Prognostic Communication Between Parents and Clinicians in Pediatric Oncology: An Integrative Review.

Background: Prognostic communication between clinicians and parents in pediatric oncology is complex. However, no review has exclusively examined research on prognostic communication in pediatric oncology. In this review, we synthesize the evidence on prognostic communication in pediatric oncology and provide recommendations for future research. Methods: We conducted an integrative review searching six databases for studies on prognostic communication in pediatric oncology as of August 2022. We applied descriptive and narrative approaches to data analysis. Results: Fourteen quantitative and five qualitative studies were included. All studies were conducted in Western developed countries. In total, 804 parents of 770 children with cancer were included. Across studies, parents were predominately female, Non-Hispanic White, and had high school or higher levels of education. Most parents reported that prognostic communication was initiated in the first year after their children's diagnosis. High-quality prognostic communication was positively associated with trust and hope and negatively associated with parental distress and decisional regret. In qualitative studies, parents suggested that prognostic communication should be open, ongoing, and delivered with sensitivity. Most studies were of moderate quality. The main gaps included inconsistent definitions of prognostic communication, and a lack of comprehensive and validated measurements, high-quality longitudinal studies, and diverse settings and participants. Conclusions: Clinicians should initiate high-quality prognostic communication early on in clinical practice. Future research should consider conducting high-quality longitudinal studies, developing prognostic communication definitions and measurements, and conducting studies across settings with diverse populations.

Development of lactoferrin-coated multifunctional copolymer micelles to cross the blood-brain barrier.

The blood-brain barrier (BBB) prevents pathogens and toxins in the bloodstream from reaching the brain, but also inhibits the delivery of agents intended to treat central nervous system disorders, such as Alzheimer's disease (AD). In this study, we prepared and evaluated a novel nano-delivery vehicle system composed of lactoferrin-conjugated (Lf-PIC@Se) micelles. We used a COOH-PEG-PAsp-PV@Se synthesis-based method to prepare the micelles, which involved self-assembly followed by EDC-NHS coupling. Using glutaminyl cyclase inhibitor 8 as a model encapsulated chemical, Lf-PIC@Se micelles achieved a good loading capacity. In vitro analysis demonstrated that Lf-PIC@Se/8 micelles were stable in both neutral and acidic pH solutions in the presence or absence of H2O2, and confirmed their biosafety and compatibility in PC12 and bEND.3 cells. Notably, the cell uptake of Lf-PIC@Se/C6 micelles was much higher than that of PIC@Se micelles, and occurred through LfR-mediated endocytosis. The presence of Se meant that Lf-PIC@Se micelles acted as ROS scavengers in PC12 cells under H2O2-induced oxidative stress, which inhibited oxidative damage and increased mitochondrial membrane potential. Hemolysis assays further demonstrated that Lf-PIC@Se represent a biocompatible carrier. Finally, in vivo experiments in mice suggested that Lf-PIC@Se micelles successfully crossed the BBB, confirming their potential as vehicles for drug delivery when treating AD and other central nervous system disorders.

Social Distancing in the COVID-19 Pandemic: Associated Factors, Health Outcomes, and Implications.

Social distancing has reemerged as a public health measure for containing the spread of COVID-19. This integrative review aims to analyze the historical use of social distancing, the current application during COVID-19, individual factors that affect social distancing practices, and consequential health outcomes. We analyzed relevant literature from searches conducted on Scopus, PubMed, and PsycINFO. We found that resources, culture, age, gender, and personality are associated with the degree to which people practice social distancing. Furthermore, social distancing changes our lifestyles and behavior and results in multifaceted health outcomes, including decreased physical activity and sunlight exposure, increased weight gain, and impaired sleep quality. On the positive side, social distancing has been linked to reduced crime rates and environmental damage, as well as better social and family ties. Future interventions may be utilized to increase adherence to social distancing practices and to mitigate the negative health effects of social distancing.

Caregiver engagement interventions on reducing the anxiety and depression of children with chronic health conditions and their caregivers: A meta-analysis of randomized controlled trials.

BACKGROUND: Anxiety and depression are common debilitating mental health issues in families of children with chronic health conditions. It is essential to consider the mediating role of caregivers between children and healthcare workers. Previous research has evaluated the effectiveness of caregiver engagement interventions in reducing anxiety and depression in chronically ill children and their caregivers, but their overall impact awaits a synthesis of the available evidence. METHODS: We performed a comprehensive search using PubMed, Embase, Web of Science, Cochrane Library, Ovid, PsycINFO, APA PsycArticles, and Cumulative Index of Nursing and Allied Health Literature (CINAHL). RESULTS: Twenty-nine studies were included. The results demonstrated that caregiver engagement interventions significantly decreased anxiety (standardized mean difference [SMD] = -0.49; 95% confidence interval [CI], -0.77 to -0.22; P < 0.001) and depression (SMD = -0.37; 95% CI, -0.55 to -0.18; P < 0.001) among caregivers, particularly in developing countries. However, no improvements in the anxiety (SMD = 0.00; 95% CI, -0.46 to 0.46; P = 0.99) and depression (SMD = -0.14; 95% CI, -0.32 to 0.04; P = 0.14) of children were observed. CONCLUSIONS: Significant evidence exists regarding the positive effects of caregiver engagement interventions on caregivers' anxiety and depression. Further recommendations for future research should focus on engagement interventions that reduce the anxiety and depression for children with chronic conditions. IMPLICATIONS: Clinicians should concentrate on the mental health of chronically ill children and their caregivers and extend caregiver engagement therapies to improve anxiety and depression resulting from managing the disease.

Design, synthesis and anti-AD effects of dual inhibitor targeting glutaminyl cyclase/GSK-3ß.

Alzheimer's disease (AD), multifactorial disease, is recognized as one of the most common forms of dementia, and the efficacy of anti-AD drugs is limited clinically. Up-regulated glutaminyl cyclase (QC) and glycogen synthase kinase-3ß (GSK-3ß) have been identified as two critical elements involved in AD recently. Here, a series of novel chemicals containing maleimide and imidazole motif were designed and synthesized as dual inhibitors targeting QC and GSK-3ß. Based on primary screening, compound 2 (2.26 µM), 5 (2.37 µM), 8 (1.34 µM), 21 (2.44 µM), 25 (0.36 µM), 27 (1.76 µM), 28 (1.04 µM), 33 (2.08 µM) and 34 (2.33 µM) exhibited notable human QC (hQC) inhibitory potency, while compound 1 (0.014 µM), 7 (0.04 µM), 8 (0.057 µM), 19 (0.034 µM), 24 (0.014 µM), 32 (0.032 µM), 38 (0.051 µM), 39 (0.044 µM), 44 (0.048 µM), 47 (0.011 µM), 49 (0.021 µM) and so on showed remarkable GSK-3ß inhibitory activities. And as expected, these chemicals possessed significant inhibitory potency on both hQC and GSK-3ß, such as compound 1 (2.80 and 0.014 µM), 8 (1.34 and 0.057 µM), 25 (0.36 and 0.15 µM), 27 (1.76 and 0.069 µM), 28 (1.04 and 0.090 µM), 33 (2.08 and 0.19 µM), 34 (2.33 and 0.11 µM), 35 (2.55 and 0.14 µM), 36 (2.34 and 0.11 µM), etc. Subsequent in vivo studies demonstrated that compound 8 attenuated cognitive deficits and decreased the anxiety-like behavior in 3 × Tg-AD mice. The treatment decreased both pE-Aß and Aß accumulation by inhibiting the activity of QC, and decreased the hyperphosphorylation of Tau by reducing the levels of GSK-3ß in the brains of AD mice. Results obtained in this research suggested that these novel compounds could be supposed as potential anti-AD agents targeting QC and GSK-3ß.

Upregulation of Glutaminyl Cyclase Contributes to ERS-Induced Apoptosis in PC12 Cells.

Glutaminyl cyclase (QC) is responsible for converting the N-terminal glutaminyl and glutamyl of the proteins into pyroglutamate (pE) through cyclization. It has been confirmed that QC catalyzes the formation of neurotoxic pE-modified Aß in the brain of AD patients. But the effects of upregulated QC in diverse diseases have not been much clear until recently. Here, RNA sequencing was applied to identify differentially expressed genes (DEGs) in PC12 cells with QC overexpressing or knockdown. A total of 697 DEGs were identified in QC overexpressing cells while only 77 in QC knockdown cells. Multiple bioinformatic approaches revealed that the DEGs in QC overexpressing group were enriched in endoplasmic reticulum stress (ERS) related signaling pathways. The gene expression patterns of 23 DEGs were confirmed by RT-qPCR, in which the genes related to ERS showed the highest consistency. We also revealed the protein levels of GRP78, PERK, CHOP, and PARP-1, and caspase family was significantly upregulated by overexpressing QC. Moreover, overexpressing QC significantly increased apoptosis of PC12 cells in a time dependent manner. However, no significant alteration was observed in QC knockdown cells. Therefore, our study indicated that upregulated QC could induce ERS and apoptosis, which consequently trigger diseases by catalyzing the generation of pE-modified mediators.

Associations Among Workplace Bullying, Resilience, Insomnia Severity, and Subjective Wellbeing in Chinese Resident Doctors.

BACKGROUND: Although workplace bullying is common among medical workers, its associations with insomnia severity and subjective wellbeing are still unclear. Our study aimed to investigate these associations among resident doctors who are more vulnerable to both workplace bullying and insomnia. METHODS: We conducted a cross-sectional survey of 1,877 resident doctors from 12 hospitals across 7 administrative regions in China. Workplace bullying, resilience, insomnia severity, and subjective wellbeing were evaluated by the Negative Acts Questionnaire-Revised (NAQ-R), the Chinese version of the Connor-Davidson Resilience Scale-10-item (CD-RISC-10), the Insomnia Severity Index, and the Index of Wellbeing, respectively. Further, a logistic regression analysis was used to analyze factors associated with insomnia. In addition, structural equation modeling (SEM) was applied to examine the associations among workplace bullying, resilience, insomnia severity, and subjective wellbeing. RESULTS: In the present study, the rates of workplace bullying and insomnia were 51.4 and 33.2%, respectively. Workplace bullying (OR = 1.056, p < 0.001) and poor resilience (OR = 0.957, p < 0.001) were the factors associated with insomnia after controlling the confounding variables. Further, SEM of the present study revealed a direct relationship between workplace bullying and subjective wellbeing (std-ß = -0.223, p < 0.001). In addition, insomnia severity (std-ß = -0.071, p < 0.001) and resilience (std-ß = -0.092, p < 0.001) can individually or collectively (std-ß = -0.008, p < 0.001) mediate the indirect associations between workplace bullying and subjective wellbeing. However, resilience was found to act as a moderator only in the direct association between workplace bullying and subjective wellbeing. CONCLUSIONS: Workplace bullying and poor resilience were the factors associated with insomnia. Further, greater resilience acted as a buffer in the direct association between workplace bullying and subjective wellbeing, whereas both insomnia severity and resilience were critical mediators in the indirect associations between them.

Repurposing FDA-Approved Compounds for the Discovery of Glutaminyl Cyclase Inhibitors as Drugs Against Alzheimer's Disease.

Alzheimer's disease (AD) is one of the most common neurodegenerative causes of dementia, the pathology of which is still not much clear. It's challenging to discover the disease modifying agents for the prevention and treatment of AD over the years. Emerging evidence has been accumulated to reveal the crucial role of up-regulated glutaminyl cyclase (QC) in the initiation of AD. In the current study, the QC inhibitory potency of a library consisting of 1621 FDA-approved compounds was assessed. A total of 54 hits, 3.33 % of the pool, exhibited QC inhibitory activities. The Ki of the top 5 compounds with the highest QC inhibitory activities were measured. Among these selected hits, compounds affecting neuronal signaling pathways and other mechanisms were recognized. Moreover, several polyphenol derivatives with QC inhibitory activities were also identified. Frameworks and subsets contained in these hits were analyzed. Taken together, our results may contribute to the discovery and development of novel QC inhibitors as potential anti-AD agents.

Nutritional Screening and Assessment, and Quality of Life in Children with Cancer: A Cross-Sectional Study in Mainland China.

PURPOSE: To apply Screening Tool for Risk on Nutritional status and Growth (STRONGkids) and the subjective global nutritional assessment (SGNA) for evaluating nutritional status, to identify the disease-related and demographic-related factors of malnutrition, and to examine the relationship between nutritional status and quality of life (QOL) in children with cancer during chemotherapy in mainland China. DESIGN AND METHODS: Children, ages 2-18, with a leukemia, lymphoma, or solid tumor diagnosis were recruited from a top cancer center in Guangzhou, China. Socio-demographic information, clinical information were collected, while nutritional status using SGNA, malnutrition risk using STRONGkids, and QOL of these children were measured. Descriptive analyses, Chi2-tests, ANOVA and logistic regression analysis were used to analyze data. RESULTS: Among included participants, 55.8% of them were malnourished, and 74.2% of them had moderate to high risk of malnutrition. The overall QOL and subscales were associated with nutritional status. In the logistic-regression model, high malnutrition risk, patients' mother having primary school education or less, worse physical functioning quality of life, and lower BMI level were strongly associated with malnutrition. CONCLUSIONS: The prevalence of malnutrition in children with cancer is high, which related to worse QOL. Patients' BMI, physical functioning QOL and mothers' educational level could help to predict their nutritional status. PRACTICE IMPLICATIONS: STRONGkids and SGNA could be widely used in mainland China. Health professionals should pay attention to patients with lower BMI and physical functioning scores, and patients' mother having primary school education or less.

Effects of a group-based physical activity program for pediatric patients with cancer on physical activity and symptom experience: A quasi-experimental study.

AIMS: To examine the effects of a group-based physical activity intervention on improvement in physical activity and mitigation of symptom distress among pediatric patients with cancer. METHODS: Based on convenience sampling, 57 pediatric patients with cancer admitted to the cancer center were included in the intervention group. The control group included 57 pediatric patients with cancer from two other hospitals matched to the patients in the intervention group by age, sex, and diagnosis. A group-based physical activity program was implemented among the children in the intervention group, whereas the children in the control group received standard care. Physical activity and symptoms were measured using the Children's Leisure Time Activities Study Survey-Chinese and using the Memorial Symptom Assessment Scale 10-18 at baseline and after the 12th exercise session in both the intervention and control groups. RESULTS: The repeated-measures analysis of variance showed that the main intervention effects on the decrease in light-intensity physical activity and increase in moderate-to-vigorous physical activity were significant between the two groups (P < .001). The group-based physical activity intervention could decrease the scores of psychological symptoms (P < .001), Global Distress Index (P < .001), and physical symptoms (P = .01) when comparing the difference between the two groups before and after the intervention. There was no significant difference in the number of symptoms or the total symptom experience score between the two groups. CONCLUSION: These findings suggest that a group-based physical activity intervention can promote physical activity and relieve psychological and physical symptom distress among pediatric patients with cancer.

A de novo Mutation in the MTUS1 Gene Decreases the Risk of Non-compaction of Ventricular Myocardium via the Rac1/Cdc42 Pathway.

Background: The MTUS1 gene encodes a microtubule-associated protein involved in multiple processes including cell polarity and microtubule balance during myocardial development. Aims: To investigate the association between a de novo c. 2617A->C mutation in MTUS1 (NM_001001924.2) and non-compaction of ventricular myocardium (NVM) and explore the potential mechanisms. Methods: A de novo mutation in MTUS1 was identified for a familial pedigree with NVM. Lentiviral vectors containing MTUS1 wild type or the mutation MTUS1 were constructed and co-infected into HEK-293 cells. MTUS1, Rac1/Cdc42, α-tubulin, α/ß-tubulin, polarity protein (PAR6), and the morphology of daughter cells were measured by real-time PCR, Western blot, and immunofluorescence assays, respectively. Results: The lentiviral vectors were constructed successfully. Immunofluorescence assays revealed the fluorescence intensity of α-tubulin to be decreased and α/ß-tubulin to be increased in the mutation MTUS1 group. The fluorescence intensity of PAR6 was higher and morphology of the daughter cells in the mutation group was different from the wild type group. The phosphorylation of Rac1/Cdc42 in the mutation group was significantly lower than in the wild type group. Conclusions: A de novo mutation in MTUS1 decreased the stability of microtubules and increased cell polarity via the Rac1/Cdc42 pathway, which may partly elucidate the mechanism underlying cellular protection in NVM.

An EGLN1 mutation may regulate hypoxic response in cyanotic congenital heart disease through the PHD2/HIF-1A pathway.

Cyanotic congenital heart disease (CCHD), a term describing the most severe congenital heart diseases are characterized by the anatomic malformation of a right to left shunt. Although the incidence of CCHD are far less than the that of congenital heart diseases (CHD), patients with CCHD always present severe clinical features such as hypoxia, dyspnea, and heart failure. Chronic hypoxia induces hypoxemia that significantly contributes to poor prognosis in CCHD. Current studies have demonstrated that the prolyl-4-hydroxylase2 (PHD2, encoded by EGLN1)/hypoxia-inducible factor-1A (HIF-1A) pathway is a key regulator of hypoxic response. Thus, we aim to assess the associations of single polymorphisms (SNPs) of the EGLN1 gene and hypoxic response in CCHD. A missense variant of EGLN1 c.380G>C (rs1209790) was found in 46 patients (46/126), with lower hypoxia incidence and higher rate of collateral vessel formation, compared with the wild type (P < 0.05). In vitro experiments, during hypoxia, EGLN1 mutation reduced EGLN1 expression compared with the wild type, with higher HIF-1A, VEGF and EPO expression levels in the mutant. No difference in HK1 expression was observed between the mutant and wild type. CCHD patients with c.380G>C showed improved response to hypoxia compared with the wild-type counterparts. The EGLN1 c.380G>C mutation improves hypoxic response through the PHD2/HIF-1A pathway, which may provide a molecular mechanism for hypoxic response in CCHD. The effects of the EGLN1 c.380G>C mutation on CCHD prognosis deserve further investigation.

A discriminant analysis prediction model of non-syndromic cleft lip with or without cleft palate based on risk factors.

BACKGROUND: A risk prediction model of non-syndromic cleft lip with or without cleft palate (NSCL/P) was established by a discriminant analysis to predict the individual risk of NSCL/P in pregnant women. METHODS: A hospital-based case-control study was conducted with 113 cases of NSCL/P and 226 controls without NSCL/P. The cases and the controls were obtained from 52 birth defects' surveillance hospitals in Hunan Province, China. A questionnaire was administered in person to collect the variables relevant to NSCL/P by face to face interviews. Logistic regression models were used to analyze the influencing factors of NSCL/P, and a stepwise Fisher discriminant analysis was subsequently used to construct the prediction model. RESULTS: In the univariate analysis, 13 influencing factors were related to NSCL/P, of which the following 8 influencing factors as predictors determined the discriminant prediction model: family income, maternal occupational hazards exposure, premarital medical examination, housing renovation, milk/soymilk intake in the first trimester of pregnancy, paternal occupational hazards exposure, paternal strong tea drinking, and family history of NSCL/P. The model had statistical significance (lambda = 0.772, chi-square = 86.044, df = 8, P < 0.001). Self-verification showed that 83.8 % of the participants were correctly predicted to be NSCL/P cases or controls with a sensitivity of 74.3 % and a specificity of 88.5 %. The area under the receiver operating characteristic curve (AUC) was 0.846. CONCLUSIONS: The prediction model that was established using the risk factors of NSCL/P can be useful for predicting the risk of NSCL/P. Further research is needed to improve the model, and confirm the validity and reliability of the model.

[Case-control study on environmental factors in congenital heart disease].

OBJECTIVE: To explore the relation between environmental factors and the occurrence of congenital heart disease (CHD). METHODS: A hospital-based case-control study was conducted. Mothers of 123 patients with congenital heart disease and 246 normal newborns were interviewed with standardized questionnaires. Chi-square test and logistic regression models were performed to analyze the influencing factors. RESULTS: As shown in multivariable logistic model, gravida with occupational exposure (OR=4.10), or gravida with chronic diseases during progestational pregnancy (OR=5.95), gravida with abnormal childbearing history (OR=6.27), and gravida catching a cold in the early stage of pregnancy (OR=2.07) would increase the risk of CHD. On the contrary, eating meat, egg (OR=0.18) and milk (OR=0.23), and taking multivitamin and microelement (OR=0.35) during the pregnancy reduced the risk of CHD. CONCLUSION: The risk of the offspring developing CHD is associated with gravida's exposure to many environmental factors during pregnancy. It is time to strengthen the intervention measures to reduce the occurrence of CHD.

[Study on enzyme-solvent extraction process of flavonoids from leaves of Ginkgo biloba].

OBJECTIVE: To study the optimum enzyme-solvent extraction conditions of flavonoids from leaves of Ginkgo biloba. METHODS: To optimize the process by single factor experiments and orthogonal test according to the yield of flavonoids. RESULTS: The optimum extraction conditions were established as follows: pH 5.7, the concentration of enzyme 0.4 mg/mL, enzymatic hydrolysis temperature 45 degrees C, enzymatic hydrolysis time 2 h, the rate of liquid to material 20:1, extraction temperature 70 degrees C, extraction time 2 h, the concentration of ethanol 70%, the average yield of flavonoids from leaves of Ginkgo biloba was 3.62%. CONCLUSION: The method is simple and can increase material utility effectively.