Undesirable Responses Research Articles

Aircraft Flutter and Aerodynamic Work

This paper is about an application of an energy approach to computational aeroelasticity. A frequency-domain calculation of aerodynamic work is presented in a form that has not been previously discussed. In large aeroelastic systems such as aircraft flutter models, the obtained expression allows us to quantify the roles played in flutter by the generalized coordinates, the phases between them, and the generalized aerodynamic forces. This is exemplified in a body-freedom flutter analysis of a flying-wing aircraft: the X-56A. Another interesting feature that is proposed is a diagram of the aerodynamic work as a function of airspeed. Such functions allow an observance of an evolution with the airspeed of the terms that are most reflective of the aeroelastic stability changes: for example, a phase between the two dominant modes. These diagrams can complement typical flutter trends in analysis documentation and aid in flutter suppression. The approach also permits a perspective on flutter as an interaction of aircraft surfaces rather than vibrational modes. Once a sensitivity of an aeroelastic eigenvalue to a surface area is measured with the presented approach, it can be used in the aircraft design to mitigate flutter and other undesirable aeroelastic responses associated with lightly damped eigenvalues. An illustration of this idea is provided. Finally, energy-based computations allow posing energy-efficient active flutter suppression problems. This has been presented before in the literature. Examples of this aspect are made here with aircraft models (for the first time, as far as the author knows).

Inflammatory reflex disruption in COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was identified in Wuhan, China, in late 2019 and caused coronavirus disease 2019 (COVID‐19), which is still a global pandemic. In most infected people, SARS‐CoV‐2 only causes moderate symptoms, whereas in other patients, it leads to severe illness and eventually death. Although the main clinical manifestation of COVID‐19 is often seen in the lungs, this disease affects almost all body organs. The excessive and prolonged release of inflammatory cytokines that might occur in COVID‐19 patients, known as cytokine storms, stimulates undesired immune responses and can cause various tissues damage. In the current review article, we focus on the potential advantages of the intrinsic cholinergic anti‐inflammatory pathway as the efferent arm of the inflammatory reflex in COVID‐19 management. Considering this endogenous protective mechanism against chronic inflammation, we focused on the effects of SARS‐CoV‐2 in the destruction of this anti‐inflammatory system. Several studies showed the interaction of SARS‐CoV‐2 with the alpha‐7 subtype of the nicotinic acetylcholine receptor as the effector molecule of the inflammatory reflex. In contrast, neurological manifestations have increasingly been identified as significant extrapulmonary manifestations of COVID‐19. The rational connection between these findings and COVID‐19 pathogenesis might be an important issue in both our understanding of and dealing with this disease. COVID‐19 is deeply rooted in our daily life and requires an urgent need for the establishment of effective therapeutic options, and all the possible treatments must be considered for the control of such inflammatory conditions.

Nectin-4-targeted immunoSPECT/CT imaging and photothermal therapy of triple-negative breast cancer

BackgroundTriple-negative breast cancer (TNBC) is more prone to distant metastasis and visceral recurrence in comparison to other breast cancer subtypes, and is related to dismal prognosis. Nevertheless, TNBC has an undesirable response to targeted therapies. Therefore, to tackle the huge challenges in the diagnosis and treatment of TNBC, Nectin-4 was selected as a theranostic target because it was recently found to be highly expressed in TNBC. We developed anti-Nectin-4 monoclonal antibody (mAbNectin-4)-based theranostic pair, 99mTc-HYNIC-mAbNectin-4 and mAbNectin-4-ICG. 99mTc-HYNIC-mAbNectin-4 was applied to conduct immuno-single photon emission computed tomography (SPECT) for TNBC diagnosis and classification, and mAbNectin-4-ICG to mediate photothermal therapy (PTT) for relieving TNBC tumor growth.MethodsNectin-4 expression levels of breast cancer cells (MDA-MB-468: TNBC cells; and MCF-7, non-TNBC cells) were proved by western blot, flow cytometry, and immunofluorescence imagning. Cell uptake assays, SPECT imaging, and biodistribution were performed to evaluate Nectin-4 targeting of 99mTc-HYNIC-mAbNectin-4. A photothermal agent (PTA) mAbNectin-4-ICG was generated and characterized. In vitro photothermal therapy (PTT) mediated by mAbNectin-4-ICG was conducted under an 808 nm laser. Fluorescence (FL) imaging was performed for mAbNectin-4-ICG mapping in vivo. In vivo PTT treatment effects on TNBC tumors and corresponding systematic toxicity were evaluated.ResultsNectin-4 is overexpressed in MDA-MB-468 TNBC cells, which could specifically uptake 99mTc-HYNIC-mAbNectin-4 with high targeting in vitro. The corresponding immunoSPECT imaging demonstrated exceptional performance in TNBC diagnosis and molecular classification. mAbNectin-4-ICG exhibited favourable biocompatibility, photothermal effects, and Nectin-4 targeting. FL imaging mapped biodistribution of mAbNectin-4-ICG with excellent tumor-targeting and retention in vivo. Moreover, mAbNectin-4-ICG-mediated PTT provided advanced TNBC tumor destruction efficiency with low systematic toxicity.ConclusionmAbNectin-4-based radioimmunoimaging provides visualization tools for the stratification and diagnosis for TNBC, and the corresponding mAbNectin-4-mediated PTT shows a powerful anti-tumor effect. Our findings demonstrate that this Nectin-4 targeting strategy offers a simple theranostic platform for TNBC.

Homogeneity of antibody-drug conjugates critically impacts the therapeutic efficacy in brain tumors.

SUMMARYGlioblastoma multiforme (GBM) is the most aggressive and fatal disease of all brain tumor types. Most therapies rarely provide clinically meaningful outcomes in the treatment of GBM. Although antibody-drug conjugates (ADCs) are promising anticancer drugs, no ADCs have been clinically successful for GBM, primarily because of poor blood-brain barrier (BBB) penetration. Here, we report that ADC homogeneity and payload loading rate are critical parameters contributing to this discrepancy. Although both homogeneous and heterogeneous conjugates exhibit comparable in vitro potency and pharmacokinetic profiles, the former shows enhanced payload delivery to brain tumors. Our homogeneous ADCs provide improved antitumor effects and survival benefits in orthotopic brain tumor models. We also demonstrate that overly drug-loaded species in heterogeneous conjugates are particularly poor at crossing the BBB, leading to deteriorated overall brain tumor targeting. Our findings indicate the importance of homogeneous conjugation with optimal payload loading in generating effective ADCs for intractable brain tumors.

A novel filler of biocomposites for long-term self-regulated delivery of immunomodulatory and antibacterial components to accelerate bone regeneration

Undesirable immune response and bacterial infection still remain critical challenges for the applications of biodegradable scaffolds. Herein, we assembled tannic acid (TA)/Zn2+ based metal-phenolic network complexes (MPNs) as a novel filler to render the scaffold with immunomodulatory and antibacterial functions. Besides the unique characteristics of combining the advanced functions of both TA (immunomodulation) and Zn2+ (antibacteria), another prominent feature of the filler was that it allowed to release its components in a sustainable constant rate manner, without initial burst release, lasting for more than 30 days, due to the supramolecular network structures and dynamic coordination bonds. Consequently, the modified scaffold could not only control the initial severe acute inflammation to a moderate level, but also displayed a full-course inhibition on later biodegradation-induced chronic inflammation. The manipulated anti-inflammatory micro-environment was more beneficial for in vivo osteogenesis. Additionally, the constant release rate of Zn2+ rendered the scaffold stable and long-term antibacterial performance, meanwhile avoiding cytotoxicity of Zn2+. As an emerging class of multi-functional metal-organic materials with a high degree of function modularity in terms of the choice of different metal ions and phenolic ligands, this work paved a new path for the applications of MPNs to advance multi-functional biocomposites.

Tellurium-containing polymer coating with glutathione peroxidase mimics capability for surface modification of intravascular implants

Interventional therapy as an effective method has saved millions of lives of human, in which the interventional devices (e.g. central venous catheters, vascular stent, etc.) play a crucial role. However, undesirable implantation responses including thrombus formation, inflammation, and hyperplasia is still the life-threatening to the patients. In this study, a novel tellurium-functionalized polycarbonate-polyurethane (PCU-TeTe) was designed and synthesized by introducing ditelluride bonds (Te-Te) into the molecular structure of polymer. The developed PCU-TeTe showed an excellent catalytic activity in the nitric oxide (NO) release with a rate of 2.8 × 10-10 mol·cm−2·min−1, hence has multiple advanced functions in the blood environment. Both in vitro and ex vivo results of hemocompatibility showed that PCU-TeTe could substantially reduce the probability of thrombogenesis. Besides, PCU-TeTe could significantly promote endothelial cell (EC) proliferation while suppress the growth of smooth muscle cell (SMC) and macrophage (MA). Moreover, the in vivo results including qualitative and quantitative date (e.g. abdominal aorta hyperplasia) demonstrated that PCU-TeTe could not only promote healthy endothelialization, but also inhibit thrombus, inflammation and hyperplasia. Such tellurium-functionalized system could be a promising strategy for the design and fabrication of vascular materials or implants, especially for blood-contacting devices in the future.

Apoptosis and Pharmacological Therapies for Targeting Thereof for Cancer Therapeutics

Apoptosis is an evolutionarily conserved sequential process of cell death to maintain a homeostatic balance between cell formation and cell death. It is a vital process for normal eukaryotic development as it contributes to the renewal of cells and tissues. Further, it plays a crucial role in the elimination of unnecessary cells through phagocytosis and prevents undesirable immune responses. Apoptosis is regulated by a complex signaling mechanism, which is driven by interactions among several protein families such as caspases, inhibitors of apoptosis proteins, B-cell lymphoma 2 (BCL-2) family proteins, and several other proteases such as perforins and granzyme. The signaling pathway consists of both pro-apoptotic and pro-survival members, which stabilize the selection of cellular survival or death. However, any aberration in this pathway can lead to abnormal cell proliferation, ultimately leading to the development of cancer, autoimmune disorders, etc. This review aims to elaborate on apoptotic signaling pathways and mechanisms, interacting members involved in signaling, and how apoptosis is associated with carcinogenesis, along with insights into targeting apoptosis for disease resolution.

Drug-drug-gene interaction risk among opioid users in the U.S. Department of Veterans Affairs.

Response to analgesic therapy is influenced by several factors including genetics and drug-drug interactions. Pharmacogenetic (PGx) variants in the CYP2D6 gene modify response to opioids by altering drug metabolism. We sought to determine the potential impact of PGx testing on the care of Veterans with noncancer pain prescribed opioids metabolized by CYP2D6 (codeine, hydrocodone, or tramadol). A retrospective analysis was performed within the Veterans Health Administration evaluating prescription records for pain medications metabolized by CYP2D6 and interacting drugs from 2012 to 2017. Among 2,436,654 Veterans Health Administration pharmacy users with at least 1 opioid prescription, 34% met the definition of chronic use (longer than 90 days with more than 10 prescriptions or 120 days-supply). Opioids were commonly coprescribed with antidepressants interacting with CYP2D6 (28%). An estimated 21.6% (n = 526,905) of these patients are at an elevated risk of an undesirable response to their opioid medication based on predicted phenotypes and drug-drug interactions: 3.5% are predicted CYP2D6 ultrarapid metabolizers and at increased risk for toxicity, 5.4% are poor metabolizers at higher risk for nonresponse, and 12.8% are normal or intermediate metabolizers coprescribed a CYP2D6 inhibitor leading to phenoconversion into poor metabolizer. Despite the high rate of coprescription of opioids and interacting drugs, CYP2D6 testing was infrequent in the sample (0.02%), and chart review suggests that test results were used to optimize antidepressant treatments rather than pain medications. Using PGx testing combined with consideration of phenoconversion may allow for an enhanced precision medicine approach to pain management in Veterans.

Assessment of immunogenicity and drug activity in patient sera by flow-induced dispersion analysis

Biopharmaceuticals have revolutionized the treatment of many diseases such as diabetes, cancer, and autoimmune disorders. These complex entities provide unique advantages like high specificity towards their target. Unfortunately, biopharmaceuticals are also prone to elicit undesired immunogenic responses (immunogenicity), compromising treatment efficacy as well as patient safety due to severe adverse effects including life threatening conditions. Current immunogenicity assays are hampered by immobilization procedures, complicated sample pre-treatment, or rely on cell-based methods which all prevent reliable and continuous monitoring of patients. In this work, we present Flow Induced Dispersion Analysis (FIDA) for assessment of immunogenicity and drug activity in serum samples from arthritis patients receiving adalimumab. FIDA is a first principle technique for size-based characterization of biomolecules and their complexes under biologically relevant conditions. The FIDA methodology rely on an absolute and quantitative readout (hydrodynamic radius) thus reducing the need for positive and negative controls. Here, FIDA is applied for evaluating active adalimumab in serum by studying the interaction with its target tumor necrosis factor alpha (TNF-α). We report proof of principle for a quantitative approach for stratifying patients exhibiting presence of neutralizing and non-neutralizing antibodies based on their individual drug activity pattern. Further, it can be applied to any biopharmaceutical having soluble drug targets and it holds potential in a companion diagnostics setting.

Modulation of outer membrane vesicle-based immune responses by cathelicidins

Antibiotic resistance is increasing and one strategy to prevent resistance development is the use of bacterial vaccines. For Gram-negative bacteria, natural outer membrane vesicles (OMVs) could be used for vaccine development. These vesicular structures are naturally produced by all Gram-negative bacteria and contain several antigens in their native environment. However, despite that the presence of lipopolysaccharide (LPS) may aid as intrinsic adjuvant, there is a risk that it may also cause undesired immune responses. Therefore, molecules to dampen LPS-induced toll-like receptor (TLR) 4 activation may be needed. Here host defense peptides (HDPs), like cathelicidins, can play an important role. They have been shown to interact with LPS and thereby neutralize LPS-induced TLR4 activation. However, there is currently no knowledge about neutralization in an OMV-based setting. Therefore, in this paper the immune modulating capacity of HDPs was investigated after macrophage stimulation with either spontaneous or heat-induced B. bronchiseptica OMVs. This revealed that the cathelicidins LL-37, CATH-2, PMAP-36 and K9CATH were able to modulate immune responses. Interestingly, immune modulation by these cathelicidins was different for spontaneous compared to heat-induced OMVs. Interaction studies revealed that the mode of binding of cathelicidins to OMVs slightly differed between OMV classes. Furthermore, TLR screening revealed that TLR2, 4, 5 and 9 were involved in stimulation of macrophages by OMVs, with TLR4-mediated activation being the most important pathway. Uptake of OMVs did not play a major role in macrophage activation. Taken together, this study shows how OMVs can activate macrophages and how cathelicidins may modulate these immune responses.

Performance Analysis of a Hybrid Electric Ship by Real-Time Verification

International maritime transport organizations are proposing regulatory actions and strategies aimed at decarbonizing the sector to reduce its greenhouse gas (GHG) emissions, which currently constitute around 3% of the global total. Hybrid propulsion systems have significant potential in this respect, as a means of power-saving in ships. This paper describes a high-fidelity benchmark for hybrid-electric vessels, combining diesel generators and batteries. The benchmark consists of detailed models, the parameters of which are provided so that the models can be reproduced. The proposed hybrid-electric ship topology and control system was validated using real-time hardware-in-the-loop (HIL) simulations on a Typhoon HIL402 platform. The results provide a detailed analysis of the operation of the different components under varying conditions, which should be useful in prototyping these kinds of systems. In addition, the response of the system was evaluated with regard to potential disturbances resulting from the control system’s operation. The results show the system performed correctly during these transitory events, with no undesirable responses.

Immunosuppressive TREM2(+) macrophages are associated with undesirable prognosis and responses to anti-PD-1 immunotherapy in non-small cell lung cancer.

Immune checkpoint blockade (ICB) has been improving patient outcomes of non-small cell lung cancer (NSCLC), but its effectiveness is highly subjective to individual tumor microenvironment. As dominant immune cells in NSCLC, tumor-associated macrophages (TAMs) display high diversity and plasticity. This study aims to find crucial TAM subtypes associated with ICB response in NSCLC. Large cohorts of NSCLC patients from The Cancer Genome Atlas and a single-cell sequencing dataset were integrated to illustrate immunosuppressive phenotypes of TAMs, followed by experimental verification. 341 NSCLC surgical samples and 40 tissue samples of NSCLC patients who received ICB treatment were collected to state the clinical importance of TAMs. We identified a TREM2 positive (+) TAM subtype in NSCLC stratifying patient responses to immunotherapy. NSCLC patients with high TREM2+ TAM infiltration exhibited advanced tumor progression, inferior prognosis and unique NSCLC molecular characteristics, especially mutations of EGFR. TREM2+ TAMs were induced in TME, but not existed in peripheral blood. TREM2+ TAMs were enriched with multiple anti-inflammatory cytokines, exhibiting a M2-like immunosuppressive phenotype, and potentiate T cell dysfunction including impaired anti-tumor activity of CD8+ T cells and enhanced differentiation towards FOXP3+ Tregs, thus facilitating immune evasion of NSCLC. Response rates to PD-1-based ICB were higher in patients with low TREM2+ TAMs (31.58%) compared to high TREM2+ TAMs (14.29%). Our findings implicated the immunosuppressive role of TREM2+ TAMs in NSCLC, and systematically reveal the clinical significance of TREM2+ TAMs as predictive and prognostic markers for NSCLC patients with ICB treatment.

VEGFA-targeting miR-agshRNAs combine efficacy with specificity and safety for retinal gene therapy

Retinal gene therapy using RNA interference (RNAi) to silence targeted genes requires both efficacy and safety. Short hairpin RNAs (shRNAs) are useful for RNAi, but high expression levels and activity from the co-delivered passenger strand may cause undesirable cellular responses. Ago2-dependent shRNAs (agshRNAs) produce no passenger strand activity. To enhance efficacy and to investigate improvements in safety, we have generated VEGFA-targeting agshRNAs and microRNA (miRNA)-embedded agshRNAs (miR-agshRNAs) and inserted these RNAi effectors in Pol II/III-driven expression cassettes and lentiviral vectors (LVs). Compared with corresponding shRNAs, agshRNAs and miR-agshRNAs increased specificity and safety, while retaining a high knockdown efficacy and abolishing passenger strand activity. The agshRNAs also caused significantly smaller reductions in cell viability and reduced competition with the processing of endogenous miR21 compared with their shRNA counterparts. RNA sequencing (RNA-seq) analysis of LV-transduced ARPE19 cells revealed that expression of shRNAs in general leads to more changes in gene expression levels compared with their agshRNA counterparts and activation of immune-related pathways. In mice, subretinal delivery of LVs encoding tissue-specific miR-agshRNAs resulted in retinal pigment epithelium (RPE)-restricted expression and significant knockdown of Vegfa in transduced RPE cells. Collectively, our data suggest that agshRNAs and miR-agshRNA possess important advantages over shRNAs, thereby posing a clinically relevant approach with respect to efficacy, specificity, and safety.

Extent and hierarchy of seismic induced inelastic demands in the substructure system of bridges on piled foundation crossing waterways

The effect of the exposed length of piles supporting bridges crossing waterways on the spread of inelasticity along the pile shaft compared with the extent of plasticity in the body of the column, and hence on the precedence of the formation of plastic hinges in the substructure system is of paramount importance. Plastic hinges may form ideally and preferably at the bottom of the column just above the pile cap, or undesirably either at the pile’s head or at any other section within the pile be it along its free/exposed length immersed in water or its embedded part in soil. A set of bridges are designed according to Eurocode for multiple configurations with various relative stiffness between the column and the group of piles featuring partly exposed shaft. Pushover as well as time history inelastic analyses under a set of ten earthquake records are performed accounting for soil-structure interaction. Results demonstrate that it is likely in some cases characterized by a remarkable increase in the flexural stiffness of the column relative to the group of piles to have spread of inelasticity and plastic hinges forming in piles prior to the column. This is undesirable for a robust, reliable and resilient seismic design as devised by universal design standards for bridges on piled foundation. While there is no clear consensus on the most effective corrective measure to such undesirable response, a few proposed remedial design actions have been formulated in order to preclude (or at least improve the behavior for the case featuring) plastic hinges deplorably forming in the piles prior to the base of the column.

Activation of the Innate Immune Checkpoint CLEC5A on Myeloid Cells in the Absence of Danger Signals Modulates Macrophages' Function but Does Not Trigger the Adaptive T Cell Immune Response.

C-Type lectin receptor 5A (CLEC5A) is a spleen tyrosine kinase- (Syk-) coupled pattern recognition receptor expressed on myeloid cells and involved in the innate immune response to viral and bacterial infections. Activation of the CLEC5A receptor with pathogen-derived antigens leads to a secretion of proinflammatory mediators such as TNF-α and IL-6 that may provoke a systemic cytokine storm, and CLEC5A gene polymorphisms are associated with the severity of DV infection. In addition, the CLEC5A receptor was mentioned in the context of noninfectious disorders like chronic obstructive pulmonary disease (COPD) or arthritis. Altogether, CLEC5A may be considered as an innate immune checkpoint capable to amplify proinflammatory signals, and this way contributes to infection or to aseptic inflammation. In this study, we determined CLEC5A receptor expression on different macrophage subsets (in vitro and ex vivo) and the functional consequences of its activation in aseptic conditions. The CLEC5A surface expression appeared the highest on proinflammatory M1 macrophages while intermediate on tumor-associated phenotypes (M2c or TAM). In contrast, the CLEC5A expression on ex vivo-derived alveolar macrophages from healthy donors or macrophages from ovarian cancer patients was hardly detectable. Targeting CLEC5A on noninflammatory macrophages with an agonistic α-CLEC5A antibody triggered a release of proinflammatory cytokines, resembling a response to dengue virus, and led to phenotypic changes in myeloid cells that may suggest their reprogramming towards a proinflammatory phenotype, e.g., upregulation of CD80 and downregulation of CD163. Interestingly, the CLEC5A agonist upregulated immune-regulatory molecules like CD206, PD-L1, and cytokines like IL-10, macrophage-derived chemokine (MDC/CCL22), and thymus and activation chemokine (TARC/CCL17) which are associated with an anti-inflammatory or a protumorigenic macrophage phenotype. In the absence of concomitant pathogenic or endogenous danger signals, the CLEC5A receptor activation did not amplify an autologous T cell response, which may represent a protective innate mechanism to avoid an undesirable autoimmune adaptive response.

A Hybrid Bipolar Active Charge Balancing Technique with Adaptive Electrode Tissue Interface (ETI) Impedance Variations for Facial Paralysis Patients.

Functional electrical stimulation (FES) is a safe, effective, and general approach for treating various neurological disorders. However, in the case of FES usage for implantable applications, charge balancing is a significant challenge due to variations in the fabrication process and electrode tissue interface (ETI) impedance. In general, an active charge balancing approach is being used for this purpose, which has limitations of additional power consumption for residual voltage calibration and undesired neurological responses. To overcome these limitations, this paper presents a reconfigurable calibration circuit to address both ETI variations and charge balancing issues. This reconfigurable calibration circuit works in two modes: An impedance measurement mode (IMM) for treating ETI variations and a hybrid charge balancing mode (HCBM) for handling charge balance issues. The IMM predicts the desired stimulation currents by measuring the ETI. The HCBM is a hybrid combination of electrode shorting, offset regulation, and pulse modulation that takes the best features of each of these techniques and applies them in appropriate situations. From the results, it is proved that the proposed IMM configuration and HCBM configuration have an optimal power consumption of less than 44 W with a power ratio ranging from 1.74 to 5.5 percent when compared to conventional approaches.

Superior laryngeal nerve block with in-line lignocaine nebulization for awake extubation response.

Background and Aims:Tracheal extubation is associated with various undesirable hemodynamic and airway responses. Various drugs are used effectively to curb these responses. But these drugs have limitations and produce side effects. Hence, the study was planned to assess the effects of superior laryngeal nerve block with inline lignocaine nebulization on awake extubation responses to suggest an alternative. The aim of this study was to assess the effect of bilateral superior laryngeal nerve block with inline lignocaine nebulization on awake extubation responses.Material and Methods:A study was conducted in 35 patients aged 18-60 years, posted for surgery less than 3 h under general anesthesia. The hemodynamic responses like heart rate, arterial blood pressure, and mean arterial pressure were recorded preoperatively and at 1, 5, and 10 min postextubation. Undesirable respiratory responses like bucking, severity of sore throat, and cough response were also assessed. Repeated measures analysis of variance followed by the Tukey HSD test was used to find the significance of hemodynamic parameters. Qualitative data were expressed as percentages.Results:Decrease in Systolic Blood Pressure, Diastolic Blood Pressure and Mean Arterial Pressure was statistically significant at 5 mins (T2) and 10 mins (T3) postextubation as compared to baseline (T0). No cough was observed postextubation in 80% patients while 20% had mild Grade 1 cough.Conclusion:Superior laryngeal nerve block with in-line lignocaine nebulization for awake extubation is effective in curbing the haemodynamic and respiratory responses of extubation.

Identification of the Chinese Population That Can Benefit Most From Postprandial Lipid Testing: Validation of the Use of Oral Fat Tolerance Testing in Clinical Practice.

BackgroundDyslipidemia has become increasingly prevalent in recent decades. Blood lipid concentrations are significantly influenced by diet; however, postprandial triglyceride concentration (PTG) is not often measured. PTG can reflect the risks of diabetes and cardiovascular disease, but not all individuals would benefit from PTG testing.ObjectiveThe aim of the present study was to determine the PTG response in a Chinese cohort and identify who would benefit from diagnostic PTG measurement.MethodsA total of 400 Chinese adults were enrolled and underwent oral fat tolerance test (OFTT), which was well tolerated. The participants were assigned to groups according to their fasting triglyceride concentration to evaluate the usefulness of PTG testing. A PTG concentration > 2.5 mmol/L was defined as high (HPTG).ResultsOf the 400 participants, 78.9% showed an undesirable PTG response. Those with FTG ≥1.0 mmol/L had a delayed PTG peak and higher peak values. Seventy-five percent of those with 1.0 mmol/L ≤FTG <1.7 mmol/L had HPTG, of whom 18.6% had impaired glucose tolerance.ConclusionsThe present data confirm the previously reported predictive value of PTG testing. Moreover, the findings indicate that Chinese people with FTGs of 1.0 -1.7 mmol/L may benefit most from the identification of postprandial hyperlipidemia through OFTT because more than half of them have occult HPTG, which may require treatment. Thus, the detection of HPTG using an OFTT represents a useful means of identifying dyslipidemia and abnormal glucose metabolism early.Clinical Trial Registration[http://www.chictr.org.cn/index.aspx], identifier ChiCTR1800019514.

A Novel High-strength Autologous Fibrin Glue Augmented with Biocompatible Polymers

ABSTRACT Commercially available fibrin glues are expensive and may cause undesired immune responses in patients. Several alternatives to this have been proposed, however, those lack behind in terms of adhesion strength, biocompatibility, and cost-effectiveness. Here, a low-cost, autologous fibrin glue augmented with biopolymer has been developed. Fibrin glue of different compositions were developed and characterized in terms of clotting time, adhesive strength, cytotoxicity, and elemental compositions. Fibrin glue was developed using 5%, 10%, and 20% (w/v) calcium chloride, where 10% was found to be optimum based on clotting time. The average time for clot formation ranged between 3 to 5 minutes and elevated temperature greatly accelerated the clotting. Sodium carboxymethyl cellulose (CMC) and methylcellulose (MC) polymers were added to the fibrin glue at concentrations varying from 0.31% to 1.25%. CMC showed a maximum adhesion strength of 80.9 g/cm2 at 0.63% concentration and MC showed 106.3 g/cm2 at 1.25% concentration. Cytotoxicity analysis (IC50) revealed that the polymers at a concentration greater than 1.25% showed decreased cell viability (<70%). This biopolymer-aided autologous fibrin glue has a very good prospect as it exhibits better performance than commercial glues and is free from the drawbacks reported for the latter ones.

The Effects of Prompt Interventions on Web Survey Response Rate and Data Quality Measures

Previous survey research has found that prompt interventions for speeding and straightlining were effective at reducing these undesirable response behaviors in web surveys. However, the effects of prompt interventions on data quality measures are mixed, and it is unclear how prompt interventions affect key survey estimates. We conducted an experiment on prompt interventions using the National Cancer Institute’s 2019 Health Information National Trends Survey Push-to-Web Pilot Study. We used two types of prompts, one targeted speeding and the other targeted straightlining. We found no significant differences between the prompt and no-prompt conditions in overall web response rates. Also, we found that web respondents assigned to the prompt condition spent more time on the survey, had a lower percent of straightlining, and a lower percent of speeding on grid questions. Regarding key survey estimates, there were significant differences on estimates for one out of 40 items tested.