RESUMO
OBJECTIVE: Examine associations between time spent in academic activities perceived as meaningful and professional well-being among academic pediatrics faculty. METHODS: The sample comprised 248 full-time pediatric faculty (76% female, 81% white, non-Hispanic, 41% instructor or assistant professor) across the United States who completed an online survey in November 2019. Survey items included sociodemographic and professional characteristics, professional well-being measures (Stanford Professional Fulfillment Index; Maslach Burnout Inventory; Intention to Leave Academic Medicine), perceived meaningfulness of academic activities and assigned time to those activities. We defined global career fit as total percentage time assigned to professional activities considered meaningful by individuals, and activity-specific career fit as percentage time assigned to each meaningful professional activity. RESULTS: As global career fit scores increased, professional fulfillment increased (r = 0.45, P < .001), whereas burnout (r = -0.29, P < .001) and intention to leave (r = -0.22, P < .001) decreased. Regarding activity-specific career fit, for individuals who considered patient care meaningful, as assigned time to patient care increased, professional fulfillment decreased (r = -0.14, P = .048) and burnout (r = 0.16, P = .02) and intention to leave (r = 0.26, P < .001) increased. There was no significant correlation between assigned time for teaching, research, or advocacy and professional well-being. Faculty were less likely to intend to leave academic medicine as assigned time increased for administrative or leadership activities if considered meaningful (r = -0.24, P = .01). CONCLUSIONS: Time assigned to meaningful work activities may relate to professional well-being of academic pediatrics faculty. More time assigned to patient care, despite being meaningful, was associated with poor self-reported professional well-being. Effort allocation among diverse academic activities needs to be optimized to improve faculty well-being.
Assuntos
Esgotamento Profissional , Docentes de Medicina , Satisfação no Emprego , Pediatras , Humanos , Feminino , Estados Unidos/epidemiologia , Masculino , Docentes de Medicina/psicologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Pediatras/psicologia , Adulto , Pediatria , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
The mechanical forces experienced during movement and the time constants of muscle activation are important determinants of the durations of behaviours, which may both be affected by size-dependent scaling. The mechanics of slow movements in small animals are dominated by elastic forces and are thus quasistatic (i.e. always near mechanical equilibrium). Muscular forces producing movement and elastic forces resisting movement should scale identically (proportional to mass2/3), leaving the scaling of the time constant of muscle activation to play a critical role in determining behavioural duration. We tested this hypothesis by measuring the duration of feeding behaviours in the marine mollusc Aplysia californica whose body sizes spanned three orders of magnitude. The duration of muscle activation was determined by measuring the time it took for muscles to produce maximum force as A. californica attempted to feed on tethered inedible seaweed, which provided an in vivo approximation of an isometric contraction. The timing of muscle activation scaled with mass0.3. The total duration of biting behaviours scaled identically, with mass0.3, indicating a lack of additional mechanical effects. The duration of swallowing behaviour, however, exhibited a shallower scaling of mass0.17. We suggest that this was due to the allometric growth of the anterior retractor muscle during development, as measured by micro-computed tomography (micro-CT) scans of buccal masses. Consequently, larger A. californica did not need to activate their muscles as fully to produce equivalent forces. These results indicate that muscle activation may be an important determinant of the scaling of behavioural durations in quasistatic systems.
Assuntos
Aplysia , Músculos , Animais , Aplysia/fisiologia , Microtomografia por Raio-X , Músculos/fisiologia , Comportamento Alimentar/fisiologia , Deglutição/fisiologiaRESUMO
BACKGROUND: Growing evidence linking social determinants of health (SDOH) to child health outcomes has prompted widespread recommendations for pediatricians to screen and refer for adverse SDOH at primary care visits. Yet there is little evidence to date demonstrating the effectiveness of practice-based SDOH screening and referral interventions on increasing family engagement with resources. This hybrid type 2 effectiveness-implementation trial aims to demonstrate the non-inferiority of a low-touch implementation strategy in order to facilitate dissemination of an existing SDOH screening and referral system (WE CARE) and demonstrate its effectiveness and sustainability in various pediatric practices. METHODS: We recruited eighteen pediatric practices in fourteen US states through two pediatric practice-based research networks. For this stepped wedge cluster RCT, practices serve as their own controls during the Usual Care phase and implement WE CARE during the intervention phase via one of two randomized implementation strategies: self-directed, pre-recorded webinar vs. study team-facilitated, live webinar. We collect data at practice, clinician/staff, and parent levels to assess outcomes grounded in the Proctor Conceptual Model of Implementation Research. We use generalized mixed effects models and differences in proportions to compare rates of resource referrals by implementation strategy, and intention-to-treat analysis to compare odds of engagement with new resources among families enrolled in the Usual Care vs. WE CARE phases. DISCUSSION: Findings from this trial may inform decisions about broader dissemination of SDOH screening systems into a diverse spectrum of pediatric practices across the US and potentially minimize the impact of adverse SDOH on children and families.
Assuntos
Pais , Determinantes Sociais da Saúde , Criança , Humanos , Inquéritos e Questionários , Atenção Primária à Saúde , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Plant-based butters from nuts and seeds have steadily increased in consumer popularity due to their unique flavors and healthy nutritional properties. Oil content is a critical parameter to measure the proper consistency and stability of plant butter and spread products. Previous work has shown that glandless cottonseed can be used to formulate cottonseed butter products to increase the values of cottonseed. As part of the efforts made in the valorization of cottonseed, this work evaluated the effects of oil content on the microstructural and textural properties of cottonseed butter/spread products. While the oil content in the raw cottonseed kernels was 35% of the kernel biomass, additional cottonseed oil was added to make cottonseed butter products with six oil content levels (i.e., 36, 43, 47, 50, 53, and 57%). The values of three textural parameters, firmness, spreadability, and adhesiveness, decreased rapidly in an exponential mode with the increasing oil content. The particle size population in these butter samples was characterized by similar trimodal distribution, with the majority in the middle mode region with particle sizes around 4.5-10 µm. Higher oil content decreased the butter particle size slightly but increased oil separation during storage. The oxidation stability with a rapid oxygen measurement was gradually reduced from 250 min with 36% oil to 65 min with 57% oil. The results of this work provide information for the further optimization of formulation parameters of cottonseed butter products.
RESUMO
Introduction: Generating physiologically relevant red blood cell extracellular vesicles (RBC-EVs) for mechanistic studies is challenging. Herein, we investigated how to generate and isolate high concentrations of RBC-EVs in vitro via shear stress and mechanosensitive piezo1 ion channel stimulation. Methods: RBC-EVs were generated by applying shear stress or the piezo1-agonist yoda1 to RBCs. We then investigated how piezo1 RBC-EV generation parameters (hematocrit, treatment time, treatment dose), isolation methods (membrane-based affinity, ultrafiltration, ultracentrifugation with and without size exclusion chromatography), and storage conditions impacted RBC-EV yield and purity. Lastly, we used pressure myography to determine how RBC-EVs isolated using different methods affected mouse carotid artery vasodilation. Results: Our results showed that treating RBCs at 6% hematocrit with 10 µM yoda1 for 30 min and isolating RBC-EVs via ultracentrifugation minimized hemolysis, maximized yield and purity, and produced the most consistent RBC-EV preparations. Co-isolated contaminants in impure samples, but not piezo1 RBC-EVs, induced mouse carotid artery vasodilation. Conclusion: This work shows that RBC-EVs can be generated through piezo1 stimulation and may be generated in vivo under physiologic flow conditions. Our studies further emphasize the importance of characterizing EV generation and isolation parameters before using EVs for mechanistic analysis since RBC-EV purity can impact functional outcomes.
RESUMO
Cytoplasmic microtubules are tubular polymers that can harbor small proteins or filaments inside their lumen. The identities of these objects and mechanisms for their accumulation have not been conclusively established. Here, we used cryogenic electron tomography of Drosophila S2 cell protrusions and found filaments inside the microtubule lumen, which resemble those reported recently in human HAP1 cells. The frequency of these filaments increased upon inhibition of the sarco/endoplasmic reticulum Ca2+ ATPase with the small molecule drug thapsigargin. Subtomogram averaging showed that the luminal filaments adopt a helical structure reminiscent of cofilin-bound actin (cofilactin). Consistent with this, we observed cofilin dephosphorylation, an activating modification, in cells under the same conditions that increased luminal filament occurrence. Furthermore, RNA interference knock-down of cofilin reduced the frequency of luminal filaments with cofilactin morphology. These results suggest that cofilin activation stimulates its accumulation on actin filaments inside the microtubule lumen.
Assuntos
Citoesqueleto de Actina , Citoesqueleto , Humanos , Citoesqueleto/metabolismo , Citoesqueleto de Actina/metabolismo , Actinas/metabolismo , Fatores de Despolimerização de Actina/metabolismo , Microtúbulos/metabolismoRESUMO
Cytoplasmic microtubules are tubular polymers that can harbor small proteins or filaments inside their lumen. The identity of these objects and what causes their accumulation has not been conclusively established. Here, we used cryogenic electron tomography (cryoET) of Drosophila S2 cell protrusions and found filaments inside the microtubule lumen, which resemble those reported recently in human HAP1 cells. The frequency of these filaments increased upon inhibition of the sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) with the small-molecule drug thapsigargin. Subtomogram averaging showed that the luminal filaments adopt a helical structure reminiscent of cofilin-bound actin (cofilactin). Consistent with this, cofilin was activated in cells under the same conditions that increased luminal filament occurrence. Furthermore, RNAi knock-down of cofilin reduced the frequency of luminal filaments with cofilactin morphology. These results suggest that cofilin activation stimulates its accumulation on actin filaments inside the microtubule lumen.
RESUMO
BACKGROUND: To examine the differential relationships between seven social risk factors (individually and cumulatively) with the prevalence and severity of asthma, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and overweight/obesity in children. METHODS: Using the 2017-2018 National Survey of Children's Health, we examined associations between social risk factors (caregiver education, caregiver underemployment, discrimination, food insecurity, insurance coverage, neighborhood support, and neighborhood safety) and the prevalence and severity of asthma, ADHD, ASD, and overweight/obesity. We used multivariable logistic regression to assess the relationship between individual and cumulative risk factors with each pediatric chronic condition, controlling for child sex and age. RESULTS: Although each social risk factor was significantly associated with increased prevalence and/or severity of at least one of the pediatric chronic conditions we investigated, food insecurity was significantly associated with higher disease prevalence and severity for all four conditions. Caregiver underemployment, low social support, and discrimination were significantly associated with higher disease prevalence across all conditions. For each additional social risk factor a child was exposed to, their odds of having each condition increased: overweight/obesity (aOR: 1.2, 95% CI: [1.2, 1.3]), asthma (aOR: 1.3, 95% CI: [1.2, 1.3], ADHD (aOR: 1.2, 95% CI: [1.2, 1.3]), and ASD (aOR: 1.4, 95% CI: [1.3, 1.5]). CONCLUSIONS: This study elucidates differential relationships between several social risk factors and the prevalence and severity of common pediatric chronic conditions. While more research is needed, our results suggest that social risks, particularly food insecurity, are potential factors in the development of pediatric chronic conditions.
Assuntos
Asma , Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Obesidade Infantil , Criança , Humanos , Transtorno do Espectro Autista/etiologia , Transtorno do Espectro Autista/complicações , Estudos Transversais , Sobrepeso/complicações , Obesidade Infantil/epidemiologia , Obesidade Infantil/complicações , Prevalência , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Asma/epidemiologia , Asma/complicaçõesRESUMO
Specimens of a tylenchid nematode were recovered in 2019 from soil samples collected from a corn field, located in Pickens County, South Carolina, USA. A moderate number of Tylenchus sp. adults (females and males) were recovered. Extracted nematodes were examined morphologically and molecularly for species identification, which indicated that the specimens of the tylenchid adults were a new species, described herein as Tylenchus zeae n. sp. Morphological examination and the morphometric details of the specimens were very close to the original descriptions of Tylenchus sherianus and T. rex. However, females of the new species can be differentiated from these species by body shape and length, shape of excretory duct, distance between anterior end and esophageal intestinal valve, and a few other characteristics given in the diagnosis. Males of the new species can be differentiated from the two closely related species by tail, spicules, and gubernaculum length. Cryo-scanning electron microscopy confirmed head bearing five or six annules; four to six cephalic sensilla represented by small pits at the rounded corners of the labial plate; a small, round oral plate; and a large, pit-like amphidial opening confined to the labial plate and extending three to four annules beyond it. Phylogenetic analysis of 18S rRNA gene sequences placed Tylenchus zeae n. sp. in a clade with Tylenchus arcuatus and several Filenchus spp., and the mitochondrial cytochrome oxidase c subunit 1 (COI) gene region separated the new species from T. arcuatus and other tylenchid species. In the 28S tree, T. zeae n. sp. showed a high level of sequence divergence and was positioned outside of the main Tylenchus-Filenchus clade.
RESUMO
Endothelial cells line all blood vessels, where they coordinate blood vessel formation and the blood-tissue barrier via regulation of cell-cell junctions. The nucleus also regulates endothelial cell behaviors, but it is unclear how the nucleus contributes to endothelial cell activities at the cell periphery. Here, we show that the nuclear-localized linker of the nucleoskeleton and cytoskeleton (LINC) complex protein SUN1 regulates vascular sprouting and endothelial cell-cell junction morphology and function. Loss of murine endothelial Sun1 impaired blood vessel formation and destabilized junctions, angiogenic sprouts formed but retracted in SUN1-depleted sprouts, and zebrafish vessels lacking Sun1b had aberrant junctions and defective cell-cell connections. At the cellular level, SUN1 stabilized endothelial cell-cell junctions, promoted junction function, and regulated contractility. Mechanistically, SUN1 depletion altered cell behaviors via the cytoskeleton without changing transcriptional profiles. Reduced peripheral microtubule density, fewer junction contacts, and increased catastrophes accompanied SUN1 loss, and microtubule depolymerization phenocopied effects on junctions. Depletion of GEF-H1, a microtubule-regulated Rho activator, or the LINC complex protein nesprin-1 rescued defective junctions of SUN1-depleted endothelial cells. Thus, endothelial SUN1 regulates peripheral cell-cell junctions from the nucleus via LINC complex-based microtubule interactions that affect peripheral microtubule dynamics and Rho-regulated contractility, and this long-range regulation is important for proper blood vessel sprouting and junction integrity.
Assuntos
Células Endoteliais , Proteínas Associadas aos Microtúbulos , Animais , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Células Endoteliais/metabolismo , Peixe-Zebra/metabolismo , Proteínas Nucleares/metabolismo , Microtúbulos/metabolismo , Junções Intercelulares/metabolismoRESUMO
Introduction: Oxidized LDL (oxLDL) is formed by the spontaneous reaction between aldehyde byproducts of lipid peroxidation and lysine residues of apolipoprotein B within LDL. Clinically, oxLDL is used as a marker of coronary artery disease and predictor of metabolic syndrome risk. Despite its popularity as a clinical marker, no systematic studies of oxLDL stability, in which serum or plasma has been pre-analytically exposed to an array of different time and temperature conditions, have been carried out. Objective: To systematically evaluate the stability of oxLDL in human serum samples exposed to thawed conditions (> -30 °C) for varying periods of time while monitoring a second protein/small molecule redox system as a positive control for non-enzymatic biomolecular activity. Methods: OxLDL was measured in serum samples, from 24 different humans, that had been pre-exposed to three different time courses at 23 °C, 4 °C and -20 °C using ELISA kits from Mercodia that employ the 4E6 mouse monoclonal antibody. A liquid chromatography/mass spectrometry-based marker of serum exposure to thawed conditions known as ΔS-Cys-Albumin was employed as a positive control. Results: OxLDL was stable in serum exposed to 23 °C for up to 48 h, 4 °C for 21 days, or -20 °C for 65 days. ΔS-Cys-Albumin changed dramatically during these time courses (p < 0.001). Conclusions: OxLDL is remarkably stable ex vivo in human serum samples exposed to thawed conditions.
RESUMO
Introduction: Coronavirus disease 2019 (COVID-19) is characterized by impaired oxygen (O2) homeostasis, including O2 sensing, uptake, transport/delivery, and consumption. Red blood cells (RBCs) are central to maintaining O2 homeostasis and undergo direct exposure to coronavirus in vivo. We thus hypothesized that COVID-19 alters RBC properties relevant to O2 homeostasis, including the hematological profile, Hb O2 transport characteristics, rheology, and the hypoxic vasodilatory (HVD) reflex. Methods: RBCs from 18 hospitalized COVID-19 subjects and 20 healthy controls were analyzed as follows: (i) clinical hematological parameters (complete blood count; hematology analyzer); (ii) O2 dissociation curves (p50, Hill number, and Bohr plot; Hemox-Analyzer); (iii) rheological properties (osmotic fragility, deformability, and aggregation; laser-assisted optical rotational cell analyzer (LORRCA) ektacytometry); and (iv) vasoactivity (the RBC HVD; vascular ring bioassay). Results: Compared to age- and gender-matched healthy controls, COVID-19 subjects demonstrated 1) significant hematological differences (increased WBC count-with a higher percentage of neutrophils); RBC distribution width (RDW); and reduced hematocrit (HCT), Hb concentration, mean corpuscular volume (MCV), and mean corpuscular hemoglobin concentration (MCHC); 2) impaired O2-carrying capacity and O2 capacitance (resulting from anemia) without difference in p50 or Hb-O2 cooperativity; 3) compromised regulation of RBC volume (altered osmotic fragility); 4) reduced RBC deformability; 5) accelerated RBC aggregation kinetics; and (6) no change in the RBC HVD reflex. Discussion: When considered collectively, homeostatic compensation for these RBC impairments requires that the cardiac output in the COVID cohort would need to increase by â¼135% to maintain O2 delivery similar to that in the control cohort. Additionally, the COVID-19 disease RBC properties were found to be exaggerated in blood-type O hospitalized COVID-19 subjects compared to blood-type A. These data indicate that altered RBC features in hospitalized COVID-19 subjects burden the cardiovascular system to maintain O2 delivery homeostasis, which appears exaggerated by blood type (more pronounced with blood-type O) and likely plays a role in disease pathogenesis.
RESUMO
Biomolecular integrity can be compromised when blood plasma/serum (P/S) specimens are improperly handled. Compromised analytes can subsequently produce erroneous results-without any indication of having done so. We recently introduced an LC/MS-based marker of P/S exposure to thawed conditions called ΔS-Cys-Albumin which, aided by an established rate law, quantitatively tracks exposure of P/S to temperatures greater than their freezing point of -30 °C. The purposes of this study were to (1) evaluate ΔS-Cys-Albumin baseline values in gastrointestinal cancer patients and cancer-free control donors, (2) empirically assess the kinetic profiles of ΔS-Cys-Albumin at 23 °C, 4 °C, and -20 °C, and (3) empirically link ΔS-Cys-Albumin to the stability of clinically relevant proteins. ΔS-Cys-Albumin was measured at ≥ 9 different time points per exposure temperature in serum and K2EDTA plasma samples from 24 separate donors in aliquots kept separately at 23 °C, 4 °C, and -20 °C. Twenty-one clinically relevant plasma proteins were measured at four time points per temperature via a multiplexed immunoassay on the Luminex platform. Protein stability was assessed by mixed effects models. Coordinated shifts in stability between ΔS-Cys-Albumin and the unstable proteins were documented by repeated measures and Pearson correlations. Plasma ΔS-Cys-Albumin dropped from approximately 20% to under 5% within 96 h at 23 °C, 28 days at 4 °C, and 65 days at -20 °C. On average, 22% of the 21 proteins significantly changed in apparent concentration at each exposure temperature (p < 0.0008 with >10% shift). A linear inverse relationship was found between the percentage of proteins destabilized and ΔS-Cys-Albumin (r = -0.61; p < 0.0001)-regardless of the specific time/temperature of exposure. ΔS-Cys-Albumin tracks cumulative thawed-state exposure. These results now enable ΔS-Cys-Albumin to approximate the percentage of clinically relevant proteins that have been compromised by incidental plasma exposure to thawed-state conditions.
Assuntos
Proteínas Sanguíneas , Plasma , Humanos , Espectrometria de Massas , Cromatografia Líquida , Plasma/metabolismo , Albumina Sérica , Biomarcadores , TemperaturaRESUMO
Crickets receive auditory information from their environment via ears located on the front legs. Ascending interneurons forward auditory activity to the brain, which houses a pattern recognition network for phonotaxis to conspecific calling songs and which controls negative phonotaxis to high-frequency sound pulses. Descending brain neurons, however, which are clearly involved in controlling these behaviors, have not yet been identified. We describe a descending auditory-responsive brain neuron with an arborization pattern that coincides with the ring-like auditory neuropil in the brain formed by the axonal arborizations of ascending and local interneurons, indicating its close link to auditory processing. Spiking activity of this interneuron occurs with a short latency to calling song patterns and the neuron copies the sound pulse pattern. The neuron preferentially responds to short sound pulses, but its activity appears to be independent of the calling song pattern recognition process. It also receives a weaker synaptic input in response to high-frequency pulses, which may contribute to its short latency spiking responses. This interneuron could be a crucial part in the auditory-to-motor transformation of the nervous system and contribute to the motor control of cricket auditory behavior.
Assuntos
Vias Auditivas , Gryllidae , Animais , Vias Auditivas/fisiologia , Gryllidae/fisiologia , Potenciais de Ação/fisiologia , Interneurônios/fisiologia , Encéfalo/fisiologia , Estimulação AcústicaRESUMO
Early predator detection is a key component of the predator-prey arms race and has driven the evolution of multiple animal hearing systems. Katydids (Insecta) have sophisticated ears, each consisting of paired tympana on each foreleg that receive sound both externally, through the air, and internally via a narrowing ear canal running through the leg from an acoustic spiracle on the thorax. These ears are pressure-time difference receivers capable of sensitive and accurate directional hearing across a wide frequency range. Many katydid species have cuticular pinnae which form cavities around the outer tympanal surfaces, but their function is unknown. We investigated pinnal function in the katydid Copiphora gorgonensis by combining experimental biophysics and numerical modelling using 3D ear geometries. We found that the pinnae in C. gorgonensis do not assist in directional hearing for conspecific call frequencies, but instead act as ultrasound detectors. Pinnae induced large sound pressure gains (20-30 dB) that enhanced sound detection at high ultrasonic frequencies (>60 kHz), matching the echolocation range of co-occurring insectivorous gleaning bats. These findings were supported by behavioural and neural audiograms and pinnal cavity resonances from live specimens, and comparisons with the pinnal mechanics of sympatric katydid species, which together suggest that katydid pinnae primarily evolved for the enhanced detection of predatory bats.
Assuntos
Quirópteros , Ecolocação , Ortópteros , Animais , Audição , Comportamento PredatórioRESUMO
BACKGROUND: Circulating IgE and subsequent severe allergic reactions to peanut are sustained and propagated by recall of peanut allergen-specific memory B cells. OBJECTIVES: This study aimed to determine whether targeting mouse and human CD22 on peanut-specific memory B cells induces tolerance to peanut allergens. METHODS: Siglec-engaging tolerance-inducing antigenic liposomes (STALs) codisplaying peanut allergens (Ara h 1, Ara h 2, or Ara h 3) and high-affinity CD22 ligand (CD22L-STALs) were employed in various mouse models (BALB/cJ, C57BL/6, human CD22 transgenic, and NSG) of peanut allergy. To investigate memory B cells, a conferred memory model was used in which splenocytes from peanut-sensitized mice were transferred into naive animals. Reconstituted mice received either CD22L-STALs or an immunogenic liposome control, followed by a peanut allergen boost and later a challenge with individual peanut allergens. To assess the effects of CD22L-STALs on human B cells, PBMCs were injected into NSG mice, followed by administration of human CD22L-STALs (hCD22L-STALs) and later a whole peanut extract boost. Blood was collected to quantify WPE- and Ara h 1-, 2-, and 3-specific immunoglobulins. RESULTS: Mouse CD22L-STALs (mCD22L-STALs) significantly suppressed systemic memory to Ara h 1, Ara h 2, and Ara h 3 in BALB/cJ and C57BL/6 mice, as demonstrated by reduced allergen-specific IgE, IgG1, and anaphylaxis on challenge. Importantly, 2 doses of mCD22L-STALs led to prolonged tolerance for at least 3 months. hCD22L-STALs displayed similar suppression in mice expressing human CD22 on B cells. Finally, human B cells were tolerized in vivo in NSG mice by hCD22L-STALs. CONCLUSIONS: Antigen-specific exploitation of CD22 on memory B cells can induce systemic immune tolerance.
Assuntos
Alérgenos , Arachis , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Células B de Memória , Tolerância Imunológica , Lectina 2 Semelhante a Ig de Ligação ao Ácido SiálicoRESUMO
BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) has well-established positive impacts on child health outcomes, including increased birth weight and decreased likelihood of underweight status. Studies in adult populations suggest that SNAP is associated with lower health care costs, although less is known in children. METHODS: Retrospective analysis of U.S. children (age <18 years) living in low-income households (< 200% of the federal poverty level) in the 2013-2017 Medical Expenditure Panel Survey. We used multivariable regression, adjusting for sociodemographic and clinical covariates, to model the effect of continuous SNAP enrollment on health expenditures as compared to non-enrollees at 12 and 24 months. RESULTS: The sample included 5,626 children, of whom 49.2% consistently received SNAP for the entire two-year survey period. Compared with SNAP non-recipients, SNAP-recipient households more often had incomes below 100% FPL (78.3% vs 37.9%), and children in SNAP-recipient households were more often publicly insured (94.9% vs 64.5%). Unadjusted expenditures were lower for children in SNAP-recipient households at 12 ($1222 vs $1603) and 24 months ($2447 vs $3009). However, when adjusting for sociodemographic and clinical differences, no statistically significant differences in health care expenditures, including emergency department, inpatient, outpatient, and prescription costs, were identified. CONCLUSION: SNAP participant children experience heightened social hardships across multiple domains. There were no differences in short term health care costs based on SNAP enrollment when accounting for differences in sociodemographic and clinical factors. Despite demonstrated child health benefits, we found that sustained enrollment in SNAP over a two-year period did not generate significant short- term health care cost reductions. Our findings suggest that although SNAP is intended to act as a benefit towards the health and well-being of its recipients, unlike among adults, it may not reduce health care costs among children.
Assuntos
Assistência Alimentar , Gastos em Saúde , Adolescente , Adulto , Criança , Características da Família , Humanos , Pobreza , Estudos RetrospectivosRESUMO
The spectraplakin family of proteins includes ACF7/MACF1 and BPAG1/dystonin in mammals, VAB-10 in Caenorhabditis elegans, Magellan in zebrafish, and Short stop (Shot), the sole Drosophila member. Spectraplakins are giant cytoskeletal proteins that cross-link actin, microtubules, and intermediate filaments, coordinating the activity of the entire cytoskeleton. We examined the role of Shot during cell migration using two systems: the in vitro migration of Drosophila tissue culture cells and in vivo through border cell migration. RNA interference (RNAi) depletion of Shot increases the rate of random cell migration in Drosophila tissue culture cells as well as the rate of wound closure during scratch-wound assays. This increase in cell migration prompted us to analyze focal adhesion dynamics. We found that the rates of focal adhesion assembly and disassembly were faster in Shot-depleted cells, leading to faster adhesion turnover that could underlie the increased migration speeds. This regulation of focal adhesion dynamics may be dependent on Shot being in an open confirmation. Using Drosophila border cells as an in vivo model for cell migration, we found that RNAi depletion led to precocious border cell migration. Collectively, these results suggest that spectraplakins not only function to cross-link the cytoskeleton but may regulate cell-matrix adhesion.