Activated PMN Exosomes: Pathogenic Entities Causing Matrix Destruction and Disease in the Lung.

Here, we describe a novel pathogenic entity, the activated PMN (polymorphonuclear leukocyte, i.e., neutrophil)-derived exosome. These CD63+/CD66b+ nanovesicles acquire surface-bound neutrophil elastase (NE) during PMN degranulation, NE being oriented in a configuration resistant to α1-antitrypsin (α1AT). These exosomes bind and degrade extracellular matrix (ECM) via the integrin Mac-1 and NE, respectively, causing the hallmarks of chronic obstructive pulmonary disease (COPD). Due to both ECM targeting and α1AT resistance, exosomal NE is far more potent than free NE. Importantly, such PMN-derived exosomes exist in clinical specimens from subjects with COPD but not healthy controls and are capable of transferring a COPD-like phenotype from humans to mice in an NE-driven manner. Similar findings were observed for another neutrophil-driven disease of ECM remodeling (bronchopulmonary dysplasia [BPD]). These findings reveal an unappreciated role for exosomes in the pathogenesis of disorders of ECM homeostasis such as COPD and BPD, providing a critical mechanism for proteolytic damage.

The Influence of Neurotrophins on the Brain-Lung Axis: Conception, Pregnancy, and Neonatal Period.

Neurotrophins (NTs) are four small proteins produced by both neuronal and non-neuronal cells; they include nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4). NTs can exert their action through both genomic and non-genomic mechanisms by interacting with specific receptors. Initial studies on NTs have identified them only as functional molecules of the nervous system. However, recent research have shown that some tissues and organs (such as the lungs, skin, and skeletal and smooth muscle) as well as some structural cells can secrete and respond to NTs. In addition, NTs perform several roles in normal and pathological conditions at different anatomical sites, in both fetal and postnatal life. During pregnancy, NTs are produced by the mother, placenta, and fetus. They play a pivotal role in the pre-implantation process and in placental and embryonic development; they are also involved in the development of the brain and respiratory system. In the postnatal period, it appears that NTs are associated with some diseases, such as sudden infant death syndrome (SIDS), asthma, congenital central hypoventilation syndrome (CCHS), and bronchopulmonary dysplasia (BPD).

Resting-State EEG Microstates and Power Spectrum in Borderline Personality Disorder: A High-Density EEG Study.

Borderline personality disorder (BPD) is a debilitating psychiatric condition characterized by emotional dysregulation, unstable sense of self, and impulsive, potentially self-harming behavior. In order to provide new neurophysiological insights on BPD, we complemented resting-state EEG frequency spectrum analysis with EEG microstates (MS) analysis to capture the spatiotemporal dynamics of large-scale neural networks. High-density EEG was recorded at rest in 16 BPD patients and 16 age-matched neurotypical controls. The relative power spectrum and broadband MS spatiotemporal parameters were compared between groups and their inter-correlations were examined. Compared to controls, BPD patients showed similar global spectral power, but exploratory univariate analyses on single channels indicated reduced relative alpha power and enhanced relative delta power at parietal electrodes. In terms of EEG MS, BPD patients displayed similar MS topographies as controls, indicating comparable neural generators. However, the MS temporal dynamics were significantly altered in BPD patients, who demonstrated opposite prevalence of MS C (lower than controls) and MS E (higher than controls). Interestingly, MS C prevalence correlated positively with global alpha power and negatively with global delta power, while MS E did not correlate with any measures of spectral power. Taken together, these observations suggest that BPD patients exhibit a state of cortical hyperactivation, represented by decreased posterior alpha power, together with an elevated presence of MS E, consistent with symptoms of elevated arousal and/or vigilance. This is the first study to investigate resting-state MS patterns in BPD, with findings of elevated MS E and the suggestion of reduced posterior alpha power indicating a disorder-specific neurophysiological signature previously unreported in a psychiatric population.

Blood pressure in preterm infants with bronchopulmonary dysplasia in the first three months of life.

BACKGROUND: Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients. METHODS: We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30 weeks gestation) with moderate or severe BPD over three years (2019-2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures. RESULTS: We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury. CONCLUSION: The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.

Theta burst stimulation add on to dialectical behavioral therapy in borderline-personality-disorder: methods and design of a randomized, single-blind, placebo-controlled pilot trial.

Specialized psychotherapeutic treatments like dialectical behavioral therapy (DBT) are recommended as first treatment for borderline personality disorder (BPD). In recent years, studies have emerged that focus on repetitive transcranial magnetic stimulation (rTMS) in BPD. Both have independently demonstrated efficacy in the treatment of BPD. Intermitted theta burst stimulation (iTBS), a modified design of rTMS, is thought to increase the excitability of neurons and could be a supplement to psychotherapy in addition to being a standalone treatment. However, no studies to date have investigated the combination of DBT and rTMS/iTBS. This study protocol describes the methods and design of a randomized, single-blinded, sham-controlled clinical pilot study in which BPD patients will be randomly assigned to either iTBS or sham during four consecutive weeks (20 sessions in total) in addition to standardized DBT treatment. The stimulation will focus on the unilateral stimulation of the left dorsolateral prefrontal cortex (DLPFC), which plays an important role in the control of impulsivity and risk-taking. Primary outcome is the difference in borderline symptomatology, while secondary target criteria are depressive symptoms, general functional level, impulsivity and self-compassion. Statistical analysis of therapy response will be conducted by Mixed Model Repeated Measurement using a 2 × 2-factorial between-subjects design with the between-subject factor stimulation (TMS vs. Sham) and the within-subject factor time (T0 vs. T1). Furthermore, structural magnetic resonance imaging (MRI) will be conducted and analyzed. The study will provide evidence and insight on whether iTBS has an enhancing effect as add-on to DBT in BPD.Trial registration: drks.de (DRKS00020413) registered 13/01/2020.

Patent ductus arteriosus and the association between lung ultrasound score and bronchopulmonary dysplasia: a secondary analysis of a prospective study.

Moderate-to-large patent ductus arteriosus (PDA) has been linked to increased risk of bronchopulmonary dysplasia (BPD), while lung ultrasound score (LUS) has been demonstrated to accurately predict BPD. We aimed to investigate the correlation of LUS as a marker of interstitial pulmonary edema and the severity of the ductal shunt in predicting future BPD development in very preterm infants. This secondary analysis of a prospective study recruited preterm infants with gestational age < 30 weeks. LUS on postnatal days 7 and 14, and echocardiographic data [PDA diameter and left atrium-to-aortic root ratio (LA/Ao)] near LUS acquisition were collected. Correlation coefficient, logistics regression analysis, and the area under the receiver operating characteristic (AUROC) procedure were used. A statistically significant and positive correlation existed between LUS and PDA diameter (ρ = 0.415, ρ = 0.581, and p < 0.001) and LA/Ao (ρ = 0.502, ρ = 0.743, and p < 0.001) at postnatal days 7 and 14, respectively, and the correlations of LUS and echocardiographic data were generally stronger in the non-BPD group. In the prediction of BPD, LUS incorporating echocardiographic data at postnatal days 7 obtained significantly higher predictive performance compared to LUS alone (AUROC 0.878 [95% CI 0.801-0.932] vs. AUROC 0.793 [95% CI 0.706-0.865]; Delong test, p = 0.013). CONCLUSIONS: There is a statistically significant correlation between LUS and echocardiographic data, suggesting their potential role as early predictors for respiratory outcomes in very preterm infants. WHAT IS KNOWN: • Lung ultrasound score (LUS) has shown good reliability in predicting bronchopulmonary dysplasia (BPD) development. • Some echocardiographic data that characterized ventricular function was reported to be used to predict severe BPD. WHAT IS NEW: • There is a positive and statistically significant correlation between LUS and echocardiographic data at postnatal days 7 and 14. • The integrated use of LUS and echocardiographic data may have potential value in predicting BPD.

Chest radiographic thoracic areas and respiratory outcomes in infants with anterior abdominal wall defects.

OBJECTIVES: Infants with anterior abdominal wall defects (AWD) can suffer from pulmonary complications. Our aims were to determine if the chest radiographic thoracic areas (CRTAs) on day one differed between infants with exomphalos or gastroschisis, whether this related to differing severity of outcomes and if they were lower than those of controls indicating abnormal antenatal lung growth. METHODS: A review of infants with exomphalos or gastroschisis born between January 2004 and January 2023 was conducted. The control group was term, newborn infants ventilated for poor respiratory drive at birth. Chest radiographs on day one were analysed and the highest CRTA in the first 24 h after birth for each infant included in the analysis. RESULTS: The 127 infants with gastroschisis had a lower gestational age and birthweight than the 62 exomphalos infants and 130 controls (all p<0.001) The CRTAs of the controls were greater than the CRTAs of the exomphalos and the gastroschisis infants (p = 0.001). The median CRTA corrected for birthweight was lower in the exomphalos infants [688, IQR 568-875 mm2/kg] than the gastroschisis infants [813, IQE 695-915 mm2/kg] No gastroschisis infant developed bronchopulmonary dysplasia (BPD). A CRTA of 1759 mm2 had a sensitivity of 81 % and specificity of 71 % in predicting BPD in infants with exomphalos. CONCLUSIONS: Infants with gastroschisis or exomphalos had lower CRTAs than controls suggesting both groups had abnormal antenatal lung development. The CRTA was lower in the exomphalos infants who also had worse respiratory outcomes, hence CRTA assessment may a useful prognostic aid.

The WHO Adult ADHD self-report Scale used in a clinical sample of patients with overlapping symptoms - psychometric properties of and scoring methods for the Swedish translation.

BACKGROUND: The WHO Adult ADHD Self-report Scale (ASRSv1.1 and ASRS-S) is used for screening for attention-deficit/hyperactivity disorder (ADHD). The capacity of the Swedish version of the scale to discriminate ADHD from borderline personality disorder (BPD) and bipolar disorder (BP) has not been tested. AIM: Evaluate scoring methods, psychometric properties, and diagnostic accuracy of the Swedish versions of ASRSv1.1/ASRS-S in a group of patients with ADHD and/or BPD and/or BP. METHOD: A total of 151 young adult psychiatric patients diagnosed with ADHD, BPD and/or BD completed ASRSv1.1 and the Wender Utah Rating Scale (WURS) for ADHD symptoms, and the Sheehan Disability Scale (SDS) for functional impairment. ADHD diagnoses were assessed with the Schedule for Affective Disorders and Schizophrenia (K-SADS) interview. Both versions of the scale were analysed through dichotomised and non-dichotomised scoring for diagnostic accuracy analysis. RESULTS: The internal consistency for ASRSv1.1/ASRS-S was satisfactory with α 0.913 and 0.743, respectively. The two-factor structure of the ASRSv1.1 and the one factor structure of ASRS-S were supported by the confirmatory factor analyses. A strong positive correlation was found between ASRSv1.1 and WURS and a moderate level of correlation was found between ASRSv1.1 and SDS. The area under the curve for both scoring methods were excellent with an area under the curve (AUC) of 0.808 and 0.817, respectively. Optimal cut-off scores were in line with the original recommendations. CONCLUSION: The Swedish translation of ASRSv1.1/ASRS-S has psychometric properties comparable to other populations and the capacity to screen for ADHD in patients with overlapping symptoms.

Social cognition in women with borderline personality disorder based on an exhaustive analysis of the Movie for Assessment of Social Cognition (MASC) categories.

A significant number of borderline personality disorder (BPD) symptoms are manifested in the interpersonal context. This can be explained by the difficulties in attributing the mental states of oneself and others, which constitutes social cognition. Errors in social cognition are interrelated with the affective, cognitive, impulsive, and interpersonal areas of the person with BPD. The aims of this study was to analyze social cognition in women with BPD compared with a control group and to analyze social cognition in BPD based on BPD symptoms and its severity. To assess social cognition, we used a full range of social cognition categories provided by the Movie for the Assessment of Social Cognition (MASC): correct theory of mind (ToM); attribution of mental states (thoughts, emotions, or intentions); errors of mentalization; types of ToM; and attribution of mental states through perceptive or cognitive cues and through hot or cold emotions. The MASC has high ecological validity and has been validated in Spanish. The sample comprised 79 women, including 47 women with BPD and 32 healthy women. Worse social cognition performance was observed in women with BPD. More severe borderline symptoms were related to worse functioning in the correct ToM and to errors of no mentalization. Involvement of the cognitive area in borderline symptoms was associated with worse functioning in correct ToM and worse social cognition in cognitive areas as well as with hypermentalization. This is the first study that uses all the MASC categories and considers BPD heterogeneity and its severity to study social cognition.

Conditional knockout of ITGB4 in bronchial epithelial cells directs bronchopulmonary dysplasia.

Neonatal respiratory system disease is closely associated with embryonic lung development. Our group found that integrin ß4 (ITGB4) is downregulated in the airway epithelium of asthma patients. Asthma is the most common chronic respiratory illness in childhood. Therefore, we suspect whether the deletion of ITGB4 would affect fetal lung development. In this study, we characterized the role of ITGB4 deficiency in bronchopulmonary dysplasia (BPD). ITGB4 was conditionally knocked out in CCSP-rtTA, Tet-O-Cre and ITGB4f/f triple transgenic mice. Lung tissues at different developmental stages were collected for experimental detection and transcriptome sequencing. The effects of ITGB4 deficiency on lung branching morphogenesis were observed by fetal mouse lung explant culture. Deleting ITGB4 from the airway epithelial cells results in enlargement of alveolar airspaces, inhibition of branching, the abnormal structure of epithelium cells and the impairment of cilia growth during lung development. Scanning electron microscopy showed that the airway epithelial cilia of the ß4ccsp.cre group appear to be sparse, shortened and lodging. Lung-development-relevant factors such as SftpC and SOX2 significantly decreased both mRNA and protein levels. KEGG pathway analysis indicated that multiple ontogenesis-regulating-relevant pathways converge to FAK. Accordingly, ITGB4 deletion decreased phospho-FAK, phospho-GSK3ß and SOX2 levels, and the correspondingly contrary consequence was detected after treatment with GSK3ß agonist (wortmannin). Airway branching defect of ß4ccsp.cre mice lung explants was also partly recovered after wortmannin treatment. Airway epithelial-specific deletion of ITGB4 contributes to lung developmental defect, which could be achieved through the FAK/GSK3ß/SOX2 signal pathway.

FGF10 Triggers De Novo Alveologenesis in a Bronchopulmonary Dysplasia Model: Impact on Resident Mesenchymal Niche Cells.

Bronchopulmonary dysplasia (BPD) is a neonatal lung disease developing in premature babies characterized by arrested alveologenesis and associated with decreased Fibroblast growth factor 10 (FGF10) expression. One-week hyperoxia (HYX) exposure of newborn mice leads to a permanent arrest in alveologenesis. To test the role of Fgf10 signaling to promote de novo alveologenesis following hyperoxia, we used transgenic mice allowing inducible expression of Fgf10 and recombinant FGF10 (rFGF10) protein delivered intraperitoneally. We carried out morphometry analysis, and IF on day 45. Alveolospheres assays were performed co-culturing AT2s from normoxia (NOX) with FACS-isolated Sca1Pos resident mesenchymal cells (rMC) from animals exposed to NOX, HYX-PBS, or HYX-FGF10. scRNAseq between rMC-Sca1Pos isolated from NOX and HYX-PBS was also carried out. Transgenic overexpression of Fgf10 and rFGF10 administration rescued the alveologenesis defects following HYX. Alveolosphere assays indicate that the activity of rMC-Sca1Pos is negatively impacted by HYX and partially rescued by rFGF10 treatment. Analysis by IF demonstrates a significant impact of rFGF10 on the activity of resident mesenchymal cells. scRNAseq results identified clusters expressing Fgf10, Fgf7, Pdgfra, and Axin2, which could represent the rMC niche cells for the AT2 stem cells. In conclusion, we demonstrate that rFGF10 administration is able to induce de novo alveologenesis in a BPD mouse model and identified subpopulations of rMC-Sca1Pos niche cells potentially representing its cellular target.

Involvement of HIF1 stabilization and VEGF signaling modulated by Grx-1 in murine model of bronchopulmonary dysplasia.

Hypoxia inducible factor (HIF)-1α could be stabilized by Grx1 deletion, which is implicated critical in the pathogenesis of bronchopulmonary dysplasia (BPD). Until now, the stabilization of HIF-1α by glutathionylation to regulate the pulmonary microcirculation in BPD is not well addressed. In this study, we investigated whether the HIF-1α stabilization modulated by Grx1 ablation could ameliorate the pathological changes in the mouse model of BPD, including angiogenesis and alveolar formation. We found that depletion of Grx1 increased levels of GSH-protein adducts, which was associated with the improvement in the numbers of alveoli, the capillary density in the pulmonary microcirculation and the survival rate in the littermates with hyperoxic exposure. Grx1 ablation could promote HIF-1α glutathionylation by increasing GSH adducts to stabilize HIF-1α and to induce VEGF-A production in the lung tissue. The above phenotype of capillary density and VEGF-A production was removed by the pharmacological administration of YC-1, the HIF-1α inhibitor, suggesting the HIF-1α dependent manner for pulmonary microcirculatory perfusion. These data indicate that HIF-1α stabilization plays an critical role in modification pulmonary microcirculatory perfusion, which is associated with the pathological damage under hyperoxic conditions, suggesting that targeting with HIF-1α stabilization should be a potential clinical and therapeutic strategy for BPD treatment.

The infant with bronchopulmonary dysplasia on home oxygen: The oxygen weaning conundrum in the absence of good evidence.

Bronchopulmonary dysplasia [BPD] is the most common complication of extremely preterm delivery and its optimal management remains challenging because of a lack of evidence to guide management. There has been improvement in the management of evolving BPD in the neonatal intensive care unit (NICU). The threshold for provision of home oxygen therapy, often occurring because of a preference for earlier discharge from the NICU, creates tensions for clincians and families. Once discharged in supplemental oxygen, the approaches for the weaning of this therapy vary considerably across the world. Regardless of guidelines and multidisciplinary team support, up to a third of families of an infant with BPD elect to withdraw home oxygen therapy independently of medical advice. There is a pressing need to derive evidence to better inform practice, generate international consensus and undertake large, appropriately funded, longitudinal studies of BPD with clinically meaningful outcomes (respiratory, cardiovascular and neurodevelopmental) from infancy to adulthood.

Life experienced as worth living and beyond: a qualitative study of the pathways to recovery and flourishing amongst individuals treated for borderline personality disorder.

BACKGROUND: Dialectical Behaviour Therapy (DBT) is recognized as a leading evidence-based treatment, effective in reducing symptoms of borderline personality disorder (BPD), as well as co-occurring clinical syndromes. However, symptom remission may not be the same as a life experienced as worth living. The purpose of the study was to understand, from the perspective of individuals with lived experience, the concepts of recovery, life experienced as worth living and flourishing after treatment for BPD, and to describe the pathways to wellness after symptom remission. METHODS: Semi-structured interviews were conducted with nine adult women previously diagnosed with BPD, co-occurring clinical syndromes and severe self-harm behaviour who self-identified as recovered for a minimum of two years, recruited from a network for individuals with lived experience. The average duration of recovery was 5.7 years with a range from 2 to 10 + years. Data were analysed using thematic analysis. RESULTS: Four main themes and 14 subthemes were generated from our analyses. Main themes indicated that loved ones helped recovery and to create a life worth living, that participants identified as recovered and as healthy and beyond, and that becoming well is a long process associated in part with reclaiming a healthy identity. Participants defined recovery as separate but related to a life worth living, which in turn was separate but related to being healthy and having lives they described as being beyond health and well-being. The wellness process was described as lengthy and non-linear, including setbacks that with time no longer derailed daily life. A proposed theoretical model depicting the wellness process over time from symptom remission to the experience of a life beyond health and wellness is presented. CONCLUSIONS: This qualitative study contributes knowledge of what a life experienced as worth living means, as well as how wellness progressed into flourishing for some participants within a sample of individuals with lived experience. Our findings may inform treatment development that targets more than symptom reduction, which in turn may shorten trajectories from symptom remission to health, wellness, and flourishing.

Influence of sex on the requirement for and outcomes following late postnatal corticosteroid treatment.

There remains a disparity between the outcomes of male and female prematurely born infants. Our aim was to assess the influence of sex on the requirement for late (> 7 days) postnatal corticosteroid (PNS) treatment and the outcomes following treatment. A retrospective whole population study of infants born at less than 28 weeks of gestation in all neonatal units in England between 2014 and 2018. The impact of exposure to at least five consecutive days of dexamethasone or hydrocortisone on bronchopulmonary dysplasia (BPD) at 36 weeks corrected gestation and survival to discharge from neonatal care was determined. Ten thousand, six hundred and fifty-five infants survived to seven days. Male sex was associated with an increased incidence of BPD (OR 1.41, 95%CI 1.287-1.552, p < 0.001) and death (OR 1.227, 95%CI 1.123-1.452, p < 0.001). Two thousand, three hundred and forty-four infants (22%) received at least one course of PNS at a median of 23 (IQR 15-40) days after birth. Males (23.6%) were more likely to receive PNS than females (20.1%), p < 0.001 and receive repeated courses (mean 1.67 compared to a mean of 1.59 in the females), p = 0.027. Multivariate regression analysis identified no significant differences in the incidence of BPD or death between male and females who received PNS.  Conclusions: Males and females had similar outcomes after receiving PNS, but a significantly greater proportion of males met the clinical threshold to receive PNS and were more likely to receive repeated courses which may expose them to a greater risk of adverse long-term outcomes. What is Known: • There remains a difference in outcomes of male and female infants born prematurely. • Prematurely born male infants were more likely to receive postnatal corticosteroids and a greater number of courses but had similar outcomes compared to female infants. What is New: • Postnatal corticosteroids have long-term adverse effects. Such outcomes should be considered when weighing up the risk-benefit ratio of prescribing postnatal corticosteroids, particularly in very prematurely born male infants.

Comparison of lung ultrasound scores with clinical models for predicting bronchopulmonary dysplasia.

Lung ultrasound scores (LUSs) have been demonstrated to accurately predict moderate-to-severe bronchopulmonary dysplasia (msBPD). This study attempted to explore the additional value of LUSs for predicting msBPD compared to clinical multivariate models in different gestational age (GA) groups. The study prospectively recruited preterm infants with GA < 32 weeks. Lung ultrasound was performed on days 3, 7, 14, and 21 after birth. A linear mixed-effects regression model was used to evaluate LUS evolution in infants born before and after 28 weeks. The receiver operating characteristic (ROC) procedure was used to analyze the reliability of LUS and clinical multivariable models for predicting msBPD. The optimal time to predict msBPD in all infants was 7 days with a cut-off point of 5 (area under the ROC (AUROC) curve: 0.78, 95% confidence interval (CI): 0.71-0.84). In infants with GA ≥ 28 weeks, LUSs provided a moderate diagnostic accuracy for all four time points (AUROC curve: 0.74-0.78), and the AUROC curve for the clinical multivariable model on day 14 was 0.91 (95% CI: 0.84-0.96), which was significantly higher than that of LUSs (AUROC curve: 0.77, 95% CI: 0.68-0.85, P < 0.05). In infants born at 23-27 weeks, LUSs showed a low diagnostic accuracy with higher cut-off points to predict msBPD, and the AUROC curve for GA to predict msBPD was 0.75 (95% CI: 0.59-0.85), providing diagnostic accuracy similar to that of LUSs.  Conclusion: The contribution of LUSs to predict msBPD in infants with different GAs remains controversial and requires further investigation. What is Known: • Lung ultrasound scores (LUSs) have been demonstrated to accurately predict moderate-to-severe bronchopulmonary dysplasia in infants with gestational age (GA)＜32 weeks. What is New: • The LUSs evolution differed between extremely preterm infants born before 28 weeks and preterm infants born at 28-32 weeks of gestation. • LUSs provided similar moderate predictive performance as GA-adjusted LUS and clinical multivariate models in infants born after 28 weeks, while LUSs seem to be less helpful in infants born before 28 weeks.

Frontal EEG asymmetry moderates the relation between borderline personality disorder features and feelings of social rejection in adolescents.

Although associations among borderline personality disorder (BPD), social rejection, and frontal EEG alpha asymmetry scores (FAA, a neural correlate of emotion regulation and approach-withdrawal motivations) have been explored in different studies, relatively little work has examined these relations during adolescence in the same study. We examined whether FAA moderated the relation between BPD features and rejection sensitivity following a validated social exclusion paradigm, Cyberball. A mixed, clinical-community sample of 64 adolescents (females = 62.5%; Mage = 14.45 years; SD = 1.6; range = 11-17 years) completed psychodiagnostic interviews and a self-report measure of BPD (Time 1). Approximately two weeks later (Time 2), participants completed a resting EEG recording followed by Cyberball. FAA moderated the relation between BPD features and overall feelings of rejection following Cyberball: individuals with greater relative left FAA had the highest and lowest feelings of social rejection depending on whether they had high and low BPD feature scores, respectively. Results remained after controlling for age, sex, gender, depression, and BPD diagnosis. These results suggest that FAA may moderate the relation between BPD features and social rejection, and that left frontal brain activity at rest may be differentially associated with those feelings in BPD. Findings are discussed in terms of the link between left frontal brain activity in the regulation and dysregulation of social approach behaviors, characteristic of BPD.

The value of pulmonary artery acceleration time in evaluating pulmonary vascular disease in preterm infants with bronchopulmonary dysplasia.

OBJECTIVES: Early screening and dynamic monitoring of pulmonary vascular disease (PVD) in bronchopulmonary dysplasia (BPD) high-risk infants is of great clinical significance. Pulmonary artery acceleration time (PAAT) is a reliable and non-invasive method for assessing PVD in children over 1 year, but to date, few studies have used PAAT to assess pulmonary hemodynamics of preterm infants, especially those with BPD. Through dynamic monitoring the main hemodynamic indicators reflected PVD after birth, this study aimed to assess the value of PAAT in evaluating early PVD in BPD infants. METHODS: All 81 preterm infants at risk of BPD were divided into BPD and non-BPD groups according to whether BPD occurred. Clinical characteristics, PAAT, right ventricular ejection time (RVET) and other main hemodynamic indicators at four different time points after birth were studied and compared. RESULTS: PAAT and PAAT/RVET increased gradually within 72 h after birth in the BPD group (p < .05), but the curve tended to be flat over time after 72 h (p > .05). At PMA32 and 36 weeks, the PAAT (49.7 ± 4.8 vs. 54.8 ± 5.7, p = .001; 50.0 ± 5.3 vs. 57.0 ± 5.3, p = .001) and PAAT/RVET (.33 ± .04 vs. .35 ± .03, p = .001; .34 ± .03 vs. .37 ± .04, p = .001) in BPD group were significantly lower than those in the non-BPD group. CONCLUSIONS: PAAT and PAAT/RVET in the BPD group infants showed different change patterns compared to non-BPD group infants. PAAT can be used as a noninvasive and reliable screening method for screening and dynamic monitoring of PVD in BPD high-risk infants.

Experiences of Diagnosis, Symptoms, and Use of Reliever Inhalers in Patients With Asthma and Concurrent Inducible Laryngeal Obstruction or Breathing Pattern Disorder: Qualitative Analysis of a UK Asthma Online Community.

BACKGROUND: Breathing pattern disorders (BPDs) and inducible laryngeal obstruction (ILO) cause similar symptoms to asthma, including dyspnea and chest tightness, with an estimated prevalence of up to one-fifth of patients with asthma. Both conditions can be comorbid with asthma, and there is evidence that they are misdiagnosed and mistreated as asthma. OBJECTIVE: This study aims to explore whether the symptoms of ILO and BPD were topics of discussion in a UK asthma online health community and patient experiences of diagnosis and treatment, in particular their use of reliever inhalers. METHODS: A qualitative thematic analysis was performed with posts from an asthma community between 2018 and 2022. A list of key ILO or BPD symptoms was created from the literature. Posts were identified using the search terms "blue inhaler" and "breath" and included if describing key symptoms. Discussion threads of included posts were also analyzed. RESULTS: The search retrieved a total of 1127 relevant posts: 1069 written by 302 users and 58 posted anonymously. All participants were adults, except 2 who were parents writing about their children. Sex and age were only available for 1.66% (5/302; 3 females and 2 males) and 9.93% (30/302) of participants (27 to 73 years old), respectively. The average number of posts written by each participant was 3.54 (range 1-63). Seven participants wrote >20 posts each. Participants experiencing undiagnosed ILO or BPD symptoms, whether or not comorbid with asthma, expressed frustration with the "one-size-fits-all" approach to diagnosis, as many felt that their asthma diagnosis did not fully explain symptoms. Some suspected or were formally diagnosed with BPD or ILO, the latter reporting relief on receiving a diagnosis and appropriate management. Participants showed awareness of their inappropriate salbutamol use or overuse due to lack of effect on symptoms. BPD and ILO symptoms were frequently comorbid with asthma. The asthma online community was a valuable resource: engagement with peers not only brought comfort but also prompted action with some going back to their clinicians and reaching a diagnosis and appropriate management. CONCLUSIONS: Undiagnosed ILO and BPD symptoms and lack of effects of asthma treatment were topics of discussion in an asthma online community, caused distress and frustration in participants, and affected their relationship with health care professionals, showing that patients experiencing BPD and ILO have unmet needs. Clinicians' education on BPD and ILO diagnosis and management, as well as increased access to appropriate management options, such as respiratory physiotherapy and speech and language therapy, are warranted particularly in primary care. Qualitative evidence that engagement with the online community resulted in patients taking action going back to their clinicians and reaching a diagnosis of ILO and BPD prompts future research on online peer support from an established online health community as a self-management resource for patients.

Vascular Endothelial Growth Factor as Molecular Target for Bronchopulmonary Dysplasia Prevention in Very Low Birth Weight Infants.

Bronchopulmonary dysplasia (BPD) still represents an important burden of neonatal care. The definition of the disease is currently undergoing several revisions, and, to date, BPD is actually defined by its treatment rather than diagnostic or clinic criteria. BPD is associated with many prenatal and postnatal risk factors, such as maternal smoking, chorioamnionitis, intrauterine growth restriction (IUGR), patent ductus arteriosus (PDA), parenteral nutrition, sepsis, and mechanical ventilation. Various experimental models have shown how these factors cause distorted alveolar and vascular growth, as well as alterations in the composition and differentiation of the mesenchymal cells of a newborn's lungs, demonstrating a multifactorial pathogenesis of the disease. In addition, inflammation and oxidative stress are the common denominators of the mechanisms that contribute to BPD development. Vascular endothelial growth factor-A (VEGFA) constitutes the most prominent and best studied candidate for vascular development. Animal models have confirmed the important regulatory roles of epithelial-expressed VEGF in lung development and function. This educational review aims to discuss the inflammatory pathways in BPD onset for preterm newborns, focusing on the role of VEGFA and providing a summary of current and emerging evidence.