosis in an endemic area. The primary risk factors for complications from CTTCB are the presence of emphysema on CT scan, lesion depth, and traversed lung length.


Assuntos
Coccidioidomicose/diagnóstico , Coccidioidomicose/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Nódulo Pulmonar Solitário/diagnóstico , Nódulo Pulmonar Solitário/patologia , Centros Médicos Acadêmicos , Idoso , Biópsia com Agulha de Grande Calibre/efeitos adversos , Diagnóstico Diferencial , Feminino , Hemoptise/etiologia , Hospitais com Alto Volume de Atendimentos , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pneumotórax/etiologia , Valor Preditivo dos Testes , Enfisema Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
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