Background: Outdoor play is vital for children's physical, mental, and social development, yet opportunities for such engagement have declined globally, including in Latin America and the Caribbean (LAC). Objectives: This brief narrative review aimed to synthesize the current landscape of outdoor play among children and adolescents in LAC, identify challenges and opportunities, and offer evidenceinformed recommendations for advancing policies and practices in the region. Methods: We searched PubMed/MEDLINE, Scopus, and SciELO between September and October 2024, using the term "outdoor play" in English, Portuguese, and Spanish, to identify all records available from inception through October 2024. Governmental and non-governmental documents and initiatives related to outdoor play in the region were identified through complementary Google searches. Results: The review highlights substantial disparities in access to outdoor play, influenced by income inequality, urban infrastructure, gender, environmental conditions, and cultural norms. It also documents successful interventions, including open street programs, nature-based learning initiatives, and community-led actions, primarily in urban contexts. However, child-focused outdoor play policies and evaluations remain scarce. The COVID-19 pandemic intensified existing barriers while reinforcing the importance of outdoor environments for child well-being. Prominent regional organizations have contributed to advocacy, policy development, and knowledge dissemination. Conclusion: The review underscores the need for culturally relevant, equity-oriented, and climateresilient strategies to promote outdoor play. Strengthening policies, infrastructure, research, and intersectoral collaboration is essential to ensure that all children in LAC have the right and opportunity to play outdoors safely and meaningfully.
Abstract: Pediatricians and acute care physicians caring for ill patients with respiratory failure often encounter the decision to intubate children for respiratory support and/or to protect the airway. There are several Standard Operating Procedures (SOPs) or protocols such as the 3-3-2 Rule, Mallampati Score, Modified Mallampati Test, and Lemon Criteria, to evaluate whether a difficult airway exists so that preparedness for successful intubation can be ensured. Pediatricians are particularly concerned that there are usually no tailor-made tools or protocols to follow. The authors think that there are a few issues associated with the 3-3-2, Mallampati, and LEMON approaches. The Mallampati approach is only part of the more comprehensive LEMON approach to oropharyngeal patency, and patient cooperation is often required. The LEMON approach amalgamates the 3-3-2 and Mallampati approaches, together with the intrinsic problems associated with these two methods. We present a novel NIMO approach that consolidates existing techniques for intubating difficult airways. By integrating assessments of the Neck (3-3-2), Incisors (Inter-incisor distance), Mouth (Mallampati), and Oropharynx (LEMON), this systematic framework optimizes and streamlines clinical workflow and minimizes the limitations of current tools.
BACKGROUND:Low Birth Weight (LBW), defined as < 2500 g, is a global public health priority. Early prediction is essential for intervention. This systematic review investigates the performance of Artificial Intelligence (AI)/Machine Learning (ML) algorithms for LBW prediction. METHODS:Following PRISMA guidelines, Scopus, Web of Science, and PubMed were searched for studies utilizing AI/ML for LBW. Methodological quality was assessed via the PROBAST tool. Due to extreme statistical heterogeneity and inconsistent reporting of metrics, a narrative synthesis approach was employed. RESULTS:Forty studies met inclusion criteria. Quality assessment revealed that 82.5% were at high or unclear risk of bias, primarily due to poor reporting of calibration and data handling. Formal metaanalysis was precluded by extreme statistical heterogeneity (I2>98%) and the role of LBW as a surrogate marker for diverse phenotypes. Narrative synthesis indicated that ensemble architectures (Random Forest, XGBoost) consistently outperformed traditional linear models. Discrimination was significantly higher in high-income settings (AUC: 0.85-0.95) than in resource-limited settings (AUC: 0.65-0.75). Models integrating dynamic data, such as longitudinal ultrasound, demonstrated superior sensitivity over those relying on static clinical history. Performance trends across settings were highly variable, and given the heterogeneity, these findings must be considered strictly exploratory. CONCLUSION:AI/ML models show promise for LBW prediction, but their efficacy is strictly contextdependent. Widespread methodological bias and lack of calibration metrics currently limit "bedside readiness." Clinical translation requires a transition toward population-specific, interpretable tools validated through rigorous external cohorts.
Introduction: This study aimed to evaluate the impact of phototherapy on serum calcium, magnesium, and vitamin D levels in term neonates. Methods: This study was conducted in accordance with the PRISMA statement. A comprehensive search of PubMed, Scopus, Web of Science, the Cochrane Library, and the Scientific Information Database (SID) was performed up to August 20, 2025. Pooled effect sizes were calculated as Hedges' g and mean differences (MD) with 95% Confidence Intervals (CIs) using random-effects models. Heterogeneity was assessed using the I2 statistic. Study quality was appraised using the Newcastle- Ottawa Scale, ROBINS-I, and RoB 2 tools, and the certainty of evidence was evaluated per GRADE methodology. Results: Twenty-seven studies were included. Phototherapy was associated with a significant decrease in serum calcium (Hedges' g = -0.67; 95% CI: -0.89 to -0.45; MD: -0.57 mg/dL; 95% CI: - 0.75 to -0.40; 22 studies; 2,406 participants) and magnesium levels (Hedges' g = -1.09; 95% CI: - 1.54 to -0.63; MD: -0.21 mg/dL; 95% CI: -0.33 to -0.10; 10 studies; 863 participants), with considerable heterogeneity observed for both outcomes. Vitamin D levels showed a non-significant overall increase (Hedges' g = 0.40; 95% CI: -0.06 to 0.87; MD: 5.86 nmol/L; 95% CI: -2.06 to 13.77; 7 studies; 517 participants; p = 0.091). The pooled prevalence of hypocalcemia and hypomagnesemia following phototherapy was 26.1% (95% CI: 20.8% to 32.3%) and 23.8% (95% CI: 18.6% to 30.0%), respectively. The certainty of evidence was rated as low for calcium and magnesium, and very low for vitamin D. Discussion: This meta-analysis indicates that phototherapy in term neonates is associated with significant decreases in serum calcium and magnesium, while its effect on vitamin D remains inconclusive. These findings highlight the need for monitoring electrolyte balance in at-risk neonates, although routine supplementation is not currently supported by the evidence. Conclusion: Phototherapy is associated with a significant decrease in calcium and magnesium levels in term neonates. Given the low certainty of evidence, high-quality randomized controlled trials with standardized protocols are warranted to guide clinical practice. PROSPERO registration number: CRD42025638904.
INTRODUCTION:Uniparental disomy (UPD) is a rare chromosomal anomaly causing significant clinical implications in many affected individuals. In the case of UPD, a pair of homologous chromosomes or segments of it is inherited from only one parent. This can disrupt genomic imprinting, create long stretches of homozygosity, leading to diverse genetic and epigenetic syndromes. This scoping review has aimed to summarize postnatally reported UPD cases, tabulate chromosomespecific clinical characteristics, molecular diagnostic methodologies being utilized, and to formulate a standardised diagnostic workflow. MATERIALS AND METHODS:A systematic literature search was conducted in PubMed, Scopus, and Web of Science up to 28 March 2025. Postnatally reported UPD cases were included. Extracted data comprised involved chromosomes, parental origin of disomy, clinical presentation of the affected individuals, and diagnostic approaches utilized. RESULTS:A total of 1507 UPD cases from 632 studies were analysed. UPDs were reported across all chromosomes, with the highest prevalence in chromosomes 11 (24.30%), 15 (18.64%), 7 (13.04%), and 14 (12.11%). The least affected were chromosomes 3, 9, 10, 12, 13, 17, 18, 19, 21, and X (<1% each). Mosaic UPD was identified in 15% of cases. Among the published cases, common clinical features included developmental delay, growth restriction, intellectual disability, and craniofacial dysmorphism. Most frequently employed diagnostic techniques included microsatellite/STR marker analysis, SNP microarray, methylation-specific MLPA, and whole-exome sequencing. DISCUSSION:Among all the chromosomes involved in UPD, the highest clinical relevance is observed in chromosomes 7, 11, 14, and 15. Among the techniques utilized for the detection and confirmation of UPDs, microsatellite/STR analysis is considered the gold standard. For higher efficiency and accuracy, better clinical interpretations, and proper genetic counselling opportunities, an integrated diagnostic workflow strategically targeting both genetic and epigenetic aspects is required. CONCLUSION:In this review, the clinical impact of different types of UPDs involving various chromosomes is highlighted. An integrated (epi/genetic) approach as a diagnostic framework is proposed.
INTRODUCTION:Retinopathy of Prematurity (ROP) is the leading cause of visual morbidity in premature infants. Omega-3 PUFA concentrated in fish oil has been shown to reduce ROP risk through its anti-ischemic, anti-inflammatory, and antioxidant properties. The SMOFlipid formulation is a rich omega‑3 source and may reduce ROP risk. We aimed to compare the ROP incidence and severity in preterm VLBW (<1501 g) infants receiving Intralipid versus SMOFlipid. METHODS:In a single-center, retrospective cohort study, we enrolled 493 preterm VLBW infants born between 2014 and 2022 at < 30 weeks GA and /or <1501g, who received either Intralipid or SMOFlipid, and were examined for ROP. RESULTS:There was no difference between the Intralipid and the SMOFlipid groups in the incidence of ROP (41.8% versus 37.1%, P=0.291) and its severity (P=0.313). Still, the SMOFlipid group had significantly higher rates of Plus (+) disease (P<0.001). Gestational age, birth weight, mode of delivery, use of steroids, length of lipid use, use of inotropes, hyperglycemia requiring insulin, and length of hospitalization were independent predictors of ROP. PDA, sepsis, NEC, BPD, and IVH were also independently associated with ROP on multivariate analysis. DISCUSSION:The study groups were comparable. Despite its omega‑3 content, evidence on SMOFlipid's effect on ROP remains inconsistent. The increased risk of disease suggests other unmeasured factors may influence severe ROP. As the largest study comparing IL and SMOFlipid, the preventive effect of SMOFlipid remains uncertain. CONCLUSION:The impact of SMOFlipid on the incidence and severity of ROP is comparable to that of soy-based lipid emulsions.
OBJECTIVE:The purpose of this article is to investigate the expression of neuropeptide family members and their correlation with inflammatory indicators in the peripheral blood of children infected with COVID-19. METHODS:Blood samples were collected from 40 hospitalized newly diagnosed children with confirmed COVID-19 infection and 17 hospitalized children with non-COVID-19 bronchial pneumonia during the same period. Baseline clinical data were collected and analyzed. Expression and correlation analysis of neuropeptide-related molecules [ACE (Angiotensin Converting Enzyme), ACE2 (Angiotensin Converting Enzyme 2), ASCL1 (achaete-scute family bHLH transcription factor 1)] in peripheral blood were detected and analyzed by ELISA. Complete blood counts with differentials, C-Reactive Protein (CRP), liver enzymes, Substance P (SP), Vasoactive Intestinal Polypeptide (VIP), and Gastrin-Releasing Peptide (GRP) were also measured. RESULTS:The results of 40 COVID-19 patients (43% males) and 17 non-COVID-19 patients (71% males) were compared. ACE2 in non-COVID-19 and moderate COVID-19 groups was higher than that in severe groups (p=0.04; p=0.03, respectively). ASCL1 in the non-COVID-19 group was higher than that in the COVID-19 group (p=0.04). ASCL1 in the non-COVID group was higher than that in the severe COVID group (p=0.02). There were no significant differences in SP, VIP, and GRP between COVID-19 and non-COVID-19 groups. ASCL1 correlated negatively with blood neutrophils (%) (r = -0.534, p<0.001), CRP (r = -0.522, p<0.001), but positively with lymphocytes (%) (r = 0.572, p<0.001), and aspartate aminotransferase (r = 0.496, p=0.001). There was no significant correlation between SCL1 and white blood cell count, platelet count, alanine transaminase, or Lactate dehydrogenase. DISCUSSION:The negative correlation between ASCL1 and neutrophil percentage (N%) and CRP suggests that ASCL1 may modulate the inflammation associated with pediatric COVID-19, positioning it as a potential biomarker and therapeutic target. The study's findings suggest that ASCL1 is downregulated in pediatric COVID-19 and correlates negatively with neutrophil percentage and CRP, indicating a potential regulatory role in COVID-19-related inflammation. Unlike adults, ACE/ACE2 are not highly expressed in children, which may partly explain the milder disease course. ASCL1 may represent a novel biomarker and therapeutic target worthy of further investigation in larger pediatric cohorts. CONCLUSION:Unlike adults, ACE and ACE2 are not highly expressed in children with COVID-19. ASCL1 in children with COVID-19 is lower than that in non-COVID-19 children. ASCL1 is negatively correlated with N% and CRP, suggesting that ASCL1 may have a role in COVID-19 inflammation.
INTRODUCTION:Community-acquired pneumonia (CAP) is a significant contributor to illness and hospitalization among children worldwide. Pediatric CAP continues to provide a challenge to clinicians, despite considerable progress in medical research and immunization initiatives, owing to its varied origin, symptomatology that overlaps with other respiratory illnesses, and evolving microbial patterns. This review aims to (1) consolidate existing knowledge on the etiology and pathogenesis of pediatric CAP, (2) critically assess the significance of emerging biomarkers and diagnostic instruments in clinical decision-making, and (3) delineate modern treatment strategies and preventive measures to enhance patient outcomes. METHODS:From scientific articles published over the last 10 years in different scientific platforms, including PubMed, Scopus, Web of Science, and Google Scholar, potentially relevant literature was compiled to update on biomarkers and innovative diagnostic tools for pediatric CAP. RESULTS:In pediatric CAP, microbial pathogenesis is a critical background metric. Eight biomarkers, including C-reactive protein (CRP), procalcitonin (PCT), the neutrophil-to-lymphocyte ratio (NLR), serum amyloid A (SAA), and S100 proteins, have been reviewed with new diagnostic algorithms and instruments to assess disease severity and prognosis. DISCUSSION:To demonstrate the current status of pediatric CAP diagnosis and therapy, seventeen clinical studies have been included. By integrating clinical expertise and developing efficient treatment strategies, this study offers a comprehensive perspective on improving outcomes for children with CAP. CONCLUSION:Understanding the disease's context is crucial for treatment, research, and prevention. In addition to minimizing diagnostic ambiguity, antibiotic usage, antimicrobial resistance, and biomarker roles and clinical value in pediatric CAP must be addressed.
In India, sexual offenses against children are gender neutralized and addressed by the Protection of Children from Sexual Offences (POCSO) Act of 2012. Still, the medical/legal literature, clinical suspicion, and judicial discourse continue to be implicitly gendered, resulting in poor detection rates of sexual offenses against male children and inadequate interpretation thereof. The available evidence base is consistent in indicating that a large proportion of child sexual abuse victims are males. Social stigma, delayed presentation, and lack of physician knowledge complicate underreporting and diagnosis. Male children present late and mostly without any visible physical injury, making it challenging to interpret and legally prove. This short communication proposes a structured and evidence-based classification of sexual offenses against male children, explicitly in line with the current Indian legal system. The classification includes penetrative sexual assaults, nonpenetrative sexual assaults, sexual harassment, sexual exploitation, and child sexual abuse materials, including aggravated and institutional abuses, in relation to the relevant sections of Bharatiya Nyaya Sanhita. Through the integration of patterns of abuse common in male victims, which include anal/sexual/penetrative abuse, coercive acts, non-contact crimes, and online abuse, with corresponding legal provisions under the POCSO Act, this classification scheme aims to address the gaps between medical diagnosis and legal determination. In addition, the article provides information on major medico-legal concerns, including the mandatory reporting law, the absence of tangible evidence, and the importance of meticulous medical documentation of the history of the abuse, behavioral symptoms, and evidence from the Internet. Collaboration among experts from various disciplines, such as pediatric medicine, forensic science, law enforcement agencies, and child protection services, is also vital. Male children should be considered vulnerable victims, too. With a POCSOoriented and male-friendly classification scheme, improved awareness and understanding in cases of child sexual abuse in India can be achieved.
BACKGROUND:Mitochondrial oxidative phosphorylation (OXPHOS) defects are clinically heterogeneous and often challenging to diagnose. Complex III deficiency caused by UQCRC2 variants is exceptionally rare, with only a limited number of patients described worldwide. Reporting new cases is essential to expand the clinical and molecular landscape of this disorder and to provide insights into potential therapeutic strategies. CASE PRESENTATION:We describe a female patient with UQCRC2-related complex III deficiency who experienced recurrent episodes of metabolic decompensation characterized by hypoglycemia, hyperlactatemia, and renal tubular dysfunction from early childhood. Brain magnetic resonance imaging revealed white matter lesions associated with mild neurological symptoms. During metabolic crises, management included intravenous glucose infusion and strict avoidance of prolonged fasting. At age 15, supplementation with coenzyme Q10 was introduced, followed by complete cessation of hospitalizations and a sustained clinical stabilization. Genetic testing identified compound heterozygosity for a known missense variant and a novel frameshift variant in UQCRC2. A literature review of previously reported cases confirmed the broad clinical variability, ranging from severe neonatal presentations to milder phenotypes with survival into adolescence. CONCLUSION:This case expands the phenotypic spectrum of UQCRC2-related complex III deficiency and suggests that targeted supplementation with coenzyme Q10 may contribute to improved longterm outcomes. Early recognition of metabolic crises, avoidance of fasting, and genetic confirmation are crucial for diagnosis and management. Further reports are needed to clarify genotype-phenotype correlations and to define the therapeutic role of coenzyme Q10 in this rare mitochondrial disorder.
INTRODUCTION:Atopic dermatitis (AD) affects 20% of children, with persistent itching and repeated scratching that may interfere with daily activity and impair quality of life. Given the chronicity of the disease and its significant impact on quality of life, many parents and patients are interested in identifying alternative and "natural" therapies for the prevention and treatment of AD, such as nutritional supplements and dietary modifications. This article provides a narrative overview of dietary and nutritional interventions for the prevention and treatment of AD. METHODS:Using PubMed Clinical Queries with the filter "Therapy," scope "Broad," and the keywords "atopic eczema" and "atopic dermatitis," the following dietary and nutritional interventions from recent meta-analyses and randomized clinical trials in the prevention and treatment of AD in children were reviewed up to May 2025: empirical maternal antigen avoidance, elimination diet in infants, hydrolyzed milk formula, gamma-linolenic acid (GLA), omega-3, vitamin D, vitamin E, and probiotics. RESULTS:There is evidence that patients with AD have lower serum 25(OH) vitamin D levels, but maternal vitamin D supplementation does not decrease the risk of AD in offspring. For treatment, there is some evidence suggesting that vitamin D can decrease disease severity. There is no strong evidence supporting the use of GLA, omega-3, vitamin E, or other micronutrient supplementation for the prevention or treatment of AD. Evidence regarding the use of probiotics is limited by methodological issues in meta-analyses attempting to pool studies that use different strains and species. DISCUSSION:Given the chronic nature of the disease and its significant impact on quality of life, many patients and parents are interested in alternative and "natural" therapies for AD, such as nutritional supplements and dietary modifications. There is substantial interest in primary prevention of AD, particularly through maternal and perinatal nutritional interventions. Some probiotics show a modest reduction in AD incidence, and formulations containing multiple bacterial strains appear to be more effective. The use of blood-specific IgE or skin prick tests to guide dietary exclusions with the goal of improving disease severity or control remains controversial, with very limited evidence of benefit. CONCLUSION:Many patients and parents are interested in alternative therapies such as nutritional supplements and dietary modifications due to the chronic, non-curable nature of AD and its associated quality-of-life impairment. There is also considerable interest in primary prevention through maternal and perinatal nutritional interventions, although strong evidence of efficacy is lacking. Some probiotics demonstrate beneficial effects with modest reductions in the rate of AD.
BACKGROUND:Over-the-counter (OTC) antidiarrheal medications are commonly used despite potential risks for diarrheal management in children. We aimed to assess the reported suspected adverse events associated with OTC antidiarrheals from the FDA Adverse Event Reporting System (FAERS). METHODS:We conducted a disproportionality analysis of suspected adverse event reports pertaining to commonly used antidiarrheals in the pediatric age group (aged < 16 years) as follows: bismuth subsalicylate, diphenoxylate, atropine/diphenoxylate, kaolin, pectin, and loperamide. Spontaneous reports from the FAERS database between March 2004 and June 2024 were obtained and analyzed using frequentist and Bayesian signal detection criteria to identify potential safety signals. RESULTS AND DISCUSSION:Loperamide accounted for the highest number of reports (n=256) of the total 311. Cardiac conduction abnormalities, lethargy, paralytic ileus, and fatalities with loperamide, and central nervous system adverse events with diphenoxylate and atropine/diphenoxylate were the key safety signals identified. Significantly higher mortality rates were observed with diphenoxylate and atropine/diphenoxylate compared to loperamide and bismuth subsalicylate (p = 0.00001). These findings are broadly consistent with existing clinical and regulatory literature and support existing recommendations cautioning against the routine use of certain antidiarrheal agents in young children. CONCLUSION:We identified significant risks associated with OTC antidiarrheal use in children. This emphasizes the need for caution among healthcare providers and caregivers. Judicious use is recommended in the pediatric age group, considering the potential severity of these adverse events. Continued pharmacovigilance is essential to ensure the safety of pediatric patients.
INTRODUCTION:The aim of the study was to investigate scientific evidence related to the protocols and effects of PEPs using theoretical and practical approaches and physical activity in school environments. METHODS:This systematic review was conducted according to the PRISMA guidelines and registered on the PROSPERO platform. The search was conducted in five electronic databases until December 2024. Randomized controlled clinical trials, non-randomized clinical trials, and quasi-experimental, interventional, and longitudinal studies published over the last 10 years were included. The studies involved children and adolescents with typical development, participating in postural education interventions in school environments that involved physical activity. Methodological quality was assessed using the PEDro Scale, and the risk of bias was evaluated using ROB 2_cluster and ROBINSI. RESULTS:From 1,147 identified records, 11 studies met the eligibility criteria, involving 35-4,695 participants aged 5-16 years. While most studies reported improvements in postural knowledge and health education, findings on postural habits, pain reduction, and muscular endurance were inconsistent. Randomized clinical trials and most other studies exhibited good and reasonable methodological qualities, respectively. High and moderate risks of bias were prevalent. DISCUSSION:Variability in assessment methods, interventions, and physical activity components limits standardization, yet studies aim to prevent postural changes and promote postural care to improve health in children and adolescents. CONCLUSION:PEPs incorporating physical activity show promise in improving postural knowledge, though evidence on long-term benefits for low back pain and postural behaviors remains inconclusive. Future research should standardize protocols and assess sustained outcomes.
Managing parental food avoidance anxiety and concerns about their children, especially those with atopic disease, can be challenging and, at times, frustrating. The purpose of this article is to describe the usage of a simple schematic algorithm to counsel food-phobic parents. Anonymized brief cases are described to illustrate the utility of the EAT graphic algorithm, which is designed to counsel parents in managing concerns about food-avoidance anxiety. The application of the EAT algorithm in five diverse cases successfully guided dietary decisions, reduced unnecessary food avoidance, and aligned parental management with clinical evidence. The EAT algorithm provides an easy-to-understand visual schematic that can empower clinicians to counsel parents effectively, potentially reducing unnecessary testing and promoting a more normalized diet.
INTRODUCTION:Neonatal sepsis (NS) is a leading cause of morbidity and mortality in newborns, particularly in developing countries, where early and accurate diagnosis remains challenging. Conventional sepsis markers, such as C-reactive protein (CRP) and hematological indices, lack sensitivity and specificity. This study aimed to evaluate serum apolipoproteinA (Apo A) and apolipoprotein B (Apo B) as potential diagnostic biomarkers in neonatal sepsis. METHODS:This case-control study included 160 neonates with sepsis (confirmed by clinical assessment, sepsis screening, and blood culture) and 80 healthy neonates as controls. Patients were classified by sepsis severity (sepsis vs. severe sepsis) and onset (early vs. late). Serum Apo A and Apo B titres were measured using an enzyme-linked immunosorbent assay. RESULTS:Serum Apo A was significantly lower in septic neonates than in controls (p < 0.001), with the lowest titres observed in severe sepsis. Apo B was significantly elevated in septic neonates, particularly in severe cases (p < 0.001). Apo A, at a cut-off of ≤57.6 mg/dL, yielded 80% sensitivity, 90% specificity, and an area under the curve (AUC) of 0.939, whereas Apo B, at a cut-off of >7.98 mg/dL, yielded 99.4% sensitivity, 75% specificity, and an AUC of 0.998. Apo A negatively correlated with hematocrit, WBC count, and neutrophil shift, while Apo B showed a negative correlation with hematocrit (p < 0.05). DISCUSSION:Data suggest that the relationship between apolipoprotein levels and sepsis can also provide insights into inflammatory pathways associated with neonatal infections. Increased understanding of these pathways can inform the therapeutic approaches, in which the modulation of lipid metabolism becomes fundamental to managing sepsis results. Therefore, the incorporation of monitoring Apo A and Apo B levels can serve as pragmatic biomarkers to evaluate not only the presence of sepsis but also the potential response to treatment protocols, thus advancing the path toward Personalized Medicine in the Neonatal Intensive Care Unit. CONCLUSION:Serum Apo A and Apo B titres are valuable adjunct diagnostic markers for NS. Apo A reduction reflects the acute-phase response, while Apo B elevation may indicate altered lipid metabolism in severe infection.
The intestine plays a central role in the immune system, continuously interacting with antigens, dietary components, and the microbiota. Intestinal immune processes are increasingly recognized for their influence on the development of both local and systemic diseases, with long-term effects on health and disease progression. This review provides an overview of intestinal development, encompassing its maturation from conception, temporal changes, regenerative capacity, interactions with the microbiota, and involvement in disease. Early life, particularly critical periods such as pregnancy and lactation, may represent a "window of opportunity," establishing lasting conditions that either increase disease risk or confer protection in adulthood. Understanding the regulatory factors, regional and temporal variations, and existing knowledge gaps is essential for guiding clinical practice, as well as for the prevention and treatment of diseases.
Pierson syndrome (PS) is a rare autosomal recessive disorder, primarily characterized by (1) congenital nephrotic syndrome, (2) ocular abnormalities, and (3) neurodevelopmental deficits. It is caused by mutations in the LAMB2 gene, which encodes the laminin β2 chain-a protein subunit that is part of a specific group of proteins known as laminins. These proteins are present in the glomerular basement membrane, neuromuscular junctions, and ocular structures. Although PS exhibits a wide spectrum of phenotypic presentations, the prognosis remains poor, with most patients not surviving beyond early childhood. Despite its rarity, PS is clinically significant due to its potential to cause end-stage kidney disease early in life. This review consolidates the latest insights into the etiopathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of PS.
INTRODUCTION:Total parenteral nutrition (TPN) is essential for growth in very-low-birthweight (VLBW) infants. The worldwide variation in TPN dosing strategies warrants investigation. This study compared clinical outcomes of aggressive, rapid-increase, and standard TPN dosing strategies in VLBW infants. METHODS:A systematic review and network meta-analysis were conducted following the PRISMA NMA guideline. Searches were performed in PubMed, Scopus, Web of Science, CINAHL, CENTRAL, and ProQuest. Dosing strategies were classified as aggressive (higher starting dose), rapid-increase (standard start with rapid escalation), and standard (NICE-based). Outcomes were analyzed using a Frequentist model in RStudio v4.4.1. RESULTS:Nine randomized controlled trials were included. Compared with aggressive and standard strategies, the rapid-increase strategy was associated with a shorter time to regain birth weight (MD = -1.43 days; 95% CI -2.82 to -0.05; P-score = 0.80). The rapid-increase strategy was also associated with a shorter length of hospitalization (MD = -0.38 days; 95% CI -6.56 to 5.80; P-score = 0.54). Regarding safety outcomes, the rapid-increase strategy had the lowest proportions of mortality (Prop = 0.043), retinopathy (Prop = 0.124), and sepsis (Prop = 0.141), but a higher proportion of patent ductus arteriosus (PDA) (Prop = 0.508). DISCUSSION:The rapid-increase approach demonstrated the most favorable balance between efficacy and safety outcomes among the included trials, although the small number of studies is a limitation. CONCLUSION:Rapid-increase TPN, using the recommended starting dose but achieving maintenance more quickly, may offer clinical advantages for VLBW infants. Further long-term studies are needed to confirm developmental and metabolic impacts.
INTRODUCTION:Hirschsprung's (HIRSH-sproongz) disease is a multifactorial disorder characterized by the failure of enteric nervous system (ENS) development and is associated with loss-of-function variants, primarily in the RET gene. Rearranged during transfection (RET) expression is tightly regulated within a complex gene regulatory network (GRN) involving many transcription factors, such as GATA2. Aberrant DNA methylation in GATA2 may indicate a reduced enhancer activity, resulting in the silencing of RET and contributing to the failure of ENS development in HIRSH. However, the epigenetic mechanisms underlying these processes have yet to be established. METHOD:We analyzed the GATA2 mRNA expression and DNA methylation levels in colonic tissues from the HIRSH patients and controls using quantitative polymerase chain reaction (qPCR) and methylation-specific quantitative PCR (MSP-qPCR). HIRSH tissues, including aganglionic and ganglionic segments, were obtained during pull-through surgery. In addition, control tissues were collected from patients with anorectal malformation (ARM) undergoing definitive surgery, and no clinical evidence of ENS issues was found. RESULTS:Our study contained 27 unrelated HIRSH patients (20 males and seven females) and 20 controls (12 males and eight females). GATA2 expression was significantly increased in HIRSH than in control colon (ganglionic: 11.78 ± 0.97 vs. 12.59 ± 0.46; p=0.049; aganglionic: 11.94 ± 0.63 vs. 12.59 ± 0.46; p=0.030). In addition, the percentage of methylation was higher in the HIRSH patients than in the control (60.71 ± 2.94% [ganglionic] vs. 79.55 ± 1.79% [aganglionic] vs. 40.43 ± 3.67% [control]). DISCUSSION:Overexpression of GATA2 in our subjects may indicate a compensatory mechanism for the loss of other TFs within RET-EDNRB or other HIRSH-associated GRN, as an in vitro study has shown that loss of GATA1 in mouse embryonic stem cells results in a marked increase of GATA2 expression, implying potential interchangeability or compensatory mechanism of GATA TFs in RET GRN. Several mechanisms on how specific DNA hypermethylation pathways can lead to upregulated gene expression have been proposed, including facilitating transcription in gene bodies by suppressing cryptic promoters and protecting the borders of promoters or enhancers against unwanted expansion or contraction. CONCLUSIONS:We demonstrated aberrant expression and methylation of GATA2 in the HIRSH patients. The findings of this study also indicate that GATA2 hypermethylation is associated with increased GATA2 expression, contradicting the established inverse association between DNA methylation and transcriptional activity. This may indicate a distinctive interplay between the epigenetics of GATA2 and RET GRN in the context of HIRSH.
