Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

Clinical efficacy of tumor organoid-guided cancer therapy for locally advanced unresectable or metastatic breast cancer.

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

A non-invasive artificial intelligence model for identifying axillary pathological complete response to neoadjuvant chemotherapy in breast cancer: a secondary analysis to multicenter clinical trial.

BACKGROUND: This study aims to develop a stacking model for accurately predicting axillary lymph node (ALN) response to neoadjuvant chemotherapy (NAC) using longitudinal MRI in breast cancer. METHODS: We included patients with node-positive breast cancer who received NAC following surgery from January 2012 to June 2022. We collected MRIs before and after NAC, and extracted radiomics features from the tumour, peritumour, and ALN regions. The Mann-Whitney U test, least absolute shrinkage and selection operator, and Boruta algorithm were used to select features. We utilised machine learning techniques to develop three single-modality models and a stacking model for predicting ALN response to NAC. RESULTS: This study consisted of a training cohort (n = 277), three external validation cohorts (n = 313, 164, and 318), and a prospective cohort (n = 81). Among the 1153 patients, 60.62% achieved ypN0. The stacking model achieved excellent AUCs of 0.926, 0.874, and 0.862 in the training, external validation, and prospective cohort, respectively. It also showed lower false-negative rates (FNRs) compared to radiologists, with rates of 14.40%, 20.85%, and 18.18% (radiologists: 40.80%, 50.49%, and 63.64%) in three cohorts. Additionally, there was a significant difference in disease-free survival between high-risk and low-risk groups (p < 0.05). CONCLUSIONS: The stacking model can accurately predict ALN status after NAC in breast cancer, showing a lower false-negative rate than radiologists. TRIAL REGISTRATION NUMBER: The clinical trial numbers were NCT03154749 and NCT04858529.

Noninvasive Artificial Intelligence System for Early Predicting Residual Cancer Burden during Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To develop an artificial intelligence (AI) system for the early prediction of residual cancer burden (RCB) scores during neoadjuvant chemotherapy (NAC) in breast cancer. SUMMARY BACKGROUND DATA: RCB III indicates drug resistance in breast cancer, and early detection methods are lacking. METHODS: This study enrolled 1048 patients with breast cancer from four institutions, who were all receiving NAC. Magnetic resonance images were collected at the pre- and mid-NAC stages, and radiomics and deep learning features were extracted. A multitask AI system was developed to classify patients into three groups (RCB 0-I, II, and III ) in the primary cohort (PC, n=335). Feature selection was conducted using the Mann-Whitney U- test, Spearman analysis, least absolute shrinkage and selection operator regression, and the Boruta algorithm. Single-modality models were developed followed by model integration. The AI system was validated in three external validation cohorts. (EVCs, n=713). RESULTS: Among the patients, 442 (42.18%) were RCB 0-I, 462 (44.08%) were RCB II and 144 (13.74%) were RCB III. Model-I achieved an area under the curve (AUC) of 0.975 in the PC and 0.923 in the EVCs for differentiating RCB III from RCB 0-II. Model-II distinguished RCB 0-I from RCB II-III, with an AUC of 0.976 in the PC and 0.910 in the EVCs. Subgroup analysis confirmed that the AI system was consistent across different clinical T stages and molecular subtypes. CONCLUSIONS: The multitask AI system offers a noninvasive tool for the early prediction of RCB scores in breast cancer, supporting clinical decision-making during NAC.

Is the mortality-fertility nexus gendered? A research note on sex differences in the impact of sibling mortality on fertility preferences.

Research guided by demographic transition theory has shown that exposure to mortality influences women's fertility preferences and behaviours. Despite the myriad contexts, methodological approaches, and linkages featured in past studies, they have shared a focus on women, leaving questions on the gendered salience of mortality exposures for adults' fertility-related outcomes unanswered. In this research note, we analyse data from three African countries with distinct fertility profiles (Nigeria, Zambia, and Zimbabwe) to examine associations between sibling mortality exposure and ideal family size among women, men, and couples. We also investigate the stability of these associations over time. The associations between adults' sibling mortality exposure and their own and their spouses' ideal family sizes vary across countries. However, the gendered nature of the results in every country and evidence of cross-spousal effects uniformly demonstrate the need to incorporate sex differences into the study of the mortality-fertility link.

Ultrasound-assisted carbon nanoparticle suspension mapping versus dual tracer-guided sentinel lymph node biopsy in patients with early breast cancer (ultraCars): phase III randomized clinical trial.

BACKGROUND: Appropriate tracing methods for sentinel lymph node biopsy (SLNB) play a key role in accurate axillary staging. This prospective, non-inferiority, phase III RCT compared the feasibility and diagnostic performance of ultrasound-assisted carbon nanoparticle suspension (CNS) mapping with dual tracer-guided SLNB in patients with early breast cancer. METHODS: Eligible patients had primary breast cancer without nodal involvement (cN0), or had clinically positive lymph nodes (cN1) that were downstaged to cN0 after neoadjuvant chemotherapy. Patients were randomly assigned (1 : 1) to undergo either ultrasound-assisted CNS sentinel lymph node (SLN) mapping (UC group) or dual tracer-guided mapping with CNS plus indocyanine green (ICG) (GC group). The primary endpoint was the SLN identification rate. RESULTS: Between 1 December 2019 and 30 April 2021, 330 patients were assigned randomly to the UC (163 patients) or GC (167 patients) group. The SLN identification rate was 94.5 (95 per cent c.i. 90.9 to 98.0) per cent in the UC group and 95.8 (92.7 to 98.9) per cent in the GC group. The observed difference of -1.3 (-5.9 to 3.3) per cent was lower than the prespecified non-inferiority margin of 6 per cent (Pnon-inferiority = 0.024). No significant difference was observed in metastatic node rate (30.5 versus 24.4 per cent; P = 0.222), median number of SLNs harvested (3 (range 1-7) versus 3 (1-8); P = 0.181), or duration of surgery (mean(s.d.) 7.53(2.77) versus 7.63(3.27) min; P = 0.316) between the groups. Among the subgroup of patients who had undergone neoadjuvant treatment, the SLN identification rate was 91.7 (82.2 to 100) per cent in the UC group and 90.7 (81.7 to 99.7) per cent in the GC group. CONCLUSION: The diagnostic performance of ultrasound-assisted CNS mapping was non-inferior to that of dual tracer-guided SLN mapping with CNS plus ICG in patients with early breast cancer. REGISTRATION NUMBER: NCT04951245 (http://www.clinicaltrials.gov).

Evaluation of the Web-Based OutsidePlay-ECE Intervention to Influence Early Childhood Educators' Attitudes and Supportive Behaviors Toward Outdoor Play: Randomized Controlled Trial.

BACKGROUND: Outdoor play is critical to children's healthy development and well-being. Early learning and childcare centers (ELCCs) are important venues for increasing children's outdoor play opportunities, and early childhood educators' (ECE) perception of outdoor play can be a major barrier to outdoor play. The OutsidePlay-ECE risk-reframing intervention is a fully automated and open access web-based intervention to reframe ECEs' perceptions of the importance of outdoor play and risk in play and to promote a change in their practice in supporting it in ELCC settings. We grounded the intervention in social cognitive theory and behavior change techniques. OBJECTIVE: The aim of this study is to evaluate the effectiveness of the OutsidePlay-ECE web-based risk-reframing intervention. METHODS: We conducted a single-blind randomized controlled trial in Canada between December 2020 and June 2021 to test the OutsidePlay-ECE risk-reframing intervention for ECEs. We recruited participants using social media and mass emails through our partner and professional networks. We invited ECEs and administrators working in an ELCC, who can speak, read, and understand English. We randomized consented participants to the intervention or control condition. The participants allocated to the intervention condition received a link to the OutsidePlay-ECE intervention. Participants allocated to the control condition read the Position Statement on Active Outdoor Play, a 4-page document on research and recommendations for action in addressing barriers to outdoor play. The primary outcome was a change in tolerance of risk in play. The secondary outcome was goal attainment. We collected data on the web via REDCap (Vanderbilt University) at baseline and 1 week and 3 months after intervention. RESULTS: A total of 563 participants completed the baseline survey, which assessed their demographics and tolerance of risk in play. They were then randomized: 281 (49.9%) to the intervention and 282 (50.1%) to the control condition. Of these, 136 (48.4%) and 220 (78%) participants completed the baseline requirements for the intervention and control conditions, respectively. At 1 week after intervention, 126 (44.8%) and 209 (74.1%) participants completed follow-up assessments, respectively, and at 3 months after intervention, 119 (42.3%) and 195 (69.1%) participants completed the assessments, respectively. Compared with participants in the control condition, participants in the intervention group had significantly higher tolerance of risk in play at 1 week (ß=.320; P=.001) and 3 months after intervention (ß=.251; P=.009). Intention-to-treat analyses replicated these findings (ß=.335; P<.001 and ß=.271; P=.004, respectively). No significant intervention effect was found for goal attainment outcomes (odds ratio 1.124, 95% CI 0.335-3.774; P=.85). CONCLUSIONS: The results of this randomized controlled trial demonstrated that the OutsidePlay-ECE intervention was effective and had a sustained effect in increasing ECEs' and administrators' tolerance of risk in play. It was not effective in increasing goal attainment. TRIAL REGISTRATION: ClinicalTrials.gov NCT04624932; https://clinicaltrials.gov/ct2/show/NCT04624932. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31041.

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OBJECTIVES: To study the value of functional echocardiographic parameters in predicting refractory septic shock in neonates. METHODS: A total of 72 neonates with septic shock were enrolled. According to the highest value of septic shock score, they were divided into two groups: refractory (n=30) and non-refractory (n=42). The two groups were compared in terms of clinical data, laboratory findings, and functional echocardiographic parameters. The receiver operating characteristic (ROC) curve was used to evaluate the performance of functional echocardiographic parameters in predicting refractory septic shock. RESULTS: Compared with the non-refractory group, the refractory group had significantly lower cardiac output and cardiac index (CI) and a significantly higher mean arterial pressure (MAP)/CI ratio (P<0.05). CI had a cut-off value of 2.6 L/(min·m2), a sensitivity of 79%, a specificity of 83%, and an area under the ROC curve (AUC) of 0.841 in predicting septic shock-related death (P<0.05), and MAP/CI ratio had a cut-off value of 11.4, a sensitivity of 83%, a specificity of 73%, and an AUC of 0.769 (P<0.05). CI had a cut-off value of 2.9 L/(min·m2), a sensitivity of 69%, a specificity of 69%, and an AUC of 0.717 in predicting all-cause death within 28 days (P<0.05). CONCLUSIONS: CI and MAP/CI ratio can be useful for early prediction of septic shock-related death in neonates.

A Web-Based and In-Person Risk Reframing Intervention to Influence Mothers' Tolerance for, and Parenting Practices Associated With, Children's Outdoor Risky Play: Randomized Controlled Trial.

BACKGROUND: Outdoor risky play, such as climbing, racing, and independent exploration, is an important part of childhood and is associated with various positive physical, mental, and developmental outcomes for children. Parental attitudes and fears, particularly mothers', are a major deterrent to children's opportunities for outdoor risky play. OBJECTIVE: The aim of this study was to evaluate the efficacy of 2 versions of an intervention to reframe mothers' perceptions of risk and change parenting behaviors: a web-based intervention or an in-person workshop, compared with the control condition. METHODS: The Go Play Outside! randomized controlled trial was conducted in Canada from 2017 to 2018. Participants were recruited through social media, snowball sampling, and community notices. Mothers of children aged 6-12 years were self-assessed through eligibility questions, and those eligible and consented to participate in the study were randomized into a fully automated web-based intervention, the in-person workshop, or the control condition. The intervention was underpinned by social cognitive theory, incorporating behavior change techniques. Participants progressed through a series of self-reflection exercises and developed a goal for change. Control participants received the Position Statement on Active Outdoor Play. The primary outcome was increase in tolerance of risky play and the secondary outcome was goal attainment. Data were collected online via REDCap at baseline, 1 week, and 3 months after the intervention. Randomization was conducted using sealed envelope. Allocations were concealed to researchers at assignment and data analysis. We conducted mediation analyses to examine whether the intervention influenced elements of social cognitive theory, as hypothesized. RESULTS: A total of 451 mothers were randomized and completed baseline sociodemographic assessments: 150 in the web-based intervention, 153 in the in-person workshop, and 148 in the control condition. Among these, a total of 351 mothers completed the intervention. At 1 week after the intervention, 113, 85, and 135 mothers completed assessments for each condition, respectively, and at 3 months after the intervention, 105, 84, and 123 completed the assessments, respectively. Compared with mothers in the control condition, mothers in the web-based intervention had significantly higher tolerance of risky play at 1 week (P=.004) and 3 months after the intervention (P=.007); and mothers in the in-person workshop had significantly higher tolerance of risky play at 1 week after the intervention (P=.02). No other significant outcomes were found. None of the potential mediators were found to significantly mediate the outcomes. CONCLUSIONS: The trial demonstrates that the web-based intervention was effective in increasing mothers' tolerance for risk in play. TRIAL REGISTRATION: ClinicalTrials.gov NCT03374683; https://clinicaltrials.gov/ct2/show/NCT03374683. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2552-4.

Calibration of the food parenting practice (FPP) item bank: tools for improving the measurement of food parenting practices of parents of 5-12-year-old children.

PURPOSE: There has been a call to improve measurement rigour and standardization of food parenting practices measures, as well as aligning the measurement of food parenting practices with the parenting literature. Drawing from an expert-informed conceptual framework assessing three key domains of food parenting practices (autonomy promotion, control, and structure), this study combined factor analytic methods with Item Response Modeling (IRM) methodology to psychometrically validate responses to the Food Parenting Practice item bank. METHODS: A sample of 799 Canadian parents of 5-12-year-old children completed the Food Parenting Practice item bank (129 items measuring 17 constructs). The factorial structure of the responses to the item bank was assessed with confirmatory factor analysis (CFA), confirmatory bi-factor item analysis, and IRM. Following these analyses, differential Item Functioning (DIF) and Differential Response Functioning (DRF) analyses were then used to test invariance properties by parents' sex, income and ethnicity. Finally, the efficiency of the item bank was examined using computerized adaptive testing simulations to identify the items to include in a short form. RESULTS: Overall, the expert-informed conceptual framework was predominantly supported by the CFA as it retained the same 17 constructs included in the conceptual framework with the exception of the access/availability and permissive constructs which were respectively renamed covert control and accommodating the child to better reflect the content of the final solution. The bi-factor item analyses and IRM analyses revealed that the solution could be simplified to 11 unidimensional constructs and the full item bank included 86-items (empirical reliability from 0.78 to 0.96, except for 1 construct) and the short form had 48 items. CONCLUSION: Overall the food parenting practice item bank has excellent psychometric properties. The item bank includes an expanded version and short version to meet various study needs. This study provides more efficient tools for assessing how food parenting practices influence child dietary behaviours. Next steps are to use the IRM calibrated item bank and draw on computerized adaptive testing methodology to administer the item bank and provide flexibility in item selection.

The physical activity parenting practices (PAPP) item Bank: a psychometrically validated tool for improving the measurement of physical activity parenting practices of parents of 5-12-year-old children.

BACKGROUND: Many tools have been developed to measure physical activity parenting practices (PAPP). Currently, there is little standardization on how PAPP constructs are operationalized for 5-12 year-old children. Given this lack of consistency our team have started the process of standardizing the measurement of PAPP by developing an item bank which was conceptually informed by 24 experts from 6 countries. PURPOSE: The purpose of this paper is to present the psychometric properties of the PAPP item bank using the expert-informed PAPP conceptual framework. METHODS: A sample (N = 626) of Canadian parents completed the PAPP item bank (100 items measuring 12 constructs). Confirmatory Factor Analyses (CFA), confirmatory bi-factor item analyses, and Item Response Modeling (IRM) were used to assess the structural validity of scores derived from the PAPP item bank. Differential Item Functioning (DIF) and Differential Response Functioning (DRF) were used to determine whether the PAPP items are invariant by parent sex, ethnicity of parent, and household income. Finally, Computerized Adaptive Testing (CAT) simulations were used to determine the efficiency of the item bank - this involved ascertaining whether each construct can be assessed with fewer items. RESULTS: The PAPP expert-informed conceptual framework was mainly supported by the CFA analyses. Notable changes included: a) collapsing smaller constructs into one general construct (modeling, co-participation, and monitoring constructs were collapsed into a construct assessing nondirective support); or b) splitting a construct into two smaller constructs (restrict for safety reason construct was split into indoor physical activity restriction and allowance for unsupervised outside physical activity). While the CFA analyses supported the structural validity of 11 constructs, the bi-factor item analyses and IRM analyses supported collapsing correlated constructs into more general constructs. These analyses further reduced the number of constructs measured by the PAPP item bank to nine constructs (65 items - reliability ranging from .79 to .94). As seven of the PAPP constructs had reliability greater than .80, CAT simulations further reduced the number of items to 31 items. CONCLUSION: Overall, the PAPP item bank has excellent psychometric properties and provides an efficient way to assess PAPP.

BRD4 and PIN1 gene polymorphisms are associated with high pulse pressure risk in a southeastern Chinese population.

BACKGROUND: BRD4 and PIN1 have been described to be involved in inflammation and vascular endothelial cell dysfunction, which in turn may increase pulse pressure. HYPOTHESIS: Genetic mutations within the BRD4 and PIN1 genes could affect the risk of high pulse pressure. METHODS: A total of four single nucleotide polymorphisms (SNPs) (BRD4: rs4808278; PIN1: rs2233678, rs2287838, and rs2233682) were genotyped in a cohort of 666 hypertensive patients and 232 normotensive controls with Chinese Han origin. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among the four SNPs within the BRD4 and PIN1 genes and diabetes. Logistic regression analysis was performed to calculate the odds ratio (ORs) (95% confidence interval (CI)) for the association between the four SNPs. RESULTS: Adjusted for age, weight, waist circumference, drinking, smoking, hypertension, and diabetes, high pulse pressure risk was significantly higher for carriers with the rs4808278-TT genotype in BRD4 than those with wild genotypes (OR: 0.400, 95% CI: 0.217-0.737, P* < 0.05). However, we did not find any significant association of rs2233678, rs2287838, and rs2233682 in PIN1 with high pulse pressure susceptibility after covariate adjustment. GMDR analysis indicated a significant three-locus model (P = 0.0107) involving rs4808278, rs2233678, and diabetes, the cross-validation consistency of the three-locus models was 9/10, and the testing accuracy was 57.47%. CONCLUSIONS: Genetic mutations within BRD4 (rs4808278) could affect the susceptibility to high pulse pressure in a southeastern Chinese population.

Effects of Storage Time and Temperature on Antioxidants in Juice from Momordica charantia L. and Momordica charantia L. var. abbreviata Ser.

This study determined the antioxidant activities of juice from Momordica charantia L. (MC) and MC var. abbreviata Ser. (MCVAS) by analyzing 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging ability, ferric reducing power (FRP), and total phenolic content (TPC). The effects of storage time and storage temperature on these antioxidant activities were investigated. Liquid chromatography-mass spectrometry was conducted to identify the major components of MC and MCVAS. The results revealed that the antioxidant activity of MCVAS was better than that of MC, possibly because of richer components of MCVAS. For MC and MCVAS, the scavenging concentrations of 50% DPPH were 3.33 and 1.19 mg/mL, respectively; moreover, the FRP values were 68.93 and 118.14 mg ascorbic acid equivalent/g dry weight, respectively; and the TPC values were 8.15 and 11.47 mg gallic acid equivalent/g dry weight, respectively. The antioxidant activities of MC and MCVAS decreased with storage time. High storage temperature decreased antioxidant activity more quickly than a low temperature. In addition, MC had exhibited a faster decline in DPPH scavenging ability and FRP than MCVAS during 24-day storage, but no difference was observed in TPC.

Comparison of risk engagement and protection survey (REPS) among mothers and fathers of children aged 6-12 years.

BACKGROUND: Parental attitudes regarding child safety and risk engagement play important roles in child injury prevention and health promotion efforts. Few studies have compared mothers' and fathers' attitudes on these topics. This study used the risk engagement and protection survey (REPS) previously validated with fathers to compare with data collected from mothers. METHODS: Multi-group confirmatory factor analysis was used with a sample of 234 mothers and 282 fathers. Eligible parents had a child 6-12 years attending a paediatric hospital for an injury-related or other reason. We tested the factor structure of the survey by examining configural, metric and scalar invariance. Following this, mothers' and fathers' mean scores on the two identified factors of child injury protection and risk engagement were compared. RESULTS: Comparing mothers' and fathers' data showed the two-factor structure of the REPS held for the mothers' data. Comparing mean scores for the two factors suggested that fathers and mothers held equivalent attitudes. For the combined sample, parent injury protection attitude scores were significantly higher for daughters versus sons. In addition, attitude scores were significantly lower for injury protection and higher for risk engagement among parents born in Canada compared with those who were not. CONCLUSIONS: The REPS allows for valid assessment of injury protection and risk engagement factors for fathers and mothers. Mothers conceptualised the two factors as distinct concepts, similar to fathers. The REPS can be used to inform parenting programme development, implementation and evaluation.

Temporal and bi-directional associations between sleep duration and physical activity/sedentary time in children: An international comparison.

The purpose of this multinational and cross-sectional study was to investigate whether nighttime sleep duration was associated with physical activity (PA) and sedentary time (SED) the following day, whether daytime PA/SED were associated with sleep duration the subsequent night, and whether the associations were modified by sex and study sites. Data from 5779 children aged 9-11years were analyzed. A waist-worn Actigraph GT3X+ accelerometer was used to assess children's 24-h movement behaviours for 7days, i.e. sleep duration, total SED, light-intensity physical activity (LPA), and moderate- to vigorous-intensity physical activity (MVPA). Multilevel linear regression models were used to account for the repeated measures nested within participants (there were up to 7 sleep→PA/SED and PA/SED→sleep pairings per participant) and schools, and adjusted for covariates. To facilitate interpretation, all sleep and PA/SED variables were standardized. Results showed that the relationship between sleep and PA/SED is bi-directional in this international sample of children. Specifically, for each one standard deviation (SD) unit increase in sleep duration, SED the following day decreased by 0.04 SD units, while LPA and MVPA increased by 0.04 and 0.02 SD units, respectively. Sleep duration decreased by 0.02 SD units and increased by 0.04 SD units for each one SD unit increase in SED and MVPA, respectively. Sleep duration was not affected by changes in LPA. These associations differed across sex and study sites in both directions. However, since the observed effect sizes are subtle, public health initiatives should consider the clinical and practical relevance of these findings.

Recombinant rabies virus expressing interleukin-6 enhances the immune response in mouse brain.

Rabies, which is caused by the rabies virus (RABV), is an ancient zoonosis that has a high mortality rate. Previous studies have indicated that recombinant RABV expressing canine interleukin-6 (rHEP-CaIL6), induced more virus-neutralizing antibodies than parental RABV in mice following intramuscular immunization. To investigate the immune response induced in the CNS by rHEP-CaIL6 after intranasal or intracranial administration in mice, the permeability of the blood-brain barrier (BBB), the infiltration of CD3 T cells, and innate immune response-related effector molecules in the CNS were examined. It was observed that infection of rHEP-CaIL6 led to enhanced BBB permeability following intranasal infection. More CD3 T cells infiltrated into the central nervous system (CNS) in mice infected with rHEP-CaIL6 than in those infected with the HEP-Flury strain. Furthermore, rHEP-CaIL6 induced an increased expression of innate immune response-related effector molecules, compared with the parental HEP-Flury strain, within the CNS. Taken together, these findings suggest that rHEP-CaIL6 induced stronger immune responses in mice brains, which is more beneficial for virus clearance. These results may also partly illustrate the role of IL6 in RABV infection.

Bi-directional association between sleep and outdoor active play among 10-13 year olds.

BACKGROUND: The purpose of this study was to investigate whether there is a bi-directional relationship between sleep characteristics (time in bed, sleep duration, sleep chronology, and sleep efficiency) and time spent participating in outdoor active play among children. METHODS: Participants consisted of 433 children aged 10-13 years from Kingston, ON, Canada. Time in bed, sleep duration, sleep chronology, and sleep efficiency were measured for 8 consecutive nights using data from a sleep log and Actical accelerometer. Outdoor active play was measured for the 7 days that fell in between these 8 nights using a combination of data from accelerometers, global positioning system loggers, and geographic information systems. Generalized estimating equation models were used to assess the relationships between sleep characteristics and outdoor active play. These models accounted for the repeated measures nested within participants and adjusted for several confounders (e.g., age, sex, family income, neighborhood traffic and green space). RESULTS: Time in bed, sleep duration, sleep chronology, and sleep efficiency were not significantly associated with the following day's outdoor active play. There was a significant (p = 0.017) association between outdoor active play and the following night's time in bed, which suggested that each hour increase in outdoor active play was associated with a 4.0 min increase in time in bed. Outdoor active play was not significantly associated with sleep duration, sleep chronology, or sleep efficiency. CONCLUSIONS: None of the sleep characteristics predicted the following day's outdoor active play. Increase time spent in outdoor active play predicted a longer time in bed, but not sleep duration, sleep chronology, or sleep efficiency.

The Intergenerational Transmission of Health Disadvantage: Can Education Disrupt It?

In low-income countries, intergenerational processes can culminate in the replication of extreme forms of health disadvantage between mothers and adult daughters, including experiencing a young child's death. The preventable nature of most child deaths raises questions of whether social resources can protect women from enduring this adversity like their mothers. This study examined whether education-widely touted as a vehicle for social mobility in resource-poor countries-disrupts the intergenerational cycle of maternal bereavement. We estimated multilevel discrete-time survival models of women's hazard of child loss using Demographic and Health Survey Program data (N = 195,744 women in 345 subnational regions in 32 African countries). Women's educational attainment minimizes the salience of their mothers' bereavement history for their own probability of child loss; however, mothers' background becomes irrelevant only among women with ≥10 years of schooling. Education's neutralizing influence is most prominent in the highest mortality-burdened communities.

Association between maximum norepinephrine dosage and mortality risk in neonates with septic shock.

The high-dose usage of norepinephrine is thought to cause high mortality in patients with septic shock. This study aims to explores the correlation between the maximum norepinephrine (NE) dosage (MND) and mortality in neonates with septic shock. This retrospective cohort study included neonates with evidence of septic shock and those who received NE infusion. The study included 123 neonates, with 106 in the survival group and 17 in the death group. The death group exhibited significantly lower birth weight (p = 0.022), 1-min Apgar score (p = 0.005), serum albumin (p < 0.001), and base excess (BE) (p = 0.001) levels, but higher lactate (LAC) levels (p = 0.009) compared to the survival group. MND demonstrated an ROC area under the curve of 0.775 (95% CI 0.63-0.92, p < 0.001) for predicting mortality, with an optimal threshold of 0.3 µg/(kg·min), a sensitivity of 82.4%, and a specificity of 75.5%. Multivariate logistic regression indicated that an MND > 0.3 µg/(kg·min) (OR, 12.08, 95% CI 2.28-64.01) was associated with a significantly higher mortality risk. Spearman rank correlation showed a positive correlation between MND and LAC (r = 0.252, p = 0.005), vasoactive-inotropic score (VIS) (r = 0.836, p < 0.001), and a negative correlation with BE (r = - 0.311, p = 0.001). MND > 0.3 µg/(kg min) is a useful predictive marker of mortality in neonatal septic shock.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy With Immunotherapy Result in Different Tumor Shrinkage Patterns in Triple-Negative Breast Cancer.

PURPOSE: This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. METHODS: This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. RESULTS: Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. CONCLUSION: Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04909554.