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1.
PLoS Genet ; 20(2): e1010660, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38363804

RESUMO

Competition among pollen or sperm (gametic selection) can cause evolution. Mating systems shape the intensity of gametic selection by determining the competitors involved, which can in turn cause the mating system itself to evolve. We model the bidirectional relationship between gametic selection and mating systems, focusing on variation in female mating frequency (monandry-polyandry) and self-fertilisation (selfing-outcrossing). First, we find that monandry and selfing both reduce the efficiency of gametic selection in removing deleterious alleles. This means that selfing can increase mutation load, in contrast to cases without gametic selection where selfing purges deleterious mutations and decreases mutation load. Second, we explore how mating systems evolve via their effect on gametic selection. By manipulating gametic selection, polyandry can evolve to increase the fitness of the offspring produced. However, this indirect advantage of post-copulatory sexual selection is weak and is likely to be overwhelmed by any direct fitness effects of mating systems. Nevertheless, gametic selection can be potentially decisive for selfing evolution because it significantly reduces inbreeding depression, which favours selfing. Thus, the presence of gametic selection could be a key factor driving selfing evolution.


Assuntos
Células Germinativas , Sementes , Espermatozoides , Alelos , Comunicação Celular
2.
Brain ; 147(5): 1914-1925, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38181433

RESUMO

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.


Assuntos
Transplante de Medula Óssea , Lesões Encefálicas Traumáticas , Transplante Autólogo , Humanos , Criança , Lesões Encefálicas Traumáticas/terapia , Masculino , Feminino , Adolescente , Método Duplo-Cego , Pré-Escolar , Transplante de Medula Óssea/métodos , Transplante Autólogo/métodos , Imageamento por Ressonância Magnética , Resultado do Tratamento , Leucócitos Mononucleares/transplante , Teorema de Bayes
3.
Proc Biol Sci ; 291(2026): 20240693, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38981518

RESUMO

The evolution of separate sexes from cosexuality requires at least two mutations: a feminizing allele to cause female development and a masculinizing allele to cause male development. Classically, the double mutant is assumed to be sterile, which leads to two-factor sex determination where male and female sex chromosomes differ at two loci. However, several species appear to have one-factor sex determination where sexual development depends on variation at a single locus. We show that one-factor sex determination evolves when the double mutant develops as a male or a female. The feminizing allele fixes when the double mutant is male, and the masculinizing allele fixes when the double mutant is female. The other locus then gives XY or ZW sex determination based on dominance: for example, a dominant masculinizer becomes a Y chromosome. Although the resulting sex determination system differs, the conditions required for feminizers and masculinizers to spread are the same as in classical models, with the important difference that the two alleles do not need to be linked. Thus, we reveal alternative pathways for the evolution of sex determination and discuss how they can be distinguished using new data on the genetics of sex determination.


Assuntos
Mutação , Processos de Determinação Sexual , Masculino , Feminino , Animais , Cromossomos Sexuais , Evolução Biológica , Modelos Genéticos , Alelos , Ligação Genética
4.
J Magn Reson Imaging ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426608

RESUMO

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

5.
J Surg Res ; 296: 142-148, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38277950

RESUMO

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of death and morbidity in the trauma population. Microglia drive the secondary neuroinflammatory response after TBI. We sought to determine if the microglial response to neurologic injury was exacerbated by a second stimulus after exposure to neurologic injury. METHODS: Sprague-Dawley rats (age 2-3 wk) were divided into injured and noninjured groups. Injured rats underwent a controlled cortical impact injury; noninjured rats remained naïve to any injury and served as the control group. Primary rat microglia were isolated and applied to in vitro cultures. After incubation for 24 h, the microglia were stimulated with lipopolysaccharide (LPS) or norepinephrine. Twenty-four hours after stimulation, cell culture supernatant was collected. Tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) production were measured by standard enzyme-linked immunosorbent assays. GraphPad Prism was used for statistical analysis. RESULTS: When compared to noninjured microglia, LPS induced a significantly greater production of TNF-α in microglia isolated from the injured ipsilateral (versus noninjured = 938.8 ± 155.1, P < 0.0001) and injured contralateral hemispheres (versus noninjured = 426.6 ± 155.1, P < 0.0001). When compared to microglia from noninjured cerebral tissue, IL-6 production was significantly greater after LPS stimulation in the injured ipsilateral hemisphere (mean difference versus noninjured = 9540 ± 3016, P = 0.0101) and the contralateral hemisphere (16,700 ± 3016, P < 0.0001). Norepinephrine did not have a significant effect on IL-6 or TNF-α production. CONCLUSIONS: LPS stimulation may amplify the release of proinflammatory cytokines from postinjury microglia. These data suggest that post-TBI complications, like sepsis, may propagate neuroinflammation by augmenting the proinflammatory response of microglia.


Assuntos
Lesões Encefálicas Traumáticas , Citocinas , Ratos , Animais , Microglia/patologia , Lipopolissacarídeos/farmacologia , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6 , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/patologia , Norepinefrina
6.
Anesth Analg ; 138(4): 713-724, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38153876

RESUMO

In November of 2022, the Anesthesia Patient Safety Foundation held a Consensus Conference on Hemodynamic Instability with invited experts. The objective was to review the science and use expert consensus to produce best practice recommendations to address the issue of perioperative hemodynamic instability. After expert presentations, a modified Delphi process using discussions, voting, and feedback resulted in 17 recommendations regarding advancing the perioperative care of the patient at risk of, or with, hemodynamic instability. There were 17 high-level recommendations. These recommendations related to the following 7 domains: Current Knowledge (5 statements); Preventing Hemodynamic Instability-Related Harm During All Phases of Care (4 statements); Data-Driven Quality Improvement (3 statements); Informing Patients (2 statements); The Importance of Technology (1 statement); Launch a National Campaign (1 statement); and Advancing the Science (1 statement). A summary of the recommendations is presented in Table 1 .


Assuntos
Anestesia , Segurança do Paciente , Humanos , Pacientes , Anestesia/efeitos adversos , Consenso , Hemodinâmica , Técnica Delphi
7.
J Magn Reson Imaging ; 57(1): 126-136, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35633284

RESUMO

BACKGROUND: Aortopathy is common with bicuspid aortic valve (BAV), and underlying intrinsic tissue abnormalities are believed causative. Valve-mediated hemodynamics are altered in BAV and may contribute to aortopathy and its progression. The contribution of intrinsic tissue defects versus altered hemodynamics to aortopathy progression is not known. PURPOSE: To investigate relative contributions of tissue-innate versus hemodynamics in progression of BAV aortopathy. STUDY TYPE: Retrospective. SUBJECTS: Four hundred seventy-three patients with aortic dilatation (diameter ≥40 mm; comprised of 281 BAV with varied AS severity, 192 tricuspid aortic valve [TAV] without AS) and 124 healthy controls. Subjects were 19-91 years (141/24% female). FIELD STRENGTH/SEQUENCE: 1.5T, 3T; time-resolved gradient-echo 3D phase-contrast (4D flow) MRI. ASSESSMENT: A surrogate measure for global aortic wall stiffness, pulse wave velocity (PWV), was quantified from MRI by standardized, automated technique based on through-plane flow cross-correlation maximization. Comparisons were made between BAV patients with aortic dilatation and varying aortic valve stenosis (AS) severity and healthy subjects and aortopathy patients with normal TAV. STATISTICAL TESTS: Multivariable regression, analysis of covariance (ANCOVA), Tukey's, student's (t), Mann-Whitney (U) tests, were used with significance levels P < 0.05 or P < 0.01 for post-hoc Bonferroni-corrected t/U tests. Bland-Altman and ICC calculations were performed. RESULTS: Multivariable regression showed age with the most significant association for increased PWV in all groups (increase 0.073-0.156 m/sec/year, R2  = 0.30-48). No significant differences in aortic PWV were observed between groups without AS (P = 0.20-0.99), nor were associations between PWV and regurgitation or Sievers type observed (P = 0.60, 0.31 respectively). In contrast, BAV AS patients demonstrated elevated PWV and a significant relationship for AS severity with increased PWV (covariate: age, R2  = 0.48). BAV and TAV patients showed no association between aortic diameter and PWV (P = 0.73). DATA CONCLUSION: No significant PWV differences were observed between BAV patients with normal valve function and control groups. However, AS severity and age in BAV patients were directly associated with PWV increases. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.


Assuntos
Doenças da Aorta , Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Doenças das Valvas Cardíacas , Humanos , Feminino , Masculino , Valva Aórtica/diagnóstico por imagem , Análise de Onda de Pulso , Doenças das Valvas Cardíacas/diagnóstico por imagem , Estudos Retrospectivos , Estenose da Valva Aórtica/complicações , Doença da Válvula Aórtica Bicúspide/complicações , Doenças da Aorta/diagnóstico por imagem , Hemodinâmica
8.
Eur Radiol ; 33(3): 1707-1718, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36307551

RESUMO

OBJECTIVES: Time-resolved, 2D-phase-contrast MRI (2D-CINE-PC-MRI) enables in vivo blood flow analysis. However, accurate vessel contour delineation (VCD) is required to achieve reliable results. We sought to evaluate manual analysis (MA) compared to the performance of a deep learning (DL) application for fully-automated VCD and flow quantification and corrected semi-automated analysis (corSAA). METHODS: We included 97 consecutive patients (age = 52.9 ± 16 years, 41 female) with 2D-CINE-PC-MRI imaging on 1.5T MRI systems at sinotubular junction (STJ), and 28/97 also received 2D-CINE-PC at main pulmonary artery (PA). A cardiovascular radiologist performed MA (reference) and corSAA (built-in tool) in commercial software for all cardiac time frames (median: 20, total contours per analysis: 2358 STJ, 680 PA). DL-analysis automatically performed VCD, followed by net flow (NF) and peak velocity (PV) quantification. Contours were compared using Dice similarity coefficients (DSC). Discrepant cases (> ± 10 mL or > ± 10 cm/s) were reviewed in detail. RESULTS: DL was successfully applied to 97% (121/125) of the 2D-CINE-PC-MRI series (STJ: 95/97, 98%, PA: 26/28, 93%). Compared to MA, mean DSC were 0.91 ± 0.02 (DL), 0.94 ± 0.02 (corSAA) at STJ, and 0.85 ± 0.08 (DL), 0.93 ± 0.02 (corSAA) at PA; this indicated good to excellent DL-performance. Flow quantification revealed similar NF at STJ (p = 0.48) and PA (p > 0.05) between methods while PV assessment was significantly different (STJ: p < 0.001, PA: p = 0.04). A detailed review showed noisy voxels in MA and corSAA impacted PV results. Overall, DL analysis compared to human assessments was accurate in 113/121 (93.4%) cases. CONCLUSIONS: Fully-automated DL-analysis of 2D-CINE-PC-MRI provided flow quantification at STJ and PA at expert level in > 93% of cases with results being available instantaneously. KEY POINTS: • Deep learning performed flow quantification on clinical 2D-CINE-PC series at the sinotubular junction and pulmonary artery at the expert level in > 93% of cases. • Location detection and contouring of the vessel boundaries were performed fully-automatic with results being available instantaneously compared to human assessments which approximately takes three minutes per location. • The evaluated tool indicates usability in daily practice.


Assuntos
Aprendizado Profundo , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Velocidade do Fluxo Sanguíneo/fisiologia , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Hemodinâmica
9.
Br J Clin Pharmacol ; 89(9): 2851-2866, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160725

RESUMO

AIM: To evaluate the impact of the COVID-19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland. METHODS: Data were collected on antibiotic use and Gram-positive and Gram-negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015-March 2020) and during (April 2020-December 2021) the pandemic. Time series intervention analysis methods were utilized. RESULTS: In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 defined daily doses (DDDs) per 1000 occupied-bed days (OBD), showing no significant change from pre-pandemic (P = .7365). During the pandemic, the use of second-generation cephalosporins, third-generation cephalosporins, co-amoxiclav and levofloxacin increased, there was a decrease in the percentage use of the hospital Access group (P = .0083) and an increase in the percentage use of Watch group (P = .0040), and the number of hospital Klebsiella oxytoca and methicillin-susceptible Staphylococcus aureus cases increased. In primary care, the mean total antibiotic consumption during the COVID-19 pandemic was 20.53 DDDs per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID-19 pandemic (P = .0071). During the pandemic, there was a decrease in the use of several antibiotic classes, an increase in the percentage use of the Reserve group (P = .0032) and an increase in the number of community-onset Pseudomonas aeruginosa cases. CONCLUSION: This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID-19 pandemic that emphasize the importance of antimicrobial stewardship in pandemic situations.


Assuntos
Antibacterianos , COVID-19 , Humanos , Antibacterianos/uso terapêutico , Pandemias , Prevalência , Irlanda do Norte/epidemiologia , COVID-19/epidemiologia , Atenção à Saúde , Cefalosporinas
10.
World J Surg ; 47(1): 11-34, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36310325

RESUMO

BACKGROUND: Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. METHODS: A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. RESULTS: A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. CONCLUSIONS: These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Visitas de Preceptoria , Humanos , Exercício Pré-Operatório , Fígado
11.
World J Surg ; 47(8): 1881-1898, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37277506

RESUMO

BACKGROUND: This is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care. METHODS: Experts in management of the high-risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. RESULTS: Components of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process. CONCLUSIONS: These guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end-of-life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Laparotomia , Assistência Perioperatória/métodos , Organizações , Procedimentos Cirúrgicos Eletivos
12.
World J Surg ; 47(8): 1850-1880, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37277507

RESUMO

BACKGROUND: This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra- and postoperative aspects of care. METHODS: Experts in aspects of management of high-risk and emergency general surgical patients were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta-analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. RESULTS: Twenty-three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. CONCLUSIONS: These guidelines are based on best available evidence for an ERAS® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high-risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Humanos , Cuidados Pós-Operatórios , Laparotomia , Assistência Perioperatória/métodos , Procedimentos Cirúrgicos Eletivos/métodos
13.
Neurocrit Care ; 38(3): 688-697, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36418766

RESUMO

BACKGROUND: Microglia are a primary mediator of the neuroinflammatory response to neurologic injury, such as that in traumatic brain injury. Their response includes changes to their cytokine expression, metabolic profile, and immunophenotype. Dexmedetomidine (DEX) is an α2 adrenergic agonist used as a sedative in critically ill patients, such as those with traumatic brain injury. Given its pharmacologic properties, DEX may alter the phenotype of inflammatory microglia. METHODS: Primary microglia were isolated from Sprague-Dawley rats and cultured. Microglia were activated using multiple mediators: lipopolysaccharide (LPS), polyinosinic-polycytidylic acid (Poly I:C), and traumatic brain injury damage-associated molecular patterns (DAMP) from a rat that sustained a prior controlled cortical impact injury. After activation, cultures were treated with DEX. At the 24-h interval, the cell supernatant and cells were collected for the following studies: cytokine expression (tumor necrosis factor-α [TNFα], interleukin-10 [IL-10]) via enzyme-linked immunosorbent assay, 6-phosphofructokinase enzyme activity assay, and immunophenotype profiling with flow cytometry. Cytokine expression and metabolic enzyme activity data were analyzed using two-way analysis of variance. Cell surface marker expression was analyzed using FlowJo software. RESULTS: In LPS-treated cultures, DEX treatment decreased the expression of TNFα from microglia (mean difference = 121.5 ± 15.96 pg/mL; p < 0.0001). Overall, DEX-treated cultures had a lower expression of IL-10 than nontreated cultures (mean difference = 39.33 ± 14.50 pg/mL, p < 0.0001). DEX decreased IL-10 expression in LPS-stimulated microglia (mean difference = 74.93 ± 12.50 pg/mL, p = 0.0039) and Poly I:C-stimulated microglia (mean difference = 23.27 ± 6.405 pg/mL, p = 0.0221). In DAMP-stimulated microglia, DEX decreased the activity of 6-phosphofructokinase (mean difference = 18.79 ± 6.508 units/mL; p = 0.0421). The microglial immunophenotype was altered to varying degrees with different inflammatory stimuli and DEX treatment. CONCLUSIONS: DEX may alter the neuroinflammatory response of microglia. By altering the microglial profile, DEX may affect the progression of neurologic injury.


Assuntos
Lesões Encefálicas Traumáticas , Dexmedetomidina , Ratos , Animais , Dexmedetomidina/farmacologia , Dexmedetomidina/metabolismo , Dexmedetomidina/uso terapêutico , Interleucina-10/metabolismo , Interleucina-10/uso terapêutico , Microglia/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ratos Sprague-Dawley , Lipopolissacarídeos/farmacologia , Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Citocinas/metabolismo , Inflamação/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Poli I/metabolismo , Poli I/uso terapêutico
14.
Cardiol Young ; 33(10): 1936-1941, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36380489

RESUMO

BACKGROUND: During the COVID-19 pandemic, Kentucky prohibited elective medical procedures from 3/18/2020-4/27/2020. We sought to determine if cessation of elective procedures in Kentucky during the COVID-19 pandemic resulted in a decrease in the proportion of rarely appropriate outpatient transthoracic echocardiograms interpreted at the open echocardiography lab at Norton Children's Hospital. METHODS: A retrospective chart review was conducted comparing proportions of rarely appropriate outpatient paediatric transthoracic echocardiograms performed pre-COVID (3/21/2019-4/28/2019) and during COVID (3/19/2020-4/27/2020). Transthoracic echocardiogram indication was determined by chart review and echocardiogram reports. Indication appropriateness was evaluated using paediatric appropriate use criteria for initial outpatient transthoracic echocardiogram or CHD follow-up as applicable. RESULTS: Of transthoracic echocardiograms pre-COVID, 100 (37.7%) were rarely appropriate versus 18 (20.2%) during COVID. Pre-COVID, paediatric cardiologists tended to order fewer rarely appropriate transthoracic echocardiograms than paediatricians (35.9% versus 46.4%), although this difference was not statistically significant. Cardiologists ordered the majority of outpatient transthoracic echocardiograms during COVID (77/89, 86.5%), limiting the ability to compare transthoracic echocardiogram indications by provider type. There was no significant difference in diagnostic yield of initial outpatient transthoracic echocardiograms with (13.0%) abnormal studies pre-COVID versus 7 (15.5%) during COVID. CONCLUSION: While elective procedures were prohibited in Kentucky during the COVID-19 pandemic, a decrease in the proportion of rarely appropriate outpatient paediatric transthoracic echocardiograms was observed. There was no significant difference in diagnostic yield of initial outpatient transthoracic echocardiograms between time periods, suggesting that clinically significant echocardiogram findings were still detected despite more prudent utilisation of echocardiography during this time.


Assuntos
COVID-19 , Pacientes Ambulatoriais , Criança , Humanos , Estudos Retrospectivos , Pandemias , COVID-19/epidemiologia , Atenção à Saúde , Ecocardiografia , Teste para COVID-19
15.
Telemed J E Health ; 29(5): 674-685, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36112346

RESUMO

Objective: To evaluate the use of telemedicine as a collaboration tool between a pediatrician and subspecialists looking to address challenges, such as the lack of health care specialists, which are present in the Dominican Republic. Study design: During this 6-year study, 65 patients were evaluated by a medical team consisting of a local pediatrician and 17 subspecialists from a leading academic medical center in the Unites States. Patient's age ranged from 2 months to 16 years of age (mean 8 years old). The most common reasons for referral were masses or malignancies, vascular malformations, urogenital anomalies, stuttering, and cochlear implant programming. Results: A total of 39 out of 65 cases (60%) carried an initial diagnosis. Of the 65 cases, a change in medical management occurred in 92.31% of cases (60 cases). There was no change in medical diagnosis or treatment in 5 of 65 cases (8%). Conclusion: This protocol exhibited high patient satisfaction with the technology and platform and direct patient savings from transportation costs. It also demonstrated the importance of thorough diagnosis in providing appropriate treatment and solutions. Telemedicine use in comparable practices should be studied further to aid in the development of policies for the diagnosis and management of chronic illnesses that require referrals to subspecialists.


Assuntos
Telemedicina , Criança , Humanos , Lactente , Encaminhamento e Consulta , Doença Crônica , Custos e Análise de Custo , Satisfação do Paciente
16.
Am J Occup Ther ; 77(Suppl 1)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37639534

RESUMO

Systematic review briefs provide a summary of findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adolescents aged 13-19 yr gathered from literature published between 2013 and 2021.


Assuntos
Transtorno Autístico , Terapia Ocupacional , Humanos , Adolescente
17.
Am J Occup Ther ; 77(Suppl 1)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656818

RESUMO

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each systematic review brief summarizes the evidence on a theme related to a systematic review topic. The authors completed a systematic review of family- and person-centered planning interventions for families of autistic1 children, or autistic adolescents and adults gathered from literature published between 2013 and 2021. This systematic review brief presents findings from the six included articles that focused on family-centered planning interventions. Emerging evidence from these six studies supports the use of coaching interventions with caregivers of children on the autism spectrum to address both child and parent outcomes. These outcomes include individualized goals; caregiver sense of competence, empowerment, or self-efficacy; occupational performance of children and mothers; and caregiver satisfaction with their child's occupational performance.


Assuntos
Transtorno Autístico , Tutoria , Terapia Ocupacional , Adolescente , Adulto , Feminino , Criança , Humanos , Mães , Pais
18.
Am J Occup Ther ; 77(Suppl 1)2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37656819

RESUMO

Systematic review briefs provide a summary of the findings from systematic reviews developed in conjunction with the Evidence-Based Practice Program of the American Occupational Therapy Association. Each systematic review brief summarizes the evidence for a theme related to a systematic review topic. This systematic review brief presents findings from a systematic review of family- and person-centered planning interventions for autistic1 adults aged 18+ years gathered from literature published between 2013 and 2021.

19.
Curr Opin Anaesthesiol ; 36(2): 202-207, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36745085

RESUMO

PURPOSE OF REVIEW: Enhanced recovery after surgery (ERAS) has revolutionized care outcomes. The purpose of this review is to provide an overview of how ERAS changed healthcare outcomes. RECENT FINDINGS: Development of multidisciplinary evidence-based ERAS guidelines for specific surgical specialties and systematic implementation of these guidelines resulted in improved healthcare outcomes, reduction in length of stay, reduction in complications and improved survival. The value of audit of the outcomes is essential for implementation and to improve healthcare. Healthcare economics analysis related to the implementation of ERAS showed significant cost savings up to a return to investment ratio of more than seven. SUMMARY: ERAS has revolutionized healthcare by developing evidence-based ERAS guidelines and systematic implementation of these guidelines. Audit of outcomes is essential, not only to improve healthcare but also to significantly save healthcare expenditures.


Assuntos
Anestesia , Recuperação Pós-Cirúrgica Melhorada , Humanos , Complicações Pós-Operatórias , Tempo de Internação , Redução de Custos
20.
Magn Reson Med ; 88(1): 449-463, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35381116

RESUMO

PURPOSE: To develop a convolutional neural network (CNN) for the robust and fast correction of velocity aliasing in 4D-flow MRI. METHODS: This study included 667 adult subjects with aortic 4D-flow MRI data with existing velocity aliasing (n = 362) and no velocity aliasing (n = 305). Additionally, 10 controls received back-to-back 4D-flow scans with systemically varied velocity-encoding sensitivity (vencs) at 60, 100, and 175 cm/s. The no-aliasing data sets were used to simulate velocity aliasing by reducing the venc to 40%-70% of the original, alongside a ground truth locating all aliased voxels (153 training, 152 testing). The 152 simulated and 362 existing aliasing data sets were used for testing and compared with a conventional velocity antialiasing algorithm. Dice scores were calculated to quantify CNN performance. For controls, the venc 175-cm/s scans were used as the ground truth and compared with the CNN-corrected venc 60 and 100 cm/s data sets RESULTS: The CNN required 176 ± 30 s to perform compared with 162 ± 14 s for the conventional algorithm. The CNN showed excellent performance for the simulated data compared with the conventional algorithm (median range of Dice scores CNN: [0.89-0.99], conventional algorithm: [0.84-0.94], p < 0.001, across all simulated vencs) and detected more aliased voxels in existing velocity aliasing data sets (median detected CNN: 159 voxels [31-605], conventional algorithm: 65 [7-417], p < 0.001). For controls, the CNN showed Dice scores of 0.98 [0.95-0.99] and 0.96 [0.87-0.99] for venc = 60 cm/s and 100 cm/s, respectively, while flow comparisons showed moderate-excellent agreement. CONCLUSION: Deep learning enabled fast and robust velocity anti-aliasing in 4D-flow MRI.


Assuntos
Aprendizado Profundo , Imageamento Tridimensional , Adulto , Velocidade do Fluxo Sanguíneo , Humanos , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Reprodutibilidade dos Testes
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