-
Journal of Neurophysiology Jul 2024Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are...
Humans rely on predictive mechanisms during visual processing to efficiently resolve incomplete or ambiguous sensory signals. While initial low-level sensory data are conveyed by feedforward connections, feedback connections are believed to shape sensory processing through conveyance of statistical predictions based on prior exposure to stimulus configurations. Individuals with autism spectrum disorder (ASD) show biases in stimulus processing toward parts rather than wholes, suggesting their sensory processing may be less shaped by statistical predictions acquired through prior exposure to global stimulus properties. Investigations of illusory contour (IC) processing in neurotypical (NT) adults have established a well-tested marker of contour integration characterized by a robust modulation of the visually evoked potential (VEP) - the - that occurs over lateral occipital scalp during the timeframe of the N1 component. Converging evidence strongly supports the notion that this indexes a signal with significant feedback contributions. Using high-density VEPs, we compared the in 6-7-year-old children with ASD (n=32) or NT development (n=53). Both groups of children generated an that was equivalent in amplitude. However, the notably onset 21ms later in ASD, even though initial VEP afference was identical across groups. This suggests that feedforward information predominated during perceptual processing for 15% longer in ASD compared to NT children. This delay in the feedback dependent , in the context of known developmental differences between feedforward and feedback fibers, suggests a potential pathophysiological mechanism of visual processing in ASD, whereby ongoing stimulus processing is less shaped by statistical prediction mechanisms.
PubMed: 38958283
DOI: 10.1152/jn.00058.2024 -
AJR. American Journal of Roentgenology Jul 2024
PubMed: 38958266
DOI: 10.2214/AJR.24.31399 -
The Journal of Antimicrobial... Jul 2024Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long...
INTRODUCTION
Dalbavancin is an antibiotic active against most Gram-positive bacteria approved for acute bacterial skin and skin structure infections (ABSSSI). Owing to its long half-life, it is being increasingly used for other indications.
PATIENTS AND METHODS
We present a case series of children and adolescents treated with dalbavancin for osteoarticular, catheter-related and other non-ABSSSI infections.
RESULTS
Dalbavancin was prescribed to 15 patients. Six (40%) were female and median age at prescription was 11.9 (IQR 1.3-18.0) years. Most of them (12/15) had significant comorbidities. Patients presented mainly with deep surgical site infections, osteoarticular infections and central-line-associated bloodstream infections. The most common isolate was Staphylococcus aureus followed by Staphylococcus epidermidis. Major reasons to prescribe dalbavancin were to ensure compliance and patients' convenience. Two patients discontinued the drug due to adverse events possibly related to it. The rest of the patients completed the treatment with dalbavancin, with a median duration of 56 days (IQR 17.5, 115.5). All achieved complete resolution and present no relapse after a median follow-up of 9.9 months (IQR 4.8, 16.6).
CONCLUSIONS
Dalbavancin was a safe, effective and convenient alternative in selected paediatric patients with complicated non-ABSSSI infections caused by Gram-positive bacteria.
PubMed: 38958260
DOI: 10.1093/jac/dkae212 -
Pediatric Pulmonology Jul 2024Preterm infants close to viability commonly require mechanical ventilation (MV) for respiratory distress syndrome. Despite commonly used lung-sparing ventilation...
INTRODUCTION
Preterm infants close to viability commonly require mechanical ventilation (MV) for respiratory distress syndrome. Despite commonly used lung-sparing ventilation techniques, rapid lung expansion during MV induces lung injury, a risk factor for bronchopulmonary dysplasia. This study investigates whether ventilation with optimized lung expansion is feasible and whether it can further minimize lung injury. Therefore, optimized lung expansion ventilation (OLEV) was compared to conventional volume targeted ventilation.
METHODS
Twenty preterm lambs were surgically delivered after 132 days of gestation. Nine animals were randomized to receive OLEV for 24 h, and seven received standard MV. Four unventilated animals served as controls (NV). Lungs were sampled for histological analysis at the end of the experimental period.
RESULTS
Ventilation with OLEV was feasible, resulting in a significantly higher mean ventilation pressure (0.7-1.3 mbar). Temporary differences in oxygenation between OLEV and MV did not reach clinically relevant levels. Ventilation in general tended to result in higher lung injury scores compared to NV, without differences between OLEV and MV. While pro-inflammatory tumor necrosis factor-α messenger RNA (mRNA) levels increased in both ventilation groups compared to NV, only animals in the MV group showed a higher number of CD45-positive cells in the lung. In contrast, mean (standard deviations) surfactant protein-B mRNA levels were significantly lower in OLEV, 0.63 (0.38) compared to NV 1.03 (0.32) (p = .023, one-way analysis of variance).
CONCLUSION
In conclusion, a small reduction in pulmonary inflammation after 24 h of support with OLEV suggests potential to reduce preterm lung injury.
PubMed: 38958257
DOI: 10.1002/ppul.27153 -
Pediatric Pulmonology Jul 2024To quantify the association of ambient air pollution (particulate matter, PM) exposure with medically attended acute respiratory illness among infants with...
OBJECTIVES
To quantify the association of ambient air pollution (particulate matter, PM) exposure with medically attended acute respiratory illness among infants with bronchopulmonary dysplasia (BPD).
STUDY DESIGN
Single center, retrospective cohort study of preterm infants with BPD in Metropolitan Philadelphia. Multivariable logistic regression quantified associations of annual mean PM exposure (per μg/m) at the census block group level with medically attended acute respiratory illness, defined as emergency department (ED) visits or hospital readmissions within a year after first hospital discharge adjusting for age at neonatal intensive care unit (NICU) discharge, year, sex, race, insurance, BPD severity, and census tract deprivation. As a secondary analysis, we examined whether BPD severity modified the associations.
RESULTS
Of the 378 infants included in the analysis, 189 were non-Hispanic Black and 235 were publicly insured. Census block PM level was not significantly associated with medically attended acute respiratory illnesses, ED visits, or hospital readmissions in the full study cohort. We observed significant effect modification by BPD grade; each 1 µg/m higher annual PM exposure was medically attended acute respiratory illness (adjusted odds ratio [aOR] 1.65, 95% CI: 1.06-2.63) among infants with Grade 1 BPD but not among infants with grade 3 BPD (aOR 0.83, 95% CI: 0.47-1.48) (interaction p = .024).
CONCLUSIONS
Cumulative PM exposure in the year after NICU discharge was not significantly associated with medically attended acute respiratory illness among infants with BPD. However, infants with Grade 1 BPD had significantly higher odds with higher exposures. If replicated, these findings could inform anticipatory guidance for families of these infants to avoid outdoor activities during high pollution days after NICU discharge.
PubMed: 38958238
DOI: 10.1002/ppul.27164 -
International Journal of Cancer Jul 2024A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent...
A lot of hope for high-risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single-agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high-risk solid tumors using the N-of-1 approach in real-world scenario. A total of 160 evaluable events occurred in 48 patients during the 4-year follow-up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P = .048) or in patients with disease control (HR = 0.16, P = .00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P = .225). A strong synergistic effect was found for immune check-point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P = .0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents.
PubMed: 38958237
DOI: 10.1002/ijc.35062 -
Child: Care, Health and Development Jul 2024Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions...
BACKGROUND
Early executive functioning (EF) skills are foundational capabilities that predict school readiness, academic development and psychiatric risk. Early interventions enhancing these capabilities could have critical import in improving outcomes. However, to develop interventions, it is necessary to identify specific EF skills that will vary with child age. Thus, we aimed to examine the characteristics and efficacy of interventions targeting EF in infancy and early childhood up to age 3.
METHODS
A comprehensive search of PubMed, Embase, CINAHL and APA PsycINFO databases was performed for studies published before December 2022. Randomized and non-randomized studies of interventions designed to improve at least one EF skill in children ≤3 years were included. EF skills included attentional control, inhibition/self-regulation, activity initiation, working memory, cognitive flexibility, planning ability, problem-solving and performance monitoring. We independently extracted data, used the revised Cochrane Risk-of-Bias tool to assess the quality of the evidence and conducted Synthesis Without Meta-analysis (SWiM). The overall quality of the evidence and the strength of recommendations was determined using elements of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Thirty-five studies met inclusion criteria (original n = 7467). Studies were highly variable in the EF skill targeted, target subject (i.e., child, parent and teacher), nature and dosage of the intervention, and timing of outcome assessment. Most interventions focused on improving impulse control and self-regulation. The overall quality of evidence was low to moderate with a high risk of bias, though six studies had low risk of bias but yielded mixed findings of efficacy.
CONCLUSIONS
The relatively small number of early EF intervention studies uses such variable methods that there is currently no converging evidence of efficacy to recommend a specific intervention. Thus, findings support the need for a more systematic, targeted approach to the design and implementation of early EF interventions for target populations.
Topics: Humans; Executive Function; Child, Preschool; Infant; Child Development; Early Intervention, Educational
PubMed: 38958229
DOI: 10.1111/cch.13298 -
Pediatric Pulmonology Jul 2024Preterm infants, particularly those with bronchopulmonary dysplasia (BPD), are at risk of lung development problems. Over the last decades, lung protective strategies...
BACKGROUND
Preterm infants, particularly those with bronchopulmonary dysplasia (BPD), are at risk of lung development problems. Over the last decades, lung protective strategies have been used, decreasing the risk of chronic lung disease.
OBJECTIVE
To evaluate the pulmonary function test (PFT) of preterm infants born after the introduction of lung protective strategies and to assess perinatal determinants of impaired lung function in this population.
METHODS
A prospective, observational, single-center study was conducted in the neonatal unit of a high-complexity hospital. The study included newborns with less than 32 weeks gestational age born between 2012 and 2014, who were followed up until they reach school age. For the main outcome, two groups were stablished: no BPD or grade 1 BPD (no BPD/1) and grade 2 or 3 BPD (BPD 2/3).
RESULTS
Out of 327 patients, 116 were included. BPD was diagnosed in 49.1% (47), with 50.9% (29) classified as grade 1, 35.1% (20) as grade 2, and 14.0% (8) as grade 3. Mean age at PFT was 8.59 years (SD 0.90). Mean FEV1% was 95.36% (SD 13.21) and FEV1 z-score -0.36 (SD 1.12); FVC% 97.53% (SD 12.59) and FVC z-score -0.20 (SD 1.06); FEV1/FVC ratio 85.84% (SD 8.34) and z-score -0.24 (SD 1.34). When comparing patients with no BPD/1 and BPD 2/3, we observed differences in all pulmonary function parameters, which persisted after adjusting for gestational age. No differences in PFT were observed between patients without BPD and those with grade 1 BPD. Most patients (76.7%, 89) had normal spirometry pattern, with obstructive pattern observed in 12.9% (15), restrictive pattern in 9.5% (11), and mixed pattern in 0.9% (1) of patients.
CONCLUSION
Preterm infants with BPD 2/3 showed a decrease in all pulmonary function parameters compared to preterm infants with no BPD/1; an effect that was independent of gestational age. Among patients with BPD who had an altered PFT pattern, the most common pattern was obstructive, followed by restrictive and then, mixed.
PubMed: 38958223
DOI: 10.1002/ppul.27158 -
British Journal of Clinical Pharmacology Jul 2024Cefoperazone is commonly used off-label in the treatment of bacterial meningitis and sepsis in children, and the pharmacokinetic (PK) data are limited in this vulnerable...
AIMS
Cefoperazone is commonly used off-label in the treatment of bacterial meningitis and sepsis in children, and the pharmacokinetic (PK) data are limited in this vulnerable population. The goal of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict pediatric cefoperazone exposure for rational dosing recommendations.
METHODS
A cefoperazone PBPK model for adults was first constructed using Simcyp V22 simulator. Subsequently, the model was extended to children based on the built in age-dependent physiological parameters, while the drug characteristics remained unchanged. The verified pediatric PBPK model was then utilized to assess the rationality of the common dosing regimens for children at different age groups.
RESULTS
Cefoperazone PBPK model included elimination via biliary excretion, glomerular filtration, and organic anion transporter 3 (OAT3)-mediated tubular secretion. 95.2% of the observed mean concentrations and 100% of the area under the plasma drug concentration-time curve (AUC) and peak concentration (C) in adults were within a twofold range of model mean predictions. Good predictive accuracy was also observed in children, including neonates. 50 mg/kg q12h cefoperazone demonstrated effective target attainment in virtual term neonates (<1 month) when the MIC was ≤1 mg/L, adhering to the stringent PK/PD target of 75% fT > MIC. 37.5 mg/kg q12h cefoperazone achieved the common 50% fT > MIC target for an MIC ≤ 0. 25 mg/L in virtual pediatric patients ranging from 1 month to 18 years of age.
CONCLUSIONS
A pediatric PBPK model was developed for cefoperazone, and it could serve as the basis for deriving rational dosing regimens in children.
PubMed: 38958222
DOI: 10.1111/bcp.16163 -
Disability and Rehabilitation Jul 2024Long COVID presents global challenges for healthcare professionals. Occupational therapists responded by seeking effective treatment strategies. The approaches of...
PURPOSE
Long COVID presents global challenges for healthcare professionals. Occupational therapists responded by seeking effective treatment strategies. The approaches of occupational therapists supporting long-haulers in German-speaking countries remain under-explored. The purpose of this study is to explore how occupational therapists in Germany, Austria and Switzerland navigate and apply profession-specific strategies in the new clinical landscape of Long COVID care.
MATERIALS AND METHODS
This study used qualitative-descriptive design and content analysis to extract insights from seven semi-structured interviews with occupational therapists in inpatient and outpatient settings from three countries.
RESULTS
Four overarching themes emerged: how Long COVID was encountered within the scope of occupational therapy, the multifaceted repertoire experts used to support long haulers, triumphs and challenges that emerged in Long COVID treatment, and recommendations and opportunities for occupational therapy practice. The results underscore the complex support needed for long-haulers, achieved through a multifaceted occupational therapy repertoire, incorporating client-centred, occupation-focused, and context-referencing strategies with shared decision-making and collaborative therapy planning.
CONCLUSIONS
Occupational therapy concepts, with their focus on human occupation, may offer new treatment options and strategies for managing emerging conditions such as Long COVID.
PubMed: 38958213
DOI: 10.1080/09638288.2024.2367603