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1.
PLoS Biol ; 19(11): e3001460, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34780461

RESUMO

A vast range of research applications in biodiversity sciences requires integrating primary species, genetic, or ecosystem data with other environmental data. This integration requires a consideration of the spatial and temporal scale appropriate for the data and processes in question. But a versatile and scale flexible environmental annotation of biodiversity data remains constrained by technical hurdles. Existing tools have streamlined the intersection of occurrence records with gridded environmental data but have remained limited in their ability to address a range of spatial and temporal grains, especially for large datasets. We present the Spatiotemporal Observation Annotation Tool (STOAT), a cloud-based toolbox for flexible biodiversity-environment annotations. STOAT is optimized for large biodiversity datasets and allows user-specified spatial and temporal resolution and buffering in support of environmental characterizations that account for the uncertainty and scale of data and of relevant processes. The tool offers these services for a growing set of near global, remotely sensed, or modeled environmental data, including Landsat, MODIS, EarthEnv, and CHELSA. STOAT includes a user-friendly, web-based dashboard that provides tools for annotation task management and result visualization, linked to Map of Life, and a dedicated R package (rstoat) for programmatic access. We demonstrate STOAT functionality with several examples that illustrate phenological variation and spatial and temporal scale dependence of environmental characteristics of birds at a continental scale. We expect STOAT to facilitate broader exploration and assessment of the scale dependence of observations and processes in ecology.


Assuntos
Biodiversidade , Computação em Nuvem , Animais , Aves/fisiologia , Bases de Dados como Assunto , Comunicações Via Satélite , Estações do Ano , Análise Espaço-Temporal , Especificidade da Espécie , Temperatura , Fatores de Tempo
2.
Analyst ; 145(19): 6291-6297, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32945826

RESUMO

Phage-based biosensors have shown significant promise in meeting the present needs of the food and agricultural industries due to a combination of sufficient portability, speed, ease of use, sensitivity, and low production cost. Although current phage-based methods do not meet the bacteria detection limit imposed by the EPA, FDA, and USDA, a better understanding of phage genetics can significantly increase their sensitivity as biosensors. In the current study, the signal sensitivity of a T4 phage-based detection system was improved via transcriptional upregulation of the reporter enzyme Nanoluc luciferase (Nluc). An efficient platform to evaluate the promoter activity of reporter T4 phages was developed. The ability to upregulate Nluc within T4 phages was evaluated using 15 native T4 promoters. Data indicates a six-fold increase in reporter enzyme signal from integration of the selected promoters. Collectively, this work demonstrates that fine tuning the expression of reporter enzymes such as Nluc through optimization of transcription can significantly reduce the limits of detection.


Assuntos
Bacteriófago T4 , Técnicas Biossensoriais , Bacteriófago T4/genética , Luciferases , Regiões Promotoras Genéticas
3.
J Biol Chem ; 292(29): 12100-12110, 2017 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-28539358

RESUMO

Kidney disease has been linked to dysregulated signaling via PKC in kidney cells such as podocytes. PKCα is a conventional isoform of PKC and a well-known binding partner of ß-catenin, which promotes its degradation. ß-Catenin is the main effector of the canonical Wnt pathway and is critical in cell adhesion. However, whether other PKC isoforms interact with ß-catenin has not been studied systematically. Here we demonstrate that PKCϵ-deficient mice, which develop proteinuria and glomerulosclerosis, display lower ß-catenin expression compared with PKC wild-type mice, consistent with an altered phenotype of podocytes in culture. Remarkably, ß-catenin showed a reversed subcellular localization pattern: Although ß-catenin exhibited a perinuclear pattern in undifferentiated wild-type cells, it predominantly localized to the nucleus in PKCϵ knockout cells. Phorbol 12-myristate 13-acetate stimulation of both cell types revealed that PKCϵ positively regulates ß-catenin expression and stabilization in a glycogen synthase kinase 3ß-independent manner. Further, ß-catenin overexpression in PKCϵ-deficient podocytes could restore the wild-type phenotype, similar to rescue with a PKCϵ construct. This effect was mediated by up-regulation of P-cadherin and the ß-catenin downstream target fascin1. Zebrafish studies indicated three PKCϵ-specific phosphorylation sites in ß-catenin that are required for full ß-catenin function. Co-immunoprecipitation and pulldown assays confirmed PKCϵ and ß-catenin as binding partners and revealed that ablation of the three PKCϵ phosphorylation sites weakens their interaction. In summary, we identified a novel pathway for regulation of ß-catenin levels and define PKCϵ as an important ß-catenin interaction partner and signaling opponent of other PKC isoforms in podocytes.


Assuntos
Podócitos/metabolismo , Proteína Quinase C-épsilon/metabolismo , Processamento de Proteína Pós-Traducional , beta Catenina/metabolismo , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Substituição de Aminoácidos , Animais , Bioensaio , Carcinógenos/toxicidade , Linhagem Celular Transformada , Regulação da Expressão Gênica/efeitos dos fármacos , Glicogênio Sintase Quinase 3 beta/metabolismo , Células HEK293 , Humanos , Camundongos Knockout , Mutagênese Sítio-Dirigida , Mutação , Fosforilação/efeitos dos fármacos , Podócitos/citologia , Podócitos/efeitos dos fármacos , Proteína Quinase C-épsilon/antagonistas & inibidores , Proteína Quinase C-épsilon/genética , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/toxicidade , Técnicas de Cultura de Tecidos , beta Catenina/antagonistas & inibidores , beta Catenina/química , beta Catenina/genética
4.
J Biol Chem ; 290(49): 29642-51, 2015 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-26487714

RESUMO

The collectin proteins are innate immune molecules found in high concentrations on the epithelial and endothelial surfaces of the lung. While these proteins are known to have important anti-inflammatory actions in the airways of the lung little is known of their functional importance in the pulmonary circulation. We recently demonstrated that the circulating collectin protein adiponectin has potent anti-inflammatory effects on the lung endothelium, leading us to reason that other structurally related proteins might have similar effects. To test this hypothesis, we investigated the anti-inflammatory actions of C1q in lung endothelial homeostasis and the pulmonary vascular response to LPS or HCl injury. We show that lung endothelium from C1q-deficient (C1q(-/-)) mice expresses higher baseline levels of the vascular adhesion markers ICAM-1, VCAM-1, and E-selectin when compared with wild-type mice. Further, we demonstrate that these changes are associated with enhanced susceptibility of the lung to injury as evident by increased expression of adhesion markers, enhanced production of pro-inflammatory cytokines, and augmented neutrophil recruitment. Additionally, we found that C1q(-/-) mice also exhibited enhanced endothelial barrier dysfunction after injury as manifested by decreased expression of junctional adherens proteins and enhanced vascular leakage. Mechanistically, C1q appears to mediate its effects by inhibiting phosphorylation of p38 mitogen-activated protein kinase (MAPK) and blocking nuclear translocation of the P65 subunit of nuclear factor (NF)-κB. In summary, our findings indicate a previously unrecognized role for C1q in pulmonary vascular homeostasis and provide added support for the hypothesis that circulating collectin proteins have protective effects on the lung endothelium.


Assuntos
Complemento C1q/deficiência , Endotélio/metabolismo , Inflamação/metabolismo , Lesão Pulmonar/metabolismo , Pulmão/patologia , Animais , Líquido da Lavagem Broncoalveolar , Adesão Celular , Colectinas/metabolismo , Complemento C1q/metabolismo , Citocinas/metabolismo , Feminino , Homeostase , Leucócitos/metabolismo , Lesão Pulmonar/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neutrófilos/metabolismo , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
5.
Clin Chem ; 62(11): 1524-1532, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27624138

RESUMO

BACKGROUND: Following immigration to the US, many Africans transition from a low-normal to a high-normal or overweight body mass index (BMI). This weight change is associated with a high rate of prediabetes in the nonobese. Studies in East Asians reveal that glycated albumin is effective in identifying prediabetes in nonobese Asians. Whether this is true in African immigrants is unknown. Therefore, we evaluated the ability of hemoglobin A1c (Hb A1c) and glycated albumin to detect prediabetes in nonobese (BMI <30 kg/m2) and obese (BMI ≥30 kg/m2) African immigrants. METHODS: Oral glucose tolerance tests (OGTTs) were performed in 236 self-identified healthy African immigrants [mean (SD) BMI 27.6 (4.4) kg/m2]. Prediabetes diagnosis was based on glucose criteria for the OGTT. Diagnostic sensitivity of Hb A1c and glycated albumin was determined by thresholds at the upper quartile for each [Hb A1c ≥5.7% (39 mmol/mol), glycated albumin ≥13.77%]. RESULTS: Based on glucose criteria for the OGTT, prediabetes was detected in 36% (85/236). BMI and Hb A1c were positively correlated (r = 0.22, P < 0.001), whereas BMI and glycated albumin were negatively correlated (r = -0.24, P < 0.001). Although the sensitivities of Hb A1c and glycated albumin were similar in nonobese immigrants (37% vs 42%, P = 0.75), prediabetes was detected in 21 nonobese Africans by glycated albumin alone, in 18 by Hb A1c alone, and in 4 by both tests. Therefore, sensitivity of the combined tests was better than for Hb A1c alone(72% vs 37%, P < 0.01). In the obese, Hb A1c was a much better diagnostic test than glycated albumin (64% vs 16%, P < 0.01) and combining the tests did not improve sensitivity (72% vs 64%, P = 0.50). CONCLUSIONS: Glycated albumin contributes by identifying prediabetes not detected by Hb A1c in nonobese African immigrants. ClinicalTrials.gov Identifier: NCT00001853.


Assuntos
Negro ou Afro-Americano , Hemoglobinas Glicadas/análise , Estado Pré-Diabético/sangue , Estado Pré-Diabético/diagnóstico , Albumina Sérica/análise , Adulto , População Negra , Índice de Massa Corporal , Estudos de Coortes , Feminino , Teste de Tolerância a Glucose , Produtos Finais de Glicação Avançada , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Albumina Sérica Glicada
6.
Am J Respir Cell Mol Biol ; 53(1): 74-86, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25409201

RESUMO

Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-ß1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATP-binding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders.


Assuntos
Células Epiteliais Alveolares/metabolismo , Células Espumosas/metabolismo , Metabolismo dos Lipídeos , Macrófagos Alveolares/metabolismo , Fibrose Pulmonar/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/farmacologia , Bleomicina/efeitos adversos , Bleomicina/farmacologia , Células Espumosas/patologia , Humanos , Lipoproteínas/genética , Lipoproteínas/metabolismo , Macrófagos Alveolares/patologia , Camundongos , Camundongos Knockout , Fosfatidilcolinas/toxicidade , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Fibrose Pulmonar/patologia
7.
J Shoulder Elbow Surg ; 24(1): 138-42, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25193486

RESUMO

BACKGROUND: Surgical techniques for proximal biceps tenodesis that include penetration of the posterior humeral cortex for fixation may pose risk to the surrounding neurovascular structures. HYPOTHESIS: The risk of neurologic injury with techniques that involve penetration of the posterior humeral cortex for fixation in proximal biceps tenodesis will increase as the tenodesis site moves proximally from the subpectoral to the suprapectoral location. METHODS: Proximal biceps tenodesis was performed on 10 cadaveric upper extremities with 3 separate techniques. The proximity of the hardware to the relevant neurovascular structures was measured. The distances between the tenodesis site and the relevant neurovascular structures were measured. RESULTS: The guide pin was in direct contact with the axillary nerve in 20% of the suprapectoral tenodeses. The distance between the axillary nerve and the tenodesis site was 10.5 ± 5.5 mm for the suprapectoral location, 36.7 ± 11.2 mm in the subpectoral scenario, and 24.1 ± 11.2 mm in the 30° cephalad scenario (P = .003). The distance between the radial nerve and the anterior tenodesis site was 41.3 ± 9.3 mm for the suprapectoral location and 48.0 ± 10.7 mm for the subpectoral location. The distance of the musculocutaneous nerve from the tenodesis site was 28.4 ± 9.2 mm for the suprapectoral location and 37.4 ± 11.2 mm for the subpectoral location. CONCLUSION: In a cadaveric model of open biceps tenodesis, penetration of the posterior humeral cortex at the suprapectoral location results in proximity to the axillary nerve and should be avoided. Subpectoral bicortical button fixation drilled perpendicular to the axis of the humerus was a uniformly safe location with respect to the axillary nerve.


Assuntos
Úmero/cirurgia , Músculo Esquelético/cirurgia , Traumatismos dos Nervos Periféricos/etiologia , Tenodese/efeitos adversos , Braço , Cadáver , Humanos , Músculo Esquelético/inervação , Segurança do Paciente , Traumatismos dos Nervos Periféricos/prevenção & controle , Tendões/inervação , Tendões/cirurgia , Tenodese/métodos , Resultado do Tratamento , Extremidade Superior/inervação , Extremidade Superior/cirurgia
8.
Am J Respir Cell Mol Biol ; 51(6): 840-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24940828

RESUMO

Chronic alcoholism impairs pulmonary immune homeostasis and predisposes to inflammatory lung diseases, including infectious pneumonia and acute respiratory distress syndrome. Although alcoholism has been shown to alter hepatic metabolism, leading to lipid accumulation, hepatitis, and, eventually, cirrhosis, the effects of alcohol on pulmonary metabolism remain largely unknown. Because both the lung and the liver actively engage in lipid synthesis, we hypothesized that chronic alcoholism would impair pulmonary metabolic homeostasis in ways similar to its effects in the liver. We reasoned that perturbations in lipid metabolism might contribute to the impaired pulmonary immunity observed in people who chronically consume alcohol. We studied the metabolic consequences of chronic alcohol consumption in rat lungs in vivo and in alveolar epithelial type II cells and alveolar macrophages (AMs) in vitro. We found that chronic alcohol ingestion significantly alters lung metabolic homeostasis, inhibiting AMP-activated protein kinase, increasing lipid synthesis, and suppressing the expression of genes essential to metabolizing fatty acids (FAs). Furthermore, we show that these metabolic alterations promoted a lung phenotype that is reminiscent of alcoholic fatty liver and is characterized by marked accumulation of triglycerides and free FAs within distal airspaces, AMs, and, to a lesser extent, alveolar epithelial type II cells. We provide evidence that the metabolic alterations in alcohol-exposed rats are mechanistically linked to immune impairments in the alcoholic lung: the elevations in FAs alter AM phenotypes and suppress both phagocytic functions and agonist-induced inflammatory responses. In summary, our work demonstrates that chronic alcohol ingestion impairs lung metabolic homeostasis and promotes pulmonary immune dysfunction. These findings suggest that therapies aimed at reversing alcohol-related metabolic alterations might be effective for preventing and/or treating alcohol-related pulmonary disorders.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Lipogênese/efeitos dos fármacos , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Adenilato Quinase/metabolismo , Álcool Desidrogenase/metabolismo , Animais , Polaridade Celular , Citocromo P-450 CYP2E1/metabolismo , Ativação Enzimática , Etanol/farmacologia , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Fagocitose , Ratos Sprague-Dawley , Triglicerídeos/metabolismo
9.
Am J Physiol Lung Cell Mol Physiol ; 306(2): L152-61, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24285266

RESUMO

Acute lung injury (ALI) is a severe inflammatory condition whose pathogenesis is irrevocably linked to neutrophil emigration to the lung. Activation and recruitment of neutrophils to the lung is mostly attributable to local production of the chemokines. However, much of our understanding of neutrophil recruitment to the lung is based on studies focusing on early time points after initiation of injury. In this study, we sought to evaluate the extended temporal relationship between neutrophil chemotactic factor expression and influx of neutrophils into the lung after intratracheal administration of either LPS or bleomycin. In both models, results demonstrated two phases of neutrophil chemotactic factor expression; first, an early phase characterized by high levels of CXCL1/keratinocyte-derived chemokine, CXCL2/monocyte-inhibitory protein-2, and CXCL5/LPS-induced chemokine expression, and second, a late phase distinguished by increases in extracellular ATP. Furthermore, we show that strategies aimed at either enhancing ATP catabolism (ip ecto-5'-nucleotidase administration) or inhibiting glycolytic ATP production (ip 2-deoxy-d-glucose treatment) reduce extracellular ATP accumulation, limit vascular leakage, and effectively block the late, but not the early, stages of neutrophil recruitment to the lung after LPS instillation. In conclusion, this study illustrates that neutrophil recruitment to the lung is mediated by the time-dependent expression of chemotactic factors and suggests that novel strategies, which reduce extracellular ATP accumulation, may attenuate late neutrophil recruitment and limit lung injury during ALI.


Assuntos
Lesão Pulmonar Aguda , Trifosfato de Adenosina/metabolismo , Infiltração de Neutrófilos/imunologia , Neutrófilos/imunologia , 5'-Nucleotidase/imunologia , 5'-Nucleotidase/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/metabolismo , Animais , Antibióticos Antineoplásicos/farmacologia , Bleomicina/farmacologia , Líquido da Lavagem Broncoalveolar/imunologia , Movimento Celular/imunologia , Quimiocinas/genética , Quimiocinas/imunologia , Quimiocinas/metabolismo , Modelos Animais de Doenças , Espaço Extracelular/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos/efeitos dos fármacos , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos
10.
Nutrients ; 16(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38732559

RESUMO

(1) Background: Fortifying maize and wheat flours with folic acid has effectively reduced neural tube defect-affected births. However, maize and wheat flours may not be widely consumed in all countries; further reduction in neural tube defect-affected births could benefit from the identification of alternative food vehicles. We aimed to use dietary intake or apparent consumption data to determine alternative food vehicles for large-scale fortification with folic acid in low-income and lower-middle-income countries (LILMICs) and identify current research related to examining the technological feasibility of fortifying alternative foods with folic acid. (2) Methods: We identified 81 LILMICs, defined by the World Bank's (WB) 2018 income classifications. To identify dietary intake or apparent consumption, we reviewed WB's Microdata Library and Global Health Data Exchange for national surveys from 1997-2018. We reviewed survey reports for dietary intake or apparent consumption data and analyzed survey datasets for population coverage of foods. We defined alternative food vehicles as those that may cover/be consumed by ≥30% of the population or households; cereal grains (maize and wheat flours and rice) were included as an alternative food vehicle if a country did not have existing mandatory fortification legislation. To identify current research on fortification with folic acid in foods other than cereal grains, we conducted a systematic review of published literature and unpublished theses, and screened for foods or food products. (3) Results: We extracted or analyzed data from 18 national surveys and countries. The alternative foods most represented in the surveys were oil (n = 16), sugar (n = 16), and salt (n = 14). The coverage of oil ranged from 33.2 to 95.7%, sugar from 32.2 to 98.4%, and salt from 49.8 to 99.9%. We found 34 eligible studies describing research on alternative foods. The most studied alternative foods for fortification with folic acid were dairy products (n = 10), salt (n = 6), and various fruit juices (n = 5). (4) Conclusions: Because of their high coverage, oil, sugar, and salt emerge as potential alternative foods for large-scale fortification with folic acid. However, except for salt, there are limited or no studies examining the technological feasibility of fortifying these foods with folic acid.


Assuntos
Grão Comestível , Ácido Fólico , Alimentos Fortificados , Defeitos do Tubo Neural , Triticum , Ácido Fólico/administração & dosagem , Humanos , Defeitos do Tubo Neural/prevenção & controle , Triticum/química , Grão Comestível/química , Farinha/análise , Zea mays/química , Países em Desenvolvimento
11.
Am J Emerg Med ; 30(1): 266.e1-2, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21277137

RESUMO

Hiccups, which are usually benign and self-limited, occasionally serve as markers of a serious underlying pathology. We present this case report to inform emergency physicians about the potential for hiccups to serve as the only presenting symptom of a myocardial infarction. The patient, a 68-year-old man with a history of diabetes mellitus, hypertension, and current tobacco use, was first seen in the emergency department after 4 days of intractable hiccups with no other complaints or symptoms. After ineffective hiccup treatment on the first visit with 2 mg Ativan and 25 intramuscular (i.m.) thorazine and a normal chest x-ray, he was discharged. Two days later, the patient returned to the emergency department with the same complaint of hiccups without any additional complaints or symptoms. An electrocardiogram displayed several abnormalities including Q waves in II, III, and aVF and T-wave inversions in aVL and V6. Troponin I was highly elevated at 4.302 ng/mL. In the catheterization laboratory, the patient exhibited severe stenosis of the left circumflex artery and obtuse marginal 1. Stents were placed in these sites, and the patient recovered uneventfully. This is the first case in which hiccups were the single presenting symptom of a myocardial infarction in the last 50 years. Although extremely common and usually benign, hiccups can occasionally be a sole symptom of serious underlying pathology, which in this case, was a non­ST-segment elevation myocardial infarction.


Assuntos
Soluço/etiologia , Infarto do Miocárdio/complicações , Idoso , Eletrocardiografia , Humanos , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia
12.
Eye Brain ; 14: 137-147, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531433

RESUMO

Introduction: Previous works on experience-dependent brain plasticity have been limited to the cortical structures, overlooking subcortical visual structures such as the lateral geniculate nucleus (LGN). Animal studies have shown substantial experience dependent plasticity and using fMRI, human studies have demonstrated similar properties in patients with cataract surgery. However, in neither animal nor human studies LGN has not been directly assessed, mainly due to its small size, tissue heterogeneity, low contrast/noise ratio, and low spatial resolution. Methods: Utilizing a new algorithm that markedly improves the LGN visibility, LGN was evaluated in a group of low vision patients before and after retinal intervention to reinstate vision and normal sighted matched controls. Results: Between and within groups comparisons showed that patients had significantly smaller left (p< 0.0001) and right (p < 0.00002) LGN volumes at baseline as compared to the one-year follow-up volumes. The same baseline and one year comparison in controls was not significant. Significant positive correlations were observed between the incremental volume increase after gene therapy of the left LGN and the incremental increase in the right (r = 0.71, p < 0.02) and left (r = 0.72, p = 0.018) visual fields. Incremental volume increase of the right LGN also showed a similar positive slope but did not reach significance. Discussion: These results show that despite significantly less volume at baseline, retinal gene therapy promotes robust expansion and increase in LGN volume. Reinstating vision may have facilitated the establishment of new connections between the retina and the LGN and/or unmasking of the dormant connections. The exact trajectory of the structural changes taking place in LGN is unclear but our data shows that even after years of low vision, the LGN in RPE65 patients has the potential for plasticity and expansion to a nearly normal volume one year after gene therapy administration.

13.
J Rural Health ; 38(1): 93-99, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33666274

RESUMO

PURPOSE: Rural areas of the United States have experienced outbreaks of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections among people who use drugs (PWUD). Pharmacy-based interventions may play a crucial role in prevention and entry into care, especially when traditional health care access is limited. The willingness of rural PWUD to use pharmacies for HIV/HCV-related services remains unknown. The purpose of this study was to describe the factors associated with the perceived likelihood of participating in free pharmacy-based HIV and HCV testing among PWUD living in rural Kentucky. METHODS: Baseline data from the CARE2HOPE study in five Appalachian counties in eastern Kentucky were used. Participants were recruited using respondent-driven sampling and completed interviewer-administered surveys. Guided by the Andersen and Newman Framework of Health Services Utilization, we examined distributions and correlates of items regarding willingness to participate in free pharmacy-based HIV/HCV testing using logistic regression. Analyses included individuals who reported being HIV (N = 304) or HCV (N = 185) negative. FINDINGS: Seventy-five percent of PWUD reported being "very likely" to participate in free pharmacy-based HIV testing and 80% for HCV testing. Two factors were associated with being less willing to participate in free HIV testing: PWUD who previously tested for HIV (OR: 0.47, CI: 0.25-0.88) and PWUD who obtained a high school diploma or equivalent compared to those who completed less (OR: 0.50, CI: 0.26-0.99). CONCLUSION: Free pharmacy-based HIV and HCV testing was invariably acceptable among most of the rural PWUD in our sample, suggesting that pharmacies might be acceptable testing venues for this population.


Assuntos
Infecções por HIV , Hepatite C , Preparações Farmacêuticas , Farmácias , Farmácia , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Teste de HIV , Hepacivirus , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Humanos , Kentucky/epidemiologia , Aceitação pelo Paciente de Cuidados de Saúde
14.
CJC Open ; 4(2): 214-222, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35198939

RESUMO

BACKGROUND: Women with physical disabilities are faced with challenges in many aspects of life-education, work, income, relationships, as well as their general health. These women are at a greater risk of developing heart disease. This study aimed to explore the cardiac pain experiences of women with physical disabilities and heart disease within a Canadian healthcare context. METHODS: In this qualitative study, 8 women with physical disabilities and heart disease from across Canada were interviewed. They were asked about their pre-, peri-, and post-diagnostic experiences in the Canadian healthcare system. Transcripts of the interviews were analyzed using a hermeneutic phenomenological approach inspired by Ricoeur. RESULTS: Two main themes were uncovered in the analysis of the transcripts, as follows: (i) the diagnostic journey; and (ii) life with cardiac symptoms and a disability. The women indicated that they had experienced difficulties in utilizing the Canadian healthcare system prior to receiving a cardiac diagnosis, including long waitlists, expensive and unreliable transport, issues with accessibility, and dealing with providers' attitudinal barriers regarding disability. Receiving a diagnosis was challenging due to poor relationships with healthcare providers; however, having a same-sex provider seemed essential to receiving adequate care. Self-managing a disability and heart disease had significant physical and psychological impact, which was lightened by financial and social supports, modified lifestyle choices, and self-advocacy. CONCLUSIONS: Women with physical disabilities are often forgotten in discussions encompassing equity and inclusion. The participants' experiences offer insight into what changes are needed within the Canadian healthcare system in order to improve outcomes for these women.


CONTEXTE: Les femmes qui présentent une incapacité physique doivent composer avec des défis dans de nombreux aspects de leur vie, notamment en ce qui touche l'éducation, le travail, le revenu, les relations et la santé en général. Le risque de cardiopathie est plus important dans leur cas. Cette étude visait à examiner comment la douleur cardiaque est vécue par les femmes présentant une incapacité physique et une cardiopathie dans le contexte des soins de santé au Canada. MÉTHODOLOGIE: Dans le cadre de cette étude qualitative, huit femmes présentant une incapacité physique et une cardiopathie ont participé à des entrevues menées à l'échelle du Canada. Elles ont été interrogées sur leurs expériences au sein du système de santé canadien au cours des périodes précédant, entourant et suivant le diagnostic. Les transcriptions des entrevues ont été analysées en fonction d'une approche phénoménologique herméneutique inspirée par Ricœur. RÉSULTATS: Deux grands thèmes ressortent de l'analyse des transcriptions, à savoir : (i) le parcours diagnostique; (ii) la vie avec des symptômes cardiaques et une incapacité physique. Les femmes interrogées ont indiqué qu'elles avaient éprouvé des difficultés dans leur parcours au sein du système de santé canadien avant de recevoir un diagnostic en cardiologie, évoquant à cet égard les longues listes d'attente, les services de transport coûteux et peu fiables, les problèmes d'accessibilité et les obstacles liés à l'attitude des fournisseurs de soins vis-à-vis de l'incapacité physique. Le fait de recevoir un diagnostic a été éprouvant en raison de rapports difficiles avec les fournisseurs de soins de santé; cependant, le fait d'avoir un fournisseur de soins de sexe féminin semblait être une condition essentielle à une prestation de soins adéquate. L'autoprise en charge d'une incapacité physique et d'une cardiopathie a eu des répercussions physiques et psychologiques importantes qui ont pu être allégées par le soutien financier et social, des modifications des habitudes de vie et l'autonomie sociale. CONCLUSIONS: Les femmes qui présentent une incapacité physique sont souvent laissées pour compte dans les discussions portant sur l'équité et l'inclusion. Le vécu des participantes donne un aperçu des changements qui doivent être apportés au sein du système de santé canadien afin d'améliorer les résultats chez ces femmes.

15.
J Biogeogr ; 49(5): 979-992, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35506011

RESUMO

Aim: Comprehensive, global information on species' occurrences is an essential biodiversity variable and central to a range of applications in ecology, evolution, biogeography and conservation. Expert range maps often represent a species' only available distributional information and play an increasing role in conservation assessments and macroecology. We provide global range maps for the native ranges of all extant mammal species harmonised to the taxonomy of the Mammal Diversity Database (MDD) mobilised from two sources, the Handbook of the Mammals of the World (HMW) and the Illustrated Checklist of the Mammals of the World (CMW). Location: Global. Taxon: All extant mammal species. Methods: Range maps were digitally interpreted, georeferenced, error-checked and subsequently taxonomically aligned between the HMW (6253 species), the CMW (6431 species) and the MDD taxonomies (6362 species). Results: Range maps can be evaluated and visualised in an online map browser at Map of Life (mol.org) and accessed for individual or batch download for non-commercial use. Main conclusion: Expert maps of species' global distributions are limited in their spatial detail and temporal specificity, but form a useful basis for broad-scale characterizations and model-based integration with other data. We provide georeferenced range maps for the native ranges of all extant mammal species as shapefiles, with species-level metadata and source information packaged together in geodatabase format. Across the three taxonomic sources our maps entail, there are 1784 taxonomic name differences compared to the maps currently available on the IUCN Red List website. The expert maps provided here are harmonised to the MDD taxonomic authority and linked to a community of online tools that will enable transparent future updates and version control.

16.
Acta Crystallogr Sect E Struct Rep Online ; 67(Pt 4): o755, 2011 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-21754052

RESUMO

In the title compound, C(12)H(9)Br(2)N, the dihedral angle between the benzene rings is 47.32 (5)°, whereas the pitch angles, or the angles between the mean plane of each aryl group 'propeller blade' and the plane defined by the aryl bridging C-N-C angle, are 18.1 (2) and 31.7 (2)°. No inter-molecular N-H hydrogen bonding is present in the crystal; however, there is a short inter-molecular Br⋯Br contact of 3.568 (1) Å.

17.
Cureus ; 13(5): e15242, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34188984

RESUMO

We present a rare case in which malignant catatonia led to acute liver failure (ALF). A 19-year-old male was admitted for psychosis and developed ALF with a peak aspartate aminotransferase and alanine aminotransferase of 5,728 U/L and 7,735 U/L, respectively, and a peak international normalized ratio of 7.1. Liver biopsy showed significant confluent necrosis involving >70% of the liver tissue. He was listed for a liver transplant but was ultimately taken off of because of significant improvement with treatment by N-acetylcysteine infusion. Through our research, we found that symptoms of hepatitis can be seen with psychotic disorders, but ALF is rare.

18.
Nutrients ; 13(2)2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33572488

RESUMO

Food fortification is designed to improve the nutritional profile of diets. The purpose of this research was to estimate the potential nutrient contribution of fortified maize flour, oil, rice, salt, and wheat flour in 153 countries, using the national intake (or availability) of the food and the nutrient levels required for fortification. This was done under two scenarios-maximum, where 100% of the food is assumed to be industrially processed and fortified, and realistic, where the maximum value is adjusted based on the percent of the food that is industrially processed and fortified. Under the maximum scenario, the median Estimated Average Requirements (EARs) met ranged from 22-75% for 14 nutrients (vitamins A, B1, B2, B3, B6, B12, D, E, folic acid and calcium, fluoride, iron, selenium and zinc), and 338% for iodine. In the realistic scenario, the median EARs met were 181% for iodine and <35% for the other nutrients. In both scenarios, the median Tolerable Upper Intake Levels (ULs) met were <55% for all nutrients. Under the realistic scenario, no country exceeded 100% of the UL for any nutrient. Current fortification practices of the five foods of interest have the global potential to contribute up to 15 nutrients to the diets of people, with minimal risk of exceeding ULs.


Assuntos
Alimentos Fortificados , Micronutrientes/administração & dosagem , Oryza , Cloreto de Sódio na Dieta/análise , Triticum , Zea mays , Ingestão de Alimentos , Farinha/análise , Humanos , Micronutrientes/análise , Nível de Efeito Adverso não Observado , Necessidades Nutricionais , Óleos de Plantas/análise
19.
Sci Total Environ ; 764: 143963, 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33385644

RESUMO

Consumption of licit and/or illicit compounds during sporting events has traditionally been monitored using population surveys, medical records, and law enforcement seizure data. This pilot study evaluated the temporal and geospatial patterns in drug consumption during a university football game from wastewater using liquid chromatography tandem mass spectrometry (LC-MS/MS). Untreated wastewater samples were collected from three locations within or near the same football stadium every 30 min during a university football game. This analysis leveraged two LCMS/ MS instruments (Waters Acquity TQD and a Shimadzu 8040) to analyze samples for 58 licit or illicit compounds and some of their metabolites. Bayesian multilevel models were implemented to estimate mass load and population-level drug consumption, while accounting for multiple instrument runs and concentrations censored at the lower limit of quantitation. Overall, 29 compounds were detected in at least one wastewater sample collected during the game. The 10 most common compounds included opioids, anorectics, stimulants, and decongestants. For compounds detected in more than 50% of samples, temporal trends in median mass load were correlated with the timing of the game; peak loads for cocaine and tramadol occurred during the first quarter of the game and for phentermine during the third quarter. Stadium-wide estimates of the number of doses of drugs consumed were rank ordered as follows: oxycodone (n = 3246) > hydrocodone (n = 2260) > phentermine (n = 513) > cocaine (n = 415) > amphetamine (n = 372) > tramadol (n = 360) > pseudoephedrine (n = 324). This analysis represents the most comprehensive assessment of drug consumption during a university football game and indicates that wastewater-based epidemiology has potential to inform public health interventions focused on reducing recreational drug consumption during large-scale sporting events.


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Teorema de Bayes , Cromatografia Líquida , Humanos , Projetos Piloto , Detecção do Abuso de Substâncias , Espectrometria de Massas em Tandem , Universidades , Águas Residuárias/análise , Poluentes Químicos da Água/análise
20.
Sci Rep ; 10(1): 18229, 2020 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-33106580

RESUMO

A major limitation hindering the widespread use of synthetic phages in medical and industrial settings is the lack of an efficient phage-engineering platform. Classical T4 phage engineering and several newly proposed methods are often inefficient and time consuming and consequently, only able to produce an inconsistent range of genomic editing rates between 0.03-3%. Here, we review and present new understandings of the CRISPR/Cas9 assisted genome engineering technique that significantly improves the genomic editing rate of T4 phages. Our results indicate that crRNAs selection is a major rate limiting factor in T4 phage engineering via CRISPR/Cas9. We were able to achieve an editing rate of > 99% for multiple genes that functionalizes the phages for further applications. We envision that this improved phage-engineering platform will accelerate the fields of individualized phage therapy, biocontrol, and rapid diagnostics.


Assuntos
Bactérias/virologia , Bacteriófago T4/genética , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Engenharia Genética/normas , Ensaio de Placa Viral/métodos , Bactérias/metabolismo , Bacteriófago T4/metabolismo , Edição de Genes/normas , Engenharia Genética/métodos
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