Search

Kwang-Hee Shin,1 Ji-Young Jeon,2 Kyungho Jang,2 Tae-Eun Kim,3 Min-Gul Kim2,4 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; 2Center for Clinical Pharmacology and Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Republic of Korea; 3Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea; 4Department of Pharmacology, School of Medicine, Chonbuk National University, Jeonju, Republic of Korea Purpose: The aim of this study was to evaluate the dose-proportional pharmacokinetic characteristics of pregabalin following the administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Subjects and methods: An open-label, randomized, single-dose, parallel study was conducted in 40 eligible subjects who were randomly assigned to receive a single 150, 300, 450, or 600 mg dose of GLA5PR GLARS-NF1. Serial blood samples were collected before and after dosing for 36 hours, and plasma concentrations were determined using liquid chromatography-tandem mass spectrometry. Safety profiles were evaluated throughout the study (trial registration number: NCT02327000).Results: Thirty-seven subjects completed the studies. The area under the plasma concentration-time curve up to the last measurable concentration of pregabalin exhibited dose proportionality following administration of GLA5PR GLARS-NF1 tablets from 150 to 600 mg while its maximum plasma concentration showed dose proportionality at a dose range of 150–450 mg. The safety evaluations showed no clinically significant finding after administration of GLA5PR GLARS-NF1 tablets (150, 300, 450, and 600 mg) in the fed state.Conclusions: The dose-proportional properties of GLA5PR GLARS-NF1 150–450 mg tablets were determined. Keywords: gamma-aminobutyric acid analog, GABA analog, maximum concentration, safety evaluation, Korean

Tae-Eun Kim,1 Kwang-Hee Shin,2 Jeong-Eun Park,2 Min-Gul Kim,3 Yeo-Min Yun,4 Dong-Hee Choi,5 Kyoung Ja Kwon,5 Jongmin Lee6 1Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea; 2Department of Pharmacotherapy & Translational Research, College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, Republic of Korea; 3Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea; 4Department of Laboratory Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea; 5Department of Medical Science, Konkuk University School of Medicine, Seoul, Republic of Korea; 6Department of Rehabilitation Medicine, Konkuk University School of Medicine, Seoul, Republic of Korea Background: Previous in vitro studies have reported the inhibitory effect of green tea on p-glycoprotein (p-gp) encoded by ABCB1. This study aimed to investigate the effect of green tea on the pharmacokinetics of digoxin, a typical probe drug of p-gp. Methods: Sixteen healthy volunteers participated in this study. At Day 1, 0.5 mg of digoxin was administered via oral route. After a 14-day washout period, 630 mg of green tea catechins (GTC) was administered via oral route, followed by 0.5 mg of digoxin 1 hour later. From Day 16 through Day 28, 630 mg of GTC was administered alone. At Day 29, 630 mg of GTC and 0.5 mg of digoxin were administered in the same way as Day 15. Blood samples for the pharmacokinetic assessments of digoxin were collected up to 8 hours after each dose. Pharmacokinetic parameters were estimated by noncompartmental analysis. Area under the curve (AUC) and peak plasma concentration (Cmax) were compared using mixed effect model between digoxin alone and digoxin with GTC. ABCB1 was genotyped to determine whether its polymorphism affects digoxin–GTC interaction. Results: Fifteen subjects completed the study. Compared to digoxin alone, the concomitant administration of digoxin and GTC significantly reduced the systemic exposure of digoxin: geometric mean ratios (GMR) and 90% confidence intervals (CI) of area under the concentration–time curve from time 0 to the last measurable time (AUClast) and Cmax were 0.69 (0.62–0.75) and 0.72 (0.61–0.85), respectively. The concomitant administration of digoxin and GTC following pretreatment of GTC (Day 29) similarly reduced the AUClast (GMR [90% CI]: 0.67 [0.61–0.74]) and Cmax (GMR [90% CI]: 0.74 [0.63–0.87]). In the comparison of the percentage changes from Day 1 (digoxin single administration) of AUClast between genotypes, C1236T variant type showed a significant difference to wild-type on Day 15 (concomitant administration of digoxin and GTC) (P=0.005). Conclusion: This study demonstrates that the coadministration of GTC reduces the systemic exposure of digoxin regardless of pretreatment of GTC. Keywords: digoxin, green tea, catechin, p-glycoprotein, pharmacokinetics, drug interaction

Kwang-Hee Shin,1 Hyeon Cheol Jeong,1 Dong-Hee Choi,2 Sung Nyun Kim,3 Tae-Eun Kim4 1College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 2Department of Medical Science, Konkuk University School of Medicine, 3Department of Psychiatry, Seoul Medical Center, 4Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea Background: Although many studies have investigated the association of a single nucleotide polymorphism in TNF-α G-308A gene with depression, their association is still controversial. To clarify this, we performed a meta-analysis.Method: Studies related to TNF-α G-308A and depression were retrieved from PubMed, Medline, Embase, and Scopus (up to April 18, 2017). The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in the models of allele comparison (G vs A), homozygote comparison (GG vs AA), dominant (GG vs GA + AA), and recessive (GG + GA vs AA) to estimate the strength of the associations.Results: A total of 10 case–control studies were included in this meta-analysis. Overall, no significant association between TNF-α G-308A and depression was found (G vs A: OR [95% CI] =1.09 [0.92, 1.29]; GG vs AA: 1.24 [0.71, 2.15]; GG vs GA + AA: 1.01 [0.76, 1.35]; GG + GA vs AA: 1.22 [0.70, 2.13]). In subgroup analyses by ethnicity or age group, no statistically significant association between TNF-α G-308A polymorphisms and depression was shown.Conclusion: This meta-analysis revealed that TNF-α G-308A polymorphism is not associated with susceptibility to depression. Keywords: TNF-α G-308A, rs1800629, genetic polymorphism, depressive disorder

Tae-Eun Kim,1 Na Ha,2 Yunjeong Kim,2 Hyunsook Kim,1 Jae Wook Lee,3 Ji-Young Jeon,2 Min-Gul Kim2,4 1Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, 2Center for Clinical Pharmacology, Biomedical Research Institute, Chonbuk National University Hospital, Jeonju, Jeonbuk, 3Nephrology Clinic, National Cancer Center, Goyang, Gyeonggi-do, 4Department of Pharmacology, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea Abstract: Previous in vitro studies have demonstrated the inhibitory effect of green tea on drug transporters. Because rosuvastatin, a lipid-lowering drug widely used for the prevention of cardiovascular events, is a substrate for many drug transporters, there is a possibility that there is interaction between green tea and rosuvastatin. The aim of this study was to investigate the effect of green tea on the pharmacokinetics of rosuvastatin in healthy volunteers. An open-label, three-treatment, fixed-sequence study was conducted. On Day 1, 20 mg of rosuvastatin was given to all subjects. After a 3-day washout period, the subjects received 20 mg of rosuvastatin plus 300 mg of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea (Day 4). After a 10-day pretreatment of EGCG up to Day 14, they received rosuvastatin (20 mg) plus EGCG (300 mg) once again (Day 15). Blood samples for the pharmacokinetic assessments were collected up to 8 hours after each dose of rosuvastatin. A total of 13 healthy volunteers were enrolled. Compared with the administration of rosuvastatin alone, the concomitant use at Day 4 significantly reduced the area under the concentration–time curve from time 0 to the last measurable time (AUClast) by 19% (geometric mean ratio 0.81, 90% confidence interval [CI] 0.67–0.97) and the peak plasma concentration (Cmax) by 15% (geometric mean ratio 0.85, 90% CI 0.70–1.04). AUClast or Cmax of rosuvastatin on Day 15 was not significantly different from that on Day 1. This study demonstrated that co-administration of EGCG reduces the systemic exposure of rosuvastatin by 19%, and pretreatment of EGCG can eliminate that effect of co-administration of EGCG. Keywords: rosuvastatin, green tea, EGCG, pharmacokinetics, drug interaction, drug transporter

Tae-Eon Kim,1–3,* Chang Gun Kim,1–3,* Jin Soo Kim,4 Songwan Jin,4 Sik Yoon,5 Hae-Rahn Bae,6 Jeong-Hwa Kim,7,8 Young Hun Jeong,7,8 Jong-Young Kwak1–3 1Department of Pharmacology, School of Medicine, 2Department of Biomedical Sciences, The Graduate School, Ajou University, Suwon, South Korea; 3Immune Network Pioneer Research Center, Ajou University Medical Center, Suwon, South Korea; 4Department of Mechanical Engineering, Korea Polytechnic University, Gyeonggi, South Korea; 5Department of Anatomy, School of Medicine, Pusan National University, Yangsan, South Korea; 6Department of Physiology, College of Medicine, Dong-A University, Busan, South Korea; 7School of Mechanical Engineering, 8Department of Mechanical Engineering, Graduate School, Kyungpook National University, Daegu, South Korea *These authors contributed equally to this work Abstract: An artificial three-dimensional (3D) culture system that mimics the tumor microenvironment in vitro is an essential tool for investigating the cross-talk between immune and cancer cells in tumors. In this study, we developed a 3D culture system using an electrospun poly(ε-caprolactone) (PCL) nanofibrous scaffold (NFS). A hybrid NFS containing an uninterrupted network of nano- and submicron-scale fibers (400 nm to 2 µm) was generated by deposition onto a stainless steel mesh instead of an aluminum plate. The hybrid NFS contained multiplanar pores in a 3D structure. Surface-seeded mouse CT26 colon cancer cells and bone marrow-derived dendritic cells (BM-DCs) were able to infiltrate the hybrid NFS within several hours. BM-DCs cultured on PCL nanofibers showed a baseline inactive form, and lipopolysaccharide (LPS)-activated BM-DCs showed increased expression of CD86 and major histocompatibility complex Class II. Actin and phosphorylated FAK were enriched where unstimulated and LPS-stimulated BM-DCs contacted the fibers in the 3D hybrid NFS. When BM-DCs were cocultured with mitoxantrone-treated CT26 cells in a 3D hybrid NFS, BM-DCs sprouted cytoplasm to, migrated to, synapsed with, and engulfed mitoxantrone-treated CT26 cancer cells, which were similar to the naturally occurring cross-talk between these two types of cells. The 3D hybrid NFS developed here provides a 3D structure for coculture of cancer and immune cells. Keywords: 3D cell culture, electrospinning, nanofibrous scaffold, dendritic cell, colon cancer cell

Jin Ah Jung,1 Tae-Eun Kim,2 Hyun Lee,3 Byeong-Ho Jeong,3 Hye Yun Park,3 Kyeongman Jeon,3 O Jung Kwon,3 Jae-Wook Ko,4 Rihwa Choi,5 Hye-In Woo,6 Won-Jung Koh,3 Soo-Youn Lee4,5 1Department of Clinical Pharmacology, Inje University College of Medicine, Inje University Busan Paik Hospital, Busan, Korea; 2Department of Clinical Pharmacology, Konkuk University Medical Center, 3Division of Pulmonary and Critical Care Medicine, Department of Medicine, 4Department of Clinical Pharmacology and Therapeutics, 5Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 6Department of Laboratory Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea Background/aim: Isoniazid (INH) is an essential component of first-line anti-tuberculosis (TB) treatment. However, treatment with INH is complicated by polymorphisms in the expression of the enzyme system primarily responsible for its elimination, N-acetyltransferase 2 (NAT2), and its associated hepatotoxicity. The objective of this study was to develop an individualized INH dosing regimen using a pharmacogenetic-driven model and to apply this regimen in a pilot study.Methods: A total of 206 patients with TB who received anti-TB treatment were included in this prospective study. The 2-hour post-dose concentrations of INH were obtained, and their NAT2 genotype was determined using polymerase chain reaction and sequencing. A multivariate regression analysis that included the variables of age, sex, body weight, and NAT2 genotype was performed to determine the best model for estimating the INH dose that achieves a concentration of 3.0–6.0 mg/L. This dosing algorithm was then used for newly enrolled 53 patients.Results: Serum concentrations of INH were significantly lower in the rapid-acetylators than in the slow-acetylators (2.55 mg/L vs 6.78 mg/L, median, P

Ankeet D Udani,1 T Edward Kim,2,3 Steven K Howard,2,3 Edward R Mariano2,3On behalf of the ADAPT (Anesthesiology-Directed Advanced Procedural Training) Research Group1Department of Anesthesiology, Duke University School of Medicine, Durham, NC, USA; 2Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; 3Anesthesiology and Perioperative Care Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USAAbstract: The emerging subspecialty of regional anesthesiology and acute pain medicine represents an opportunity to evaluate critically the current methods of teaching regional anesthesia techniques and the practice of acute pain medicine. To date, there have been a wide variety of simulation applications in this field, and efficacy has largely been assumed. However, a thorough review of the literature reveals that effective teaching strategies, including simulation, in regional anesthesiology and acute pain medicine are not established completely yet. Future research should be directed toward comparative-effectiveness of simulation versus other accepted teaching methods, exploring the combination of procedural training with realistic clinical scenarios, and the application of simulation-based teaching curricula to a wider range of learner, from the student to the practicing physician.Keywords: regional anesthesia, simulation, medical education, ultrasound, nerve block, simulator

Jin Ah Jung,1 Soo-Yun Lee,2 Tae-Eun Kim,3 Jung-Ryul Kim,1 Chin Kim,4 Wooseong Huh,1,5 Jae-Wook Ko1,2 1Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, 2Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, 3Department of Clinical Pharmacology, Konkuk University Medical Center, 4Clinical Research Team, CKD Pharmaceuticals, 5Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Aims: Lobeglitazone has been developed for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate potential drug–drug interactions between lobeglitazone and warfarin, an anticoagulant with a narrow therapeutic index.Methods: In this open-label, three-treatment, crossover study, 24 healthy male subjects were administered lobeglitazone (0.5 mg) for 1–12 days with warfarin (25 mg) on day 5 in one period. After a washout interval, subjects were administered warfarin (25 mg) alone in the other period. Pharmacokinetics of R- and S-warfarin and lobeglitazone, as well as pharmacodynamics of warfarin, as measured by international normalized ratio (INR) and factor VII activity, were assessed. Results: The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) for area under the curve from time zero to the time of the last quantifiable concentration (AUClast) for warfarin + lobeglitazone: warfarin alone were 1.0076 (90% CI: 0.9771, 1.0391) for R-warfarin and 0.9880 (90% CI: 0.9537, 1.0235) for S-warfarin. The maximum observed plasma concentration (Cmax) values were 1.0167 (90% CI: 0.9507, 1.0872) for R-warfarin and 1.0028 (90% CI: 0.9518, 1.0992) for S-warfarin, both of which were contained in the interval 0.80–1.25. Lobeglitazone had no effect on the area under the effect–time curve from time 0 to 168 hours (AUEC) of INR and factor VII activity, as demonstrated by the GMRs of 1.0091 (90% CI: 0.9872, 1.0314) and 0.9355 (90% CI: 0.9028, 0.9695), respectively. In addition, the pharmacokinetics of lobeglitazone was also unaffected by warfarin.Conclusion: Concomitant administration of lobeglitazone and warfarin was well tolerated. Lobeglitazone had no meaningful effect on the pharmacokinetics or pharmacodynamics of warfarin. These findings indicate that lobeglitazone and warfarin can be coadministered without dosage adjustments for either drug. Keywords: lobeglitazone, thiazolidinedione, warfarin, pharmacokinetics, pharma­codynamics

Namyi Gu,1,3,* Min Kyu Park,1,4,* Tae-Eun Kim,1,5 Mi Young Bahng,2 Kyoung Soo Lim,1 Sang-Heon Cho,1 Seo Hyun Yoon,1 Joo-Youn Cho,1 In-Jin Jang,1 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea; 2Clinical Development Department, Dong-A ST Co, Ltd, Seoul, Republic of Korea; 3Department of Clinical Pharmacology and Therapeutics, Dongguk University College of Medicine and Ilsan Hospital, Goyang, Gyeonggi-do, Republic of Korea; 4Department of Clinical Pharmacology and Therapeutics, Dong-A University College of Medicine and Hospital, Busan, Republic of Korea; 5Department of Clinical Pharmacology and Therapeutics, Kunkuk University Medical Center, Seoul, Republic of Korea *These authors contributed equally to this work Purpose: Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase IV (DPP-IV) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles and tolerability of evogliptin after repeated oral administration in healthy subjects.Patients and methods: A block-randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study was performed in a total of 30 subjects. Repeated once-daily doses of 5, 10, or 20 mg evogliptin or the same doses of placebo were orally administered to ten subjects in each dosage group for 10 days. Subjects in each group were randomized to receive evogliptin or placebo with a ratio of 8:2. Pharmacokinetics of evogliptin were evaluated, with its concentrations in serial plasma and urine samples collected following the first and last administrations. DPP-IV activity and glucagon-like peptide-1, glucose, and insulin levels were quantified to evaluate evogliptin's pharmacodynamics on the first and last dosing days.Results: All participants completed the study without any serious or severe adverse event. The evogliptin plasma concentration reached its peak within 4–5 hours and decreased relatively slowly, with a terminal elimination half-life of 33–39 hours. Repeated administration resulted in a 1.4- to 1.5-fold accumulation. Evogliptin's systemic exposure and inhibition of plasma DPP-IV activity increased in a dose-dependent manner. Inhibition of DPP-IV activity >80% was sustained over 24 hours in all evogliptin dose groups and provided an increase in postprandial active glucagon-like peptide-1 levels by 1.5- to 2.4-fold. Postprandial glucose levels in the evogliptin-treated groups were reduced 20%–35% compared to placebo, but were not accompanied by increased insulin levels.Conclusion: Repeated administration of evogliptin in healthy subjects was well tolerated and exhibited linear pharmacokinetics within the 5–20 mg dose range. A once-daily regimen of 5–20 mg evogliptin effectively inhibited DPP-IV activity.Keywords: DPP-IV, GLP-1, insulin, glucagon-like peptide-1, glucose

Seonghae Yoon,1,* Howard Lee,2,* Tae-Eun Kim,1 SeungHwan Lee,1 Dong-Hyun Chee,3 Joo-Youn Cho,1 Kyung-Sang Yu,1 In-Jin Jang1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, 2Clinical Trials Center, Seoul National University Hospital, 3AbbVie Ltd., Seoul, Republic of Korea *These authors contributed equally to this work Background: This study was conducted to compare the oral bioavailability of an itopride extended-release (ER) formulation with that of the reference immediate-release (IR) formulation in the fasting state. The effect of food on the bioavailability of itopride ER was also assessed. Methods: A single-center, open-label, randomized, multiple-dose, three-treatment, three-sequence, crossover study was performed in 24 healthy male subjects, aged 22–48 years, who randomly received one of the following treatments for 4 days in each period: itopride 150 mg ER once daily under fasting or fed conditions, or itopride 50 mg IR three times daily in the fasting state. Steady-state pharmacokinetic parameters of itopride, including peak plasma concentration (Cmax) and area under the plasma concentration versus time curve over 24 hours after dosing (AUC0–24h), were determined by noncompartmental analysis. The geometric mean ratio of the pharmacokinetic parameters was derived using an analysis of variance model. Results: A total of 24 healthy Korean subjects participated, 23 of whom completed the study. The geometric mean ratio and its 90% confidence interval of once-daily ER itopride versus IR itopride three times a day for AUC0–24h were contained within the conventional bioequivalence range of 0.80–1.25 (0.94 [0.88–1.01]), although Cmax was reached more slowly and was lower for itopride ER than for the IR formulation. Food delayed the time taken to reach Cmax for itopride ER, but AUC0–24h was not affected. There were no serious adverse events and both formulations were generally well tolerated. Conclusion: At steady state, once-daily itopride ER at 150 mg has a bioavailability comparable with that of itopride IR at 50 mg given three times a day under fasting conditions. Food delayed the absorption of itopride ER, with no marked change in its oral bioavailability. Keywords: itopride, extended-release, immediate-release, bioavailability, pharmacokinetics

Non-Hermitian systems can be tuned to exhibit exceptional points, where both eigenvalues and eigenstates coalesce concurrently. The inherent adaptability of photonic non-Hermitian systems in configuring gain and loss has allowed us to observe a plethora of counterintuitive phenomena, largely as a consequence of the eigenspace reduction at these exceptional points. In this work, we propose a non-Hermitian metasurface that, through the incorporation of gain, enables complete asymmetric polarization conversion at an exceptional point with a zero eigenvalue. Specifically, we provide numerical evidence for this concept by designing a non-Hermitian metasurface that facilitates polarization conversion from right to left circular polarization, while preventing conversion in the reverse direction and co-polarized transmission. Furthermore, our investigation reveals that this specific form of complete asymmetric polarization conversion results in maximum circular dichroism in transmission, thereby eliminating the need for external chirality or three-dimensional helical structures. This non-Hermitian technique offers an intriguing approach to designing polarization-sensitive optical devices and systems, further expanding their functionalities and capabilities.

Next-generation 6G communication holds the potential to revolutionize data transfer, enabling the realization of eXtended Reality (XR) with enhanced sensory experiences. To achieve this, advanced components such as high-performance intensity/phase modulators, waveguides, multiplexers, splitters, combiners, and filters operating in terahertz (THz) regime, specifically within the frequency range of 0.1–1 THz, are essential. However, existing microwave equipment and vector network analyzers designed for this frequency range suffer from limitations in resolution, stability, and accuracy when evaluating the intensity and phase responses of critical 6G THz devices. In this comprehensive review, we delve into the critical device requirements and emerging trends in next-generation 6G communication, essential performance evaluation parameters, comparisons between microwave and nano/microphotonic devices for testing, and the application of high-resolution THz sensors in 6G Internet-of-Things (IoT) scenarios. Notably, a frequency comb in the photonic regime emerges as the prime candidate for achieving precision evaluations of 6G networks and devices. Consequently, this review highlights the latest research in frequency comb measurements in the 6G THz frequency regime, with a particular emphasis on nano/microphotonic devices and metamaterials. The integration of frequency comb measurements into 6G and THz photonic devices and networks promises to accelerate the realization of high-density next-generation 6G communication.

Theory of situational privacy and self-disclosure posits that perceived levels of privacy are determined by perceptions of the environment, and that certain levels of privacy are necessary for self-disclosure. In video consultations, auditory and visual aspects of the doctor’s environment can cause patients to experience more or less privacy. To provide empirical evidence for these theoretical assumptions, we conducted a 2 (auditory environmental factor: doctor wearing headphones vs. not) by 2 (visual environmental factor: doctor showing the entire office vs. not) between-subjects scenario-based experiment (N = 163). Participants imagined themselves in a video consultation with a doctor and reported their information and territory privacy concerns and willingness to disclose to the doctor. Results showed that the ability to see the doctor’s entire office led to lower information privacy concerns, which – in turn – were associated with increased willingness to disclose medical information to a doctor. Wearing headphones by the doctor did not affect privacy concerns and self-disclosure. Manipulations of both the auditory and visual environment were not significantly associated with territory privacy concerns. These results provide direction for further research on environmental factors and their impact on patients’ privacy concerns and self-disclosure during medical video communications.

Abstract Undeveloped eggs occur frequently in birds and are often considered infertile, and discarded. However, the majority of undeveloped eggs may in fact have been fertilised and embryos might have died at an early stage. Such eggs contain valuable information, for example about offspring sex and paternity, and level of inbreeding. Obtaining such information may also give insight into the patterns and causes of early embryo mortality. Here we describe a simple technique for removing embryo cells from the blastoderm to obtain DNA to genotype the offspring and unequivocally ascertain fertilisation status, while retaining the overlying perivitelline layer (PVL) for sperm counts over the entire membrane. We tested this method on freshly collected eggs (high‐quality material), as well as on eggs from abandoned clutches and unhatched eggs (potentially deteriorated material) of blue tits (Cyanistes caeruleus). We sampled a total of 707 eggs from a wild population of blue tits, extracted DNA from the eggs' blastoderm using a Qiagen kit, and genotyped the samples with 14 polymorphic microsatellite markers, plus one sexing marker. Overall, we successfully genotyped 97% of all eggs. Our study is the most extensive dataset of genotyped undeveloped eggs to date and demonstrates that one can reliably genotype undeveloped fertile eggs as well as retain the PVL for observations of sperm and embryo cells.

Anisotropic materials with chirality or birefringence can be used to manipulate the polarization states of electromagnetic waves. However, the comparatively low anisotropy of natural materials hinders the miniaturization of optical components and devices at terahertz frequencies. In this study, we experimentally demonstrate that the relative phase retardation of a THz wave can be electrically controlled by integrating patterned mono- and bilayer graphene onto an otherwise isotropic metasurface. Specifically, we show that a refractive index for one of the orthogonal polarization states can be electrically controlled by modulating graphene’s conductivity, thereby weakening the capacitive coupling between adjacent meta-atoms in an anisotropic manner. With monolayer graphene, phase retardation of 15° to 81° between two orthogonal polarization states can be achieved. Maximum phase retardation of 90° through a metasurface with bilayer graphene suggests its use as a tunable quarter-wave plate. Continuous control from linear- to circular-polarization states may provide a wide range of opportunities for the development of compact THz polarization devices and polarization-sensitive THz technology.

Objective Video consultations (VCs) were made available to the general population during the COVID-19 pandemic to compensate for the cutback of face-to-face doctor–patient interactions. However, little is known about what patient-related (e.g. age), physician-related (e.g. patient–physician relationship) and technology-related (e.g. online privacy concerns) factors contribute to video consultation satisfaction among patients. This study aims to gain a better understanding of what makes patients satisfied with video consultations. Methods A total of 180 patients who recently engaged in a video consultation were invited to answer questions about patient-, physician- and technology-related variables and their satisfaction with the video consultation. To examine which factors predict patient video consultation satisfaction, a multiple hierarchical regression analysis was performed. Results Overall, patients were satisfied with their video consultation. The final hierarchical model, including all patient-related, physician-related and technology-related factors, significantly contributed to patient video consultation satisfaction. Predictors of higher patient video consultation satisfaction were experiencing less technical issues, having higher general positive attitudes towards online communication, reporting higher importance of less travel time and being more satisfied with physicians’ affective and instrumental communication. Conclusions Video consultations can be appropriate in a variety of situations, provided that technical issues can be minimized, patients have a positive attitude towards online communication and attach value to reduced travel time and online patient–physician interactions can be experienced as affective and instrumental. Findings from this study contribute to understanding how video consultations can be best utilized for effective patient–physician communication.

Background: Thyroid dysfunction may have adverse effects on Fontan hemodynamics. Data on thyroid function in pediatric Fontan patients with or without protein-losing enteropathy (PLE) are limited. Methods: This retrospective multicenter study included 67 Fontan patients (median age 10.9 years; 35.8% female; 28.4% PLE) in whom thyroid function testing was performed. Results: Subclinical hypothyroidism (SHT) was present in 16 (23.9%) patients. Subjects with SHT had significantly lower systolic blood pressure (p = 0.014) and body weight z-score (p = 0.006), were in a worse New York Heart Association (NYHA) functional class (p = 0.004), were more often pacing dependent (p = 0.007), and were more likely to have PLE (p = 0.033, 8/19 (42.1%) patients). Serum thyroid stimulating hormone (TSH) levels were significantly higher in patients with NYHA class ≥ II (p = 0.005), significant atrioventricular valve regurgitation (p = 0.023), elevated serum natriuretic peptides (p = 0.031), and in those with PLE (p = 0.002). Patients with active PLE had significantly higher TSH levels than those in remission (p = 0.003). A strong inverse relationship was found between lower free triiodothyronine (fT3) levels and natriuretic peptides (r: −0.599, p = 0.040). Using binary logistic regression analysis we found that worse NYHA class was an independent predictor of SHT (OR 4.2; 95% CI 1.1–16.1, p = 0.036). Conclusions: Subclinical thyroid dysfunction is common in Fontan, particularly in patients with hemodynamic derangements and PLE. Future studies are needed to address the prognostic implications of thyroid dysfunction in the Fontan population.

BackgroundThe birth of a premature infant and subsequent hospitalization are stressful events for parents. Therefore, accurate and easy-to-understand communication between parents and health care professionals is crucial during this period. Mobile health (mHealth) technologies have the potential to improve communication with parents at any time and place and possibly reduce their stress. ObjectiveWe aimed to conduct a 2-part explorative needs assessment in which the interaction between the pediatrician and parents was examined along with their digital communication technology needs and interest in an mHealth app with the aim of improving interpersonal communication and information exchange. MethodsOverall, 19 consultations between parents of preterm infants and pediatricians were observed to determine which themes are discussed the most and the number of questions asked. Afterward, the parents and the pediatrician were interviewed to evaluate the process of communication and gauge their ideas about a neonatal communication mHealth app. ResultsThe observations revealed the following most prevalent themes: breastfeeding, criteria for discharge, medication, and parents’ personal life. Interview data showed that the parents were satisfied with the communication with their pediatrician. Furthermore, both parents and pediatricians expected that a neonatal mHealth app could further improve the communication process and the hospital stay. Parents valued app features such as asking questions, growth graphs, a diary function, hospital-specific information, and medical rounds reports. ConclusionsBoth parents of hospitalized preterm infants and pediatricians expect that the hypothetical mHealth app has the potential to cater to the most prevalent themes and improve communication and information exchange. Recommendations for developing such an app and its possible features are also discussed. On the basis of these promising results, it is suggested to further develop and study the effects of the mHealth app together with all stakeholders.

Exceptional points (EPs), also known as non-Hermitian degeneracies, have been observed in parity-time symmetric metasurfaces as parity-time symmetry breaking points. However, the parity-time symmetry condition puts constraints on the metasurface parameter space, excluding the full examination of unique properties that stem from an EP. Here, we thus design a general non-Hermitian metasurface with a unit cell containing two orthogonally oriented split-ring resonators (SRRs) with overlapping resonance but different scattering rates and radiation efficiencies. Such a design grants us full access to the parameter space around the EP. The parameter space around the EP is first examined by varying the incident radiation frequency and coupling between SRRs. We further demonstrate that the EP is also observable by varying the incident radiation frequency along with the incident angle. Through both methods, we validate the existence of an EP by observing unique level crossing behavior, eigenstate swapping under encirclement, and asymmetric transmission of circularly polarized light.

Category: Ankle; Sports Introduction/Purpose: Chronic ankle instability is a common condition that can be treated with lateral ankle ligament repair. These procedures have a reported success rate greater than 85% in the literature, but little has been reported about the differences in postoperative outcomes between males and females. The purpose of this study was to evaluate sex-specific outcomes following lateral ankle ligament repair. Methods: In this systematic review and meta-analysis, we utilized Preferred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) criteria to search for articles on electronic databases. Inclusion criteria consisted of English-language, in-vivo clinical studies, mean follow-up of at least one year, sex-specific evaluation of outcomes, and study participants who underwent primary lateral ligament repair. Functional postoperative outcomes for males and females were recorded and statistically analyzed. Results: Out of 2,768 studies, eight (0.29%) met inclusion criteria and were analyzed in this review. These studies included 631 patients (409 males [65%] and 222 females [35%]) who underwent primary lateral ligament repair for ankle instability. There was no statistically significant difference between males and females in terms of Karlsson scores (93.5 +- 1.6 for males, 92.7+- 2.3 for females, P =.1582) or American Orthopaedic Foot & Ankle Society (AOFAS) scores (90.44 +- 4.82 for males, 90.19 +- 3.54 for females, P =.1586). Postoperative success was defined as a 'good' or 'excellent' Karlsson score (>81), and success rate analysis revealed no statistically significant difference between males and females (86% +- 7.1% for males, 87% +- 3.5% for females, P =.9374). Conclusion: There was no difference in postoperative mean Karlsson scores, AOFAS scores, or success rates between males and females who underwent primary lateral ankle ligament repair. This surgical procedure appears to have comparable outcomes in both sexes; however, more research is warranted to further assess the impact of patient sex on postoperative outcomes.

Background:. It has been postulated that the process of—and stresses associated with—medical training may cause a loss of empathy among trainees. Because empathy is considered an important value for clinicians and may even be associated with better patient outcomes, we assessed the empathy of orthopaedic surgery trainees and identified factors associated with empathy. Methods:. Between June and September 2020, an anonymous survey was distributed electronically to trainees in 23 Accreditation Council for Graduate Medical Education-accredited orthopaedic surgery residency programs via the Collaborative Orthopaedic Educational Research Group. The survey comprised the validated Short-Form 8-Item Empathy Quotient (EQ-8) questionnaire—scored on a scale of 0, least empathetic, to 16, most empathetic—and single-item measure of emotional exhaustion and depersonalization derived from the Maslach Burnout Index—scored using a frequency scale. In total, 438 of 605 (72%) trainees completed the survey. The scores were compared via one-way analysis of variance, with Bonferroni correction and Tukey post-hoc testing, α = 0.05. Results:. The mean (±SD) EQ-8 score among respondents was 11.3 ± 3.3. Women scored significantly higher (mean, 12.2 ± 2.8) than men (mean, 11.2 ± 3.3) (p = 0.02). Mean scores were significantly higher for trainees planning on a career in academic medicine (12.0 ± 2.9) than those intending to pursue private practice (10.9 ± 3.3) or those with a military commitment (10.4 ± 3.4) (p = 0.01). An inverse relationship was found between EQ-8 scores and single-item Maslach Burnout Index measures in depersonalization and emotional exhaustion (both, p < 0.01). No significant differences were found in EQ-8 scores across postgraduate year, program location, primary training setting, intended fellowship, relationship status, or whether they reported having children. Conclusions:. We found no association between postgraduate year and EQ-8 score. Women and those intending to pursue a career in academic medicine had significantly higher levels of empathy. A significant inverse relationship was found between burnout and empathy. Respondents with higher levels of emotional exhaustion and depersonalization had lower levels of empathy.

Objective To assess the diagnostic accuracy of antigen compared with reverse transcriptase (RT)-PCR testing in an asymptomatic athlete screening programme and to monitor infection in college athletes.Methods Quidel Sofia-2 SARS-CoV-2 Antigen Tests were performed daily before sports participation for football, basketball, wrestling and water polo from 29 September 2020 to 28 February 2021. Paired RT-PCR and antigen tests were performed at least once a week. Positive antigen tests were confirmed with RT-PCR.Results 81 175 antigen and 42 187 RT-PCR tests were performed, including 23 462 weekly paired antigen/RT-PCR screening tests in 1931 athletes. One hundred and seventy-two athletes had a positive screening RT-PCR (0.4%), of which 83 (48%) occurred on paired testing days. The sensitivity of antigen tests varied with the frequency of RT-PCR testing and prevalence of COVID-19. The sensitivity of antigen testing was 35.7% (95% CI: 17% to 60%) and specificity 99.8% (95% CI: 99.7% to 99.9%) with once-a-week RT-PCR testing after adjusting for school prevalence. Daily antigen testing was similar to RT-PCR testing two to three times a week in identifying infection. Antigen testing identified infection before the next scheduled PCR on 89 occasions and resulted in 234 days where potentially infectious athletes were isolated before they would have been isolated with RT-PCR testing alone. Two athletic-related outbreaks occurred; 86% of total infections were community acquired.Conclusion Antigen testing has high specificity with a short turnaround time but is not as sensitive as RT-PCR. Daily antigen testing or RT-PCR testing two to three times a week is similar. There are benefits and drawbacks to each testing approach.

OBJECTIVES: Noninvasive technology may assist the emergency department (ED) physician in determining the hemodynamic status in critically ill patients. The objective of our study was to show that ED physicians can accurately measure cardiac index (CI) by performing a bedside focused cardiac ultrasound examination. METHODS: A convenience sample of adult subjects were prospectively enrolled. Cardiac index, left ventricular outflow tract (LVOT) diameter, velocity time integral (VTI), stroke volume index, and heart rate were obtained by trained ED physicians and a certified cardiac sonographer. The primary outcome was percent of optimal LVOT diameter and VTI measurements as verified by an expert cardiologist. RESULTS: One hundred patients were enrolled, with obtainable CI measurements in 97 patients. Cardiac index, LVOT diameter, VTI, stroke volume index, and heart rate measurements by ED physician were 2.42 ± 0.70 L min(-1) m(-2), 2.07 ± 0.22 cm, 18.30 ± 3.71 cm, 32.34 ± 7.92 mL beat(-1) m(-2), and 75.32 ± 13.45 beats/min, respectively. Measurements of LVOT diameter by ED physicians and sonographer were optimal in 90.0% (95% confidence interval, 82.6%-94.5) and 91.3% (73.2%-97.6%) of patients, respectively. Optimal VTI measurements were obtained in 78.4% (69.2%-85.4%) and 78.3% (58.1%-90.3%) of patients, respectively. In 23 patients, the correlation (r) for CI between ED physician and sonographer was 0.82 (0.60-0.92), with bias and limits of agreement of -0.11 (-1.06 to 0.83) L min(-1) m(-2) and percent difference of 12.4% ± 10.1%. CONCLUSIONS: Emergency department ED physicians can accurately measure CI using standard bedside ultrasound. A focused ultrasound cardiac examination to derive CI has potential use in the management of critical ill patients in the ED. [ABSTRACT FROM AUTHOR]

Abstract Objective: Lobeglitazone as a thiazolidinedione antihyperglycemic agent activates peroxisome proliferator-activated receptor (PPAR) [gamma] and may be suitable as monotherapy or in combination with other antihyperglycemic agents. The primary objective of this study was to investigate potential pharmacokinetic interactions between lobeglitazone and metformin in healthy Korean subjects. Methods: A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence, crossover study was conducted in 24 healthy Korean male volunteers. Serial blood samples were collected after lobeglitazone (0.5 mg/day) and metformin (1000 mg/day) were administered alone or concomitantly for 5 days in each period, and drug concentrations were determined by liquid chromatography-tandem mass spectrometry. Clinical trail registration number: NCT01005160. Results: The steady-state maximum plasma concentrations (C(max, ss); mean ± standard deviation) of lobeglitazone and metformin alone were 29.38 ± 5.25 ng/mL and 1661.84 ± 471.88 ng/mL, respectively; the C(max, ss) during co-administration were 27.15 ± 5.75 ng/mL and 1779.92 ± 405.20 ng/mL, respectively. The steady-state areas under the concentration-time curves during the dose interval (AUC(, ss); mean ± standard deviation) of sole administration of lobeglitazone and metformin were 277.53 ± 65.25 ng*h/mL and 9650.27 ± 2089.81 ng*h/mL, respectively. When lobeglitazone and metformin were administered concomitantly, the AUC(, ss) were 257.29 ± 60.61 ng*h/mL and 10600.58 ± 1960.40 ng*h/mL, respectively. The geometric mean ratios (90% confidence interval) of co-medication to lobeglitazone alone were 0.92 (0.87-0.97; C(max, ss)) and 0.93 (0.87-0.99; AUC(, ss)), and those for co-medication to metformin monotherapy were 1.09 (0.99-1.19; C(max, ss)) and 1.11 (1.04-1.19; AUC(, ss)). Both monotherapies and combination therapy were well tolerated; 52 self-resolving, non-serious adverse events were reported from 17 subjects. Conclusion: Lobeglitazone did not significantly affect the pharmacokinetics of metformin or vice versa when both drugs were co-administered. Lobeglitazone can be co-administered with metformin without dose adjustment for either agent. Therefore further patient studies are needed to corroborate these results. [ABSTRACT FROM AUTHOR]

Palm fatty acid distillate (PFAD), is a by-product of the crude palm oil refining process. It comprises mainly of free fatty acids—around 45% palmitic and 33% oleic acids—as the major components. Ultra-violet (UV) curable urethane acrylate (UA) oligomers could be synthesized from PFAD, by the following procedure. A hydroxyl terminated macromer was first prepared by reacting PFAD with a mixture of isophthalic acid, phthalic anhydride, neopentagylcol (NPG), and pentaerythritol. The macromer was then reacted with 2-hydroxylethylacrylate (2HEA) and toluene diisocynate (TDI) to generate a resin, containing acrylate side chains for UV curable application. A series of UA resins were prepared by using 15, 25, 45, 55, and 70% of PFAD, respectively. The UA resin has Mw in the range of 3,200 to 27,000. They could be cured by UV irradiation at an intensity of 225 mW/cm2. Glass transition temperature (Tg) of the cured film was measured by differential scanning calorimeter (DSC), and hardness of the film was determined by a pendulum hardness tester, according to American Society for Testing and Materials (ASTM)4366. The resins were used in a wood-coating application. All of the cured films showed good adhesion, hardness, and chemical resistance except for the one using the 70% PFAD, which did not cure properly.

CpG-DNA activates the host immune system to resist bacterial infections. In this study, we examined the protective effect of CpG-DNA in mice against Escherichia coli (E. coli) K1 infection. Administration of CpG-DNA increased the survival of mice after E. coli K1 infection, which reduces the numbers of bacteria in the organs. Pre-injection of mice with CpG-DNA before E. coli K1 infection increased the levels of the complement C3 but not C3a and C3b. The survival of the mice after E. coli K1 infection was significantly decreased when the mice were pre-injected with the cobra venom factor (CVF) removing the complement compared to the non-CVF-treated mice group. It suggests that the complement has protective roles against E. coli K1 infection. In addition, the survival of complement-depleted mice was increased by CpG-DNA pre-administration before E. coli K1 infection. Therefore, we suggest that CpG-DNA enhances the anti-bacterial activity of the immune system by augmenting the levels of complement systems after E. coli K1 infection and triggering other factors as well. Further studies are required to investigate the functional roles of the CpG-DNA-induced complement regulation and other factors against urgent bacterial infection. [ABSTRACT FROM AUTHOR]