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Human breath contains biomarkers (odorants) that can be targeted for early disease detection. It is well known that honeybees have a keen sense of smell and can detect a wide variety of odors at low concentrations. Here, we employ honeybee olfactory neuronal circuitry to classify human lung cancer volatile biomarkers at different concentrations and their mixtures at concentration ranges relevant to biomarkers in human breath from parts-per-billion to parts-per-trillion. We also validated this brain-based sensing technology by detecting human non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines using the 'smell' of the cell cultures. Different lung cancer biomarkers evoked distinct spiking response dynamics in the honeybee antennal lobe neurons indicating that those neurons encoded biomarker-specific information. By investigating lung cancer biomarker-evoked population neuronal responses from the honeybee antennal lobe, we classified individual human lung cancer biomarkers successfully (88% success rate). When we mixed six lung cancer biomarkers at different concentrations to create 'synthetic lung cancer' vs. 'synthetic healthy' human breath, honeybee population neuronal responses were able to classify those complex breath mixtures reliably with exceedingly high accuracy (93-100% success rate with a leave-one-trial-out classification method). Finally, we employed this sensor to detect human NSCLC and SCLC cell lines and we demonstrated that honeybee brain olfactory neurons could distinguish between lung cancer vs. healthy cell lines and could differentiate between different NSCLC and SCLC cell lines successfully (82% classification success rate). These results indicate that the honeybee olfactory system can be used as a sensitive biological gas sensor to detect human lung cancer.
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Biomarcadores de Tumor , Técnicas Biosensibles , Neoplasias Pulmonares , Olfato , Humanos , Animales , Neoplasias Pulmonares/patología , Abejas , Técnicas Biosensibles/métodos , Técnicas Biosensibles/instrumentación , Olfato/fisiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Odorantes/análisis , Pruebas Respiratorias/métodos , Pruebas Respiratorias/instrumentación , Carcinoma Pulmonar de Células Pequeñas/patología , Compuestos Orgánicos Volátiles/análisisRESUMEN
The presence of contaminants in cacao-derived products, especially in chocolates, has raised concerns regarding food safety and human health. The study assessed the concentration variation of 16 elements in 155 chocolate samples from the US market by cacao content and country of geographic origin. The study further examined the potential health risks posed by toxic metals and determined the contribution of essential elements to the Daily Recommended Intake (DRI), estimated based on an ounce (â¼28.4 g) of daily chocolate consumption. Dark chocolates with ≥50 % cacao exhibited consecutively increasing mean levels from 1.2 to 391 µg/kg for U, Tl, Th, As, Pb, Se, Cd, and Co. Similarly, Ni, Sr, Cu, Mn, Zn, Fe, Ca, and Mg had mean concentrations from 4.0 to 1890 mg/kg. Dark chocolates sourced from Central and South America exhibited the highest mean levels of Cd, and South America samples also contained elevated Pb, whereas those from West Africa and Asia had low Cd and Pb, respectively. Cacao contents showed increasingly strong association with Cd, Co, Mn, Sr, Ni, Cu, Zn, and Mg (r = 0.60-0.84), and moderately with Se, Fe, As, and Tl (r = 0.35-0.49), indicating these elements are primarily derived from cacao beans. Weak association of cacao contents with Pb, Th, and U levels (r < 0.25), indicates post-harvest contaminations. Hazard Quotient (HQ) > 1 was found only for Cd in 4 dark chocolates, and Hazard Index (HI) > 1 for cumulative risk of Cd, Pb, Ni, As, and U was found in 33 dark chocolates, indicating potential non-carcinogenic risks for 15 kg children but none for 70 kg adults. Dark chocolate also substantially contributed to 47-95 % of the DRI of Cu for children and 50 % for adults. Dark chocolates also provided notable Fe, Mn, Mg, and Zn contributions to the DRI. These essential elements are recognized to reduce the bioavailability of toxic metals such as Cd, Pb, or Ni, thereby potentially lowering associated health risks. This study informs consumers, food industries, and regulatory agencies to target cacao origins or chocolate brands with lower toxic metal contents for food safety and minimizing adverse health effects.
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Cacao , Chocolate , Contaminación de Alimentos , Metales Pesados , Metales Pesados/análisis , Medición de Riesgo , Chocolate/análisis , Humanos , Cacao/química , Contaminación de Alimentos/análisis , Estados Unidos , Oligoelementos/análisis , Ingesta Diaria RecomendadaRESUMEN
OBJECTIVE: Comprehensive studies examining longitudinal predictors of dietary change during the coronavirus disease 2019 pandemic are lacking. Based on an ecological framework, this study used longitudinal data to test if individual, social and environmental factors predicted change in dietary intake during the peak of the coronavirus 2019 pandemic in Los Angeles County and examined interactions among the multilevel predictors. DESIGN: We analysed two survey waves (e.g. baseline and follow-up) of the Understanding America Study, administered online to the same participants 3 months apart. The surveys assessed dietary intake and individual, social, and neighbourhood factors potentially associated with diet. Lagged multilevel regression models were used to predict change from baseline to follow-up in daily servings of fruits, vegetables and sugar-sweetened beverages. SETTING: Data were collected in October 2020 and January 2021, during the peak of the coronavirus disease 2019 pandemic in Los Angeles County. PARTICIPANTS: 903 adults representative of Los Angeles County households. RESULTS: Individuals who had depression and less education or who identified as non-Hispanic Black or Hispanic reported unhealthy dietary changes over the study period. Individuals with smaller social networks, especially low-income individuals with smaller networks, also reported unhealthy dietary changes. After accounting for individual and social factors, neighbourhood factors were generally not associated with dietary change. CONCLUSIONS: Given poor diets are a leading cause of death in the USA, addressing ecological risk factors that put some segments of the community at risk for unhealthy dietary changes during a crisis should be a priority for health interventions and policy.
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COVID-19 , Dieta , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Los Angeles/epidemiología , Femenino , Masculino , Adulto , Persona de Mediana Edad , Dieta/estadística & datos numéricos , Factores Socioeconómicos , Estudios Longitudinales , Verduras , Pandemias , Frutas , Características de la Residencia/estadística & datos numéricos , Anciano , Adulto Joven , Conducta Alimentaria , Bebidas Azucaradas/estadística & datos numéricosRESUMEN
Over the past decade, thousands of bacteriophage genomes have been sequenced and annotated. A striking observation from this work is that known structural features and functions cannot be assigned for >65% of the encoded proteins. One approach to begin experimentally elucidating the function of these uncharacterized gene products is genome-wide screening to identify phage genes that confer phenotypes of interest like inhibition of host growth. This study describes the results of a screen evaluating the effects of overexpressing each gene encoded by the temperate Cluster F1 mycobacteriophage Girr on the growth of the host bacterium Mycobacterium smegmatis. Overexpression of 29 of the 102 Girr genes (~28% of the genome) resulted in mild to severe cytotoxicity. Of the 29 toxic genes described, 12 have no known function and are predominately small proteins of <125 amino acids. Overexpression of the majority of these 12 cytotoxic no known functions proteins resulted in moderate to severe growth reduction and represent novel antimicrobial products. The remaining 17 toxic genes have predicted functions, encoding products involved in phage structure, DNA replication/modification, DNA binding/gene regulation, or other enzymatic activity. Comparison of this dataset with prior genome-wide cytotoxicity screens of mycobacteriophages Waterfoul and Hammy reveals some common functional themes, though several of the predicted Girr functions associated with cytotoxicity in our report, including genes involved in lysogeny, have not been described previously. This study, completed as part of the HHMI-supported SEA-GENES project, highlights the power of parallel, genome-wide overexpression screens to identify novel interactions between phages and their hosts.
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Genoma Viral , Micobacteriófagos , Mycobacterium smegmatis , Mycobacterium smegmatis/virología , Micobacteriófagos/genética , Proteínas Virales/genética , Proteínas Virales/metabolismoRESUMEN
Objective: The aim of the present study is to utilize a natural experiment and examine changes in dietary patterns of predominantly low-income, racial and ethnic minority children who live in a public housing community following the opening of a new supermarket. Methods: Data comes from the Watts Neighborhood Health Study (WNHS), an ongoing study in South Los Angeles, United States, that follows residents of Jordan Downs, a public housing community undergoing redevelopment. Surveys were administered to children aged 9-17 years (n = 297), as well as an adult in the household. The second baseline data collection was conducted June-December 2019, and follow-up was conducted June 2020-April 2021, shortly after the introduction of the new supermarket in January 2020. ANCOVA linear regression models were estimated to examine the association between children's proximity to the new supermarket with dietary outcomes at follow-up. Interactions with barriers to food access were also explored. Results: Living close to the new supermarket was not significantly associated with dietary outcomes at follow-up. However, for children who lived in households with no vehicle access, living close to the new supermarket was associated with increased fruit and vegetable consumption, compared to children in the comparison group. Conclusion: Proximity to the new supermarket was not associated with improved dietary outcomes among children unless they had transportation barriers. This adds to the growing body of literature that suggests that the effects of neighborhood food environments may be modified by individuals' mobility, and that comprehensive interventions are needed.
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Using the cognitive appraisal theory of coping and the self-determination theory of motivation, we examined the shared variance of motivational orientations, attachment relationships, and gender on adaptive and maladaptive coping among youth experiencing homelessness. Several scales including The Global Motivation Scale (assessing motivational orientations; i.e., autonomous and controlled motivation), the Brief Cope (adaptive and maladaptive coping strategies), and the Inventory of Parent and Peer Attachment (self-perceptions of relationships with mothers, fathers, and peers) were administered to 102 youth aged between 16 and 24 (Mage = 20, SD = 2.07) years recruited from an evening program for youth experiencing homelessness in Montreal, Canada. Autonomous motivation was positively associated with engagement in effective coping strategies, while controlled motivation was positively linked to maladaptive coping. Moderation analyses were used to examine whether gender and relationships with attachment figures moderated the relationship between motivation and coping. A significant main effect of peer attachment on adaptive coping emerged, in which greater peer attachment was related to more adaptive coping among the youth. No interaction effects resulted. Although no significant moderating effects were associated with essential relationships and gender, further research implementing a more nuanced approach to assessing the interaction between these constructs may be warranted. Overall, the findings highlight the importance of intervention programs for youth experiencing homelessness, that focus on enhancing autonomous motivation and utilizing peer support to optimize the use of adaptive coping strategies.
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Personas con Mala Vivienda , Motivación , Pruebas Psicológicas , Autoinforme , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Adaptación Psicológica , Relaciones InterpersonalesRESUMEN
Secretariat and Hydrus are phages grouped into the DJ cluster that were isolated on Gordonia rubripertincta NRRL B-16540. The phages have 75% nucleotide identity and share 73% gene content. Secretariat has a genome with 84 predicted genes, while Hydrus has 91 predicted genes and can also infect Gordonia terrae 3612.
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OBJECTIVE: The COVID-19 pandemic increased food insufficiency: a severe form of food insecurity. Drawing on an ecological framework, we aimed to understand factors that contributed to changes in food insufficiency from April to December 2020, in a large urban population hard hit by the pandemic. DESIGN: We conducted internet surveys every 2 weeks in April-December 2020, including a subset of items from the Food Insecurity Experience Scale. Longitudinal analysis identified predictors of food insufficiency, using fixed effects models. SETTING: Los Angeles County, which has a diverse population of 10 million residents. PARTICIPANTS: A representative sample of 1535 adults in Los Angeles County who are participants in the Understanding Coronavirus in America tracking survey. RESULTS: Rates of food insufficiency spiked in the first year of the pandemic, especially among participants living in poverty, in middle adulthood and with larger households. Government food assistance from the Supplemental Nutrition Assistance Program was significantly associated with reduced food insufficiency over time, while other forms of assistance such as help from family and friends or stimulus funds were not. CONCLUSIONS: The findings highlight that during a crisis, there is value in rapidly monitoring food insufficiency and investing in government food benefits.
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COVID-19 , Asistencia Alimentaria , Adulto , Humanos , Pandemias , Los Angeles/epidemiología , Factores Protectores , COVID-19/epidemiologíaRESUMEN
BACKGROUND: Public housing residents, who tend to be predominantly female and racial/ethnic minorities, are at a particularly high risk for chronic health conditions. Prior studies have suggested that a lack of access to healthy and affordable food may be an important barrier in public housing communities, but evidence is mixed on the association between the neighborhood food environment and dietary quality, suggesting the need to examine food access patterns in low-income, minority communities more deeply. The purpose of this study was to examine the variability in grocery shopping patterns, and the factors that predict them, among low-income minority women in public housing. METHODS: Interviewer-administered surveys and body composition measurements were collected in the Watts Neighborhood Health Study, an ongoing longitudinal cohort study of low-income urban public housing residents located in South Los Angeles. Descriptive analyses were conducted to understand the variation in grocery shopping patterns among women. Logistic and ordered logistic regression models were estimated to examine the association between resident characteristics and grocery shopping patterns. RESULTS: There was considerable variability in grocery shopping patterns, including the types of grocery stores accessed, distance travelled, frequency of shopping, and reasons behind grocery store choice. Grocery shopping patterns were associated with several participant characteristics, including race/ethnicity, working status, access to a car, income, and education. Hispanic participants were less likely to shop at a supermarket, travel further distances to shop, shop more frequently, and were more likely to prioritize price in their choice of primary grocery store than non-Hispanic Black women participants. CONCLUSIONS: There was considerable variability in grocery shopping patterns, even within this low-income, minority community despite access to the same neighborhood food environment. Convenience and quality, in addition to price, were priorities for choice of primary grocery store, and differences by race/ethnicity suggest that initiatives to improve the neighborhood food environment should consider quality of food, cultural factors, and availability of foods desired by the surrounding community, in addition to price and proximity of grocery stores.
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Abastecimiento de Alimentos , Vivienda Popular , Comercio , Femenino , Humanos , Estudios Longitudinales , Masculino , Pobreza , Características de la ResidenciaRESUMEN
Women and children enrolled in federally funded home visitation services are at an increased risk for unhealthy diet and physical activity patterns. Home visitors have a privileged relationship with their clients and hold a unique perspective of the multilevel influences surrounding these behaviors. This study explored the question: "What are home visitors' perspectives and experiences with their families' diet and physical activity behaviors?" Home visitors enrolled in a larger trial were invited to participate in focus group sessions (n=13). Topics covered their clients' constraints and capacity building opportunities for healthful diet and activity practices. Reflexive thematic analysis was used to analyze the data. The home visitors discussed key influences on diet and activity, and three overarching themes were identified: (a) acute periods of crises and mental health issues; (b) the role of the mother within the family; and (c) support and barriers within mothers' broader social network. The themes identified in this study highlight the complex, multidimensional influences on the dietary and physical activity patterns of these families, and pinpoint key areas of opportunity for intervention.
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Poor diets are historically the leading cause of morbidity and mortality in the United States (U.S.), causing over 44,000 deaths each month. Dietary patterns have likely changed during the COVID-19 pandemic due to major shifts and crises in social, economic, and food systems. This study examines self-reported dietary changes in Los Angeles (L.A.) County during COVID-19, and identifies factors associated with making healthy and unhealthy changes. Data are from the Understanding Coronavirus in America Study, an internet panel of adults representative of L.A. County households (N = 1080). Multinomial logistic regression was used to test if self-reported change in diet healthiness assessed in July 2020 was associated with socio-ecological factors known to be associated with diet, assessed between April-July 2020. More than half of L.A. County residents reported making changes to their diet: 28.3% reported eating healthier food since the beginning of the pandemic, while 24.8% reported eating less healthy food. Individuals who were significantly more likely to report healthy changes were Non-Hispanic Black or Hispanic/Latino (vs. Non-Hispanic White), had received unemployment insurance, or had larger social networks. Individuals who were significantly more likely to report unhealthy changes were younger, of mixed race, had children in their household, had transportation barriers, or had obesity. Individuals who were significantly more likely to report both healthy and unhealthy changes were Asian, had experienced food insecurity, or had challenges getting food due to store closures. The pandemic may be exacerbating diet-related disease risk in some groups, such as communities of color, and among individuals with obesity and those facing transportation barriers.
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COVID-19 , Pandemias , Adulto , Niño , Humanos , Los Angeles/epidemiología , SARS-CoV-2 , Autoinforme , Estados Unidos/epidemiologíaRESUMEN
VanLee is a singleton phage that was isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540 as the host. The genome is 84,560 bp and has a GC content of 67.8%. VanLee has 164 predicted protein-coding genes and one tRNA. VanLee can infect Gordonia terrae with the same efficiency as G. rubripertincta.
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BACKGROUND: Few studies have assessed neurodevelopmental outcomes in normocephalic infants born to women with Zika virus (ZIKV) infection during pregnancy in Mexico. We sought to evaluate ZIKV exposed infants in Yucatan, Mexico, with performance-based and eye-gaze measures of neurodevelopment, removing observer bias. METHODS: We enrolled 60 infants about 6-month old born to women with PCR + test for ZIKV during pregnancy. Infants were normocephalic and asymptomatic. Sixty infants born to women without a history of ZIKV infection were included as comparison. Children were assessed with the Mullen scales of early learning (MSEL), a test with scales in motor, language, and overall cognitive skills development, and the Fagan test of infant intelligence (FTII) using automated eye-tracking instrumentation to evaluate infant visual preference of human faces, where longer gaze lengths to unfamiliar (i.e., new) faces are expected. RESULTS: All MSEL subscale scores, except expressive language, were significantly lower among ZIKV exposed children compared to controls, including the overall standard composite (80 ± 10 vs. 87 ± 7.4, respectively; p < 0.001). FTII eye-tracking measures of fixation and gaze length were in the expected direction, with longer times recorded among infants in the control group (i.e., higher attention), but none reached statistical significance. In adjusted linear regressions, the FTII high novelty score (expected preference for a novel face) predicted fine motor (ß = 3.61, p = 0.04) and receptive language (ß = 2.55, p = 0.03) scores. CONCLUSIONS: Nonmicrocephalic children born to women with ZIKV during pregnancy in Mexico merit early neurodevelopmental evaluation to allow for appropriate interventions and clinical follow-up. It is possible that long-term monitoring of cognitive deficits may need to be established for a proportion of affected cases.
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Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Virus Zika , Niño , Preescolar , Femenino , Humanos , Lactante , Inteligencia , México/epidemiología , Embarazo , Complicaciones Infecciosas del Embarazo/epidemiología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/epidemiologíaRESUMEN
OBJECTIVES: Most research evaluating relationships between social network attributes and loneliness have focused on older adult and adolescent networks. The present study examines the relationships between social network size (number of relationships), social network density (whether named relationships are connected to one another) and maternal loneliness during pregnancy. METHODS: Eligible women were enrolled at the time of their dating ultrasound (between 8 and 12 weeks of gestation). Interested women provided written consent and completed demographic, social network and loneliness measures. Participants completed the same surveys in their third trimester. Mixed-regression models, adjusted for age, race, ethnicity, and insurance type, were used to assess the relationship between social network size, network density, and loneliness. RESULTS: A total of 94 pregnant women (mean age = 23.77, 70.2% Black, 87.2% public insurance) completed baseline study measures, and 60 participants completed both assessment time points. Completers and non-completers did not differ on key characteristics. Social network density, but not social network size, predicted maternal loneliness ([Formula: see text]= - 1.27, 95% CI - 2.53, - 0.01, p = 0.0489) in the first and third trimester. CONCLUSIONS: These findings indicate that pregnant women's social network density may be more intimately related to feelings of loneliness than the objective number of relationships. This knowledge can begin to inform the design of supportive approaches to improve women's health.
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Negro o Afroamericano/psicología , Soledad/psicología , Mujeres Embarazadas/psicología , Aislamiento Social/psicología , Red Social , Esposos/psicología , Adolescente , Adulto , Alabama , Femenino , Humanos , Masculino , Embarazo , Mujeres Embarazadas/etnología , Apoyo Social , Salud de la Mujer , Adulto JovenRESUMEN
Recordings and stimulations of neuronal electrical activity are topics of great interest in neuroscience. Many recording techniques, and even treatment of neurological disorders, can benefit from a microelectrode that is flexible, chemically inert, and electrically conducting and preferentially transfers electrons via capacitive charge injection. Commercial electrodes that currently exist and other electrodes that are being tested with the purpose of facilitating and improving the electron transport between solid materials and biological tissues still have some limitations. This paper discusses carbon nanotube (CNT)-based microelectrodes to record and stimulate neurons and compares their electron transport capabilities to noble metals such as Au and Ag. The recording ability of electrodes is tested through electroretinography on Sarcophaga bullata fly eyes by using Au and Ag wires and CNT fibers as electrodes. Stimulation is demonstrated through the implantation of Au wire and CNT fibers into the antennas of the Madagascar hissing cockroach (Gromphadorhina portentosa) to control their locomotion. Our results demonstrate that a particular property of the CNT fiber is its high rate of electron transfer, leading to an order of magnitude lower impedance compared to Au and Ag and an impressive 15.09 charge injection capacity. We also established that this carbon nanomaterial assembly performs well for in vivo electrophysiology, rendering it a promising prospect for neurophysiological applications.
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OBJECTIVES: To determine the association of the use of the multiplex assay meningitis/encephalitis panel with clinical management of suspected meningitis. METHODS: A cross-sectional study was conducted with children 0 to 18 years of age who received a lumbar puncture within 48 hours of admission for an infectious workup. Patient demographic and presenting information, laboratory studies, and medication administration were collected. The primary measure was length of stay (LOS) with secondary measures: time on antibiotics, time to narrowing antibiotics, and acyclovir doses. LOS and antibiotic times were stratified for outcomes occurring before 36 hours. Logistic regression analysis was used to account for potential confounding factors associated with both the primary and secondary outcomes. A value of P < .05 was considered statistically significant. RESULTS: Meningitis panel use was associated with a higher likelihood of a patient LOS <36 hours (P = .04; odds ratio = 1.7; 95% confidence interval [CI]: 1.03-2.87), a time to narrowing antibiotics <36 hours (P = .008; odds ratio = 1.89; 95% CI: 1.18-2.87), and doses of acyclovir (P < .001; incidence rate ratio = 0.37; 95% CI: 0.26-0.53). When controlling for potential confounding factors, these associations persisted. CONCLUSIONS: Use of the meningitis panel was associated with a decreased LOS, time to narrowing of antibiotics, and fewer acyclovir doses. This likely is a result of the rapid turnaround time as compared with cerebrospinal fluid cultures. Additional studies to examine the outcomes related to this change in management are warranted.
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Encefalitis por Herpes Simple/diagnóstico , Infecciones por Enterovirus/diagnóstico , Meningitis Bacterianas/diagnóstico , Meningitis Neumocócica/diagnóstico , Meningitis Viral/diagnóstico , Infecciones por Roseolovirus/diagnóstico , Aciclovir/uso terapéutico , Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Estudios Transversales , Encefalitis por Herpes Simple/líquido cefalorraquídeo , Encefalitis por Herpes Simple/tratamiento farmacológico , Infecciones por Enterovirus/líquido cefalorraquídeo , Infecciones por Enterovirus/tratamiento farmacológico , Femenino , Humanos , Lactante , Recién Nacido , Tiempo de Internación/estadística & datos numéricos , Masculino , Meningitis Bacterianas/líquido cefalorraquídeo , Meningitis Bacterianas/tratamiento farmacológico , Meningitis Neumocócica/líquido cefalorraquídeo , Meningitis Neumocócica/tratamiento farmacológico , Meningitis Viral/líquido cefalorraquídeo , Meningitis Viral/tratamiento farmacológico , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Infecciones por Roseolovirus/líquido cefalorraquídeo , Infecciones por Roseolovirus/tratamiento farmacológico , Punción EspinalRESUMEN
Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood-brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity. The effect of replacing phenylalanine's carboxylic acid with a tetrazole, acylsulfonamide and hydroxamic acid (HA) bioisostere was examined. Compounds were tested for their ability to be LAT1 substrates using both cis-inhibition and trans-stimulation cell assays. As HA-Phe demonstrated weak substrate activity, its structure-activity relationship (SAR) was further explored by synthesis and testing of HA derivatives of other LAT1 amino acid substrates (i.e., Tyr, Leu, Ile, and Met). The potential for a false positive in the trans-stimulation assay caused by parent amino acid was evaluated by conducting compound stability experiments for both HA-Leu and the corresponding methyl ester derivative. We concluded that HA's are transported by LAT1. In addition, our results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site.
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Ácidos Carboxílicos/metabolismo , Ácidos Hidroxámicos/metabolismo , Transportador de Aminoácidos Neutros Grandes 1/metabolismo , Barrera Hematoencefálica , Ácidos Carboxílicos/química , Cromatografía Líquida de Alta Presión , Células HEK293 , Humanos , Ácidos Hidroxámicos/química , Espectroscopía de Resonancia Magnética , Relación Estructura-ActividadRESUMEN
OBJECTIVE: Discrimination is posited to underlie racial disparities in hypertension. Extant literature suggests a possible association between racial discrimination and blood pressure, although inconsistent findings have been reported. The aim of this comprehensive systematic review was to quantitatively evaluate the association between perceived racial discrimination with hypertensive status and systolic, diastolic, and ambulatory blood pressure. METHOD: Electronic database search of PubMed and PsycINFO (keywords: blood pressure/hypertension/diastolic/systolic, racism/discrimination/prejudice/unfair treatment) was combined with descendancy and ascendancy approaches. Forty-four articles (N = 32,651) met inclusion criteria. Articles were coded for demographics, hypertensive diagnosis, blood pressure measurement, discrimination measure and constructs, study quality, and effect sizes. RESULTS: Random effects meta-analytic models were tested based on Fisher's Z, the derived common effect size metric. Overall, perceived racial discrimination was associated with hypertensive status, Zhypertension = 0.048, 95% CI [.013, .087], but not with resting blood pressure, Zsystolic = 0.011, 95% CI [-.006, .031], Zdiastolic = .016, 95% CI [-.006, .034]. Moderators that strengthened the relation included sex (male), race (Black), age (older), education (lower), and hypertensive status. Perceived discrimination was most strongly associated with nighttime ambulatory blood pressure, especially among Blacks. CONCLUSIONS: Despite methodological limitations in the existing literature, there was a small, significant association between perceived discrimination and hypertension. Future studies should consider ambulatory nighttime blood pressure, which may more accurately capture daily variation attributable to experienced racial discrimination. Perceived discrimination may partly explain racial health disparities.
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Negro o Afroamericano/psicología , Hipertensión/etnología , Racismo/etnología , Percepción Social , Negro o Afroamericano/estadística & datos numéricos , Presión Sanguínea , Humanos , Hipertensión/psicología , Racismo/psicologíaRESUMEN
INTRODUCTION: Participation, a construct within the disability/functioning framework, is evaluated on a person's involvement in life situations including family, community, work, social, and civic life. In the context of recovering from a major health event, participation is a treatment goal and it is known to correlate with the quality of life. OBJECTIVE: The purpose of this study is to track the dynamics of participation post-stroke in relationship to the dynamics of walking capacity, social support, and mood. METHODS: An inception cohort was followed over the first post-stroke year. Group-based trajectory analysis, a form of latent class analysis, was used to identify distinctive groups of individuals with similar trajectories. Dual trajectories were used to estimate concordance between participation trajectory and trajectories for each of the three constructs under study. RESULTS: From the sample of 102 persons (mean age 70), four trajectories of participation were identified, two of which were qualified as excellent and very good, and two qualified as fair and poor. All those with excellent walking showed excellent participation. However, people with excellent (and very good) community participation had a range of walking capacities. Most (82%) people with normal mood showed excellent participation. People with good mood but not meeting norms for age showed the complete range of participation trajectories from excellent to poor. The higher proportion of people with excellent or good social support (57%) showed excellent participation. CONCLUSION: Two treatable component causes of participation, walking capacity and mood, were identified; of these, only excellent walking capacity could be considered a sufficient cause.