Comparable Efficacy of Lopinavir/Ritonavir and Remdesivir in Reducing Viral Load and Shedding Duration in Patients with COVID-19.

The spread of COVID-19 has significantly increased research on antiviral drugs and measures such as case isolation and contact tracing. This study compared the effects of lopinavir/ritonavir and remdesivir on COVID-19 patients with a control group receiving no antiviral drugs. Patients confirmed to have a SARS-CoV-2 infection via real-time RT-PCR were divided into three groups: lopinavir/ritonavir, remdesivir, and control. We assessed the efficacy of these drugs in reducing viral load and viral shedding duration using real-time RT-PCR and Vero E6 cell cultures. Lopinavir/ritonavir led to no detectable infectious SARS-CoV-2, with a median viral clearance time of one day, whereas one remdesivir-treated case remained culture-positive until day 12. Lopinavir/ritonavir significantly reduced viral load compared to remdesivir and control groups (p = 0.0117 and p = 0.0478). No infectious virus was detected in the lopinavir/ritonavir group, and the non-infectious SARS-CoV-2 proportion remained constant at 90%, higher than in the remdesivir and control groups (p = 0.0097). There was a significant difference in culture positivity among the groups (p = 0.0234), particularly between the lopinavir/ritonavir and remdesivir groups (p = 0.0267). These findings suggest that lopinavir/ritonavir reduces viral load and shortens the viral shedding duration compared to remdesivir, despite not being an effective treatment option.

Mechanism of DAPK1 for Regulating Cancer Stem Cells in Thyroid Cancer.

Death-associated protein kinase 1 (DAPK1) is a calcium/calmodulin (Ca2+/CaM)-dependent serine/threonine (Ser/Thr) protein kinase and is characteristically downregulated in metastatic cancer. Several studies showed that DAPK1 is involved in both the early and late stages of cancer. DAPK1 downregulation is elaborately controlled by epigenetic, transcriptional, posttranscriptional, and posttranslational processes. DAPK1 is known to regulate not only cancer cells but also stromal cells. Recent studies showed that DAPK1 was involved not only in tumor suppression but also in epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation in colon and thyroid cancers. CSCs are major factors in determining cancer aggressiveness in cancer metastasis and treatment prognosis by influencing EMT. However, the molecular mechanism involved in the regulation of cancer cells by DAPK1 remains unclear. In particular, little is known about the existence of CSCs and how they are regulated in papillary thyroid carcinoma (PTC) among thyroid cancers. In this review, we describe the molecular mechanism of CSC regulation by DAPK1 in PTC progression.

The Association between Low Fetal Fraction of Non-Invasive Prenatal Testing and Adverse Pregnancy Outcomes for Placental Compromise.

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications (p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes.

Oral habits and temporomandibular joint disorders according to stress levels among military personnel in South Korea: A cross-sectional study.

BACKGROUND: Military personnel suffer from stress-induced temporomandibular joint disorders (TMD). No previous studies have evaluated the oral habits and TMD in military personnel based on their stress levels. OBJECTIVES: To examine the correlation between oral habits and TMD based on stress levels. In addition, we assessed the relationship between stress levels and TMD by military rank as well as the impact of oral habits on TMD. METHOD: This cross-sectional survey included 89 military personnel who visited the Armed Forces Medical Center in Korea with discomfort in the temporomandibular joint (TMJ) discomfort. Oral habits, stress level, TMD and general characteristics of the subjects were investigated. A questionnaire was distributed to the subjects who agreed to the study, and they were asked to respond in a self-written form. Multiple linear regression analysis was performed to examine the factors that affect oral habits and TMJ symptoms. RESULTS: Stress scores and oral habits were highest in the 'Private' rank. In contrast, temporomandibular joint symptoms were highest in the 'Corporal' rank. Additionally, the high-risk stress group exhibited higher scores in oral habits and TMD compared to the potential stress group. Furthermore, there was a positive correlation between an increase in high-risk stress scores and a rise in oral habits. And individuals with more oral habits are at an increased likelihood of experiencing TMD. CONCLUSION: Our study findings suggest that military personnel with prevent TMD and improve oral habits by addressing stress levels.

Etiological agent and clinical characteristics of haemorrhagic fever with renal syndrome in the southern Republic of Korea: a genomic surveillance study.

OBJECTIVES: High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS. METHODS: Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment. RESULTS: High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments. DISCUSSION: These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b–4 chronic kidney disease and osteoporosis

Background/Aims@#We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. @*Methods@#Twenty-seven postmenopausal women with Stage 3b–4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. @*Results@#After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. @*Conclusions@#If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b–4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Efficacy and safety of denosumab treatment for Korean patients with Stage 3b-4 chronic kidney disease and osteoporosis.

BACKGROUND/AIMS: We evaluated the efficacy and safety of denosumab treatment in severe chronic kidney disease (CKD) patients with osteoporosis. We also investigated whether the treatment affects the coronary artery calcifications. METHODS: Twenty-seven postmenopausal women with Stage 3b-4 CKD and osteoporosis were enrolled. Twenty patients received denosumab plus calcium carbonate and vitamin D, and seven controls received calcium carbonate and vitamin D for 1 year. Dual-energy X-ray absorptiometry and coronary artery calcium (CAC) scoring computed tomography were performed before and after treatment. Hypocalcemic symptoms and serum calcium levels were evaluated. RESULTS: After 1 year of treatment, the percent changes of femur neck (3.6 ± 3.2% vs. -0.7 ± 4.4%, p = 0.033) and total hip (3.4 ± 3.8% vs. -1.9 ± 2.1%, p = 0.001) bone mineral density (BMD) were significantly increased in the denosumab treated group compared to the control group. However, the percent change of lumbar spine BMD did not differ between two groups (5.6 ± 5.9% vs. 2.7 ± 3.9%, p = 0.273). The percent change of bone alkaline phosphatase was significantly different in the denosumab-treated group and control group (-31.1 ± 30.0% vs. 0.5 ± 32.0%, p = 0.027). CAC scores did not differ between groups. No hypocalcemic events occurred in both groups. CONCLUSION: If carefully monitored and supplemented with calcium and vitamin D, denosumab treatment for 1 year provides significant benefits in patients with Stage 3b-4 CKD and osteoporosis. However, denosumab treatment did not affect coronary artery calcifications in these patients.

Cpne7 deficiency induces cellular senescence and premature aging of dental pulp.

Once tooth development is complete, odontoblasts and their progenitor cells in the dental pulp play a major role in protecting tooth vitality from external stresses. Hence, understanding the homeostasis of the mature pulp populations is just as crucial as understanding that of the young, developing ones for managing age-related dentinal damage. Here, it is shown that loss of Cpne7 accelerates cellular senescence in odontoblasts due to oxidative stress and DNA damage accumulation. Thus, in Cpne7-null dental pulp, odontoblast survival is impaired, and aberrant dentin is extensively formed. Intraperitoneal or topical application of CPNE7-derived functional peptide, however, alleviates the DNA damage accumulation and rescues the pathologic dentin phenotype. Notably, a healthy dentin-pulp complex lined with metabolically active odontoblasts is observed in 23-month-old Cpne7-overexpressing transgenic mice. Furthermore, physiologic dentin was regenerated in artificial dentinal defects of Cpne7-overexpressing transgenic mice. Taken together, Cpne7 is indispensable for the maintenance and homeostasis of odontoblasts, while promoting odontoblastic differentiation of the progenitor cells. This research thereby introduces its potential in oral disease-targeted applications, especially age-related dental diseases involving dentinal loss.

Effect of White Noise on Pain Response, Heart Rate, and Oxygen Saturation During Heel Puncture in Premature Infants: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate the effect of white noise on pain response, heart rate, and oxygen saturation during heel puncture in premature infants. METHODS: A randomized, controlled, pretest-posttest design was used. The participants were premature infants admitted to the neonatal intensive care unit of a university hospital in Gyeonggi Province. Sixty premature infants were assigned to either an experimental (n = 30) or control (n = 30) group. The experimental group was exposed to white noise during heel puncture, and the measured variables were pain response, heart rate, and oxygen saturation. The data were analyzed using the independent t test, chi-squared test, and analysis of covariance. RESULTS: Premature infants in the experimental group had a lower pain response and heart rate than the control group (F = 81.26, P < .01; F = 7.05, P = .01), and higher oxygen saturation than the control group (F = 4.76, P = .03). CONCLUSION: These results demonstrated that the white noise intervention is an effective nursing intervention to reduce the pain response and stabilize heart rate and oxygen saturation in premature infants during heel puncture.

Predicting preterm birth using machine learning techniques in oral microbiome.

Preterm birth prediction is essential for improving neonatal outcomes. While many machine learning techniques have been applied to predict preterm birth using health records, inflammatory markers, and vaginal microbiome data, the role of prenatal oral microbiome remains unclear. This study aimed to compare oral microbiome compositions between a preterm and a full-term birth group, identify oral microbiome associated with preterm birth, and develop a preterm birth prediction model using machine learning of oral microbiome compositions. Participants included singleton pregnant women admitted to Jeonbuk National University Hospital between 2019 and 2021. Subjects were divided into a preterm and a full-term birth group based on pregnancy outcomes. Oral microbiome samples were collected using mouthwash within 24 h before delivery and 16S ribosomal RNA sequencing was performed to analyze taxonomy. Differentially abundant taxa were identified using DESeq2. A random forest classifier was applied to predict preterm birth based on the oral microbiome. A total of 59 women participated in this study, with 30 in the preterm birth group and 29 in the full-term birth group. There was no significant difference in maternal clinical characteristics between the preterm and the full-birth group. Twenty-five differentially abundant taxa were identified, including 22 full-term birth-enriched taxa and 3 preterm birth-enriched taxa. The random forest classifier achieved high balanced accuracies (0.765 ± 0.071) using the 9 most important taxa. Our study identified 25 differentially abundant taxa that could differentiate preterm and full-term birth groups. A preterm birth prediction model was developed using machine learning of oral microbiome compositions in mouthwash samples. Findings of this study suggest the potential of using oral microbiome for predicting preterm birth. Further multi-center and larger studies are required to validate our results before clinical applications.

Developmental outcomes of very low birth weight infants with catch-up head growth: a nationwide cohort study.

BACKGROUND: As the survival rates of very low birth weight (VLBW) infants have increased, their neurodevelopmental outcomes are of concern. This study aims to determine the demographic and perinatal characteristics of premature infant according to head growth, identify clinical factors affecting growth catch-up, and explore differences in developmental outcomes according to catch-up states. METHODS: This nationwide prospective cohort study of Korean Neonatal Network data analyzed premature infants with very low birth weight (< 1,500 g) between 2014 and 2017. A total of 253 eligible infants who had completed the Bayley Scales of Infant and Toddler Development, Third Edition, were assigned into two groups: a catch-up (CU) group with a head circumference above the 10th percentile and a no catch-up (NCU) group with a head circumference below the 10th percentile at 18-24 months of corrected age (CA). RESULTS: Most (81.4%, 206/253) premature infants exhibited catch-up growth at 18-24 months of CA. Rates of microcephaly, intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), sepsis, necrotizing enterocolitis (NEC), length of NICU stay, ventilation care, and parenteral nutrition were significantly greater in the NCU group (P < 0.05). On multiple linear regression analysis, BPD status was the most influential clinical factor affecting catch-up head growth after adjusting for gestational age, birth weight, and birth head circumference (adjusted OR 4.586, 95% CI 1.960-10.729). At 18-24 months of CA, the NCU group exhibited lower developmental indices and a higher rate of developmental delay than the CU group. Motor developmental delay was the most significant factor relevant to catch-up head growth, and the motor development difference between the two groups was only statistically significant after adjusting for four major neonatal morbidities: IVH, BPD, sepsis, and NEC status (adjusted OR 10.727, 95% CI 1.922-59.868). CONCLUSION: As association was observed between head growth catch-up status and developmental outcomes in VLBW infants at 18-24 months of CA. Key clinical factors associated with catch-up status included BPD and NEC status, length of parenteral nutrition, and ventilator care. Further study is needed to establish causality and explore additional factors that may influence developmental outcomes in this population.

Feasibility of fetoscopic laser coagulation in triplet pregnancy.

OBJECTIVE: To report the experiences of triplet pregnancies complicated by twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser coagulation at a single center. METHODS: Herein, we conducted a retrospective analysis to investigate the management and perinatal outcomes of triplet pregnancies with TTTS treated at a single institution between 2017 and 2022. RESULTS: Seven of the 98 triplet pregnancies (7.1%) encountered were complicated by TTTS, and all were dichorionic triamniotic triplets. Of the seven triplet pregnancies complicated by TTTS, four were treated with fetoscopic laser coagulation at our center, at a median gestational age of 20 weeks. No procedure-related complications or maternal complications were observed. The survival rate was higher and perinatal outcomes were better in fetoscopic laser coagulation cases than in other management cases. Four donor and four recipient triplets survived, with a median gestational age of 33 weeks at delivery. Although there were no cases of poor neonatal outcomes, one case was diagnosed with white matter injury, suspected to be hypoxic-ischemic encephalopathy on postnatal investigation. CONCLUSION: Fetoscopic laser coagulation is a feasible treatment option for triplet TTTS, provided the attending specialists have extensive experience with this technique.

Net clinical benefit of oral anticoagulants in Korean atrial fibrillation patients with low to intermediate stroke risk: A report from the Clinical Survey on Stroke Prevention in patients with Atrial Fibrillation (CS-SPAF).

Background: The balance of stroke risk reduction and potential bleeding risk associated with antithrombotic treatment (ATT) remains unclear in atrial fibrillation (AF) at non-gender CHA2DS2-VASc scores 0-1. A net clinical benefit (NCB) analysis of ATT may guide stroke prevention strategies in AF with non-gender CHA2DS2-VASc scores 0-1. Methods: This multi-center cohort study evaluated the clinical outcomes of treatment with a single antiplatelet (SAPT), vitamin K antagonist (VKA), and non-VKA oral anticoagulant (NOAC) in non-gender CHA2DS2-VASc score 0-1 and further stratified by biomarker-based ABCD score (Age [≥60 years], B-type natriuretic peptide [BNP] or N-terminal pro-BNP [≥300 pg/mL], creatinine clearance [<50 mL/min], and dimension of the left atrium [≥45 mm]). The primary outcome was the NCB of ATT, including composite thrombotic events (ischemic stroke, systemic embolism, and myocardial infarction) and major bleeding events. Results: We included 2465 patients (age 56.2 ± 9.5 years; female 27.0%) followed-up for 4.0 ± 2.8 years, of whom 661 (26.8%) were treated with SAPT; 423 (17.2%) with VKA; and 1040 (42.2%) with NOAC. With detailed risk stratification using the ABCD score, NOAC showed a significant positive NCB compared with the other ATTs (SAPT vs. NOAC, NCB 2.01, 95% confidence interval [CI] 0.37-4.66; VKA vs. NOAC, NCB 2.38, 95% CI 0.56-5.40) in ABCD score ≥1. ATT failed to show a positive NCB in patients with truly low stroke risk (ABCD score = 0). Conclusions: In the Korean AF cohort at non-gender CHA2DS2-VASc scores 0-1, NOAC showed significant NCB advantages over VKA or SAPT with ABCD score ≥1.

TGFß4 alleviates the phenotype of Charcot-Marie-Tooth disease type 1A.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFß4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFß4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFß4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFß4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A.

Reelin and APP Cooperatively Modulate Dendritic Spine Formation In Vitro and In Vivo.

Amyloid precursor protein (APP) plays an important role in the pathogenesis of Alzheimer's disease (AD), but the normal function of APP at synapses is poorly understood. We and others have found that APP interacts with Reelin and that each protein is individually important for dendritic spine formation, which is associated with learning and memory, in vitro. However, whether Reelin acts through APP to modulate dendritic spine formation or synaptic function remains unknown. In the present study, we found that Reelin treatment significantly increased dendritic spine density and PSD-95 puncta number in primary hippocampal neurons. An examination of the molecular mechanisms by which Reelin regulates dendritic spinogenesis revealed that Reelin enhanced hippocampal dendritic spine formation in a Ras/ERK/CREB signaling-dependent manner. Interestingly, Reelin did not increase dendritic spine number in primary hippocampal neurons when APP expression was reduced or in vivo in APP knockout (KO) mice. Taken together, our data are the first to demonstrate that Reelin acts cooperatively with APP to modulate dendritic spine formation and suggest that normal APP function is critical for Reelin-mediated dendritic spinogenesis at synapses.

Associations of dual use of tobacco cigarettes and e-cigarettes, sleep duration, physical activity and depressive symptoms among middle-aged and older Korean adults.

AIM: There is limited evidence of the association between dual tobacco-e-cigarette use and health-related variables in Korea. Thus, this study aimed to investigate the associations between types of cigarette smoking, sleep duration, physical activity and depressive symptoms among Korean adults. DESIGN: A cross-sectional study design using the 2019 Korean Community Health Survey. METHODS: The study subjects consisted of 179,004 adults older than 40 years from a total of 229,099 individuals. Self-reported general characteristics, smoking history, sleep duration, physical activity and depressive symptoms were analysed. RESULTS: In multinomial logistic regression, dual users of tobacco cigarettes and e-cigarettes were more likely to have sleep duration of less than 7 h per day and to report both mild and moderate-to-severe depressive symptoms than non-smokers. Single use of either cigarettes or e-cigarettes increased the risk of short sleep duration and moderate-to-severe depressive symptoms.

Seroprevalence of severe fever with thrombocytopenia syndrome using specimens from the Korea National Health & Nutrition Examination Survey.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile disease caused by bites from ticks infected with the SFTS virus. In Korea, SFTS patients are observed nationwide, including Jeju Island, but there are currently no data regarding the national prevalence of SFTS, including that of residents of 16 cities and provinces. This study aimed to investigate the seroprevalence of SFTS in Korea. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1500 participants were selected through random sampling from the 2014-2015 Korea National Health and Nutrition Examination Survey (KNHANES). An indirect immunofluorescence antibody assay (IFA) was performed to assess immunoglobulin (Ig) G and IgM antibody titers against SFTS virus. RESULTS: Of the 1500 participants, 55 (3.7%) tested positive for IgG and 1 (0.1%) tested positive for IgM, with antibody titer of ≥ 1:32. Approximately 3.9% and 2.5% of participants in urban and rural areas, respectively, had a positive titer of ≥ 1:32. There was a significant correlation between SFTS incidence per 100,000 population and seroprevalence using an IgG titer ≥ 1:64 as the cut-off value. CONCLUSION: This is the first study to investigate national SFTS seroprevalence in all 16 cities and provinces representing Korea. Our study will also provide useful guidelines for the development of preventive measures against SFTS.

Tubular dentin formation by TGF-ß/BMP signaling in dental epithelial cells.

OBJECTIVES: This study aimed to identify formation of tubular dentin induced by transforming growth factor-ß (TGF-ß) and bone morphogenic protein (BMP) signaling pathway in dental epithelial cells. METHODS: We collected conditioned medium (CM) of rTGF-ß1/rBMP-2-treated HAT-7 and treated to MDPC-23 cells. The expression levels of odontoblast differentiation markers, KLF4, DMP1, and DSP were evaluated by real-time PCR and Western blot analysis. To evaluate whether CM of rTGF-ß1/rBMP-2 induces tubular dentin formation, we made a beagle dog tooth defect model. RESULTS: Here, we show that Cpne7 is regulated by Smad4-dependent TGF-ß1/BMP2 signaling pathway in dental epithelial cells. CM of rTGF-ß1/rBMP-2 treated HAT-7 or rCPNE7 raises the expression levels of KLF4, DMP1, and DSP in MDPC-23 cells. When rTGF-ß1 or rBMP-2 is directly treated to MDPC-23 cells, however, expression levels of Cpne7-regulated genes remain unchanged. In a beagle dog defect model, application of rTGF-ß1/BMP2-treated CM resulted in tubular tertiary dentin mixed with osteodentin at cavity-prepared sites, while rTGF-ß1 group exhibited homogenous osteodentin. CONCLUSIONS: Taken together, Smad4-dependent TGF-ß1/BMP2 signaling regulates Cpne7 in dental epithelial cells, and CPNE7 protein secreted from pre-ameloblasts mediates odontoblast differentiation via epithelial-mesenchymal interaction.

Risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA environmental contamination in rooms of patients with coronavirus disease 2019 (COVID-19).

The risk factors of environmental contamination by SARS-CoV-2 are largely unknown. We analyzed 1,320 environmental samples obtained from COVID-19 patients over 1 year. The risk factors for contamination of COVID-19 patients' surrounding environment were higher viral load in the respiratory tract and shorter duration from symptom onset to sample collection.

The Effects of a Smartphone-Based Education Program Designed to Help Mothers Safely Administer Medication to Their Children.

This study aimed to determine the effect of a smartphone-based medication education program to help mothers safely administer medication to their children at home. A quasi-experimental, non-equivalent control group, pretest-posttest design was utilized. There were 33 participants in the experimental group and 30 in the control group. The experimental group participated in the KidsMedi program for 6 weeks. The experimental group, receiving the KidsMedi program, had a statistically significant higher perception of antipyretic analgesics and higher eHealth literacy than the control group. The medication education program developed in this study is a mobile Web-based program. It is an effective program for mothers to improve their knowledge about administering drugs to children at home. This program is not affected by time and place, allowing repetitive self-directed learning. Nurses can utilize this program in daycare centers, schools, hospitals, communities, and public institutions to educate parents about safe medication for children.