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1.
J Med Chem ; 67(9): 6922-6937, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38648167

RESUMEN

Tauopathy, neuronal atrophy, and psychological impairments are hallmarks of neurodegenerative diseases, such as Alzheimer's disease, that currently lack efficacious clinical treatments capable of rectifying these issues. To address these unmet needs, we used rational drug design to combine the pharmacophores of DYRK1A inhibitors and isoDMTs to develop psychoplastogenic DYRK1A inhibitors. Using this approach, we discovered a nonhallucinogenic compound capable of promoting cortical neuron growth and suppressing tau hyperphosphorylation while also having the potential to mitigate the biological and psychological symptoms of dementia. Together, our results suggest that hybridization of the DYRK1A and psychoplastogen pharmacophores represents a promising strategy for identifying compounds that might address the cognitive as well as the behavioral and psychological symptoms of dementia.


Asunto(s)
Enfermedad de Alzheimer , Quinasas DyrK , Inhibidores de Proteínas Quinasas , Proteínas Serina-Treonina Quinasas , Proteínas Tirosina Quinasas , Proteínas tau , Enfermedad de Alzheimer/tratamiento farmacológico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/metabolismo , Humanos , Animales , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/síntesis química , Proteínas tau/metabolismo , Proteínas tau/antagonistas & inhibidores , Ratones , Fosforilación , Diseño de Fármacos
2.
J Mol Cell Cardiol ; 187: 101-117, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38331556

RESUMEN

AIMS: The sympathetic nervous system regulates numerous critical aspects of mitochondrial function in the heart through activation of adrenergic receptors (ARs) on cardiomyocytes. Mounting evidence suggests that α1-ARs, particularly the α1A subtype, are cardioprotective and may mitigate the deleterious effects of chronic ß-AR activation by shared ligands. The mechanisms underlying these adaptive effects remain unclear. Here, we tested the hypothesis that α1A-ARs adaptively regulate cardiomyocyte oxidative metabolism in both the uninjured and infarcted heart. METHODS: We used high resolution respirometry, fatty acid oxidation (FAO) enzyme assays, substrate-specific electron transport chain (ETC) enzyme assays, transmission electron microscopy (TEM) and proteomics to characterize mitochondrial function comprehensively in the uninjured hearts of wild type and α1A-AR knockout mice and defined the effects of chronic ß-AR activation and myocardial infarction on selected mitochondrial functions. RESULTS: We found that isolated cardiac mitochondria from α1A-KO mice had deficits in fatty acid-dependent respiration, FAO, and ETC enzyme activity. TEM revealed abnormalities of mitochondrial morphology characteristic of these functional deficits. The selective α1A-AR agonist A61603 enhanced fatty-acid dependent respiration, fatty acid oxidation, and ETC enzyme activity in isolated cardiac mitochondria. The ß-AR agonist isoproterenol enhanced oxidative stress in vitro and this adverse effect was mitigated by A61603. A61603 enhanced ETC Complex I activity and protected contractile function following myocardial infarction. CONCLUSIONS: Collectively, these novel findings position α1A-ARs as critical regulators of cardiomyocyte metabolism in the basal state and suggest that metabolic mechanisms may underlie the protective effects of α1A-AR activation in the failing heart.


Asunto(s)
Contracción Miocárdica , Infarto del Miocardio , Animales , Ratones , Ácidos Grasos/metabolismo , Ratones Noqueados , Mitocondrias/metabolismo , Infarto del Miocardio/metabolismo , Estrés Oxidativo , Receptores Adrenérgicos alfa 1/metabolismo
3.
ChemSusChem ; 17(8): e202301418, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38189582

RESUMEN

Waste PCBs the core of e-waste is rich in copper, tin, zinc, iron, and nickel. Leaching base metals from PCB used to be done in toxic, corrosive acidic/alkali mediums. In this work, an environmentally friendly method for leaching metals from thermally treated PCBs (TPCBs) of mobile phones was proposed using choline chloride based deep eutectic solvents (DES). DES selectivity and solubility of metals from metal oxides were the main screening criteria. FA-ChCl had the maximum solubility of Cu, Fe, and Ni, while Urea-ChCl had high Zn selectivity and solubility. Oxalic acid has high selectivity for Sn. FA-ChCl extracted Cu and Fe best at 16 h, 100 °C, and 1/30 g/mL. Urea-ChCl extracted Zn (90.4±2.9 %) from TPCBs at 100 °C, 21 h, 1/20 g/mL, and 400 rpm. Oxalic acid (1 M) removed 92.3±2.1 % Sn from TPCBs in 1 h at 80 °C and 1/20 g/mL. The shrinking core model-based kinetic investigation of FA-ChCl for Cu extraction showed a diffusion-controlled process. The proposed method is greener than mineral acids utilized for metal extraction.

6.
Behav Neurosci ; 137(4): 254-267, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37104777

RESUMEN

Substance use disorder (SUD) is associated with a cluster of cognitive disturbances that engender vulnerability to ongoing drug seeking and relapse. Two of these endophenotypes-risky decision-making and impulsivity-are amplified in individuals with SUD and are augmented by repeated exposure to illicit drugs. Identifying genetic factors underlying variability in these behavioral patterns is critical for early identification, prevention, and treatment of SUD-vulnerable individuals. Here, we compared risky decision-making and different facets of impulsivity between two fully inbred substrains of Lewis rats-LEW/NCrl and LEW/NHsd. We performed whole genome sequencing of both substrains to identify almost all relevant variants. We observed substantial differences in risky decision-making and impulsive behaviors. Relative to LEW/NHsd, the LEW/NCrl substrain accepts higher risk options in a decision-making task and higher rates of premature responses in the differential reinforcement of low rates of responding task. These phenotypic differences were more pronounced in females than males. We defined a total of ∼9,000 polymorphisms between these substrains at 40× whole genome short-read coverage. Roughly half of variants are located within a single 1.5 Mb region of Chromosome 8, but none impact protein-coding regions. In contrast, other variants are widely distributed, and of these, 38 are predicted to cause protein-coding variants. In conclusion, Lewis rat substrains differ significantly in risk-taking and impulsivity and only a small number of easily mapped variants are likely to be causal. Sequencing combined with a reduced complexity cross should enable identification of one or more variants underlying multiple complex addiction-relevant behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Asunto(s)
Conducta Adictiva , Trastornos Relacionados con Sustancias , Masculino , Ratas , Animales , Femenino , Toma de Decisiones , Ratas Endogámicas Lew , Conducta Impulsiva , Refuerzo en Psicología , Asunción de Riesgos
7.
J Toxicol Environ Health A ; 86(8): 246-262, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-36859793

RESUMEN

Despite the perception that e-cigarettes are safer than conventional cigarettes, numerous findings demonstrated that e-cigarette aerosol (EC) exposure induced compromised immune functionality, vascular changes even after acute exposure, and lung injury. Notably, altered neutrophil functionality and platelet hemodynamics have been observed post-EC exposure. It was hypothesized that EC exposure initiates an inflammatory response resulting in altered neutrophil behavior and increased neutrophil-platelet interaction in the pulmonary microvasculature. Neutrophil and platelet responses were examined up to 48 hrs following whole-body, short-term EC exposure without flavorants or nicotine in a murine model, which most closely modeled secondhand exposure. This study is the first to investigate the impact of EC exposure through lung intravital imaging. Compared to room air-exposed mice, EC-exposed mice displayed significantly increased 1.7‒1.9-fold number of neutrophils in the pulmonary microvasculature associated with no marked change in neutrophils within whole blood or bronchoalveolar lavage fluid (BALF). Neutrophil-platelet interactions were also significantly elevated 1.9‒2.5-fold in exposed mice. Plasma concentration of myeloperoxidase was markedly reduced 1.5-fold 48 hr following exposure cessation, suggesting suppressed neutrophil antimicrobial activity. Cytokine expression exhibited changes indicating vascular damage. Effects persisted for 48 hr post-EC exposure. Data demonstrated that EC exposure repeated for 3 consecutive days in 2.5 hr intervals in the absence of flavorants or nicotine resulted in modified pulmonary vasculature hemodynamics, altered immune functionality, and a pro-inflammatory state in female BALB/cJ mice.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Neutrófilos , Femenino , Ratones , Animales , Neutrófilos/metabolismo , Agregación Plaquetaria , Nicotina/metabolismo , Infiltración Neutrófila , Aerosoles y Gotitas Respiratorias , Pulmón/metabolismo , Microvasos
8.
ACS Chem Neurosci ; 14(3): 351-358, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36630260

RESUMEN

Psychedelic compounds have displayed antidepressant potential in both humans and rodents. Despite their promise, psychedelics can induce undesired effects that pose safety concerns and limit their clinical scalability. The rational development of optimized psychedelic-related medicines will require a full mechanistic understanding of how these molecules produce therapeutic effects. While the hallucinogenic properties of psychedelics are generally attributed to activation of serotonin 2A receptors (5-HT2ARs), it is currently unclear if these receptors also mediate their antidepressant effects as several nonhallucinogenic analogues of psychedelics with antidepressant-like properties have been developed. Moreover, many psychedelics exhibit promiscuous pharmacology, making it challenging to identify their primary therapeutic target(s). Here, we use a combination of pharmacological and genetic tools to demonstrate that activation of 5-HT2A receptors is essential for tryptamine-based psychedelics to produce antidepressant-like effects in rodents. Our results suggest that psychedelic tryptamines can induce hallucinogenic and therapeutic effects through activation of the same receptor.


Asunto(s)
Alucinógenos , Animales , Humanos , Alucinógenos/farmacología , Alucinógenos/uso terapéutico , Triptaminas/farmacología , Roedores
9.
J Periodontol ; 94(5): 622-629, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36527199

RESUMEN

BACKGROUND: The amount of time it takes for bone allograft particles to be replaced with new vital bone during ridge preservation is unclear. The purpose of this article was to compare the wound healing and vital bone formation following ridge preservation using a combination allograft of 70% mineralized and 30% demineralized freeze-dried bone allograft at 4 months (short-term, ST) versus 12 months (long-term, LT). METHODS: Fifty-seven patients were enrolled in the study who required extraction of a single tooth (excluding second and third molars) and were planned for replacement with a dental implant. After tooth extraction, all sites were grafted with a combination allograft procured from a single donor, and patients were randomized into the ST or LT healing groups. Patients returned for implant placement and an 8-mm bone core biopsy was harvested using a trephine drill during initial implant osteotomy preparation. The cores were then analyzed histologically to determine the percentages of vital bone formation, residual graft particles, and connective tissue/other. RESULTS: There was significantly greater vital bone formation in the LT group (51.38%) compared with the ST group (31.39%) (p = 0.0025) and significantly fewer residual graft particles in the LT group (18.04%) compared with the ST group (40.38%). CONCLUSIONS: A longer healing time following ridge preservation results in more vital bone formation and less residual graft particles at the time of implant placement. However, residual allograft material still remains at 12 months after ridge preservation.


Asunto(s)
Proceso Alveolar , Aumento de la Cresta Alveolar , Humanos , Proceso Alveolar/cirugía , Alveolo Dental/cirugía , Aloinjertos/cirugía , Cicatrización de Heridas , Tejido Conectivo/trasplante , Extracción Dental , Trasplante Óseo/métodos , Aumento de la Cresta Alveolar/métodos
10.
Res Rep Health Eff Inst ; (214): 1-41, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38286761

RESUMEN

INTRODUCTION: Early ecological studies have suggested a link between air pollution and Coronavirus Diseases 2019 (COVID-19); however, the evidence from individual-level prospective cohort studies is still sparse. Here, we have examined, in a general population, whether long-term exposure to air pollution is associated with the risk of contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and developing severe COVID-19, resulting in hospitalization or death and who is most susceptible. We also examined whether long-term exposure to air pollution is associated with hospitalization or death due to COVID-19 in those who have tested positive for SARS-CoV-2. METHODS: We included all Danish residents 30 years or older who resided in Denmark on March 1, 2020. and followed them in the National COVID-19 Surveillance System until first positive test (incidence), COVID-19 hospitalization, or death until April 26, 2021. We estimated mean levels of nitrogen dioxide (NO2), particulate matter with an aerodynamic diameter <2.5 µm (PM2.5), black carbon (BC), and ozone (O3) at cohort participants' residence in 2019 by the Danish Eulerian Hemispheric Model/Urban Background Model. We used Cox proportional hazard models to estimate the associations of air pollutants with COVID-19 incidence, hospitalization, and mortality adjusting for age, sex, and socioeconomic status (SES) at the individual and area levels. We examined effect modification by age, sex, SES (education, income, wealth, employment), and comorbidities with cardiovascular disease, respiratory disease, acute lower respiratory infections, diabetes, lung cancer, and dementia. We used logistic regression to examine association of air pollutants with COVID-19-related hospitalization or death among SARS-CoV-2 positive patients, adjusting for age, sex, individual- and area-level SES. RESULTS: Of 3,721,810 people, 138,742 were infected, 11,270 hospitalized, and 2,557 died from COVID-19 during 14 months of follow-up. We detected strong positive associations with COVID-19 incidence, with hazard ratio (HR) and 95% confidence interval (CI) of 1.10 (CI: 1.05-1.14) per 0.5-µg/m3 increase in PM2.5 and 1.18 (CI: 1.14-1.23) per 3.6-µg/m3 increase in NO2. For COVID-19 hospitalizations and for COVID-19 deaths, corresponding HRs and 95% CIs were 1.09 (CI: 1.01-1.17) and 1.19 (CI: 1.12-1.27), respectively for PM2.5, and 1.23 (CI: 1.04-1.44) and 1.18 (CI: 1.03-1.34), respectively for NO2. We also found strong positive and statistically significant associations with BC and negative associations with O3. Associations were strongest in those aged 65 years old or older, participants with the lowest SES, and patients with chronic cardiovascular, respiratory, metabolic, lung cancer, and neurodegenerative disease. Among 138,742 individuals who have tested positive for SARS-Cov-2, we detected positive association with COVID-19 hospitalizations (N = 11,270) with odds ratio and 95% CI of 1.04 (CI: 1.01- 1.08) per 0.5-µg/m3 increase in PM2.5 and 1.06 (CI: 1.01-1.12) per 3.6-µg/m3 increase in NO2, but no association with PM with an aerodynamic diameter <10 µm (PM10), BC, or O3, and no association between any of the pollutants and COVID-19 mortality (N = 2,557). CONCLUSIONS: This large nationwide study provides strong new evidence in support of association between long-term exposure to air pollution and COVID-19.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Enfermedades Cardiovasculares , Neoplasias Pulmonares , Enfermedades Neurodegenerativas , Humanos , Anciano , Dióxido de Nitrógeno/toxicidad , Estudios Prospectivos , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , COVID-19/epidemiología , SARS-CoV-2 , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Material Particulado/efectos adversos , Material Particulado/análisis , Incidencia , Dinamarca/epidemiología
11.
Prog Community Health Partnersh ; 16(2): 205-215, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35662147

RESUMEN

BACKGROUND: Community-based public health advocacy efforts are crucial to sustaining the low-cost/free breast cancer services that support underserved populations. OBJECTIVES: We introduce two ways in which narrative theory may be a useful tool for developing advocacy materials and provide an example, using a community-academic partnership to promote Latina breast health in Chicago, Illinois. METHODS: Community and academic partners 1) engaged 25 Spanish-speaking Latinas in an advocacy workshop, 2) leveraged narrative theory to develop multi-media advocacy materials, and 3) disseminated materials to policymakers. LESSONS LEARNED: Our project highlights 1) that narrative theory may be useful to describe how Latinas engage policy-makers in relation to their needs and cultural norms, 2) the importance of flexibility and offering community members multiple options to engage policymakers, and 3) the importance of leveraging partners' complementary strengths. CONCLUSIONS: Narrative theory may be a useful tool for developing advocacy materials in community-academic partnerships.


Asunto(s)
Neoplasias de la Mama , Investigación Participativa Basada en la Comunidad , Femenino , Hispánicos o Latinos , Humanos , Área sin Atención Médica , Poblaciones Vulnerables
12.
Ann Vasc Surg ; 85: 406-417, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35395375

RESUMEN

Acute perioperative changes in arterial pressure occur frequently, particularly in patients with cardiovascular disease or those receiving vasoactive medications, or in relation to certain cardiovascular surgical procedures. Hemodynamic Instability (HI) is common in patients undergoing carotid revascularization because of unique patho-physiological and surgical factors. The operation, by necessity, disrupts the afferent pathway of the baroreflex, which can lead to postendarterectomy HI. Poor arterial pressure control is associated with increased morbidity and mortality after carotid revascularization, but good control of arterial pressure is often difficult to achieve in practice. The incidence, implications, and etiology of HI associated with carotid surgery are reviewed, and some recommendations made for its management. Close monitoring and titration of therapy are probably the most important considerations rather than specific choice of agents.


Asunto(s)
Estenosis Carotídea , Endarterectomía Carotidea , Barorreflejo/fisiología , Arterias Carótidas , Estenosis Carotídea/diagnóstico por imagen , Estenosis Carotídea/cirugía , Endarterectomía Carotidea/efectos adversos , Humanos , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares
13.
J Foot Ankle Surg ; 61(5): 1109-1113, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35236617

RESUMEN

This study aims to examine the duration and rate of delayed diagnosis in Charcot foot. We systematically reviewed articles published in Medline, SCOPUS, and Cumulative Index of Nursing and Allied Health Literature to identify articles discussing delayed or misdiagnosis of Charcot foot. Random-effects models were generated to determine the average time from symptom onset to correct diagnosis (diagnostic delay duration) and proportion of patients misdiagnosed prior to being correctly diagnosed (delayed diagnosis rate). Our search identified 142 articles, 7 of which are included in this review. The review found that 53.2% of cases of Charcot osteoarthropathy experienced a delay in diagnosis (95% CI: 28.9%-77.4%). Overall, the duration of diagnostic delay was determined to be 86.9 days (95% CI: 10.5-162.1). We found that patients with Charcot foot experienced prolonged delays from symptom onset to correct diagnosis, and a majority of patients are misdiagnosed. These delays in diagnosis contribute to worse patient outcomes.


Asunto(s)
Artropatía Neurógena , Pie Diabético , Artropatía Neurógena/diagnóstico , Artropatía Neurógena/cirugía , Diagnóstico Tardío , Pie Diabético/cirugía , Errores Diagnósticos , Humanos , Extremidad Inferior
14.
Biosensors (Basel) ; 12(2)2022 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-35200382

RESUMEN

Novel metal oxide nanoparticle (NP) contrast agents may offer safety and functionality advantages over conventional gadolinium-based contrast agents (GBCAs) for cancer diagnosis by magnetic resonance imaging. However, little is known about the behavior of metal oxide NPs, or of their effect, upon coming into contact with the innate immune system. As neutrophils are the body's first line of defense, we sought to understand how manganese oxide and iron oxide NPs impact leukocyte functionality. Specifically, we evaluated whether contrast agents caused neutrophils to release web-like fibers of DNA known as neutrophil extracellular traps (NETs), which are known to enhance metastasis and thrombosis in cancer patients. Murine neutrophils were treated with GBCA, bare manganese oxide or iron oxide NPs, or poly(lactic-co-glycolic acid) (PLGA)-coated metal oxide NPs with different incorporated levels of poly(ethylene glycol) (PEG). Manganese oxide NPs elicited the highest NETosis rates and had enhanced neutrophil uptake properties compared to iron oxide NPs. Interestingly, NPs with low levels of PEGylation produced more NETs than those with higher PEGylation. Despite generating a low rate of NETosis, GBCA altered neutrophil cytokine expression more than NP treatments. This study is the first to investigate whether manganese oxide NPs and GBCAs modulate NETosis and reveals that contrast agents may have unintended off-target effects which warrant further investigation.


Asunto(s)
Trampas Extracelulares , Nanopartículas del Metal , Nanopartículas , Animales , Medios de Contraste , Humanos , Ratones , Neutrófilos/metabolismo , Óxidos
15.
J Periodontol ; 93(8): 1183-1190, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35044692

RESUMEN

BACKGROUND: To date, the efficacy of ridge preservation in the maintenance of the residual alveolar ridge dimension beyond 6 months after treatment is unknown. The purpose of this study was to compare the differences in alveolar ridge dimensional change following ridge preservation between 4- and 12-month healing time points using cone-beam computed tomography (CBCT). METHODS: Fifty seven patients planned for tooth extraction and implant placement were enrolled. Following extraction, ridge preservation was performed. CBCT scans were taken within 72 hours following extraction with a customized resin stent containing a fixed radiographic marker. At either 4 months (short-term, ST group) or 12 months (long-term, LT group) after ridge preservation, patients had a second CBCT taken and an implant placed. Changes in ridge height and width were measured using the standardized radiographic marker. RESULTS: No significant differences were detected between the ST and LT groups in loss of buccal and lingual ridge height. Similarly, when adjusted for baseline ridge width, no significant differences were detected in ridge width loss at 3, 5, and 7 mm apical to the crest between the ST and LT groups. CONCLUSIONS: The efficacy of ridge preservation in the maintenance of ridge width and height at the 12-month time point is similar to that of the 4-month time point. Clinicians may feel confident that a delay in implant placement for up to a year has no significant negative impact on the height and width of the healed ridge.


Asunto(s)
Pérdida de Hueso Alveolar , Aumento de la Cresta Alveolar , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/prevención & control , Proceso Alveolar/diagnóstico por imagen , Aumento de la Cresta Alveolar/métodos , Tomografía Computarizada de Haz Cónico , Humanos , Extracción Dental/métodos , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/cirugía , Cicatrización de Heridas
16.
Environ Pollut ; 294: 118631, 2022 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-34871646

RESUMEN

Ultrafine particles (UFP), harmful to human health, are emitted at high levels from motorized traffic. Bicycle commuting is increasingly encouraged to reduce traffic emissions and increase physical activity, but higher breathing rates increase inhaled UFP concentrations while in traffic. We assessed exposure to UFP while cycling along a fixed 8.5 km inner-city route in Copenhagen, on weekdays over six weeks (from September to October 2020), during morning and afternoon rush-hour, as well as morning non-rush-hour, traffic time periods starting from 07:45, 15:45, and 09:45 h, respectively. Continuous measurements were made (each second) of particle number concentration (PNC) and location. PNC levels were summarized and compared across time periods. We used generalized additive models to adjust for meteorological factors, weekdays and trends. A total of 61 laps were completed, during 28 days (∼20 per time period). Overall mean PNC was 18,149 pt/cm3 (range 256-999,560 pt/cm3) with no significant difference between morning rush-hour (18003 pt/cm3), afternoon rush-hour (17560 pt/cm3) and late morning commute (17560 pt/cm3) [p = 0.85]. There was substantial spatial variation of UFP exposure along the route with highest PNC levels measured at traffic intersections (∼38,000-42000 pt/cm3), multiple lane roads (∼38,000-40000 pt/cm3) and construction sites (∼44,000-51000 pt/cm3), while lowest levels were measured at smaller streets, areas with open built environment (∼12,000 pt/cm3), as well as at a bus-only zone (∼15,000 pt/cm3). UFP exposure in inner-city Copenhagen did not differ substantially when bicycling in either rush-hour or non-rush-hour, or morning or afternoon, traffic time periods. UFP exposure varied substantially spatially, with highest concentrations around intersections, multiple lane roads, and construction sites. This suggests that exposure to UFP is not necessarily reduced by avoiding rush-hours, but by avoiding sources of pollution along the bicycling route.


Asunto(s)
Contaminantes Atmosféricos , Material Particulado , Contaminantes Atmosféricos/análisis , Ciclismo , Dinamarca , Exposición a Riesgos Ambientales/análisis , Monitoreo del Ambiente , Humanos , Tamaño de la Partícula , Material Particulado/análisis , Transportes , Emisiones de Vehículos/análisis
17.
J Fluoresc ; 32(1): 307-318, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34787776

RESUMEN

Coumarins are bioactive molecules that often serve as defenses in plant and animal systems, and understanding their fundamental behavior is essential for understanding their bioactivity. Aesculetin (6,7-dihydroxycoumarin) has recently attracted attention due to its ability to act as an antioxidant, but little is known about its photophysical properties. The fluorescence lifetimes of its neutral and anion form in water are 19 ± 2 ps and 2.3 ± 0.1 ns, respectively. Assuming the short lifetime of the neutral is determined by ESPT, we estimate kPT ~ 5 × 1010 s-1. Using steady-state and time-resolved fluorescence spectroscopy, we determine its ground and excited-state [Formula: see text] to be 7.3 and -1, respectively, making it one of the strongest photoacids of the natural coumarins. Aesculetin exhibits a strong pH dependence of the relative fluorescence quantum yield becoming much more fluorescent above [Formula: see text]. The aesculetin anion [Formula: see text] slightly photobasic character. We also report that aesculetin forms a fluorescent catechol-like complex with boric acid, and this complex has a [Formula: see text] of 5.6.


Asunto(s)
Fluorescencia , Espectrometría de Fluorescencia/métodos , Umbeliferonas , Ácidos Bóricos/química , Cumarinas , Concentración de Iones de Hidrógeno , Procesos Fotoquímicos , Umbeliferonas/química , Agua/química
18.
Wearable Technol ; 3: e6, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-38486893

RESUMEN

This paper proposes a novel origami-inspired adult diaper design that improves discretion by reducing sag and increasing wicking across the entire diaper pad. While other diapers rely on supporting elastics to reduce the sag of the diaper as a whole, this paper proposes an absorbent core that uses liquid activated shaping to take a specified shape. Origami-based folds are also incorporated into the diaper design to increase wicking performance. The paper introduces a disposable compliant mechanism waistband used to deploy the diaper, making it easier to put onto one's body.

19.
Int J Mol Sci ; 22(22)2021 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-34830344

RESUMEN

Electronic cigarettes are frequently viewed as a safer alternative to conventional cigarettes; however, evidence to support this perspective has not materialized. Indeed, the current literature reports that electronic cigarette use is associated with both acute lung injury and subclinical dysfunction to the lung and vasculature that may result in pathology following chronic use. E-cigarettes can alter vascular dynamics, polarize innate immune populations towards a proinflammatory state, compromise barrier function in the pulmonary endothelium and epithelium, and promote pre-oncogenic phenomena. This review will summarize the variety of e-cigarette products available to users, discuss current challenges in e-cigarette study design, outline the range of pathologies occurring in cases of e-cigarette associated acute lung injury, highlight disease supporting tissue- and cellular-level changes resulting from e-cigarette exposure, and briefly examine how these changes may promote tumorigenesis. Continued research of the mechanisms by which e-cigarettes induce pathology benefit users and clinicians by resulting in increased regulation of vaping devices, informing treatments for emerging diseases e-cigarettes produce, and increasing public awareness to reduce e-cigarette use and the onset of preventable disease.


Asunto(s)
Lesión Pulmonar Aguda/patología , Enfermedades Cardiovasculares/patología , Sistemas Electrónicos de Liberación de Nicotina , Neoplasias Pulmonares/patología , Vapeo/patología , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/inmunología , Animales , Plaquetas/efectos de los fármacos , Plaquetas/inmunología , Plaquetas/patología , Carcinogénesis/inmunología , Carcinogénesis/patología , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/inmunología , Citocinas/biosíntesis , Citocinas/inmunología , Humanos , Inmunidad Innata/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/patología , Neovascularización Patológica/inducido químicamente , Neovascularización Patológica/inmunología , Neovascularización Patológica/patología , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/patología , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/patología , Roedores , Vapeo/inmunología
20.
Sci Total Environ ; 791: 148301, 2021 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-34412377

RESUMEN

Ultrafine particles (UFP; particulate matter <0.1 µm diameter) emitted from motorized traffic may be highly detrimental to health. Active mobility (walking, bicycling) is increasingly encouraged as a way to reduce traffic congestion and increase physical activity levels. However, it has raised concerns of increased exposure to UFP, due to increased breathing rates in traffic microenvironments, immediately close to their source. The recent Coronavirus Disease 2019 (COVID-19) societal closures reduced commuting needs, allowing a natural experiment to estimate contributions from motorized traffic to UFP exposure while walking or bicycling. From late-March to mid-July 2020, UFP was repeatedly measured while walking or bicycling, capturing local COVID-19 closure ('Phase 0') and subsequent phased re-opening ('Phase 1', '2', '2.1' & '3'). A DiSCmini continuously measured particle number concentration (PNC) in the walker/bicyclist's breathing zone. PNC while walking or bicycling was compared across phased re-openings, and the effect of ambient temperature, wind speed and direction was determined using regression models. Approximately 40 repeated 20-minute walking and bicycling laps were made over 4 months during societal re-opening phases related to the COVID-19 pandemic (late-March to mid-July 2020) in Copenhagen. Highest median PNC exposure of both walking (13,170 pt/cm3, standard deviation (SD): 3560 pt/cm3) and bicycling (21,477 pt/cm3, SD: 8964) was seen during societal closures (Phase 0) and decreased to 5367 pt/cm3 (SD: 2949) and 8714 pt/cm3 (SD: 4309) in Phase 3 of re-opening. These reductions in PNC were mainly explained by meteorological conditions, with most of the deviation explained by wind speed (14-22%) and temperature (10-13%). Highest PNC was observed along major roads and intersections. In conclusion, we observed decreases in UFP exposure while walking and bicycling during societal re-opening phases related to the COVID-19 pandemic, due largely to meteorological factors (e.g., wind speed and temperature) and seasonal variations in UFP levels.


Asunto(s)
COVID-19 , Material Particulado , Ciclismo , Dinamarca , Humanos , Pandemias , Tamaño de la Partícula , Material Particulado/análisis , SARS-CoV-2 , Caminata
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