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2.
PLoS Biol ; 21(3): e3002035, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36996009

RESUMEN

Cerebrospinal fluid (CSF) flow maintains healthy brain homeostasis, facilitating solute transport and the exchange of brain waste products. CSF flow is thus important for brain health, but the mechanisms that control its large-scale movement through the ventricles are not well understood. While it is well established that CSF flow is modulated by respiratory and cardiovascular dynamics, recent work has also demonstrated that neural activity is coupled to large waves of CSF flow in the ventricles during sleep. To test whether the temporal coupling between neural activity and CSF flow is in part due to a causal relationship, we investigated whether CSF flow could be induced by driving neural activity with intense visual stimulation. We manipulated neural activity with a flickering checkerboard visual stimulus and found that we could drive macroscopic CSF flow in the human brain. The timing and amplitude of CSF flow was matched to the visually evoked hemodynamic responses, suggesting neural activity can modulate CSF flow via neurovascular coupling. These results demonstrate that neural activity can contribute to driving CSF flow in the human brain and that the temporal dynamics of neurovascular coupling can explain this effect.


Asunto(s)
Acoplamiento Neurovascular , Vigilia , Humanos , Encéfalo/fisiología , Acoplamiento Neurovascular/fisiología , Hemodinámica , Sueño , Imagen por Resonancia Magnética
3.
Insect Mol Biol ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38923717

RESUMEN

Epigenetic mechanisms, such as DNA methylation, have been proposed to mediate plastic responses in insects. The pea aphid (Acyrthosiphon pisum), like the majority of extant aphids, displays cyclical parthenogenesis - the ability of mothers to switch the reproductive mode of their offspring from reproducing parthenogenetically to sexually in response to environmental cues. The pea aphid genome encodes two paralogs of the de novo DNA methyltransferase gene, dnmt3a and dnmt3x. Here we show, using phylogenetic analysis, that this gene duplication event occurred at least 150 million years ago, likely after the divergence of the lineage leading to the Aphidomorpha (phylloxerans, adelgids and true aphids) from that leading to the scale insects (Coccomorpha) and that the two paralogs are maintained in the genomes of all aphids examined. We also show that the mRNA of both dnmt3 paralogs is maternally expressed in the viviparous aphid ovary. During development both paralogs are expressed in the germ cells of embryos beginning at stage 5 and persisting throughout development. Treatment with 5-azactyidine, a chemical that generally inhibits the DNA methylation machinery, leads to defects of oocytes and early-stage embryos and causes a proportion of later stage embryos to be born dead or die soon after birth. These phenotypes suggest a role for DNA methyltransferases in reproduction, consistent with that seen in other insects. Taking the vast evolutionary history of the dnmt3 paralogs, and the localisation of their mRNAs in the ovary, we suggest there is a role for dnmt3a and/or dnmt3x in early development, and a role for DNA methylation machinery in reproduction and development of the viviparous pea aphid.

4.
Adapt Phys Activ Q ; 41(1): 67-87, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37339770

RESUMEN

The aim of this study was to identify contextual factors that negatively affect activity and participation among powerchair football (PF) players. Thirty-seven semistructured interviews were conducted with PF players (Mage = 27.9 ± 8.2 years) in France (n = 18) and the United States (n = 19). Participants reported acute back and neck pain as the primary morbidities resulting from PF participation, with sustained atypical posture in the sport chair as the primary cause. Competition-related physical and mental stress were also identified as participation outcomes. Accompanying the many benefits of PF, participants recognized negative impacts of discomfort, physical fatigue, and mental fatigue. Interventions such as seating modifications, thermotherapy to combat pain, napping to combat acute physical stress, and mental preparation to manage state anxiety were all identified as prospective interventions.


Asunto(s)
Fútbol , Deportes para Personas con Discapacidad , Humanos , Estudios Prospectivos , Estados Unidos , Adulto Joven , Adulto , Atletas , Dolor de Espalda , Dolor de Cuello , Estrés Fisiológico , Estrés Psicológico
5.
Neuroimage ; 273: 120092, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37028736

RESUMEN

Simultaneous EEG-fMRI is a powerful multimodal technique for imaging the brain, but its use in neurofeedback experiments has been limited by EEG noise caused by the MRI environment. Neurofeedback studies typically require analysis of EEG in real time, but EEG acquired inside the scanner is heavily contaminated with ballistocardiogram (BCG) artifact, a high-amplitude artifact locked to the cardiac cycle. Although techniques for removing BCG artifacts do exist, they are either not suited to real-time, low-latency applications, such as neurofeedback, or have limited efficacy. We propose and validate a new open-source artifact removal software called EEG-LLAMAS (Low Latency Artifact Mitigation Acquisition Software), which adapts and advances existing artifact removal techniques for low-latency experiments. We first used simulations to validate LLAMAS in data with known ground truth. We found that LLAMAS performed better than the best publicly-available real-time BCG removal technique, optimal basis sets (OBS), in terms of its ability to recover EEG waveforms, power spectra, and slow wave phase. To determine whether LLAMAS would be effective in practice, we then used it to conduct real-time EEG-fMRI recordings in healthy adults, using a steady state visual evoked potential (SSVEP) task. We found that LLAMAS was able to recover the SSVEP in real time, and recovered the power spectra collected outside the scanner better than OBS. We also measured the latency of LLAMAS during live recordings, and found that it introduced a lag of less than 50 ms on average. The low latency of LLAMAS, coupled with its improved artifact reduction, can thus be effectively used for EEG-fMRI neurofeedback. A limitation of the method is its use of a reference layer, a piece of EEG equipment which is not commercially available, but can be assembled in-house. This platform enables closed-loop experiments which previously would have been prohibitively difficult, such as those that target short-duration EEG events, and is shared openly with the neuroscience community.


Asunto(s)
Camélidos del Nuevo Mundo , Neurorretroalimentación , Adulto , Animales , Humanos , Imagen por Resonancia Magnética/métodos , Electroencefalografía/métodos , Artefactos , Potenciales Evocados Visuales
6.
Plant Cell Environ ; 46(5): 1691-1704, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36654510

RESUMEN

Soil micronutrient availability, including zinc (Zn), is a limiting factor for crop yield. Arbuscular mycorrhizal (AM) fungi can improve host plant growth and nutrition through the mycorrhizal pathway of nutrient uptake. Although the physiology of Zn uptake through the mycorrhizal pathway is well established, the identity of the related molecular components are unknown. Here, RNA-seq analysis was used to identify genes differentially-regulated by AM colonization and soil Zn concentration in roots of Medicago truncatula. The putative Zn transporter gene MtZIP14 was markedly up-regulated in M. truncatula roots when colonized by Rhizophagus irregularis. MtZIP14 restored yeast growth under low Zn availability. Loss-of-function mutant plants (mtzip14) had reduced shoot biomass compared to the wild-type when colonized by AM fungi and grown under low and sufficient soil Zn concentration; at high soil Zn concentration, there were no genotypic differences in shoot biomass. The vesicular and arbuscular colonization of roots was lower in the mtzip14 plants regardless of soil Zn concentration. We propose that MtZIP14 is linked to AM colonization in M. truncatula plants, with the possibility that MtZIP14 function with AM colonization is linked to plant Zn nutrition.


Asunto(s)
Medicago truncatula , Micorrizas , Micorrizas/fisiología , Medicago truncatula/metabolismo , Raíces de Plantas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Suelo , Simbiosis
7.
Blood ; 137(20): 2838-2847, 2021 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-33824972

RESUMEN

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.


Asunto(s)
COVID-19/complicaciones , Tromboembolia/epidemiología , Tromboembolia/etiología , Anciano , Anticoagulantes/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Alta del Paciente , Sistema de Registros , Factores de Riesgo , SARS-CoV-2 , Tromboembolia/prevención & control
8.
Brain Behav Immun ; 113: 145-155, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37453452

RESUMEN

Dopamine transmission from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) regulates important aspects of motivation and is influenced by the neuroimmune system. The neuroimmune system is a complex network of leukocytes, microglia and astrocytes that detect and remove foreign threats like bacteria or viruses and communicate with each other to regulate non-immune (e.g neuronal) cell activity through cytokine signaling. Inflammation is a key regulator of motivational states, though the effects of specific cytokines on VTA circuitry and motivation are largely unknown. Therefore, electrophysiology, neurochemical, immunohistochemical and behavioral studies were performed to determine the effects of the anti-inflammatory cytokine interleukin-10 (IL-10) on mesolimbic activity, dopamine transmission and conditioned behavior. IL-10 enhanced VTA dopamine firing and NAc dopamine levels via decreased VTA GABA currents in dopamine neurons. The IL-10 receptor was localized on VTA dopamine and non-dopamine cells. The IL-10 effects on dopamine neurons required post-synaptic phosphoinositide 3-kinase activity, and IL-10 appeared to have little-to-no efficacy on presynaptic GABA terminals. Intracranial IL-10 enhanced NAc dopamine levels in vivo and produced conditioned place aversion. Together, these studies identify the IL-10R on VTA dopamine neurons as a potential regulator of motivational states.


Asunto(s)
Dopamina , Área Tegmental Ventral , Dopamina/farmacología , Neuronas Dopaminérgicas/fisiología , Interleucina-10/farmacología , Fosfatidilinositol 3-Quinasas , Núcleo Accumbens , Ácido gamma-Aminobutírico/farmacología
9.
Int J Mol Sci ; 24(20)2023 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-37894974

RESUMEN

Research evaluating the role of the 5,10-methylenetetrahydrofolate reductase (MTHFR C677T) gene in schizophrenia has not yet provided an extended understanding of the proximal pathways contributing to the 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme's activity and the distal pathways being affected by its activity. This review investigates these pathways, describing mechanisms relevant to riboflavin availability, trace mineral interactions, and the 5-methyltetrahydrofolate (5-MTHF) product of the MTHFR enzyme. These factors remotely influence vitamin cofactor activation, histamine metabolism, catecholamine metabolism, serotonin metabolism, the oxidative stress response, DNA methylation, and nicotinamide synthesis. These biochemical components form a broad interactive landscape from which candidate markers can be drawn for research inquiry into schizophrenia and other forms of mental illness. Candidate markers drawn from this functional biochemical background have been found to have biomarker status with greater than 90% specificity and sensitivity for achieving diagnostic certainty in schizophrenia and schizoaffective psychosis. This has implications for achieving targeted treatments for serious mental illness.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Genotipo , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , Biomarcadores
10.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-37958826

RESUMEN

Diagnostic uncertainty and relapse rates in schizophrenia and schizoaffective disorder are relatively high, indicating the potential involvement of other pathological mechanisms that could serve as diagnostic indicators to be targeted for adjunctive treatment. This study aimed to seek objective evidence of methylenetetrahydrofolate reductase MTHFR C677T genotype-related bio markers in blood and urine. Vitamin and mineral cofactors related to methylation and indolamine-catecholamine metabolism were investigated. Biomarker status for 67 symptomatically well-defined cases and 67 asymptomatic control participants was determined using receiver operating characteristics, Spearman's correlation, and logistic regression. The 5.2%-prevalent MTHFR 677 TT genotype demonstrated a 100% sensitive and specific case-predictive biomarkers of increased riboflavin (vitamin B2) excretion. This was accompanied by low plasma zinc and indicators of a shift from low methylation to high methylation state. The 48.5% prevalent MTHFR 677 CC genotype model demonstrated a low-methylation phenotype with 93% sensitivity and 92% specificity and a negative predictive value of 100%. This model related to lower vitamin cofactors, high histamine, and HPLC urine indicators of lower vitamin B2 and restricted indole-catecholamine metabolism. The 46.3%-prevalent CT genotype achieved high predictive strength for a mixed methylation phenotype. Determination of MTHFR C677T genotype dependent functional biomarker phenotypes can advance diagnostic certainty and inform therapeutic intervention.


Asunto(s)
Trastornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Ácido Fólico/metabolismo , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Genotipo , Biomarcadores , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , Riboflavina/uso terapéutico , Riboflavina/genética , Vitaminas , Catecolaminas
11.
Am J Hum Genet ; 105(5): 1057-1068, 2019 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-31668705

RESUMEN

Average arterial oxyhemoglobin saturation during sleep (AvSpO2S) is a clinically relevant measure of physiological stress associated with sleep-disordered breathing, and this measure predicts incident cardiovascular disease and mortality. Using high-depth whole-genome sequencing data from the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) project and focusing on genes with linkage evidence on chromosome 8p23,1,2 we observed that six coding and 51 noncoding variants in a gene that encodes the GTPase-activating protein (DLC1) are significantly associated with AvSpO2S and replicated in independent subjects. The combined DLC1 association evidence of discovery and replication cohorts reaches genome-wide significance in European Americans (p = 7.9 × 10-7). A risk score for these variants, built on an independent dataset, explains 0.97% of the AvSpO2S variation and contributes to the linkage evidence. The 51 noncoding variants are enriched in regulatory features in a human lung fibroblast cell line and contribute to DLC1 expression variation. Mendelian randomization analysis using these variants indicates a significant causal effect of DLC1 expression in fibroblasts on AvSpO2S. Multiple sources of information, including genetic variants, gene expression, and methylation, consistently suggest that DLC1 is a gene associated with AvSpO2S.


Asunto(s)
Cromosomas Humanos Par 8/genética , Proteínas Activadoras de GTPasa/genética , Oxihemoglobinas/genética , Sueño/genética , Proteínas Supresoras de Tumor/genética , Ligamiento Genético/genética , Estudio de Asociación del Genoma Completo , Humanos , Secuenciación Completa del Genoma/métodos
12.
BMC Public Health ; 22(1): 1002, 2022 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-35585536

RESUMEN

BACKGROUND: Research on associations between social integration and wellbeing holds promise to inform policy and practice targets for health promotion. Yet, studies of social connection too frequently rely on overly simplistic measures and give inadequate attention to manifestation and meanings of social integration across diverse groups. We use the term socio-cultural integration to describe expanded assessment of both social and cultural aspects of belonging and connection. METHODS: We examined 7 distinct indicators of socio-cultural integration, identified heterogeneous patterns of responses across these indicators using latent profile analysis, and determined their relevance for wellbeing using survey data from a study with Indigenous communities in the U.S. and Canada. Wellbeing was measured using holistic ratings of self-rated physical, emotional, and spiritual health. RESULTS: Latent profile analysis (LPA) of responses to the 7 socio-cultural integration variables yielded a 3-class model, which we labeled low, moderate, and high integration. Mean scores on self-rated physical, mental and spiritual health were significantly associated with LPA profiles, such that those in the low integration group had the lowest self-rated health scores and those in the high integration group had the highest health scores. With the exception of similar ratings of cultural identification between low and moderate integration profiles, patterns of responses to the diverse socio-cultural integration measures varied significantly across the 3 latent profiles. CONCLUSIONS: Results underscore the importance of expanding our assessment of social integration with attention to the interrelationships of family, community, culture, and our environment. Such concepts align with Indigenous conceptions of wellbeing, and have relevance for health across cultures. More concretely, the indicators of socio-cultural integration used in this study (e.g., cultural identity, having a sense of connectedness to nature or family, giving or receiving social support) represent malleable targets for inclusion in health promotion initiatives.


Asunto(s)
Salud Holística , Apoyo Social , Canadá , Promoción de la Salud , Humanos , Encuestas y Cuestionarios , Adulto Joven
13.
Mycorrhiza ; 32(3-4): 257-267, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35596782

RESUMEN

Arbuscular mycorrhizal (AM) fungi colonise plant roots, and by doing so forge the 'mycorrhizal uptake pathway(s)' (MUP) that provide passageways for the trade of resources across a specialised membrane at the plant-fungus interface. The transport of nutrients such as phosphorus (P), nitrogen and zinc from the fungus, and carbon from the plant, via the MUP have mostly been quantified using stable or radioactive isotope labelling of soil in a specialised hyphae-only compartment. Recent advances in the study of AM fungi have used tracing studies to better understand how the AM association will function in a changing climate, the extent to which the MUP can contribute to P uptake by important crops, and how AM fungi trade resources in interaction with plants, other AM fungi, and friend and foe in the soil microbiome. The existing work together with well-designed future experiments will provide a valuable assessment of the potential for AM fungi to play a role in the sustainability of managed and natural systems in a changing climate.


Asunto(s)
Micorrizas , Nitrógeno , Raíces de Plantas/microbiología , Suelo , Simbiosis
14.
Adapt Phys Activ Q ; 39(2): 197-213, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-34740988

RESUMEN

The purpose of this study was to initiate the development of an evidence-based sport classification system for powerchair football, a sport that serves athletes with physical impairments. Sport classification is designed to increase participation by minimizing the impact of impairment on competition outcome, and powerchair football lacks an evidence-based system of classification which is required of Paralympic sports. A number of approaches were used to build the theoretical model of sport performance (Step 2 of the International Paralympic Committee model). Key sport activities were identified through surveys of stakeholders and underlying determinants of those key activities were identified through game and database analyses. Current findings support drive control, ball control, communication, and adjustment to the ball as key activities in powerchair football with joint-specific strength and range of motion, sensory, and neurological variables identified as underlying determinants.


Asunto(s)
Rendimiento Atlético , Personas con Discapacidad , Fútbol Americano , Fútbol , Atletas , Humanos
15.
J Cogn Neurosci ; 33(10): 2132-2148, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34496022

RESUMEN

Our attention is critically important for what we remember. Prior measures of the relationship between attention and memory, however, have largely treated "attention" as a monolith. Here, across three experiments, we provide evidence for two dissociable aspects of attention that influence encoding into long-term memory. Using spatial cues together with a sensitive continuous report procedure, we find that long-term memory response error is affected by both trial-by-trial fluctuations of sustained attention and prioritization via covert spatial attention. Furthermore, using multivariate analyses of EEG, we track both sustained attention and spatial attention before stimulus onset. Intriguingly, even during moments of low sustained attention, there is no decline in the representation of the spatially attended location, showing that these two aspects of attention have robust but independent effects on long-term memory encoding. Finally, sustained and spatial attention predicted distinct variance in long-term memory performance across individuals. That is, the relationship between attention and long-term memory suggests a composite model, wherein distinct attentional subcomponents influence encoding into long-term memory. These results point toward a taxonomy of the distinct attentional processes that constrain our memories.


Asunto(s)
Atención , Memoria a Largo Plazo , Señales (Psicología) , Humanos , Memoria a Corto Plazo , Recuerdo Mental , Análisis Multivariante , Memoria Espacial
16.
Am J Transplant ; 21(7): 2522-2531, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33443778

RESUMEN

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).


Asunto(s)
COVID-19 , Trasplante de Órganos , Adulto , Humanos , Terapia de Inmunosupresión , SARS-CoV-2 , Receptores de Trasplantes
17.
Biochem Biophys Res Commun ; 529(3): 805-811, 2020 08 27.
Artículo en Inglés | MEDLINE | ID: mdl-32736711

RESUMEN

Zika virus (ZIKV) is a mosquito-borne flavivirus associated with Congenital Zika Syndrome (CZS), reflecting a wide range of congenital abnormalities in fetuses and infants infected with ZIKV before birth. ZIKV infections have also been associated with the neurological autoimmune disorder known as Guillian-Barré syndrome (GBS). To date, no vaccines or antiviral strategies are licensed for ZIKV. We used rational design to develop a novel ZIKV vaccine candidate using a Woodchuck Hepatitis core Antigen (WHcAg) Virus-Like Particle (VLP) scaffold for displaying selected antigens from the ZIKV Envelope (E) protein. A Zika-VLP vaccine candidate containing the CD Loop sub-structural domain from ZIKV E protein Domain III (WHcAg CD Loop) elicited a strong immune response in a murine model. Analysis of serum immunoglobulins demonstrated induction of both Th1- and Th2- mediated immune response. No cross-reacting antibodies were detected between Zika, dengue and yellow fever virus, demonstrating a high level of specificity for the ZIKV CD Loop antigen. Immunization with the WHcAg CD Loop vaccine candidate demonstrated immunoprotection in a murine model of ZIKV infection, stimulating protective antibodies associated with antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) activities. The WHcAg CD Loop candidate may represent a safer vaccine for preventing antibody dependent enhancement (ADE).


Asunto(s)
Vacunas de Partículas Similares a Virus/uso terapéutico , Proteínas del Envoltorio Viral/uso terapéutico , Infección por el Virus Zika/prevención & control , Virus Zika/inmunología , Animales , Modelos Animales de Enfermedad , Femenino , Inmunidad , Ratones , Ratones Endogámicos C57BL , Vacunas de Partículas Similares a Virus/inmunología , Proteínas del Envoltorio Viral/inmunología , Infección por el Virus Zika/inmunología
18.
Oncology (Williston Park) ; 34(6): 216-223, 2020 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-32609869

RESUMEN

A multitude of factors contribute to cancer disparities, including, but not limited to, differences in diet, lifestyle, environmental exposures, cultural beliefs, genetic and biological factors related to ancestry, socioeconomic status (SES), and access to health care. More investigation is needed in evaluating these factors in less common cancers and hematological malignancies. Addressing disparities in cancer incidence, prevalence, burden of disease, mortality, and survivorship that have been documented among racial/ethnic minority populations with blood cancers will require multilevel models of the interactions between relevant factors and performance of translational research that uses knowledge of cancer biology to develop and test the feasibility of interventions that can impact human end points. Such work must address a wide range of research areas, including prevention, early detection, diagnosis, treatment, epidemiology, cancer control, treatment, and survivorship. To be effective, efforts should be made to advance these research findings to applications that can transform clinical practice and health care delivery. We reviewed the literature to define a framework for overcoming disparities for patients with hematologic malignancies and to improve patient enrollment on clinical trials.


Asunto(s)
Ensayos Clínicos como Asunto , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Neoplasias Hematológicas/terapia , Selección de Paciente , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/economía , Humanos , Cobertura del Seguro , Persona de Mediana Edad , Factores de Riesgo , Población Rural , Factores Socioeconómicos , Resultado del Tratamiento
19.
Med J Aust ; 213(6): 269-275, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32770850

RESUMEN

OBJECTIVE: To evaluate associations between exposure during early life to mine fire smoke and parent-reported indicators of respiratory and atopic illness 2-4 years later. DESIGN, SETTING: The Hazelwood coalmine fire exposed a regional Australian community to markedly increased air pollution during February - March 2014. During June 2016 - October 2018 we conducted a prospective cohort study of children from the Latrobe Valley. PARTICIPANTS: Seventy-nine children exposed to smoke in utero, 81 exposed during early childhood (0-2 years of age), and 129 children conceived after the fire (ie, unexposed). EXPOSURE: Individualised mean daily and peak 24-hour fire-attributable fine particulate matter (PM2.5 ) exposure during the fire period, based on modelled air quality and time-activity data. MAIN OUTCOME MEASURES: Parent-reported symptoms, medications use, and contacts with medical professionals, collected in monthly online diaries for 29 months, 2-4 years after the fire. RESULTS: In the in utero exposure analysis (2678 monthly diaries for 160 children exposed in utero or unexposed), each 10 µg/m3 increase in mean daily PM2.5 exposure was associated with increased reports of runny nose/cough (relative risk [RR], 1.09; 95% CI, 1.02-1.17), wheeze (RR, 1.56; 95% CI, 1.18-2.07), seeking health professional advice (RR, 1.17; 95% CI 1.06-1.29), and doctor diagnoses of upper respiratory tract infections, cold or flu (RR, 1.35; 95% CI, 1.14-1.60). Associations with peak 24-hour PM2.5 exposure were similar. In the early childhood exposure analysis (3290 diaries for 210 children exposed during early childhood, or unexposed), each 100 µg/m3 increase in peak 24-hour PM2.5 exposure was associated with increased use of asthma inhalers (RR, 1.26; 95% CI, 1.01-1.58). CONCLUSIONS: Exposure to mine fire smoke in utero was associated with increased reports by parents of respiratory infections and wheeze in their children 2-4 years later.


Asunto(s)
Incendios , Exposición Materna/efectos adversos , Ruidos Respiratorios/etiología , Infecciones del Sistema Respiratorio/etiología , Humo/efectos adversos , Contaminación del Aire , Australia/epidemiología , Preescolar , Carbón Mineral , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Material Particulado/análisis , Embarazo , Estudios Prospectivos , Análisis de Regresión , Infecciones del Sistema Respiratorio/epidemiología , Humo/análisis
20.
BMC Plant Biol ; 19(1): 133, 2019 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-30967108

RESUMEN

BACKGROUND: Increasing zinc (Zn) concentrations in crops is important for alleviation of human Zn deficiency. Arbuscular mycorrhizal fungi (AMF) contribute to plant Zn uptake, but their contribution to Zn in the edible portion of crops has not yet been investigated. This study aimed to quantify the mycorrhizal pathway of Zn uptake into grain of wheat and barley under varying soil Zn availabilities. Bread wheat (Triticum aestivum) and barley (Hordeum vulgare) were grown in pots with a hyphal compartment containing 65Zn. Plants were inoculated with Rhizophagus irregularis and grown at three soil Zn concentrations. Radioactive Zn in grain and straw was measured and the contribution of AMF to Zn uptake was calculated. RESULTS: The mycorrhizal pathway of Zn uptake contributed up to 24.3% of total above-ground Zn in wheat, and up to 12.7% of that Zn in barley. The greatest contribution by the mycorrhizal pathway was observed in barley at the lowest Zn addition, and in wheat at the highest one. In addition, grain yield of bread wheat was increased by AMF. CONCLUSIONS: These results suggest that AMF have a substantial role in uptake of Zn into cereals, and the proportional contribution by the MPU is dependent on plant species, as well as available soil Zn.


Asunto(s)
Hordeum/microbiología , Micorrizas/fisiología , Triticum/microbiología , Zinc/metabolismo , Grano Comestible/metabolismo , Grano Comestible/microbiología , Hordeum/metabolismo , Suelo/química , Triticum/metabolismo
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