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1.
Chem Rev ; 123(6): 2737-2831, 2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36898130

RESUMO

Confined fluids and electrolyte solutions in nanopores exhibit rich and surprising physics and chemistry that impact the mass transport and energy efficiency in many important natural systems and industrial applications. Existing theories often fail to predict the exotic effects observed in the narrowest of such pores, called single-digit nanopores (SDNs), which have diameters or conduit widths of less than 10 nm, and have only recently become accessible for experimental measurements. What SDNs reveal has been surprising, including a rapidly increasing number of examples such as extraordinarily fast water transport, distorted fluid-phase boundaries, strong ion-correlation and quantum effects, and dielectric anomalies that are not observed in larger pores. Exploiting these effects presents myriad opportunities in both basic and applied research that stand to impact a host of new technologies at the water-energy nexus, from new membranes for precise separations and water purification to new gas permeable materials for water electrolyzers and energy-storage devices. SDNs also present unique opportunities to achieve ultrasensitive and selective chemical sensing at the single-ion and single-molecule limit. In this review article, we summarize the progress on nanofluidics of SDNs, with a focus on the confinement effects that arise in these extremely narrow nanopores. The recent development of precision model systems, transformative experimental tools, and multiscale theories that have played enabling roles in advancing this frontier are reviewed. We also identify new knowledge gaps in our understanding of nanofluidic transport and provide an outlook for the future challenges and opportunities at this rapidly advancing frontier.

2.
J Neurosci Res ; 102(5): e25338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706427

RESUMO

The enzyme indoleamine 2,3 dioxygenase 1 (IDO1) catalyzes the rate-limiting step in the kynurenine pathway (KP) which produces both neuroprotective and neurotoxic metabolites. Neuroinflammatory signals produced as a result of pathological conditions can increase production of IDO1 and boost its enzymatic capacity. IDO1 and the KP have been implicated in behavioral recovery after human traumatic brain injury (TBI), but their roles in experimental models of TBI are for the most part unknown. We hypothesized there is an increase in KP activity in the fluid percussion injury (FPI) model of TBI, and that administration of an IDO1 inhibitor will improve neurological recovery. In this study, adult male Sprague Dawley rats were subjected to FPI or sham injury and received twice-daily oral administration of the IDO1 inhibitor PF-06840003 (100 mg/kg) or vehicle control. FPI resulted in a significant increase in KP activity, as demonstrated by an increased ratio of kynurenine: tryptophan, in the perilesional neocortex and ipsilateral hippocampus 3 days postinjury (DPI), which normalized by 7 DPI. The increase in KP activity was prevented by PF-06840003. IDO1 inhibition also improved memory performance as assessed in the Barnes maze and anxiety behaviors as assessed in open field testing in the first 28 DPI. These results suggest increased KP activity after FPI may mediate neurological dysfunction, and IDO1 inhibition should be further investigated as a potential therapeutic target to improve recovery.


Assuntos
Lesões Encefálicas Traumáticas , Indolamina-Pirrol 2,3,-Dioxigenase , Masculino , Animais , Ratos Sprague-Dawley , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/enzimologia , Cinurenina/metabolismo , Modelos Animais de Doenças , Indóis/administração & dosagem , Succinimidas/administração & dosagem , Administração Oral
3.
Analyst ; 149(3): 968-974, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38197474

RESUMO

DNA nanotechnology deals with the design of non-naturally occurring DNA nanostructures that can be used in biotechnology, medicine, and diagnostics. In this study, we introduced a nucleic acid five-way junction (5WJ) structure for direct electrochemical analysis of full-length biological RNAs. To the best of our knowledge, this is the first report on the interrogation of such long nucleic acid sequences by hybridization probes attached to a solid support. A hairpin-shaped electrode-bound oligonucleotide hybridizes with three adaptor strands, one of which is labeled with methylene blue (MB). The four strands are combined into a 5WJ structure only in the presence of specific DNA or RNA analytes. Upon interrogation of a full-size 16S rRNA in the total RNA sample, the electrode-bound MB-labeled 5WJ association produces a higher signal-to-noise ratio than electrochemical nucleic acid biosensors of alternative design. This advantage was attributed to the favorable geometry on the 5WJ nanostructure formed on the electrode's surface. The 5WJ biosensor is a cost-efficient alternative to the traditional electrochemical biosensors for the analysis of nucleic acids due to the universal nature of both the electrode-bound and MB-labeled DNA components.


Assuntos
Técnicas Biossensoriais , Ácidos Nucleicos , RNA Ribossômico 16S , DNA/química , Sondas de DNA/química , Nanotecnologia , Técnicas Eletroquímicas , Hibridização de Ácido Nucleico , Azul de Metileno/química
4.
Can J Neurol Sci ; 51(2): 161-172, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36991574

RESUMO

As COVID-19 continues, a safe, cost-effective treatment strategy demands continued inquiry. Chronic neuroinflammatory disorders may appear to be of little relevance in this regard; often indolent and progressive disorders characterized by neuroinflammation (such as Alzheimer's disease (AD)) are fundamentally dissimilar in etiology and symptomology to COVID-19's rapid infectivity and pathology. However, the two disorders share extensive pathognomonic features, including at membrane, cytoplasmic, and extracellular levels, culminating in analogous immunogenic destruction of their respective organ parenchyma. We hypothesize that these mechanistic similarities may extent to therapeutic targets, namely that it is conceivable an agent against AD's immunopathy may have efficacy against COVID-19 and vice versa. It is notable that while extensively investigated, no agent has yet demonstrated significant therapeutic efficacy against AD's cognitive and memory declines. Yet this very failure has driven the development of numerous agents with strong mechanistic potential and clinical characteristics. Having already approved for clinical trials, these agents may be an expedient starting point in the urgent search for an effective COVID-19 therapy. Herein, we review the overlapping Alzheimer's/ COVID-19 targets and theorize several initial platforms.


Assuntos
Doença de Alzheimer , COVID-19 , Humanos , Doença de Alzheimer/tratamento farmacológico , Reposicionamento de Medicamentos
5.
Am J Addict ; 33(4): 385-392, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38353562

RESUMO

BACKGROUND AND OBJECTIVES: Hispanic young adults in the United States have consistently high rates of risky drinking, adverse childhood experiences (ACEs), depression, and anxiety. There is a positive association between ACEs and alcohol use among Hispanic populations; it is unknown if mental health symptomatology mediates this relationship. The purpose of this study was to test whether depression and anxiety mediated the relationship between ACEs and risky drinking among Hispanic young adults who engage in risky drinking. METHODS: Data from 264 Hispanic young adults, ages 19 to 30, were collected via an online questionnaire. Participants were recruited via social media, emails/listservs across colleges, the community, and web-panels. The questionnaire assessed ACEs, risky drinking, depression, and anxiety. We conducted a mediational analysis to test whether depression and anxiety mediated the relationship between ACEs and risky drinking. RESULTS: Of the sample, 59.8% identified as female and 40.2% as male. The average age was 24.37 (SD = 3.069). Participants (61%) identified as Mexican, Mexican American, or Chicano, and 84.1% identified as second-generation. ACEs were positively associated with risky drinking, depression, and anxiety. Depression mediated the relationship between ACEs and risky drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Depression explained the association between ACEs and risky drinking among Hispanic young adults, adding to our understanding of how mediators can illustrate pathways that lead from ACEs to risky drinking. Practitioners and interventionists should continue supporting Hispanic youth by integrating them into early prevention programs to mitigate the mental health consequences of ACEs that could lead to risky drinking.


Assuntos
Experiências Adversas da Infância , Ansiedade , Depressão , Hispânico ou Latino , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Experiências Adversas da Infância/estatística & dados numéricos , Experiências Adversas da Infância/psicologia , Hispânico ou Latino/psicologia , Hispânico ou Latino/estatística & dados numéricos , Depressão/epidemiologia , Depressão/psicologia , Depressão/etnologia , Ansiedade/psicologia , Ansiedade/epidemiologia , Ansiedade/etnologia , Assunção de Riscos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Consumo de Bebidas Alcoólicas/etnologia , Estados Unidos/epidemiologia , Inquéritos e Questionários
6.
J Environ Manage ; 365: 121365, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897080

RESUMO

Effective engagement is crucial for enhancing environmental decision-making processes, fostering more sustainable and equitable outcomes. However, the success of engagement is highly variable and context-dependent. While theoretical frameworks have been developed to explain outcome variance in engagement in environmental decision-making, they have not yet been tested in digital contexts, leaving their applicability to digital engagement processes unclear. More broadly, there are unanswered questions about the effectiveness of digital tools in achieving the goals of engagement, which have become increasingly pertinent amidst growing concerns about the potential of digital technologies for exacerbating exclusions, ethical issues, and systematically undermining democratic progress. This paper addresses this evidence gap by presenting findings from interviews with practitioners in UK public, private, and third sector organisations. Our results provide empirical insights into the technical, ethical, and inclusivity debates surrounding digital tools and their effectiveness in promoting accessible engagement, high-quality social interaction, place-based decision-making, and more trustworthy and credible outcomes. Our findings indicate that while current engagement theories are applicable to digital environments, the key explanatory factors acquire new dimensions in digital compared to in-person contexts. Drawing on the findings, this study contributes novel insights to expand current theory for explaining "what works" in engagement in environmental decisions, enhancing its relevance and applicability in the digital age. The paper concludes with evidence-led recommendations for environmental practitioners to improve engagement processes in digital and remote settings.


Assuntos
Tomada de Decisões , Humanos , Tecnologia Digital , Conservação dos Recursos Naturais/métodos
7.
J Neurosci ; 41(36): 7687-7696, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34290080

RESUMO

Alzheimer's disease is associated with poor sleep, but the impact of tau and ß-amyloid (Aß) pathology on sleep remains largely unknown. Here, we test the hypothesis that tau and Aß predict unique impairments in objective and self-perceived human sleep under real-life, free-living conditions. Eighty-nine male and female cognitively healthy older adults received 18F-FTP-tau and 11C-PIB-Aß PET imaging, 7 nights of sleep actigraphy and questionnaire measures, and neurocognitive assessment. Tau burden, but not Aß, was associated with markedly worse objective sleep. In contrast, Aß and tau were associated with worse self-reported sleep quality. Of clinical relevance, Aß burden predicted a unique perceptual mismatch between objective and subject sleep evaluation, with individuals underestimating their sleep. The magnitude of this mismatch was further predicted by worse executive function. Thus, early-stage tau and Aß deposition are linked with distinct phenotypes of real-world sleep impairment, one that includes a cognitive misperception of their own sleep health.SIGNIFICANCE STATEMENT Alzheimer's disease is associated with sleep disruption, often before significant memory decline. Thus, real-life patterns of sleep behavior have the potential to serve as a window into early disease progression. In 89 cognitive healthy older adults, we found that tau burden was associated with worse wristwatch actigraphy-measured sleep quality, and that both tau and ß-amyloid were independently predictive of self-reported sleep quality. Furthermore, individuals with greater ß-amyloid deposition were more likely to underestimate their sleep quality, and sleep quality underestimation was associated with worse executive function. These data support the role of sleep impairment as a key marker of early Alzheimer's disease, and offer the possibility that actigraphy may be an affordable and scalable tool in quantifying Alzheimer's disease-related behavioral changes.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Sono/fisiologia , Proteínas tau/metabolismo , Actigrafia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/metabolismo , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Autorrelato , Inquéritos e Questionários
8.
Chemistry ; 28(35): e202200360, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35491534

RESUMO

Two stereocontrolled, efficient, and modular syntheses of eicosanoid lipoxin B4 (LXB4 ) are reported. One features a stereoselective reduction followed by an asymmetric epoxidation sequence to set the vicinal diol stereocentres. The dienyne was installed via a one-pot Wittig olefination and base-mediated epoxide ring opening cascade. The other approach installed the diol through an asymmetric dihydroxylation reaction followed by a Horner-Wadsworth-Emmons olefination to afford the common dienyne intermediate. Finally, a Sonogashira coupling and an alkyne hydrosilylation/proto-desilylation protocol furnished LXB4 in 25 % overall yield in just 10 steps. For the first time, LXB4 has been fully characterized spectroscopically with its structure confirmed as previously reported. We have demonstrated that the synthesized LXB4 showed similar biological activity to commercial sources in a cellular neuroprotection model. This synthetic route can be employed to synthesize large quantities of LXB4 , enable synthesis of new analogs, and chemical probes for receptor and pathway characterization.


Assuntos
Lipoxinas , Doenças Neuroinflamatórias , Eicosanoides , Humanos , Lipoxinas/metabolismo
9.
Intern Med J ; 52(6): 959-967, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33342022

RESUMO

BACKGROUND: Arthritis is a common condition, which frequently involves the hands. Patients with inflammatory arthritis have been shown to experience significant delays in diagnosis. AIM: To develop and test a screening tool combining an image of a patient's hands, a short series of questions and a single examination technique to determine the most likely diagnosis in a patient presenting with hand arthritis. Machine learning techniques were used to develop separate algorithms for each component, which were combined to produce a diagnosis. METHODS: A total of 280 consecutive new patients presenting to a rheumatology practice with hand arthritis were enrolled. Each patient completed a nine-part questionnaire, had photographs taken of each hand and had a single examination result recorded. The rheumatologist diagnosis was recorded following a 45-min consultation. The photograph algorithm was developed from 1000 previous hand images and machine learning techniques were applied to the questionnaire results, training several models against the diagnosis from the rheumatologist. RESULTS: The combined algorithms in the present study were able to predict inflammatory arthritis with an accuracy, precision, recall and specificity of 96.8%, 97.2%, 98.6% and 90.5% respectively. Similar results were found when inflammatory arthritis was subclassified into rheumatoid arthritis and psoriatic arthritis. The corresponding figures for osteoarthritis were 79.6%, 85.9%, 61.9% and 92.6%. CONCLUSION: The present study demonstrates a novel application combining image processing and a patient questionnaire with applied machine-learning methods to facilitate the diagnosis of patients presenting with hand arthritis. Preliminary results are encouraging for the application of such techniques in clinical practice.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Reumatologia , Algoritmos , Artrite Reumatoide/diagnóstico , Humanos , Aprendizado de Máquina , Projetos Piloto
10.
BMC Musculoskelet Disord ; 23(1): 433, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534813

RESUMO

BACKGROUND: Arthritis is a common condition, and the prompt and accurate assessment of hand arthritis in primary care is an area of unmet clinical need. We have previously developed and tested a screening tool combining machine-learning algorithms, to help primary care physicians assess patients presenting with arthritis affecting the hands. The aim of this study was to assess the validity of the screening tool among a number of different Rheumatologists. METHODS: Two hundred and forty-eight consecutive new patients presenting to 7 private Rheumatology practices across Australia were enrolled. Using a smartphone application, each patient had photographs taken of their hands, completed a brief 9-part questionnaire, and had a single examination result (wrist irritability) recorded. The Rheumatologist diagnosis was entered following a 45-minute consultation. Multiple machine learning models were applied to both the photographic and survey/examination results, to generate a screening outcome for the primary diagnoses of osteoarthritis, rheumatoid and psoriatic arthritis. RESULTS: The combined algorithms in the application performed well in identifying and discriminating between different forms of hand arthritis. The algorithms were able to predict rheumatoid arthritis with accuracy, precision, recall and specificity of 85.1, 80.0, 88.1 and 82.7% respectively. The corresponding results for psoriatic arthritis were 95.2, 76.9, 90.9 and 95.8%, and for osteoarthritis were 77.4, 78.3, 80.6 and 73.7%. The results were maintained when each contributor was excluded from the analysis. The median time to capture all data across the group was 2 minutes and 59 seconds. CONCLUSIONS: This multicentre study confirms the results of the pilot study, and indicates that the performance of the screening tool is maintained across a group of different Rheumatologists. The smartphone application can provide a screening result from a combination of machine-learning algorithms applied to hand images and patient symptom responses. This could be used to assist primary care physicians in the assessment of patients presenting with hand arthritis, and has the potential to improve the clinical assessment and management of such patients.


Assuntos
Artrite Psoriásica , Osteoartrite , Reumatologia , Artrite Psoriásica/diagnóstico , Humanos , Osteoartrite/diagnóstico , Projetos Piloto , Reumatologia/métodos , Smartphone
11.
Environ Manage ; 69(1): 31-44, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34633488

RESUMO

The exponential rise of information available means we can now, in theory, access knowledge on almost any question we ask. However, as the amount of unverified information increases, so too does the challenge in deciding which information to trust. Farmers, when learning about agricultural innovations, have historically relied on in-person advice from traditional 'experts', such as agricultural advisers, to inform farm management. As more farmers go online for information, it is not clear whether they are now using digital information to corroborate in-person advice from traditional 'experts', or if they are foregoing 'expert' advice in preference for peer-generated information. To fill this knowledge gap, we sought to understand how farmers in two contrasting European countries (Hungary and the UK) learnt about sustainable soil innovations and who influenced them to innovate. Through interviews with 82 respondents, we found farmers in both countries regularly used online sources to access soil information; some were prompted to change their soil management by farmer social media 'influencers'. However, online information and interactions were not usually the main factor influencing farmers to change their practices. Farmers placed most trust in other farmers to learn about new soil practices and were less trusting of traditional 'experts', particularly agricultural researchers from academic and government institutions, who they believed were not empathetic towards farmers' needs. We suggest that some farmers may indeed have had enough of traditional 'experts', instead relying more on their own peer networks to learn and innovate. We discuss ways to improve trustworthy knowledge exchange between agricultural stakeholders to increase uptake of sustainable soil management practices, while acknowledging the value of peer influence and online interactions for innovation and trust building.


Assuntos
Agricultura , Fazendeiros , Europa (Continente) , Fazendas , Humanos , Solo
12.
Alcohol Clin Exp Res ; 45(9): 1829-1839, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34341999

RESUMO

BACKGROUND: Pregnant women with a substance-related diagnosis, such as an alcohol use disorder, are a vulnerable population that may experience higher rates of severe maternal morbidity, such as hemorrhage and eclampsia, than pregnant women with no substance-related diagnosis. METHODS: This retrospective cross-sectional study reviewed electronic health record data on women (aged 18-44 years) who delivered a single live birth or stillbirth at ≥ 20 weeks of gestation from March 1, 2016, to August 30, 2019. Women with and without a substance-related diagnosis were matched on key demographic characteristics, such as age, at a 1:1 ratio. Adjusting for these covariates, odds ratios and 95% confidence intervals were calculated. RESULTS: A total of 10,125 deliveries met the eligibility criteria for this study. In the matched cohort of 1,346 deliveries, 673 (50.0%) had a substance-related diagnosis, and 94 (7.0%) had severe maternal morbidity. The most common indicators in women with a substance-related diagnosis included hysterectomy (17.7%), eclampsia (15.8%), air and thrombotic embolism (11.1%), and conversion of cardiac rhythm (11.1%). Having a substance-related diagnosis was associated with severe maternal morbidity (adjusted odds ratio = 1.81 [95% CI, 1.14-2.88], p-value = 0.0126). In the independent matched cohorts by substance type, an alcohol-related diagnosis was significantly associated with severe maternal morbidity (adjusted odds ratio = 3.07 [95% CI, 1.58-5.95], p-value = 0.0009), while the patterns for stimulant- and nicotine-related diagnoses were not as well resolved with severe maternal morbidity and opioid- and cannabis-related diagnoses were not associated with severe maternal morbidity. CONCLUSION: We found that an alcohol-related diagnosis, although lowest in prevalence of the substance-related diagnoses, had the highest odds of severe maternal morbidity of any substance-related diagnosis assessed in this study. These findings reinforce the need to identify alcohol-related diagnoses in pregnant women early to minimize potential harm through intervention and treatment.


Assuntos
Alcoolismo/complicações , Alcoolismo/epidemiologia , Complicações na Gravidez/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adolescente , Adulto , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/epidemiologia , Cannabis/efeitos adversos , Estudos de Coortes , Estudos Transversais , Eclampsia/induzido quimicamente , Eclampsia/epidemiologia , Feminino , Humanos , Histerectomia , Nicotina/efeitos adversos , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Fatores Socioeconômicos , Natimorto/epidemiologia , Trombose/induzido quimicamente , Trombose/epidemiologia , Adulto Jovem
13.
J Chem Phys ; 154(20): 204704, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34241182

RESUMO

Carbon nanotube porins (CNTPs) are biomimetic membrane channels that demonstrate excellent biocompatibility and unique water and ion transport properties. Gating transport in CNTPs with external voltage could increase control over ion flow and selectivity. Herein, we used continuum modeling to probe the parameters that enable and further affect CNTP gating efficiency, including the size and composition of the supporting lipid membrane, slip flow in the carbon nanotube, and the intrinsic electronic properties of the nanotube. Our results show that the optimal gated CNTP device consists of a semiconducting CNTP inserted into a small membrane patch containing an internally conductive layer. Moreover, we demonstrate that the ionic transport modulated by gate voltages is controlled by the charge distribution along the CNTP under the external gate electric potential. The theoretical understanding developed in this study offers valuable guidance for the design of gated CNTP devices for nanofluidic studies, novel biomimetic membranes, and cellular interfaces in the future.


Assuntos
Simulação de Dinâmica Molecular , Nanotubos de Carbono/química , Porinas/química , Transporte de Íons , Eletricidade Estática
14.
J Ethn Subst Abuse ; 19(3): 435-452, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30614780

RESUMO

Poppers (nitrite inhalants) are legal, commonly used by men who have sex with men, and associated with HIV acquisition, yet research is lacking on popper use and associated adverse outcomes. People living with HIV (PLWH) in the U.S.-Mexico border region lead binational lives, including accessing care and having sex and drug use partners on both sides of the border, with broad personal and public health implications. Understanding popper use provides crucial information to guide policy and develop targeted interventions for binational PLWH. We examine prevalence and correlates of popper use among HIV-positive Latinos in the border region, an underserved population at risk for poor health outcomes. This cross-sectional study recruited a convenience sample from agencies in San Diego and Tijuana to complete quantitative surveys. Participants (N = 121) were primarily male (82.6%) and gay/bisexual (62%). Lifetime substance use (excluding cannabis) was reported by 72% of participants, and 25.6% reported lifetime popper use. Individuals recruited in the U.S. were significantly more likely to report use of poppers than were participants recruited in Mexico. Our regression model found that identifying as gay/bisexual and having bought, sold, or traded sex for money, drugs, or other goods were independently associated with popper use. Findings shed light on the profile of individuals who use poppers and lay the foundation for further research to understand the context of popper use as it relates to high-risk behavior among PLWH in this region of high transborder mobility. Binational collaborative approaches are needed to improve regional HIV care outcomes and reduce transmission risk.


Assuntos
Nitrito de Amila/administração & dosagem , Infecções por HIV/etnologia , Comportamentos de Risco à Saúde , Hispânico ou Latino/estatística & dados numéricos , Homossexualidade Masculina/etnologia , Transtornos Relacionados ao Uso de Substâncias/etnologia , Vasodilatadores/administração & dosagem , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , México/etnologia , Prevalência , Minorias Sexuais e de Gênero/estatística & dados numéricos , Sudoeste dos Estados Unidos/etnologia
15.
J Environ Manage ; 229: 88-101, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30077401

RESUMO

Invasive alien species are a major driver of global environmental change and a range of management interventions are needed to manage their effects on biodiversity, ecosystem services, human well-being and local livelihoods. Stakeholder engagement is widely advocated to integrate diverse knowledge and perspectives in the management of invasive species and to deal with potential conflicts of interest. We reviewed the literature in the ISI Web of Science on stakeholder engagement (the process of involving stakeholders (actors) in decision making, management actions and knowledge creation) in invasion science to assess and understand what has been done (looking at approaches and methodologies used, stakeholders involved, and outcomes from engagement) and to make recommendations for future work. Research on stakeholder engagement in invasion science has increased over the last decade, helping to improve scientific knowledge and contributing towards policy formulation and co-implementation of management. However, many challenges remain and engagement could be made more effective. For example, most studies engage only one stakeholder group passively using questionnaires, primarily for assessing local knowledge and perceptions. Although useful for management and policy planning, these stakeholders are not active participants and there is no two-way flow of knowledge. To make stakeholder involvement more useful, we encourage more integrative and collaborative engagement to (1) improve co-design, co-creation and co-implementation of research and management actions; (2) promote social learning and provide feedback to stakeholders; (3) enhance collaboration and partnerships beyond the natural sciences and academia (interdisciplinary and transdisciplinary collaboration); and (4) discuss some practical and policy suggestions for improving stakeholder engagement in invasion science research and management. This will help facilitate different stakeholders to work better together, allowing problems associated with biological invasions to be tackled more holistically and successfully.


Assuntos
Espécies Introduzidas , Participação dos Interessados , Animais , Biodiversidade , Tomada de Decisões , Humanos , Projetos de Pesquisa
16.
Anal Chem ; 90(3): 1941-1950, 2018 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-29281259

RESUMO

Enterotoxins increase intestinal fluid secretion through modulation of ion channels as well as activation of the enteric nervous and immune systems. Colonic organoids, also known as colonoids, are functionally and phenotypically similar to in vivo colonic epithelium and have been used to study intestinal ion transport and subsequent water flux in physiology and disease models. In conventional cultures, organoids exist as spheroids embedded within a hydrogel patty of extracellular matrix, and they form at multiple depths, impairing efficient imaging necessary to capture data from statistically relevant sample sizes. To overcome these limitations, an analytical platform with colonic organoids localized to the planar surface of a hydrogel layer was developed. The arrays of densely packed colonoids (140 µm average diameter, 4 colonoids/mm2) were generated in a 96-well plate, enabling assay of the response of hundreds of organoids so that organoid subpopulations with distinct behaviors were identifiable. Organoid cell types, monolayer polarity, and growth were similar to those embedded in hydrogel. An automated imaging and analysis platform efficiently tracked over time swelling due to forskolin and fluid movement across the cell monolayer stimulated by cholera toxin. The platform was used to screen compounds associated with the enteric nervous and immune systems for their effect on fluid movement across epithelial cells. Prostaglandin E2 promoted increased water flux in a subset of organoids that resulted in organoid swelling, confirming a role for this inflammatory mediator in diarrheal conditions but also illustrating organoid differences in response to an identical stimulus. By allowing sampling of a large number of organoids, the arrayed organoid platform permits identification of organoid subpopulations intermixed within a larger group of nonresponding organoids. This technique will enable automated, large-scale screening of the impact of drugs, toxins, and other compounds on colonic physiology.


Assuntos
Colo/citologia , Enterotoxinas/metabolismo , Organoides/citologia , Secretagogos/análise , Análise Serial de Tecidos/métodos , Animais , Toxina da Cólera/metabolismo , Colo/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Organoides/metabolismo , Secretagogos/imunologia , Técnicas de Cultura de Tecidos/métodos
17.
Anal Chem ; 90(22): 13331-13340, 2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30350627

RESUMO

Animal models are frequently used for in vitro physiologic and drug transport studies of the colon, but there exists significant pressure to improve assay throughput as well as to achieve tighter control of experimental variables than can be achieved with animals. Thus, development of a primary in vitro colonic epithelium cultured as high resistance with transport protein expression and functional behavior similar to that of a native colonic would be of enormous value for pharmaceutical research. A collagen scaffold, in which the degree of collagen cross-linking was present as a gradient, was developed to support the proliferation of primary colonic cells. The gradient of cross-linking created a gradient in stiffness across the scaffold, enabling the scaffold to resist deformation by cells. mRNA expression and quantitative proteomic mass spectrometry of cells growing on these surfaces as a monolayer suggested that the transporters present were similar to those in vivo. Confluent monolayers acted as a barrier to small molecules so that drug transport studies were readily performed. Transport function was evaluated using atenolol (a substrate for passive paracellular transport), propranolol (a substrate for passive transcellular transport), rhodamine 123 (Rh123, a substrate for P-glycoprotein), and riboflavin (a substrate for solute carrier transporters). Atenolol was poorly transported with an apparent permeability ( Papp) of <5 × 10-7 cm s-1, while propranolol demonstrated a Papp of 9.69 × 10-6 cm s-1. Rh123 was transported in a luminal direction ( Papp,efflux/ Papp,influx = 7) and was blocked by verapamil, a known inhibitor of P-glycoprotein. Riboflavin was transported in a basal direction, and saturation of the transporter was observed at high riboflavin concentrations as occurs in vivo. It is anticipated that this platform of primary colonic epithelium will find utility in drug development and physiological studies, since the tissue possesses high integrity and active transporters and metabolism similar to that in vivo.


Assuntos
Transporte Biológico/fisiologia , Colo/fisiologia , Epitélio/fisiologia , Engenharia Tecidual/métodos , Animais , Atenolol/metabolismo , Células CACO-2 , Galinhas , Colágeno/química , Humanos , Camundongos , Propranolol/metabolismo , Rodamina 123/metabolismo , Riboflavina/metabolismo
18.
Anal Chem ; 89(21): 11325-11331, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29039202

RESUMO

Silicon nanowire field effect transistors (NWFETs) are low noise, low power, ultrasensitive biosensors that are highly amenable to integration. However, using NWFETs to achieve direct protein detection in physiological buffers such as blood serum remains difficult due to Debye screening, nonspecific binding, and stringent functionalization requirements. In this work, we performed an indirect sandwich immunoassay in serum combined with exponential DNA amplification and pH measurement by ultrasensitive NWFET sensors. Measurements of model cytokine interleukin-2 concentrations from <20 fM to >200 pM were demonstrated, surpassing the conventional NWFET urease-based readout. Our approach paves way for future development of universal, highly sensitive, miniaturized, and integrated nanoelectronic devices that can be applied to a wide variety of analytes.


Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Interleucina-2/análise , Nanofios/química , Reação em Cadeia da Polimerase/métodos , Transistores Eletrônicos , Biomarcadores/química , Técnicas Biossensoriais/instrumentação , Técnicas Eletroquímicas/instrumentação , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Silício/química
19.
Small ; 13(48)2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29125720

RESUMO

Mechanical fragility and insufficient light absorption are two major challenges for thin flexible crystalline Si-based solar cells. Flexible hybrid single-walled carbon nanotube (SWNT)/Si solar cells are demonstrated by applying scalable room-temperature processes for the fabrication of solar-cell components (e.g., preparation of SWNT thin films and SWNT/Si p-n junctions). The flexible SWNT/Si solar cells present an intrinsic efficiency ≈7.5% without any additional light-trapping structures. By using these solar cells as model systems, the charge transport mechanisms at the SWNT/Si interface are investigated using femtosecond transient absorption. Although primary photon absorption occurs in Si, transient absorption measurements show that SWNTs also generate and inject excited charge carriers to Si. Such effects can be tuned by controlling the thickness of the SWNTs. Findings from this study could open a new pathway for designing and improving the efficiency of photocarrier generation and absorption for high-performance ultrathin hybrid SWNT/Si solar cells.

20.
Alcohol Clin Exp Res ; 41(8): 1492-1501, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28683518

RESUMO

BACKGROUND: Few studies have examined the context in which drinkers underestimate their breath alcohol concentration (BrAC) in natural drinking environments. This study examined factors associated with bar patrons' self-estimated BrAC in high-risk college town settings. METHODS: Guided interview and BrAC data were collected from 510 participants recruited as they exited bars located close to large universities: 1 in Florida and 1 in Texas. RESULTS: Participants with the highest measured BrACs underestimated their BrAC levels the most. Findings from multivariable linear regression analysis indicated that BrAC (std ß = 0.014, p < 0.001), number of alcoholic drinks consumed (std ß = 0.006, p < 0.01), and perceived drunkenness (std ß = 0.024, p < 0.001) had significant positive associations with BrAC self-estimates, where the regression coefficients were scaled by values approximately equal to each variable's interquartile range. Among the 321 participants with BrAC levels ≥ 0.08 g/dl, 21.2% believed their BrAC was below the legal per se driving limit of 0.08 g/dl. Results from a logistic regression analysis indicated that higher levels of perceived drunkenness were associated with better self-recognition that one's BrAC level exceeded the legal driving threshold (OR = 3.312, p < 0.001). Further, participants under 26 years of age had reduced odds of recognizing that their BrAC was greater than 0.079 g/dl (OR = 0.245, p < 0.05). CONCLUSIONS: These findings highlight the inaccuracy of self-estimated BrAC when drinking, particularly among younger drinkers. Adjusting for BrAC, situational factors were strongly associated with self-estimated BrAC. Future research is needed to better understand how altering drinking environments may improve accuracy of BrAC self-estimates and deter driving after drinking.


Assuntos
Consumo de Bebidas Alcoólicas/psicologia , Bebidas Alcoólicas , Intoxicação Alcoólica/psicologia , Autoimagem , Inquéritos e Questionários/normas , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Intoxicação Alcoólica/diagnóstico , Intoxicação Alcoólica/epidemiologia , Testes Respiratórios/métodos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Estudantes/psicologia , Adulto Jovem
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