Uterine and placental expression of TRPV6 gene is regulated via progesterone receptor- or estrogen receptor-mediated pathways during pregnancy in rodents

Transient receptor potential cation channel, subfamily V, member 6 (TRPV6) is an epithelial Ca2+ channel protein expressed in calcium absorbing organs. In the present study, we investigated the expression and regulation of uterine and placental TRPV6 during gestation in rodents. Uterine TRPV6 peaked at pregnancy day (P) 0.5, P5.5 and, P13.5 and was detected in uterine epithelium and glands of rats, while placental TRPV6 mRNA levels increased in mid-gestation. Uterine and placental TRPV6 mRNA levels in rats appear to cyclically change during pregnancy, suggesting that TRPV6 may participate in the implantation process. In addition, uterine TRPV6 mRNA is only expressed in placenta-unattached areas of the uterus, and uterine TRPV6 immunoreactivity was observed in luminal and glandular epithelial cells. In the placenta, TRPV6 was detected in the labyrinth and spongy zone. These results may indicate that TRPV6 has at least two functions: implantation of the embryo and maintenance of pregnancy. To investigate the pathway(s) mediating TRPV6 expression in rodents, anti-steroid hormone antagonists were injected prior to maximal TRPV6 expression. In rats, TRPV6 expression was reduced by RU486 (an anti-progesterone) through progesterone receptors, and ICI 182,780 (an anti-estrogen) blocked TRPV6 expression via estrogen receptors in mice. The juxtaposition of uterine and placental TRPV6 expressed in these tissues supports the notion that TRPV6 participates in transferring calcium ions between the maternal and fetal compartments. Taken together, TRPV6 gene may function as a key element in controlling calcium transport in the uterus between the embryo and the placenta during pregnancy

Pharmacoeconomic Guidelines and Their Implementation in the Positive List System in South Korea

ABSTRACTThis article reviews the change in the reimbursement and pricing system in South Korea, which was the precursor to the eventual implementation of evidence-based decision-making. There has been pressure on Korea's National Health Insurance system to control its skyrocketing expenditures on drugs. As a result, a series of cost-containment policies have been implemented. The idea of economic evidence-based decision-making was first introduced in Korea in 2001 when the government announced cost-effectiveness as one of the criteria for reimbursement decisions. After this announcement, the Health Insurance Review and Assessment Service (HIRA) developed guidelines, which became the standard for economic evaluations.In 2006, the drug listing system for reimbursement was changed from a negative to a positive system under the drug expenditure rationalization plan. Under this new system, only drugs that are proven economically and clinically valuable can be listed, and applicants have to submit economic evaluation studies to support the cost-effectiveness of their drugs. Once new applications are submitted, HIRA reviews them, and the Drug Reimbursement Evaluation Committee (DREC) decides whether or not to recommend the submitted drugs. In its reimbursement decisions, the DREC considers not only cost-effectiveness but also the availability of therapeutic alternatives, the severity of the condition treated, and the impact on the budget, among other measures. After the introduction of the positive list system, 56% of drugs were determined to be appropriate for reimbursement by the DREC. Despite limited human resources, experience, and quality local data, Korea is continuing to make efforts to establish a system of evidence-based decision-making

Pharmacokinetics of a telmisartan, amlodipine and hydrochlorothiazide fixed-dose combination: A replicate crossover study in healthy Korean male subjects

Purpose: To compare the tolerability and pharmacokinetic profiles of telmisartan, amlodipine, and hydrochlorothiazide (HCTZ) in a fixed-dose combination (FDC, test product) with a co-administered telmisartan/amlodipine FDC and HCTZ in a single-entity tablet (reference product)Methods: This was a single-dose, randomized, open-label, replicate crossover study conducted in healthy male Korean volunteers aged 19 – 50 years. Fasting randomized subjects received a newly developed test product (telmisartan/ amlodipine/HCTZ, 80/10/25 mg) or two tablets of Twynsta® (40/5 mg) and one tablet of HCTZ (25 mg) as reference products. After a washout period, each group replicated the exposure of the other group.Results: The AUClast (h•ng/mL) geometric mean was 3,194.87 and 3,273.77 for the telmisartan test and reference products, respectively; 329.92 and 315.13 for the amlodipine test and reference products; 1,203.98 and 1,150.86 for the HCTZ test and reference products, respectively. The geometric mean of Cmax (ng/mL) was 543.04 and 497.81 for the telmisartan test and reference products, respectively; 7.74 and 7.34 for the amlodipine test and reference products; 218.71 and 184.39 for the HCTZ test and reference products, respectively. For telmisartan, the 90 % CI of GMRs of AUClast (h•ng/mL) and Cmax (ng/mL) were 0.9414 – 1.0496 and 1.0246 – 1.2792, respectively; the coefficient of variation (CV) of telmisartan Cmax was 41.96 %.Conclusion: A formulated FDC tablet containing a telmisartan/amlodipine/HCTZ combination (80/10/25mg) was bioequivalent to a co-administrated commercially available telmisartan/amlodipine combination and HCTZ tablets at equivalent concentrations.Keywords: Fixed-dose combination, Hypertension, Telmisartan, Amlodipine besylate, Hydrochlorothiazide, Pharmacokinetic

DeepHealthNet: Adolescent Obesity Prediction System Based on a Deep Learning Framework

Childhood and adolescent obesity rates are a global concern because obesity is associated with chronic diseases and long-term health risks. Artificial intelligence technology has emerged as a promising solution to accurately predict obesity rates and provide personalized feedback to adolescents. This study emphasizes the importance of early identification and prevention of obesity-related health issues. Factors such as height, weight, waist circumference, calorie intake, physical activity levels, and other relevant health information need to be considered for developing robust algorithms for obesity rate prediction and delivering personalized feedback. Hence, by collecting health datasets from 321 adolescents, we proposed an adolescent obesity prediction system that provides personalized predictions and assists individuals in making informed health decisions. Our proposed deep learning framework, DeepHealthNet, effectively trains the model using data augmentation techniques, even when daily health data are limited, resulting in improved prediction accuracy (acc: 0.8842). Additionally, the study revealed variations in the prediction of the obesity rate between boys (acc: 0.9320) and girls (acc: 0.9163), allowing the identification of disparities and the determination of the optimal time to provide feedback. The proposed system shows significant potential in effectively addressing childhood and adolescent obesity

Nonlinear forced change and nonergodicity: The case of ENSO-Indian monsoon and global precipitation teleconnections

We study the forced response of the teleconnection between the El Nino-Southern Oscillation (ENSO) and global precipitation in general and the Indian summer monsoon (IM) in particular in the Max Planck Institute Grand Ensemble. The forced response of the teleconnection is defined as the time-dependence of a correlation coefficient evaluated over the ensemble. The ensemble-wise variability is taken either wrt. spatial averages or dominant spatial modes in the sense of Maximal Covariance Analysis or Canonical Correlation Analysis or EOF analysis. We find that the strengthening of the ENSO-IM teleconnection is robustly or consistently featured in view of all four teleconnection representations, whether sea surface temperature (SST) or sea level pressure (SLP) is used to characterise ENSO, and both in the historical period and under the RCP8.5 forcing scenario. The main contributor to this strengthening in terms of a linear regression model is the regression coefficient, which can outcompete even a declining ENSO variability in view of using the SLP. We also find that the forced change of the teleconnection is typically nonlinear by (1) formally rejecting the hypothesis that ergodicity holds, i.e., that expected values of temporal correlation coefficients with respect to the ensemble equal the ensemble-wise correlation coefficient itself, and also showing that (2) the trivial contributions of the forced changes of e.g. the mean SST and/or precipitation to temporal correlations are insignificant here. We also provide, in terms of the test statistics, global maps of the degree of nonlinearity/nonergodicity of the forced change of the teleconnection between local precipitation and ENSO

Quantum-dot light-emitting diodes utilizing CdSe/ZnS nanocrystals embedded in TiO(2) thin film

Quantum-dot (QD) light-emitting diodes (LEDs) are demonstrated on Si wafers by embedding core-shell CdSe/ZnS nanocrystals in TiO(2) thin films via plasma-enhanced metallorganic chemical vapor deposition. The n-TiO(2)/QDs/p-Si LED devices show typical p-n diode current-voltage and efficient electroluminescence characteristics, which are critically affected by the removal of QD surface ligands. The TiO(2)/QDs/Si system we presented can offer promising Si-based optoelectronic and electronic device applications utilizing numerous nanocrystals synthesized by colloidal solution chemistry.open181

Development of a Numerical Tablet Model in WLAN Band for SAR Study

This research proposes a numerical model for a tablet in the wireless local area network band for specific absorption rate (SAR) study. The design criteria, such as the tablet size, operating frequencies, antenna position, and target 1-g peak spatial-average SAR (psSAR) values in the flat phantom, are determined based on the SAR test reports of tablets distributed in South Korea from 2013 to 2017. An internal antenna is designed in a tablet platform to operate in dual bands of 2,450 MHz and 5,500 MHz. The numerical results illustrate that the 1-g psSAR values of the proposed numerical tablet model are within ±10% of the target values. Moreover, the return loss of the designed tablet model is larger than 10 dB, regardless of flat phantom, while its radiation efficiency is higher than 90% in free space

Lack of Mitochondrial DNA Sequence Divergence between Two Subspecies of the Siberian Weasel from Korea: Mustela sibirica coreanus from the Korean Peninsula and M. s. quelpartis from Jeju Island

The objective of this study was to determine the degree of mitochondrial DNA (mtDNA) divergence between two subspecies of Mustela sibirica from Korea (M. s. coreanus on the Korean Peninsula and M. s. quelpartis on Jeju Island) and to examine the taxonomic status of M. s. quelpartis. Thus, we obtained complete sequences of mtDNA cytochrome b gene (1,140 bp) from the two subspecies, and these sequences were compared to a corresponding haplotype of M. s. coreanus, downloaded from GenBank. From this analysis, it was observed that the sequences from monogenic M. s. quelpartis on Jeju Island were identical to the sequences of four M. s. coreanus from four locations across the Korean Peninsula, and that the two subspecies formed a single clade; the average nucleotide distance between the two subspecies was 0.26% (range, 0.00 to 0.53%). We found that the subspecies quelpartis is not genetically distinct from the subspecies coreanus, and that this cytochrome b sequencing result does not support the current classification, distinguishing these two subspecies by pelage color. Further systematic analyses using morphometric characters and other DNA markers are necessary to confirm the taxonomic status of M. s. quelpartis