Project description:BackgroundOpioids are commonly used for the management of postoperative pain, but their use is limited by important adverse events, such as respiratory depression and the potential for addiction. Multimodal opioid-sparing analgesia regimens can be effectively employed to manage postoperative pain and reduce exposure to opioids. Gabapentinoids (pregabalin and gabapentin) represent an attractive class of drugs for use in multimodal regimens. The American Pain Society recommends the use of gabapentinoids during the perioperative period; however, evidence to inform such a recommendation is unclear.MethodsWe will conduct a systematic review and meta-analysis of randomized clinical trials evaluating the use of systemic gabapentinoids, in comparison to other analgesic regimens or placebo in adult patients undergoing surgery. We will search MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), the Web of Science, and ClinicalTrials.gov databases for relevant citations. Our primary outcome will be intensity of postoperative acute pain (12 h). Our secondary outcomes will be postoperative pain intensity at 6, 24, 48 h, and 72 h, cumulative dose of opioids administered within 24, 48, and 72 h following surgery, the length of stay, chronic pain, and adverse events. Two investigators will independently select trials and extract data. We will evaluate the risk of bias of included trials using the Cochrane risk of bias tools. We will represent pooled continuous data as weighted mean differences and pooled dichotomous data as risk ratios with a 95% confidence interval. We will use random effect models and assess statistical heterogeneity with the I2 index.DiscussionOur study will provide the best level of evidence to inform the effect of gabapentinoids in the management of postoperative acute pain.Systematic review registrationPROSPERO CRD42017067029.
Project description:AbstractGabapentinoid drugs (pregabalin and gabapentin) have been successfully used in the treatment of neuropathic pain and in focal seizure prevention. Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue, oxidative stress, and inflammation, which matches the mechanism of action via voltage-gated calcium channels. In this review, we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids. We systematically summarize the preclinical and clinical research on gabapentinoids in stroke, including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, seizures after stroke, cortical spreading depolarization after stroke, pain after stroke, and nerve regeneration after stroke. This review also discusses the potential targets of gabapentinoids in stroke; however, the existing results are still uncertain regarding the effect of gabapentinoids on stroke and related diseases. Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke. Therefore, gabapentinoids have both opportunities and challenges in the treatment of stroke.
Project description:ImportanceThe increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.ObjectiveTo investigate the overall association between gabapentinoids and the risk of hip fractures and the stratified association across age groups, frailty status, and history of chronic kidney disease.Design, setting, and participantsThis was a case-case-time-control study in patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least 1 prescription for a gabapentinoid before fracture. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% CI for gabapentinoid dispensing in the index (1-60 days prefracture) compared with the reference (121-180 days prefracture) period. To adjust for the underlying time trend in gabapentinoid use, each index case was matched with up to 5 controls, selected from future cases of the same age and sex. Subgroup analyses were conducted in subgroups with or without chronic kidney disease (CKD), frailty scores less than 5, and frailty scores 5 and above. Frailty was computed using the Hospital Frailty Risk Score (HFRS). Data were analyzed from November 2023 to April 2024.ExposureGabapentinoids (pregabalin or gabapentin).Main outcome and measureHip fracture.ResultsOf 28 293 patients hospitalized for hip fractures, 2946 (1752 [59.5%] aged ≥80 years; 2099 [71.2%] female) were dispensed a gabapentinoid before hip fracture. Gabapentinoid dispensing was associated with increased odds of hip fractures (OR, 1.96; 95% CI, 1.66-2.32). After adjusting for the exposure-time trend and concomitant use of other central nervous system medications, the odds of hip fractures remained elevated (OR, 1.30; 95% CI, 1.07-1.57). The association between gabapentinoid dispensing and hip fracture was higher in patients with HFRS 5 and above (OR, 1.75; 95% CI, 1.31-2.33) and CKD (OR, 2.41; 95% CI, 1.65-3.52).Conclusions and relevanceIn this case-case-time-control study of Australian residents hospitalized for hip fracture, gabapentinoid use was associated with an increased risk of hip fractures, especially in patients who were frail or had chronic kidney disease. In addition to the known risk associated with kidney impairment, frailty status may be an important risk factor when considering use of gabapentinoids.
Project description:IntroductionThe combination of opioids and central nervous system depressants such as benzodiazepines and barbiturates has an additive effect on the frequency of oversedation and respiratory depression requiring naloxone use in hospitalized patients. Gabapentinoids (gabapentin and pregabalin) are frequently prescribed with opioids for their opioid-sparing and adjuvant analgesic effects. There is limited literature on the risk of respiratory depression due to the combination of opioids and gabapentinoids requiring naloxone administration.MethodsThis retrospective study evaluated patients who were prescribed opioids and at least one dose of naloxone between March 1, 2014 and September 30, 2016. The primary objective of this study was to compare the frequency of respiratory depression among patients who received naloxone and opioids (non-gabapentinoid group) with those who received naloxone, opioids, and gabapentinoids (gabapentinoid group). Secondary objectives included comparing the association of oversedation, using the Pasero Opioid-induced Sedation Scale, and various risk factors with those in the gabapentinoid group.ResultsA total of 153 patient episodes of naloxone administration (102 in the non-gabapentinoid and 51 in the gabapentinoid groups) in 125 unique patients were included in the study. For the primary objective, there were 33 episodes of respiratory depression associated with the non-gabapentinoid group (33/102=32.4%) versus 17 episodes of respiratory depression with the gabapentinoid group (17/51=33.3%) (p=0.128). Secondary objectives showed a significant association between respiratory depression and surgery in the previous 24 hours (p=0.036) as well as respiratory depression and age >65 years (p=0.031) for patients in the non-gabapentinoid group compared to the gabapentinoid group.ConclusionThere was no significant association of respiratory depression in the gabapentinoid group versus the non-gabapentinoid group. There was an increased risk of respiratory depression in the gabapentinoid group, specifically in patients who had surgery within the previous 24 hours.
Project description:The miniaturization boiling (micro-bubble emission boiling [MEB]) phenomenon, with a high heat removal capacity that contributes considerably to the cooling of the divertor of the nuclear fusion reactor, was discovered in the early 1980s. Extensive research on MEB has been performed since its discovery. However, the progress of the application has been delayed because the generation mechanism of MEB remains unclear. Reasons for this lack of clarity include the complexity of the phenomenon itself and the high-speed phase change phenomenon in which boiling and condensation are rapidly generated. In addition, a more advanced thermal technique is required to realize the MEB phenomenon at the laboratory scale. To the authors' knowledge, few studies have discussed the rush mechanism of subcooled liquid to the heating surface, which is critical to elucidating the mechanism behind MEB. This study used photographic images to verify that the cavitation phenomenon spreads to the inside of the superheated liquid on the heating surface and thus clarify the mechanism of MEB.
Project description:IntroductionConcurrent use of prescription opioids with gabapentinoids may pose risks of serious drug interactions. Yet, little is known about the trends in and patient characteristics associated with concurrent opioid-gabapentinoid use among older Medicare opioid users with chronic noncancer pain.MethodsA cross-sectional study was conducted among Medicare older beneficiaries (aged ≥65 years) with chronic noncancer pain who filled ≥1 opioid prescription within 3 months after a randomly selected chronic noncancer pain diagnosis (index date) in a calendar year between 2011 and 2018. Patient characteristics were measured in the 6-month baseline before the index date, and concurrent opioid-gabapentinoid use for ≥1 day was measured in the 3-month follow-up after the index date. Multivariable modified Poisson regression hwas used to assess the trends and characteristics of concurrent opioid-gabapentinoid use. Analyses were conducted from January to June 2021.ResultsAmong 464,721 eligible older beneficiaries with chronic noncancer pain and prescription opioids, the prevalence of concurrent opioid-gabapentinoid use increased from 17.0% in 2011 to 23.5% in 2018 (adjusted prevalence ratio=1.48, 95% CI=1.45, 1.53). Concurrent users versus opioid-only users tended to be non-Black, low-income subsidy recipients, and Southern residents. The clinical factors associated with concurrent opioid-gabapentinoid use included having a diagnosis of neuropathic pain, polypharmacy, and risk factors for opioid-related adverse events.ConclusionsConcurrent opioid-gabapentinoid use among older Medicare beneficiaries with chronic noncancer pain and prescription opioids has increased significantly between 2011 and 2018. Future studies are warranted to investigate the impact of concurrent use on outcomes in older patients. Interventions that reduce inappropriate concurrent use may target older patients with identified characteristics.
Project description:Bubbles have been extensively explored as energy carriers ranging from boiling heat transfer and targeted cancer diagnosis. Yet, despite notable progress, the kinetic energy inherent in small bubbles remains difficult to harvest. Here, we develop a transistor-inspired bubble energy generator for directly and efficiently harvesting energy from small bubbles. The key points lie in designing dielectric surface with high-density electric charges and tailored surface wettability as well as transistor-inspired electrode configuration. The synergy between these features facilitates fast bubble spreading and subsequent departure, transforms the initial liquid/solid interface into gas/solid interface under the gating of bubble, and yields an output at least one order of magnitude higher than existing studies. We also show that the output can be further enhanced through rapid bubble collapse at the air/liquid interface and multiple bubbles synchronization. We envision that our design will pave the way for small bubble-based energy harvesting in liquid media.
Project description:Current lithography techniques, which employ photon, electron, or ion beams to induce chemical or physical reactions for micro/nano-fabrication, have remained challenging in patterning chemically synthesized colloidal particles, which are emerging as building blocks for functional devices. Herein, we develop a new technique - bubble-pen lithography (BPL) - to pattern colloidal particles on substrates using optically controlled microbubbles. Briefly, a single laser beam generates a microbubble at the interface of colloidal suspension and a plasmonic substrate via plasmon-enhanced photothermal effects. The microbubble captures and immobilizes the colloidal particles on the substrate through coordinated actions of Marangoni convection, surface tension, gas pressure, and substrate adhesion. Through directing the laser beam to move the microbubble, we create arbitrary single-particle patterns and particle assemblies with different resolutions and architectures. Furthermore, we have applied BPL to pattern CdSe/ZnS quantum dots on plasmonic substrates and polystyrene (PS) microparticles on two-dimensional (2D) atomic-layer materials. With the low-power operation, arbitrary patterning and applicability to general colloidal particles, BPL will find a wide range of applications in microelectronics, nanophotonics, and nanomedicine.
Project description:Natural and artificial flower pollination are critical processes in the life cycle of flowering plants. Declines in the number of global pollinator insects, the heavy labor of conducting artificial pollination manually, and the rising cost of pollen grains are considered to be significant worldwide problems. Here we show that chemically functionalized soap bubbles exhibit effective and convenient delivery of pollen grains to the targeted flowers thanks to their stickiness, softness, high flexibility, and enhancement of pollen activity. By exploring the physicochemical properties of functional soap bubbles, we could prepare mechanically stabilized soap bubbles capable of withstanding the windmills produced by robotic pollination. An unmanned aerial vehicle equipped with a soap bubble maker was autonomously controlled to pollinate flowers. Such technology of automatic intelligent robotic pollination with functional soft materials would lead to innovative agricultural systems that can tackle the global issues of pollination.
Project description:One of the important issues in advanced cell culture development is to create an accurate and controlled micro-environment surrounding the cell while meeting the requirements for processes such as cell differentiation, gene function or pharmacological screening tests. In this sight, we were aimed at designing and developing a micro-scale culture system suitable to analyze the synergic effects of extracellular matrix proteins and soluble environment on cell phenotype in high-throughput fashion. Moreover we were interested in the opportunity to create a more “tissue-friendly” microenvironment than traditional culture methods simulating liquids movements. According to these purposes, cell arrays were produced deposing micrometer-scale protein islands on polyacrylamide hydrogels using a robotic DNA microarrayer and were used both in conventional culture methods and by automated stable and constant perfusion. We produced a mathematical modeling assisting the experimental design and assessing efficient mass transport and proper fluidodynamic regimes. It was validated using a particle tracking experiment used to predict the constant value of the velocities over the cell arrays which ensure the same mass transport regime over the cultured cell arrays. Cell-array permits the maintenance of the correct phenotype of cells cultured on 500 μm islands both in static and dynamic conditions. Immunostaining and gene expression analysis confirmed the ability for cells to proliferate and differentiate in response to changed stimuli. Microarray gene expression analysis evidenced activation of specific skeletal muscle genes like MYL2, confirmed by qRT-PCR, and troponins and tropomyosins. Keywords: cell array, dynamic, perfusion, C2C12, hydrogel, ECM