Intranasal administration of DSM 32444 Bacillus subtilis spores: safety and tolerability.

Introduction. Administered nasally, spores of the Gram-positive bacterium Bacillus subtilis have been shown to be able to induce innate immunity sufficient to confer protection to influenza and respiratory syncytial virus.Hypothesis. Although members of the aerobiome, intranasal delivery of high numbers of live spores carries potential safety issues.Aim. To address the potential safety risk of using live spores, we assessed the safety of spores that had been completely inactivated using heat sterilization.Methodology. Using autoclaved, and therefore killed, spores of a generally recognized as safe-notified B. subtilis strain (DSM 32444), safety was assessed in vitro (biotype, genome and cell based cytoxicity) and in vivo, using intranasal administration in rodent models and lastly in human volunteers.Results. Using a 15-day, repeat-dose, regimen in a rodent model, no indication of toxicity was observed. In a registered human study (NCT05984004), a formulated preparation of inactivated DSM 32444 spores referred to as SPEROVID was developed, and tolerance in human volunteers was assessed following 7 days of nasal dosing (2-4 times/day).Conclusion. Our study demonstrated that in humans an intranasal dose of up to 3×108 killed spores was safe and well tolerated.

The Influence of Prenatal Breastfeeding Self-Efficacy on Breastfeeding Behavior of Taiwanese Pregnant Women.

BACKGROUND: The benefits of breastfeeding for mothers and infants are well known. However, in Taiwan, the average breastfeeding rate remains below the World Health Organization recommendations. Breastfeeding self-efficacy is a known predictor of breastfeeding. RESEARCH AIMS: To determine: (1) the relationship of sociodemographic factors to prenatal breastfeeding self-efficacy, and (2) the relationship of sociodemographic factors and prenatal breastfeeding self-efficacy to breastfeeding behavior at 8 weeks postpartum among women living in Taiwan. METHODS: This was a prospective cohort study of 206 pregnant women collected in an outpatient clinic located in Taiwan. The validated Chinese version of the Prenatal Breastfeeding Self-Efficacy Scale (PBSES) was used to measure self-efficacy for breastfeeding during pregnancy. At 8 weeks postpartum, participants were contacted by telephone to obtain information regarding infant feeding method and duration. RESULTS: The mean age of the pregnant women was 32 years, and the mean prenatal breastfeeding self-efficacy score was 78.6 (SD = 10.6). Scores differed across levels of maternal education, previous breastfeeding experience, and support systems. Prenatal breastfeeding self-efficacy scores were highest among participants reporting spouse support versus other types of support. Maternal age and prenatal breastfeeding self-efficacy were predictive of breastfeeding duration. A 1-year increase in maternal age was associated with a 6% lower likelihood of breastfeeding for at least 2 months postpartum, and a 1-point increase in the prenatal breastfeeding self-efficacy score was associated with a 14% increase in the likelihood of breastfeeding for at least 2 months postpartum. CONCLUSIONS: Prenatal breastfeeding self-efficacy may help predict breastfeeding continuation among Taiwanese women in the first 2 months postpartum.

Study and Application on the Electromagnetic Stainless Steel: Microstructure, Tensile Mechanical Behavior, and Magnetic Properties.

Stainless steel grade 430 is a type of soft magnetic electromagnetic material with rapid magnetization and demagnetization properties. Considering the delay phenomenon during operation, this study selected 430 stainless steel as the material and explored various metallurgical methods such as magnetic annealing and the addition of Mo as well as increasing the Si content to investigate the microstructure, mechanical behavior, and magnetic properties of each material, aiming to improve the magnetic properties of 430 stainless steel. Experimental results showed that the four electromagnetic steel materials (430F, 430F-MA, 434, and KM31) had equiaxed grain matrix structures, and excellent tensile and elongation properties were observed for each specimen. Additionally, the magnetic properties of the 430F specimen were similar under the DC and AC-10 Hz conditions. According to the hysteresis curves under different AC frequencies (10, 100, 1000 Hz), both magnetic annealing and the addition of Mo could reduce the Bm, Br, and Hc values of the raw 430F material. Increasing the Si content resulted in a decrease in Hc values and an increase in Bm and Br values.

Determining cut-off values and predictors for the Snaith-Hamilton Pleasure Scale: comparison between clinical and school settings.

BACKGROUND: Few previous studies have established Snaith-Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. AIMS: To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. METHOD: This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. RESULTS: The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. CONCLUSIONS: Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Epitaxial Growth of GaN Films on Chemical-Vapor-Deposited 2D MoS2 Layers by Plasma-Assisted Molecular Beam Epitaxy.

The van der Waals epitaxy of wafer-scale GaN on 2D MoS2 and the integration of GaN/MoS2 heterostructures were investigated in this report. GaN films have been successfully grown on 2D MoS2 layers using three different Ga fluxes via a plasma-assisted molecular beam epitaxy (PA-MBE) system. The substrate for the growth was a few-layer 2D MoS2 deposited on sapphire using chemical vapor deposition (CVD). Three different Ga fluxes were provided by the gallium source of the K-cell at temperatures of 825, 875, and 925 °C, respectively. After the growth, RHEED, HR-XRD, and TEM were conducted to study the crystal structure of GaN films. The surface morphology was obtained using FE-SEM and AFM. Chemical composition was confirmed by XPS and EDS. Raman and PL spectra were carried out to investigate the optical properties of GaN films. According to the characterizations of GaN films, the van der Waals epitaxial growth mechanism of GaN films changed from 3D to 2D with the increase in Ga flux, provided by higher temperatures of the K-cell. GaN films grown at 750 °C for 3 h with a K-cell temperature of 925 °C demonstrated the greatest crystal quality, chemical composition, and optical properties. The heterostructure of 3D GaN on 2D MoS2 was integrated successfully using the low-temperature PA-MBE technique, which could be applied to novel electronics and optoelectronics.

APLF facilitates interstrand DNA crosslink repair and replication fork protection to confer cisplatin resistance.

Replication stress converts the stalled forks into reversed forks, which is an important protection mechanism to prevent fork degradation and collapse into poisonous DNA double-strand breaks (DSBs). Paradoxically, the mechanism also acts in cancer cells to contribute to chemoresistance against various DNA-damaging agents. PARP1 binds to and is activated by stalled forks to facilitate fork reversal. Aprataxin and polynucleotide kinase/phosphatase-like factor (APLF) binds to PARP1 through the poly(ADP-ribose) zinc finger (PBZ) domain and is known to be involved in non-homologous end joining (NHEJ). Here, we identify a novel function of APLF involved in interstrand DNA crosslink (ICL) repair and fork protection. We demonstrate that PARP1 activity facilitates the APLF recruitment to stalled forks, enabling the FANCD2 recruitment to stalled forks. The depletion of APLF sensitizes cells to cisplatin, impairs ICL repair, reduces the FANCD2 recruitment to stalled forks, and results in nascent DNA degradation by MRE11 nucleases. Additionally, cisplatin-resistant cancer cells show high levels of APLF and homologous recombination-related gene expression. The depletion of APLF sensitizes cells to cisplatin and results in fork instability. Our results reveal the novel function of APLF to facilitate ICL repair and fork protection, thereby contributing to cisplatin-resistant phenotypes of cancer cells.

TEM1/endosialin/CD248 promotes pathologic scarring and TGF-ß activity through its receptor stability in dermal fibroblasts.

BACKGROUND: Pathologic scars, including keloids and hypertrophic scars, represent a common form of exaggerated cutaneous scarring that is difficult to prevent or treat effectively. Additionally, the pathobiology of pathologic scars remains poorly understood. We aim at investigating the impact of TEM1 (also known as endosialin or CD248), which is a glycosylated type I transmembrane protein, on development of pathologic scars. METHODS: To investigate the expression of TEM1, we utilized immunofluorescence staining, Western blotting, and single-cell RNA-sequencing (scRNA-seq) techniques. We conducted in vitro cell culture experiments and an in vivo stretch-induced scar mouse model to study the involvement of TEM1 in TGF-ß-mediated responses in pathologic scars. RESULTS: The levels of the protein TEM1 are elevated in both hypertrophic scars and keloids in comparison to normal skin. A re-analysis of scRNA-seq datasets reveals that a major profibrotic subpopulation of keloid and hypertrophic scar fibroblasts greatly expresses TEM1, with expression increasing during fibroblast activation. TEM1 promotes activation, proliferation, and ECM production in human dermal fibroblasts by enhancing TGF-ß1 signaling through binding with and stabilizing TGF-ß receptors. Global deletion of Tem1 markedly reduces the amount of ECM synthesis and inflammation in a scar in a mouse model of stretch-induced pathologic scarring. The intralesional administration of ontuxizumab, a humanized IgG monoclonal antibody targeting TEM1, significantly decreased both the size and collagen density of keloids. CONCLUSIONS: Our data indicate that TEM1 plays a role in pathologic scarring, with its synergistic effect on the TGF-ß signaling contributing to dermal fibroblast activation. Targeting TEM1 may represent a novel therapeutic approach in reducing the morbidity of pathologic scars.

Exploring the impact of a multilevel intervention focused on reducing the practices of seclusion and restraint in acute mental health units in an Australian mental health service.

Reducing and eliminating seclusion and restraint in inpatient settings has been a key area of focus in mental health policy and research for many years. To address this issue, numerous programmes aimed at minimising the use of these practices have been developed over the past two decades, with varying degrees of success. This article reports on research focused on the implementation of a localised, multilevel complex intervention that targeted both organisational and individual factors related to the use of seclusion and restraint. The researchers followed the impact of the intervention by interviewing medical, nursing and allied health staff who worked within the service (N = 12) and analysing the rates of seclusion and restraint over an 18-month period. Post-adoption, participants identified that there were clear changes in practice culture. Seclusion clearly became a practice of last resort and other options became prominent in staff's practice. Participants identified that there was a sense of shared purpose across the multidisciplinary team. The clinical environment was viewed as being more therapeutic for service users and less frightening for staff. There was a significant difference in the total number of seclusion events between pre- (Mean = 6.22, SD = 5.82) and post-implementation (Mean = 2.55, SD = 2.44, p = 0.002, d = 0.94), demonstrating a significantly lower number of seclusions was observed after the intervention. Similarly, a significant difference in restraint events between pre- (Mean = 5.50, SD = 3.77) and post-implementations (Mean = 3.38, SD = 3.21, p = 0.037, d = 0.62) was observed.

Dual-Specificity Phosphatase 6 Deficiency Attenuates Arterial-Injury-Induced Intimal Hyperplasia in Mice.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration, while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1ß induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 reduced IL-1ß-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1ß-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1ß, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1ß decreased the levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs, whereas lack of DUSP6 maintained their high levels, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

Genome-wide search algorithms for identifying dynamic gene co-expression via Bayesian variable selection.

A wealth of gene expression data generated by high-throughput techniques provides exciting opportunities for studying gene-gene interactions systematically. Gene-gene interactions in a biological system are tightly regulated and are often highly dynamic. The interactions can change flexibly under various internal cellular signals or external stimuli. Previous studies have developed statistical methods to examine these dynamic changes in gene-gene interactions. However, due to the massive number of possible gene combinations that need to be considered in a typical genomic dataset, intensive computation is a common challenge for exploring gene-gene interactions. On the other hand, oftentimes only a small proportion of gene combinations exhibit dynamic co-expression changes. To solve this problem, we propose Bayesian variable selection approaches based on spike-and-slab priors. The proposed algorithms reduce the computational intensity by focusing on identifying subsets of promising gene combinations in the search space. We also adopt a Bayesian multiple hypothesis testing procedure to identify strong dynamic gene co-expression changes. Simulation studies are performed to compare the proposed approaches with existing exhaustive search heuristics. We demonstrate the implementation of our proposed approach to study the association between gene co-expression patterns and overall survival using the RNA-sequencing dataset from The Cancer Genome Atlas breast cancer BRCA-US project.

PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves.

BACKGROUND: Cardiac valve disease is observed in 2.5% of the general population and 10% of the elderly people. Effective pharmacological treatments are currently not available, and patients with severe cardiac valve disease require surgery. PROX1 (prospero-related homeobox transcription factor 1) and FOXC2 (Forkhead box C2 transcription factor) are transcription factors that are required for the development of lymphatic and venous valves. We found that PROX1 and FOXC2 are expressed in a subset of valvular endothelial cells (VECs) that are located on the downstream (fibrosa) side of cardiac valves. Whether PROX1 and FOXC2 regulate cardiac valve development and disease is not known. METHODS: We used histology, electron microscopy, and echocardiography to investigate the structure and functioning of heart valves from Prox1ΔVEC mice in which Prox1 was conditionally deleted from VECs. Isolated valve endothelial cells and valve interstitial cells were used to identify the molecular mechanisms in vitro, which were tested in vivo by RNAScope, additional mouse models, and pharmacological approaches. The significance of our findings was tested by evaluation of human samples of mitral valve prolapse and aortic valve insufficiency. RESULTS: Histological analysis revealed that the aortic and mitral valves of Prox1ΔVEC mice become progressively thick and myxomatous. Echocardiography revealed that the aortic valves of Prox1ΔVEC mice are stenotic. FOXC2 was downregulated and PDGF-B (platelet-derived growth factor-B) was upregulated in the VECs of Prox1ΔVEC mice. Conditional knockdown of FOXC2 and conditional overexpression of PDGF-B in VECs recapitulated the phenotype of Prox1ΔVEC mice. PDGF-B was also increased in mice lacking FOXC2 and in human mitral valve prolapse and insufficient aortic valve samples. Pharmacological inhibition of PDGF-B signaling with imatinib partially ameliorated the valve defects of Prox1ΔVEC mice. CONCLUSIONS: PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain the extracellular matrix composition and prevent myxomatous degeneration of cardiac valves.

Long-term patient-reported donor-site morbidity after free peroneal fasciocutaneous flap in head and neck reconstruction.

OBJECTIVE: Fasciocutaneous free flap based on the peroneal artery (boneless version) is an option in our practice for head and neck reconstruction. However, the associated donor-site morbidity has rarely been discussed. Thus, this study investigated the long-term patient-reported donor-site morbidity associated with peroneal flaps. METHODS: In this single-center, retrospective, observational study, 39 patients who underwent a free peroneal flap were enrolled. We evaluated donor-site morbidity with a modified questionnaire from Enneking et al. and Bodde et al. RESULTS: Patient-reported daily life limitation was relatively low (5/39; 12.9%). Donor-site morbidities, namely pain (4/39; 10.3%), sensory disturbance (9/39; 23.1%), and walking limitation (9/39; 23.1%) were reported; most were rated minimal in severity. Among patients with walking limitation, muscle weakness (3/39; 7.7%), ankle instability (6/39; 15.4%), and gait alternation (6/39; 15.4%) were reported. Six patients developed claw toe. CONCLUSION: Balancing successful reconstruction and donor-site morbidity is challenging. This long-term patient-reported survey revealed that harvesting peroneal flaps resulted in minimal or minor donor-site morbidity with no obvious impacts on the patients' daily quality of life. Although free radial forearm flaps and anterolateral thigh flaps are standard, free peroneal flaps have been proven reliable, with acceptable donor-site morbidity.

Probucol treatment after traumatic brain injury activates BDNF/TrkB pathway, promotes neuroregeneration and ameliorates functional deficits in mice.

BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important in brain repair and functional recovery. In this study, probucol, a cholesterol-lowering drug with established safety profiles, was examined for its therapeutic effects and neuroregenerative actions in TBI. EXPERIMENTAL APPROACH: Male mice were subjected to the controlled cortical impact model of TBI, followed by daily administration of probucol. Neurological and cognitive functions were evaluated. Histological analyses of the neocortex and hippocampus were performed to detect the lesion, dendritic degeneration (microtubule-associated protein 2), synaptic density (synaptophysin), neurogenesis (doublecortin), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) activation. Involvement of BDNF/TrkB pathway in probucol-mediated effects was examined in primary cultures of cortical neurons. KEY RESULTS: Probucol reduced brain lesion volume, enhanced the recovery of body symmetry, improved motor function and attenuated memory dysfunction after TBI. Meanwhile, probucol promoted post-injury dendritic growth and synaptogenesis and increased hippocampal proliferating neuronal progenitor cells, along with the formation as well as the survival of newborn neurons. Moreover, probucol enhances BDNF expression and TrkB activation. In vitro, probucol promoted neurite outgrowth, which was inhibited by a selective TrkB antagonist ANA-12. CONCLUSIONS AND IMPLICATIONS: Probucol enhanced functional restoration and ameliorated cognitive impairment after TBI by promoting post-injury neuronal remodelling and neurogenesis. Increased activation of BDNF/TrkB pathway by probucol, at least in part, contributed to the neuroregenerative effects of probucol. Together, it may be promising to repurpose probucol for TBI.

The Role of GaN in the Heterostructure WS2/GaN for SERS Applications.

In the application of WS2 as a surface-enhanced Raman scattering (SERS) substrate, enhancing the charge transfer (CT) opportunity between WS2 and analyte is an important issue for SERS efficiency. In this study, we deposited few-layer WS2 (2-3 layers) on GaN and sapphire substrates with different bandgap characteristics to form heterojunctions using a chemical vapor deposition. Compared with sapphire, we found that using GaN as a substrate for WS2 can effectively enhance the SERS signal, with an enhancement factor of 6.45 × 104 and a limit of detection of 5 × 10-6 M for probe molecule Rhodamine 6G according to SERS measurement. Analysis of Raman, Raman mapping, atomic force microscopy, and SERS mechanism revealed that The SERS efficiency increased despite the lower quality of the WS2 films on GaN compared to those on sapphire, as a result of the increased number of transition pathways present in the interface between WS2 and GaN. These carrier transition pathways could increase the opportunity for CT, thus enhancing the SERS signal. The WS2/GaN heterostructure proposed in this study can serve as a reference for enhancing SERS efficiency.

Birth outcomes following pelvic ring injury: A retrospective study.

OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.

The influence of breastfeeding attitudes on breastfeeding behavior of postpartum women and their spouses.

Purpose: This study aimed to explore: (1) the influence of maternal sociodemographic factors on breastfeeding attitudes, (2) the relationship between breastfeeding attitudes of postpartum women and their spouses, (3) the predictors of breastfeeding behavior (mixed breastfeeding) at two months postpartum, and (4) to establish the reliability of the Chinese version of the paternal Iowa Infant Feeding Attitude Scale (IIFAS) in Taiwan. Methods: A correlational and follow-up study design was used on a convenience sample of 215 women and 215 fathers recruited from a regional teaching hospital in central Taiwan from July 2020 to December 2020. The participants completed the IIFAS during postpartum hospitalization and a follow-up via telephone at 8 weeks postpartum for information on feeding methods and duration. The Cox proportional hazards model was used to analyze the predictors of breastfeeding duration. Results: Maternal breastfeeding attitude scores ranged from 42 to 79, with a mean score of 59.78 (SD ± 6.68). Spouses' breastfeeding attitude scores ranged from 46 to 81, with a mean score of 59.60 (SD ± 6.93). Mother and spouse's IIFAS scores were highly correlated (r = 0.50, p < 0.001), and the scores of both parents were significantly associated with the duration of breastfeeding. With each increased point on maternal and paternal IIFAS scores, the odds of breastfeeding during the first 8 weeks increased 6% and 10%, respectively. Conclusion: This is the first study to validate the IIFAS (Chinese version) with paternal participants in Taiwan. Identifying and understanding the infant feeding attitudes of mothers and their spouses should be an early step in designing and implementing breastfeeding interventions.

Identifying differential trajectories and predictors for depressive symptoms in adolescents using latent class growth analysis: A population-based cohort study.

INTRODUCTION: This study investigated the differential trajectories and relevant determinants of depressive symptoms in adolescents by following cohorts that included junior, senior, and vocational high school adolescents, over a 3-year period in Taiwan. METHODS: Longitudinal data were obtained from 575 adolescents who participated in the Taiwan Adolescent to Adult Longitudinal Study. Data analysis included latent class growth with time-varying covariate, univariate, and multivariate analysis. RESULTS: A three-class ("low but increasing trajectory," "moderate and stable trajectory," and "high but decreasing trajectory") model fit the data of the cohort. Our findings indicated that 29%, 38%, and 33% of the adolescents were in the low but increasing, moderate and stable, and high but decreasing trajectories, respectively. After confounders were controlled for, bullying experiences were identified as a risk factor for depressive symptoms. The protective factors against depressive symptoms included resilience and peer and social support. CONCLUSIONS: The transitions between different educational stages critically influence the depressive symptoms of adolescents, and the adolescents follow different depressive trajectories, that have different etiology. Therefore, identifying adolescents at high risk for depression and designing student-centered intervention programs through individualized and multidimensional assessment of depressive symptoms are crucial for adolescents.

Changes in the Proteome Profile of A549 Cells Following Helichrysetin-Induced Apoptosis Suggest the Involvement of DNA Damage Response and Cell Cycle Arrest-Associated Proteins.

Our previous findings demonstrated that Helichrysetin possessed promising anti-cancer activity. It was able to induce apoptosis in the A549 cell line. However, its mechanism of action is unknown. The present study aimed to unravel possible underlying molecular mechanisms of helichrysetin-induced apoptosis in A549 (human lung carcinoma) cells using comparative quantitative proteomics (iTRAQ labeled), followed by an exhaustive bioinformatics analysis. Our results suggested that DNA damage response (DDR) and cell cycle arrest were responsible for lung cancer cell death with helichrysetin treatment. Among proteins that changed in abundance were Nrf2 and HMOX1. They are oxidative stress-related proteins and were increased in abundance. BRAT1 was also increased in abundance, suggesting an increase in DNA damage repair, indicating the occurrence of DNA damage due to oxidative stress. However, several essential DDR downstream proteins such as p-ATM, BRCA1, FANCD2, and Rb1 that would further increase DNA damage were found to be dramatically decreased in relative abundance. Cell cycle-related proteins, p53, p21, and cyclin D1, were increased while cyclin A, cyclin E, and cdk2 were decreased. This is predicted to facilitate S-phase arrest. Furthermore, excessive DNA damage and prolonged arrest would in turn result in the induction of mitochondrial-mediated apoptosis. Based on these observations, we postulate that the effects of helichrysetin were in part via the suppression of DNA damage response which led to DNA damage and prolonged cell cycle arrest. Subsequently, this event initiated mitochondrial-mediated apoptosis in A549 lung cancer cells.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.

OBJECTIVE: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by overgrowth and multiple anomalies. Most clinical diagnoses of SGBS1 are made postnatally. We present the case of a pregnant woman in whom the fetus presented with a thick nuchal fold 5.6 mm at 15 weeks of gestation, leading to the prenatal diagnosis of SGBS1 with Xq26.2 (133408101-134221889) deletion. CASE REPORT: We report the case of a 34-year-old pregnant woman with the initial presentation of fetal thick nuchal fold 5.6 mm at 15 weeks of gestation. Amniocentesis of the fetal karyotype revealed a normal 46, XY, and single nucleotide polymorphism array showed Xq26.2 (133408101-134221889) deletion. Prenatal ultrasound at 21 weeks of gestation revealed a thick nuchal fold, hepatomegaly, nephromegaly, congenital diaphragmatic hernia, hypospadias, and polyhydramnios. Fetal magnetic resonance imaging revealed hepatomegaly, nephromegaly, congenital diaphragmatic hernia, and right lung hypoplasia. The woman had her pregnancy terminated at 24 weeks of gestation. The proband had a general appearance of low-set ears, hypertelorism, a large tongue, and hypospadias and some unique findings on autopsy, including hepatomegaly, right hiatal hernia, liver extensive extramedullary hematopoiesis, kidney marked congestion, and focal hemorrhage. DISCUSSION: The main prenatal ultrasound findings that alert clinical doctors about the possible diagnosis of SGBS1 included macrosomia, polyhydramnios, organomegaly, renal malformations, congenital diaphragmatic hernia, and cardiac anomalies. Our case underscores the importance of fetal karyotyping combined with single nucleotide polymorphism array when a thick nuchal fold is found. Genetic counseling is essential in SGBS1, and prenatal testing or preimplantation testing for subsequent pregnancies is necessary to identify possible pathogenic variants.

Trans-arterial embolization for intractable primary postpartum hemorrhage caused by arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally: a case report.

Failure of conservative management for controlling postpartum hemorrhage (PPH) is not uncommon, particularly when PPH is caused by vascular lesions. Awareness of this possibility and initiating timely trans-arterial embolization (TAE) are essential for improving the outcome. Herein, we describe the case of a 34-year-old woman presenting with arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally, which caused intractable PPH. Conservative management failed to resolve the PPH; however, TAE successfully controlled the bleeding, and the patient recovered smoothly. Knowledge of this possible etiology for intractable PPH is crucial for timely TAE. This case report aims to highlight the pivotal role of TAE in detecting and treating this unusual cause of PPH.