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1.
PLoS Pathog ; 19(12): e1011901, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38157379

RESUMO

Substitutions that fix between SARS-CoV-2 variants can transform the mutational landscape of future evolution via epistasis. For example, large epistatic shifts in mutational effects caused by N501Y underlied the original emergence of Omicron, but whether such epistatic saltations continue to define ongoing SARS-CoV-2 evolution remains unclear. We conducted deep mutational scans to measure the impacts of all single amino acid mutations and single-codon deletions in the spike receptor-binding domain (RBD) on ACE2-binding affinity and protein expression in the recent Omicron BQ.1.1 and XBB.1.5 variants, and we compared mutational patterns to earlier viral strains that we have previously profiled. As with previous deep mutational scans, we find many mutations that are tolerated or even enhance binding to ACE2 receptor. The tolerance of sites to single-codon deletion largely conforms with tolerance to amino acid mutation. Though deletions in the RBD have not yet been seen in dominant lineages, we observe tolerated deletions including at positions that exhibit indel variation across broader sarbecovirus evolution and in emerging SARS-CoV-2 variants of interest, most notably the well-tolerated Δ483 deletion in BA.2.86. The substitutions that distinguish recent viral variants have not induced as dramatic of epistatic perturbations as N501Y, but we identify ongoing epistatic drift in SARS-CoV-2 variants, including interaction between R493Q reversions and mutations at positions 453, 455, and 456, including F456L that defines the XBB.1.5-derived EG.5 lineage. Our results highlight ongoing drift in the effects of mutations due to epistasis, which may continue to direct SARS-CoV-2 evolution into new regions of sequence space.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Enzima de Conversão de Angiotensina 2/genética , Mutação , Aminoácidos , Códon , Glicoproteína da Espícula de Coronavírus/genética
2.
Arch Womens Ment Health ; 27(1): 89-97, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37740096

RESUMO

US female veterans have higher rates of mental health (MH) disorders compared to US civilian females and, consequently, are at risk for poor MH outcomes during pregnancy. This study evaluated the MH burden and identified the prevalence of antidepressant prescription and discontinuation among pregnant veterans (PGVets). The electronic health records (EHR) of PGVets using the US Veterans Administration's (VA) maternity care benefits over a two-year period were retrospectively reviewed. Inclusion criteria for this study were a current MH diagnosis of depression, anxiety, or posttraumatic stress disorder (PTSD) at the onset of pregnancy (n=351). Outcomes examined included antidepressant use prior to pregnancy, the use and discontinuation of antidepressants during pregnancy, and risk factors for discontinuation. PGVets had a high MH burden, as indicated by multiple comorbid diagnoses of unipolar depression, anxiety, and PTSD in 67% of the sample. At the onset of pregnancy, 163 (46%) were treated with an antidepressant. Only 56 (34%) continued using antidepressants through the pregnancy. Self-discontinuation (34%) and VA provider discontinuation (31%) of antidepressants were found. Among PGVets with documented past suicidal behaviors, 90% discontinued their active antidepressants. PGVets with indicators for more severe MH diagnoses were most likely to discontinue. The MH burden of PGVets and high rates of antidepressant discontinuation have implications for engaging this population in a higher level of perinatal monitoring and intervention. The findings suggest that VA providers and veterans would benefit from risks and benefits education regarding antidepressant use during pregnancy as well as the provision of alternative therapies.


Assuntos
Serviços de Saúde Materna , Veteranos , Feminino , Humanos , Gravidez , Veteranos/psicologia , Estudos Retrospectivos , Prevalência , Antidepressivos/uso terapêutico
3.
Pediatr Exerc Sci ; 36(2): 66-74, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37758263

RESUMO

PURPOSE: Studying physical activity in toddlers using accelerometers is challenging due to noncompliance with wear time (WT) and activity log (AL) instructions. The aims of this study are to examine relationships between WT and AL completion and (1) demographic and socioeconomic variables, (2) parenting style, and (3) whether sedentary time differs by AL completion. METHODS: Secondary analysis was performed using baseline data from a community wellness program randomized controlled trial for parents with toddlers (12-35 mo). Parents had toddlers wear ActiGraph wGT3x accelerometers and completed ALs. Valid days included ≥600-minute WT. Analysis of variance and chi-square analyses were used. RESULTS: The sample (n = 50) comprised racial and ethnically diverse toddlers (mean age = 27 mo, 58% male) and parents (mean age = 31.7 y, 84% female). Twenty-eight families (56%) returned valid accelerometer data with ALs. Participants in relationships were more likely to complete ALs (P < .05). Toddler sedentary time did not differ between those with ALs and those without. CONCLUSIONS: We found varied compliance with WT instructions and AL completion. Returned AL quality was poor, presenting challenges in correctly characterizing low-activity counts to improve internal validity of WT and physical activity measures. Support from marital partners may be important for adherence to study protocols.


Assuntos
Exercício Físico , Comportamento Sedentário , Humanos , Masculino , Feminino , Pré-Escolar , Adulto , Pais , Cooperação do Paciente , Acelerometria
4.
Hosp Pharm ; 59(2): 228-233, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38450349

RESUMO

Purpose: Critical care pharmacists are considered essential members of the healthcare team; however, justification and recruitment of new positions, especially in the evening or weekend shifts, remains a significant challenge. The purpose of this study was to investigate the number of interventions, type of interventions, and associated cost savings with the addition of 1 board certified critical care clinical pharmacist to evening shift. Methods: This was a prospective collection and characterization of 1 evening shift critical care pharmacist's clinical interventions over a 12-week period. Interventions were collected and categorized daily from 13:00 to 22:00 Monday through Friday. After collection was complete, cost savings estimates were calculated using pharmacy wholesaler acquisition cost. Results: Interventions were collected on 52 of 60 weekdays. A total of 510 interventions were collected with an average of 9.8 interventions accepted per day. The most common interventions included transitions of care, medication dose adjustment, and antibiotic de-escalation and the highest proportion of interventions occurred in the medical intensive care unit. An estimated associated cost avoidance of $66 537.80 was calculated for an average of $1279.57 saved per day. Additionally, 22 (4.1%) of interventions were considered high yield interventions upon independent review by 2 pharmacists. Conclusion: The addition of 1 board-certified critical care pharmacist to evening shift resulted in multiple interventions across several categories and a significant cost avoidance when calculated using conservative measures.

5.
Artigo em Inglês | MEDLINE | ID: mdl-37932518

RESUMO

The COVID-19 pandemic resulted in increased feelings of emotional distress and disruptions in care across diverse patients subgroups, including those with chronic medical conditions such as inflammatory bowel diseases (IBD). We sought to understand the impact of the pandemic on the physical and emotional well-being of individuals with IBD and concurrent depression and/or anxiety symptoms. We conducted qualitative interviews after the beginning of the pandemic with 46 adults with IBD. Participants reported increased levels of emotional distress, feelings of social isolation, and uncertainty over whether IBD medications put them at increased risk. Young adults discussed feeling as if their lives had been disrupted. In addition, several individuals demonstrated resiliency and emphasized positives about the pandemic, including increased connectivity with family and friends, the convenience of being able to work from home despite their IBD symptoms, and lessened feelings of "missing out." Our findings highlight several opportunities to improve the health and well-being of individuals with IBD and beyond including increased support for combatting social isolation, enhanced counseling about medication risks and benefits, and the incorporation of resiliency skills building.

6.
Hosp Pharm ; 58(6): 569-574, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38560536

RESUMO

Purpose: The purpose of this study was to determine the relationship between medication regimen complexity-intensive care unit (MRC-ICU) score at 24 hours and medication errors identified throughout the ICU. Methods: A single-center, observational study was conducted from August to October 2021. The primary outcome was the association between MRC-ICU at 24 hours and total medication errors identified. During the prospective component, ICU pharmacists recorded medication errors identified over an 8-week period. During the retrospective component, the electronic medical record was reviewed to collect patient demographics, outcomes, and MRC-ICU score at 24 hours. The primary outcome of the relationship of MRC-ICU at 24 hours to medication errors was assessed using Pearson correlation. Results: A total of 150 patients were included. There were 2 pharmacists who recorded 634 errors during the 8-week study period. No significant relationship between MRC-ICU and medication errors was observed (r2 = .13, P = .11). Exploratory analyses of MRC-ICU relationship to major interventions and harm scores showed that MRC-ICU scores >10 had more major interventions (27 vs 14, P = .27) and higher harm scores (15 vs 7, P = .33), although these values were not statistically significant. Conclusion: Medication errors appear to occur independently of medication regimen complexity. Critical care pharmacists were responsible for mitigating a large number of medication errors.

7.
Neurosurg Focus ; 52(5): E2, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35535824

RESUMO

OBJECTIVE: Neurocutaneous syndromes have variable multisystem involvement. The multiorgan involvement, potential pathologies, and various treatment options necessitate collaboration and open discussion to ensure optimal treatment in any given patient. These disorders provide quintessential examples of chronic medical conditions that require a lifelong, multidisciplinary approach. The objectives of this study were to 1) perform a systematic review, thoroughly assessing different multidisciplinary clinic layouts utilized in centers worldwide; and 2) characterize an institutional experience with the management of these conditions, focusing on the patient demographics, clinical presentation, complications, and therapeutic strategies seen in a patient population. METHODS: A systematic review of studies involving multidisciplinary clinics and their reported structure was performed according to PRISMA guidelines using the PubMed database. Then a retrospective chart review of patients enrolled in the Oklahoma Children's Hospital Neurocutaneous Syndromes Clinic was conducted. RESULTS: A search of the PubMed database yielded 251 unique results. Of these, 15 papers were included in the analysis, which identified 16 clinics that treated more than 2000 patients worldwide. The majority of these clinics treated patients with neurofibromatosis (13/16). The remaining clinics treated patients with von Hippel-Lindau syndrome (n = 1), tuberous sclerosis complex (n = 1), and multiple neurocutaneous syndromes (n = 1). The most commonly represented subspecialties in these clinics were genetics (15/16) and neurology (13/16). Five clinics (31%) solely saw pediatric patients, 10 clinics saw a combination of children and adults, and the final clinic had separate pediatric and adult clinics. The retrospective chart review of the Neurocutaneous Syndromes Clinic demonstrated that 164 patients were enrolled and seen in the clinic from April 2013 to December 2021. Diagnoses were made based on clinical findings or results of genetic testing; 115 (70%) had neurofibromatosis type 1, 9 (5.5%) had neurofibromatosis type 2, 35 (21%) had tuberous sclerosis complex, 2 (1%) had von Hippel-Lindau syndrome, 2 (1%) had Gorlin syndrome, and the remaining patient (0.6%) had Aarskog-Scott syndrome. Patient demographics, clinical presentation, complications, and therapeutic strategies are also discussed. CONCLUSIONS: To the best of the authors' knowledge, this is the first detailed description of a comprehensive pediatric neurocutaneous clinic in the US that serves patients with multiple syndromes. There is currently heterogeneity between described multidisciplinary clinic structures and practices. More detailed accounts of clinic compositions and practices along with patient data and outcomes are needed in order to establish the most comprehensive and efficient multidisciplinary approach for neurocutaneous syndromes.


Assuntos
Síndromes Neurocutâneas , Neurofibromatose 1 , Esclerose Tuberosa , Doença de von Hippel-Lindau , Adulto , Criança , Humanos , Síndromes Neurocutâneas/diagnóstico , Síndromes Neurocutâneas/genética , Síndromes Neurocutâneas/terapia , Neurofibromatose 1/complicações , Neurofibromatose 1/genética , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética
8.
Medicina (Kaunas) ; 59(1)2022 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-36676669

RESUMO

Cardiothoracic surgical critical care medicine (CT-CCM) is a medical discipline centered on the perioperative care of diverse groups of patients. With an aging demographic and an increase in burden of chronic diseases the utilization of cardiothoracic surgical critical care units is likely to escalate in the coming decades. Given these projections, it is important to assess the state of cardiothoracic surgical intensive care, to develop goals and objectives for the future, and to identify knowledge gaps in need of scientific inquiry. This two-part review concentrates on CT-CCM as its own subspeciality of critical care and cardiothoracic surgery and provides aspirational goals for its practitioners and scientists. In part one, a list of guiding principles and a call-to-action agenda geared towards growth and promotion of CT-CCM are offered. In part two, an evaluation of selected scientific data is performed, identifying gaps in CT-CCM knowledge, and recommending direction to future scientific endeavors.


Assuntos
Anestesiologia , Procedimentos Cirúrgicos Cardíacos , Humanos , Cuidados Críticos , Unidades de Terapia Intensiva , Assistência Perioperatória
9.
Genet Med ; 23(4): 653-660, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33299146

RESUMO

PURPOSE: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. METHODS: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through collaboration with international colleagues, matchmaking platforms, and literature review. For each individual, detailed phenotyping, classification, and structural modeling of the identified variant were performed. RESULTS: The cohort comprises 23 individuals with pathogenic or likely pathogenic de novo variants in SNAP25. Intellectual disability and early-onset epilepsy were identified as the core symptoms of SNAP25-DEE, with recurrent findings of movement disorders, cerebral visual impairment, and brain atrophy. Structural modeling for all variants predicted possible functional defects concerning SNAP25 or impaired interaction with other components of the SNARE complex. CONCLUSION: We provide a comprehensive description of SNAP25-DEE with intellectual disability and early-onset epilepsy mostly occurring before the age of two years. These core symptoms and additional recurrent phenotypes show an overlap to genes encoding other components or associated proteins of the SNARE complex such as STX1B, STXBP1, or VAMP2. Thus, these findings advance the concept of a group of neurodevelopmental disorders that may be termed "SNAREopathies."


Assuntos
Encefalopatias , Epilepsia , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Proteína 25 Associada a Sinaptossoma/genética , Pré-Escolar , Epilepsia/genética , Humanos , Transtornos do Neurodesenvolvimento/genética , Fenótipo
10.
Appetite ; 167: 105608, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34302899

RESUMO

Parents serve as role models and household policy makers for their children's home social environment. Also, parents may influence the home physical environment through the provision of resources to support their children's dietary, activity, and sleep behaviors. Understanding the parental characteristics related to children's home environment may allow for tailoring obesity interventions to families' needs. This study aimed to explore parental qualities (general parenting styles, parent feeding practices, and parental BMI) related to healthy home food, physical activity, media and sleep environment of toddlers. A total of 50 multi-ethnic parents with toddler age children who were enrolled in a randomized pilot study of a wellness program completed the Structure and Control in Parent Feeding (SCPF) questionnaire and Comprehensive General Parenting Questionnaire (CGPQ). Parental BMI was calculated using self-reported weight and height data. The Healthy Home Survey, the Home Food Inventory, the Sleep Environment Questionnaire, and items developed for this study were standardized and summed to create home food, physical activity, screen media, and sleep environment scores; high scores reflected healthier environments. To examine the relationships between parental qualities and the home environment, Pearson's correlation test was performed. Parental BMI and overall healthy home environment were inversely associated (r = -0.306; p = 0.032). Structure in general parenting and parental feeding practice were positively correlated with the overall healthy home environment (r = 0.336; p = 0.026) and healthy home food environment (r = 0.415; p = 0.003), respectively. The coercive control general parenting was inversely related to overall healthy home environment score (r = -0.333; p = 0.022). Based on the findings from this study, parents who provide clear communication, set consistent rules, avoid pressure to control their child's behavior, and have lower BMI tend to live in a home environment that support children's health behaviors.


Assuntos
Poder Familiar , Pais , Pré-Escolar , Dieta , Comportamento Alimentar , Humanos , Relações Pais-Filho , Projetos Piloto , Inquéritos e Questionários
11.
Hosp Pharm ; 56(4): 241-246, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34381256

RESUMO

Purpose/Background: Percutaneous left ventricular assist devices (pVADs) require a continuous purge solution containing heparin to prevent pump thrombosis and device failure. Data regarding alternative options in patients who have suspected heparin-induced thrombocytopenia (HIT) are limited. Methods: In this report, we describe a 68-year-old white man with cardiogenic shock with an Impella CP device managed with a low concentration argatroban-based purge solution secondary to a suspected diagnosis of HIT. Results: The purge solution was initiated as argatroban in dextrose 10% at a concentration of 0.12 mg/mL and was subsequently decreased twice to 0.06 and 0.015 mg/mL based on the patient's clinical course. Conclusions: This case report describes the safe and effective use of argatroban purge solution necessary for anticoagulation although further studies are needed to confirm these findings.

12.
J Biomol NMR ; 74(10-11): 595-611, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32761504

RESUMO

The presence of suitable cavities or pockets on protein structures is a general criterion for a therapeutic target protein to be classified as 'druggable'. Many disease-related proteins that function solely through protein-protein interactions lack such pockets, making development of inhibitors by traditional small-molecule structure-based design methods much more challenging. The 22 kDa bacterial thiol oxidoreductase enzyme, DsbA, from the gram-negative bacterium Burkholderia pseudomallei (BpsDsbA) is an example of one such target. The crystal structure of oxidized BpsDsbA lacks well-defined surface pockets. BpsDsbA is required for the correct folding of numerous virulence factors in B. pseudomallei, and genetic deletion of dsbA significantly attenuates B. pseudomallei virulence in murine infection models. Therefore, BpsDsbA is potentially an attractive drug target. Herein we report the identification of a small molecule binding site adjacent to the catalytic site of oxidized BpsDsbA. 1HN CPMG relaxation dispersion NMR measurements suggest that the binding site is formed transiently through protein dynamics. Using fragment-based screening, we identified a small molecule that binds at this site with an estimated affinity of KD ~ 500 µM. This fragment inhibits BpsDsbA enzymatic activity in vitro. The binding mode of this molecule has been characterized by NMR data-driven docking using HADDOCK. These data provide a starting point towards the design of more potent small molecule inhibitors of BpsDsbA.


Assuntos
Ressonância Magnética Nuclear Biomolecular/métodos , Proteína Dissulfeto Redutase (Glutationa)/química , Animais , Sítios de Ligação , Burkholderia pseudomallei/enzimologia , Burkholderia pseudomallei/patogenicidade , Domínio Catalítico , Ligantes , Camundongos , Oxirredução , Ligação Proteica , Conformação Proteica , Proteína Dissulfeto Redutase (Glutationa)/genética , Relação Quantitativa Estrutura-Atividade , Proteínas Recombinantes , Bibliotecas de Moléculas Pequenas/química , Solubilidade , Tiazóis/química
13.
J Anim Physiol Anim Nutr (Berl) ; 104(3): 802-811, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32083351

RESUMO

Evidence suggests that lipopolysaccharide (LPS) absorbed from the large intestine may contribute to the inflammatory response to high starch feeding in dairy cows. This work evaluated the impact of buffers or alkalinizing agents with expected large intestinal activity on faecal indicators of intestinal fermentation and LPS. Ten late-lactation cows were used in a replicated 5 × 5 Latin square design with 7-day periods. Cows were fed a diet containing 265 g/kg dry matter of starch and were abomasally infused with 1 g/kg body weight cornstarch daily. Treatments were control (CON), ration supplementation with 200 g/day sodium bicarbonate (FSB), 200 g/day calcium carbonate (FCC) or 125 g/day calcium carbonate plus 75 g/day of magnesium oxide (FCCM), or abomasal infusion of a lipid encapsulate providing 200 g/day sodium bicarbonate (ISB). The FCC, FCCM and ISB treatments were hypothesized to have large intestinal buffering effects, and FSB was included as a secondary control. Milk, feed, rumen and faecal samples were collected on day 7 of each period. Treatment did not affect intake, milk yield or milk composition. There were no effects of treatment on ruminal measures except that ISB tended to reduce and the post-ruminal treatments as a whole (FCC, FCCM and ISB) reduced rumen butyrate compared with CON. Faecal pH was greater for FCCM compared with all other treatments. Total faecal VFA tended to increase with FCC and FCCM compared with CON and was increased by the post-ruminal treatments as a whole compared with CON. Treatment did not affect faecal dry matter, lactate or LPS or apparent total tract nutrient digestibility. Although some treatments altered fermentation as evidenced by the change in faecal VFA, this was not accompanied by a decrease in faecal LPS. The strategies employed in this study had limited effects on large intestinal fermentation.


Assuntos
Carbonato de Cálcio/farmacologia , Óxido de Magnésio/farmacologia , Rúmen/fisiologia , Bicarbonato de Sódio/farmacologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Carbonato de Cálcio/administração & dosagem , Bovinos , Dieta/veterinária , Fezes/química , Fermentação , Óxido de Magnésio/administração & dosagem , Bicarbonato de Sódio/administração & dosagem
14.
J Am Psychiatr Nurses Assoc ; 26(2): 206-211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31342836

RESUMO

INTRODUCTION: Measurement-based care (MBC) uses standardized measurement to systematically monitor treatment response over time. Although MBC is underutilized in mental health settings, primary care-mental health integration (PC-MHI) settings are expected to provide MBC. This article describes a quality improvement (QI) process to increase Patient Health Questionnaire-9 (PHQ9) utilization within a PC-MHI setting. AIMS: Pre-intervention, rates of baseline and follow-up PHQ9 administration for veterans with a depressive disorder were 76% and 35%, respectively. This article describes a QI process to increase PHQ9 utilization rates within a PC-MHI setting, with the goal to improve provider PHQ9 utilization rates at baseline and within 4-week follow-up to 90%. METHOD: An educational intervention and weekly motivational enhancement sessions were implemented in 2017. Chart review data compared PHQ9 utilization rates from fall 2016 and 2017. RESULTS: Following intervention, provider PHQ9 utilization rates increased to 98% and 88% at baseline and follow-up. CONCLUSIONS: These findings demonstrate that a brief education-based intervention can increase clinician use of MBC within a PC-MHI setting. Meaningful use of MBC to inform treatment was not evaluated in this QI project and is an area for future investigation.


Assuntos
Prestação Integrada de Cuidados de Saúde , Pessoal de Saúde/educação , Serviços de Saúde Mental , Questionário de Saúde do Paciente/estatística & dados numéricos , Atenção Primária à Saúde , Melhoria de Qualidade , Transtorno Depressivo/terapia , Feminino , Humanos , Masculino , Motivação , Aceitação pelo Paciente de Cuidados de Saúde , Fatores de Tempo , Veteranos
15.
Transfusion ; 59(2): 714-722, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30450617

RESUMO

BACKGROUND: Dried plasmas can overcome logistical barriers that prevent fresh frozen plasma (FFP) usage in acute resuscitation, but processing of these products can detrimentally alter the composition. Spray-dried plasma (SpDP) from single units is deficient in high-molecular-weight multimers of von Willebrand factor (vWF), a critical facilitator of platelet adhesion and thrombus formation. We hypothesized that converting high-molecular-weight multimers to smaller-molecular-weight multimers would retain vWF's capacity to mediate platelet adhesion. STUDY DESIGN AND METHODS: SpDP obtained from untreated FFP was reconstituted with glycine-hydrochloric acid (HCl) and glycine (20 mM:50 mM) or pretreated with glycine-HCl (20 mM) or glycine-glycine-HCl (20 mM:50 mM) and reconstituted with water. In vitro hemostatic potential of SpDPs versus FFP or FFP spiked with 70 mM of glycine was evaluated, leading to a more detailed in vitro study of glycine-HCl-glycine (20 mM:50 mM) pretreated SpDP. Plasmas were combined with RBCs and platelets to observe global coagulation response. RESULTS: While vWF-ristocetin cofactor activity is significantly decreased (-41.13%; p < .0001) in SpDP, a model of vWF-mediated platelet adhesion to collagen under flow showed enhanced function (+13%; p < .01). Fewer microparticles, particularly of platelet origin, were observed in SpDP versus FFP (p < .0001). Small but significant differences in thromboelastography results were observed, although SpDP and FFP were within normal ranges. CONCLUSION: Comparable coagulability was observed in FFP and SpDP. The apparent paradox between vWF-ristocetin cofactor assay and vWF-mediated platelet adhesion may be explained by the increase in smaller multimers of vWF in SpDP, producing different outcomes in these assays.


Assuntos
Coagulação Sanguínea , Plaquetas/metabolismo , Hemostasia , Hemostáticos/análise , Plasma/química , Adesividade Plaquetária , Fator de von Willebrand/análise , Dessecação , Feminino , Humanos , Masculino , Fator de von Willebrand/química
16.
Transfusion ; 59(S2): 1490-1498, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980737

RESUMO

BACKGROUND: Current limitations of platelet shelf life to 5 days have led to an increasingly greater demand for hemostatic agents with greater longevity. The objective of this study was to evaluate the function of a lyophilized platelet-derived hemostatic product (thrombosome [TS]) as a potential alternative to fresh platelets. METHODS: Platelets were collected from whole blood from healthy donors. TSs were reconstituted with water and added to various configurations of reassembled whole blood (platelets, plasma, and RBCs); measures included rotational thromboelastometry (ROTEM), optical aggregometry, mitochondrial function, calibrated automated thrombogram, collagen adhesion under flow (shear flow assay), and flow cytometry. RESULTS: In ROTEM, no differences were observed between maximum clot formation values for contact pathway activation thromboelastometry tests with TSs or platelet samples. Significantly decreased aggregation was observed in the TSs versus platelets (p < 0.001 for all agonists). Flow cytometry measures demonstrated significant decreases in glycoprotein Ib expression and increases in phosphatidylserine expression in the TS group (p < 0.01). The calibrated automated thrombogram assay was suggestive (lag time and peak thrombin) that the TSs might have some thrombogenic properties. Measurements of mitochondrial function revealed that TSs had no functional mitochondria. CONCLUSION: In this study, TSs were shown to have nonfunctional mitochondria. ROTEM measures revealed that the TSs had no impact on clot strength. Likewise, compared to platelets, the TSs displayed minimal aggregation, had significantly more phosphatidylserine (measure of activation status), but had the ability to adhere to a collagen surface under flow conditions and contribute to clot formation and induced greater thrombin generation.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Plaquetas , Citometria de Fluxo , Hemostáticos , Agregação Plaquetária/efeitos dos fármacos , Plaquetas/química , Plaquetas/metabolismo , Liofilização , Hemostáticos/química , Hemostáticos/farmacologia , Humanos , Mitocôndrias/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Tromboelastografia
17.
Nucleic Acids Res ; 45(3): 1281-1296, 2017 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-28003475

RESUMO

Molecular changes underlying stem cell differentiation are of fundamental interest. scRNA-seq on murine hematopoietic stem cells (HSC) and their progeny MPP1 separated the cells into 3 main clusters with distinct features: active, quiescent, and an un-characterized cluster. Induction of anemia resulted in mobilization of the quiescent to the active cluster and of the early to later stage of cell cycle, with marked increase in expression of certain transcription factors (TFs) while maintaining expression of interferon response genes. Cells with surface markers of long term HSC increased the expression of a group of TFs expressed highly in normal cycling MPP1 cells. However, at least Id1 and Hes1 were significantly activated in both HSC and MPP1 cells in anemic mice. Lineage-specific genes were differently expressed between cells, and correlated with the cell cycle stages with a specific augmentation of erythroid related genes in the G2/M phase. Most lineage specific TFs were stochastically expressed in the early precursor cells, but a few, such as Klf1, were detected only at very low levels in few precursor cells. The activation of these factors may correlate with stages of differentiation. This study reveals effects of cell cycle progression on the expression of lineage specific genes in precursor cells, and suggests that hematopoietic stress changes the balance of renewal and differentiation in these homeostatic cells.


Assuntos
Perfilação da Expressão Gênica/métodos , Células-Tronco Hematopoéticas/fisiologia , Análise de Célula Única/métodos , Anemia/genética , Animais , Linhagem da Célula/genética , Eritropoese/genética , Feminino , Regulação da Expressão Gênica , Células-Tronco Hematopoéticas/citologia , Masculino , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA/métodos , Fatores de Transcrição HES-1/genética , Fatores de Transcrição/genética
19.
J Emerg Med ; 53(5): 771-777, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28987297

RESUMO

BACKGROUND: Victims of intimate partner violence (IPV) frequently do not disclose abuse to medical providers. Therefore, research has examined the most effective screening and referral methods to help identify victims of abuse and connect them to needed resources. OBJECTIVES: To determine the efficacy of referrals intended to connect IPV victims with behavioral health resources, while taking into consideration demographic and mental health variables. METHODS: We examined a convenience sample of medically stable individuals in an emergency department setting. Participants were given the Mini-International Neuropsychiatric Interview and Partner Violence Screen measures to assess mental health and IPV victimization. Individuals that screened positive were randomized to a basic or enhanced referral and given a follow-up interview to determine referral success. Referrals were considered successful if an individual scheduled an appointment with provided behavioral health resources within the follow-up interval. RESULTS: Two-hundred and one individuals were enrolled. Forty-one (20.4%) participants screened positive for IPV victimization. Male and female participants in the enhanced referral group were more likely to have a successful referral than those in the basic referral group, with a large effect size such that 72.7% of participants in the enhanced referral and 15.7% of participants in the basic referral group contacted referral resources. Both referral type and marital status significantly predicted referral success. CONCLUSION: Comorbidity with mental health concerns measured as high within those that screened positive for IPV victimization. The enhanced referral showed to be an effective way to encourage participants to contact behavioral health resources.


Assuntos
Violência por Parceiro Íntimo/psicologia , Encaminhamento e Consulta/classificação , População Urbana/estatística & dados numéricos , Adulto , Distribuição de Qui-Quadrado , Vítimas de Crime/psicologia , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Psicometria/instrumentação , Psicometria/métodos , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/estatística & dados numéricos
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