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2.
J Health Commun ; 29(4): 256-264, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38461495

RESUMEN

Community structure analysis compared city characteristics and newspaper coverage of state/local government responses to COVID-19 in 25 major U.S. cities, sampling all 250+ word articles from 4/4/20 to 7/6/20. The resulting 588 articles were coded for "prominence" and "direction" (favorable/unfavorable/balanced-neutral coverage), then combined into each newspaper's composite "Media Vector" (range=0.3552 to -0.5197, or 0.8749). Twenty-one of 25 newspapers (84%) displayed unfavorable coverage of local COVID-19 responses. Pearson correlations and regression analysis confirmed a muscular "violated way of life" pattern, when a community perceives itself as threatened by a "biological threat or a threat to a cherished way of life." Political and belief system polarization (in particular percent Evangelical and percent voting Republican) were strongly associated with unfavorable coverage of local pandemic responses, compared to more favorable responses linked to percent voting Democratic or percent Catholic. Vulnerability (percent uninsured) was also linked to negative coverage. Conversely, two different measures of access to healthcare (percent municipal spending on health and welfare, and physicians/100,000) were significantly linked to favorable coverage of the same local government efforts. Community structure theory's grass roots "bottom up" expectations linking community demographics to variations in reporting on critical issues were robustly confirmed.


Asunto(s)
COVID-19 , Ciudades , Periódicos como Asunto , Humanos , COVID-19/epidemiología , Estados Unidos , Periódicos como Asunto/estadística & datos numéricos , Medios de Comunicación de Masas/estadística & datos numéricos , Política , Gobierno Local , Comunicación en Salud/métodos
3.
Malar J ; 22(1): 323, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37880774

RESUMEN

BACKGROUND: Indoor residual spraying (IRS) is a common vector control strategy in countries with high malaria burden. Historically, social norms have prevented women from working in IRS programmes. The Bioko Island Malaria Elimination Project has actively sought to reduce gender inequality in malaria control operations for many years by promoting women's participation in IRS. METHODS: This study investigated the progress of female engagement and compared spray productivity by gender from 2010 to 2021, using inferential tests and multivariable regression. Spray productivity was measured by rooms sprayed by spray operator per day (RSOD), houses sprayed by spray operator per day (HSOD), and the daily productivity ratio (DPR), defined as the ratio of RSOD to HSOD, which standardized productivity by house size. RESULTS: The percentage of women participating in IRS has increased over time. The difference in DPR comparing male and female spray operators was only statistically significant (p < 0.05) for two rounds, where the value was higher for women compared to men. Regression analyses showed marginal, significant differences in DPR between men and women, but beta coefficients were extremely small and thus not indicative of a measurable effect of gender on operational performance. CONCLUSIONS: The quantitative analyses of spray productivity are counter to stigmatizing beliefs that women are less capable than male counterparts during IRS spray rounds. The findings from this research support the participation of women in IRS campaigns, and a renewed effort to implement equitable policies and practices that intentionally engage women in vector control activities.


Asunto(s)
Insecticidas , Malaria , Humanos , Masculino , Femenino , Guinea Ecuatorial , Control de Mosquitos , Malaria/prevención & control
4.
Sci Rep ; 13(1): 15229, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37709807

RESUMEN

Activated macrophages play a critical role in the orchestration of inflammation and inflammatory pain in several chronic diseases. We present here the first perfluorocarbon nanoemulsion (PFC NE) that is designed to preferentially target activated macrophages and can deliver up to three payloads (two fluorescent dyes and a COX-2 inhibitor). Folate receptors are overexpressed on activated macrophages. Therefore, we introduced a folate-PEG-cholesterol conjugate into the formulation. The incorporation of folate conjugate did not require changes in processing parameters and did not change the droplet size or fluorescent properties of the PFC NE. The uptake of folate-conjugated PFC NE was higher in activated macrophages than in resting macrophages. Flow cytometry showed that the uptake of folate-conjugated PFC NE occurred by both phagocytosis and receptor-mediated endocytosis. Furthermore, folate-conjugated PFC NE inhibited the release of proinflammatory cytokines (TNF-α and IL-6) more effectively than nonmodified PFC NE, while drug loading and COX-2 inhibition were comparable. The PFC NEs reported here were successfully produced on multiple scales, from 25 to 200 mL, and by using two distinct processors (microfluidizers: M110S and LM20). Therefore, folate-conjugated PFC NEs are viable anti-inflammatory theranostic nanosystems for macrophage drug delivery and imaging.


Asunto(s)
Fluorocarburos , Medicina de Precisión , Ciclooxigenasa 2 , Macrófagos , Colorantes Fluorescentes , Ácido Fólico
5.
J Biol Chem ; 299(7): 104884, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37269946

RESUMEN

The unfolded protein response (UPR) is sensitive to proteotoxic and membrane bilayer stress, both of which are sensed by the ER protein Ire1. When activated, Ire1 splices HAC1 mRNA, producing a transcription factor that targets genes involved in proteostasis and lipid metabolism, among others. The major membrane lipid phosphatidylcholine (PC) is subject to phospholipase-mediated deacylation, producing glycerophosphocholine (GPC), followed by reacylation of GPC through the PC deacylation/reacylation pathway (PC-DRP). The reacylation events occur via a two-step process catalyzed first by the GPC acyltransferase Gpc1, followed by acylation of the lyso-PC molecule by Ale1. However, whether Gpc1 is critical for ER bilayer homeostasis is unclear. Using an improved method for C14-choline-GPC radiolabeling, we first show that loss of Gpc1 results in abrogation of PC synthesis through PC-DRP and that Gpc1 colocalizes with the ER. We then probe the role of Gpc1 as both a target and an effector of the UPR. Exposure to the UPR-inducing compounds tunicamycin, DTT, and canavanine results in a Hac1-dependent increase in GPC1 message. Further, cells lacking Gpc1 exhibit increased sensitivity to those proteotoxic stressors. Inositol limitation, known to induce the UPR via bilayer stress, also induces GPC1 expression. Finally, we show that loss of GPC1 induces the UPR. A gpc1Δ mutant displays upregulation of the UPR in strains expressing a mutant form of Ire1 that is unresponsive to unfolded proteins, indicating that bilayer stress is responsible for the observed upregulation. Collectively, our data indicate an important role for Gpc1 in yeast ER bilayer homeostasis.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Aciltransferasas/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Fosfatidilcolinas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Represoras/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Respuesta de Proteína Desplegada
6.
Int J Mol Sci ; 24(11)2023 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-37298117

RESUMEN

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of activating transcription factor 3 (Atf3), however, only the female DRG shows decreased expression following drug treatment. Alternatively, S100A8 and S100A9 expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.


Asunto(s)
Neuralgia , Caracteres Sexuales , Femenino , Humanos , Masculino , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , RNA-Seq , Medicina de Precisión , Neuralgia/tratamiento farmacológico , Neuralgia/genética , Neuralgia/metabolismo , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/genética , Hiperalgesia/metabolismo , Expresión Génica , Inflamación/tratamiento farmacológico , Inflamación/genética , Inflamación/metabolismo , ARN/metabolismo , Ganglios Espinales/metabolismo
7.
Sci Rep ; 12(1): 8472, 2022 05 30.
Artículo en Inglés | MEDLINE | ID: mdl-35637203

RESUMEN

Neuropathic pain affects millions of people worldwide, yet the molecular mechanisms of how it develops and persists are poorly understood. Given that males have historically been utilized as the primary sex in preclinical studies, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. Macrophages contribute to the development of neuroinflammatory pain via the activation of their cyclooxygenase-2 (COX-2) enzyme, which leads to the production of prostaglandin E2 (PGE2). PGE2 activates nociception and influences additional leukocyte infiltration. Attenuation of COX-2 activity decreases inflammatory pain, most commonly achieved by nonsteroidal anti-inflammatory drugs (NSAIDs), yet NSAIDs are considered ineffective for neuropathic pain due to off target toxicity. Using chronic constriction injury of the rat sciatic nerve, we show that males and females exhibit quantitatively the same degree of mechanical allodynia post injury. Furthermore, a low-dose nanotherapeutic containing the NSAID celecoxib is phagocytosed by circulating monocytes that then naturally accumulate at sites of injury as macrophages. Using this nanotherapeutic, we show that treated males exhibit complete reversal of hypersensitivity, while the same dose of nanotherapeutic in females provides an attenuated relief. The difference in behavioral response to the nanotherapy is reflected in the reduction of infiltrating macrophages at the site of injury. The observations contained in this study reinforce the notion that female neuroinflammation is different than males.


Asunto(s)
Neuralgia , Caracteres Sexuales , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Celecoxib/farmacología , Celecoxib/uso terapéutico , Ciclooxigenasa 2 , Femenino , Humanos , Masculino , Neuralgia/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Prostaglandinas E , Ratas
8.
PLOS Digit Health ; 1(5): e0000025, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-36812503

RESUMEN

Public health interventions require evidence-based decision-making to maximize impact. Spatial decision support systems (SDSS) are designed to collect, store, process and analyze data to generate knowledge and inform decisions. This paper discusses how the use of a SDSS, the Campaign Information Management System (CIMS), to support malaria control operations on Bioko Island has impacted key process indicators of indoor residual spraying (IRS): coverage, operational efficiency and productivity. We used data from the last five annual IRS rounds (2017 to 2021) to estimate these indicators. IRS coverage was calculated as the percentage of houses sprayed per unit area, represented by 100x100 m map-sectors. Optimal coverage was defined as between 80% and 85%, and under and overspraying as coverage below 80% and above 85%, respectively. Operational efficiency was defined as the fraction of map-sectors that achieved optimal coverage. Daily productivity was expressed as the number of houses sprayed per sprayer per day (h/s/d). These indicators were compared across the five rounds. Overall IRS coverage (i.e. percent of total houses sprayed against the overall denominator by round) was highest in 2017 (80.2%), yet this round showed the largest proportion of oversprayed map-sectors (36.0%). Conversely, despite producing a lower overall coverage (77.5%), the 2021 round showed the highest operational efficiency (37.7%) and the lowest proportion of oversprayed map-sectors (18.7%). In 2021, higher operational efficiency was also accompanied by marginally higher productivity. Productivity ranged from 3.3 h/s/d in 2020 to 3.9 h/s/d in 2021 (median 3.6 h/s/d). Our findings showed that the novel approach to data collection and processing proposed by the CIMS has significantly improved the operational efficiency of IRS on Bioko. High spatial granularity during planning and deployment together with closer follow-up of field teams using real-time data supported more homogeneous delivery of optimal coverage while sustaining high productivity.

9.
Theriogenology ; 172: 1-7, 2021 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-34082221

RESUMEN

At LFB USA, Inc., transgenic goats are utilized for the production of recombinant human protein therapeutics in their milk through the rPRO™ Technology platform. This retrospective analysis and report describes the results of induced parturition and its use as a management tool in this large herd of dairy goats. Over a three-year period, 342 does received pronuclear microinjected (MI) embryos transferred into the oviductal lumen via midline laparotomy (day 1). To initiate the induction process, does were given intramuscular injections (IM) of 10 mg each of prostaglandin (Lutalyse®) and dexamethasone to induce parturition on days 144-148 of pregnancy. Mean and Standard Deviation (±SD) time to parturition was 36.7 (±6.5) hours. Does were given these injections at 4pm on Sundays with an expected kidding time of late Monday into Tuesday morning. Of the 342 does, 333 or 97% had kidded by 3pm the following Tuesday, and 313 or 91% kidded in the 18 h between 9pm Monday and 3pm on Tuesday or between 29 and 47 h post induction. By the end of Tuesday, most kids had received colostrum and were transferred to the nursery. The incidences of kid mortality and retained placenta were 2.5% and 1.5%, respectively, clearly achieving a priority at this commercial operation for generating a high percentage of live kids (97.5%) of marked value being produced. The use of induced parturition allowed this large dairy operation to designate two 9-h time blocks in which to concentrate parturition times within the herd. This facilitated strategic scheduling to optimize availability of staff, in order to assist with parturition, separate kids from the dam at birth, and ensure adequate and prompt feeding of colostrum. Predicting the time of kidding in this way can serve as an effective management tool, especially to help reduce kid mortality and prevent disease spread by restricting suckling of colostrum.


Asunto(s)
Cabras , Parto , Animales , Calostro , Femenino , Humanos , Leche , Embarazo , Estudios Retrospectivos
10.
SSM Popul Health ; 15: 100812, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34141850

RESUMEN

We tested associations between social capital or vulnerability and health outcome measures of adult obesity, adult diabetes, and life expectancy at the county level in the United States with data from 2015 to 2018. This ecological cross-sectional study utilized secondary data from four open access databases: The Geography of Social Capital (U.S. Congress, 2018), County Health Rankings (2018), CDC's Behavioral Risk Factor Surveillance System (BRFSS, 2018) and the Kaiser Family Foundation (KFF, 2015). Our dependent variables were adult obesity, adult diabetes, and life expectancy. We identified the highest and lowest states' prevalence for each of three health outcomes in each of the four U.S. regions-Northeast, South, Midwest, and West. Each dependent variable was assessed using a sample of 32 counties (N = 32). Data analysis consisted of bivariate and regression analysis. Our results showed that the most consistent measure of "vulnerability" linked significantly to all three health conditions studied was percent births to unmarried women (Obesity p < .001; Diabetes p = .049; Life Expectancy p = .019). The most consistent measure of "social capital" linked to all three health conditions was recreation establishments per 1,000 inhabitants (Obesity p = .006; Diabetes p = .005; Life Expectancy p = .018). We concluded that measures of vulnerability were strongly associated with obesity, diabetes, and life expectancy when compared with social capital indicators. However, measures of social capital consistently accounted for the second-greatest proportion of the variance. Social and community contexts should be constantly addressed by both public health governmental- and scholarly-research agendas in the United States.

11.
Int J Nurs Sci ; 7(Suppl 1): S16-S18, 2020 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-32995374

RESUMEN

Instead of studying the impact of media on society, the traditional "top down" orientation of most communication studies scholars, this keynote presentation adopted the opposite perspective, exploring the "bottom-up" impact of "society" on "media". Unlike conventional "agenda-setting theory", which suggests that nationally prominent news media set issue "agendas" for other news media and public opinion, and also unlike the "guard dog" view that media essentially protect the interests of political and economic elites, the "community structure theory" explores links between different community (typically city or nation-state) demographics and variations in reporting on critical health concerns. Summarizing his scholarship on health communication presented and published over decades, the speaker outlined community structure theory's illumination of two overall patterns in US and cross-national coverage of health communication issues. In US coverage, broad measures of economically "buffered" privilege (educational, income, or occupational advantage) are linked to "favorable" or "government responsibility" coverage of health issues, and specific measures of "health" privilege (physicians, hospitals) are connected to "favorable" or "government responsibility" coverage promoting selected health issues. In cross-national coverage, specific measures of national "health vulnerability" (such as percent without improved water access, infant mortality rate) are linked to "government" responsibility coverage for selected health issues (human trafficking, water handling/contamination). In addition, broad measures of "macro" vulnerability conditions (agricultural dependence, political instability) are associated with "government" responsibility coverage for a wide range of health issues (genetically modified foods, drug trafficking, condom promotion, and food security). Overall, community structure theory's "bottom up" perspective reveals how the vulnerable are empowered by their demographic alignment with variations in health communication.

12.
Mol Pain ; 16: 1744806920943309, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32762277

RESUMEN

Chronic constriction injury of the sciatic nerve in rats causes peripheral neuropathy leading to pain-like behaviors commonly seen in humans. Neuropathy is a leading cause of neuropathic pain, which involves a complex cellular and molecular response in the peripheral nervous system with interactions between neurons, glia, and infiltrating immune cells. In this study, we utilize a nonsteroidal anti-inflammatory drug -loaded nanoemulsion to deliver the cyclooxygenase-2 inhibitor, Celecoxib, directly to circulating monocytes following nerve injury, which provides long-lasting pain relief. However, it is not fully understood how cyclooxygenase-2 inhibition in a macrophage traveling to the site of injury impacts gene expression in the dorsal root ganglia. To elucidate aspects of the molecular mechanisms underlying pain-like behavior in chronic constriction injury, as well as subsequent pain relief with treatment, we employ RNAseq transcriptome profiling of the dorsal root ganglia associated with the injured sciatic nerve in rats. Using high throughput RNA sequencing in this way provides insight into the molecular mechanisms involved in this neuroinflammatory response. We compare the transcriptome from the dorsal root ganglias of the following study groups: chronic constriction injury animals administered with cyclooxygenase-2 inhibiting celecoxib-loaded nanoemulsion, chronic constriction injury animals administered with vehicle treatment, a drug-free nanoemulsion, and a group of naïve, unoperated and untreated rats. The results show an extensive differential expression of 115 genes. Using the protein annotation through evolutionary relationship classification system, we have revealed pain-related signaling pathways and underlying biological mechanisms involved in the neuroinflammatory response. Quantitative polymerase chain reaction validation confirms expression changes for several genes. This study shows that by directly inhibiting cyclooxygenase-2 activity in infiltrating macrophages at the injured sciatic nerve, there is an associated change in the transcriptome in the cell bodies of the dorsal root ganglia.


Asunto(s)
Celecoxib/farmacología , Inhibidores de la Ciclooxigenasa 2/farmacología , Ganglios Espinales/metabolismo , Nanomedicina/métodos , Neuralgia/tratamiento farmacológico , Manejo del Dolor/métodos , Transcriptoma/genética , Animales , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Inflamación/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Monocitos/efectos de los fármacos , RNA-Seq , Ratas , Ratas Sprague-Dawley , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones
13.
J STEM Outreach ; 3(1)2020.
Artículo en Inglés | MEDLINE | ID: mdl-34017940

RESUMEN

Sports-related concussions affect over 280,000 adolescents each year while the general public remains ill-informed about concussions, signs/symptoms, and treatments. Adolescents may be at an increased risk for experiencing adverse physiological and psychological effects from concussions, underscoring the critical need for effective concussion education strategies. While mobile apps are increasingly being used in education and healthcare settings, none were found to offer comprehensive concussion education capable of reaching diverse audiences. The interactive mobile app "Rebound: Beating Concussions" has the potential to be an effective teaching tool for school athletic programs and medical professionals to communicate important concussion-related information to student athletes, parents, and sports coaches. A mixed methods study was used to determine the app's ability to convey information about concussions to student athletes in grades 5 through 12, parents of student athletes, and sports coaches. Concussion knowledge and participant opinions were assessed via a pre/post model and administered before and after app use. Participants demonstrated knowledge gains in the identification of concussion symptoms, treatments, and misconceptions. Additionally, participants demonstrated positive opinions on the content of the app, its relevance to everyday life, and its potential as a teaching tool.

14.
Int J Mol Sci ; 20(21)2019 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-31652890

RESUMEN

The neuroinflammatory response to peripheral nerve injury is associated with chronic pain and significant changes in the molecular expression profiles of mRNAs in neurons, glia and infiltrating immune cells. Chronic constriction injury (CCI) of the rat sciatic nerve provides an opportunity to mimic neuropathic injury and quantitatively assess behavior and differential gene expression in individual animals. Previously, we have shown that a single intravenous injection of nanoemulsion containing celecoxib (0.24 mg/kg) reduces inflammation of the sciatic nerve and relieves pain-like behavior for up to 6 days. Here, we use this targeted therapy to explore the impact on mRNA expression changes in both pain and pain-relieved states. Sciatic nerve tissue recovered from CCI animals is used to evaluate the mRNA expression profiles utilizing quantitative PCR. We observe mRNA changes consistent with the reduced recruitment of macrophages evident by a reduction in chemokine and cytokine expression. Furthermore, genes associated with adhesion of macrophages, as well as changes in the neuronal and glial mRNAs are observed. Moreover, genes associated with neuropathic pain including Maob, Grin2b/NMDAR2b, TrpV3, IL-6, Cacna1b/Cav2.2, Itgam/Cd11b, Scn9a/Nav1.7, and Tac1 were all found to respond to the celecoxib loaded nanoemulsion during pain relief as compared to those animals that received drug-free vehicle. These results demonstrate that by targeting macrophage production of PGE2 at the site of injury, pain relief includes partial reversal of the gene expression profiles associated with chronic pain.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Regulación de la Expresión Génica , Macrófagos/metabolismo , Neuralgia/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/patología , ARN Mensajero/metabolismo , Nervio Ciático/metabolismo , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Celecoxib/química , Celecoxib/farmacología , Celecoxib/uso terapéutico , Quimiocinas/genética , Quimiocinas/metabolismo , Ciclooxigenasa 2/química , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Emulsiones/química , Inflamación/metabolismo , Inflamación/patología , Macrófagos/citología , Macrófagos/efectos de los fármacos , Masculino , Nanoestructuras/química , Neuralgia/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Ratas , Ratas Sprague-Dawley
15.
Acta Neuropathol Commun ; 7(1): 108, 2019 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-31277709

RESUMEN

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve, by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, and is the rationale for intravenous delivery at this time-point. Pain relief is evident within 24 h, lasting approximately 6 days. The ipsilateral sciatic nerve and associated L4 and L5 dorsal root ganglia (DRG) tissue of both nanomedicine and control (nanoemulsion without drug) treated animals was investigated by immunofluorescence and confocal microscopy at the peak of pain relief (day-12 post-surgery), and when pain-like hypersensitivity returns (day-18 post-surgery). At day-12, a significant reduction of infiltrating macrophages, mast cells and mast cell degranulation was observed at the sciatic nerve following treatment. In the DRG, there was no effect of treatment at both day-12 and day-18. Conversely, at the DRG, there is a significant increase in macrophage infiltration and mast cell degranulation at day-18. The treatment effect on immune pathology in the sciatic nerve was investigated further by assessing the expression of macrophage cyclooxygenase-2 (COX-2)-the drug target-and extracellular prostaglandin E2 (PGE2), as well as the proportion of M1 (pro-inflammatory) and M2 (anti-inflammatory) macrophages. At day-12, there is a significant reduction of COX-2 positive macrophages, extracellular PGE2, and a striking reversal of macrophage polarity. At day-18, these measures revert to levels observed in control-treated animals. Here we present a new paradigm of immune neuropathology research, by employing a nanomedicine to target a mechanism of neuropathic pain-resulting in long-lasting pain relief--whilst revealing novel immune pathology at the injured nerve and associated DRG.


Asunto(s)
Polaridad Celular/fisiología , Macrófagos/metabolismo , Mastocitos/metabolismo , Nanomedicina/métodos , Neuralgia/metabolismo , Dimensión del Dolor/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Celecoxib/administración & dosificación , Polaridad Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Macrófagos/efectos de los fármacos , Mastocitos/efectos de los fármacos , Ratones , Neuralgia/tratamiento farmacológico , Neuralgia/patología , Dimensión del Dolor/métodos , Células RAW 264.7 , Ratas
16.
Educ Technol Res Dev ; 67(3): 711-731, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31148910

RESUMEN

Backward design is a well-established design strategy that has been used to produce educational curriculum for decades. While traditionally used to plan and create classroom-based curriculum, in this paper we explore the use of backward design as a design strategy for the development of an educational mobile application, BiblioTech™ "CityHacks: In Search of Sleep." We discuss the process from initial conception to launch and updates, as well as plans for future research.

17.
J Vis Exp ; (146)2019 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-31058897

RESUMEN

Intravenous (IV) administration of agents into the tail vein of rats can be both difficult and inconsistent. Optimizing tail vein injections is a key part of many experimental procedures where reagents need to be introduced directly into the bloodstream. Unwittingly, the injection can be subcutaneous, possibly altering the scientific outcomes. Utilizing a nanoemulsion-based biological probe with an incorporated near-infrared fluorescent (NIRF) dye, this method offers the capability of imaging a successful tail vein injection in vivo. With the use of a NIRF imager, images are taken before and after the injection of the agent. An acceptable IV injection is then qualitatively or quantitatively determined based on the intensity of the NIRF signal at the site of injection.


Asunto(s)
Colorantes Fluorescentes/administración & dosificación , Inyecciones Intravenosas/métodos , Animales , Masculino , Guías de Práctica Clínica como Asunto , Ratas , Ratas Sprague-Dawley , Cola (estructura animal)
18.
J Neuroimmunol ; 318: 72-79, 2018 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-29519721

RESUMEN

Neuroinflammation involving macrophages elevates Prostaglandin E2, associated with neuropathic pain. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) inhibits cyclooxygenase, reducing PGE2. However, NSAIDs cause physiological complications. We developed nanoemulsions incorporating celecoxib and near infrared dye. Intravenous injected nanoemulsion is incorporated into monocytes that accumulate at the injury; revealed in live animals by fluorescence. A single dose (celecoxib 0.24 mg/kg) provides targeted delivery in chronic constriction injury rats, resulting in significant reduction in the visualized inflammation, infiltration of macrophages, COX-2 and PGE2. Animals exhibit relief from hypersensitivity persisting at least four-days. The total body burden of drug is reduced by >2000 fold over oral drug delivery.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Celecoxib/farmacología , Macrófagos/efectos de los fármacos , Nervio Ciático/efectos de los fármacos , Nervio Ciático/lesiones , Animales , Emulsiones , Inyecciones Intravenosas , Masculino , Nanotecnología , Neuralgia/tratamiento farmacológico , Ratas , Ratas Sprague-Dawley
19.
Vet Rec ; 182(17): 483, 2018 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-29431145

RESUMEN

This retrospective analysis and report describes the successful eradication and posteradication surveillance programme for Johne's disease (Mycobacterium avium subspecies paratuberculosis (MAP)) in a closed herd of dairy goats. In 1994, MAP's presence in the goat herd was first suspected through individual annual serological screening and then subsequently confirmed through faecal culture and histopathology in 1997 when implementation of a more aggressive programme of testing and eradication of the diseased animals began. This programme included frequent serological screening of all adult goats using ELISA and agar gel immunodiffusion assays. Faecal cultures for bacteria were performed on suspect or positive animals and for all goats found dead or euthanased, and tissues were submitted for histopathology and acid-fast staining. Additional disease eradication measures included maintaining a closed herd and minimising faecal-oral transmission of MAP. Following a more aggressive testing regimen and euthanasia of goats with positive faecal culture, the herd was first considered free of MAP in 2003 and has remained free to the present day.


Asunto(s)
Industria Lechera , Erradicación de la Enfermedad , Enfermedades de las Cabras/prevención & control , Paratuberculosis/prevención & control , Animales , Heces/microbiología , Femenino , Enfermedades de las Cabras/microbiología , Cabras , Mycobacterium avium subsp. paratuberculosis/aislamiento & purificación , Nueva Zelanda/epidemiología , Evaluación de Programas y Proyectos de Salud , Estudios Retrospectivos
20.
J STEM Outreach ; 1(1)2018.
Artículo en Inglés | MEDLINE | ID: mdl-32656506

RESUMEN

Charles Darwin is largely unknown and poorly understood as a historical figure. Similarly the fundamental principles of evolution are often misstated, misunderstood, or entirely rejected by large numbers of Americans. Simply trying to communicate more facts about Darwin, or facts supporting the principles of evaluation, is inadequate; neither students nor members of the public will care or retain the information. On the contrary, building facts into a one-on-one conversational narrative creates a memorable opportunity to learn. Here we create a digital media, self-guided question and answer 'synthetic interview' with Charles Darwin. Questions are derived from a survey of nearly 1,000 people. Answers spoken by an actor portraying Darwin are derived from Darwin's own writings. Questions on modern topics are answered by scientists, theologians, and lawyers. First produced as a museum exhibit and then later reproduced as an app (iOS/Android), the Darwin Synthetic Interview has been evaluated with more than 3,000 surveyed users, of which 69% indicated that they learned and more than 75% would recommend the experience. Students who interacted with the synthetic interview in a classroom setting found answers were unexpected and clarifying. Using a format of personal narrative, the Darwin Synthetic Interview creates a new way to engage students and the public in a process of self-directed discovery of a topic that is often considered difficult to teach.

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