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1.
Nature ; 592(7855): 564-570, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33883735

RESUMO

The social cost of methane (SC-CH4) measures the economic loss of welfare caused by emitting one tonne of methane into the atmosphere. This valuation may in turn be used in cost-benefit analyses or to inform climate policies1-3. However, current SC-CH4 estimates have not included key scientific findings and observational constraints. Here we estimate the SC-CH4 by incorporating the recent upward revision of 25 per cent to calculations of the radiative forcing of methane4, combined with calibrated reduced-form global climate models and an ensemble of integrated assessment models (IAMs). Our multi-model mean estimate for the SC-CH4 is US$933 per tonne of CH4 (5-95 per cent range, US$471-1,570 per tonne of CH4) under a high-emissions scenario (Representative Concentration Pathway (RCP) 8.5), a 22 per cent decrease compared to estimates based on the climate uncertainty framework used by the US federal government5. Our ninety-fifth percentile estimate is 51 per cent lower than the corresponding figure from the US framework. Under a low-emissions scenario (RCP 2.6), our multi-model mean decreases to US$710 per tonne of CH4. Tightened equilibrium climate sensitivity estimates paired with the effect of previously neglected relationships between uncertain parameters of the climate model lower these estimates. We also show that our SC-CH4 estimates are sensitive to model combinations; for example, within one IAM, different methane cycle sub-models can induce variations of approximately 20 per cent in the estimated SC-CH4. But switching IAMs can more than double the estimated SC-CH4. Extending our results to account for societal concerns about equity produces SC-CH4 estimates that differ by more than an order of magnitude between low- and high-income regions. Our central equity-weighted estimate for the USA increases to US$8,290 per tonne of CH4 whereas our estimate for sub-Saharan Africa decreases to US$134 per tonne of CH4.


Assuntos
Mudança Climática/economia , Metano/economia , Justiça Social , Seguridade Social/economia , Incerteza , África Subsaariana , Calibragem , Modelos Climáticos , Justiça Ambiental , Humanos , Dinâmica não Linear , Probabilidade , Justiça Social/economia , Temperatura , Estados Unidos
2.
J Neurosci ; 43(9): 1492-1508, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36653191

RESUMO

NG2 is a structurally unique transmembrane chondroitin sulfate proteoglycan (CSPG). Its role in damaged spinal cord is dual. NG2 is considered one of key inhibitory factors restricting axonal growth following spinal injury. Additionally, we have recently detected its novel function as a blocker of axonal conduction. Some studies, however, indicate the importance of NG2 presence in the formation of synaptic contacts. We hypothesized that the optimal treatment would be neutralization of inhibitory functions of NG2 without its physical removal. Acute intraspinal injections of anti-NG2 monoclonal antibodies reportedly prevented an acute block of axonal conduction by exogenous NG2. For prolonged delivery of NG2 function neutralizing antibody, we have developed a novel gene therapy: adeno-associated vector (AAV) construct expressing recombinant single-chain variable fragment anti-NG2 antibody (AAV-NG2Ab). We examined effects of AAV-NG2Ab alone or in combination with neurotrophin NT-3 in adult female rats with thoracic T10 contusion injuries. A battery of behavioral tests was used to evaluate locomotor function. In vivo single-cell electrophysiology was used to evaluate synaptic transmission. Lower urinary tract function was assessed during the survival period using metabolic chambers. Terminal cystometry, with acquisition of external urethral sphincter activity and bladder pressure, was used to evaluate bladder function. Both the AAV-NG2Ab and AAV-NG2Ab combined with AAV-NT3 treatment groups demonstrated significant improvements in transmission, locomotion, and bladder function compared with the control (AAV-GFP) group. These functional improvements associated with improved remyelination and plasticity of 5-HT fibers. The best results were observed in the group that received combinational AAV-NG2Ab+AAV-NT3 treatment.SIGNIFICANCE STATEMENT We recently demonstrated beneficial, but transient, effects of neutralization of the NG2 proteoglycan using monoclonal antibodies delivered intrathecally via osmotic mini-pumps after spinal cord injury. Currently, we have developed a novel gene therapy tool for prolonged and clinically relevant delivery of a recombinant single-chain variable fragment anti-NG2 antibody: AAV-rh10 serotype expressing scFv-NG2 (AAV-NG2Ab). Here, we examined effects of AAV-NG2Ab combined with transgene delivery of Neurotrophin-3 (AAV-NT3) in adult rats with thoracic contusion injuries. The AAV-NG2Ab and AAV-NG2Ab+AAV-NT3 treatment groups demonstrated significant improvements of locomotor function and lower urinary tract function. Beneficial effects of this novel gene therapy on locomotion and bladder function associated with improved transmission to motoneurons and plasticity of axons in damaged spinal cord.


Assuntos
Contusões , Anticorpos de Cadeia Única , Traumatismos da Medula Espinal , Sistema Urinário , Animais , Feminino , Ratos , Contusões/terapia , Locomoção , Fatores de Crescimento Neural , Recuperação de Função Fisiológica/genética , Medula Espinal , Transmissão Sináptica , Neurotrofina 3
3.
Ann Surg ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557806

RESUMO

OBJECTIVE: To identify the modifiable and non-modifiable risk factors associated with post-intubation hypotension (PIH) among trauma patients who required endotracheal intubation (ETI) in the trauma bay. SUMMARY BACKGROUND DATA: ETI has been associated with hemodynamic instability, termed PIH, yet its risk factors in trauma patients remain under-investigated. METHODS: This is a prospective observational study at a level I trauma center over 4 years (2019-2022). All adult (≥18) trauma patients requiring ETI in the trauma bay were included. Blood pressure was monitored both pre- and post-intubation. Multivariable logistic regression analysis was performed to identify the modifiable and non-modifiable factors associated with PIH. RESULTS: 708 patients required ETI in the trauma bay, of which, 435 (61.4%) developed PIH. The mean (SD) age was 43 (21) and 71% were male. Median [IQR] arrival GCS was 7 [3-13]. Patients who developed PIH had a lower mean (SD) pre-intubation SBP (118 (46) vs. 138 (28), P<0.001) and higher median [IQR] ISS (27 [21-38] vs. 21 [9-26], P<0.001). Multivariable regression analysis identified BMI>25, increasing ISS, penetrating injury, spinal cord injury, Pre-intubation PRBC requirements, and diabetes mellitus as non-modifiable risk factors associated with increased odds of PIH. In contrast, pre-intubation administration of 3% hypertonic saline and vasopressors were identified as the modifiable factors significantly associated with reduced PIH. CONCLUSION: More than half of the patients requiring ETI in the trauma bay developed PIH. This study identified modifiable and non-modifiable risk factors that influence the development of PIH, which will help physicians when considering ETI upon patient arrival. LEVEL OF EVIDENCE: Level III, Prognostic Study.

4.
Sensors (Basel) ; 24(8)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38676123

RESUMO

This paper describes the use of wireless smart sensors for examining the underlying mechanism for the wind-induced vibration of high-mast illumination pole (HMIP) structures. HMIPs are tall, slender structures with low inherent damping. Video recordings of multiple HMIPs showed considerable vibrations of these HMIPs under wind loading in the state of Kansas. The HMIPs experienced cyclic large-amplitude displacements at the top, which can produce high-stress demand and lead to fatigue cracking at the bottom of the pole. In this study, the natural frequencies of the HMIP were assessed using pluck tests and finite element modeling, and the recorded vibration frequencies were obtained through computer vision-based video analysis. Meanwhile, a 30.48 m tall HMIP with three LED luminaires made of galvanized steel located in Wakeeney, Kansas, was selected for long-term vibration monitoring using wireless smart sensors to investigate the underlying mechanism for the excessive wind-induced vibrations. Data analysis with the long-term monitoring data indicates that while vortex-induced vibration occurs frequently at relatively low amplitude, buffeting-induced vibration was the leading cause of the excessive vibrations of the monitored HMIP. The findings provide crucial information to guide the design of vibration mitigation strategies for these HMIP structures.

5.
Sensors (Basel) ; 24(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38894475

RESUMO

A significant percentage of bridges in the United States are serving beyond their 50-year design life, and many of them are in poor condition, making them vulnerable to fatigue cracks that can result in catastrophic failure. However, current fatigue crack inspection practice based on human vision is time-consuming, labor intensive, and prone to error. We present a novel human-centered bridge inspection methodology to enhance the efficiency and accuracy of fatigue crack detection by employing advanced technologies including computer vision and augmented reality (AR). In particular, a computer vision-based algorithm is developed to enable near-real-time fatigue crack detection by analyzing structural surface motion in a short video recorded by a moving camera of the AR headset. The approach monitors structural surfaces by tracking feature points and measuring variations in distances between feature point pairs to recognize the motion pattern associated with the crack opening and closing. Measuring distance changes between feature points, as opposed to their displacement changes before this improvement, eliminates the need of camera motion compensation and enables reliable and computationally efficient fatigue crack detection using the nonstationary AR headset. In addition, an AR environment is created and integrated with the computer vision algorithm. The crack detection results are transmitted to the AR headset worn by the bridge inspector, where they are converted into holograms and anchored on the bridge surface in the 3D real-world environment. The AR environment also provides virtual menus to support human-in-the-loop decision-making to determine optimal crack detection parameters. This human-centered approach with improved visualization and human-machine collaboration aids the inspector in making well-informed decisions in the field in a near-real-time fashion. The proposed crack detection method is comprehensively assessed using two laboratory test setups for both in-plane and out-of-plane fatigue cracks. Finally, using the integrated AR environment, a human-centered bridge inspection is conducted to demonstrate the efficacy and potential of the proposed methodology.


Assuntos
Algoritmos , Realidade Aumentada , Humanos , Processamento de Imagem Assistida por Computador/métodos
6.
J Surg Res ; 282: 129-136, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36272231

RESUMO

INTRODUCTION: Bladder and ureteral injuries are uncommon in trauma patients but are associated with increased morbidity and mortality. Patients presenting with such injuries may undergo either open surgical repair or laparoscopic repair. We aimed to compare outcomes of open surgical approach and laparoscopy in trauma patients with isolated bladder and ureteral injury. We hypothesized that laparoscopy is associated with improved outcomes. METHODS: We performed a 2017 review of American College of Surgeons Trauma Quality Improvement Program and identified trauma patients with bladder and ureteral injury who underwent open surgical repair or laparoscopy. A 1:1 propensity score matching was performed adjusting for demographics, emergency department vitals (systolic blood pressure, heart rate, Glasgow Coma Scale), mechanism of injury, Injury Severity Score, each body region Abbreviated Injury Scale score, and transfusion units. Outcomes were rates of in-hospital major complications and mortality. RESULTS: Of the 1,004,440 trauma patients, 384 patients (open: 192 and laparoscopy: 192) were matched and included. The mean age was 36 ± 15 y, Injury Severity Score was 27 [27-48], 77% were males, and 56% of patients had a blunt mechanism of injury, and 44% had penetrating injuries. Overall mortality was 7.3%. On univariate analysis, mortality was lower in the open group as compared to the laparoscopy group (10.4% versus 4.2%, P = 0.019) and survivor-only hospital length of stay was longer in the open group (8 [8-9] versus 7 [5-11], P = 0.008). There was no difference in overall major complications (23% versus 21%, P = 0.621). On multivariate analysis, open surgical repair was independently associated with lower odds of mortality (adjusted odds ratio: 0.405, 95% confidence interval: [0.17-0.95], P-value = 0.038) CONCLUSIONS: In our analysis open surgical repair of bladder and ureteral injuries was associated with lower mortality with other outcomes being similar when compared to laparoscopy. Laparoscopic surgical repair may not have an advantage over the open surgical repair for bladder and ureteral injuries. Further prospective studies are needed to delineate the ideal surgical approach for these injuries.


Assuntos
Traumatismos Abdominais , Laparoscopia , Doenças Urológicas , Masculino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Feminino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos , Escala de Gravidade do Ferimento , Pontuação de Propensão , Laparoscopia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
7.
Opt Express ; 30(14): 24326-24351, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36236990

RESUMO

The atmospheric concentration of methane has more than doubled since the start of the Industrial Revolution. Methane is the second-most-abundant greenhouse gas created by human activities and a major driver of climate change. This APS-Optica report provides a technical assessment of the current state of monitoring U.S. methane emissions from oil and gas operations, which accounts for roughly 30% of U.S. anthropogenic methane emissions. The report identifies current technological and policy gaps and makes recommendations for the federal government in three key areas: methane emissions detection, reliable and systematized data and models to support mitigation measures, and effective regulation.


Assuntos
Poluentes Atmosféricos , Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Humanos , Metano/análise
8.
Allergy ; 77(1): 173-185, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34080210

RESUMO

BACKGROUND: It is unclear whether asthma and its allergic phenotype are risk factors for hospitalization or severe disease from SARS-CoV-2. METHODS: All patients over 28 days old testing positive for SARS-CoV-2 between March 1 and September 30, 2020, were retrospectively identified and characterized through electronic analysis at Stanford. A sub-cohort was followed prospectively to evaluate long-term COVID-19 symptoms. RESULTS: 168,190 patients underwent SARS-CoV-2 testing, and 6,976 (4.15%) tested positive. In a multivariate analysis, asthma was not an independent risk factor for hospitalization (OR 1.12 [95% CI 0.86, 1.45], p = .40). Among SARS-CoV-2-positive asthmatics, allergic asthma lowered the risk of hospitalization and had a protective effect compared with non-allergic asthma (OR 0.52 [0.28, 0.91], p = .026); there was no association between baseline medication use as characterized by GINA and hospitalization risk. Patients with severe COVID-19 disease had lower eosinophil levels during hospitalization compared with patients with mild or asymptomatic disease, independent of asthma status (p = .0014). In a patient sub-cohort followed longitudinally, asthmatics and non-asthmatics had similar time to resolution of COVID-19 symptoms, particularly lower respiratory symptoms. CONCLUSIONS: Asthma is not a risk factor for more severe COVID-19 disease. Allergic asthmatics were half as likely to be hospitalized with COVID-19 compared with non-allergic asthmatics. Lower levels of eosinophil counts (allergic biomarkers) were associated with a more severe COVID-19 disease trajectory. Recovery was similar among asthmatics and non-asthmatics with over 50% of patients reporting ongoing lower respiratory symptoms 3 months post-infection.


Assuntos
Asma , COVID-19 , Asma/diagnóstico , Asma/epidemiologia , Teste para COVID-19 , Humanos , Fenótipo , Estudos Retrospectivos , SARS-CoV-2
9.
Allergy ; 77(5): 1389-1407, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35073410

RESUMO

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) health impacts of climate change. These impacts vary depending on vulnerability (i.e., existing diseases) and the international, economic, political, and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.


Assuntos
Mudança Climática , Saúde Global , Poluição Ambiental , Humanos
10.
Sensors (Basel) ; 22(14)2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35890756

RESUMO

This paper presents a field implementation of the structural health monitoring (SHM) of fatigue cracks for steel bridge structures. Steel bridges experience fatigue cracks under repetitive traffic loading, which pose great threats to their structural integrity and can lead to catastrophic failures. Currently, accurate and reliable fatigue crack monitoring for the safety assessment of bridges is still a difficult task. On the other hand, wireless smart sensors have achieved great success in global SHM by enabling long-term modal identifications of civil structures. However, long-term field monitoring of localized damage such as fatigue cracks has been limited due to the lack of effective sensors and the associated algorithms specifically designed for fatigue crack monitoring. To fill this gap, this paper proposes a wireless large-area strain sensor (WLASS) to measure large-area strain fatigue cracks and develops an effective algorithm to process the measured large-area strain data into actionable information. The proposed WLASS consists of a soft elastomeric capacitor (SEC) used to measure large-area structural surface strain, a capacitive sensor board to convert the signal from SEC to a measurable change in voltage, and a commercial wireless smart sensor platform for triggered-based wireless data acquisition, remote data retrieval, and cloud storage. Meanwhile, the developed algorithm for fatigue crack monitoring processes the data obtained from the WLASS under traffic loading through three automated steps, including (1) traffic event detection, (2) time-frequency analysis using a generalized Morse wavelet (GM-CWT) and peak identification, and (3) a modified crack growth index (CGI) that tracks potential fatigue crack growth. The developed WLASS and the algorithm present a complete system for long-term fatigue crack monitoring in the field. The effectiveness of the proposed time-frequency analysis algorithm based on GM-CWT to reliably extract the impulsive traffic events is validated using a numerical investigation. Subsequently, the developed WLASS and algorithm are validated through a field deployment on a steel highway bridge in Kansas City, KS, USA.


Assuntos
Tecnologia de Sensoriamento Remoto , Aço , Colapso Estrutural , Humanos
11.
Allergy ; 76(6): 1640-1660, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33811364

RESUMO

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.


Assuntos
COVID-19 , Hipersensibilidade , Vacinas , Vacinas contra COVID-19 , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/epidemiologia , Hipersensibilidade/etiologia , Pandemias , SARS-CoV-2 , Vacinas/efeitos adversos
12.
Philos Trans A Math Phys Eng Sci ; 379(2195): 20190545, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33641458

RESUMO

We examine the resolution dependence of errors in extreme sub-daily precipitation in available high-resolution climate models. We find that simulated extreme precipitation increases as horizontal resolution increases but that appropriately constructed model skill metrics do not significantly change. We find little evidence that simulated extreme winter or summer storm processes significantly improve with the resolution because the model performance changes identified are consistent with expectations from scale dependence arguments alone. We also discuss the implications of these scale-dependent limitations on the interpretation of simulated extreme precipitation. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.

13.
Sensors (Basel) ; 21(21)2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34770326

RESUMO

The authors have previously proposed corrugated soft elastomeric capacitors (cSEC) to create ultra compliant scalable strain gauges. The cSEC technology has been successfully demonstrated in engineering and biomechanical applications for in-plane strain measurements. This study extends work on the cSEC to evaluate its performance at measuring angular rotation when installed folded at the junction of two plates. The objective is to characterize the sensor's electromechanical behavior anticipating applications to the monitoring of welded connections in steel components. To do so, an electromechanical model that maps the cSEC signal to bending strain induced by angular rotation is derived and adjusted using a validated finite element model. Given the difficulty in mapping strain measurements to rotation, an algorithm termed angular rotation index (ARI) is formulated to link measurements to angular rotation directly. Experimental work is conducted on a hollow structural section (HSS) steel specimen equipped with cSECs subjected to compression to generate angular rotations at the corners within the cross-section. Results confirm that the cSEC is capable of tracking angular rotation-induced bending strain linearly, however with accuracy levels significantly lower than found over flat configurations. Nevertheless, measurements were mapped to angular rotations using the ARI, and it was found that the ARI mapped linearly to the angle of rotation, with an accuracy of 0.416∘.


Assuntos
Aço , Fenômenos Biomecânicos , Elasticidade , Pressão
14.
Am J Obstet Gynecol ; 223(1): 85.e1-85.e19, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32251649

RESUMO

The coronavirus disease 2019 pandemic warrants an unprecedented global healthcare response requiring maintenance of existing hospital-based services while simultaneously preparing for high-acuity care for infected and sick individuals. Hospitals must protect patients and the diverse healthcare workforce by conserving personal protective equipment and redeployment of facility resources. While each hospital or health system must evaluate their own capabilities and surge capacity, we present principles of management of surgical services during a health emergency and provide specific guidance to help with decision making. We review the limited evidence from past hospital and community responses to various health emergencies and focus on systematic methods for adjusting surgical services to create capacity, addressing the specific risks of coronavirus disease 2019. Successful strategies for tiered reduction of surgical cases involve multidisciplinary engagement of the entire healthcare system and use of a structured risk-assessment categorization scheme that can be applied across the institution. Our institution developed and operationalized this approach over 3 working days, indicating that immediate implementation is feasible in response to an unforeseen healthcare emergency.


Assuntos
Infecções por Coronavirus/epidemiologia , Ginecologia/organização & administração , Obstetrícia/organização & administração , Pneumonia Viral/epidemiologia , Centro Cirúrgico Hospitalar/organização & administração , Betacoronavirus , COVID-19 , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pandemias , Gravidez , Medição de Risco , SARS-CoV-2
15.
Health Commun ; 34(10): 1075-1084, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-29634356

RESUMO

This study highlights the role of local communities in creating culturally rooted health information resources based on comparative effectiveness research (CER), depicting the role of culture in creating entry points for building community-grounded communication structures for evidence-based health knowledge. We report the results from running a year-long culture-centered campaign that was carried out among African American communities in two counties, Lake and Marion County, in Indiana addressing basic evidence-based knowledge on four areas of cardiovascular disease (CVD). Campaign effectiveness was tested through an experimental design with post-test knowledge of CER among African Americans in these counties compared to CER knowledge among African Americans in a comparable control county (Allen). Our campaign, based on the principles of the culture-centered approach (CCA), increased community CER knowledge in the experimental communities relative to a community that did not receive the culturally centered health information campaign. The CCA-based campaign developed by community members and distributed through the mass media, community wide channels such as health fairs and church meetings, postcards, and face-to-face interventions explaining the postcards improved CER knowledge in specific areas (ACE-I/ARBs, atrial fibrillation, and renal artery stenosis) in the CCA communities as compared to the control community.


Assuntos
Negro ou Afro-Americano , Doenças Cardiovasculares/etnologia , Participação da Comunidade/métodos , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde/organização & administração , Disseminação de Informação/métodos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Comunicação , Pesquisa Comparativa da Efetividade/organização & administração , Carência Cultural , Prática Clínica Baseada em Evidências , Disparidades nos Níveis de Saúde , Humanos , Indiana , Participação do Paciente
16.
Proc Natl Acad Sci U S A ; 112(11): 3463-8, 2015 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-25733901

RESUMO

Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders.


Assuntos
Comportamento Animal , Encéfalo/metabolismo , Dopamina/metabolismo , Resistência à Insulina , Envelhecimento/patologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Ansiedade/metabolismo , Ansiedade/patologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/ultraestrutura , Depressão/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Mitocôndrias/ultraestrutura , Estresse Oxidativo/efeitos dos fármacos , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Eur J Neurosci ; 45(1): 106-120, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27564091

RESUMO

The mesocortical and mesolimbic dopamine systems regulate cognitive and motivational processes and are strongly implicated in neuropsychiatric disorders in which these processes are disturbed. Sex differences and sex hormone modulation are also known for these dopamine-sensitive behaviours in health and disease. One relevant mechanism of hormone impact appears to be regulation of cortical and subcortical dopamine levels. This study asked whether this regulation of dopamine tone is a consequence of sex or sex hormone impact on the firing modes of ventral midbrain dopamine neurons. To address this, single unit extracellular recordings made in the ventral tegmental area and substantia nigra were compared among urethane-anaesthetized adult male, female, gonadectomized male rats. These comparisons showed that gonadectomy had no effect on nigral cells and no effects on pacemaker, bursty, single-spiking or random modes of dopamine activity in the ventral tegmental area. However, it did significantly and selectively increase burst firing in these cells in a testosterone-sensitive, estradiol-insensitive manner. Given the roles of prefrontal cortex (PFC) in modulating midbrain dopamine cell firing, we next asked whether gonadectomy's effects on dopamine cell bursting had correlated effects on the activity of ventral tegmentally projecting prefrontal cortical neurons. We found that gonadectomy indeed significantly and selectively increased burst firing in ventral tegmentally projecting but not neighbouring prefrontal cells. These effects were also androgen-sensitive. Together, these findings suggest a working model wherein androgen influence over the activity of PFC neurons regulates its top-down modulation of mesocortical and mesolimbic dopamine systems and related dopamine-sensitive behaviours.


Assuntos
Castração , Dopamina/metabolismo , Neurônios Dopaminérgicos/citologia , Córtex Pré-Frontal/fisiologia , Substância Negra/citologia , Tegmento Mesencefálico/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Castração/métodos , Feminino , Masculino , Ratos Sprague-Dawley , Caracteres Sexuais
19.
Proc Natl Acad Sci U S A ; 111(46): 16297-302, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25368189

RESUMO

Presently, there are no global measurement constraints on the surface emissivity at wavelengths longer than 15 µm, even though this surface property in this far-IR region has a direct impact on the outgoing longwave radiation (OLR) and infrared cooling rates where the column precipitable water vapor (PWV) is less than 1 mm. Such dry conditions are common for high-altitude and high-latitude locations, with the potential for modeled climate to be impacted by uncertain surface characteristics. This paper explores the sensitivity of instantaneous OLR and cooling rates to changes in far-IR surface emissivity and how this unconstrained property impacts climate model projections. At high latitudes and altitudes, a 0.05 change in emissivity due to mineralogy and snow grain size can cause a 1.8-2.0 W m(-2) difference in the instantaneous clear-sky OLR. A variety of radiative transfer techniques have been used to model the far-IR spectral emissivities of surface types defined by the International Geosphere-Biosphere Program. Incorporating these far-IR surface emissivities into the Representative Concentration Pathway (RCP) 8.5 scenario of the Community Earth System Model leads to discernible changes in the spatial patterns of surface temperature, OLR, and frozen surface extent. The model results differ at high latitudes by as much as 2°K, 10 W m(-2), and 15%, respectively, after only 25 y of integration. Additionally, the calculated difference in far-IR emissivity between ocean and sea ice of between 0.1 and 0.2, suggests the potential for a far-IR positive feedback for polar climate change.

20.
Health Commun ; 32(10): 1241-1251, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27484329

RESUMO

Across the life course, African Americans bear an unequal burden of disease compared to other racial groups. In spite of the widespread acknowledgment of racial health disparities, the voices of African Americans, their articulations of health and their local etiologies of health disparities are limited. In this article, we highlight the important role of communication scholarship to understand the everyday enactment of health disparities. Drawing upon the culture-centered approach (CCA) to co-construct narratives of health with African Americans residents of Lake County, Indiana, we explore the presence of stress in the everyday narratives of health. These narratives voice the social and structural sources of stress, and articulate resistive coping strategies embedded in relationship to structures.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Narração , Estresse Psicológico/psicologia , Adaptação Psicológica , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/mortalidade , Humanos , Indiana , Entrevistas como Assunto
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