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BACKGROUND: Ingestion of prebiotics during pregnancy and lactation may have immunomodulatory benefits for the developing fetal and infant immune system and provide a potential dietary strategy to reduce the risk of allergic diseases. OBJECTIVE: The aim of this trial was to determine whether maternal supplementation with dietary prebiotics reduces the risk of allergic outcomes in infants with hereditary risk. METHODS: We undertook a double-blind, randomized controlled trial in which pregnant women were allocated to consume prebiotics (14.2g daily of galacto-oligosaccharides and fructo-oligosaccharides in ratio 9:1) or placebo (8.7g daily maltodextrin) powder from <21 weeks gestation until 6-months postnatal during lactation. Eligible women had infants with a first-degree relative with a history of medically diagnosed allergic disease. The primary outcome was infant medically diagnosed eczema by 1-year of age, and secondary outcomes included allergen sensitization, food allergy, and recurrent wheeze by 1-year of age. RESULTS: 652 women were randomized between June 2016 and November 2021 (n=329 prebiotics, n=323 placebo). There was no significant difference between groups in the percentage of infants with medically diagnosed eczema by 1-year of age (prebiotics 31.5% (103/327 infants) compared to placebo 32.6% (105/322 infants); adjusted relative risk 0.98 (95% CI 0.77, 1.23; p=0.84). Secondary outcomes and safety measures also did not significantly differ between groups. CONCLUSION: We found little evidence that maternal prebiotics supplementation during pregnancy and lactation reduces the risk of infant medically diagnosed eczema by 1-year of age in infants who are at hereditary risk of allergic disease.
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Purpose: We introduce a deep learning-based biomarker proposal system for the purpose of accelerating biomarker discovery in age-related macular degeneration (AMD). Design: Retrospective analysis of a large data set of retinal OCT images. Participants: A total of 3456 adults aged between 51 and 102 years whose OCT images were collected under the PINNACLE project. Methods: Our system proposes candidates for novel AMD imaging biomarkers in OCT. It works by first training a neural network using self-supervised contrastive learning to discover, without any clinical annotations, features relating to both known and unknown AMD biomarkers present in 46 496 retinal OCT images. To interpret the learned biomarkers, we partition the images into 30 subsets, termed clusters, that contain similar features. We conduct 2 parallel 1.5-hour semistructured interviews with 2 independent teams of retinal specialists to assign descriptions in clinical language to each cluster. Descriptions of clusters achieving consensus can potentially inform new biomarker candidates. Main Outcome Measures: We checked if each cluster showed clear features comprehensible to retinal specialists, if they related to AMD, and how many described established biomarkers used in grading systems as opposed to recently proposed or potentially new biomarkers. We also compared their prognostic value for late-stage wet and dry AMD against an established clinical grading system and a demographic baseline model. Results: Overall, both teams independently identified clearly distinct characteristics in 27 of 30 clusters, of which 23 were related to AMD. Seven were recognized as known biomarkers used in established grading systems, and 16 depicted biomarker combinations or subtypes that are either not yet used in grading systems, were only recently proposed, or were unknown. Clusters separated incomplete from complete retinal atrophy, intraretinal from subretinal fluid, and thick from thin choroids, and, in simulation, outperformed clinically used grading systems in prognostic value. Conclusions: Using self-supervised deep learning, we were able to automatically propose AMD biomarkers going beyond the set used in clinically established grading systems. Without any clinical annotations, contrastive learning discovered subtle differences between fine-grained biomarkers. Ultimately, we envision that equipping clinicians with discovery-oriented deep learning tools can accelerate the discovery of novel prognostic biomarkers. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Background: Cystic fibrosis (CF) is a multi-organ disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Individuals with CF often have gastrointestinal (GI) dysbiosis due to chronic inflammation and antibiotic use. Previous studies suggested a role for vitamin D in reversing the GI dysbiosis found in CF. Objective: To explore the potential role of a combination of high-dose oral cholecalciferol (vitamin D3) and fermentable dietary fiber, inulin, to impact bacterial composition, richness, and diversity of intestinal and airway microbiota in adults with CF. Methods: This was a 2 × 2 factorial, double-blinded, placebo-controlled, randomized, pilot clinical trial in which adults with CF received oral cholecalciferol (vitamin D3) (50,000 IU/week) and/or inulin (12 g/day) for 12 weeks. Thus, there were 4 study groups (n = 10 subjects per group); 1) placebo 2) vitamin D3 3) inulin 4) vitamin D3 plus inulin. Stool and sputum samples were collected at baseline (just before) and after the intervention and were analysed using 16S ribosomal RNA gene sequencing for gut and airway microbiota composition. Statistical analyses assessed alpha and beta diversity to evaluate microbial community changes. Results: Of a total of 254 screened participants, 40 eligible participants were randomized to one of the 4 treatment arms. Participants receiving vitamin D3 plus inulin exhibited greater changes in microbiome indexes in both intestinal and airway relative to those in the other study groups. Specific taxonomic changes supported the potential beneficial influence of this combination to mitigate both intestinal and airway dysbiosis in adults with CF. Conclusion: This pilot study established that the combination of oral vitamin D3 and the prebiotic inulin was well tolerated over 12 weeks in adults with CF and altered gut and airway bacterial communities. Future research appear warranted to define clinical outcomes and the role of microbiota changes therein with this approach.
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AbstractClinical trials investigating novel or high-risk interventions often use data monitoring committees (DMCs) to ensure that the participants' best interests are safeguarded. The typical DMC charter describes procedures by which the DMC operates, including important details concerning organizational structure, membership, meeting frequency, statistical monitoring guidelines, and contents of DMC reports for interim review. These charters, however, are not routinely publicly available; in some cases, their access could be important to the interpretation of trial results. We recommend including DMC charters for such trials in ClinicalTrials.gov at the time of trial completion; trial protocols, informed consent documents, and statistical analysis plans are already available in this repository.
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Comités de Monitoreo de Datos de Ensayos Clínicos , Humanos , Comités de Monitoreo de Datos de Ensayos Clínicos/organización & administración , Ensayos Clínicos como Asunto , Acceso a la InformaciónRESUMEN
We describe our approach to addressing a nation-wide supply issue for blood culture bottles. Aerobic blood culture bottles received from our distributor July 1-15, 2024 was <1% of typical usage. Through education and ordering restrictions blood culture designed to minimize risk, orders were reduced by 49% over a one-week period.
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BACKGROUND: Cryoballoon ablation for treatment of atrial fibrillation (AF) reduces procedure times, but limited data is available about its impact on electrophysiology (EP) lab efficiency in Central and Eastern Europe (CEE). Using CEE-specific procedure data, the present study modeled cryoballoon ablation procedures on EP lab resource consumption to improve efficiency. METHODS: A discrete event simulation model was developed to assess EP efficiency with cryoballoon ablation. Model inputs were taken from CEE sites within the Cryo Global Registry, namely Czech Republic, Hungary, Poland, Serbia, and Slovakia. The main endpoints were percentage of days that resulted in overtime and percentage of days with time for one extra simple EP procedure. Use of the 'figure of 8' (Fo8) closure technique to reduce procedure time was also examined. RESULTS: The mean lab occupancy time across all CEE sites was 133 ± 47 minutes (min: 104 minutes, max:181 minutes). Cryoballoon ablation in the base-case scenario resulted in 14.6% of days with overtime and 64.8% of days with time for an extra simple EP procedure. Use of the Fo8 closure technique enhanced these values to 5.5% and 85.3%, respectively. Model endpoints were most sensitive to changes in lab occupancy times and overtime start time. CONCLUSIONS: In this CEE-specific analysis of EP lab efficiency it was found that 3 cryoballoon ablation procedures could be performed in 1 lab day, leaving time for a 4th simple EP procedure on most days. As such, use cryoballoon ablation for PVI is an effective way to improve EP lab efficiency.
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Caloric restriction and intermittent fasting prolong the lifespan and healthspan of model organisms and improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection and reduced incidence of cardiovascular and neurodegenerative diseases across species borders. Here, we asked whether the cellular and physiological consequences of caloric restriction and fasting depend on polyamine metabolism. We report that spermidine levels increased upon distinct regimens of fasting or caloric restriction in yeast, flies, mice and human volunteers. Genetic or pharmacological blockade of endogenous spermidine synthesis reduced fasting-induced autophagy in yeast, nematodes and human cells. Furthermore, perturbing the polyamine pathway in vivo abrogated the lifespan- and healthspan-extending effects, as well as the cardioprotective and anti-arthritic consequences of fasting. Mechanistically, spermidine mediated these effects via autophagy induction and hypusination of the translation regulator eIF5A. In summary, the polyamine-hypusination axis emerges as a phylogenetically conserved metabolic control hub for fasting-mediated autophagy enhancement and longevity.
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Introduction: Human Cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in immunocompromised transplant recipients. Immunotherapy with CD8 T cells specific for HCMV antigens presented on HLA class-I molecules is explored as strategy for long-term relief to such patients, but the antiviral effectiveness of T cell preparations cannot be efficiently predicted by available methods. Methods: We developed an Assay for Rapid Measurement of Antiviral T-cell Activity (ARMATA) by real-time automated fluorescent microscopy and used it to study the ability of CD8 T cells to neutralize HCMV and control its spread. As a proof of principle, we used TCR-transgenic T cells specific for the immunodominant HLA-A02-restricted tegumental phosphoprotein pp65. pp65 expression follows an early/late kinetic, but it is not clear at which stage of the virus cycle it acts as an antigen. We measured control of HCMV infection by T cells as early as 6 hours post infection (hpi). Results: The timing of the antigen recognition indicated that it occurred before the late phase of the virus cycle, but also that virion-associated pp65 was not recognized during virus entry into cells. Monitoring of pp65 gene expression dynamics by reporter fluorescent genes revealed that pp65 was detectable as early as 6 hpi, and that a second and much larger bout of expression occurs in the late phase of the virus cycle by 48 hpi. Since transgenic (Tg)-pp65 specific CD8 T cells were activated even when DNA replication was blocked, our data argue that pp65 acts as an early virus gene for immunological purposes. Discussion: ARMATA does not only allow same day identification of antiviral T-cell activity, but also provides a method to define the timing of antigen recognition in the context of HCMV infection.
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Linfocitos T CD8-positivos , Infecciones por Citomegalovirus , Citomegalovirus , Fosfoproteínas , Proteínas de la Matriz Viral , Linfocitos T CD8-positivos/inmunología , Citomegalovirus/inmunología , Citomegalovirus/genética , Fosfoproteínas/inmunología , Fosfoproteínas/genética , Humanos , Proteínas de la Matriz Viral/inmunología , Proteínas de la Matriz Viral/genética , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/virología , Regulación Viral de la Expresión Génica , Antígenos Virales/inmunología , Antígeno HLA-A2/inmunología , Antígeno HLA-A2/genéticaRESUMEN
Embedding a catalytically competent transition metal into a protein scaffold affords an artificial metalloenzyme (ArM). Such hybrid catalysts display features that are reminiscent of both homogeneous and enzymatic catalysts. Pioneered by Whitesides and Kaiser in the late 1970s, this field of ArMs has expanded over the past two decades, marked by ever-increasing diversity in reaction types, cofactors, and protein scaffolds. Recent noteworthy developments include i) the use of earth-abundant metal cofactors, ii) concurrent cascade reactions, iii) synergistic catalysis, and iv) in vivo catalysis. Thanks to significant progress in computational protein design, ArMs based on de novo-designed proteins and tailored chimeric proteins promise a bright future for this exciting field.
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Metaloproteínas , Ingeniería de Proteínas , Metaloproteínas/química , Metaloproteínas/metabolismo , Ingeniería de Proteínas/métodos , Catálisis , Enzimas/metabolismo , Enzimas/químicaRESUMEN
The continued evolution of SARS-CoV-2 variants capable of subverting vaccine and infection-induced immunity suggests the advantage of a broadly protective vaccine against betacoronaviruses (ß-CoVs). Recent studies have isolated monoclonal antibodies (mAbs) from SARS-CoV-2 recovered-vaccinated donors capable of neutralizing many variants of SARS-CoV-2 and other ß-CoVs. Many of these mAbs target the conserved S2 stem region of the SARS-CoV-2 spike protein, rather the receptor binding domain contained within S1 primarily targeted by current SARS-CoV-2 vaccines. One of these S2-directed mAbs, CC40.8, has demonstrated protective efficacy in small animal models against SARS-CoV-2 challenge. As the next step in the pre-clinical testing of S2-directed antibodies as a strategy to protect from SARS-CoV-2 infection, we evaluated the in vivo efficacy of CC40.8 in a clinically relevant non-human primate model by conducting passive antibody transfer to rhesus macaques (RM) followed by SARS-CoV-2 challenge. CC40.8 mAb was intravenously infused at 10mg/kg, 1mg/kg, or 0.1 mg/kg into groups (n=6) of RM, alongside one group that received a control antibody (PGT121). Viral loads in the lower airway were significantly reduced in animals receiving higher doses of CC40.8. We observed a significant reduction in inflammatory cytokines and macrophages within the lower airway of animals infused with 10mg/kg and 1mg/kg doses of CC40.8. Viral genome sequencing demonstrated a lack of escape mutations in the CC40.8 epitope. Collectively, these data demonstrate the protective efficiency of broadly neutralizing S2-targeting antibodies against SARS-CoV-2 infection within the lower airway while providing critical preclinical work necessary for the development of pan-ß-CoV vaccines.
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The epithelial Na + channel (ENaC) resides on the apical surfaces of specific epithelia in vertebrates and plays a critical role in extracellular fluid homeostasis. Evidence that ENaC senses the external environment emerged well before the molecular identity of the channel was reported three decades ago. This article discusses progress toward elucidating the mechanisms through which specific external factors regulate ENaC function, highlighting insights gained from structural studies of ENaC and related family members. It also reviews our understanding of the role of ENaC regulation by the extracellular environment in physiology and disease. After familiarizing the reader with the channel's physiological roles and structure, we describe the central role protein allostery plays in ENaC's sensitivity to the external environment. We then discuss each of the extracellular factors that directly regulate the channel: proteases, cations and anions, shear stress, and other regulators specific to particular extracellular compartments. For each regulator, we discuss the initial observations that led to discovery, studies investigating molecular mechanism, and the physiological and pathophysiological implications of regulation. © 2024 American Physiological Society. Compr Physiol 14:5407-5447, 2024.
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Canales Epiteliales de Sodio , Humanos , Canales Epiteliales de Sodio/metabolismo , Canales Epiteliales de Sodio/fisiología , AnimalesRESUMEN
Estrogens regulate numerous physiological and pathological processes, including wide-ranging effects in wound healing. The effects of estrogens are mediated through multiple estrogen receptors (ERs), including the classical nuclear ERs (ERα and ER ß ), that typically regulate gene expression, and the 7-transmembrane G protein-coupled estrogen receptor (GPER), that predominantly mediates rapid "non-genomic" signaling. Estrogen modulates the expression of various genes involved in epidermal function and regeneration, inflammation, matrix production, and protease inhibition, all critical to wound healing. Our previous work demonstrated improved myocutaneous wound healing in female mice compared to male mice. In the current study, we employed male and female GPER knockout mice to investigate the role of this estrogen receptor in wound revascularization and tissue viability. Using a murine myocutaneous flap model of graded ischemia, we measured real-time flap perfusion via laser speckle perfusion imaging. We conducted histologic and immunohistochemical analyses to assess skin and muscle viability, microvascular density and vessel morphology. Our results demonstrate that GPER is crucial in wound healing, mediating effects that are both dependent and independent of sex. Lack of GPER expression is associated with increased skin necrosis, reduced flap perfusion and altered vessel morphology. These findings contribute to understanding GPER signaling in wound healing and suggest possible therapeutic opportunities by targeting GPER.
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Ratones Noqueados , Neovascularización Fisiológica , Receptores de Estrógenos , Receptores Acoplados a Proteínas G , Cicatrización de Heridas , Animales , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/genética , Masculino , Ratones , Femenino , Piel/metabolismo , Piel/irrigación sanguínea , Isquemia/metabolismo , Colgajos QuirúrgicosRESUMEN
As lifelong interphase cells, neurons face an array of unique challenges. A key challenge is regulating nuclear pore complex (NPC) biogenesis and localization, the mechanisms of which are largely unknown. Here we identify neuronal maturation as a period of strongly upregulated NPC biogenesis. We demonstrate that the AAA+ protein torsinA, whose dysfunction causes the neurodevelopmental movement disorder DYT-TOR1A dystonia and co-ordinates NPC spatial organization without impacting total NPC density. We generated an endogenous Nup107-HaloTag mouse line to directly visualize NPC organization in developing neurons and find that torsinA is essential for proper NPC localization. In the absence of torsinA, the inner nuclear membrane buds excessively at sites of mislocalized nascent NPCs, and the formation of complete NPCs is delayed. Our work demonstrates that NPC spatial organization and number are independently determined and identifies NPC biogenesis as a process vulnerable to neurodevelopmental disease insults.
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Respiration of lipids by copepods during diapause (overwintering dormancy) contributes to ocean carbon sequestration via the seasonal lipid pump (SLP). Parameterizing this flux in predictive models requires a mechanistic understanding of how life history adaptation in copepods shapes their timing of exit from diapause. We investigate the optimal phenology of Calanus finmarchicus in the Norwegian Sea using an individual-based model in which diapause exit is represented as a trait characterized by phenotypic mean and variance. Without interannual variability, optimal exit correlated with the onset of the spring phytoplankton bloom and phenotypic variance was of no benefit. In contrast, copepods endured reduced fitness and adopted bet-hedging strategies when exposed to interannual variability in bloom timing and predation: later exit from diapause and phenotypic variance maintained adult numbers in anomalous late-bloom years. Exit nevertheless remained well before the peak of the bloom which is a favorable strategy when low predation early in the year enhances survival of eggs and early developmental stages. Our work highlights the complex interactions between C. finmarchicus and its environment and the need for improved understanding of bet-hedging strategies and the cues of diapause exit to progress the representation of the SLP in global biogeochemical models.
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Historically, neonatal neuroscience boasted a robust and successful preclinical pipeline for therapeutic interventions, in particular for the treatment of hypoxic-ischemic encephalopathy (HIE). However, since the successful translation of therapeutic hypothermia (TH), several high-profile failures of promising adjunctive therapies, in addition to the lack of benefit of TH in lower resource settings, have brought to light critical issues in that same pipeline. Using recent data from clinical trials of erythropoietin as an example, the authors highlight several key challenges facing preclinical neonatal neuroscience for HIE therapeutic development and propose key areas where model development and collaboration across the field in general can ensure ongoing success in treatment development for HIE worldwide.
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Eritropoyetina , Hipotermia Inducida , Hipoxia-Isquemia Encefálica , Humanos , Hipoxia-Isquemia Encefálica/terapia , Recién Nacido , Eritropoyetina/uso terapéutico , Hipotermia Inducida/métodos , Animales , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Melatonin is commonly used to treat sleep disturbance in children and adolescents, although uncertainties about its optimal use remain. OBJECTIVE: To determine to what extent prescribing of melatonin complies with evidence-based clinical practice standards. METHODS: As part of a quality improvement programme, the Prescribing Observatory for Mental Health conducted a retrospective clinical audit in UK services for children and adolescents. FINDINGS: Data were submitted for 4151 children and adolescents up to 18 years of age, treated with melatonin: 3053 (74%) had a diagnosis of neurodevelopmental disorder. In 2655 (73%) of the 3651 patients prescribed melatonin to be taken regularly, the main reason was to reduce sleep latency (time taken to fall asleep). In 409 patients recently starting melatonin, a non-pharmacological intervention had already been tried in 279 (68%). The therapeutic response of patients early in treatment (n=899) and on long-term treatment (n=2353) had been assessed and quantified in 36% and 31%, respectively, while for review of side effects, the respective proportions were 46% and 43%. Planned treatment breaks were documented in 317 (13%) of those on long-term treatment. CONCLUSIONS: Melatonin was predominantly prescribed for evidence-based clinical indications, but the clinical review and monitoring of this treatment fell short of best practice. CLINICAL IMPLICATIONS: With limited methodical review of melatonin use in their patients, clinicians will fail to garner reliable information on its risks and benefits for individual patients. The lack of such practice-based evidence may increase the risk of melatonin being inappropriately targeted or continued despite being ineffective or no longer indicated.
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Auditoría Clínica , Melatonina , Humanos , Melatonina/uso terapéutico , Melatonina/administración & dosificación , Niño , Adolescente , Reino Unido , Femenino , Masculino , Estudios Retrospectivos , Preescolar , Trastornos del Sueño-Vigilia/tratamiento farmacológico , Lactante , Depresores del Sistema Nervioso Central/uso terapéuticoRESUMEN
Background: Tracking the spread of antibiotic resistant bacteria is critical to reduce global morbidity and mortality associated with human and animal infections. There is a need to understand the role that wild animals in maintenance and transfer of antibiotic resistance genes (ARGs). Methods: This study used metagenomics to identify and compare the abundance of bacterial species and ARGs detected in the gut microbiomes from sympatric humans and wild mouse lemurs in a forest-dominated, roadless region of Madagascar near Ranomafana National Park. We examined the contribution of human geographic location toward differences in ARG abundance and compared the genomic similarity of ARGs between host source microbiomes. Results: Alpha and beta diversity of species and ARGs between host sources were distinct but maintained a similar number of detectable ARG alleles. Humans were differentially more abundant for four distinct tetracycline resistance-associated genes compared to lemurs. There was no significant difference in human ARG diversity from different locations. Human and lemur microbiomes shared 14 distinct ARGs with highly conserved in nucleotide identity. Synteny of ARG-associated assemblies revealed a distinct multidrug-resistant gene cassette carrying dfrA1 and aadA1 present in human and lemur microbiomes without evidence of geographic overlap, suggesting that these resistance genes could be widespread in this ecosystem. Further investigation into intermediary processes that maintain drug-resistant bacteria in wildlife settings is needed.
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Microbioma Gastrointestinal , Metagenoma , Animales , Madagascar , Humanos , Metagenoma/genética , Microbioma Gastrointestinal/genética , Simpatría , Población Rural , Metagenómica , Bacterias/genética , Bacterias/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Genes Bacterianos , Cheirogaleidae/genética , Cheirogaleidae/microbiologíaRESUMEN
When an electromagnetic (EM) wave propagates in a medium whose properties are varied abruptly in time, the wave experiences refractions and reflections known as time-refractions and time-reflections, both manifesting spectral translation as a consequence of the abrupt change of the medium and the conservation of momentum. However, while the time-refracted wave continues to propagate with the same wave-vector, the time-reflected wave propagates backward with a conjugate phase despite the lack of any spatial interface. Importantly, while time-refraction is always significant, observing time-reflection poses a major challenge - because it requires a large change in the medium occurring within a single cycle of the EM wave. For that reason, time-reflection of EM waves was observed only recently. Here, we present the observation of microwave pulses at the highest frequency ever observed (0.59 GHz), and the experimental evidence of the phase-conjugation nature of time-reflected waves. Our experiments are carried out in a periodically-loaded microstrip line with optically-controlled picosecond-switchable photodiodes. Our system paves the way to the experimental realization of Photonic Time-Crystals at GHz frequencies.
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From its inception as a two-dimensional snapshot of the beating heart, echocardiography has become an indelible part of cardiovascular diagnostics. The integration of ultrasound enhancing agents (UEAs) marks a pivotal transition, enhancing its diagnostic acumen beyond myocardial perfusion. These agents have refined echocardiography's capacity to visualize complex cardiac anatomy and pathology with unprecedented clarity, especially in non-coronary artery disease contexts. UEAs aid in detailed assessments of myocardial viability, endocardial border delineation in left ventricular opacification, and identification of intracardiac masses. Recent innovations in UEAs, accompanied by advancements in echocardiographic technology, offer clinicians a more nuanced view of cardiac function and blood flow dynamics. This review explores recent developments in these applications and future contemplated studies.
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Medios de Contraste , Ecocardiografía , Humanos , Ecocardiografía/métodos , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Aumento de la Imagen/métodos , MicroburbujasRESUMEN
BACKGROUND: This study's purpose was to assess whether larger volumes of reinfused unwashed shed autologous blood (SAB) were associated with adverse events within 30 days for patients undergoing open thoracoabdominal aortic aneurysm (TAAA) repair. During TAAA repair, our institution uses a system wherein SAB is filtered, but not washed or centrifuged, and then returned to the patient via a rapid-infusion device. By reinfusing SAB, the system preserves the patient's autologous whole blood and may reduce the number of allogenic transfusions required during TAAA repair, but the end-organ effects of reinfusing unwashed SAB have not been extensively evaluated. METHODS: Using a prospectively maintained database, we retrospectively analyzed data from 972 consecutive patients who underwent open TAAA repair at our institution from 2007 to 2021 and who received SAB. Multivariable logistic regressions were performed to assess whether SAB reinfusion volume was associated with a composite outcome of adverse events, as well as operative mortality, a composite of cardiac complications, a composite of pulmonary complications, or persistent paraplegia, stroke, or postoperative renal failure. RESULTS: Among the cohort of 972 patients, the median volume of reinfused SAB was 4159 mL (quartile1-quartile3 [Q1-Q3]: 2524-6790 mL). Greater reinfusion volumes of unwashed SAB were not associated with greater odds of composite adverse events (odds ratio [OR], 1.02 per 1000 mL increase, 97.5% confidence interval [CI], 0.94-1.09, P = .624), nor with any individual outcome-operative mortality (OR, 1.02 per 1000 mL increase, 97.5% CI, 0.93-1.12, P = .617), a composite of cardiac complications (OR, 0.98 per 1000 mL increase, 97.5% CI, 0.93-1.04, P = .447), a composite of pulmonary complications (OR, 1.00 per 1000 mL increase, 97.5% CI, 0.94-1.06, P = .963), renal failure necessitating hemodialysis (OR, 1.01 per 1000 mL increase, 97.5% CI, 0.92-1.11, P = .821), persistent paraplegia (OR, 0.97 per 1000 mL increase, 97.5% CI, 0.84-1.13, P = .676), persistent stroke (OR, 0.85 per 1000 mL increase, 97.5% CI, 0.70-1.04, P = .070), or reoperation to control bleeding (OR, 0.99, 97.5% CI, 0.87-1.13, P = .900)-when adjusted for confounders. CONCLUSIONS: For patients undergoing open TAAA repair, larger reinfusion volumes of unwashed SAB were not associated with greater odds of major early postoperative complications.