Beyond the Runway: Respiratory health effects of ultrafine particles from aviation in children.

Aviation has been shown to cause high particle number concentrations (PNC) in areas surrounding major airports. Particle size distribution and composition differ from motorized traffic. The objective was to study short-term effects of aviation-related UFP on respiratory health in children. In 2017-2018 a study was conducted in a school panel of 7-11 year old children (n = 161) living North and South of Schiphol Airport. Weekly supervised spirometry and exhaled nitric oxide (eNO) measurements were executed. The school panel, and an additional group of asthmatic children (n = 19), performed daily spirometry tests at home and recorded respiratory symptoms. Hourly concentrations of various size fractions of PNC and black carbon (BC) were measured at three school yards. Concentrations of aviation-related particles were estimated at the residential addresses using a dispersion model. Linear and logistic mixed models were used to investigate associations between daily air pollutant concentrations and respiratory health. PNC20, a proxy for aviation-related UFP, was virtually uncorrelated with BC and PNC50-100 (reflecting primarily motorized traffic), supporting the feasibility of separating PNC from aviation and other combustion sources. No consistent associations were found between various pollutants and supervised spirometry and eNO. Major air pollutants were significantly associated with an increase in various respiratory symptoms. Odds Ratios for previous day PNC20 per 3,598pt/cm3 were 1.13 (95%CI 1.02; 1.24) for bronchodilator use and 1.14 (95%CI 1.03; 1.26) for wheeze. Modelled aviation-related UFP at the residential addresses was also positively associated with these symptoms, corroborating the PNC20 findings. PNC20 was not associated with daily lung function, but PNC50-100 and BC were negatively associated with FEV1. PNC of different sizes indicative of aviation and other combustion sources were independently associated with an increase of respiratory symptoms and bronchodilator use in children living near a major airport. No consistent associations between aviation-related UFP with lung function was observed.

Bidirectional Within-Family Effects of Restrictive Mediation Practices and Adolescents' Problematic Social Media Use.

Much remains unknown about whether restrictive mediation is an effective parenting strategy to prevent or reduce problematic social media use among adolescents. Therefore, this study examined bidirectional within-family effects between two restrictive mediation practices (rule-setting and reactive restrictions) and problematic social media use using random-intercept cross-lagged panel modeling. Three-wave survey data collected among Dutch adolescents (T1: N = 1928, Mage = 13.31 years, SD = 0.91, 43.3% girl) with a 1 year-interval were used. Results showed that within-family changes in problematic social media use symptoms predicted subsequent within-family changes in perceived parental restrictive mediation. More specifically, an increase in symptoms predicted a decrease in rule-setting and an increase in reactive restrictions 1 year later. Within-family changes in perceived parental restrictive mediation practices did not predict within-family changes in problematic social media use symptoms, suggesting that the relation is unidirectional. However, concluding that limiting adolescents' Internet use is ineffective to prevent problematic social media use would be premature. Future research should investigate whether it may be an effective parenting strategy for a certain subgroup of adolescents or under certain circumstances.

Phase Behavior and Conformational Asymmetry near the Comb-to-Bottlebrush Transition in Linear-Brush Block Copolymers.

This study explores how conformational asymmetry influences the bulk phase behavior of linear-brush block copolymers. We synthesized 60 diblock copolymers composed of poly(trifluoroethyl methacrylate) as the linear block and poly[oligo(ethylene glycol) methyl ether methacrylate] as the brush block, varying the molecular weight, composition, and side-chain length to introduce different degrees of conformational asymmetry. Using small-angle X-ray scattering, we determined the morphology and phase diagrams for three different side-chain length systems, mainly observing lamellar and cylindrical phases. Increasing the side-chain length of the brush block from three to nine ethylene oxide units introduces sufficient asymmetry between the blocks to alter the phase behavior, shifting the lamellar-to-cylindrical transitions toward lower brush block compositions and transitioning the brush block from the dense comb-like regime to the bottlebrush regime. Coarse-grained simulations support our experimental observations and provide a mapping between the composition and conformational asymmetry. A comparison of our findings to strong stretching theory across multiple phase boundary predictions confirms the transition between the dense comb-like regime and the bottlebrush regime.

From greenwashing to screenwashing?

In this viewpoint, we introduce the term 'screenwashing', which describes the phenomenon whereby social media platforms, such as TikTok and Instagram, pretend to be more socially responsible than they actually are. That is, social media platforms pretend to be thoughtful about children's health and the prevention of problematic social media use, but this often turns out to be nothing more than "a lick of paint". We describe how features like the one-hour notification on TikTok and Instagram are considered screenwashing and why we believe so. Screenwashing, an unethical practice, has the potential to mislead parents and young users. Consequently, we advocate for increased government intervention to protect our youth from the potential hazards associated with problematic social media use.

Indirect cardiac output assessment in a swine pediatric acute respiratory distress syndrome model.

PURPOSE: To investigate the correlation between volume of carbon dioxide elimination (V̇CO2) and end-tidal carbon dioxide (PETCO2) with cardiac output (CO) in a swine pediatric acute respiratory distress syndrome (ARDS) model. METHODS: Respiratory and hemodynamic variables were collected from twenty-six mechanically ventilated juvenile pigs under general anesthesia before and after inducing ARDS, using oleic acid infusion. RESULTS: Prior to ARDS induction, mean (SD) CO, V̇CO2, PETCO2, and dead space to tidal volume ratio (Vd/Vt) were 4.16 (1.10) L/min, 103.69 (18.06) ml/min, 40.72 (3.88) mmHg and 0.25 (0.09) respectively. Partial correlation coefficients between average CO, V̇CO2, and PETCO2 were 0.44 (95% confidence interval: 0.18-0.69) and 0.50 (0.18-0.74), respectively. After ARDS induction, mean CO, V̇CO2, PETCO2, and Vd/Vt were 3.33 (0.97) L/min, 113.71 (22.97) ml/min, 50.17 (9.73) mmHg and 0.40 (0.08). Partial correlations between CO and V̇CO2 was 0.01 (-0.31 to 0.37) and between CO and PETCO2 was 0.35 (-0.002 to 0.65). CONCLUSION: ARDS may limit the utility of volumetric capnography to monitor CO.

Entropic Penalty Switches Li+ Solvation Site Formation and Transport Mechanisms in Mixed Polarity Copolymer Electrolytes.

Emerging solid polymer electrolyte (SPE) designs for efficient Li-ion (Li+) conduction have relied on polarity and mobility contrast to improve conductivity. To further develop this concept, we employ simulations to examine Li+ solvation and transport in poly(oligo ethylene methacrylate) (POEM) and its copolymers with poly(glycerol carbonate methacrylate) (PGCMA). We find that Li+ is solvated by ether oxygens instead of the highly polar PGCMA, due to lower entropic penalties. The presence of PGCMA promotes single-chain solvation, thereby suppressing interchain Li+ hopping. The conductivity difference between random copolymer PGCMA-r-POEM and block copolymer PGCMA-b-POEM is explained in terms of a hybrid solvation site mechanism. With diffuse microscopic interfaces between domains, PGCMA near the POEM contributes to Li+ transport by forming hybrid solvation sites. The formation of such sites is hindered when PGCMA is locally concentrated. These findings help explain how thermodynamic driving forces govern Li+ solvation and transport in mixed SPEs.

Phase 1 study of JNJ-64619178, a protein arginine methyltransferase 5 inhibitor, in patients with lower-risk myelodysplastic syndromes.

Splicing factor (SF) gene mutations are frequent in myelodysplastic syndromes (MDS), and agents that modulate RNA splicing are hypothesized to provide clinical benefit. JNJ-64619178, a protein arginine methyltransferase 5 (PRMT5) inhibitor, was evaluated in patients with lower-risk (LR) MDS in a multi-part, Phase 1, multicenter study. The objectives were to determine a tolerable dose and to characterize safety, pharmacokinetics, pharmacodynamics, and preliminary clinical activity. JNJ-64619178 was administered on a 14 days on/7 days off schedule or every day on a 21-day cycle to patients with International Prognostic Scoring System (IPSS) Low or Intermediate-1 risk MDS who were red blood cell transfusion-dependent. Twenty-four patients were enrolled; 15 (62.5 %) patients had low IPSS risk score, while 18 (75.0 %) had an SF3B1 mutation. Median duration of treatment was 3.45 months (range: 0.03-6.93). No dose limiting toxicities were observed. The 0.5 mg once daily dose was considered better tolerated and chosen for dose expansion. Twenty-three (95.8 %) patients experienced treatment-emergent adverse events (TEAE). The most common TEAEs were neutropenia (15 [62.5 %]) and thrombocytopenia (14 [58.3 %]). JNJ-64619178 pharmacokinetics was dose-dependent. Target engagement as measured by plasma symmetric di-methylarginine was observed across all dose levels; however, variant allele frequency of clonal mutations in bone marrow or blood did not show sustained reductions from baseline. No patient achieved objective response or hematologic improvement per International Working Group 2006 criteria, or transfusion independence. A tolerable dose of JNJ-64619178 was identified in patients with LR MDS. However, no evidence of clinical benefit was observed.

Constitutive Turbodomains enhance expansion and antitumor activity of allogeneic BCMA CAR T cells in preclinical models.

The magnitude of CAR T cell expansion has been associated with clinical efficacy. Although cytokines can augment CAR T cell proliferation, systemically administered cytokines can result in toxicities. To gain the benefits of cytokine signaling while mitigating toxicities, we designed constitutively active synthetic cytokine receptor chimeras (constitutive Turbodomains) that signal in a CAR T cell-specific manner. The modular design of Turbodomains enables diverse cytokine signaling outputs from a single homodimeric receptor chimera and allows multiplexing of different cytokine signals. Turbodomains containing an IL-2/15Rß-derived signaling domain closely mimicked IL-15 signaling and enhanced CAR T cell potency. Allogeneic TurboCAR T cells targeting BCMA showed no evidence of aberrant proliferation yet displayed enhanced expansion and antitumor activity, prolonging survival and preventing extramedullary relapses in mouse models. These results illustrate the potential of constitutive Turbodomains to achieve selective potentiation of CAR T cells and demonstrate the safety and efficacy of allogeneic BCMA TurboCAR T cells, supporting clinical evaluation in multiple myeloma.

Phase 1 Study of JNJ-64619178, a Protein Arginine Methyltransferase 5 Inhibitor, in Advanced Solid Tumors.

PURPOSE: In this first-in-human, Phase 1, open-label, multicenter study, we evaluated JNJ-64619178, a selective and potent PRMT5 inhibitor, in patients with advanced malignant solid tumors or non-Hodgkin lymphomas (NHL). The primary objective was to evaluate the safety and to identify a recommended Phase 2 dose (RP2D) of JNJ-64619178. PATIENTS AND METHODS: Adult patients with treatment-refractory advanced solid tumors or NHL and measurable disease received escalating doses of JNJ-64619178 following two schedules (Schedule A: 14 days on/7 days off; Schedule B: every day on a 21-day cycle). Safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity were evaluated. RESULTS: Ninety patients received JNJ-64619178. Thrombocytopenia was identified as the only dose-limiting toxicity. JNJ-64619178 showed dose-proportional PK and robust target engagement, as measured by plasma symmetric dimethylarginine, across all dose levels. The objective response rate was 5.6% (5 of 90). Patients with adenoid cystic carcinoma (ACC) had an ORR of 11.5% (3 of 26) and a median progression-free survival of 19.1 months. CONCLUSIONS: JNJ-64619178 demonstrated manageable dose-dependent toxicity and preliminary evidence of antitumor activity in ACC and other tumor types. Plasma exposure was dose dependent, and target inhibition was maintained with intermittent and continuous dosing. On the basis of safety, clinical activity, PK, and PD findings, two provisional RP2Ds were selected: 1.5 mg intermittently and 1.0 mg once daily. Aside from ACC, clinical benefit was limited, and biomarkers to enrich for responsiveness to PRMT5 inhibition will be needed for further development.

Predicting Adolescents' Problematic Social Media Use From Profiles of Internet-Specific Parenting Practices and General Parenting Dimensions.

Although both Internet-specific and general parenting have been linked to adolescents' problematic social media use, until now they have been investigated as separate predictors of this behavior. As specific parenting practices occur in the broader general parenting context, this study examined how different Internet-specific parenting practices (Internet-specific rule setting, reactive restrictions towards Internet use, and co-use) and general parenting dimensions (responsiveness and autonomy-granting) co-occur, and act together in predicting adolescents' problematic social media use. Four-wave data of 400 adolescents (T1: M age = 13.51 years, SD = 2.15, 54% girls) were used. Latent profile analysis identified three parenting profiles: Limiting and less supportive (13.5%), Tolerant and supportive (25.5%), and Limiting and supportive (60.8%). Membership to Tolerant and supportive predicted lower scores on prospective problematic social media use than membership to the other profiles. Besides, membership to Limiting and supportive predicted lower scores on problematic social media use than membership to Limiting and less supportive. No robust moderation effects of adolescents' age and gender were found. These findings suggest that a supportive general parenting context rather than Internet use restrictions should be the focus when considering the prevention of adolescents' problematic social media use.

A cross-sectional study on gaming intensity and social vulnerability in adolescents that have a chronic condition.

Background: Adolescents growing up with a chronic condition might experience more social vulnerabilities compared to their healthy peers as an indirect result of their conditions. This can lead to a relatedness need frustration for these adolescents. Consequently, they might spend more time playing video games compared to their peers. Research shows that both social vulnerability and gaming intensity are predictors for problematic gaming. Therefore, we investigated if social vulnerability and gaming intensity are more pronounced in adolescents that have a chronic condition compared to the general population; and if these levels reflect the levels of a clinical group being treated for Internet Gaming Disorder (IGD). Methods: Data on peer problems and gaming intensity were compared from three separate samples: a national representative sample of adolescents, a clinical sample of adolescents that are undergoing treatment for IGD, and a sample of adolescents diagnosed with a chronic condition. Results: No differences were found on either peer problems or gaming intensity between the group of adolescents that have chronic conditions and the national representative group. The group with chronic conditions scored significantly lower on gaming intensity than the clinical group. No significant differences were found between these groups on peer problems. We repeated the analyses for boys only. Similar results were found for the group with chronic conditions compared to the national representative group. The group with chronic conditions now scored significantly lower on both peer problems and gaming intensity than the clinical group. Conclusion: Adolescents growing up with a chronic condition appear similar in their gaming intensity and peer problems compared to their healthy peers.

Adolescent use of social media and associations with sleep patterns across 18 European and North American countries.

OBJECTIVE: Over the past decade, concurrent with increasing social media use (SMU), there has been a shift toward poorer sleep among adolescents in many countries. The purpose of this study was to examine the cross-national associations between adolescent SMU and sleep patterns, by comparing 4 different categories of SMU (nonactive, active, intense, and problematic use). DESIGN, SETTING, AND PARTICIPANTS: Data were from 86,542 adolescents in 18 European and North American countries that participated in the 2017/18 Health Behaviour in School-aged study. MEASUREMENTS: Mixed-effects linear regression models were used to examine cross-national associations between 4 SMU categories and adolescent sleep duration, bedtime and social jetlag derived from self-reported data. RESULTS: For all countries combined, nonactive SMU was associated with longer sleep, earlier bedtimes, and less social jetlag, compared to active SMU, although the differences were minor. By comparison, intense and problematic SMU were associated with less sleep and later bedtimes on both school and nonschool days, and greater social jetlag, compared to active SMU. While findings were relatively consistent between countries, some differences were observed, suggesting that the national and cultural context may be important in interpreting results. CONCLUSIONS: These findings suggest that both intense and problematic SMU are associated with poorer sleep patterns in adolescents across most countries. Further research is needed to identify effective policies, programs, and messaging to promote the healthy use of social media and prevent potential negative impacts on adolescent sleep.

Developmental Programming in Animal Models: Critical Evidence of Current Environmental Negative Changes.

The Developmental Origins of Health and Disease (DOHaD) approach answers questions surrounding the early events suffered by the mother during reproductive stages that can either partially or permanently influence the developmental programming of children, predisposing them to be either healthy or exhibit negative health outcomes in adulthood. Globally, vulnerable populations tend to present high obesity rates, including among school-age children and women of reproductive age. In addition, adults suffer from high rates of diabetes, hypertension, cardiovascular, and other metabolic diseases. The increase in metabolic outcomes has been associated with the combination of maternal womb conditions and adult lifestyle-related factors such as malnutrition and obesity, smoking habits, and alcoholism. However, to date, "new environmental changes" have recently been considered negative factors of development, such as maternal sedentary lifestyle, lack of maternal attachment during lactation, overcrowding, smog, overurbanization, industrialization, noise pollution, and psychosocial stress experienced during the current SARS-CoV-2 pandemic. Therefore, it is important to recognize how all these factors impact offspring development during pregnancy and lactation, a period in which the subject cannot protect itself from these mechanisms. This review aims to introduce the importance of studying DOHaD, discuss classical programming studies, and address the importance of studying new emerging programming mechanisms, known as actual lifestyle factors, during pregnancy and lactation.

MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques.

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.

Flow blockage disrupts cilia-driven fluid transport in the epileptic brain.

A carpet of ependymal motile cilia lines the brain ventricular system, forming a network of flow channels and barriers that pattern cerebrospinal fluid (CSF) flow at the surface. This CSF transport system is evolutionary conserved, but its physiological function remains unknown. Here we investigated its potential role in epilepsy with studies focused on CDKL5 deficiency disorder (CDD), a neurodevelopmental disorder with early-onset epilepsy refractory to seizure medications and the most common cause of infant epilepsy. CDKL5 is a highly conserved X-linked gene suggesting its function in regulating cilia length and motion in the green alga Chlamydomonas might have implication in the etiology of CDD. Examination of the structure and function of airway motile cilia revealed both the CDD patients and the Cdkl5 knockout mice exhibit cilia lengthening and abnormal cilia motion. Similar defects were observed for brain ventricular cilia in the Cdkl5 knockout mice. Mapping ependymal cilia generated flow in the ventral third ventricle (v3V), a brain region with important physiological functions showed altered patterning of flow. Tracing of cilia-mediated inflow into v3V with fluorescent dye revealed the appearance of a flow barrier at the inlet of v3V in Cdkl5 knockout mice. Analysis of mice with a mutation in another epilepsy-associated kinase, Yes1, showed the same disturbance of cilia motion and flow patterning. The flow barrier was also observed in the Foxj1± and FOXJ1CreERT:Cdkl5y/fl mice, confirming the contribution of ventricular cilia to the flow disturbances. Importantly, mice exhibiting altered cilia-driven flow also showed increased susceptibility to anesthesia-induced seizure-like activity. The cilia-driven flow disturbance arises from altered cilia beating orientation with the disrupted polarity of the cilia anchoring rootlet meshwork. Together these findings indicate motile cilia disturbances have an essential role in CDD-associated seizures and beyond, suggesting cilia regulating kinases may be a therapeutic target for medication-resistant epilepsy.