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The rising humid heat is regarded as a severe threat to human survivability, but the proper integration of humid heat into heat-health alerts is still being explored. Using state-of-the-art epidemiological and climatological datasets, we examined the association between multiple heat stress indicators (HSIs) and daily human mortality in 739 cities worldwide. Notable differences were observed in the long-term trends and timing of heat events detected by HSIs. Air temperature (Tair) predicts heat-related mortality well in cities with a robust negative Tair-relative humidity correlation (CT-RH). However, in cities with near-zero or weak positive CT-RH, HSIs considering humidity provide enhanced predictive power compared to Tair. Furthermore, the magnitude and timing of heat-related mortality measured by HSIs could differ largely from those associated with Tair in many cities. Our findings provide important insights into specific regions where humans are vulnerable to humid heat and can facilitate the further enhancement of heat-health alert systems.
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Background: Transitional medication safety is crucial, as miscommunication about medication changes can lead to significant risks. Unclear or incomplete documentation during care transitions can result in outdated or incorrect medication lists at discharge, potentially causing medication errors, adverse drug events, and inadequate patient education. These issues are exacerbated by extended hospital stays and multiple care events, making accurate medication recall challenging at discharge. Objective: Thus, we aimed to investigate how real-time documentation of in-hospital medication changes prevents undocumented medication changes at discharge and improves physician-pharmacist communication. Methods: We conducted a retrospective cohort study in a tertiary hospital. Two pharmacists reviewed medical records of patients admitted to the acute medical unit from April to June 2020. In-hospital medication discrepancies were determined by comparing preadmission and hospitalization medication lists and it was verified whether the physician's intent of medication changes was clarified by documentation. By a documentation rate of medication changes of 100% and <100%, respectively, fully documented (FD) and partially documented (PD) groups were defined. Any undocumented medication changes at discharge were considered a "documentation error at discharge". Pharmacists' survey was conducted to assess the impact of appropriate documentation on the pharmacists. Results: After reviewing 400 medication records, patients were categorized into FD (61.3%) and PD (38.8%) groups. Documentation errors at discharge were significantly higher in the PD than in the FD group. Factors associated with documentation errors at discharge included belonging to the PD group, discharge from a non-hospitalist-managed ward, and having three or more intentional discrepancies. Pharmacists showed favorable attitudes towards physician's documentation. Conclusion: Appropriate documentation of in-hospital medication changes, facilitated by free-text communication, significantly decreased documentation errors at discharge. This analysis underlines the importance of communication between pharmacists and hospitalists in improving patient safety during transitions of care.
During transitions of care, communication failures among healthcare professionals can lead to medication errors. Therefore, effective sharing of information is essential, especially when intentional changes in prescription orders are made. Documenting medication changes facilitates real-time communication, potentially improving medication reconciliation and reducing discrepancies. However, inadequate documentation of medication changes is common in clinical practice. This retrospective cohort study underlines the importance of real-time documentation of in-hospital medication changes. There was a significant reduction in documentation errors at discharge in fully documented group, where real-time documentation of medication changes was more prevalent. Pharmacists showed favorable attitudes toward the physician's real-time documenting of medication changes because it provided valuable information on understanding the physician's intent and improving communication and also saved time for pharmacists. This study concludes that physicians' documentation on medication changes may reduce documentation errors at discharge, meaning that proper documentation of medication changes could enhance patient safety through effective communication.
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De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice. Unexpectedly, these DEPs, in conjunction with previously identified CYFIP2 brain interactors, included not only other WRC components but also numerous proteins associated with membraneless organelles (MLOs) involved in mRNA processing and translation within cells, including the nucleolus, stress granules, and processing bodies. Additionally, single-cell transcriptomic analysis of the Cyfip2 knock-out forebrain revealed gene expression changes linked to cellular stress responses and MLOs. We also observed morphological changes in MLOs in Cyfip2 knock-out brains and CYFIP2 knock-down cells under basal and stress conditions. Lastly, we demonstrated that CYFIP2 knock-down in cells, potentially through WRC-dependent actin regulation, suppressed the phosphorylation levels of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), thereby enhancing protein synthesis. These results suggest a physical and functional connection between CYFIP2 and various MLO proteins and also extend CYFIP2's role within the WRC from actin regulation to influencing eIF2α phosphorylation and protein synthesis. With these dual functions, CYFIP2 may fine-tune the balance between MLO formation/dynamics and protein synthesis, a crucial aspect of proper mRNA processing and translation.
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In this article, we present a comprehensive compilation of open access daily time-series datasets tailored to assess the temperature-mortality association. The data consists of daily mortality counts and average ambient temperature at various levels of geographic aggregation, including data from four cities, ten regions, and two counties, which have been utilised in previously published studies. These datasets are applicable for time-series regression analysis to estimate location-specific temperature-mortality associations. Additionally, the availability of data from multiple geographical locations enabled the exploration of geographical differences by pooling associations using meta-analysis. This compilation aims to serve as a valuable resource for researchers, educators, and students, facilitating their application of time-series regression modelling for research endeavours and training activities.
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Surface-enhanced Raman spectroscopy (SERS) tagging using silica(SiO2)@Ag nanoparticles (NPs) is easy to handle and is being studied in various fields, including SERS imaging and immunoassays. This is primarily due to its structural advantages, characterized by high SERS activity. However, the Ag NPs introduced onto the SiO2 surface may undergo structural transformation owing to the Ostwald ripening phenomenon under various conditions. As a result, the consistency of the SERS signal decreases, reducing their usability as SERS substrates. Until recently, research has been actively conducted to improve the stability of single Ag NPs. However, research on SiO2@Ag NPs used as a SERS-tagging material is still lacking. In this study, we utilized a Raman labeling compound (RLC) to prevent the structural deformation of SiO2@Ag NPs under various conditions and proposed excellent SiO2@Ag@RLC-Pre NPs as a SERS-tagging material. Using various RLCs, we confirmed that 4-mercaptobenzoic acid (4-MBA) is the RLC that maintains the highest stability for 2 months. These results were also observed for the SiO2@Ag NPs, which were unstable under various pH and temperature conditions. We believe that SERS tags using SiO2@Ag NPs and 4-MBA can be utilized in various applications on based SERS because of the high stability and consistency of the resulting SERS signal.
Subject(s)
Metal Nanoparticles , Silicon Dioxide , Silver , Spectrum Analysis, Raman , Silicon Dioxide/chemistry , Silver/chemistry , Metal Nanoparticles/chemistry , Surface Properties , Sulfhydryl Compounds/chemistry , Benzoates/chemistryABSTRACT
The cytoplasmic FMR1-interacting protein 2 (CYFIP2) have diverse molecular functions in neurons, including the regulation of actin polymerization, mRNA translation, and mitochondrial morphology and function. Mutations in the CYFIP2 gene are associated with early-onset epilepsy and neurodevelopmental disorders, while decreases in its protein levels are linked to Alzheimer's disease (AD). Notably, previous research has revealed AD-like phenotypes, such as dendritic spine loss, in the hippocampal CA1 pyramidal neurons of 12-month-old Cyfip2 heterozygous mice but not of age-matched CA1 pyramidal neuron-specific Cyfip2 conditional knock-out (cKO) mice. This study aims to investigate whether dendritic spine loss in Cyfip2 cKO mice is merely delayed compared to Cyfip2 heterozygous mice, and to explore further neuronal phenotypes regulated by CYFIP2 in aged mice. We characterized dendrite and dendritic protrusion morphologies, along with excitatory/inhibitory synapse densities in CA1 pyramidal neurons of 17-month-old Cyfip2 cKO mice. Overall dendritic branching was normal, with a reduction in the length of basal, not apical, dendrites in CA1 pyramidal neurons of Cyfip2 cKO mice. Furthermore, while dendritic protrusion density remained normal, alterations were observed in the length of mushroom spines and the head volume of stubby spines in basal, not apical, dendrites of Cyfip2 cKO mice. Although excitatory synapse density remained unchanged, inhibitory synapse density increased in apical, not basal, dendrites of Cyfip2 cKO mice. Consequently, a cell-autonomous reduction of CYFIP2 appears insufficient to induce dendritic spine loss in CA1 pyramidal neurons of aged mice. However, CYFIP2 is required to maintain normal dendritic length, dendritic protrusion morphology, and inhibitory synapse density.
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Nanoparticles, exhibiting functionally relevant structural heterogeneity, are at the forefront of cutting-edge research. Now, high-throughput single-particle imaging (SPI) with X-ray free-electron lasers (XFELs) creates opportunities for recovering the shape distributions of millions of particles that exhibit functionally relevant structural heterogeneity. To realize this potential, three challenges have to be overcome: (1) simultaneous parametrization of structural variability in real and reciprocal spaces; (2) efficiently inferring the latent parameters of each SPI measurement; (3) scaling up comparisons between 105 structural models and 106 XFEL-SPI measurements. Here, we describe how we overcame these three challenges to resolve the nonequilibrium shape distributions within millions of gold nanoparticles imaged at the European XFEL. These shape distributions allowed us to quantify the degree of asymmetry in these particles, discover a relatively stable "shape envelope" among nanoparticles, discern finite-size effects related to shape-controlling surfactants, and extrapolate nanoparticles' shapes to their idealized thermodynamic limit. Ultimately, these demonstrations show that XFEL SPI can help transform nanoparticle shape characterization from anecdotally interesting to statistically meaningful.
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The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein's crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.
Subject(s)
Catalytic Domain , Coronavirus 3C Proteases , Cysteine , Disulfides , Oxidation-Reduction , SARS-CoV-2 , Disulfides/chemistry , Disulfides/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/chemistry , Coronavirus 3C Proteases/metabolism , Coronavirus 3C Proteases/chemistry , Cysteine/chemistry , Cysteine/metabolism , Crystallography, X-Ray , Humans , Models, Molecular , Protein Multimerization , COVID-19/virologyABSTRACT
BACKGROUND: Despite extensive findings on the hazardous impacts of environmental heat exposure, little is known about the effect on people with disabilities. This study aimed to estimate the association between environmental heat exposure and emergency department admissions for people with disabilities compared with people without disabilities. METHODS: In this nationwide, case-crossover study, we linked data on emergency department admissions (cases) for any cause in the warm season in South Korea from the Korean National Health Insurance Service (NHIS)-National Sample Cohort database (a nationally representative database of 1 million systematically sampled beneficiaries covering all ages) from Jan 1, 2002, to Dec 31, 2019, and short-term daily mean temperature exposure (measured via Google Earth Engine at a 9 km spatial grid, aggregated to district). We defined beneficiaries with disabilities as those who were registered as disabled in the NHIS; disabilities included in our study were physical disability, brain lesion disorders, blindness or vision loss, and deafness or hearing loss. Other types of disability were not included for confidentiality reasons. A time-stratified case-crossover design, in which participants served as their own control, was used with conditional logistic regression to estimate the association between heat and emergency department admissions in people with and without disabilities. FINDINGS: 23â792 emergency department admissions were recorded for 59â527 people with disabilities. Of these 23â792 admissions, 10â234 (43·0%) individuals were female and 13â558 (57·0%) were male. The odds ratio (OR) of emergency department admissions associated with heat (99th temperature percentile vs 75th percentile) was 1·15 (95% CI 1·07-1·24) in people with disabilities and 1·06 (1·04-1·09) in people without disabilities. The annual excess number of emergency department admissions attributable to heat per 100â000 persons-years was 27·81 admissions (95% CI 9·20-45·69) and excess medical costs were US$638â739·47 (95% CI 201â900·12-1â059â641·87) in people with disabilities; these values were more than four times that of the non-disabled population. People with brain lesion disorders, people with severe physical disabilities, female individuals, and those aged 65 years or older showed higher heat risks. The risks of emergency department admissions due to mental disorder (1·89, 95% CI 1·18-3·00) and respiratory diseases (1·34, 1·06-1·70) also showed higher heat risks than for the other two analysed causes of admission (cardiovascular and genitourinary diseases). INTERPRETATION: Heat was associated with increased risk of emergency department admissions for people with and without disabilities, but the risk appeared to be higher for those with disabilities. These results can inform policy makers when establishing action plans for people with disabilities. FUNDING: National Research Foundation of Korea, the South Korean Ministry of Environment, and the South Korean Ministry of Education.
Subject(s)
Disabled Persons , Nervous System Diseases , Humans , Male , Female , Cross-Over Studies , Hot Temperature , Republic of Korea/epidemiology , HospitalsABSTRACT
Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.
Subject(s)
Benzodiazepines , Deep Sedation , Dexmedetomidine , Propofol , Humans , Retrospective Studies , Apnea , Hypnotics and SedativesABSTRACT
Ag nanoparticles have garnered significant attention for their excellent plasmonic properties and potential use as plasmonic cavities, primarily because of their intrinsically low ohmic losses and optical properties in the visible range. These are particularly crucial in systems involving quantum dots that absorb light at low wavelengths, where the need for a high threshold energy of interband transitions necessitates the incorporation of Ag nanostructures. However, the synthesis of Ag nanoparticles still encounters challenges in achieving structural uniformity and monodispersity, along with chemical stability, consequentially inducing inconsistent and poorly reliable optical responses. Here, we present a two-step approach for synthesizing highly uniform spherical Ag nanoparticles involving depletion-induced flocculation and Cu(II)-mediated oxidative etching. We found that the selective flocculation of multitwinned Ag nanocrystals significantly enhances the uniformity of the resulting Ag nanostructures, leaving behind only single-crystalline and single-twinned nanostructures. Subsequent oxidative etching, in which cupric ions are directly involved in the reaction, was designed based on Pourbaix diagrams to proceed following thermodynamically favorable states and circumvent the generation of reactive chemical species such as H2O2. This leads to perfectly spherical shapes of final Ag nanoparticles with a synthetic yield of 99.5% and additionally reduces the overall reaction time. Furthermore, we explore the potential applications of these monodisperse Ag nanospheres as uniform plasmonic cavities. The fabricated Ag nanosphere films uniformly enhanced the photoluminescence of InP/ZnSe/ZnS quantum dots, showcasing their capabilities in exhibiting consistent plasmonic responses across a large area.
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Background: Air conditioners can prevent heat-related illness and mortality, but the increased use of air conditioners may enhance susceptibility to heat-related illnesses during large-scale power failures. Here, we examined the risks of heat-related illness ambulance transport (HIAT) and mortality associated with typhoon-related electricity reduction (ER) in the summer months in the Tokyo metropolitan area. Methods: We conducted event study analyses to compare temperature-HIAT and mortality associations before and after the power outage (July to September 2019). To better understand the role of temperature during the power outage, we then examined whether the temperature-HIAT and mortality associations were modified by different power outage levels (0%, 10%, and 20% ER). We computed the ratios of relative risks to compare the risks associated with various ER values to the risks associated without ER. Results: We analyzed the data of 14,912 HIAT cases and 74,064 deaths. Overall, 93,200 power outage cases were observed when the typhoon hit. Event study results showed that the incidence rate ratio was 2.01 (95% confidence interval [CI] = 1.42, 2.84) with effects enduring up to 6 days, and 1.11 (95% CI = 1.02, 1.22) for mortality on the first 3 days after the typhoon hit. Comparing 20% to 0% ER, the ratios of relative risks of heat exposure were 2.32 (95% CI = 1.41, 3.82) for HIAT and 0.95 (95% CI = 0.75, 1.22) for mortality. Conclusions: A 20% ER was associated with a two-fold greater risk of HIAT because of summer heat during the power outage, but there was little evidence for the association with all-cause mortality.
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The case-crossover design is widely used in environmental epidemiology as an effective alternative to the conventional time-series regression design to estimate short-term associations of environmental exposures with a range of acute events. This tutorial illustrates the implementation of the time-stratified case-crossover design to study aggregated health outcomes and environmental exposures, such as particulate matter air pollution, focusing on adjusting covariates and investigating effect modification using conditional Poisson regression. Time-varying confounders can be adjusted directly in the conditional regression model accounting for the adequate lagged exposure-response function. Time-invariant covariates at the subpopulation level require reshaping the typical time-series data set into a long format and conditioning out the covariate in the expanded stratum set. When environmental exposure data are available at geographical units, the stratum set should combine time and spatial dimensions. Moreover, it is possible to examine effect modification using interaction models. The time-stratified case-crossover design offers a flexible framework to properly account for a wide range of covariates in environmental epidemiology studies.
Subject(s)
Air Pollution , Humans , Cross-Over Studies , Air Pollution/adverse effects , Environmental Exposure/adverse effects , Environmental Exposure/analysis , Particulate Matter , Time FactorsABSTRACT
Background: Previous studies have indicated that renal disease mortality is sensitive to ambient temperatures. However, most have been limited to the summer season with inconclusive evidence for changes in population vulnerability over time. Objective: This study aims to examine the association between short-term exposure to ambient temperatures and mortality due to renal diseases in Japan, and how this association varied over time. Methods: We conducted a two-stage, time-stratified case-crossover study from 1979 to 2019 across 47 prefectures of Japan. We obtained the data of daily mortality counts for all renal diseases, acute renal failure, and chronic renal disease. We fitted a conditional quasi-Poisson regression model with a distributed lag nonlinear model. A random-effects meta-analysis was applied to calculate national averages. We performed additional analyses by four subperiods, sex, and age groups. Results: We analyzed 997,590 renal mortality cases and observed a reversed J-shaped association. Lower temperatures were associated with increased mortality in all renal disease categories. The cumulative relative risks at 2.5th percentile compared to the minimum mortality temperature percentile were 1.34 (95% confidence interval [CI] = 1.29, 1.40), 1.51 (95% CI = 1.33, 1.71), and 1.33 (95% CI = 1.24, 1.43) for all renal, acute renal failure, and chronic renal disease mortality, respectively. The associations were observed in individuals of both sexes and aged 65 years and above. The associations of kidney mortality with low temperature remained consistent, while the associations with high temperature were pronounced in the past, but not in recent periods. Conclusions: Protection for individuals with impaired renal function from exposure to low temperatures during cold seasons is warranted.
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Gold nanoshells have been actively applied in industries beyond the research stage because of their unique optical properties. Although numerous methods have been reported for gold nanoshell synthesis, the labor-intensive and time-consuming production process is an issue that must be overcome to meet industrial demands. To resolve this, we report a high-throughput synthesis method for nanogap-rich gold nanoshells based on a core silica support (denoted as SiO2@Au NS), affording a 50-fold increase in scale by combining it with a dual-channel infusion pump system. By continuously dropping the reactant solution through the pump, nanoshells with closely packed Au nanoparticles were prepared without interparticle aggregation. The thickness of the gold nanoshells was precisely controlled at 2.3-17.2 nm by regulating the volume of the reactant solution added dropwise. Depending on the shell thickness, the plasmonic characteristics of SiO2@Au NS prepared by the proposed method could be tuned. Moreover, SiO2@Au NS exhibited surface-enhanced Raman scattering activity comparable to that of gold nanoshells prepared by a previously reported low-throughput method at the same reactant ratio. The results indicate that the proposed high-throughput synthesis method involving the use of a dual-channel infusion system will contribute to improving the productivity of SiO2@Au NS with tunable plasmonic characteristics.
Subject(s)
Metal Nanoparticles , Nanoshells , Gold , Silicon DioxideABSTRACT
Recently, silica nanoparticles (NPs) have attracted considerable attention as biocompatible and stable templates for embedding noble metals. Noble-metal-embedded silica NPs utilize the exceptional optical properties of novel metals while overcoming the limitations of individual novel metal NPs. In addition, the structure of metal-embedded silica NPs decorated with small metal NPs around the silica core results in strong signal enhancement in localized surface plasmon resonance and surface-enhanced Raman scattering. This review summarizes recent studies on metal-embedded silica NPs, focusing on their unique designs and applications. The characteristics of the metal-embedded silica NPs depend on the type and structure of the embedded metals. Based on this progress, metal-embedded silica NPs are currently utilized in various spectroscopic applications, serving as nanozymes, detection and imaging probes, drug carriers, photothermal inducers, and bioactivation molecule screening identifiers. Owing to their versatile roles, metal-embedded silica NPs are expected to be applied in various fields, such as biology and medicine, in the future.
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PURPOSE: Several technical aspects of the Fick method limit its use intraoperatively. A data-driven modification of the Fick method may enable its use in intraoperative settings. METHODS: This two-center retrospective observational study included 57 (28 and 29 in each center) patients who underwent off-pump coronary artery bypass graft (OPCAB) surgery. Intraoperative recordings of physiological data were obtained and divided into training and test datasets. The Fick equation was used to calculate cardiac output (CO-Fick) using ventilator-determined variables, intraoperative hemoglobin level, and SvO2, with continuous thermodilution cardiac output (CCO) used as a reference. A modification CO-Fick was derived and validated: CO-Fick-AD, which adjusts the denominator of the original equation. RESULTS: Increased deviation between CO-Fick and CCO was observed when oxygen extraction was low. The root mean square error of CO-Fick was decreased from 6.07 L/min to 0.70 L/min after the modification. CO-Fick-AD showed a mean bias of 0.17 (95% CI 0.00-0.34) L/min, with a 36.4% (95% CI 30.6-44.4%) error. The concordance rates of CO-Fick-AD ranged from 73.3 to 87.1% depending on the time interval and exclusion zone. CONCLUSIONS: The original Fick method is not reliable when oxygen extraction is low, but a modification using data-driven approach could enable continuous estimation of cardiac output during the dynamic intraoperative period with minimal bias. However, further improvements in precision and trending ability are needed.
Subject(s)
Coronary Artery Bypass, Off-Pump , Humans , Cardiac Output/physiology , Monitoring, Physiologic , Oxygen Consumption , Oxygen , Thermodilution/methodsABSTRACT
BACKGROUND: Among the various diaphragm-sparing alternatives to interscalene block, costoclavicular block (CCB) demonstrated a low hemidiaphragmatic paresis (HDP) occurrence but an inconsistent analgesic effect in arthroscopic shoulder surgery. We hypothesized that a larger volume of local anesthetic for CCB could provide sufficient analgesia by achieving sufficient supraclavicular spreading. METHODS: Sixty patients scheduled for arthroscopic rotator cuff repair were randomly assigned to receive CCB using one of two volumes of local anesthetic (CCB20, 0.75% ropivacaine 20 ml; CCB40, 0.375% ropivacaine 40 ml). The primary outcome was the rate of complete analgesia (0 on the numeric rating scale of pain) at 1 h postoperatively. The secondary outcomes included a sonographic assessment of local anesthetic spread, diaphragmatic function, pulmonary function, postoperative opioid use, and other pain-related experiences within 24 h postoperatively. RESULTS: The rates of complete analgesia were not significantly different (23.3% [7/30] and 33.3% [10/30] in the CCB20 and CCB40 groups, respectively; risk difference 10%, 95% CI [-13, 32], P = 0.567). There were no significant differences in other pain-related outcomes. Among the clinical factors considered, the only factor significantly associated with postoperative pain was the sonographic observation of supraclavicular spreading. There were no significant differences in the incidence of HDP and the change in pulmonary function between the two groups. CONCLUSIONS: Using 40 ml of local anesthetic does not guarantee supraclavicular spread during CCB. Moreover, it does not result in a higher rate of complete analgesia compared to using 20 ml of local anesthetic in arthroscopic shoulder surgery.
Subject(s)
Anesthetics, Local , Shoulder , Humans , Shoulder/surgery , Ropivacaine , Analgesics , Pain, Postoperative/etiology , Pain, Postoperative/prevention & controlABSTRACT
Proteases function as pivotal molecular switches, initiating numerous biological events. Notably, potyviral protease, derived from plant viruses, has emerged as a trusted proteolytic switch in synthetic biological circuits. To harness their capabilities, we have developed a single-component photocleavable switch, termed LAUNCHER (Light-Assisted UNcaging switCH for Endoproteolytic Release), by employing a circularly permutated tobacco etch virus protease and a blue-light-gated substrate, which are connected by fine-tuned intermodular linkers. As a single-component system, LAUNCHER exhibits a superior signal-to-noise ratio compared with multi-component systems, enabling precise and user-controllable release of payloads. This characteristic renders LAUNCHER highly suitable for diverse cellular applications, including transgene expression, tailored subcellular translocation and optochemogenetics. Additionally, the plug-and-play integration of LAUNCHER into existing synthetic circuits facilitates the enhancement of circuit performance. The demonstrated efficacy of LAUNCHER in improving existing circuitry underscores its significant potential for expanding its utilization in various applications.
Subject(s)
Peptide Hydrolases , Potyvirus , Blue Light , Proteolysis , Signal-To-Noise RatioABSTRACT
BACKGROUND: Recent studies have reported that air pollution is related to kidney diseases. However, the global evidence on the risk of death from acute kidney injury (AKI) owing to air pollution is limited. Therefore, we investigated the association between short-term exposure to air pollution-particulate matter ≤ 2.5 µm (PM2.5), ozone (O3), and nitrogen dioxide (NO2)-and AKI-related mortality using a multi-country dataset. METHODS: This study included 41,379 AKI-related deaths in 136 locations in six countries during 1987-2018. A novel case time-series design was applied to each air pollutant during 0-28 lag days to estimate the association between air pollution and AKI-related deaths. Moreover, we calculated AKI deaths attributable to non-compliance with the World Health Organization (WHO) air quality guidelines. RESULTS: The relative risks (95% confidence interval) of AKI-related deaths are 1.052 (1.003, 1.103), 1.022 (0.994, 1.050), and 1.022 (0.982, 1.063) for 5, 10, and 10 µg/m3 increase in lag 0-28 days of PM2.5, warm-season O3, and NO2, respectively. The lag-distributed association showed that the risk appeared immediately on the day of exposure to air pollution, gradually decreased, and then increased again reaching the peak approximately 20 days after exposure to PM2.5 and O3. We also found that 1.9%, 6.3%, and 5.2% of AKI deaths were attributed to PM2.5, warm-season O3, and NO2 concentrations above the WHO guidelines. CONCLUSIONS: This study provides evidence that public health policies to reduce air pollution may alleviate the burden of death from AKI and suggests the need to investigate the several pathways between air pollution and AKI death.