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1.
PLoS Comput Biol ; 19(6): e1011147, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37285341

RESUMO

Aquatic systems worldwide can exist in multiple ecosystem states (i.e., a recurring collection of biological and chemical attributes), and effectively characterizing multidimensionality will aid protection of desirable states and guide rehabilitation. The Upper Mississippi River System is composed of a large floodplain river system spanning 2200 km and multiple federal, state, tribal and local governmental units. Multiple ecosystem states may occur within the system, and characterization of the variables that define these ecosystem states could guide river rehabilitation. We coupled a long-term (30-year) highly dimensional water quality monitoring dataset with multiple topological data analysis (TDA) techniques to classify ecosystem states, identify state variables, and detect state transitions over 30 years in the river to guide conservation. Across the entire system, TDA identified five ecosystem states. State 1 was characterized by exceptionally clear, clean, and cold-water conditions typical of winter (i.e., a clear-water state); State 2 had the greatest range of environmental conditions and contained most the data (i.e., a status-quo state); and States 3, 4, and 5 had extremely high concentrations of suspended solids (i.e., turbid states, with State 5 as the most turbid). The TDA mapped clear patterns of the ecosystem states across several riverine navigation reaches and seasons that furthered ecological understanding. State variables were identified as suspended solids, chlorophyll a, and total phosphorus, which are also state variables of shallow lakes worldwide. The TDA change detection function showed short-term state transitions based on seasonality and episodic events, and provided evidence of gradual, long-term changes due to water quality improvements over three decades. These results can inform decision making and guide actions for regulatory and restoration agencies by assessing the status and trends of this important river and provide quantitative targets for state variables. The TDA change detection function may serve as a new tool for predicting the vulnerability to undesirable state transitions in this system and other ecosystems with sufficient data. Coupling ecosystem state concepts and TDA tools can be transferred to any ecosystem with large data to help classify states and understand their vulnerability to state transitions.


Assuntos
Ecossistema , Rios , Clorofila A , Estações do Ano , Água , Monitoramento Ambiental/métodos
2.
Biochem Biophys Res Commun ; 505(2): 498-504, 2018 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-30268495

RESUMO

BACKGROUND: Insulin resistance (IR), a common co-morbidity of chronic obstructive pulmonary disease (COPD), aggravates airway inflammation in COPD patients, but its mechanism is unclear. Sfrp5, a novel anti-inflammatory adipocytokine, inhibits macrophage-mediated inflammation of adipose tissue and abrogates IR. However, few studies have been conducted on the regulatory role of Sfrp5 in lung inflammation. METHODS: In the present study, 30 SD rats were divided into two groups: the normal food (NF) group and the high-fat diet (HFD) group. Oral glucose tolerance test (OGTT) and insulin release test were performed to assess whether a successful IR rat model was established. The expression of Sfrp5 and key downstream moleculars of Wnt5a/JNKl signaling was detected. Lung tissue pathomorphology and macrophage activation were observed. In addition, we counted the number of inflammatory cells and measured inflammatory cytokines in bronchoalveolar lavage fluid (BALF). In vitro, rat lung macrophages were isolated and treated with Wnt5a, Sfrp5, and/or JNK inhibitor SP600125. JNK activity and inflammatory cytokines expression were examined. RESULTS: We found that in a rat model of IR, Sfrp5 expression of lung tissue was downregulated, while the Wnt5a/JNKl pathway was activated and the lung inflammatory response was enhanced. Meanwhile, Sfrp5 significantly suppressed Wnt5a/JNKl-induced macrophage activation. CONCLUSIONS: Collectively, IR reduces Sfrp5 expression of lung tissue and activates the Wnt5a/JNK1 pathway, promoting macrophage activation and contributing to the lung's inflammatory response. In contrast, Sfrp5 suppresses the inflammatory response by inhibiting the Wnt5a/JNKl pathway, which could be a target of treatment of COPD.


Assuntos
Adipocinas/metabolismo , Resistência à Insulina , Macrófagos/metabolismo , Pneumonia/metabolismo , Transdução de Sinais , Animais , Regulação para Baixo , Ativação de Macrófagos , Masculino , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Pneumonia/enzimologia , Pneumonia/patologia , Ratos Sprague-Dawley , Proteína Wnt-5a/metabolismo
3.
J Biol Chem ; 290(2): 1281-94, 2015 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-25471374

RESUMO

Nitrite signaling likely occurs through its reduction to nitric oxide (NO). Several reports support a role of erythrocytes and hemoglobin in nitrite reduction, but this remains controversial, and alternative reductive pathways have been proposed. In this work we determined whether the primary human erythrocytic nitrite reductase is hemoglobin as opposed to other erythrocytic proteins that have been suggested to be the major source of nitrite reduction. We employed several different assays to determine NO production from nitrite in erythrocytes including electron paramagnetic resonance detection of nitrosyl hemoglobin, chemiluminescent detection of NO, and inhibition of platelet activation and aggregation. Our studies show that NO is formed by red blood cells and inhibits platelet activation. Nitric oxide formation and signaling can be recapitulated with isolated deoxyhemoglobin. Importantly, there is limited NO production from erythrocytic xanthine oxidoreductase and nitric-oxide synthase. Under certain conditions we find dorzolamide (an inhibitor of carbonic anhydrase) results in diminished nitrite bioactivation, but the role of carbonic anhydrase is abrogated when physiological concentrations of CO2 are present. Importantly, carbon monoxide, which inhibits hemoglobin function as a nitrite reductase, abolishes nitrite bioactivation. Overall our data suggest that deoxyhemoglobin is the primary erythrocytic nitrite reductase operating under physiological conditions and accounts for nitrite-mediated NO signaling in blood.


Assuntos
Eritrócitos/metabolismo , Hemoglobinas/metabolismo , Óxido Nítrico/biossíntese , Oxirredução , Plaquetas/metabolismo , Anidrases Carbônicas/efeitos dos fármacos , Espectroscopia de Ressonância de Spin Eletrônica , Hemoglobinas/isolamento & purificação , Humanos , Óxido Nítrico/metabolismo , Nitrito Redutases/metabolismo , Nitritos/metabolismo , Transdução de Sinais , Sulfonamidas/administração & dosagem , Tiofenos/administração & dosagem
4.
BMC Geriatr ; 16(1): 164, 2016 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-27662829

RESUMO

BACKGROUND: Most patients with dementia or cognitive impairment receive care from family members, often untrained for this challenging role. Caregivers may not access publicly available caregiving information, and caregiver education programs are not widely implemented clinically. Prior large surveys yielded broad quantitative understanding of caregiver information needs, but do not illuminate the in-depth, rich, and nuanced caregiver perspectives that can be gleaned using qualitative methodology. METHODS: We aimed to understand perspectives about information sources, barriers and preferences, through semi-structured interviews with 27 caregivers. Content analysis identified important themes. RESULTS: We interviewed 19 women, 8 men; mean age 58.5 years; most adult children (15) or spouses (8) of the care recipient. Dementia symptoms often developed insidiously, with delayed disease acknowledgement and caregiver self-identification. While memory loss was common, behavioral symptoms were most troublesome, often initially unrecognized as disease indicators. Emerging themes: 1.) Barriers to seeking information often result from knowledge gaps, rather than reluctance to assume the caregiver role; 2.) Most caregivers currently receive insufficient information. Caregivers are open to many information sources, settings, and technologies, including referrals to other healthcare professionals, print material, and community and internet resources, but expect the primary care provider (PCP) to recommend, endorse, and guide them to specific sources. CONCLUSIONS: These findings replicated and expanded on results from previous quantitative surveys and, importantly, revealed a previously unrecognized essential factor: despite receiving insufficient information, caregivers place critical value on their relationship with care recipient PCPs to receive recommendations, guidance and endorsement to sources of caregiving information. Implications include: 1.) Greater public education is needed to help caregivers identify and describe diverse cognitive, functional and behavioral symptoms that lead to dementia, and recognize the benefits of early detection in accessing information regarding multi-modality management and care; 2.) Improved methods are needed for PCPs to detect and manage cognitive and behavioral changes, as well as mechanisms that facilitate the busy PCP, either directly or via referral, to provide caregiver information, education, support, and services. The critical relationship between caregivers and PCPs should not be circumvented but should be facilitated to provide more effective guidance regarding dementia caregiver needs.

5.
Am J Respir Cell Mol Biol ; 51(3): 363-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24669775

RESUMO

We recently proposed that mitotic asynchrony in repairing tissue may underlie chronic inflammation and fibrosis, where immune cell infiltration is secondary to proinflammatory cross-talk among asynchronously repairing adjacent tissues. Building on our previous finding that mitotic asynchrony is associated with proinflammatory/fibrotic cytokine secretion (e.g., transforming growth factor [TGF]-ß1), here we provide evidence supporting cause-and-effect. Under normal conditions, primary airway epithelial basal cell populations undergo mitosis synchronously and do not secrete proinflammatory or profibrotic cytokines. However, when pairs of nonasthmatic cultures were mitotically synchronized at 12 hours off-set and then combined, the mixed cell populations secreted elevated levels of TGF-ß1. This shows that mitotic asynchrony is not only associated with but is also causative of TGF-ß1 secretion. The secreted cytokines and other mediators from asthmatic cells were not the cause of asynchronous regeneration; synchronously mitotic nonasthmatic epithelia exposed to conditioned media from asthmatic cells did not show changes in mitotic synchrony. We also tested if resynchronization of regenerating asthmatic airway epithelia reduces TGF-ß1 secretion and found that pulse-dosed dexamethasone, simvastatin, and aphidicolin were all effective. We therefore propose a new model for chronic inflammatory and fibrotic conditions where an underlying factor is mitotic asynchrony.


Assuntos
Asma/metabolismo , Células Epiteliais/metabolismo , Mitose , Fator de Crescimento Transformador beta1/metabolismo , Afidicolina/administração & dosagem , Brônquios/metabolismo , Brônquios/patologia , Células Cultivadas , Meios de Cultivo Condicionados/química , Dexametasona/administração & dosagem , Epitélio/metabolismo , Fibrose , Humanos , Inflamação , Mucosa Respiratória/metabolismo , Sinvastatina/administração & dosagem , Fatores de Tempo
6.
J Osteopath Med ; 123(4): 187-194, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36724116

RESUMO

CONTEXT: Despite the increase of importance placed on research, both by residency program directors and the medical field at large, osteopathic medical students (OMS) have significantly fewer research experiences than United States (U.S.) allopathic medical students and non-U.S. international medical graduates. However, few studies have addressed this long-standing discrepancy, and none directly have focused on osteopathic medical students to assess their unique needs. The literature would benefit from identifying the barriers osteopathic medical students encounter when participating in research and understanding the currently available resources. OBJECTIVES: To assess the barriers that OMS face when seeking research opportunities, identify resources currently available to osteopathic medical students at their respective schools, and investigate factors that contribute to an osteopathic medical student's desire to pursue research opportunities. Additionally, to investigate osteopathic medical students' confidence in research methodology. METHODS: A survey was created by the investigators and administered to participants over a three-month period via a GoogleForm. Research participants were surveyed for demographic information, as well as their involvement in research projects in the past, mentor availability, institutional resources, motivation to participate in research, individual barriers to participation, and confidence in their ability to do independent research. Responses were de-identified and analyzed using Microsoft Excel functions to count data and calculate percentages, as well as Pearson's chi square analysis. RESULTS: After relevant exclusion, 668 responses were included. Of the students surveyed, 85.9% (574) indicated they currently and/or in the past were involved in research. More than half of the respondents that are not currently involved in research are interested in pursuing it (86.9%; 344). The primary barriers students reported facing include lack of time (57.8%; 386), feeling overwhelmed and unsure how to start (53.4%; 357), and lack of access to research (53%; 354). 34.7% (232) of students stated they either did not have resources from their school or were unsure whether these resources were available. The two most cited motivations to pursue research included boosting their residency application and/or interest in the area of study. Male gender and current research were associated with reported confidence in research ( [4, n=662]=10.6, p<0.05). CONCLUSIONS: Findings from this study provide a synopsis of the barriers to research opportunities among osteopathic medical students. Notably, ⅓ of OMSs reported an absence or unawareness of available research resources at their osteopathic medical schools.


Assuntos
Internato e Residência , Medicina Osteopática , Médicos Osteopáticos , Estudantes de Medicina , Humanos , Masculino , Estados Unidos , Medicina Osteopática/educação , Inquéritos e Questionários
7.
Cureus ; 15(7): e41565, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37554600

RESUMO

Obesity has long been linked to adverse health effects over time. As the prevalence of obesity continues to rise, it is important to anticipate and minimize the complications that obesity brings in the anesthesia setting during surgery. Anesthetic departments must recognize the innumerable risks when managing patients with obesity undergoing surgery, including anatomical and physiological changes as well as comorbidities such as diabetes, cardiovascular diseases, and malignancies. Therefore, the purpose of this review is to analyze the current literature and evaluate the current and recent advances in anesthetic care of obese patients undergoing surgery, to better understand the specific challenges this patient population faces. A greater understanding of the differences between anesthetic care for obese patients can help to improve patient care and the specificity of treatment. The examination of the literature will focus on differing patient outcomes and safety precautions in obese patients as compared to the general population. Specifically highlighting the differences in pre-operative, intra-operative, and post-operative care, with the aim to identify issues and present possible solutions.

8.
Clin Case Rep ; 11(11): e8097, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37953890

RESUMO

Key Clinical Message: Jacobs syndrome and congenital adrenal hyperplasia are separate entities but share common clinical features such as ambiguous genitalia. Further studies are needed to conclude the relationship between Jacobs syndrome and congenital adrenal hyperplasia. Abstract: A 5-month-old male infant was evaluated for ambiguous genitalia. Examination revealed cryptorchidism, inguinal hernia, long phallus, and Grade 3 scrotal hypospadias. Serum 17-OH progesterone was high and chromosomal analysis showed 47XYY/45XO. A diagnosis of Jacobs and CAH was made. The parents were counseled about the patient's condition. He was given hydrocortisone and referred to the pediatric surgeon for further management.

9.
bioRxiv ; 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36865095

RESUMO

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were unknown. By studying phages that encode the major phage nucleus protein chimallin, including previously sequenced yet uncharacterized phages, we discovered that chimallin-encoding phages share a set of 72 highly conserved genes encoded within seven distinct gene blocks. Of these, 21 core genes are unique to this group, and all but one of these unique genes encode proteins of unknown function. We propose that phages with this core genome comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryo-electron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication encoded in the core genome are conserved among diverse chimalliviruses, and reveal that non-core components can confer intriguing variations on this replication mechanism. For instance, unlike previously studied nucleus-forming phages, RAY doesn't degrade the host genome, and its PhuZ homolog appears to form a five-stranded filament with a lumen. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.

10.
Cell Rep ; 42(5): 112432, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37120812

RESUMO

We recently discovered that some bacteriophages establish a nucleus-like replication compartment (phage nucleus), but the core genes that define nucleus-based phage replication and their phylogenetic distribution were still to be determined. Here, we show that phages encoding the major phage nucleus protein chimallin share 72 conserved genes encoded within seven gene blocks. Of these, 21 core genes are unique to nucleus-forming phage, and all but one of these genes encode proteins of unknown function. We propose that these phages comprise a novel viral family we term Chimalliviridae. Fluorescence microscopy and cryoelectron tomography studies of Erwinia phage vB_EamM_RAY confirm that many of the key steps of nucleus-based replication are conserved among diverse chimalliviruses and reveal variations on this replication mechanism. This work expands our understanding of phage nucleus and PhuZ spindle diversity and function, providing a roadmap for identifying key mechanisms underlying nucleus-based phage replication.


Assuntos
Bacteriófagos , Erwinia , Bacteriófagos/genética , Bacteriófagos/metabolismo , Erwinia/genética , Erwinia/metabolismo , Filogenia , Genoma Viral , DNA Viral/genética , DNA Viral/metabolismo
11.
Polit Behav ; 44(3): 1533-1554, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35340916

RESUMO

Most Americans think that the country is politically divided and polarization will only get worse, not better. Such perceptions of polarization are widespread, but we do not know enough about their effects, especially those unrelated to political variables. This study examines the consequences of perceived polarization for levels of social trust in the United States. Trust in fellow citizens is the backbone of a well-functioning democracy, given its role in promoting social cohesion and facilitating collective action. Using nationally representative panel data, as well as an original survey experiment, I find that perceived polarization directly undermines Americans' trust in each other. A belief that members of society share common values fosters social trust, but perceptions of partisan divisions and polarization make people less trusting of their fellow citizens. Due to perceived polarization, people are less likely to believe that others can be trusted to do the right thing, which in turn decreases their willingness to cooperate for good causes. I discuss the implications of these findings for society's ability to work together toward common goals. Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-022-09787-1.

12.
Nat Hum Behav ; 6(7): 951-963, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35589827

RESUMO

The dominant narrative among scholars and political pundits characterizes American partisanship as overwhelmingly negative, portraying citizens as more repelled by the opposing party than attached to their own party. To assess the valence of partisan identity, we use various measures collected from several new and existing nationally representative surveys and behavioural outcomes obtained from two experiments. Our findings consistently depart from the negative partisanship narrative. For the majority of Americans, partisanship is either equally positive and negative or more positive than negative. Only partisan leaners stand out as negative partisans. We pair these observational findings with experimental data that differentiate between positive group behaviour and negative group behaviour in the partisan context. We find that the behavioural manifestations of party identity similarly include both positive and negative biases in balance, reinforcing our conclusion that descriptions of partisanship as primarily negative are exaggerated.


Assuntos
Política , Humanos , Inquéritos e Questionários , Estados Unidos
13.
J Biol Chem ; 285(17): 12862-72, 2010 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-20154085

RESUMO

Coronavirus membrane (M) protein can form virus-like particles (VLPs) when coexpressed with nucleocapsid (N) or envelope (E) proteins, suggesting a pivotal role for M in virion assembly. Here we demonstrate the self-assembly and release of severe acute respiratory syndrome coronavirus (SARS-CoV) M protein in medium in the form of membrane-enveloped vesicles with densities lower than those of VLPs formed by M plus N. Although efficient N-N interactions require the presence of RNA, we found that M-M interactions were RNA-independent. SARS-CoV M was observed in both the Golgi area and plasma membranes of a variety of cells. Blocking M glycosylation does not appear to significantly affect M plasma membrane labeling intensity, M-containing vesicle release, or VLP formation. Results from a genetic analysis indicate involvement of the third transmembrane domain of M in plasma membrane-targeting signal. Fusion proteins containing M amino-terminal 50 residues encompassing the first transmembrane domain were found to be sufficient for membrane binding, multimerization, and Golgi retention. Surprisingly, we found that fusion proteins lacking all three transmembrane domains were still capable of membrane binding, Golgi retention, and interacting with M. The data suggest that multiple SARS-CoV M regions are involved in M self-assembly and subcellular localization.


Assuntos
Membrana Celular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Multimerização Proteica/fisiologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , Proteínas da Matriz Viral/metabolismo , Animais , Membrana Celular/genética , Membrana Celular/virologia , Chlorocebus aethiops , Proteínas M de Coronavírus , Proteínas do Nucleocapsídeo de Coronavírus , Glicosilação , Complexo de Golgi/genética , Complexo de Golgi/metabolismo , Complexo de Golgi/virologia , Células HeLa , Humanos , Proteínas de Membrana/genética , Proteínas do Nucleocapsídeo/genética , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Células Vero , Proteínas da Matriz Viral/genética
14.
Vet Clin North Am Exot Anim Pract ; 24(3): 567-608, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34366011

RESUMO

Management of epizootics of exotic companion mammal herds relies on careful observance of animals, proper management and husbandry, adequate nutrition, and stress reduction. Many diseases occur because of the stress of weaning so anticipating this and maximizing sanitation and ventilation, minimizing overcrowding and concurrent disease, and providing enough fiber for herbivores is prudent. Antimicrobial therapy must be carefully considered in the route of administration and the likely risk of enterotoxemia development. Separation of affected animals, rapid diagnostic testing, and implementation of treatment and supportive care minimizes losses during epizootics. Knowledge of potential zoonotic pathogens is important for veterinarians and staff.


Assuntos
Criação de Animais Domésticos/métodos , Animais Exóticos , Surtos de Doenças/veterinária , Médicos Veterinários , Bem-Estar do Animal , Animais , Surtos de Doenças/prevenção & controle , Humanos , Mamíferos , Animais de Estimação
15.
Pediatr Neonatol ; 62(1): 3-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33349597

RESUMO

A literature review was conducted to determine norms for practice in neonatal intensive care units (NICU) around the world, given the harmful risks associated with radiation exposure at a very young age; risk of radiation-induced harm later in life increases with every X-ray image taken, more so for younger premature babies. Empirical studies including a measurement of radiation dose in a NICU, published after the year 2000 in a peer-reviewed journal, were collected. Measured doses to patients or X-ray phantoms, number of X-rays per stay and conclusions with recommendations made in response to these values were compared for 25 studies from around the world. The number of X-rays a patient underwent during a NICU stay ranged from 0 to 159. Younger, lower birth weight patients consistently had the greatest number of X-rays per stay. Recommended action based on measured dose ranged from extensive (to minimize risk to neonates) to minimal (to reduce risk) to none (because imaging benefits outweigh patient risk), with no consistent pattern linking recommended action with dose quantity. This demonstrates a broad range of interpretations of the As Low As Reasonably Achievable (ALARA) concept. These findings indicate a disparity in the response to neonatal X-ray dose concerns on a global scale, posing a public health risk to this particular neonatal population. More up-to-date imaging protocols and dose limits specifically for the NICU environment with standardized dose monitoring would help minimize this risk to achieve the public health goals of prevention and harm reduction.


Assuntos
Doenças do Prematuro/diagnóstico por imagem , Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Exposição à Radiação/estatística & dados numéricos , Saúde Global , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/etiologia , Terapia Intensiva Neonatal/métodos , Terapia Intensiva Neonatal/normas , Segurança do Paciente , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Exposição à Radiação/normas , Radiografia
16.
J Trauma Acute Care Surg ; 90(2): 203-214, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33060537

RESUMO

BACKGROUND: Hemorrhagic shock (HS) and trauma induce endothelial barrier compromise, inflammation, and aberrant clotting. We have shown that fresh human platelets (Plts) and Plt extracellular vesicles mitigate vascular leak in murine models of injury. Here, we investigate the potential of freeze-dried platelets (FDPlts) to attenuate pulmonary vascular permeability, decrease inflammation, and promote clotting in a murine model of HS. METHODS: Human FDPlts were characterized using in vitro assays of Plt marker expression, aggregation, coagulation, and endothelial cell permeability. An intravital model of vascular injury in the mouse cremaster muscle was used to assess the ability of FDPlts to incorporate into clots. Mouse groups subjected to controlled hemorrhage for 90 minutes were (1) lactated Ringer solution (LR), (2) FDPlts, (3) fresh human Plts, (4) murine whole blood (WB), and (5) shams (only instrumented). Hemorrhagic shock mouse endpoints included coagulation, pulmonary vascular permeability, and lung injury. RESULTS: Freeze-dried Plts expressed Plt-specific markers and retained functionality similar to fresh Plts. In in vitro assays of Plt aggregation, differences were noted. In vivo, FDPlts and Plts were found to incorporate into clots in postcapillary venules in the mouse cremaster muscle. Hemorrhagic shock mice resuscitated with LR displayed increased pulmonary vascular permeability compared with sham (sham, 686.6 ± 359.7; shock-LR, 2,637 ± 954.7; p = 0.001), and treatment with FDPlts or WB attenuated permeability compared with shock: shock-FDPlts, 1,328 ± 462.6 (p = 0.05), and shock-WB, 1,024 ± 370.5 (p = 0.0108). However, human Plts (Days 1-3) did not attenuate vascular leak in HS mice compared with shock-LR (shock-Plts, 3,601 ± 1,581; p = 0.33). CONCLUSION: FDPlts contribute to clot formation similar to fresh human Plts. FDPlts also attenuated vascular permeability in vitro and in vivo. Mouse WB resuscitation but not fresh human Plts attenuated vascular permeability after HS. These data suggest that the effect of FDPlts may be a suitable alternative to fresh Plts in modulating hemostasis and the endotheliopathy associated with injury.


Assuntos
Plaquetas/fisiologia , Permeabilidade Capilar/fisiologia , Modelos Animais de Doenças , Células Endoteliais/fisiologia , Liofilização , Hemostasia/fisiologia , Pulmão/irrigação sanguínea , Transfusão de Plaquetas , Choque Hemorrágico/terapia , Trombose/sangue , Animais , Humanos , Camundongos , Choque Hemorrágico/sangue
17.
Med Phys ; 48(7): e671-e696, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33930183

RESUMO

BACKGROUND: Physicians use fixed C-arm fluoroscopy equipment with many interventional radiological and cardiological procedures. The associated effective dose to a patient is generally considered low risk, as the benefit-risk ratio is almost certainly highly favorable. However, X-ray-induced skin injuries may occur due to high absorbed patient skin doses from complex fluoroscopically guided interventions (FGI). Suitable action levels for patient-specific follow-up could improve the clinical practice. There is a need for a refined metric regarding follow-up of X-ray-induced patient injuries and the knowledge gap regarding skin dose-related patient information from fluoroscopy devices must be filled. The most useful metric to indicate a risk of erythema, epilation or greater skin injury that also includes actionable information is the peak skin dose, that is, the largest dose to a region of skin. MATERIALS AND METHODS: The report is based on a comprehensive review of best practices and methods to estimate peak skin dose found in the scientific literature and situates the importance of the Digital Imaging and Communication in Medicine (DICOM) standard detailing pertinent information contained in the Radiation Dose Structured Report (RDSR) and DICOM image headers for FGI devices. Furthermore, the expertise of the task group members and consultants have been used to bridge and discuss different methods and associated available DICOM information for peak skin dose estimation. RESULTS: The report contributes an extensive summary and discussion of the current state of the art in estimating peak skin dose with FGI procedures with regard to methodology and DICOM information. Improvements in skin dose estimation efforts with more refined DICOM information are suggested and discussed. CONCLUSIONS: The endeavor of skin dose estimation is greatly aided by the continuing efforts of the scientific medical physics community, the numerous technology enhancements, the dose-controlling features provided by the FGI device manufacturers, and the emergence and greater availability of the DICOM RDSR. Refined and new dosimetry systems continue to evolve and form the infrastructure for further improvements in accuracy. Dose-related content and information systems capable of handling big data are emerging for patient dose monitoring and quality assurance tools for large-scale multihospital enterprises.


Assuntos
Radiometria , Pele , Fluoroscopia , Humanos , Doses de Radiação , Radiografia Intervencionista , Radiologia Intervencionista
18.
Front Psychol ; 11: 552828, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33041919

RESUMO

This study examines the association between calling and crafting behavior by proposing a moderated mediation model. Drawing from the job crafting perspective and self-determination theory (SDT), career commitment is identified as the mediator, and occupational self-efficacy and job autonomy are identified as the moderators in the model, respectively. The authors tested the proposed relationships with an SPSS macro that utilizes a sample of 338 employees in a three-wave procedure. Results support all the hypotheses. The findings reveal calling to be significantly associated with employees' job crafting behavior. Such a process begins with one's career commitment and is strengthened by the level of occupational self-efficacy in the first stage as well as the level of job autonomy in the second stage, thus yielding a pattern of moderated mediation. These findings answer recent calls for an integrative examination of calling in the workplace by demonstrating that career commitment along with occupational self-efficacy and job autonomy represent key mechanisms in transferring one's calling into job crafting behavior. As such, this study complements existing literature on the theoretical and practical implications of calling.

20.
J Med Imaging (Bellingham) ; 4(2): 025501, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28491907

RESUMO

This study aimed to determine whether a reduction in radiation dose was found for percutaneous coronary interventional (PCI) patients using a cardiac interventional x-ray system with state-of-the-art image enhancement and x-ray optimization, compared to the current generation x-ray system, and to determine the corresponding impact on clinical image quality. Patient procedure dose area product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray system were compared using a Wilcoxon test on median values. Significant reductions in patient dose ([Formula: see text]) were found for the new system with no significant change in fluoroscopy duration ([Formula: see text]); procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and "cine" acquisition DAP by 76%. The image quality of 15 patient angiograms from each x-ray system (30 total) was scored by 75 clinical professionals on a continuous scale for the ability to determine the presence and severity of stenotic lesions; image quality scores were analyzed using a two-sample [Formula: see text]-test. Image quality was reduced by 9% ([Formula: see text]) for the new x-ray system. This demonstrates a substantial reduction in patient dose, from acquisition more than fluoroscopy imaging, with slightly reduced image quality, for the new x-ray system compared to the current generation system.

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