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1.
Appl Opt ; 62(12): 3242-3251, 2023 Apr 20.
Article in English | MEDLINE | ID: mdl-37133175

ABSTRACT

This paper presents a technique for rapid site-selective control of the quantum state of particles in a large array using the combination of a fast deflector (e.g., an acousto-optic deflector) and a relatively slow spatial light modulator (SLM). The use of SLMs for site-selective quantum state manipulation has been limited due to slow transition times that prevent rapid, consecutive quantum gates. By partitioning the SLM into multiple segments and using a fast deflector to transition between them, it is possible to substantially reduce the average time increment between scanner transitions by increasing the number of gates that can be performed for a single SLM full-frame setting. We analyzed the performance of this device in two different configurations: In configuration 1, each SLM segment addresses the full qubit array; in configuration 2, each SLM segment addresses a subarray and an additional fast deflector positions that subarray with respect to the full qubit array. With these hybrid scanners, we calculated qubit addressing rates that are tens to hundreds of times faster than using an SLM alone.

2.
Opt Express ; 31(5): 8632-8640, 2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36859974

ABSTRACT

Liquid crystal (LC) devices for terahertz phase shifters inevitably use a thick cell gap for the required retardation, severely delaying the LC response. To improve the response, we virtually demonstrate novel LC switching between in-plane and out-of-plane for reversible switching between three orthogonal orientation states, broadening the range of continuous phase shifts. This LC switching is realized using a pair of substrates, each with two pairs of orthogonal finger-type electrodes and one grating-type electrode for in- and out-of-plane switching. An applied voltage generates an electric field that drives each switching process between the three distinct orientation states, enabling a rapid response.

3.
Proc Biol Sci ; 289(1989): 20221649, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36515119

ABSTRACT

Ecosystem structure and function are increasingly threatened by changing climate, with profound effects observed globally in recent decades. Based on standardized visual censuses of reef biodiversity, we describe 27 years of community-level change for fishes, mobile macroinvertebrates and macroalgae in the Tasmanian ocean-warming hotspot. Significant ecological change was observed across 94 reef sites (5-10 m depth range) spanning four coastal regions between three periods (1992-95, 2006-07, 2017-19), which occurred against a background of pronounced sea temperature rise (+0.80°C on average). Overall, fish biomass increased, macroinvertebrate species richness and abundance decreased and macroalgal cover decreased, particularly during the most recent decade. While reef communities were relatively stable and warming was slight between the 1990s and mid-2000s (+0.12°C mean temperature rise), increased abundances of warm affinity fishes and invertebrates accompanied warming during the most recent decade (+0.68°C rise). However, significant rises in the community temperature index (CTI) were only found for fishes, invertebrates and macroalgae in some regions. Coastal warming was associated with increased fish biomass of non-targeted species in fished zones but had little effect on reef communities within marine reserves. Higher abundances of larger fishes and lobsters inside reserves appeared to negate impacts of 'thermophilization'.


Subject(s)
Ecosystem , Seaweed , Animals , Biodiversity , Invertebrates , Temperature , Fishes , Coral Reefs
4.
Sci Rep ; 12(1): 21042, 2022 12 05.
Article in English | MEDLINE | ID: mdl-36470939

ABSTRACT

A comprehensive understanding of controlling the iridescence of cellulose films by manipulating the alignment and helical pitch of cellulose nanocrystals (CNCs) is required to advance cellulose photonics and its optoelectronic applications. Aqueous suspensions of CNCs exhibit a cholesteric liquid crystal (LC) phase with structural color; however, attaining a uniformly colored film is extremely difficult. Presumably, because multiple interrelated factors influence the CNC molecular alignment and helical pitch, existing models are not necessarily conclusive and remain a subject of debate. To eventually achieve homogeneously colored films, we compare aqueous CNC suspensions as a lyotropic liquid LC with thermotropic ones, and we spectroscopically confirm that the coloration of CNC droplets originates from the periodic CNC structure. The suspension drying process significantly influences the quality of iridescence of CNC films. Rapidly drying a droplet of a CNC suspension forms a concentric rainbow film, with red edges and a blue center, typical of the coffee-ring effect observed in air-dried films. By contrast, slow drying under controlled humidity, which reduces capillary flow, provides higher uniformity and a large blue area. Orbitally shaking films while drying under high humidity further improves the uniformity. Therefore, the evaporation rate significantly influences the thermodynamically stabilized helical pitch of CNCs, which determines the structural color. We qualitatively model the kinetic arrest induced by the rapid evaporation of lyotropic LCs in a manner equivalent to that induced by the rate of temperature change in thermotropic LCs and other materials.


Subject(s)
Cellulose , Nanoparticles , Cellulose/chemistry , Freezing , Suspensions , Nanoparticles/chemistry , Water
5.
Sci Rep ; 12(1): 5482, 2022 03 31.
Article in English | MEDLINE | ID: mdl-35361796

ABSTRACT

To unveil a novel switching mechanism in liquid crystal (LC)-based phase shifters for the THz range, we analyse how the dimensions of the electrode structures enable a new type of switching, namely, THz in-plane and THz out-of-plane (TIP-TOP) switching. Specifically, we determine how varying these electrode dimensions influences the LC in-plane states with the corresponding phase shifts by calculating these effects in virtual devices. Interestingly, we found that significant dimensional effects of the in-plane electrode structures statically and dynamically influence the phase shift and response time of LC switching. Analysing the electromagnetic fields in the TIP-TOP cell clearly reveals that these dimensional effects are due to changes in the electric field strengths caused by lateral bus-line electrodes that were originally assumed not to contribute to the switching. Further, we discover that the ultimate dimensional effect produces a novel type of LC switching, which results in hexadirectional switching between the initial, intrinsic in-plane, and out-of-plane reorientations of the LCs, suggesting a broader range of phase shifts while maintaining a rapid response.

7.
ACS Omega ; 5(49): 31880-31890, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33344842

ABSTRACT

Interactions between hydrated Ce3+ and various carboxylates are of fundamental interest. Anomalously strong interactions with Ce3+ occur when diglycolic acid (DGA) is added into a Ce3+ aqueous solution, unlike various other carboxylic acids. Herein, the complex-formation constants of Ce3+ with these acids are evaluated via absorption and emission spectra. Hydrated Ce3+ emits fluorescence with unity quantum yield; however, addition of various carboxylates statically quenches the fluorescence when Ce3+-carboxylate complexes form because the fluorescence lifetime is constant irrespective of the carboxylate concentration. In the observed static quenching, the complex-formation constants obtained from the absorption and emission spectra (K abs and K em) agree well. The binding of Ce3+ by the conjugate Lewis bases, i.e., carboxylates, is approximately inversely proportional to the pH. Adding DGA into the system also statically quenches the fluorescence, but far more efficiently, even in a much weaker solution. We rigorously deduce K abs and K em of Ce3+ with DGA without any approximation using comparable concentrations. Careful fittings provide equivalent K em and K abs values, and by varying the pH and ionic strength, we confirm that this equivalence is an inherent property of the Ce3+-DGA system. The Lewis acid-base theory cannot explain why DGA binds to Ce3+ ∼1000 times more strongly than the other carboxylates. This anomalously strong binding may be due to a chelate effect caused by the DGA's central oxygen atom, which forms a five-membered ring with the conjugate Lewis bases of DGA; double chelate rings can also form, while bis-deprotonated DGA binds to Ce3+, facilitated by the central oxygen. Therefore, DGA enables efficient quenching through the chelate effect when it binds to Ce3+.

8.
Poult Sci ; 99(6): 3286-3291, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32475464

ABSTRACT

This study investigated the combined effects of cooking temperature and time on the meat and eating quality characteristics of the sous-vide chicken breast. For the control group, chicken breast samples were cooked in a convection oven until the internal temperature reached 71°C. Each sample for sous-vide cooking was vacuum packaged and then cooked under continuous thermocontrolled conditions in a water bath at 6 combinations of cooking temperature (60 and 70°C) and time (1, 2, and 3 h). Sous-vide cooked chicken meat at 60°C for 1 h (SV60-1h) showed lower cooking loss (6.58 vs. 26.5%, P < 0.05), Warner-Bratzler shear force (21.7 vs. 29.1 N, P < 0.05), and hardness (9.40 vs. 17.3 N, P < 0.05) than meat cooked by conventional oven. Similar to the objective tenderness parameters, cooked chicken meat from the SV60 treatments for all cooking times showed higher scores in all the tenderness attributes than the control group (P < 0.05). However, a higher flavor intensity was observed in the SV70-3h and control groups than in the SV60 treatments (P < 0.05). Owing to a lesser developed flavor in chicken meat from the SV60-1h treatment, the SV60-2h and 3h treatments were assigned a higher acceptability rating for overall impression (P < 0.05). Therefore, cooking temperature and time of sous-vide significantly influenced the physicochemical and palatability characteristics of chicken breast. In this study, the optimum conditions for the sous-vide chicken breast are to continuously cook at 60°C for 2 to 3 h to improve sensory quality characteristics without reducing the water-holding capacity.


Subject(s)
Cooking/methods , Meat/analysis , Pectoralis Muscles/physiology , Taste , Animals , Chickens , Temperature
9.
Nat Commun ; 10(1): 5524, 2019 12 04.
Article in English | MEDLINE | ID: mdl-31797930

ABSTRACT

CRISPR-Cas systems have revolutionized genome editing across a broad range of biotechnological endeavors. Many CRISPR-Cas nucleases have been identified and engineered for improved capabilities. Given the modular structure of such enzymes, we hypothesized that engineering chimeric sequences would generate non-natural variants that span the kinetic parameter landscape, and thus provide for the rapid selection of nucleases fit for a particular editing system. Here, we design a chimeric Cas12a-type library with approximately 560 synthetic chimeras, and select several functional variants. We demonstrate that certain nuclease domains can be recombined across distantly related nuclease templates to produce variants that function in bacteria, yeast, and human cell lines. We further characterize selected chimeric nucleases and find that they have different protospacer adjacent motif (PAM) preferences and the M44 chimera has higher specificity relative to wild-type (WT) sequences. This demonstration opens up the possibility of generating nuclease sequences with implications across biotechnology.


Subject(s)
CRISPR-Cas Systems , Endonucleases/metabolism , Gene Editing/methods , Recombinant Fusion Proteins/metabolism , Bacteria/genetics , Biotechnology/methods , Endonucleases/genetics , Gene Library , HEK293 Cells , Humans , Mutation , Recombinant Fusion Proteins/genetics , Reproducibility of Results , Yeasts/genetics
10.
ACS Omega ; 4(1): 39-47, 2019 Jan 31.
Article in English | MEDLINE | ID: mdl-31459310

ABSTRACT

We observe potential randomization and constraint of molecular alignment and orientation in an organic semiconductor molecule with increasing temperature up to the phase-transition temperature. Variable-angle spectroscopic ellipsometry and second-harmonic generation are used to study the changes in the molecular alignment in vapor-deposited organic thin films as samples are heated and cooled in a cycle from room temperature to the phase-transition temperature. The films consist of sterically bulky and cross-shaped molecules, 2-cyano-9,10-di(2-naphthyl)anthracene, and the anisotropy of its two moieties is probed. Anisotropic molecular alignment with respect to the surface normal in as-deposited amorphous films changes with the film thickness, which increases slightly with increasing substrate temperature. Moreover, the axis near the long axis of the anthracene moiety changes significantly with respect to the surface normal from the magic angle to isotropic alignment, showing monotonically decreasing anisotropy. Interestingly, the anisotropy of the axis near the long axis of the anthracene moiety disappears before the phase-transition temperature. In contrast, the axis near the short axis of the anthracene moiety exhibits a notable characteristic change in the temperature-dependent alignment during the heating process; although the anisotropy initially decreases, it significantly increases as the temperature approaches the phase transition. At a certain temperature during heating, the film thickness shows a discontinuous jump, similar to a first phase transition, while the anisotropic molecular alignment completely disappears. During the cooling process after the phase transition, however, the properties of the films are irreversibly changed, and anisotropic molecular alignment is no longer observed; thus, the samples become completely isotropic.

12.
Br J Anaesth ; 121(5): 1005-1012, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30336844

ABSTRACT

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions. Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).


Subject(s)
Anesthesia/adverse effects , Anesthesia/psychology , Cognition Disorders/etiology , Cognition Disorders/psychology , Postoperative Complications/psychology , Terminology as Topic , Cognition Disorders/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Emergence Delirium/psychology , Humans , Incidence , Neuropsychological Tests , Preexisting Condition Coverage , Research Design
13.
Can J Anaesth ; 65(11): 1248-1257, 2018 11.
Article in English | MEDLINE | ID: mdl-30324338

ABSTRACT

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).


Subject(s)
Anesthesia/adverse effects , Cognitive Dysfunction/etiology , Postoperative Complications/epidemiology , Surgical Procedures, Operative/adverse effects , Terminology as Topic , Aged , Anesthesia/methods , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cognitive Dysfunction/diagnosis , Delphi Technique , Diagnostic and Statistical Manual of Mental Disorders , Humans , Incidence , Postoperative Complications/diagnosis , Surgical Procedures, Operative/methods , Time Factors
14.
Anesth Analg ; 127(5): 1189-1195, 2018 11.
Article in English | MEDLINE | ID: mdl-30325748

ABSTRACT

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).


Subject(s)
Anesthesia/adverse effects , Cognition Disorders/classification , Cognition , Delirium/classification , Surgical Procedures, Operative/adverse effects , Terminology as Topic , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Consensus , Delirium/diagnosis , Delirium/epidemiology , Delirium/psychology , Delphi Technique , Humans , Incidence , Risk Assessment , Risk Factors , Treatment Outcome
15.
Anesthesiology ; 129(5): 872-879, 2018 11.
Article in English | MEDLINE | ID: mdl-30325806

ABSTRACT

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines (Diagnostic and Statistical Manual for Mental Disorders, fifth edition [DSM-5] and National Institute for Aging and the Alzheimer Association [NIA-AA]) are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).


Subject(s)
Anesthesia/adverse effects , Cognition Disorders/chemically induced , Postoperative Complications/chemically induced , Surgical Procedures, Operative/adverse effects , Terminology as Topic , Aged , Humans
16.
J Alzheimers Dis ; 66(1): 1-10, 2018.
Article in English | MEDLINE | ID: mdl-30347621

ABSTRACT

Cognitive change affecting patients after anaesthesia and surgery has been recognised for more than 100 yr. Research into cognitive change after anaesthesia and surgery accelerated in the 1980s when multiple studies utilised detailed neuropsychological testing for assessment of cognitive change after cardiac surgery. This body of work consistently documented decline in cognitive function in elderly patients after anaesthesia and surgery, and cognitive changes have been identified up to 7.5 yr afterwards. Importantly, other studies have identified that the incidence of cognitive change is similar after non-cardiac surgery. Other than the inclusion of non-surgical control groups to calculate postoperative cognitive dysfunction, research into these cognitive changes in the perioperative period has been undertaken in isolation from cognitive studies in the general population. The aim of this work is to develop similar terminology to that used in cognitive classifications of the general population for use in investigations of cognitive changes after anaesthesia and surgery. A multispecialty working group followed a modified Delphi procedure with no prespecified number of rounds comprised of three face-to-face meetings followed by online editing of draft versions.Two major classification guidelines [Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5) and National Institute for Aging and the Alzheimer Association (NIA-AA)] are used outside of anaesthesia and surgery, and may be useful for inclusion of biomarkers in research. For clinical purposes, it is recommended to use the DSM-5 nomenclature. The working group recommends that 'perioperative neurocognitive disorders' be used as an overarching term for cognitive impairment identified in the preoperative or postoperative period. This includes cognitive decline diagnosed before operation (described as neurocognitive disorder); any form of acute event (postoperative delirium) and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months (postoperative neurocognitive disorder).


Subject(s)
Anesthesia/adverse effects , Cognition Disorders/classification , Cognition/physiology , Postoperative Complications/classification , Terminology as Topic , Cognition Disorders/diagnosis , Cognition Disorders/etiology , Humans , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Time Factors
17.
Acta Anaesthesiol Scand ; 62(9): 1223-1228, 2018 10.
Article in English | MEDLINE | ID: mdl-29926892

ABSTRACT

BACKGROUND: The cricothyroid membrane is the most commonly accessed location for invasive surgical airway. Although the laryngeal handshake method is recommended for identifying the cricothyroid membrane, there is no clinical data regarding the utility of the laryngeal handshake method in cricothyroid membrane identification. The objective of this study was to compare the accuracy of cricothyroid membrane identification between the laryngeal handshake method and simple palpation. METHODS: After anaesthesia induction, the otorhinolaryngology resident and anaesthesia resident identified and marked the needle insertion point for cricothyroidotomy using simple palpation and the laryngeal handshake method, respectively. The cricothyroid membrane was confirmed with ultrasonography. Identification was determined successful if the marked point was placed within the longitudinal area of the cricothyroid membrane and within 5 mm from midline transversely. The accuracy of cricothyroid membrane identification using the laryngeal handshake method and simple palpation was compared. RESULTS: A total of 123 patients were enrolled. The cricothyroid membrane was correctly identified in 87 (70.7%, 95% confidence interval 61.8-78.6%) patients using the laryngeal handshake method compared to 78 (63.4%, 95% confidence interval 54.3-71.9%) patients using simple palpation (P = .188). The time required to identify the cricothyroid membrane was longer when using the laryngeal handshake method (15 [3-48] seconds vs 10.9 [3-55] seconds, P = .003). CONCLUSION: The success rate of identifying the cricothyroid membrane was similar among the anesthesiologists who performed the laryngeal handshake method and also among otorhinolaryngologists who used simple palpation.


Subject(s)
Laryngeal Muscles/anatomy & histology , Larynx/anatomy & histology , Physical Examination/methods , Adult , Aged , Aged, 80 and over , Anesthesiologists/statistics & numerical data , Clinical Competence/statistics & numerical data , Female , Humans , Laryngeal Muscles/diagnostic imaging , Larynx/diagnostic imaging , Male , Middle Aged , Palpation/methods , Reproducibility of Results , Ultrasonography , Young Adult
18.
Gene Ther ; 25(1): 54-65, 2018 01.
Article in English | MEDLINE | ID: mdl-28925992

ABSTRACT

Current treatments of hepatocellular carcinoma (HCC) are ineffective and unsatisfactory in many aspects. Cancer-targeting gene virotherapy using oncolytic adenoviruses (OAds) armed with anticancer genes has shown efficacy and safety in clinical trials. Nowadays, both inhibitor of growth 4 (ING4), as a multimodal tumor suppressor gene, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as a potent apoptosis-inducing gene, are experiencing a renaissance in cancer gene therapy. Herein we investigated the antitumor activity and safety of mono- and combined therapy with OAds armed with ING4 (Ad-ΔB/ING4) and TRAIL (Ad-ΔB/TRAIL) gene, respectively, on preclinical models of human HCC. OAd-mediated expression of ING4 or TRAIL transgene was confirmed. Ad-ΔB/TRAIL and/or Ad-ΔB/ING4 exhibited potent killing effect on human HCC cells (HuH7 and Hep3B) but not on normal liver cells. Most importantly, systemic therapy with Ad-ΔB/ING4 plus Ad-ΔB/TRAIL elicited more eradicative effect on an orthotopic mouse model of human HCC than their monotherapy, without causing obvious overlapping toxicity. Mechanistically, Ad-ΔB/ING4 and Ad-ΔB/TRAIL were remarkably cooperated to induce antitumor apoptosis and immune response, and to repress tumor angiogenesis. This is the first study showing that concomitant therapy with Ad-ΔB/ING4 and Ad-ΔB/TRAIL may provide a potential strategy for HCC therapy and merits further investigations to realize its possible clinical translation.


Subject(s)
Carcinoma, Hepatocellular/therapy , Cell Cycle Proteins/genetics , Genetic Therapy , Homeodomain Proteins/genetics , Liver Neoplasms/therapy , Oncolytic Virotherapy , TNF-Related Apoptosis-Inducing Ligand/genetics , Tumor Suppressor Proteins/genetics , Animals , Apoptosis , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/immunology , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Cytopathogenic Effect, Viral , Humans , Liver Neoplasms/blood supply , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Mice , Mice, Nude , Neovascularization, Pathologic/prevention & control , Transfection , Tumor Microenvironment , Xenograft Model Antitumor Assays
19.
J Clin Pharm Ther ; 42(6): 689-694, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28806472

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: Evogliptin (DA-1229), a novel dipeptidyl peptidase (DPP)-4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome (CYP) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. METHODS: An open-label, two-phase, crossover study was conducted with 12 healthy subjects. On day 1, a single dose of evogliptin 5 mg was administered alone to assess the reference PK profile of evogliptin. On day 10, after a 2-day pretreatment with clarithromycin, evogliptin 5 mg was administered again to evaluate the effect of CYP inhibition on the PK profile of evogliptin. Administration of clarithromycin continued until day 14. Blood sampling in the reference and test phases was performed until 96 and 168 hours after dosing, respectively for PK assays. RESULTS: Eleven of the 12 subjects completed the study, and their data were analysed. In the presence of clarithromycin, exposure to evogliptin increased without any serious adverse events and the geometric mean peak plasma concentration (Cmax ) and area under the concentration-time curve from time 0 extrapolated to infinity (AUC0-∞ ) of evogliptin increased by 116.5% and 89.6%, respectively. WHAT IS NEW AND CONCLUSION: Administration of clarithromycin significantly increased exposure to evogliptin in healthy subjects.


Subject(s)
Clarithromycin/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/pharmacokinetics , Hypoglycemic Agents/pharmacokinetics , Piperazines/pharmacokinetics , Adult , Area Under Curve , Cross-Over Studies , Cytochrome P-450 CYP3A Inhibitors , Diabetes Mellitus, Type 2/drug therapy , Drug Interactions , Healthy Volunteers , Humans , Middle Aged , Republic of Korea , Young Adult
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