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1.
Acad Emerg Med ; 31(4): 326-338, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38112033

RESUMO

BACKGROUND: Telehealth has been proposed as one strategy to improve the quality of time-sensitive sepsis care in rural emergency departments (EDs). The purpose of this study was to measure the association between telehealth-supplemented ED (tele-ED) care, health care costs, and clinical outcomes among patients with sepsis in rural EDs. METHODS: Cohort study using Medicare fee-for-service claims data for beneficiaries treated for sepsis in rural EDs between February 1, 2017, and September 30, 2019. Our primary hospital-level analysis used multivariable generalized estimating equations to measure the association between treatment in a tele-ED-capable hospital and 30-day total costs of care. In our supporting secondary analysis, we conducted a propensity-matched analysis of patients who used tele-ED with matched controls from non-tele-ED-capable hospitals. Our primary outcome was total health care payments among index hospitalized patients between the index ED visit and 30 days after hospital discharge, and our secondary outcomes included hospital mortality, hospital length of stay, 90-day mortality, 28-day hospital-free days, and 30-day inpatient readmissions. RESULTS: In our primary analysis, sepsis patients in tele-ED-capable hospitals had 6.7% higher (95% confidence interval [CI] 2.1%-11.5%) total health care costs compared to those in non-tele-ED-capable hospitals. In our propensity-matched patient-level analysis, total health care costs were 23% higher (95% CI 16.5%-30.4%) in tele-ED cases than matched non-tele-ED controls. Clinical outcomes were similar. CONCLUSIONS: Tele-ED capability in a mature rural tele-ED network was not associated with decreased health care costs or improved clinical outcomes. Future work is needed to reduce rural-urban sepsis care disparities and formalize systems of regionalized care.


Assuntos
Sepse , Telemedicina , Humanos , Idoso , Estados Unidos , Estudos de Coortes , Medicare , Serviço Hospitalar de Emergência , Sepse/diagnóstico , Sepse/terapia
2.
bioRxiv ; 2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37873284

RESUMO

We previously reported that acute myeloid leukemia stem cells (LSCs) are uniquely reliant on oxidative phosphorylation (OXPHOS) for survival. Moreover, maintenance of OXPHOS is dependent on BCL2, creating a therapeutic opportunity to target LSCs using the BCL2 inhibitor drug venetoclax. While venetoclax-based regimens have indeed shown promising clinical activity, the emergence of drug resistance is prevalent. Thus, in the present study, we investigated how mitochondrial properties may influence mechanisms that dictate venetoclax responsiveness. Our data show that utilization of mitochondrial calcium is fundamentally different between drug responsive and non-responsive LSCs. By comparison, venetoclax-resistant LSCs demonstrate a more active metabolic (i.e., OXPHOS) status with relatively high steady-state levels of calcium. Consequently, we tested genetic and pharmacological approaches to target the mitochondrial calcium uniporter, MCU. We demonstrate that inhibition of calcium uptake sharply reduces OXPHOS and leads to eradication of venetoclax-resistant LSCs. These findings demonstrate a central role for calcium signaling in the biology of LSCs and provide a therapeutic avenue for clinical management of venetoclax resistance.

3.
Cancer Discov ; 13(9): 2032-2049, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37358260

RESUMO

The BCL2 inhibitor venetoclax has recently emerged as an important component of acute myeloid leukemia (AML) therapy. Notably, use of this agent has revealed a previously unrecognized form of pathogenesis characterized by monocytic disease progression. We demonstrate that this form of disease arises from a fundamentally different type of leukemia stem cell (LSC), which we designate as monocytic LSC (m-LSC), that is developmentally and clinically distinct from the more well-described primitive LSC (p-LSC). The m-LSC is distinguished by a unique immunophenotype (CD34-, CD4+, CD11b-, CD14-, CD36-), unique transcriptional state, reliance on purine metabolism, and selective sensitivity to cladribine. Critically, in some instances, m-LSC and p-LSC subtypes can co-reside in the same patient with AML and simultaneously contribute to overall tumor biology. Thus, our findings demonstrate that LSC heterogeneity has direct clinical significance and highlight the need to distinguish and target m-LSCs as a means to improve clinical outcomes with venetoclax-based regimens. SIGNIFICANCE: These studies identify and characterize a new type of human acute myeloid LSC that is responsible for monocytic disease progression in patients with AML treated with venetoclax-based regimens. Our studies describe the phenotype, molecular properties, and drug sensitivities of this unique LSC subclass. This article is featured in Selected Articles from This Issue, p. 1949.


Assuntos
Leucemia Mieloide Aguda , Humanos , Antígenos CD34/metabolismo , Antígenos CD34/uso terapêutico , Leucemia Mieloide Aguda/genética , Células-Tronco Neoplásicas/metabolismo , Progressão da Doença
4.
Antibiotics (Basel) ; 11(1)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35052990

RESUMO

Denture stomatitis (DS) is an inflammatory disease resulting from a polymicrobial biofilm perturbation at the denture surface-palatal mucosa interface. Recommendations made by dental health care professionals often lack clarity for appropriate denture cleaning. This study investigated the efficacy of brushing with off-the-shelf denture cleanser (DC) tablets (Poligrip®) vs. two toothpastes (Colgate® and Crest®) in alleviating the viable microorganisms (bacteria and fungi) in an in vitro denture biofilm model. Biofilms were grown on poly(methyl)methacrylate (PMMA) discs, then treated daily for 7 days with mechanical disruption (brushing), plus Poligrip® DC, Colgate® or Crest® toothpastes. Weekly treatment with Poligrip® DC on day 7 only was compared to daily modalities. All treatment parameters were processed to determine viable colony forming units for bacteria and fungi using the Miles and Misra technique, and imaged by confocal laser scanning microscopy (CLSM). Brushing with daily DC therapy was the most effective treatment in reducing the viable biofilm over 7 days of treatment. Brushing only was ineffective in controlling the viable bioburden, which was confirmed by CLSM imaging. This data indicates that regular cleansing of PMMA with DC was best for polymicrobial biofilms.

5.
Pediatr Emerg Care ; 38(2): e961-e966, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34282092

RESUMO

OBJECTIVES: The purpose of the study was to evaluate patterns of fall-related injury through childhood and identify risk factors for more severe fall-related injuries with the goal of informing targeted prevention strategies for different ages. METHODS: The study population consisted of pediatric patients in the Iowa Trauma Registry from January 1, 2010, to December 31, 2014, who sustained an unintentional fall-related injury (N = 3856 patients). Multinomial logistic regression analysis was used to predict injury severity. Adjusted odds ratios were calculated characterizing the relationship between fall severity and age, sex, race, and fall type. RESULTS: More males (62%) sustained a fall-related injury during the study period when compared with females (38%; P < 0.0001). Head injuries were the most common type of injury in the younger than 1 year age group (77%), whereas fractures were the predominant injury type in all other age groups, followed by head injuries. Those younger than 1 year (adjusted odds ratio, 4.0; 95% confidence interval, 2.36-6.90) and aged 15 to 18 years (adjusted odds ratio, 1.9; 95% confidence interval, 1.17-3.03) were more likely to have an Injury Severity Score of ≥16 than those aged 10 to 14 years. CONCLUSIONS: Recommendations and prevention strategies need to focus on specific risk factors to reduce the harm of multilevel falls. As we have shown, patterns of fall injuries presenting to trauma hospitals differ by age, thus suggesting that prevention strategies focus on specific age groups.


Assuntos
Traumatismos Craniocerebrais , Fraturas Ósseas , Ferimentos e Lesões , Acidentes por Quedas , Criança , Traumatismos Craniocerebrais/epidemiologia , Traumatismos Craniocerebrais/etiologia , Feminino , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Escala de Gravidade do Ferimento , Masculino , Sistema de Registros , Estudos Retrospectivos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/etiologia
6.
RSC Adv ; 11(13): 7527-7537, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-35423271

RESUMO

Biophysical screening of compound libraries for the identification of ligands that interact with a protein is efficient, but does typically not reveal if (or how) ligands may interfere with its functional properties. For this a biochemical/functional assay is required. But for proteins whose function is dependent on a conformational change, such assays are typically complex or have low throughput. Here we have explored a high-throughput second-harmonic generation (SHG) biosensor to detect fragments that induce conformational changes upon binding to a protein in real time and identify dynamic regions. Multiwell plate format SHG assays were developed for wild-type and six engineered single-cysteine mutants of acetyl choline binding protein (AChBP), a homologue to ligand gated ion channels (LGICs). They were conjugated with second harmonic-active labels via amine or maleimide coupling. To validate the assay, it was confirmed that the conformational changes induced in AChBP by nicotinic acetyl choline receptor (nAChR) agonists and antagonists were qualitatively different. A 1056 fragment library was subsequently screened against all variants and conformational modulators of AChBP were successfully identified, with hit rates from 9-22%, depending on the AChBP variant. A subset of four hits was selected for orthogonal validation and structural analysis. A time-resolved grating-coupled interferometry-based biosensor assay confirmed the interaction to be a reversible 1-step 1 : 1 interaction, and provided estimates of affinities and interaction kinetic rate constants (K D = 0.28-63 µM, k a = 0.1-6 µM-1 s-1, k d = 1 s-1). X-ray crystallography of two of the fragments confirmed their binding at a previously described conformationally dynamic site, corresponding to the regulatory site of LGICs. These results reveal that SHG has the sensitivity to identify fragments that induce conformational changes in a protein. A selection of fragment hits with a response profile different to known LGIC regulators was characterized and confirmed to bind to dynamic regions of the protein.

7.
Microorganisms ; 9(1)2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379333

RESUMO

Background: Existing standardized biofilm assays focus on simple mono-species or bacterial-only models. Incorporating Candida albicans into complex biofilm models can offer a more appropriate and relevant polymicrobial biofilm for the development of oral health products. Aims: This study aimed to assess the importance of interkingdom interactions in polymicrobial oral biofilm systems with or without C. albicans, and test how these models respond to oral therapeutic challenges in vitro. Materials and Methods: Polymicrobial biofilms (two models containing 5 and 10 bacterial species, respectively) were created in parallel in the presence and absence of C. albicans and challenged using clinically relevant antimicrobials. The metabolic profiles and biomasses of these complex biofilms were estimated using resazurin dye and crystal violet stain, respectively. Quantitative PCR was utilized to assess compositional changes in microbial load. Additional assays, for measurements of pH and lactate, were included to monitor fluctuations in virulence "biomarkers." Results: An increased level of metabolic activity and biomass in the presence of C. albicans was observed. Bacterial load was increased by more than a factor of 10 in the presence of C. albicans. Assays showed inclusion of C. albicans impacted the biofilm virulence profiles. C. albicans did not affect the biofilms' responses to the short-term incubations with different treatments. Conclusions: The interkingdom biofilms described herein are structurally robust and exhibit all the hallmarks of a reproducible model. To our knowledge, these data are the first to test the hypothesis that yeasts may act as potential "keystone" components of oral biofilms.

8.
Telemed J E Health ; 26(6): 760-768, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31549903

RESUMO

Background: The use of text messaging is a growing trend. Usual care for follow-up with patients (no dedicated communication) has proven unreliable, and alternative communication methods may be beneficial. Introduction: The objective was to evaluate the effect of text messaging as a means of follow-up communication compared to usual care on patient satisfaction among patients discharged from the emergency department (ED). Materials and Methods: Participants completed a baseline survey about their text message usage and ED visit satisfaction. The participants completed a follow-up survey 2 weeks later. Participants randomized to text messaging received a text message at 24 h, 1 week, and 2 weeks after discharge. Control participants received usual care (typically no dedicated communication). Bivariate analyses were performed, and intent-to-treat and per protocol analyses were completed to examine follow-up satisfaction with ED communication/care. Results: A total of 802 subjects were recruited (text messaging-398 subjects, usual care-404 subjects). In the intent-to-treat analysis, text messaging subjects were not more likely to report satisfaction with follow-up communication (adjusted odds ratio [aOR] 0.90 [0.46-1.75]) or follow-up care (aOR 0.66 [0.30-1.46]) than usual care subjects. In per-protocol analysis, text messaging subjects had 2.95 (1.52-5.73) higher odds of reporting satisfaction with follow-up communication and 3.24 (1.46-7.16) higher odds of reporting satisfaction with follow-up care. Discussion: The use of text messaging for follow-up, when comparing satisfaction with follow-up communication and follow-up care after discharge, performs at least equally as well as usual follow-up. Conclusions: Text messaging is a provider time-saving and resource-conserving technology allowing health care providers to potentially reach a larger proportion of patients, making it a valuable form of follow-up communication.


Assuntos
Envio de Mensagens de Texto , Serviço Hospitalar de Emergência , Seguimentos , Humanos , Alta do Paciente , Satisfação do Paciente
9.
Nat Microbiol ; 4(12): 2523-2537, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31527793

RESUMO

Enteroviruses (EVs) comprise a large genus of positive-sense, single-stranded RNA viruses whose members cause a number of important and widespread human diseases, including poliomyelitis, myocarditis, acute flaccid myelitis and the common cold. How EVs co-opt cellular functions to promote replication and spread is incompletely understood. Here, using genome-scale CRISPR screens, we identify the actin histidine methyltransferase SET domain containing 3 (SETD3) as critically important for viral infection by a broad panel of EVs, including rhinoviruses and non-polio EVs increasingly linked to severe neurological disease such as acute flaccid myelitis (EV-D68) and viral encephalitis (EV-A71). We show that cytosolic SETD3, independent of its methylation activity, is required for the RNA replication step in the viral life cycle. Using quantitative affinity purification-mass spectrometry, we show that SETD3 specifically interacts with the viral 2A protease of multiple enteroviral species, and we map the residues in 2A that mediate this interaction. 2A mutants that retain protease activity but are unable to interact with SETD3 are severely compromised in RNA replication. These data suggest a role of the viral 2A protein in RNA replication beyond facilitating proteolytic cleavage. Finally, we show that SETD3 is essential for in vivo replication and pathogenesis in multiple mouse models for EV infection, including CV-A10, EV-A71 and EV-D68. Our results reveal a crucial role of a host protein in viral pathogenesis, and suggest targeting SETD3 as a potential mechanism for controlling viral infections.


Assuntos
Enterovirus/metabolismo , Enterovirus/patogenicidade , Histona Metiltransferases/metabolismo , Metiltransferases/metabolismo , Animais , Sistemas CRISPR-Cas , Viroses do Sistema Nervoso Central/virologia , Modelos Animais de Doenças , Encefalite Viral , Enterovirus/genética , Infecções por Enterovirus/virologia , Histona Metiltransferases/genética , Camundongos , Mielite/virologia , Doenças Neuromusculares/virologia , Proteólise , Proteínas Virais , Replicação Viral
10.
J Med Microbiol ; 68(11): 1573-1584, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31524581

RESUMO

Over the past century, numerous studies have used oral biofilm models to investigate growth kinetics, biofilm formation, structure and composition, antimicrobial susceptibility and host-pathogen interactions. In vivo animal models provide useful models of some oral diseases; however, these are expensive and carry vast ethical implications. Oral biofilms grown or maintained in vitro offer a useful platform for certain studies and have the advantages of being inexpensive to establish and easy to reproduce and manipulate. In addition, a wide range of variables can be monitored and adjusted to mimic the dynamic environmental changes at different sites in the oral cavity, such as pH, temperature, salivary and gingival crevicular fluid flow rates, or microbial composition. This review provides a detailed insight for early-career oral science researchers into how the biofilm models used in oral research have progressed and improved over the years, their advantages and disadvantages, and how such systems have contributed to our current understanding of oral disease pathogenesis and aetiology.


Assuntos
Bactérias/isolamento & purificação , Biofilmes , Boca/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Fenômenos Fisiológicos Bacterianos , Humanos
11.
Inj Epidemiol ; 6: 31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240171

RESUMO

BACKGROUND: The goal of predictive modelling is to identify the likelihood of future events, such as the predictive modelling used in climate science to forecast weather patterns and significant weather occurrences. In public health, increasingly sophisticated predictive models are used to predict health events in patients and to screen high risk individuals, such as for cardiovascular disease and breast cancer. Although causal modelling is frequently used in epidemiology to identify risk factors, predictive modelling provides highly useful information for individual risk prediction and for informing courses of treatment. Such predictive knowledge is often of great utility to physicians, counsellors, health education specialists, policymakers or other professionals, who may then advice course correction or interventions to prevent adverse health outcomes from occurring. In this manuscript, we use an example dataset that documents farm vehicle crashes and conventional statistical methods to forecast the risk of an injury or death in a farm vehicle crash for a specific individual or a scenario. RESULTS: Using data from 7094 farm crashes that occurred between 2005 and 2010 in nine mid-western states, we demonstrate and discuss predictive model fitting approaches, model validation techniques using external datasets, and the calculation and interpretation of predicted probabilities. We then developed two automated risk prediction tools using readily available software packages. We discuss best practices and common limitations associated with predictive models built from observational datasets. CONCLUSIONS: Predictive analysis offers tools that could aid the decision making of policymakers, physicians, and environmental health practitioners to improve public health.

12.
Telemed J E Health ; 25(2): 93-100, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29958087

RESUMO

BACKGROUND: Meeting time goals for patients with time-sensitive conditions can be challenging in rural emergency departments (EDs), and adopting policies is critical. ED-based telemedicine has been proposed to improve quality and timeliness of care in rural EDs. INTRODUCTION: The objective of this study was to test the hypothesis that diagnostic testing in telemedicine-supplemented ED care for patients with myocardial infarction (MI) and stroke would be faster than nontelemedicine care in rural EDs. MATERIALS AND METHODS: This observational cohort study included all ED patients with MI or stroke in 19 rural critical access hospitals served by a single real-time contract-based telemedicine provider in the upper Midwest (2007-2015). The primary outcome for the MI cohort was time-to-electrocardiogram (EKG) and for the stroke cohort was time-to-head computed tomography (CT) interpretation. To measure the relationship between telemedicine and timeliness parameters, generalized estimating equations models were used, clustering on presenting hospital. RESULTS: Of participating ED visits, 756 were included in the MI cohort (29% used telemedicine) and 140 were included in the stroke cohort (30% used telemedicine). Time-to-EKG did not differ when telemedicine was used (1% faster, 95% confidence interval [CI] -4% to 7%), or after telemedicine was implemented (4% faster, 95% CI -3% to 10%). Head CT interpretation was faster for telemedicine cases (15% faster, 95% CI 4-26%). No differences were observed in time to reperfusion therapy. CONCLUSIONS: Telemedicine implementation was associated with more timely head CT interpretation for rural patients with stroke, but no difference in early MI care. Future work will focus on the specific manner in which telemedicine changes ED care processes and ongoing professional education.


Assuntos
Serviço Hospitalar de Emergência/organização & administração , Hospitais Rurais/organização & administração , Infarto do Miocárdio/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Telemedicina/organização & administração , Eletrocardiografia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitais Rurais/estatística & dados numéricos , Humanos , Masculino , Acidente Vascular Cerebral/diagnóstico por imagem , Telemedicina/estatística & dados numéricos , Fatores de Tempo , Tomografia Computadorizada por Raios X
13.
Methods Enzymol ; 610: 167-190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30390798

RESUMO

Second-harmonic generation (SHG) has recently emerged as a biophysical tool for conformational sensing of a target biomolecule upon binding to ligands such as small molecules, fragments, proteins, peptides, and oligonucleotides. To date, SHG has been used to measure conformational changes of targets such as soluble proteins, protein complexes, intrinsically disordered proteins, peripheral and integral membrane proteins, peptides, and oligonucleotides upon binding of ligands over a wide range of affinities. In this chapter, we will provide a technology overview, detailed protocols for optimizing assays and screening, practical considerations, and an example case study to guide the reader in developing robust and informative measurements using the Biodesy Delta SHG platform.


Assuntos
Descoberta de Drogas/métodos , Ensaios de Triagem em Larga Escala/métodos , Oligonucleotídeos/metabolismo , Peptídeos/metabolismo , Proteínas/metabolismo , Animais , Descoberta de Drogas/instrumentação , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/instrumentação , Humanos , Ligantes , Conformação de Ácido Nucleico/efeitos dos fármacos , Oligonucleotídeos/química , Peptídeos/química , Conformação Proteica/efeitos dos fármacos , Proteínas/química
14.
FEBS Open Bio ; 8(9): 1412-1423, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30186743

RESUMO

Many clinically approved protein kinase inhibitors stabilize an inactive conformation of their kinase target. Such inhibitors are generally highly selective compared to active conformation inhibitors, and consequently, general methods to identify inhibitors that stabilize an inactive conformation are much sought after. Here, we have applied a high-throughput, second-harmonic generation (SHG)-based conformational approach to identify small molecule stabilizers of the inactive conformation of interleukin-2-inducible T-cell kinase (ITK). A single-site cysteine mutant of the ITK kinase domain was created, labeled with an SHG-active dye, and tethered to a supported lipid bilayer membrane. Fourteen tool compounds, including stabilizers of the inactive and active conformations as well as nonbinders, were first examined for their effect on the conformation of the labeled ITK protein in the SHG assay. As a result, inactive conformation inhibitors were clearly distinguished from active conformation inhibitors by the intensity of SHG signal. Utilizing the SHG assay developed with the tool compounds described above, we identified the mechanism of action of 22 highly selective, inactive conformation inhibitors within a group of 105 small molecule inhibitors previously identified in a high-throughput biochemical screen. We describe here the first use of SHG for identifying and classifying inhibitors that stabilize an inactive vs. an active conformation of a protein kinase, without the need to determine costructures by X-ray crystallography. Our results suggest broad applicability to other proteins, particularly with single-site labels reporting on specific protein movements associated with selectivity.

15.
J Immunol ; 201(7): 2094-2106, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30104245

RESUMO

IL-2 has been used to treat diseases ranging from cancer to autoimmune disorders, but its concurrent immunostimulatory and immunosuppressive effects hinder efficacy. IL-2 orchestrates immune cell function through activation of a high-affinity heterotrimeric receptor (composed of IL-2Rα, IL-2Rß, and common γ [γc]). IL-2Rα, which is highly expressed on regulatory T (TReg) cells, regulates IL-2 sensitivity. Previous studies have shown that complexation of IL-2 with the JES6-1 Ab preferentially biases cytokine activity toward TReg cells through a unique mechanism whereby IL-2 is exchanged from the Ab to IL-2Rα. However, clinical adoption of a mixed Ab/cytokine complex regimen is limited by stoichiometry and stability concerns. In this study, through structure-guided design, we engineered a single agent fusion of the IL-2 cytokine and JES6-1 Ab that, despite being covalently linked, preserves IL-2 exchange, selectively stimulating TReg expansion and exhibiting superior disease control to the mixed IL-2/JES6-1 complex in a mouse colitis model. These studies provide an engineering blueprint for resolving a major barrier to the implementation of functionally similar IL-2/Ab complexes for treatment of human disease.


Assuntos
Anticorpos/metabolismo , Doenças Autoimunes/imunologia , Colite/imunologia , Citocinas/metabolismo , Imunoterapia/métodos , Receptores de Interleucina-2/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Linfócitos T Reguladores/imunologia , Animais , Anticorpos/genética , Doenças Autoimunes/terapia , Proliferação de Células , Células Cultivadas , Colite/terapia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Humanos , Ativação Linfocitária , Camundongos , Engenharia de Proteínas , Proteínas Recombinantes de Fusão/genética
16.
Accid Anal Prev ; 113: 257-262, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29444480

RESUMO

INTRODUCTION: Emergency vehicles, such as police, ambulances, and fire vehicles, need to arrive at the scene of emergencies as quickly as possible, and thus they often travel in emergency mode - using their lights and sirens and often bypassing traffic signals. We examined whether travelling in emergency mode increased crash risk among police, ambulance and fire vehicles. METHODS: We conducted a quasi-induced exposure analysis using data from the Iowa Crash Database for the period of 2005 through 2013. The data are maintained by the Iowa Department of Transportation (IADOT), Office of Driver Services (ODS) and includes all investigating police officer's reports of motor vehicle crashes. The quasi-induced exposure method is an approach to calculate crash risk in the absence of exposure data using vehicles without a contributing cause (did not contribute to the crash) as a proxy for the baseline driving population. RESULTS: From 2005 - 2013, police vehicles were involved in 2406 crashes and ambulances and fire vehicles were involved in 528 crashes. Police vehicles were 1.8 times more likely to crash while driving in emergency mode than usual mode; this was a statistically significant increase. Ambulance and fire vehicles were not more likely to crash in emergency mode compared with usual mode. For police, other factors that contributed to crash risk included gender, age, icy/snowy roads, unpaved roads, and intersections. For ambulances and fire vehicles, other factors that contributed to crash risk included gender, age, weekends, icy/snowy roads and urban locations. CONCLUSION: Crash risk increased when police vehicles drove with lights and sirens but did not increase for ambulance and fire vehicles. Further research is necessary to develop and evaluate strategies to mitigate crash risk among police vehicles. Cultural approaches which prioritize transportation safety in conjunction with reaching the scene as quickly as possible may be warranted.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Ambulâncias/estatística & dados numéricos , Condução de Veículo , Socorristas/estatística & dados numéricos , Iluminação , Adulto , Fatores Etários , Bases de Dados Factuais , Feminino , Humanos , Iowa , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
17.
Telemed J E Health ; 24(8): 582-593, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29293413

RESUMO

BACKGROUND: Emergency department (ED)-based telemedicine has been implemented in many rural hospitals to provide specialty care and expertise to patients with critical time-sensitive conditions. INTRODUCTION: The purpose of this study was to measure the impact of ED-based telemedicine on timeliness of care in participating rural hospitals. MATERIALS AND METHODS: Matched cohort study of patients seen in 1 of 14 rural hospitals in a large Midwestern telemedicine network. Telemedicine cases were matched 2:1 with controls based on age, diagnosis, and hospital. The primary outcome was door-to-provider time, and secondary outcomes included ED length-of-stay (LOS) and time-to-transfer in those transferred to other hospitals. RESULTS: Of 127,928 qualifying ED encounters, 2,857 consulted telemedicine and were matched with nontelemedicine controls. Door-to-provider time was shorter in telemedicine patients by 6.0 min (95% confidence interval [CI] 4.3-7.8 min). The first provider seeing the patient was a telemedicine provider in 41.7% of telemedicine encounters, and in these cases, telemedicine was 14.7 min earlier than local providers. ED LOS was 22.1 min shorter (95% CI 3.1-41.2) among transferred patients, but total ED LOS was longer (40.2 min, 95% CI 30.8-49.6 min) for all telemedicine patients. CONCLUSIONS: Telemedicine decreases ED door-to-provider time, most commonly because the telemedicine provider was the first provider seeing a patient. Among transferred patients, ED LOS at the first hospital was shorter in patients who had telemedicine consulted. Future work will focus on the clinical impact of more timely rural ED care.


Assuntos
Serviços Médicos de Emergência/métodos , Tempo de Internação/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Serviços de Saúde Rural/organização & administração , Telemedicina/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , População Rural , Fatores de Tempo , Adulto Jovem
18.
Nat Commun ; 8(1): 781, 2017 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-28974687

RESUMO

Nipah virus is an emergent paramyxovirus that causes deadly encephalitis and respiratory infections in humans. Two glycoproteins coordinate the infection of host cells, an attachment protein (G), which binds to cell surface receptors, and a fusion (F) protein, which carries out the process of virus-cell membrane fusion. The G protein binds to ephrin B2/3 receptors, inducing G conformational changes that trigger F protein refolding. Using an optical approach based on second harmonic generation, we show that monomeric and dimeric receptors activate distinct conformational changes in G. The monomeric receptor-induced changes are not detected by conformation-sensitive monoclonal antibodies or through electron microscopy analysis of G:ephrinB2 complexes. However, hydrogen/deuterium exchange experiments confirm the second harmonic generation observations and reveal allosteric changes in the G receptor binding and F-activating stalk domains, providing insights into the pathway of receptor-activated virus entry.Nipah virus causes encephalitis in humans. Here the authors use a multidisciplinary approach to study the binding of the viral attachment protein G to its host receptor ephrinB2 and show that monomeric and dimeric receptors activate distinct conformational changes in G and discuss implications for receptor-activated virus entry.


Assuntos
Efrina-B2/metabolismo , Vírus Nipah/metabolismo , Proteínas do Envelope Viral/metabolismo , Regulação Alostérica , Anticorpos Monoclonais/metabolismo , Medição da Troca de Deutério , Células HEK293 , Humanos , Espectrometria de Massas , Proteínas Mutantes/metabolismo , Proteínas Mutantes/ultraestrutura , Coloração Negativa , Ligação Proteica , Multimerização Proteica
19.
Artigo em Inglês | MEDLINE | ID: mdl-28758942

RESUMO

Burn-related injuries are a significant burden in children, particularly in low- and middle-income countries (LMICs), where more than 90% of burn-related pediatric deaths occur. Lack of adult supervision of children is a major risk for pediatric burn injuries. The goal of this paper was to examine the general characteristics of burns and identify burn injury outcomes among adult-supervised children compared to those who were not supervised. The study examined burn injury and clinical characteristics among all burn patients admitted to two trauma hospitals in The Gambia, West Africa. At intake in the emergency room, the treating physician or nurse determined the need for admission based on body surface area burned (BSAB), depth of burn, and other clinical considerations such as co-occurring injuries and co-morbidities. During the study period of 1 April 2014 through 31 October 2016, 105 burn patients were admitted and data were collected by the treating physician for all of them. Information about supervision was only asked for children aged five years or less. More than half (51%) of the burn patients were children under 18 years, and 22% were under 5 years. Among children under five, most (86.4%) were supervised by an adult at the time of burn event. Of the 19 supervised children, 16 (84.2%) had body area surface burned (BSAB) of less than 20%. Two of the three children without adult supervision at the time of burn event had BSAB ≥ 20%. Overall, 59% of the patients had 20% + BSAB. Females (aOR = 1.25; 95% CI = 0.43-3.62), those burned in rural towns and villages (aOR = 2.29; 95% CI = 0.69-7.57), or burned by fire or flames (aOR = 1.47; 95% CI = 0.51-4.23) had increased odds of having a BSAB ≥ 20%, although these differences were not statistically significant. Children 0-5 years or 5-18 years (aOR = 0.04, 95% CI = 0.01-0.17; aOR = 0.07, 95% CI = 0.02-0.23, respectively) were less likely to have BSAB ≥ 20% than adults. Those burned in a rural location (aOR = 9.23, 95% CI = 2.30-37.12) or by fire or flames (aOR = 6.09, 95% CI = 1.55-23.97) were more likely to die. Children 0-5 years or 5-18 years (aOR = 0.2, 95% CI = 0.03-1.18; aOR = 0.38; 95% CI = 0.11-1.570, respectively) were less likely to die. Children constitute a significant proportion of admitted burn patients, and most of them were supervised at the time of the burn event. Supervised children (compared to unsupervised children) had less severe burns. Programs that focus on burn prevention at all levels including child supervision could increase awareness and reduce burns or their severity. Programs need to be designed and evaluated with focus on the child development stage and the leading causes of burns by age group.


Assuntos
Queimaduras/epidemiologia , Criança Hospitalizada/estatística & dados numéricos , Adolescente , Cuidadores , Criança , Pré-Escolar , Feminino , Incêndios , Gâmbia/epidemiologia , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Centros de Traumatologia/estatística & dados numéricos
20.
J Environ Public Health ; 2017: 8612953, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28512475

RESUMO

We identified risk factors for road traffic injuries among road users who received treatment at two major trauma hospitals in urban Gambia. The study includes pedestrians, bicyclists, motorcyclists, and drivers/passengers of cars and trucks. We examined distributions of injury by age, gender, collision vehicle types and vehicle category, and driver and environment factors. Two hundred and fifty-four patients were included in the study. Two-thirds were male and one-third female. Two-thirds (67%) of road traffic injuries involved pedestrians, bicyclists, and motorcyclists; and these were more common during weekdays (74%) than weekends. Nearly half (47%) of road traffic injuries involved pedestrians. One-third (34%) of injured patients were students (mean age of students was less than 14 years), more than half (51%) of whom were injured on the roadway as pedestrians. Head/skull injuries were common. Concussion/brain injuries were 3.5 times higher among pedestrians, bicyclists, and motorcyclists than vehicle occupants. Crashes involving pedestrians were more likely to involve young people (<25 years; aOR 6.36, 95% CI: 3.32-12.17) and involve being struck by a motor car (aOR 3.95, 95% CI: 2.09-7.47). Pedestrians contribute the largest proportion of hospitalizations in the Gambia. Young pedestrians are at particularly high risk. Prevention efforts should focus on not only vehicle and driver factors, but also protecting pedestrians, bicyclists, and motorcyclists.


Assuntos
Acidentes de Trânsito/classificação , Acidentes de Trânsito/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Adulto , Feminino , Gâmbia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Fatores de Risco , Ferimentos e Lesões/etiologia , Adulto Jovem
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