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The decay of an excited atom undergoing spontaneous photon emission into the fluctuating quantum-electrodynamic vacuum is an emblematic example of the dynamics of an open quantum system. Recent experiments have demonstrated that the gapped photon dispersion in periodic structures, which prevents photons in certain frequency ranges from propagating, can give rise to unusual spontaneous-decay behaviour, including the formation of dissipative bound states1-3. So far, these effects have been restricted to the optical domain. Here we demonstrate similar behaviour in a system of artificial emitters, realized using ultracold atoms in an optical lattice, which decay by emitting matter-wave, rather than optical, radiation into free space. By controlling vacuum coupling and the excitation energy, we directly observe exponential and partly reversible non-Markovian dynamics and detect a tunable bound state that contains evanescent matter waves. Our system provides a flexible platform for simulating open-system quantum electrodynamics and for studying dissipative many-body physics with ultracold atoms4-6.
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BACKGROUND: Many clinicians overestimate mortality and disability rates in infants born extremely preterm. We developed a digital tool ('NIC-PREDICT') that predicts infant mortality and survival with and without major disability in infants born 23-27 weeks' gestation. AIMS: To determine if clinicians could use NIC-PREDICT accurately, and if their perceptions of infant outcomes improved after its release in 2021. MATERIALS AND METHODS: Midwives, nurses, obstetricians, neonatologists and paediatricians working in tertiary and non-tertiary hospitals in Victoria were asked to use NIC-PREDICT to estimate three mutually exclusive outcomes: (i) mortality; (ii) survival free of major disability; and (iii) survival with major disability for six different scenarios where a liveborn infant was offered survival-focused care after birth. The proportions who completed the survey (responded to all six scenarios) and the proportions able to provide 100% accurate results for all scenarios were determined. Estimates of the three outcomes were compared with true rates. RESULTS: A total of 85 clinicians responded: 70 (82%) completed the survey, with an overall accuracy of 76%. Overall, predictions of mortality were accurate (mean difference from true value 0.7% (95% confidence interval (CI) -0.7, 2.1) P = 0.33), as were predictions of survival without major disability (mean difference - 0.7 (95% CI -3.0, 1.7) P = 0.58). However, survival with major disability was overestimated by 4.9% ((95% CI 1.7, 8.0) P = 0.003). CONCLUSIONS: Most perinatal clinicians who responded used NIC-PREDICT correctly to estimate expected outcomes in infants born extremely preterm who are offered intensive care. Undue pessimism about survival with major disability remains an ongoing concern.
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Mortalidade Infantil , Lactente Extremamente Prematuro , Humanos , Recém-Nascido , Vitória , Feminino , Lactente , Inquéritos e Questionários , Gravidez , Idade Gestacional , Atitude do Pessoal de SaúdeRESUMO
Chemical contaminants, such as pesticides, pharmaceuticals and industrial compounds are ubiquitous in surface water and sediment in areas subject to human activity. While targeted chemical analysis is typically used for water and sediment quality monitoring, there is growing interest in applying effect-based methods with in vitro bioassays to capture the effects of all active contaminants in a sample. The current study evaluated the biological effects in surface water and sediment from two contrasting catchments in Aotearoa New Zealand, the highly urbanised Whau River catchment in Tamaki Makaurau (Auckland) and the urban and mixed agricultural Koreti (New River) Estuary catchment. Two complementary passive sampling devices, Chemcatcher for polar chemicals and polyethylene (PED) for non-polar chemicals, were applied to capture a wide range of contaminants in water, while composite sediment samples were collected at each sampling site. Bioassays indicative of induction of xenobiotic metabolism, receptor-mediated effects, genotoxicity, cytotoxicity and apical effects were applied to the water and sediment extracts. Most sediment extracts induced moderate to strong estrogenic and aryl hydrocarbon (AhR) activity, along with moderate toxicity to bacteria. The water extracts showed similar patterns to the sediment extracts, but with lower activity. Generally, the polar Chemcatcher extracts showed greater estrogenic activity, photosynthesis inhibition and algal growth inhibition than the non-polar PED extracts, though the PED extracts showed greater AhR activity. The observed effects in the water extracts were compared to available ecological effect-based trigger values (EBT) to evaluate the potential risk. For the polar extracts, most sites in both catchments exceeded the EBT for estrogenicity, with many sites exceeding the EBTs for AhR activity and photosynthesis inhibition. Of the wide range of endpoints considered, estrogenic activity, AhR activity and herbicidal activity appear to be the primary risk drivers in both the Whau and Koreti Estuary catchments.
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Rios , Poluentes Químicos da Água , Humanos , Rios/química , Água/análise , Poluentes Químicos da Água/análise , Agricultura , Bioensaio , Polietileno , Monitoramento Ambiental/métodos , Sedimentos Geológicos/químicaRESUMO
OBJECTIVE: To determine if risk-adjusted survival of patients with CDH has improved over the last 25 years within centers that are long-term, consistent participants in the CDH Study Group (CDHSG). SUMMARY BACKGROUND DATA: The CDHSG is a multicenter collaboration focused on evaluation of infants with CDH. Despite advances in pediatric surgical and intensive care, CDH mortality has appeared to plateau. Herein, we studied CDH mortality rates amongst long-term contributors to the CDHSG. METHODS: We divided registry data into 5-year intervals, with Era 1 (E1) beginning in 1995, and analyzed multiple variables (operative strategy, defect size, and mortality) to assess evolution of disease characteristics and severity over time. For mortality analyses, patients were risk stratified using a validated prediction score based on 5-minute Apgar (Apgar5) and birth weight. A risk-adjusted, observed to expected (O:E) mortality model was created using E1 as a reference. RESULTS: 5203 patients from 23 centers with >22years of participation were included. Birth weight, Apgar5, diaphragmatic agenesis, and repair rate were unchanged over time (all P > 0.05). In E5 compared to E1, minimally invasive and patch repair were more prevalent, and timing of diaphragmatic repair was later (all P < 0.01). Overall mortality decreased over time: E1 (30.7%), E2 (30.3%), E3 (28.7%), E4 (26.0%), E5 (25.8%) ( P = 0.03). Risk-adjusted mortality showed a significant improvement in E5 compared to E1 (OR 0.78, 95% CI 0.62-0.98; P = 0.03). O:E mortality improved over time, with the greatest improvement in E5. CONCLUSIONS: Risk-adjusted and observed-to-expected CDH mortality have improved over time.
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Hérnias Diafragmáticas Congênitas , Lactente , Criança , Humanos , Hérnias Diafragmáticas Congênitas/cirurgia , Peso ao Nascer , Sistema de RegistrosRESUMO
In mammalian cells, growth factor-induced intracellular signaling and protein synthesis play a critical role in cellular physiology and homeostasis. In the brain's glymphatic system (GS), the water-conducting activity of aquaporin-4 (AQPN-4) membrane channels (expressed in polarized fashion on astrocyte end-feet) mediates the clearance of wastes through the convective transport of fluid and solutes through the perivascular space. The glycoprotein erythropoietin (EPO) has been shown to induce the astrocyte expression of AQPN-4 via signaling through the EPO receptor and the JAK/STAT signaling pathway. Here, we self-assemble EPO in a multivalent fashion onto the surface of semiconductor quantum dots (QDs) (driven by polyhistidine-based self-assembly) to drive the interaction of the bioconjugates with EPOR on human astrocytes (HA). This results in a 2-fold augmentation of JAK/STAT signaling activity and a 1.8-fold enhancement in the expression of AQPN-4 in cultured primary HA compared to free EPO. This translates into a 2-fold increase in the water transport rate in HA cells as measured by the calcein AM water transport assay. Importantly, EPO-QD-induced augmented AQPN-4 expression does not elicit any deleterious effect on the astrocyte viability. We discuss our results in the context of the implications of EPO-nanoparticle (NP) bioconjugates for use as research tools to understand the GS and their potential as therapeutics for the modulation of GS function. More generally, our results illustrate the utility of NP bioconjugates for the controlled modulation of growth factor-induced intracellular signaling.
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Aquaporinas , Eritropoetina , Pontos Quânticos , Animais , Humanos , Astrócitos/metabolismo , Receptores da Eritropoetina/metabolismo , Eritropoetina/metabolismo , Eritropoetina/farmacologia , Água/metabolismo , Aquaporinas/metabolismo , Aquaporinas/farmacologia , Mamíferos/metabolismoRESUMO
Among zygomaticomaxillary complex (ZMC) fractures presenting to a tertiary urban academic center, the authors hypothesized the presence of both clinical and radiographic predictors of operative management. The investigators conducted a retrospective cohort study of 1,914 patients with facial fractures managed at an academic medical center in New York City between 2008 and 2017. The predictor variables were based on both clinical data and features of pertinent imaging studies, and the outcome variable was an operative intervention. Descriptive and bivariate statistics were computed and the p-value was set at 0.05. In total, 196 patients sustained ZMC fractures (5.0%) and 121 (61.7%) ZMC fractures were treated surgically. All patients who presented with globe injury, blindness, retrobulbar injury, restricted gaze, or enophthalmos and a concurrent ZMC fracture were managed surgically. The most common surgical approach was the gingivobuccal corridor (31.9% of all approaches), and there were no significant immediate postoperative complications. Younger patients (38.9 ± 18 years vs. 56.1 ± 23.5 years, p < 0.0001) and patients with greater than or equal to 4 mm of orbital floor displacement were more likely to receive surgical treatment than observation (82 vs. 56%, p = 0.045), as were patients with comminuted orbital floor fractures (52 vs. 26%, p = 0.011). In this cohort, patients more likely to undergo surgical reduction were young patients with ophthalmologic symptoms on presentation and at least 4 mm displacement of the orbital floor. Low kinetic energy ZMC fractures may warrant surgical management as often as high-energy ZMC fractures. While orbital floor comminution has been shown to be a predictor for operative reduction, in this study we also demonstrated a difference in the rate of reduction based on the severity of orbital floor displacement. This may have significant implications in both the triage and selection of patients most suitable for operative repair.
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Fraturas Cominutivas , Fraturas Maxilares , Fraturas Orbitárias , Fraturas Cranianas , Fraturas Zigomáticas , Humanos , Estudos Retrospectivos , Fraturas Zigomáticas/cirurgia , Fraturas Maxilares/cirurgia , Fraturas Orbitárias/complicações , Fraturas Cominutivas/complicaçõesRESUMO
BACKGROUND: Age-related macular degeneration (AMD) is a common retinal degenerative disorder among older individuals. Amyloid deposits, a hallmark of cerebral amyloid angiopathy (CAA), may be involved in the pathogenesis of AMD. Since amyloid deposits may contribute to the development of both AMD and CAA, we hypothesized that patients with AMD have a higher prevalence of CAA. OBJECTIVE: To compare the prevalence of CAA in patients with or without AMD matched for age. METHODS: We conducted a cross-sectional, 1:1 age-matched, case-control study of patients ≥40 years of age at the Mayo Clinic who had undergone both retinal optical coherence tomography and brain MRI from 2011 to 2015. Primary dependent variables were probable CAA, superficial siderosis, and lobar and deep cerebral microbleeds (CMBs). The relationship between AMD and CAA was assessed using multivariable logistic regression and was compared across AMD severity (none vs early vs late AMD). RESULTS: Our analysis included 256 age-matched pairs (AMD 126, no AMD 130). Of those with AMD, 79 (30.9%) had early AMD and 47 (19.4%) had late AMD. The mean age was 75±9 years, and there was no significant difference in vascular risk factors between groups. Patients with AMD had a higher prevalence of CAA (16.7% vs 10.0%, p=0.116) and superficial siderosis (15.1% vs 6.2%, p=0.020), but not deep CMB (5.2% vs 6.2%, p=0.426), compared to those without AMD. After adjusting for covariates, having late AMD was associated with increased odds of CAA (OR 2.83, 95% CI 1.10-7.27, p=0.031) and superficial siderosis (OR 3.40, 95%CI 1.20-9.65, p=0.022), but not deep CMB (OR 0.7, 95%CI 0.14-3.51, p=0.669). CONCLUSIONS: AMD was associated with CAA and superficial siderosis but not deep CMB, consistent with the hypothesis that amyloid deposits play a role in the development of AMD. Prospective studies are needed to determine if features of AMD may serve as biomarkers for the early diagnosis of CAA.
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Angiopatia Amiloide Cerebral , Degeneração Macular , Siderose , Humanos , Idoso , Idoso de 80 Anos ou mais , Adulto , Hemorragia Cerebral/etiologia , Estudos de Casos e Controles , Estudos Transversais , Placa Amiloide/complicações , Angiopatia Amiloide Cerebral/complicações , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Angiopatia Amiloide Cerebral/epidemiologia , Imageamento por Ressonância Magnética/efeitos adversos , Degeneração Macular/diagnóstico por imagem , Degeneração Macular/epidemiologiaRESUMO
Effective sampling for severe acute respiratory syndrome 2 (SARS-CoV-2) is a common approach for monitoring disinfection efficacy and effective environmental surveillance. This study evaluated sampling efficiency and limits of detection (LODs) of macrofoam swab and sponge stick sampling methods for recovering infectious SARS-CoV-2 and viral RNA (vRNA) from surfaces. Macrofoam swab and sponge stick methods were evaluated for collection of SARS-CoV-2 suspended in a soil load from 6-in2 coupons composed of four materials: stainless steel (SS), acrylonitrile butadiene styrene (ABS) plastic, bus seat fabric, and Formica. Recovery of infectious SARS-CoV-2 was more efficient than vRNA recovery on all materials except Formica (macrofoam swab sampling) and ABS (sponge stick sampling). Macrofoam swab sampling recovered significantly more vRNA from Formica than ABS and SS, and sponge stick sampling recovered significantly more vRNA from ABS than Formica and SS, suggesting that material and sampling method choice can affect surveillance results. Time since initial contamination significantly affected infectious virus recovery from all materials, with vRNA recovery showing limited to no difference, suggesting that SARS-CoV-2 vRNA can remain detectable after viral infectivity has dissipated. This study showed that a complex relationship exists between sampling method, material, time from contamination to sampling, and recovery of SARS-CoV-2. In conclusion, data show that careful consideration be used when selecting surface types for sampling and interpreting SARS-CoV-2 vRNA recovery with respect to presence of infectious virus.
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COVID-19 , SARS-CoV-2 , Humanos , Tato , Aço InoxidávelRESUMO
Cognitive processes that require spatial information rely on synaptic plasticity in the dorsal CA1 area (dCA1) of the hippocampus. Since the function of the hippocampus is impaired in aged individuals, it remains unknown how aged animals make spatial choices. Here, we used IntelliCage to study behavioral processes that support spatial choices of aged female mice living in a group. As a proxy of training-induced synaptic plasticity, we analyzed the morphology of dendritic spines and the expression of a synaptic scaffold protein, PSD-95. We observed that spatial choice training in young adult mice induced correlated shrinkage of dendritic spines and downregulation of PSD-95 in dCA1. Moreover, long-term depletion of PSD-95 by shRNA in dCA1 limited correct choices to a reward corner, while reward preference was intact. In contrast, old mice used behavioral strategies characterized by an increased tendency for perseverative visits and social interactions. This strategy resulted in a robust preference for the reward corner during the spatial choice task. Moreover, training decreased the correlation between PSD-95 expression and the size of dendritic spines. Furthermore, PSD-95 depletion did not impair place choice or reward preference in old mice. Thus, our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices, old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment.SIGNIFICANCE STATEMENT It remains poorly understood how aging affects behavioral and molecular processes that support cognitive functions. It is, however, essential to understand these processes to develop therapeutic interventions that support successful cognitive aging. Our data indicate that while young mice require PSD-95-dependent synaptic plasticity in dCA1 to make correct spatial choices (i.e., choices that require spatial information), old animals observe cage mates and stick to a preferred corner to seek the reward. This strategy is resistant to the depletion of PSD-95 in the CA1 area. Overall, our study demonstrates that aged mice combine alternative behavioral and molecular strategies to approach and consume rewards in a complex environment. Second, the contribution of PSD-95-dependent synaptic functions in spatial choice changes with age.
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Região CA1 Hipocampal/fisiologia , Comportamento de Escolha/fisiologia , Proteína 4 Homóloga a Disks-Large/fisiologia , Percepção Espacial/fisiologia , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Espinhas Dendríticas/fisiologia , Proteína 4 Homóloga a Disks-Large/genética , Meio Ambiente , Feminino , Regulação da Expressão Gênica/genética , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Recompensa , Interação SocialRESUMO
AIMS: Antimicrobial coatings, for use in combination with routine cleaning and disinfection, were evaluated for their effectiveness in reducing virus concentration on stainless steel surfaces. METHODS: Twenty antimicrobial coating products, predominantly composed of organosilane quaternary ammonium compounds, were applied to stainless steel coupons, dried overnight and evaluated for efficacy against Φ6, an enveloped bacteriophage. Additionally, two peel and stick polymer-based films, a copper-based film and three copper alloys were evaluated. Efficacy was determined by comparison of recoveries from uncoated (positive control) and coated (test) surfaces. RESULTS: The results indicated that some of the coating products initially demonstrated >3-log reduction of Φ6; no direct correlation of efficacy was observed with an active ingredient or its concentration. The peel and stick films and copper alloys each demonstrated efficacy in initial testing. However, none of the spray-based products retained efficacy after subjecting the coating to abrasion with either a hypochlorite or quaternary ammonium-based solution applied in accordance with EPA Interim Guidance for Evaluating the Efficacy of Antimicrobial Surface Coatings. Of the products tested for this durability, only one peel and stick polymeric film retained efficacy; the copper alloys were not tested for their durability in this study. CONCLUSIONS: These results suggest that while some organosilane quaternary ammonium compound-based products demonstrate antiviral efficacy, more research and development is needed to understand effective formulations with sufficient durability to perform as supplements to routine cleaning and disinfection.
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Anti-Infecciosos , Bacteriófagos , Antibacterianos , Anti-Infecciosos/farmacologia , Desinfecção , Aço InoxidávelRESUMO
AIMS: This study aimed to provide operationally relevant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface disinfection efficacy information. METHODS AND RESULTS: Three EPA-registered disinfectants (Vital Oxide, Peroxide, and Clorox Total 360) and one antimicrobial formulation (CDC bleach) were evaluated against SARS-CoV-2 on material coupons and were tested using Spray (no touch with contact time) and Spray & Wipe (wipe immediately post-application) methods immediately and 2 h post-contamination. Efficacy was evaluated for infectious virus, with a subset tested for viral RNA (vRNA) recovery. Efficacy varied by method, disinfectant, and material. CDC bleach solution showed low efficacy against SARS-CoV-2 (log reduction < 1.7), unless applied via Spray & Wipe. Additionally, mechanical wiping increased the efficacy of treatments against SARS-CoV-2. The recovery of vRNA post-disinfection suggested that vRNA may overestimate infectious virus remaining. CONCLUSIONS: Efficacy depends on surface material, chemical, and disinfection procedure, and suggests that mechanical wiping alone has some efficacy at removing SARS-CoV-2 from surfaces. We observed that disinfectant treatment biased the recovery of vRNA over infectious virus. SIGNIFICANCE AND IMPACT OF STUDY: These data are useful for developing effective, real-world disinfection procedures, and inform public health experts on the utility of PCR-based surveillance approaches.
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AIMS: This study evaluated the residual efficacy of commercially available antimicrobial coatings or films against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on non-porous surfaces. METHODS AND RESULTS: Products were applied to stainless steel or ABS plastic coupons and dried overnight. Coupons were inoculated with SARS-CoV-2 in the presence of 5% soil load. Recovered infectious SARS-CoV-2 was quantified by TCID50 assay. Tested product efficacies ranged from <1.0 to >3.0 log10 reduction at a 2-h contact time. The log10 reduction in recovered infectious SARS-CoV-2 ranged from 0.44 to 3 log10 reduction on stainless steel and 0.25 to >1.67 log10 on ABS plastic. The most effective products tested contained varying concentrations (0.5%-1.3%) of the same active ingredient: 3-(trihydroxysilyl) propyldimethyloctadecyl ammonium chloride. Products formulated with other quaternary ammonium compounds were less effective against SARS-CoV-2 in this test. CONCLUSIONS: The residual antimicrobial products tested showed varied effectiveness against SARS-CoV-2 as a function of product tested. Several products were identified as efficacious against SARS-CoV-2 on both stainless steel and ABS plastic surfaces under the conditions evaluated. Differences in observed efficacy may be due to variation in active ingredient formulation; efficacy is, therefore, difficult to predict based upon listed active ingredient and its concentration. SIGNIFICANCE AND IMPACT: This study highlights the formulation-specific efficacy of several products against SARS-CoV-2 and may inform future development of residual antiviral products for use on non-porous surfaces. The identification of antimicrobial coatings or films showing promise to inactivate SARS-CoV-2 suggests that these products may be worth future testing and consideration.
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Anti-Infecciosos , Tratamento Farmacológico da COVID-19 , Antibacterianos , Anti-Infecciosos/farmacologia , Antivirais/farmacologia , Humanos , SARS-CoV-2RESUMO
PURPOSE: Understanding the impact of fluid in different retinal compartments is critical to developing treatment paradigms that optimize visual acuity and reduce treatment burden in neovascular age-related macular degeneration. This systematic review aimed to determine the impact of persistent/new subretinal fluid, intraretinal fluid, and subretinal pigment epithelial fluid on visual acuity over 1 year of treatment. METHODS: Publication eligibility and data extraction were conducted according to Cochrane methods: 27 of the 1,797 screened records were eligible. RESULTS: Intraretinal fluid negatively affected visual acuity at baseline and throughout treatment, with foveal intraretinal fluid associated with lower visual acuity than extrafoveal intraretinal fluid. Some studies found that subretinal fluid (particularly subfoveal) was associated with higher visual acuity at Year 1 and longer term, and others suggested subretinal fluid did not affect visual acuity at Years 1 and 2. Data on the effects of subretinal pigment epithelial fluid were scarce, and consensus was not reached. Few studies reported numbers of injections associated with fluid status. CONCLUSION: To optimally manage neovascular age-related macular degeneration, clinicians should understand the impact of fluid compartments on visual acuity. After initial treatment, antivascular endothelial growth factor regimens that tolerate stable subretinal fluid (if visual acuity is stable/improved) but not intraretinal fluid may enable patients to achieve their best possible visual acuity. Confirmatory studies are required to validate these findings.
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Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese/uso terapêutico , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Ranibizumab/uso terapêutico , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
PURPOSE: To evaluate the safety and therapeutic effects of orally administered AKST4290 (formerly BI 144807 and ALK4290) in treatment-naive patients with neovascular age-related macular degeneration. METHODS: In this prospective, multicenter, open-label Phase 2a pilot clinical study, 30 patients with newly diagnosed neovascular age-related macular degeneration self-administered AKST4290 (400 mg) orally twice daily for 6 weeks. Patients were examined weekly for safety, to measure best-corrected visual acuity (BCVA), and to perform exploratory morphologic assessments. The primary endpoint was the mean change in BCVA from baseline to end of treatment, and the secondary endpoint was safety. Exploratory endpoints investigated potential changes in macular morphology. RESULTS: Mean BCVA improved by +7.0 letters (95% CI, 2.2-11.7); 24 patients (82.8%) had stable or improved BCVA, with 6 (20.7%) gaining ≥15 letters. No patients experienced severe or serious adverse events. CONCLUSION: In this 6-week study, AKST4290 treatment was associated with improved BCVA scores in patients with treatment-naive neovascular age-related macular degeneration. All adverse events were mild or moderate in severity and no safety issues were identified. Treatment of neovascular age-related macular degeneration with AKST4290 warrants further investigation in randomized, placebo-controlled trials.
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Degeneração Macular , Degeneração Macular Exsudativa , Inibidores da Angiogênese , Humanos , Injeções Intravítreas , Degeneração Macular/tratamento farmacológico , Estudos Prospectivos , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Degeneração Macular Exsudativa/induzido quimicamente , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/tratamento farmacológicoRESUMO
When the COVID-19 pandemic suddenly prevented medical students from attending their clinical attachments, the faculty involved in the third year of medical school (MBChB3) at the University of Glasgow created Virtual Wards. The focus of the Virtual Wards was to continue teaching of clinical reasoning remotely whilst COVID-19 restrictions were in place. Virtual Wards were mapped to the common and important presentations and conditions and provided opportunity for history-taking, clinical examination skills, requesting investigations, interpreting results, diagnosis and management. The Virtual Wards were successful, and further wards were developed the following academic year for MBChB4 students. This chapter describes the theoretical underpinnings of the Virtual Wards and the technological considerations, followed by a description of the Wards themselves. We then analyse an evaluation of the Virtual Wards and provide both a faculty and student perspective. Throughout the chapter, we provide tips for educators developing Virtual Ward environments.
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COVID-19 , Estudantes de Medicina , Competência Clínica , Humanos , Pandemias/prevenção & controle , SARS-CoV-2RESUMO
An Australian estuarine isolate of Penicillium sp. MST-MF667 yielded 3 tetrapeptides named the bilaids with an unusual alternating LDLD chirality. Given their resemblance to known short peptide opioid agonists, we elucidated that they were weak (Ki low micromolar) µ-opioid agonists, which led to the design of bilorphin, a potent and selective µ-opioid receptor (MOPr) agonist (Ki 1.1 nM). In sharp contrast to all-natural product opioid peptides that efficaciously recruit ß-arrestin, bilorphin is G protein biased, weakly phosphorylating the MOPr and marginally recruiting ß-arrestin, with no receptor internalization. Importantly, bilorphin exhibits a similar G protein bias to oliceridine, a small nonpeptide with improved overdose safety. Molecular dynamics simulations of bilorphin and the strongly arrestin-biased endomorphin-2 with the MOPr indicate distinct receptor interactions and receptor conformations that could underlie their large differences in bias. Whereas bilorphin is systemically inactive, a glycosylated analog, bilactorphin, is orally active with similar in vivo potency to morphine. Bilorphin is both a unique molecular tool that enhances understanding of MOPr biased signaling and a promising lead in the development of next generation analgesics.
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Analgésicos Opioides/farmacologia , Proteínas Fúngicas/farmacologia , Oligopeptídeos/farmacologia , Penicillium/química , Receptores Opioides mu/agonistas , Analgésicos Opioides/química , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Proteínas Fúngicas/química , Células HEK293 , Humanos , Camundongos , Simulação de Acoplamento Molecular , Oligopeptídeos/química , Ligação Proteica , Receptores Opioides mu/química , Receptores Opioides mu/metabolismoRESUMO
BACKGROUND: Decision-making for infants born at 23-25 weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. AIMS: To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25 weeks' gestation, and if accuracy had changed over a decade. MATERIALS AND METHODS: A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. RESULTS: Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P < 0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P < 0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. CONCLUSIONS: Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25 weeks' gestation, which may translate into overly pessimistic counselling of parents.
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Recém-Nascido Prematuro , Tocologia , Feminino , Idade Gestacional , Humanos , Lactente , Mortalidade Infantil , Recém-Nascido , Parto , Gravidez , Inquéritos e QuestionáriosRESUMO
This study evaluated the efficacy of detergent-based surface cleaning methods against Murine Hepatitis Virus A59 (MHV) as a surrogate coronavirus for SARS-CoV-2. MHV (5% soil load in culture medium or simulated saliva) was inoculated onto four different high-touch materials [stainless steel (SS), Acrylonitrile Butadiene Styrene plastic (ABS), Formica, seat fabric (SF)]. Immediately and 2-hr post-inoculation, coupons were cleaned (damp wipe wiping) with and without pretreatment with detergent solution or 375 ppm hard water. Results identified that physical removal (no pretreatment) removed >2.3 log10 MHV on ABS, SS, and Formica when surfaces were cleaned immediately. Pretreatment with detergent or hard water increased effectiveness over wet wiping 2-hr post-inoculation; pretreatment with detergent significantly increased (p ≤ 0.05) removal of MHV in simulated saliva, but not in culture media, over hard water pretreatment (Formica and ABS). Detergent and hard water cleaning methods were ineffective on SF under all conditions. Overall, efficacy of cleaning methods against coronaviruses are material- and matrix-dependent; pre-wetting surfaces with detergent solutions increased efficacy against coronavirus suspended in simulated saliva. This study provides data highlighting the importance of incorporating a pre-wetting step prior to detergent cleaning and can inform cleaning strategies to reducing coronavirus surface transmission.
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COVID-19 , Vírus da Hepatite Murina , Animais , Detergentes , Humanos , Camundongos , Porosidade , SARS-CoV-2RESUMO
OBJECTIVE. The study's aim was to assess MRI, in cases in which MRI was deemed clinically necessary, to determine its diagnostic accuracy for placental adhesion disorder (PAD) and prognostic accuracy for massive postpartum hemorrhage (PPH). Additionally, we investigated the diagnostic utility of MRI in the antenatal workup of PAD as an adjunct to clinical assessment and ultrasound. MATERIALS AND METHODS. We retrospectively identified patients who underwent antenatal MRI for suspicion of PAD. Images were reviewed by two radiologists who were blinded to surgical and pathologic outcomes. Diagnostic utility of various clinical, ultrasound, and MRI features of PAD were estimated by ROC analysis. Logistic regression analysis was performed to assess various diagnostic models for PAD and prognostic models for massive PPH, with model selection based on Bayesian information criterion. RESULTS. Fifty-six patients met the inclusion criteria. Sensitivity and specificity of MRI in the diagnosis of PAD were 93% and 81%, respectively. The most accurate MRI features for PAD were myometrial thinning (AUC = 0.881), heterogeneous placenta (AUC = 0.864), and placental bulge (AUC = 0.845). The most accurate MRI features for massive PPH were heterogeneous placenta (AUC = 0.872) and dark intraplacental bands (AUC = 0.736). The addition of MRI to a model based on clinical and ultrasound features was preferred for both diagnosis of PAD and prognosis of massive PPH. CONCLUSION. This study shows the utility of certain MRI features for identification of PAD and massive PPH. Furthermore, our data show a substantial incremental benefit of the addition of MRI in the antenatal workup for PAD compared with clinical assessment and ultrasound alone.
Assuntos
Imageamento por Ressonância Magnética/métodos , Placenta Acreta/diagnóstico por imagem , Placenta Prévia/diagnóstico por imagem , Placentação , Hemorragia Pós-Parto/diagnóstico por imagem , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Placenta/diagnóstico por imagem , Valor Preditivo dos Testes , Gravidez , Diagnóstico Pré-Natal/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto JovemRESUMO
The design of nanoparticles is critical for their efficient use in many applications ranging from biomedicine to sensing and energy. While shape and size are responsible for the properties of the inorganic nanoparticle core, the choice of ligands is of utmost importance for the colloidal stability and function of the nanoparticles. Moreover, the selection of ligands employed in nanoparticle synthesis can determine their final size and shape. Ligands added after nanoparticle synthesis infer both new properties as well as provide enhanced colloidal stability. In this article, we provide a comprehensive review on the role of the ligands with respect to the nanoparticle morphology, stability, and function. We analyze the interaction of nanoparticle surface and ligands with different chemical groups, the types of bonding, the final dispersibility of ligand-coated nanoparticles in complex media, their reactivity, and their performance in biomedicine, photodetectors, photovoltaic devices, light-emitting devices, sensors, memory devices, thermoelectric applications, and catalysis.