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Abstract Aim The purpose of our study was to construct the context of the nursing action/role in oncofertility care. Design Qualitative research. Methods We applied grounded theory to guide the qualitative study. Data were collected through in‐depth interviews with 12 nurses in Taipei. The data were collected from August 2018 to February 2019. Results The core theme that described the role of nurses’ decision‐making in oncofertility care focused on understanding oncofertility from the self to the other. Care roles or actions in oncofertility that involved the process of psychological cognition were divided into four dimensions: perceiving the patient's changes and needs, triggering the self's emotions, empathizing with patient's situations and introspective care roles. Nurses who had experienced the phase of empathizing with the patient's situations developed more diverse roles and had positive actions toward oncofertility care. Based on the psychological changes for oncofertility decision‐making process, implementing contextual training in oncofertility could help nurses create more positive actions in oncofertility care.

Background/purpose: Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. Materials and methods: This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. Results: In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. Conclusion: The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation.

Abstract The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch‐clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety‐like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3‐d subacute restraint stress (SRS), a well‐validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS‐induced anxiety‐related behaviors, whereas hM3Dq‐mediated chemogenetic or SRS‐induced activation of vHPC astrocytes enhances anxiety‐like behaviors, which are reversed by intra‐vHPC application of the ionotropic glutamate N‐methyl‐d‐aspartate receptor antagonists. Furthermore, intra‐vHPC or systemic application of the N‐methyl‐d‐aspartate receptor antagonist memantine, a U.S. FDA‐approved drug for Alzheimer's disease, fully rescues SRS‐induced anxiety‐like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety‐related disorders.

Abstract Background In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers’ smart device usage and behavioral outcomes, are limited. Understanding the impact of parent–child interactions on this relationship is crucial for enhancing toddlers’ developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers’ behaviors, as well as the positive effects of mother–child interactions on this influence. Methods We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children’s behavior by using the Child Behavior Checklist (for ages 11/2–5 years), (2) assessments of mother–child interactions by using the Brigance Parent–Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression. Results A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aβ) = 2.17, 95% confidence interval (CI) = 0.39–3.95, p-value = 0.01], withdrawal (aβ = 2.42, 95% CI = 0.15–4.69, p-value = 0.04), and aggressive behavior (aβ = 6.53, 95% CI = 0.25–12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother–child interaction. Nevertheless, positive mother–child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother–child interactions. Conclusion Early mother–child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.

Abstract Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.

BackgroundPsychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This study aims to determine if relationships between social, health, behavioral, and socioeconomic factors on PWB among older Taiwanese adults are affected by gender.MethodsData were obtained from the 2016 Taiwan Mental Health Survey. A representative sample, of 2,286 individuals, was created using multistage proportional probability. Participants were interviewed at their homes using a structured questionnaire. Inclusion criteria were Taiwanese citizenship, age ≥ 55 years, and the ability to provide informed consent. Participants 65 years and above were selected for the study sample n = 1,533. An 18-item version of Ryff’s PWB scale was used to determine PWB. The median value was used to categorize low and high PWB. Logistic regression analyses were used to examine predictors of PWB stratified by gender.ResultsChronic disease, unemployment, and financial dependence negatively impacted men’s PWB. Satisfaction with living environment and family relationships positively impacted women’s PWB. Unique characteristics of older men, women, and culture account for this.ConclusionGender-specific interventions aimed at promoting PWB in older adults are needed. Recommendations include educational programs, social support workshops, and community engagement initiatives.

Objective: There is limited safety data on the use of everolimus during pregnancy. In this study, we present the maternal and neonatal outcomes of everolimus used throughout the course of pregnancy and conducted a systematic review of reports of everolimus use after organ transplantation during pregnancy. Case report: A woman with type 1 diabetes who underwent kidney transplantation was treated with tacrolimus, everolimus, and prednisolone. Two years later, she became pregnant. At 27 weeks of gestation, an emergent cesarean delivery was performed owing to severe preeclampsia and fetal distress. No congenital malformation was noted in the baby at a corrected age of 4 months, and the maternal renal function remained stable. Conclusion: Our systematic review did not identify evidence of teratogenicity in babies exposed to everolimus as an immunosuppressant after transplantation. To better assess the risk of exposure to everolimus during pregnancy, all cases of new pregnancies occurring in transplant recipients receiving treatment with mammalian target of rapamycin inhibitor inhibitors should be reported.

DNA vaccines for infectious diseases and cancer have been explored for years. To date, only one DNA vaccine (ZyCoV-D) has been authorized for emergency use in India. DNA vaccines are inexpensive and long-term thermostable, however, limited by the low efficiency of intracellular delivery. The recent success of mRNA/lipid nanoparticle (LNP) technology in the coronavirus disease 2019 (COVID-19) pandemic has opened a new application for nucleic acid-based vaccines. Here, we report that plasmid encoding a trimeric spike protein with LNP delivery (pTS/LNP), similar to those in Moderna’s COVID-19 vaccine, induced more effective humoral responses than naked pTS or pTS delivered via electroporation. Compared with TSmRNA/LNP, pTS/LNP immunization induced a comparable level of neutralizing antibody titers and significant T helper 1-biased immunity in mice; it also prolonged the maintenance of higher antigen-specific IgG and neutralizing antibody titers in hamsters. Importantly, pTS/LNP immunization exhibits enhanced cross-neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and protects hamsters from the challenge of SARS-CoV-2 (Wuhan strain and the Omicron BA.1 variant). This study indicates that pDNA/LNPs as a promising platform could be a next-generation vaccine technology.

Oxidative stress attacks cells, causing the accumulation of reactive oxygen species, leading to aging and age-related diseases. The trace mineral selenium (Se) has the ability to protect against oxidative stress. The mushroom, Tropicoporus linteus (TL), has health-promoting properties; however, its ability to combat oxidative stress is still under investigation. In this study, we aimed to study whether TL and Se-enriched TL (Se-TL) possess antioxidant properties. We observed that the Se content in Se-TL mycelium was higher than that in TL mycelium. Both TL and Se-TL mycelia exhibited antioxidant activities in vitro. Both TL and Se-TL mycelium extended the lifespan of female Drosophila melanogaster (D. melanogaster). Under H2O2 conditions, TL or Se-TL mycelium increased the survival time of D. melanogaster, while Se-TL mycelium was more pronounced. Furthermore, TL and Se-TL mycelium modulated the antioxidant system, including non-enzymatic and enzymatic antioxidant defences in H2O2-treated D. melanogaster. Our data suggest that Se-TL is a promising functional food for modulating the antioxidant system against ROS-induced cellular damage, thus improving the anti-aging effect of TL.

Drugs acting on dopamine D2 receptors are widely used for the treatment of several neuropsychiatric disorders, including schizophrenia and depression. Social deficits are a core symptom of these disorders. Pharmacological manipulation of dopamine D2 receptors (Drd2), a Gi-coupled subtype of dopamine receptors, in the medial prefrontal cortex (mPFC) has shown that Drd2 is implicated in social behaviors. However, the type of neurons expressing Drd2 in the mPFC and the underlying circuit mechanism regulating social behaviors remain largely unknown. Here, we show that Drd2 were mainly expressed in pyramidal neurons in the mPFC and that the activation of the Gi-pathway in Drd2+ pyramidal neurons impaired social behavior in male mice. In contrast, the knockdown of D2R in pyramidal neurons in the mPFC enhanced social approach behaviors in male mice and selectively facilitated the activation of mPFC neurons projecting to the nucleus accumbens (NAc) during social interaction. Remarkably, optogenetic activation of mPFC-to-NAc-projecting neurons mimicked the effects of conditional D2R knockdown on social behaviors. Altogether, these results demonstrate a cell type-specific role for Drd2 in the mPFC in regulating social behavior, which may be mediated by the mPFC-to-NAc pathway.

The outbreak of the novel coronavirus pneumonia (COVID-19) in 2019 and the 2022 war in Ukraine have had profound global impacts on travel and logistics, disrupted the material supply chain, significantly influenced the cost and progress of construction projects, and further impacted the operational effectiveness of firms. Despite some existing studies providing valuable insights into the impact of COVID-19 on the construction industry, there remain research gaps that need to be addressed. Prior studies have mainly focused on the immediate impact factors of the pandemic, such as supply chain disruptions and workforce shortages, and strategies for effectively reducing or eliminating these risks. However, there is a need for research that delves into the long-term implications of these disruptions. So far, no relevant research has quantified the broader impact of the epidemic. Thus, this study aims to analyze the effects of the pandemic and the war on 136 construction industry professionals, their projects, and firms through literature review, questionnaire surveys, and expert interviews. The study compiles a list of significant risk factors for construction projects between 2019–2022, including their probability of occurrence, impact over time, and overall cost. The study also analyzes and discusses the impact of these high-risk factors as of 2022. To quantify the impact, cost, and level of exposure to these risks suffered by actual construction projects over this period, the Monte Carlo simulation method is introduced. This approach provides contractors with early prediction of risks and appropriate responses to mitigate risks.

Abstract We examined the potential mediating roles of anxiety and loneliness on the association of concurrent food insecurity (FI) and being bullied (BB) with suicidal behavior (SB) in Eswatini, a lower-middle-income country. We used data from the Global School-based Student Health Survey (GSHS; N = 3264), which employed a two-stage cluster sampling: first, 25 schools were selected based on the proportionate probability of enrollment; second, classes were randomly selected. A self-reported 84-item GSHS questionnaire was used to collect data for students aged 13–17 years. FI was measured by requesting students to recall how often they went hungry because of a lack of food at home in the 30 days before the study. Multiple logistic regressions and binary mediation function was applied to examine mediating factors of SB. The prevalence of SB, FI, and BB among adolescents was 27.5%, 7.7%, and 30.2%, respectively. Moreover, the relationship between FI and BB with SB was partly (approximately 24%) mediated by anxiety and loneliness. Our results highlight the mediating roles of anxiety and loneliness in suicidal adolescents who experience FI and BB. In conclusion, interventions for alleviating SB in high-risk adolescents experiencing FI and BB should also be aimed at ameliorating anxiety and loneliness.

Abstract Smokers of any age can reap substantial health benefits from quitting or reducing their smoking. E-cigarettes have been promoted as a potentially promising product for tobacco harm reduction because e-cigarettes deliver nicotine vapor without many of the hazardous chemical combustion byproducts produced by combustible cigarette smoking. However, there remains an ongoing debate on whether the use of e-cigarettes is effective in combustible cigarette smoking cessation or reduction in both adolescents and adults. Our study uses data from the 2015 (baseline) and from the 2017 (follow-up) waves of the Taiwan Adolescent to Adult Longitudinal Study (TAALS), which is a large nationwide representative cohort study of health behaviors among adolescents in Taiwan. We analyzed the data using logistic regression and multivariate regression with a post-stratification weighting procedure. Among the 474 adolescent combustible cigarette users at baseline, the use of e-cigarettes had no association with smoking cessation (aRR = 0.99, 95% CI = 0.66, 1.50). Furthermore, the use of e-cigarettes was also not associated with change in combustible cigarette consumption among all adolescent combustible cigarette users at follow-up (Coef. = 0.62, 95% CI = − 36.85, 38.09). In summary, our findings suggest that e-cigarettes may not aid tobacco control among adolescent smokers. Policy makers should be cautious of the potential harms that e-cigarette may bring to young people when they are developing e-cigarette regulations.

IntroductionRecombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes.MethodsIn this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively.ResultsWe found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors.DiscussionOur findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

This retrospective observational case series is to evaluate the histopathological findings of drooping eyelids in patients with infantile-onset Pompe disease and assess the feasibility of levator muscle resection combined with conjoint fascial sheath suspension for ptosis correction. It included six patients from a single tertiary referral center with ptosis and infantile-onset Pompe disease between January 1, 2013, and December 31, 2021. They most suffered from recurrent ptosis after initial surgical correction (6/11 eyes, 54.55%). The recurrence rate was high in eyes with levator muscle resection alone (4/6 eyes, 66.67%). No recurrence of ptosis was observed in eyes with levator muscle resection combined with conjoint fascial sheath suspension. The follow-up period was approximately 16–94 months. Histopathological examination revealed that the levator muscle had the most abundant glycogen accumulation-related vacuolar changes, followed by Müller's muscle and extraocular muscles. No vacuolar changes were observed in the conjoint fascial sheath. For patients with infantile-onset Pompe disease-related ptosis, performing levator muscle resection alone is not sufficient, while utilizing conjoint fascial sheath suspension can achieve the desired long-term outcomes with minimal recurrence. These findings may have important implications for the management of ophthalmic complications in patients with infantile-onset Pompe disease.

Abstract This study is aimed to determine the appropriate timing of performing surgical reduction on trapdoor fractures for bringing out better visual outcomes and the factors influencing surgical outcomes in this special subgroup of fracture victims. Data for 72 patients of orbital trapdoor fracture were analyzed retrospectively. Post-operative diplopia is the main posttreatment outcome of orbital bone fracture reduction. The receiver-operating characteristic (ROC) analysis indicated the cut-off point of surgical reduction timing at day 10 post-fracture. The rate of postoperative diplopia showed a significant difference between patients who underwent surgical reduction within 10 days and those who did after 10 days of injury (5.3% vs. 38.2%). Multivariate analysis revealed that preoperative infra-duction limitation (p = 0.02), muscle incarceration (p = 0.01), duration from injury to surgical reduction (p = 0.004), and postoperative supra-duction limitation (p = 0.004) were independent factors for poor surgical outcomes. In younger patients with head injury, the diagnosis of orbital trapdoor fracture should be kept in mind. Timely recognition and surgical reduction, especially within 10 days, can result in better visual outcomes without the occurrence of postoperative diplopia.

Background: Cardiac pressure overload induces cardiac hypertrophy and eventually leads to heart failure. One distinct feature of pathological cardiac hypertrophy is fetal-gene re-expression, but not every cardiomyocyte exhibits fetal gene re-expression in the diseased heart. Adult cardiomyocytes are terminally differentiated cells, so we do not know how the heterogeneity is determined and whether the differential fetal-gene reprogramming indicates a different degree of remodeling among cardiomyocytes. We hypothesized that fetal gene-expressed cardiomyocytes show more pathological features in the pressure-overloaded heart. Results: We induced pressure overload in mice by transverse aortic constriction (TAC) and observed a cardiomyocyte population with expression of β-myosin heavy chain (βMHC, a fetal gene encoded by Myh7) after TAC for 3 days. On transcriptomic and proteomic analyses, βMHC-expressed cardiomyocytes of 3-day TAC hearts were enriched in genes in cardiomyopathy-associated pathways and glycolytic processes. Moreover, results of immunoblotting and enzyme activity assay suggested higher glycolytic activity in βMHC-expressed than non-expressed cardiomyocytes. When we inhibited the glycolytic flux by 2-deoxy-d-glucose, a widely used glycolysis inhibitor, the number of βMHC-expressed cardiomyocytes was reduced, and the level of TEA domain family member 1 (TEAD1), a transcriptional enhancer, was decreased. Also, our spatial transcriptomic results demonstrated that naïve and 3-day TAC hearts had fetal-gene–rich tissue domains that were enriched in pathways in extracellular matrix organization and tissue remodeling. As well, gene levels of glycolytic enzymes were higher in Myh7-positive than Myh7-negative domains. Conclusions: Our data suggest that βMHC-expressed cardiomyocytes progress to pathological remodeling in the early stages of cardiac hypertrophy. In addition, the diverse glycolytic activity among cardiomyocytes might play a role in regulating gene expression via TEAD1 signaling.

Abstract In recent years, the rapid development of fresh food e-commerce in China has brought about more development opportunities for the cold chain logistics industry but has also presented new challenges. With the development of cloud computing and big data technology, it is increasingly important to study the application of big data and cloud computing technology in cold chain logistics. The purpose of this paper is to study the intelligent algorithm of cold chain logistics distribution optimization based on big data cloud computing analysis. Based on the constituent elements of the cold chain distribution problem and using cloud computing technology to obtain real-time traffic information in the transportation system through a unified access interface, this article analyses the distribution time and cost of refrigerated vehicles, thereby establishing a cold chain distribution vehicle path optimization model. By analysing the parallel programming mode of cloud computing, the parallel design and analysis of a coarse-grained genetic algorithm are used to solve the simulation model of the established optimization model. The experimental results show that the method of optimizing cold chain logistics vehicle routing using cloud computing is effective. When comparing 1, 2, 4, and 8 processors, the execution times are 19.89, 14.52, 8.12, and 6.41, respectively. It can be seen that the more processors there are, the shorter the calculation time.

IntroductionResilience refers to the ability to adapt to difficult situation or adversity. Resilience is what gives people the psychological strength to cope with stress and hardship. Previous studies have investigated the relationship between resilience and bullying victimization and mental health problems. But whether the moderating effect of resilience against depression varies among victims of different types of bullying victimization remains unknown.MethodsThe study used data from the Taiwan Adolescent to Adult Longitudinal Study (TAALS), which was a school based, nationwide, longitudinal study conducted among adolescents in Taiwan. Between 2015 and 2019, the survey was repeated three times to capture changes in health behaviors. Meanwhile, our study is a cross-sectional study focusing on the 2nd follow-up survey of the TAALS, where we recruited 4,771 Grade 7 (12–13 years) and Grade 10 (15–16 years) students who had experienced bullying at school.ResultsThis study confirms the protective effect of resilience on depression among adolescents who have experienced bullying. The mode resilience score was used as a reference group. Compared to the reference group, victims of verbal bullying from the lowest resilience group were at the greatest risk of depression (OR = 5.91, CI = 4.38–7.99). Compared to the reference group, victims of cyber bullying from the highest resilience group had the lowest risk of depression (OR = 0.72, CI = 0.57–0.90).ConclusionRegardless of the type of bullying victimization, resilience has been shown to offer protection against depression. Specifically, higher resilience levels offer the greatest protection against depression for victims of cyber bullying compared to other three types of bullying victimization. Early interventions to reduce negative effects of bullying victimization may start with increasing an individual's resilience during adolescence.

Urothelial carcinoma (UC) is characterized by a high incidence of TP53 mutation, and overcoming resistance to cisplatin-based chemotherapy in UC is a major concern. Wee1 is a G2/M phase regulator that controls the DNA damage response to chemotherapy in TP53-mutant cancers. The combination of Wee1 blockade with cisplatin has shown synergistic efficacy in several types of cancers, but little is known regarding UC. The antitumor efficacy of the Wee1 inhibitor (AZD-1775) alone or in combination with cisplatin was evaluated in UC cell lines and a xenograft mouse model. AZD-1775 enhanced the anticancer activity of cisplatin by increasing cellular apoptosis. AZD-1775 inhibited the G2/M checkpoint, improving the sensitivity of mutant TP53 UC cells to cisplatin by enhancing the DNA damage process. We confirmed that AZD-1775 combined with cisplatin reduced tumor volume and proliferation activity and increased the markers of cell apoptosis and DNA damage in the mouse xenograft model. In summary, the Wee1 inhibitor AZD-1775 combined with cisplatin elicited a promising anticancer efficacy in UC, and constitutes an innovative and promising therapeutic strategy.

Abstract Background Although maternal mental illnesses have been found to influence child health and development, little is known about the impact of maternal positive well-being on child health and development. Therefore, this longitudinal study investigated the effects of prenatal subjective well-being on birth outcomes and child development by considering the potential modifier effect of parity. Methods Pregnant women in early stages of pregnancy were recruited at five selected hospitals in Taipei, Taiwan, during their prenatal appointments since 2011. Self-reported evaluations were conducted at seven time points up to 2 years postpartum. Linear regression and generalized estimating equation models were used for examination. Results Higher prenatal eudaimonic well-being was associated with longer gestational length (adjusted beta [aβ] = 0.36, 95% confidence interval [CI] = 0.03, 0.68) and higher birth weight (aβ = 124.71, 95% CI = 35.75, 213.66). Higher positive and negative affect were associated with longer gestational length (aβ = 0.38, 95% CI = 0.06, 0.70) and smaller birth weight (aβ = −93.51, 95% CI = −178.35, −8.67), respectively. For child’s outcomes, we found an association between higher prenatal eudaimonic well-being and decreased risks of suspected developmental delay, particularly for children of multiparous mothers (adjusted odds ratio = 0.18, 95% CI = 0.05, 0.70). Higher levels of prenatal depression and anxiety were significantly associated with increased risks of suspected developmental delay for children of primiparous mothers. Conclusions Positive prenatal maternal mental health may benefit birth outcomes and child development, particularly for children of multiparous mothers. Interventions for improving prenatal mental health may be beneficial for child development.

Anxiety-related disorders respond to cognitive behavioral therapies, which involved the medial prefrontal cortex (mPFC). Previous studies have suggested that subregions of the mPFC have different and even opposite roles in regulating innate anxiety. However, the specific causal targets of their descending projections in modulating innate anxiety and stress-induced anxiety have yet to be fully elucidated. Here, we found that among the various downstream pathways of the prelimbic cortex (PL), a subregion of the mPFC, PLmediodorsal thalamic nucleus (MD) projection, and PL-ventral tegmental area (VTA) projection exhibited antagonistic effects on anxiety-like behavior, while the PL-MD projection but not PL-VTA projection was necessary for the animal to guide anxiety-related behavior. In addition, MD-projecting PL neurons bidirectionally regulated remote but not recent fear memory retrieval. Notably, restraint stress induced high-anxiety state accompanied by strengthening the excitatory inputs onto MD-projecting PL neurons, and inhibiting PL-MD pathway rescued the stress-induced anxiety. Our findings reveal that the activity of PL-MD pathway may be an essential factor to maintain certain level of anxiety, and stress increased the excitability of this pathway, leading to inappropriate emotional expression, and suggests that targeting specific PL circuits may aid the development of therapies for the treatment of stress-related disorders. [ABSTRACT FROM AUTHOR]

Background: Psychological well-being (PWB) facilitates good health. Few studies have taken into consideration gender and how it can affect PWB within a sociocultural context. This study aims to determine if relationships between social, health, behavioral, and socioeconomic factors on PWB among older Taiwanese adults are affected by gender. Methods: Data were obtained from the 2016 Taiwan Mental Health Survey. A representative sample, of 2,286 individuals, was created using multistage proportional probability. Participants were interviewed at their homes using a structured questionnaire. Inclusion criteria were Taiwanese citizenship, age = 55 years, and the ability to provide informed consent. Participants 65 years and above were selected for the study sample n = 1,533. An 18-item version of Ryff's PWB scale was used to determine PWB. The median value was used to categorize low and high PWB. Logistic regression analyses were used to examine predictors of PWB stratified by gender. Results: Chronic disease, unemployment, and financial dependence negatively impacted men's PWB. Satisfaction with living environment and family relationships positively impacted women's PWB. Unique characteristics of older men, women, and culture account for this. Conclusion: Gender-specific interventions aimed at promoting PWB in older adults are needed. Recommendations include educational programs, social support workshops, and community engagement initiatives. [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (SA) bacteremia is responsible for over 10,000 deaths in the hospital setting each year. Both conventional CD4+ T cells and γδ T cells play protective roles in SA infection through secretion of IFN-γ and IL-17. However, the role of other unconventional T cells in SA infection is largely unknown. Natural killer T (NKT) cells, a subset of innate-like T cells, are activated rapidly in response to a wide range of self and microbial lipid antigens presented by MHC I-like molecule CD1d. NKT cells are divided into two groups, invariant NKT (iNKT) and type II NKT cells, based on TCR usage. Using mice lacking either iNKT cells or both types of NKT cells, we show that both NKT cell subsets are activated after systemic SA infection and produce IFN-γ in response to SA antigen, however type II NKT cells are sufficient to control bacterial burden and inflammatory infiltrate in infected organs. This protective capacity was specific for NKT cells, as mice lacking mucosal associated invariant T (MAIT) cells, another innate-like T cell subset, had no increased susceptibility to SA systemic infection. We identify polar lipid species from SA that induce IFN-γ production from type II NKT cells, which requires both CD1d-TCR engagement and IL-12 production by antigen presenting cells. We also demonstrate that a population of T cells enriched for type II NKT cells are increased in PBMC of SA bacteremic patients compared to healthy controls. Therefore, type II NKT cells perform effector functions that enhance control of SA infection prior to conventional T cell activation and recognize SA-derived lipid antigens. As CD1d is highly conserved in humans, these CD1d-restricted SA lipid antigens could be used in the design of next generation SA vaccines targeting cell-mediated immunity.

Objective: To investigate the incidence and risk factors of retinopathy of prematurity (ROP) in very and extremely preterm (28+0-

Craniofacial osteomas, which involve orbits, can cause several problems, such as displacement of the globe, diplopia, and refractive changes. We report the case of a young man with diplopia and blurred vision, with a giant osteoma occupying right frontal and ethmoid sinuses, encroaching into his right orbit. The symptoms resolved 3 months after surgery. Our case highlights the successful surgery for a symptomatic craniofacial osteoma with orbital invasion.

Abstract Background Malaria in pregnancy is a critical public health challenge, and intermittent preventive treatment for malaria during pregnancy (IPTp) has proven to be an effective intervention. However, access to and use of malaria interventions, including IPTp, remains a considerable problem among African women. This cross-sectional study investigated factors, including antenatal care (ANC) attendance (both numbers of visits and timing of the first visit) and socio-demographics, associated with the uptake of the recommended IPTp dose among Malawian women. Methods A nationally representative sample of women with a live birth in the 2 years preceding the survey from the Malawi Demographic Health Survey 2015–2016 dataset was analysed. Self-reported data on socio-demographics, ANC attendance and IPTp uptake were collected using a questionnaire and analysed using logistic models. Results Of the 6549 included women, 1981 (30.2%) took the recommended three or more IPTp doses. Despite inadequate ANC visits, early ANC initiation increased the likelihood of these women taking the recommended IPTp dose; women who initiated ANC in the first [adjusted odds ratio (aOR) = 2.24; 95% confidence interval (CI) = 1.44–3.49] and second (aOR = 2.19; 95% CI = 1.56–3.08) trimesters were more likely to take the recommended IPTp dose compared to late initiators. The effect of the number of ANC visits on IPTp uptake was significant in married women (aOR = 1.68, 95% CI = 1.42–1.98), and the timing of first ANC visit was associated with IPTp uptake only among rural women (aOR = 2.13, 95% CI = 1.54–2.95). Conclusion ANC attendance is vital in IPTp uptake. The results highlight the need for health care providers to encourage women, particularly those in high-risk groups, to make frequent ANC visits and receive early ANC initiation to ensure high coverage of the recommended IPTp dose.

Abstract Although evidence suggests that homocysteine levels are elevated in severe mental illness in children, findings regarding homocysteine levels in youth with anxiety and depression are scarce. Therefore, this study examined the association of homocysteine levels with anxiety and depression in a community sample of students aged 6–13 years. In total, 649 students were selected from the first, fourth, and seventh grades of schools in Taipei, Taiwan, in 2010. These students completed a hospital-based health examination, which included physical examination, blood sample collection, and questionnaire administration. The data were analysed through multiple linear regression. Among the seventh-grade boys, both depression (adjusted β = 0.044, 95% confidence interval (CI) = 0.004–0.084) and anxiety (adjusted β = 0.052, 95% CI = 0.013–0.091) were independently associated with increased homocysteine levels. In further dichotomisation, compared with students with low anxiety levels, those with moderate to high anxiety levels were significantly positively associated with elevated serum homocysteine levels (adjusted β = 0.091, 95% CI = 0.003–0.180). Our results suggest that increased depression and anxiety may be positively associated with higher serum homocysteine levels in older boys. Our results provide essential data on the biological aspects underlying anxiety and depression in the studied population.

Background Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal lymphoma with growth mainly in the lumina of vessels. We studied a small series of IVLBCL and focused on its central nervous system (CNS) involvement. Methods Searching the medical records of Northwestern Memorial Hospital, we identified five cases of IVLBCL from January 2007 to January 2015. Clinical information, hematoxylin and eosin stained histologic slides and immunohistochemistry studies were reviewed for all cases. Polymerase chain reaction (PCR) analysis for the immunoglobulin (Ig) heavy and light chain gene rearrangement was performed on all five cases. Results Three of the five cases of IVLBCL were autopsies. Patients’ age ranged from 56 to 84. CNS involvement was present in two cases—in both patients, the CNS involvement showed an extravascular pattern with confluent sheet-like formation. PCR analysis confirmed that in one case the systemic intravascular and CNS extravascular components were clonally identical. Conclusions In a small case series of IVLBCL, we observed that CNS involvement by IVLBCL often has an extravascular morphology, but is clonally identical to the intravascular counterpart by PCR analysis. As IVLBCL can have a rapidly progressing poor outcome, it should be kept in the differential diagnoses for patients presenting with lymphoma of the CNS. The presence of extravascular growth patterns in the CNS should not exclude IVLBCL as a diagnosis.

Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Conclusions and importance: Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy. Keywords: Lymphoma, Triple-hit lymphoma, Orbital mass

Abstract Background Previous studies have stressed the importance of tobacco exposure for the mood disorders of depression and anxiety. Although a few studies have focused on perinatal women, none have specifically considered the effects of smoking and secondhand smoke exposure on perinatal suicidal ideation. Thus, this study aimed to investigate the relationships of smoking/secondhand smoke exposure status with suicidal ideation, depression, and anxiety from the first trimester to the first month post partum. Methods This cross-sectional study based on self-reported data was conducted at five hospitals in Taipei, Taiwan from July 2011 to June 2014. The questionnaire inquired about women’s pregnancy history, sociodemographic information, and pre-pregnancy smoking and secondhand smoke exposure status, and assessed their suicidal ideation, depression, and anxiety symptoms. Logistic regression models were used for analysis. Results In the 3867 women in the study, secondhand smoke exposure was positively associated with perinatal depression and suicidal ideation. Compared with women without perinatal secondhand smoke exposure, women exposed to secondhand smoke independently exhibited higher risks for suicidal ideation during the second trimester (odds ratio (OR) = 7.63; 95 % confidence interval (CI) = 3.25–17.93) and third trimester (OR = 4.03; 95 % CI = 1.76–9.23). Women exposed to secondhand smoke had an increased risk of depression, especially those aged 26–35 years (OR = 1.71; 95 % CI = 1.27–2.29). Conclusions Secondhand smoke exposure also considerably contributes to adverse mental health for women in perinatal periods, especially for the severe outcome of suicidal ideation. Our results strongly support the importance of propagating smoke-free environments to protect the health of perinatal women.

Epidemiological evidence shows the association between air pollutants and several mental health outcomes, including depression, sleep disturbance, dementia, childhood neurodevelopment and suicide. Pregnant women are believed to be more susceptible and vulnerable to environmental pollutants, and postpartum depression (PPD) is a prevalent debilitating mental disorder. However, data on the effects of exposure to air pollution during pregnancy and postpartum period on the risk of PPD remain limited. This study aimed to evaluate the association between exposure to ambient air pollution during pregnancy and postpartum period and the incidence of PPD. The Taiwan Birth Cohort Study recruited representative 12% of all newborn in 2005 and their mothers by two-stage stratified sampling, including 21 248 mother–infant pairs. The occurrence of PPD was assessed by a self-reported questionnaire. Exposure to air pollutants during pregnancy and postpartum period was estimated using hybrid kriging/land-use regression (LUR) and integrated LUR-machine learning model based on data from the air monitoring stations. Logistic regression was then conducted to determine adjusted odds ratios (aORs) of PPD in relation to air pollutants. A total of 21 188 women were included in the final analysis, among whom 3,648 (17.2%) developed PPD within 6 months postpartum. The occurrence of PPD was significantly related to exposure to ambient concentrations of nitrogen dioxide (NO _2 ) during first trimester after adjustment [aOR: 1.081 per interquartile range (10.67 ppb), 95% confidence interval: 1.003, 1.165], but not to particulate matter ⩽2.5 µ m in diameter or carbon monoxide. Exposure to ambient NO _2 during early pregnancy was significantly related to the occurrence of PPD among the women investigated in this population-based study.