A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability.

Mutations truncating a single copy of the tumor suppressor, BRCA2, cause cancer susceptibility. In cells bearing such heterozygous mutations, we find that a cellular metabolite and ubiquitous environmental toxin, formaldehyde, stalls and destabilizes DNA replication forks, engendering structural chromosomal aberrations. Formaldehyde selectively depletes BRCA2 via proteasomal degradation, a mechanism of toxicity that affects very few additional cellular proteins. Heterozygous BRCA2 truncations, by lowering pre-existing BRCA2 expression, sensitize to BRCA2 haploinsufficiency induced by transient exposure to natural concentrations of formaldehyde. Acetaldehyde, an alcohol catabolite detoxified by ALDH2, precipitates similar effects. Ribonuclease H1 ameliorates replication fork instability and chromosomal aberrations provoked by aldehyde-induced BRCA2 haploinsufficiency, suggesting that BRCA2 inactivation triggers spontaneous mutagenesis during DNA replication via aberrant RNA-DNA hybrids (R-loops). These findings suggest a model wherein carcinogenesis in BRCA2 mutation carriers can be incited by compounds found pervasively in the environment and generated endogenously in certain tissues with implications for public health.

Early B-cell development and B-cell maturation are impaired in patients with active hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by hyperinflammation and multiorgan dysfunction. Infections, including the reactivation of viruses, contribute to significant disease mortality in HLH. Although T-cell and natural killer cell-driven immune activation and dysregulation are well described, limited data exist on the status of B-cell compartment and humoral immune function in HLH. We noted marked suppression of early B-cell development in patients with active HLH. In vitro B-cell differentiation studies after exposure to HLH-defining cytokines, such as interferon gamma (IFN-γ) and tumor necrosis factor, recapitulated B-cell development arrest. Messenger RNA sequencing of human CD34+ cells exposed to IFN-γ demonstrated changes in genes and pathways affecting B-cell development and maturation. In addition, patients with active HLH exhibited a marked decrease in class-switched memory B (CSMB) cells and a decrease in bone marrow plasmablast/plasma cell compartments. The decrease in CSMB cells was associated with a decrease in circulating T follicular helper (cTfh) cells. Finally, lymph node and spleen evaluation in a patient with HLH revealed absent germinal center formation and hemophagocytosis with associated lymphopenia. Reassuringly, the frequency of CSMB and cTfh improved with the control of T-cell activation. Taken together, in patients with active HLH, these changes in B cells may affect the humoral immune response; however, further immune studies are needed to determine its clinical significance.

Drosophila melanogaster Sting mediates Coxiella burnetii infection by reducing accumulation of reactive oxygen species.

The Gram-negative bacterium Coxiella burnetii is the causative agent of query fever in humans and coxiellosis in livestock. C. burnetii infects a variety of cell types, tissues, and animal species including mammals and arthropods, but there is much left to be understood about the molecular mechanisms at play during infection in distinct species. Human stimulator of interferon genes (STING) induces an innate immune response through the induction of type I interferons (IFNs), and IFN promotes or suppresses C. burnetii replication, depending on tissue type. Drosophila melanogaster contains a functional STING ortholog (Sting) which activates NF-κB signaling and autophagy. Here, we sought to address the role of D. melanogaster Sting during C. burnetii infection to uncover how Sting regulates C. burnetii infection in flies. We show that Sting-null flies exhibit higher mortality and reduced induction of antimicrobial peptides following C. burnetii infection compared to control flies. Additionally, Sting-null flies induce lower levels of oxidative stress genes during infection, but the provision of N-acetyl-cysteine (NAC) in food rescues Sting-null host survival. Lastly, we find that reactive oxygen species levels during C. burnetii infection are higher in Drosophila S2 cells knocked down for Sting compared to control cells. Our results show that at the host level, NAC provides protection against C. burnetii infection in the absence of Sting, thus establishing a role for Sting in protection against oxidative stress during C. burnetii infection.

A finite element analysis of stress distribution with various directions of intermaxillary fixation using orthodontic mini-implants and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy.

OBJECTIVE: This finite element analysis (FEA) aimed to assess the stress distribution in the mandible and fixation system with various directions of the intermaxillary fixation (IMF) using mini-implants (MIs) and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy (BSSRO). MATERIALS AND METHODS: A total of nine mandibular advancement models were set according to the position of the MIs (1.6 mm in diameter, 8 mm in length) and direction of the IMF elastics (1/4 inch, 5 oz). Major and minor principal stresses in the cortical and cancellous bones, von Mises stresses in the fixation system (miniplate and monocortical screws), and bending angles of the miniplate were analysed. RESULTS: Compressive and tensile stress distributions in the mandible and von Mises stress distributions in the fixation system were greater in models with a Class III IMF elastic direction and a higher IMF elastic force than in models with a Class II IMF elastic direction and a lower IMF elastic force. The bending angle of the miniplate was negligible. CONCLUSIONS: Stress distributions in the bone and fixation system varied depending on the direction, amount of force, and position of IMF elastics and MIs. Conclusively, IMF elastics in the Class II direction with minimal load in the area close to the osteotomy site should be recommended.

Interdisciplinary treatment of mutilated dentition and transverse maxillary deficiency with microimplant-assisted rapid palatal expansion, microimplants, and dental implants.

OBJECTIVE: This case report demonstrates an interdisciplinary approach to treat a 26-year-old male patient with hyperdivergent Class II skeletal pattern, maxillary transverse deficiency, slight anterior open bite, and multiple hopeless teeth with root rests. CLINICAL CONSIDERATIONS: An interdisciplinary treatment was required for oral hygiene improvement, caries treatment, extraction of residual roots and hopeless teeth, maxillary expansion using microimplant-assisted rapid palatal expansion, improvement of skeletal and dental relationship using orthodontic microimplants, and prosthetic restorations with the aid of dental implants. CONCLUSION: Consequently, esthetic and functional occlusal rehabilitation was achieved. CLINICAL SIGNIFICANCE: Hyperdivergent Class II facial and skeletal patterns with multiple missing teeth can be effectively treated using orthodontic skeletal anchorage. In young adults, the transverse discrepancy can be resolved using MARPE, which is also useful for improving the sagittal and vertical relationships. In the case of multiple missing teeth, orthodontic treatment can provide the proper space to facilitate dental implants to achieve optimal esthetics and function.

Interdisciplinary treatment of a mutilated dentition with multiple missing teeth and horizontal impaction of a mandibular third molar using an orthodontic skeletal anchorage and dental implants-Case report.

OBJECTIVE: This case report presents a female adult patient who exhibits poor oral hygiene, a mutilated dentition with multiple missing teeth, and skeletal asymmetry. CLINICAL CONSIDERATIONS: Interdisciplinary treatment was necessary to maintain oral hygiene, treat caries, extract residual roots, and upright a horizontally impacted third molar using a miniplate. Additionally, orthodontic mini-implants were utilized as anchorage to improve sagittal relationship and space closing. Space management was completed with orthodontic treatment, followed by restoration of the multiple missing teeth with dental implants. CONCLUSION: Consequently, an esthetic smile and functional occlusion were achieved by interdisciplinary treatment using orthodontic skeletal anchorage devices and dental implants. CLINICAL SIGNIFICANCE: Missing mandibular first molar spaces were closed with retraction of the anterior teeth and protraction of the mandibular second molars using orthodontic mini-implants. The mandibular right third molar, which should have erupted, was protracted with the second molar, while the horizontally impacted mandibular left third molar was uprighted using a miniplate and was protracted with an orthodontic mini-implant. The missing maxillary lateral incisors were replaced with the maxillary canines, and the maxillary canines were replaced with the maxillary first premolars. The missing maxillary right second premolar and first molar and left first and second molars were successfully restored with dental implants.

Particulate Matter-Induced Neurotoxicity: Unveiling the Role of NOX4-Mediated ROS Production and Mitochondrial Dysfunction in Neuronal Apoptosis.

Urban air pollution, a significant environmental hazard, is linked to adverse health outcomes and increased mortality across various diseases. This study investigates the neurotoxic effects of particulate matter (PM), specifically PM2.5 and PM10, by examining their role in inducing oxidative stress and subsequent neuronal cell death. We highlight the novel finding that PM increases mitochondrial ROS production via stimulating NOX4 activity, not through its expression level in Neuro-2A cells. Additionally, PMs provoke ROS production via increasing the expression and activity of NOX2 in SH-SY5Y human neuroblastoma cells, implying differential regulation of NOX proteins. This increase in mitochondrial ROS triggers the opening of the mitochondrial permeability transition pore (mPTP), leading to apoptosis through key mediators, including caspase3, BAX, and Bcl2. Notably, the voltage-dependent anion-selective channel 1 (VDAC1) increases at 1 µg/mL of PM2.5, while PM10 triggers an increase from 10 µg/mL. At the same concentration (100 µg/mL), PM2.5 causes 1.4 times higher ROS production and 2.4 times higher NOX4 activity than PM10. The cytotoxic effects induced by PMs were alleviated by NOX inhibitors GKT137831 and Apocynin. In SH-SY5Y cells, both PM types increase ROS and NOX2 levels, leading to cell death, which Apocynin rescues. Variability in NADPH oxidase sources underscores the complexity of PM-induced neurotoxicity. Our findings highlight NOX4-driven ROS and mitochondrial dysfunction, suggesting a potential therapeutic approach for mitigating PM-induced neurotoxicity.

Job crafting, positive psychological capital, and social support as predictors of job embeddedness on among clinical nurses- a structural model design.

BACKGROUND: This study establishes the relationships among role conflict, positive psychological capital, social support, job crafting, and job embeddedness among clinical nurses. The results are expected to provide a basis for efficient human resource management in hospitals. METHODS: Considering a 15% dropout rate, we distributed 300 copies of our questionnaire, of which 290 were returned. We used 260 responses in the final analysis after excluding 40 responses that were incomplete or showed an identical pattern in the item responses. Participants were clinical nurses with less than one year of experience in general and tertiary general hospitals in G province and D metropolitan city in South Korea. A structured questionnaire was administered from January 10 to February 28, 2022. The collected data were analyzed using SPSS 26.0 and AMOS 26.0. We assessed the statistical significance using the bootstrapping method. RESULTS: The direct and total effects (both ß = 0.806, p =.007) of positive psychological capital on job crafting were significant. The direct and total effects (both ß = 0.451, p =.004) of social support on job crafting were significant. The direct (γ = 0.292, p =.055), indirect (γ = -. 671, p =.003), and total (γ = - 0.379, p =.008) effects of role conflict on job crafting were significant. The direct (γ = - 0.382, p =.007), indirect (γ = - 0.208 p =.003), and total (γ = - 0.589, p =.006) effects of role conflict on job embeddedness were significant. The direct and total (both ß = 0.548, p =.005) effects of job crafting on job embeddedness were significant. CONCLUSIONS: Nurses' job embeddedness is directly influenced by their job crafting, which is shaped by high levels of positive psychological capital and social support. When job crafting takes place, role conflict increases, and if job crafting becomes difficult because of severe role conflict, job embeddedness decreases. Therefore, to increase job embeddedness among clinical nurses, hospitals must implement support systems and programs to increase job autonomy, and positive psychological capital to promote job crafting.

Effects of Rehabilitation Robot Training on Physical Function, Functional Recovery, and Daily Living Activities in Patients with Sub-Acute Stroke.

Stroke often results in sensory deficits, muscular weakness, and diminished postural control, thereby restricting mobility and functional capabilities. It is important to promote neuroplasticity by implementing task-oriented exercises that induce changes in patients. Therefore, this study aimed to investigate the effects of rehabilitation robot training on physical function, functional recovery, and activities of daily living (ADLs) in patients with subacute stroke. The study participants were patients with subacute stroke receiving treatment at Hospitals A and B. They were selected as research subjects based on selection and exclusion criteria. The experimental group received rehabilitation robot training in sessions of 30 min, five times weekly, for a total of 20 sessions over four weeks. Conversely, the control group underwent standard rehabilitation equipment training with an identical frequency, duration, and number of sessions. Measurements were taken before and after the training period to assess changes in physical function, functional recovery, and activities of daily living using tools such as the MMT, BBS, FBG, FAC, FIM, and MBI. The results were as follows: in the within-group comparison, the rehabilitation robot training group showed significant differences in MMT, BBS, FBG, FAC, FIM, and MBI (p < 0.05), while the control group showed significant differences in FIM (p < 0.05). Statistically significant differences were observed in the time, group, and time × group interaction effects among the MMT, static seated FBG, dynamic seated FBG, FIM, and MBI (p < 0.05). Based on these results, rehabilitation robotic training resulted in significant improvements in physical function, functional recovery, and activities of daily living in patients with subacute stroke. Based on these findings, providing a basic protocol for a rehabilitation program that applies rehabilitation robot training to patients with subacute stroke may offer more effective treatment and outcomes in the future.

Effects of Upper Limb Control on the Less-Affected Side on Upper Limb Function, Respiration, Balance, and Activities of Daily Living in Stroke.

Background and Objectives: This study aimed to investigate the effects of upper limb control exercises on upper limb function, respiration, balance, and activities of daily living in patients with stroke. Materials and Methods: The 28 patients who met the selection criteria were randomly assigned to two groups of 14 patients each. Subsequently, upper limb control exercises using real-time feedback were applied. The same interventional exercise was applied to both the less-affected and affected limbs of the study participants, who were classified into a less-affected side upper limb control group and an affected side upper limb control exercise group. Interventional exercises, 30 min each, were performed five times weekly for 4 weeks, and follow-up examinations were performed 2 weeks after the end of exercise. Electronic muscle strength measurements and an electronic goniometer were used to evaluate upper limb function. A spirometer was used to measure respiration. Balance ability was evaluated using a force plate pressure distribution measuring system with a sensor that detects the movement of the body center on the ground. Daily life movements were evaluated using the Korean version of the modified Barthel index. Results: When examining the results, the upper limb function on the paralyzed side showed an increase in the electromyographic strength of shoulder joint depression and flexion angle. Improvements were also observed in respiration (forced vital capacity [L] and forced expiratory volume in 1 s [L]), balance (95% confidence ellipse area [mm2] and center of pressure displacement [mm]), and daily life activities, all of which showed statistically significant differences in the time × group interaction effect (p < 0.05). Conclusions: Thus, it was found that the upper limb control exercise on the less-affected side had a significant effect when the exercise was performed together with treatment on the affected side in patients with stroke. It is anticipated that this study will provide basic data for evaluating both the trunk and upper limbs of the less-affected and affected sides.

Effects of Gluteal Muscle Strengthening Exercise-Based Core Stabilization Training on Pain and Quality of Life in Patients with Chronic Low Back Pain.

Background: The World Health Organization reports that back pain is a major cause of disorder worldwide. It is the most common musculoskeletal disorder with limited pain, muscle tension, and stiffness, and 70-80% of all individuals experience it once in their lifetime, with higher prevalence in women than in men. This study aimed to investigate the effects of gluteal muscle strengthening exercise- based core stabilization training (GSE-based CST) on pain, function, fear-avoidance patterns, and quality of life in patients with chronic back pain. Methods: This study included 34 patients with non-specific chronic low back pain. Seventeen individuals each were included in GSE-based CST and control groups. The GSE-based CST group performed GSE and CST for 15 min, three times a week for four weeks, and the control group performed CST for 30 min a day, three times a week for four weeks. The numeric pain rating scale was used to evaluate pain before and after treatment, Roland-Morris disability questionnaire was used to evaluate function, fear-avoidance beliefs questionnaire was used to evaluate fear-avoidance patterns, and quality of life was measured using the short form-36. Results: In this study, pain, function, and fear-avoidance pattern decreased significantly in both groups (All p < 0.05). During the evaluation of quality of life, both groups showed significant increase in physical and mental factors (p < 0.05). There were significant differences in pain and quality of life (p < 0.05) between the GSE-based CST and control groups. Conclusions: Therefore, GSE-based CST can be used as a basis for effective intervention to enhance pain, function, fear-avoidance patterns, and quality of life, emphasizing the need for gluteal muscle strengthening exercises in patients with non-specific chronic back pain in the future.

Hydride-Free Hydrogenation: Unraveling the Mechanism of Electrocatalytic Alkyne Semihydrogenation by Nickel-Bipyridine Complexes.

Hydrogenation reactions of carbon-carbon unsaturated bonds are central in synthetic chemistry. Efficient catalysis of these reactions classically recourses to heterogeneous or homogeneous transition-metal species. Whether thermal or electrochemical, C-C multiple bond catalytic hydrogenations commonly involve metal hydrides as key intermediates. Here, we report that the electrocatalytic alkyne semihydrogenation by molecular Ni bipyridine complexes proceeds without the mediation of a hydride intermediate. Through a combined experimental and theoretical investigation, we disclose a mechanism that primarily involves a nickelacyclopropene resting state upon alkyne binding to a low-valent Ni(0) species. A following sequence of protonation and electron transfer steps via Ni(II) and Ni(I) vinyl intermediates then leads to olefin release in an overall ECEC-type pattern as the most favored pathway. Our results also evidence that pathways involving hydride intermediates are strongly disfavored, which in turn promotes high semihydrogenation selectivity by avoiding competing hydrogen evolution. While bypassing catalytically competent hydrides, this type of mechanism still retains inner-metal-sphere characteristics with the formation of organometallic intermediates, often essential to control regio- or stereoselectivity. We think that this approach to electrocatalytic reductions of unsaturated organic groups can open new paradigms for hydrogenation or hydroelementation reactions.

Repeat uterine artery embolization (UAE) for recurrent postpartum hemorrhage in patients who underwent UAE after a previous delivery: a multicenter study.

OBJECTIVE: To evaluate angiographic findings and outcomes of repeat uterine artery embolization (UAE) for recurrent postpartum hemorrhage (PPH) in patients who previously underwent UAE for PPH after a previous delivery. MATERIALS AND METHODS: Among 1805 patients who underwent UAE for PPH from 2007 to 2020 at four participating hospitals, the data of 21 (1.16%) patients who underwent UAE for PPH after subsequent delivery were collected and analyzed retrospectively. The rate of placental abnormalities, causes of PPH, angiographic findings, and clinical success rate were evaluated. RESULTS: The technical success rates were 100% and 95.2%, and clinical success rates were 85.7% and 95.2% in association with first and second UAEs, respectively. The time intervals between first and second UAEs ranged from 15.6 to 103.3 months (46.5 ± 25.0 months). The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). The causes of PPH were different between first and second UAEs with borderline significance (p = 0.049); uterine atony (81.0%) and placenta accreta spectrum (57.1%) were most common in association with first and second UAEs, respectively. During second UAEs, obliterated arteries were observed in 27 uterine arteries (27/42, 64.3%) of 16 patients (16/21, 76.2%), with partial obliteration predominating over total obliteration. Collateral arteries were observed in 15 patients during second UAEs. CONCLUSION: Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE. Obliteration of UAs and formation of collateral arteries are common at the second UAEs. KEY POINTS: • The rate of placental abnormalities was significantly higher in association with second UAEs than with first UAEs (71.4% vs. 42.8%, p = 0.034). • Obliteration of UAs and formation of collateral arteries are common at the second UAEs. • Repeat UAE is safe and effective for recurrent PPH after subsequent delivery in patients with prior UAE.

Cancer-causing BRCA2 missense mutations disrupt an intracellular protein assembly mechanism to disable genome maintenance.

Cancer-causing missense mutations in the 3418 amino acid BRCA2 breast and ovarian cancer suppressor protein frequently affect a short (∼340 residue) segment in its carboxyl-terminal domain (DBD). Here, we identify a shared molecular mechanism underlying their pathogenicity. Pathogenic BRCA2 missense mutations cluster in the DBD's helical domain (HD) and OB1-fold motifs, which engage the partner protein DSS1. Pathogenic - but not benign - DBD mutations weaken or abolish DSS1-BRCA2 assembly, provoking mutant BRCA2 oligomers that are excluded from the cell nucleus, and disable DNA repair by homologous DNA recombination (HDR). DSS1 inhibits the intracellular oligomerization of wildtype, but not mutant, forms of BRCA2. Remarkably, DSS1 expression corrects defective HDR in cells bearing pathogenic BRCA2 missense mutants with weakened, but not absent, DSS1 binding. Our findings identify a DSS1-mediated intracellular protein assembly mechanism that is disrupted by cancer-causing BRCA2 missense mutations, and suggest an approach for its therapeutic correction.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

Corrigendum to "Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents" [J Exercise Sci Fitness 21(1) (2023) 26-33].

[This corrects the article DOI: 10.1016/j.jesf.2022.10.014.].

Physical activity in the era of climate change and COVID-19 pandemic: Results from the South Korea's 2022 Report Card on physical activity for children and adolescents.

Background: With intensifying air pollutant levels and the COVID-19 pandemic, physical inactivity of South Korean children and adolescents may be threatened. Therefore, monitoring and surveillance of physical activity (PA) and relevant indicators are important for policy making pertaining to health promotion. Report Card is a third comprehensive evaluation of PA-related behaviors among and the sources of influence for South Korean children and adolescents. Purpose: To provide the outcome of the South Korea's 2022 Report Card on PA for children and adolescents. Methods: Based on a variety of sources including national surveys collected pre- and during-COVID-19 and information collected from government webpages, 11 indicators were graded by a committee of experts informed by the best available evidence. Data from during-COVID-19 were available for Overall PA, Sedentary Behavior, and Sleep and considered together in generating the overall grades. Results: Grades were assigned to behavioral indicators (Overall PA: D-; Active Transportation: B+; Sedentary Behavior: D; Sleep: F) and sources of Influence (Family and Peers: C-; School: A; Community and Environment: B-; Government: A). Organized Sport and PA, Active Play, and Physical Fitness could not be graded due to the lack of data. The results largely indicated that children and adolescents show unfavorable behavioral grades even with favorable grades observed for the sources of influence indicators. Trivial differences were observed pre- and during-pandemic for Overall PA (≥60 min of MVPA for ≥4 d/wk: 20.8% vs 19.9%) and Sleep (met age-specific recommendation: 14.1% vs 15.0%); however, a marked increase in Sedentary Behavior was observed (≤2 h/d screen time: 28.8% vs 20.1%). A stark weekday vs weekend difference was observed in sleep duration. In terms of PA related sources of influence, high accessibility to PA facilities (81.1%) and high satisfaction of neighborhood public transit (74.6%) and safety (80.7%) were well reflected in our Active Transportation grade (B+). Nonetheless, perception of green environments including outdoor air quality (44.0%), noise (39.6%) and green space (56.5%) showed lower scores, suggesting that new barriers to active lifestyles are emerging for South Korean children and adolescents. Gender differences were also observed for overall PA (≥60 min of MVPA for ≥4 d/wk: 29.1% for boys vs 11.3% for girls) and sleep (met age-specific recommendations: 17.3% for boys vs 11.4% for girls), but not for sedentary behavior (≤2 h/d screen time: 26.4% for boys and 24.9% for girls). Conclusions: Government and school policies/programs and the built environment are, in general, conducive to physically active lifestyles for South Korean children and adolescents; however, behavioural indicators received poor grades except for Active Transportation. A thorough evaluation of policies/programs at government, local, and school levels is needed to ensure that the efforts to have PA-enhancing infrastructure and systems are actually being translated into the behavior of children and adolescents in South Korea. Furthermore, improving PA surveillance, monitoring, and advocacy to ultimately establish healthy lifestyle patterns among children and adolescents is a top priority.

Daphne odora Exerts Depigmenting Effects via Inhibiting CREB/MITF and Activating AKT/ERK-Signaling Pathways.

Daphne odora, a blooming shrub, has been traditionally used for various medicinal purposes. However, information on its anti-melanogenic activity and dermal application is limited. In this study, the Daphne odora extract (DOE), with constituents including daphnetin, was used to investigate depigmenting activity and the underlying mechanism of Daphne odora. DOE inhibited in vitro and cellular tyrosinase activity in a dose-dependent manner, and reduced the α-MSH-induced melanin biosynthesis to a control level. The protein expressions of melanin synthesis-related enzymes were also significantly reduced by DOE. Moreover, DOE decreased the phosphorylation of cAMP-response element binding proteins (CREBs) induced by α-MSH in B16F10 cells, while it activated phosphorylated extra-cellular signal-regulated kinases (ERKs) and protein kinase B (AKT) expression. These results suggest that DOE might inhibit the melanogenesis signaling pathways by activating ERK- and AKT-signaling pathways to regulate the expression of CREB and MITF and its downstream pathways. Therefore, DOE could potentially be developed as a depigmenting agent.

Postnatal Imaging for Prediction of Outcome in Patients with Left-sided Congenital Diaphragmatic Hernia.

OBJECTIVE: To evaluate associations between postnatal imaging features and outcome of left-sided congenital diaphragmatic hernia, as defined by overall survival and a requirement for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Newborns diagnosed prenatally with left-sided congenital diaphragmatic hernia between January 2013 and September 2021 were studied retrospectively. The esophageal deviation index was newly defined as the largest diameter from the midline to deviated gastric tube divided by the largest transverse diameter of the thoracic cavity on the radiograph. Regression analyses were performed to identify postnatal imaging features associated with overall survival and a requirement for ECMO. The predictive power (ie, area under the curve [AUC] of a time-dependent receiver operating characteristic curve) of prenatal, postnatal, and intraoperative findings for predicting survival were calculated. RESULTS: Ninety-seven patients (54 males; mean gestational age, 38.3 ± 1.9 weeks; mean birth weight, 2956.5 ± 540.0 g) were analyzed. The esophageal deviation index (adjusted hazard ratio [HR], moderate [≥0.19 to <0.24], 6.427 [P = .029]; severe [≥0.24], 33.007 [P < .001]) and right pneumothorax (adjusted HR, 8.763; P = .002) were associated with overall survival and with a requirement for ECMO. Liver herniation on postnatal ultrasound also was associated with overall survival (P < .001) and need for ECMO (P = .001). In addition, the AUC for prediction of 1-year survival from postnatal ultrasound was comparable with that of prenatally or intraoperatively detected liver herniation (0.93; 95% CI, 0.88-0.97). CONCLUSIONS: The esophageal deviation index, right pneumothorax, and liver herniation observed by postnatal imaging have prognostic value in patients with left-sided congenital diaphragmatic hernia.