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Fc-mediated antibody effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), can contribute to the containment HIV-1 replication but whether such activities are sufficient for protection is unclear. We previously identified an antibody to the variable 2 (V2) apex of the HIV-1 Env trimer (PGT145) that potently directs the lysis of SIV-infected cells by NK cells but poorly neutralizes SIV infectivity. To determine if ADCC is sufficient for protection, separate groups of six rhesus macaques were treated with PGT145 or a control antibody (DEN3) by intravenous infusion followed five days later by intrarectal challenge with SIVmac239. Despite high concentrations of PGT145 and potent ADCC activity in plasma on the day of challenge, all animals became infected and viral loads did not differ between the PGT145- and DEN3-treated animals. To determine if PGT145 can protect against a neutralization-sensitive virus, two additional groups of six macaques were treated with PGT145 and DEN3 and challenged with an SIVmac239 variant with a single amino acid change in Env (K180S) that increases PGT145 binding and renders the virus susceptible to neutralization by this antibody. Although there was no difference in virus acquisition, peak and chronic phase viral loads were significantly lower and time to peak viremia was significantly delayed in the PGT145-treated animals compared to the DEN3-treated control animals. Env changes were also selected in the PGT145-treated animals that confer resistance to both neutralization and ADCC. These results show that ADCC is not sufficient for protection by this V2-specific antibody. However, protection may be achieved by increasing the affinity of antibody binding to Env above the threshold required for neutralization.
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Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Macaca mulatta , Anticorpos Antivirais , Citotoxicidade Celular Dependente de AnticorposRESUMO
While both dysphagia and poor health-related quality of life frequently occur in United States (US) Veterans, swallowing-related quality of life in this population has not been systematically examined. This retrospective clinical observation study aimed to determine the independent predictors of swallowing-related quality of life for a sample of US Veterans. We examined the following variables in a multivariate analysis to determine the predictors of Swallowing Quality of Life Questionnaire scores: demographic information, Modified Barium Swallow Impairment Profile (MBSImP) scores, Penetration-Aspiration Scale scores, anterior lingual pressures, and Functional Oral Intake Scale scores. MBSImP oral phase score was the only variable that reached statistical significance (p ≤ 0.01), demonstrating that a more severe physiologic impairment in the oral phase of swallowing was independently predictive of worse swallowing-related quality of life. These findings highlight the need for clinicians to consider how impairments in swallowing physiology may impact the quality of life more broadly for patients with dysphagia.
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Transtornos de Deglutição , Veteranos , Humanos , Deglutição/fisiologia , Qualidade de Vida , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. METHODS: A retrospective study of adult patients with proven blastomycosis from 2004-2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid-organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). RESULTS: A total of 106 cases met the inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (P = .03), more severe infection (P = .007), respiratory failure (P = .010), and increased mortality (P = .02). Receipt of SOT primarily accounted for increased severity, respiratory failure, and mortality in immunosuppressed patients. SOT recipients had an 18-fold higher annual incidence of blastomycosis than the general population. The rate of disseminated blastomycosis was similar among NIC, SOT, and non-SOT IC. Relapse rates were low (5.3-7.7%). CONCLUSIONS: Immunosuppression had implications regarding the acuity, severity, and respiratory failure. The rate of dissemination was similar across the immunologic spectrum, which is in sharp contrast to other endemic fungi. This suggests that pathogen-related factors have a greater influence on dissemination for blastomycosis than immune defense.
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Blastomicose , Adulto , Antifúngicos/uso terapêutico , Blastomyces , Blastomicose/tratamento farmacológico , Blastomicose/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Estudos RetrospectivosRESUMO
The presence of thin myelin sheaths in the adult CNS is recognized as a marker of remyelination, although the reason there is not a recovery from demyelination to normal myelin sheath thickness remains unknown. Remyelination is the default pathway after myelin loss in all mammalian species, in both naturally occurring and experimental disease. However, there remains uncertainty about whether these thin sheaths thicken with time and whether they remain viable for extended periods. We provide two lines of evidence here that thin myelin sheaths may persist indefinitely in long-lived animal models. In the first, we have followed thin myelin sheaths in a model of delayed myelination during a period of 13 years that we propose results in the same myelin sheath deficiencies as seen in remyelination; that is, thin myelin sheaths and short internodes. We show that the myelin sheaths remain thin and stable on many axons throughout this period with no detrimental effects on axons. In a second model system, in which there is widespread demyelination of the spinal cord and optic nerves, we also show that thinly remyelinated axons with short internodes persist for over the course of 2 y. These studies confirm the persistence and longevity of thin myelin sheaths and the importance of remyelination to the long-term health and function of the CNS.
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Axônios/fisiologia , Bainha de Mielina/fisiologia , Remielinização/fisiologia , Medula Espinal/fisiologia , Animais , Doenças Desmielinizantes/fisiopatologia , Cães , Feminino , Masculino , Modelos Animais , Regeneração Nervosa/fisiologia , Fenômenos Fisiológicos do Sistema Nervoso , Nervo Óptico/fisiologiaRESUMO
The mouse is a critical model in diabetes research, but most research in mice has been limited to a small number of mouse strains and limited genetic variation. Using the eight founder strains and both sexes of the Collaborative Cross (C57BL/6J (B6), A/J, 129S1/SvImJ (129), NOD/ShiLtJ (NOD), NZO/HILtJ (NZO), PWK/PhJ (PWK), WSB/EiJ (WSB), and CAST/EiJ (CAST)), we investigated the genetic dependence of diabetes-related metabolic phenotypes and insulin secretion. We found that strain background is associated with an extraordinary range in body weight, plasma glucose, insulin, triglycerides, and insulin secretion. Our whole-islet proteomic analysis of the eight mouse strains demonstrates that genetic background exerts a strong influence on the islet proteome that can be linked to the differences in diabetes-related metabolic phenotypes and insulin secretion. We computed protein modules consisting of highly correlated proteins that enrich for biological pathways and provide a searchable database of the islet protein expression profiles. To validate the data resource, we identified tyrosine hydroxylase (Th), a key enzyme in catecholamine synthesis, as a protein that is highly expressed in ß-cells of PWK and CAST islets. We show that CAST islets synthesize elevated levels of dopamine, which suppresses insulin secretion. Prior studies, using only the B6 strain, concluded that adult mouse islets do not synthesize l-3,4-dihydroxyphenylalanine (l-DOPA), the product of Th and precursor of dopamine. Thus, the choice of the CAST strain, guided by our islet proteomic survey, was crucial for these discoveries. In summary, we provide a valuable data resource to the research community, and show that proteomic analysis identified a strain-specific pathway by which dopamine synthesized in ß-cells inhibits insulin secretion.
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Diabetes Mellitus Tipo 2/metabolismo , Dopamina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Proteoma/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Dopamina/genética , Feminino , Variação Genética , Glucagon/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Fenótipo , Proteoma/genética , ProteômicaRESUMO
BACKGROUND: Mood disturbance, pain, and fatigue are prevalent and distressing concerns for patients with hematologic cancer recovering from hematopoietic stem cell transplantation (HSCT). The way in which individuals approach difficult thoughts and emotions may affect symptoms and functioning. Specifically, mindfulness has been associated with more optimal psychological and physical functioning, whereas experiential avoidance has been associated with poorer outcomes. PURPOSE: The primary objective was to determine whether mindfulness and experiential avoidance measured prior to HSCT were associated with recovery of psychological and physical functioning following HSCT. We also evaluated dimensions of mindfulness to determine which were most robustly associated with outcomes. METHODS: Participants completed measures of mindfulness and experiential avoidance prior to HSCT. Depression and anxiety symptoms and pain and fatigue interference with daily activities were assessed prior to HSCT and 1, 3, and 6 months post-HSCT. RESULTS: Participants who reported better ability to describe their internal experiences and who were better able to act with awareness experienced less depression, anxiety, and fatigue interference following HSCT. Participants who were nonjudgmental and nonreactive toward thoughts and emotions experienced less depression and anxiety following HSCT, but these traits were not associated with pain or fatigue interference. Being a good observer of internal experiences was not associated with outcomes, nor was experiential avoidance. CONCLUSIONS: Results suggest that most facets of mindfulness may optimize psychological functioning following HSCT, and the ability to describe one's internal experience and to focus on the present moment may have a beneficial influence on physical functioning.
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Ansiedade/psicologia , Aprendizagem da Esquiva , Depressão/psicologia , Fadiga/psicologia , Transplante de Células-Tronco Hematopoéticas/psicologia , Atenção Plena , Dor Pós-Operatória/psicologia , Adulto , Idoso , Neoplasias Hematológicas/terapia , Humanos , Pessoa de Meia-IdadeRESUMO
PURPOSE: To compare patient outcomes following magnetic resonance angiography (MRA) versus computed tomographic angiography (CTA) ordered for suspected pulmonary embolism (PE). METHODS: In this IRB-approved, single-center, retrospective, case-control study, we reviewed the medical records of all patients evaluated for PE with MRA during a 5-year period along with age- and sex-matched controls evaluated with CTA. Only the first instance of PE evaluation during the study period was included. After application of our exclusion criteria to both study arms, the analysis included 1173 subjects. The primary endpoint was major adverse PE-related event (MAPE), which we defined as major bleeding, venous thromboembolism, or death during the 6 months following the index imaging test (MRA or CTA), obtained through medical record review. Logistic regression, chi-square test for independence, and Fisher's exact test were used with a p < 0.05 threshold. RESULTS: The overall 6-month MAPE rate following MRA (5.4%) was lower than following CTA (13.6%, p < 0.01). Amongst outpatients, the MAPE rate was lower for MRA (3.7%) than for CTA (8.0%, p = 0.01). Accounting for age, sex, referral source, BMI, and Wells' score, patients were less likely to suffer MAPE than those who underwent CTA, with an odds ratio of 0.44 [0.24, 0.80]. Technical success rate did not differ significantly between MRA (92.6%) and CTA (90.5%) groups (p = 0.41). CONCLUSION: Within the inherent limitations of a retrospective case-controlled analysis, we observed that the rate of MAPE was lower (more favorable) for patients following pulmonary MRA for the primary evaluation of suspected PE than following CTA.
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Angiografia por Tomografia Computadorizada/métodos , Angiografia por Ressonância Magnética/métodos , Embolia Pulmonar/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.
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Blastomyces/metabolismo , Fatores de Transcrição GATA/metabolismo , Homeostase/fisiologia , Ferro/metabolismo , Metabolismo dos Lipídeos/fisiologia , Fungos/metabolismo , Regulação Fúngica da Expressão Gênica/genética , Genes Fúngicos/genética , Metabolismo dos Lipídeos/genéticaRESUMO
This investigation explores memory performance using the California Verbal Learning Test in relation to morphometric and connectivity measures of the memory network in severe traumatic brain injury. Twenty-two adolescents with severe traumatic brain injury were recruited for multimodal MRI scanning 1-2 years post-injury at 13 participating sites. Analyses included hippocampal volume derived from anatomical T1-weighted imaging, fornix white matter microstructure from diffusion tensor imaging, and hippocampal resting-state functional magnetic resonance imaging connectivity as well as diffusion-based structural connectivity. A typically developing control cohort of forty-nine age-matched children also underwent scanning and neurocognitive assessment. Results showed hippocampus volume was decreased in traumatic brain injury with respect to controls. Further, hippocampal volume loss was associated with worse performance on memory and learning in traumatic brain injury subjects. Similarly, hippocampal fornix fractional anisotropy was reduced in traumatic brain injury with respect to controls, while decreased fractional anisotropy in the hippocampal fornix also was associated with worse performance on memory and learning in traumatic brain injury subjects. Additionally, reduced structural connectivity of left hippocampus to thalamus and calcarine sulcus was associated with memory and learning in traumatic brain injury subjects. Functional connectivity in the left hippocampal network was also associated with memory and learning in traumatic brain injury subjects. These regional findings from a multi-modal neuroimaging approach should not only be useful for gaining valuable insight into traumatic brain injury induced memory and learning disfunction, but may also be informative for monitoring injury progression, recovery, and for developing rehabilitation as well as therapy strategies.
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Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Adolescente , Humanos , Criança , Imageamento por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos , Lesões Encefálicas Traumáticas/patologia , Hipocampo/patologia , NeuroimagemRESUMO
Importance: Traumatic brain injury (TBI) is a leading cause of death and disability in children, and predicting functional outcome after TBI is challenging. Magnetic resonance imaging (MRI) is frequently conducted after severe TBI; however, the predictive value of MRI remains uncertain. Objectives: To identify early MRI measures that predict long-term outcome after severe TBI in children and to assess the added predictive value of MRI measures over well-validated clinical predictors. Design, Setting, and Participants: This preplanned prognostic study used data from the Approaches and Decisions in Acute Pediatric TBI (ADAPT) prospective observational comparative effectiveness study. The ADAPT study enrolled 1000 consecutive children (aged <18 years) with severe TBI between February 1, 2014, and September 30, 2017. Participants had a Glasgow Coma Scale (GCS) score of 8 or less and received intracranial pressure monitoring. Magnetic resonance imaging scans performed as part of standard clinical care within 30 days of injury were collected at 24 participating sites in the US, UK, and Australia. Summary imaging measures were correlated with the Glasgow Outcome Scale-Extended for Pediatrics (GOSE-Peds), and the predictive value of MRI measures was compared with the International Mission for Prognosis and Analysis of Clinical Trials in TBI (IMPACT) core clinical predictors. Data collection, image analysis, and data analyses were completed in July 2023. Exposures: Pediatric severe TBI with an MRI scan performed as part of clinical care. Main Outcomes and Measures: All measures were selected a priori. Magnetic resonance imaging measures included contusion, ischemia, diffuse axonal injury, intracerebral hemorrhage, and brainstem injury. Clinical predictors included the IMPACT core measures (GCS motor score and pupil reactivity). All models adjusted for age and sex. Outcome measures included the GOSE-Peds score obtained at 3, 6, and 12 months after injury. Results: This study included 233 children with severe TBI who were enrolled at participating sites and had an MRI scan and preselected clinical predictors available. Their median age was 6.9 (IQR, 3.0-13.3) years, and more than half of participants (134 [57.5%]) were male. In a multivariable model including MRI measures and IMPACT core clinical variables, contusion volume (odds ratio [OR], 1.13; 95% CI, 1.02-1.26), brain ischemia (OR, 2.11; 95% CI, 1.58-2.81), brainstem lesions (OR, 5.40; 95% CI, 1.90-15.35), and pupil reactivity were each independently associated with GOSE-Peds score. Adding MRI measures to the IMPACT clinical predictors significantly improved model fit and discrimination between favorable and unfavorable outcomes compared with IMPACT predictors alone (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.72-0.85 vs 0.67; 95% CI, 0.61-0.76 for GOSE-Peds score >3 at 6 months after injury). Conclusions and Relevance: In this prognostic study of children with severe TBI, the addition of MRI measures significantly improved outcome prediction over well-established and validated clinical predictors. Magnetic resonance imaging should be considered in children with severe TBI to inform prognosis and may also promote stratification of patients in future clinical trials.
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Lesões Encefálicas Traumáticas , Imageamento por Ressonância Magnética , Humanos , Criança , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Adolescente , Estudos Prospectivos , Prognóstico , Pré-Escolar , Valor Preditivo dos Testes , Escala de Coma de Glasgow , Austrália , Escala de Resultado de Glasgow , Lactente , Estados Unidos , Reino UnidoRESUMO
BACKGROUND: Medical students represent the next generation of physician educators, yet may not be prepared to meet future teaching responsibilities. METHODS: An electronic survey was sent to medical students at a US allopathic institution to assess their experience, interest, and confidence in teaching. RESULTS: Most students indicated interest in teaching medical students (n = 91, 62%) or residents (n = 88, 60%) postresidency. Less than half expressed confidence in teaching clinical interviewing/physical exam skills (n = 71, 49%), lecture/didactic (n = 62, 42%), and procedural techniques (n = 41, 28%). DISCUSSION: Many medical students identified having only nascent medical teaching skills and expressed interest in elective opportunities. Formal teaching programs are necessary to cultivate medical students as effective physician educators.
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Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Humanos , Currículo , Inquéritos e Questionários , EnsinoRESUMO
Objective The aim of this study was to measure the effect of obesity and systemic opioids on respiratory events within the first 24 hours following cesarean. Methods Opioid-naive women undergoing cesarean between January 2016 and December 2017 were included in this retrospective cohort study. The primary outcome was the proportion of women experiencing at least one composite respiratory outcome (oxygen saturation less than 95% lasting 30+ seconds or need for respiratory support) within 24 hours of cesarean. The impact of obesity and total systemic opioid dose in 24 hours (measured in morphine milligram equivalents [MMEs]) on the composite respiratory compromise outcome were evaluated. Results Of 2,230 cesarean births, 790 women had at least one composite respiratory event. Predictors of the composite respiratory outcome included body mass index (BMI) as a continuous variable (odds ratio = 1.063 for every one unit increase in BMI [95% confidence interval (CI): 1.021-1.108], p = 0.003), and MME (odds ratio = 1.005 [95% CI: 1.002-1.008], p = 0.003), adjusting for magnesium sulfate use. The interaction between obesity and opioid dose demonstrated an odds ratio of 1.000 (95% CI: 0.999-1.000, p = 0.030). Conclusion The proportion of women experiencing respiratory events following cesarean birth increases with the degree of obesity and opioid dose. Key Points Respiratory events increase with obesity.Respiratory events increase with systemic opioid use.Odds ratio of respiratory events is 1.063/unit BMI increase.
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BACKGROUND: Optimal post-cesarean pain control is important. With the rising opioid epidemic it is imperative to maximize non-opioid based primary approaches to post-cesarean pain control. In 2018, we implemented a standardized post-cesarean analgesia regimen. OBJECTIVE: To determine if implementation of a standardized postoperative analgesic regimen decreases opioid use following cesarean birth. STUDY DESIGN: A standardized postoperative analgesia protocol was implemented in June 2018, which included scheduled oral acetaminophen (975 mg every 6 h) and nonsteroidal anti-inflammatory drugs (NSAIDs) (ketorolac 15 mg IV every 6 h for 5 doses followed by ibuprofen 600 mg oral every 6 h) with opioids available for breakthrough pain. There was no prior standardized protocol. A before-and-after study design was used to compare oral morphine milligram equivalents (MME) for nine months prior to and nine months after this protocol was implemented, excluding the two month period of protocol rollout. Women with opioid use disorder or postoperative intubation were excluded. The primary outcome was the cumulative MME used in the first 72 h postoperatively. Total dose at 12, 24, and 48 h were also compared. RESULTS: Of 2340 women who underwent cesarean birth during the study period (1 July 2017 - 30 April 2019), 2001 women met inclusion criteria (914 before 10 April 2018 (pre-protocol) and 1087 after 17 June 2018 (post-protocol)). Baseline characteristics of the two groups were similar, including gestational age at delivery, maternal body mass index (BMI), planned versus unplanned cesarean birth, and type of intraoperative anesthesia used. The cumulative opioid dose in the first 72 h postoperatively was 216.3 ± 84.3 MME prior to implementation compared to 171.5 ± 91.5 MME following implementation (p < .001). The average cumulative MME use was higher in the pre-protocol period compared to post-protocol at all time periods: 12 h (57.3 ± 23.8 vs 48.6 ± 26.2 MME, p < .001), 24 h (98.1 ± 34.1 vs 82.1 ± 38.8 MME, p < .001), and 48 h (165.8 ± 58.3 vs 134.9 ± 66.2 MME, p < .001). The average pain scores were lower in the pre-protocol group (3 vs 3.3, p < .001). CONCLUSION: Scheduled administration of acetaminophen and NSAIDs following cesarean birth significantly decreased the cumulative dose of opioids used in the first 72 h postoperatively.
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Analgesia , Transtornos Relacionados ao Uso de Opioides , Gravidez , Feminino , Humanos , Acetaminofen , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Dor Pós-Operatória/epidemiologia , Medição da Dor/métodos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Analgésicos Opioides , Período Pós-Parto , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos RetrospectivosRESUMO
Purpose: To measure native T1 values, a marker of diffuse fibrosis, by using cardiac MRI (CMR) in young adults born prematurely. Materials and Methods: This secondary analysis of a prospective cohort study included young adults born moderately to extremely preterm and age-matched, term-born participants. CMR was performed with a 3.0-T imager that included cine imaging for the quantification of left ventricular (LV) and right ventricular (RV) volumes and function and native saturation recovery T1 mapping for the assessment of diffuse myocardial fibrosis. Values between preterm and term were compared by using the Student t test. Associations between T1 values and other variables were analyzed by using linear regression and multivariate regression. Results: Of the 50 young-adult participants, 32 were born preterm (mean age, 25.8 years ± 4.2 [SD]; 23 women) and 18 were born at term (mean age, 26.2 years ± 5.4; 10 women). Native T1 values were significantly higher in participants born preterm than in participants born at term (1477 msec ± 77 vs 1423 msec ± 71, respectively; unadjusted P = .0019). Native T1 values appeared to be positively associated with indexed LV end-diastolic and end-systolic volumes (ß = 2.1, standard error = 0.7 and ß = 3.8, standard error = 1.2, respectively), the RV end-diastolic volume index (ß = 1.3, standard error = 0.6), and the LV mass index (ß = 2.5, standard error = 0.9). Higher T1 values may be associated with reduced cardiac systolic strain measures and diastolic strain measures. Five-minute Apgar scores were inversely associated with native T1 values. Conclusion: Young adults born moderately to extremely preterm exhibited significantly higher native T1 values than age-matched, term-born young adults.Keywords: MRI, Cardiac, Heart, Left Ventricle, CardiomyopathiesClinical trial registration no. NCT03245723Published under a CC BY 4.0 license Supplemental material is available for this article.
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Young children with severe traumatic brain injury (TBI) have frequently been excluded from studies due to age and/or mechanism of injury. Magnetic resonance imaging (MRI) is now frequently being utilized to detect parenchymal injuries and early cerebral edema. We sought to assess MRI findings in infants with severe TBI, and to determine the association between specific MRI findings and mechanisms of injury, including abusive head trauma (AHT). MRI scans performed within the first 30 days after injury were collected and coded according to NIH/NINDS Common Data Elements (CDEs) for Neuroimaging in subjects age < 2 years old with severe TBI enrolled in the Approaches and Decisions in Acute Pediatric Traumatic Brain Injury Trial. Demographics and injury characteristics were analyzed. A total of 81 children were included from ADAPT sites with MRI scans. Median age was 0.77 years and 57% were male. Most common MRI finding was ischemia, present in 57/81 subjects (70%), in a median of 7 brain regions per subject. Contusion 46/81 (57%) and diffuse axonal injury (DAI) 36/81 (44.4%) subjects followed. Children were dichotomized based on likelihood of AHT with 43/81 subjects classified as AHT. Ischemia was found to be significantly associated with AHT (p = 0.001) and "inflicted" injury mechanism (p = 0.0003). In conclusion, the most common intracerebral injury seen on MRI of infants with severe TBI was ischemia, followed by contusion and DAI. Ischemia was associated with AHT, and ischemia affecting > 4 brain regions was predictive of AHT.
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Metabolic syndrome increases risk of complicating co-morbidities. Current clinical indicators reflect established metabolic impairment, preventing earlier intervention strategies. Here we show that circulating sphingolipids are altered in the very early stages of insulin resistance development. The study involved 16 paired overweight but healthy monkeys, one-half of which spontaneously developed metabolic syndrome over the course of 2 years. Importantly, animals did not differ in adiposity and were euglycemic throughout the study period. Using mass spectrometry, circulating sphingolipids, including ceramides and sphingomyelins, were detected and quantified for healthy and impaired animals at both time points. At time of diagnosis, several ceramides were significantly different between healthy and impaired animals. Correlation analysis revealed differences in the interactions among ceramides in impaired animals at diagnosis and pre-diagnosis when animals were clinically indistinguishable from controls. Furthermore, correlations between ceramides and early-stage markers of insulin resistance, diacylglycerols and non-esterified fatty acids, were distinct for healthy and impaired states. Regression analysis identifies coordinated changes in lipid handling across lipid classes as animals progress from healthy to insulin resistant. Correlations between ceramides and the adipose-derived adipokine adiponectin were apparent in healthy animals but not in the metabolically impaired animals, even in advance of loss in insulin sensitivity. These data suggest that circulating ceramides are clinically relevant in identifying disease risk independent of differences in adiposity, and may be important in devising preventative strategies.
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Resistência à Insulina , Síndrome Metabólica , Animais , Ceramidas , Macaca mulatta , Síndrome Metabólica/etiologia , Obesidade/metabolismo , EsfingolipídeosRESUMO
BACKGROUND: Allogeneic hematopoietic cell transplantation (HCT) is a widely used treatment for hematologic cancers, with survival rates ranging from 25% to 78%. Known risk factors for chronic graft-versus-host disease (cGVHD), a serious and common long-term complication, disease relapse, and mortality following HCT have been identified, but much of the variability in HCT outcomes is unexplained. Biobehavioral symptoms including depression, sleep disruption, and fatigue are some of the most prevalent and distressing for patients; yet research on biobehavioral risk factors for HCT outcomes is limited. This study evaluated patient-reported depression, sleep disruption, and fatigue as risk factors for cGVHD, disease relapse, and mortality. METHODS: Adults receiving allogeneic HCT for a hematologic malignancy (N = 241) completed self-report measures of depression symptoms, sleep quality, and fatigue (severity, interference) pre-HCT and 100 days post-HCT. Clinical outcomes were monitored for up to 6 years. RESULTS: Cox proportional hazard models (2-tailed) adjusting for patient demographic and medical characteristics revealed that high pre-HCT sleep disruption (Pittsburgh Sleep Quality Index >9; hazard ratio [HR] = 2.74, 95% confidence interval [CI] = 1.27 to 5.92) and greater post-HCT fatigue interference (HR = 1.32, 95% CI = 1.05 to 1.66) uniquely predicted increased risk of mortality. Moderate pre-HCT sleep disruption (Pittsburgh Sleep Quality Index 6-9) predicted increased risk of relapse (HR = 1.99, 95% CI = 1.02 to 3.87). Biobehavioral symptoms did not predict cGVHD incidence. CONCLUSIONS: Biobehavioral symptoms, particularly sleep disruption and fatigue interference, predicted an increased risk for 6-year relapse and mortality after HCT. Because these symptoms are amenable to treatment, they offer specific targets for intervention to improve HCT outcomes.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Depressão/epidemiologia , Depressão/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Recidiva Local de Neoplasia/etiologia , SonoRESUMO
OBJECTIVE: To compare the optic disc and visual field (VF) alterations in primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). DESIGN: Observational case series. PARTICIPANTS: A total of 146 persons (217 eyes), 110 with POAG and 36 with PACG, recruited from a university glaucoma service. METHODS: Each subject underwent visual acuity measurement, applanation tonometry, gonioscopy, slit-lamp examination, dilated optic disc and retinal examination, axial eye length measurement, central corneal pachymetry, automated perimetry, optical coherence tomography (OCT) nerve fiber layer (NFL) examination, and Heidelberg Retina Tomograph (HRT) optic disc evaluation. Parameters of interest were studied by multivariate regression models. MAIN OUTCOME MEASURES: Heidelberg Retina Tomograph parameters compared between POAG and PACG. RESULTS: Primary open-angle glaucoma and PACG groups were similar in age, ethnic background, and treated intraocular pressure, but the PACG group had significantly more women, shorter eye length, more hyperopia, and a larger disc area (all Ps < 0.001). The VF average mean deviation (MD) did not significantly differ between POAG and PACG, but the PACG group had lower pattern standard deviation (PSD) for a given MD (P = 0.001). Although 3 HRT parameters differed somewhat between POAG and PACG (cup area, rim area, and cup-to-disc area ratio), they did not significantly differ after correction for multiple comparisons. Mean deviation and disc area were much more significant predictors of the HRT measures than was diagnosis. Similar results were obtained when using OCT NFL thickness as a structural measure of damage as opposed to MD as a functional measure. When controlling for MD, current IOP was not significantly associated with disc parameters in POAG. CONCLUSIONS: When the amount of optic nerve damage is taken into account by adjusting for VF MD or OCT NFL thickness, those with POAG and PACG have no significant differences in optic disc topography. Visual field damage in PACG was more diffuse than that in POAG, as measured by a lower PSD for a given level of MD. There was no corresponding difference in the uniformity of structural damage as measured by OCT NFL thickness.
Assuntos
Glaucoma de Ângulo Fechado/diagnóstico , Glaucoma de Ângulo Aberto/diagnóstico , Disco Óptico/patologia , Doenças do Nervo Óptico/diagnóstico , Transtornos da Visão/diagnóstico , Campos Visuais , Idoso , Feminino , Gonioscopia , Humanos , Pressão Intraocular , Masculino , Fibras Nervosas/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica , Tonometria Ocular , Acuidade Visual , Testes de Campo VisualRESUMO
BACKGROUND: Limited data are published on the ultrasound biomicroscope (UBM) findings of the anterior chamber angle. This work provides a population-based assessment of angle findings and compares 3 modalities for assessing angle dimensions. METHODS: A sample of 268 persons who had participated in a population-based study of glaucoma prevalence in Singapore were reexamined by UBM (nasal, temporal, and inferior angles only), Scheimpflug photography of angle width, and gonioscopy. Angle findings were compared, and age and sex influences evaluated. RESULTS: The temporal angle was the widest of the 3 angles imaged with the UBM, and the inferior angle was the narrowest (nearly 20% more narrow than the temporal angle, P<0.005). Women were found to have narrower angles than men and older persons had more narrow angles. Scheimpflug photography did not provide enough detail of the angle to increase our understanding of angle anatomy. CONCLUSIONS: The data reported support earlier findings that the anterior chamber angle is narrower in older individuals and women. Methods of assessing the angle may themselves influence the appearance of the angle. Limited agreement exists between the angle quantification methods studied. An ideal method of angle assessment would not contact the eye and would not require light be directed at the eye.
Assuntos
Câmara Anterior/anatomia & histologia , Gonioscopia/métodos , Iris/anatomia & histologia , Microscopia Acústica/métodos , Fotografação/métodos , Malha Trabecular/anatomia & histologia , Adulto , Fatores Etários , Idoso , Câmara Anterior/diagnóstico por imagem , Povo Asiático/etnologia , Feminino , Humanos , Iris/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Singapura/epidemiologia , Malha Trabecular/diagnóstico por imagemRESUMO
INTRODUCTION: Asking family members to leave during invasive procedures has historically been common practice; however, evidence-based recommendations have altered the trend of family presence during pediatric procedures. The aim of this study was to determine factors related to family members' choice to be present or absent during fracture reductions in a pediatric emergency department (ED), and their satisfaction with that choice. METHODS: We administered role-specific, anonymous surveys to a convenience sample of patients' family members in the ED of a Level I pediatric trauma center. All family members were given a choice of where to be during the procedure. RESULTS: Twenty-five family members of 18 patients completed surveys. Seventeen family members chose to stay in the room. Family member satisfaction with their decision to be inside or outside the room during the procedure (median = very satisfied) was almost uniformly high and not associated with any of the following variables: previous presence during a medical procedure; provider-reported procedure difficulty, or anxiety levels. Family member perception of procedure success (median = extremely well) was also high and not associated with other variables. Location during the procedure was associated with a desire to be in the same location in the future (Fisher's exact test, p=0.001). Common themes found among family members' reasons for their location decisions and satisfaction levels were a desire to support the patient, high staff competence, and their right as parents to choose their location. CONCLUSION: Family members self-select their location during their child's fracture reduction to high levels of satisfaction, and they considered the ability to choose their location as important.