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24 pages, 511 KiB  
Article
The Effects of a Reproductive Health Voucher Program on Out-of-Pocket Family Planning and Safe Motherhood Service Expenses: A Yemeni Study
by Omar Z. Al-Sakkaf, El-Morsy A. El-Morsy, Shaimaa A. Senosy, Al Shaimaa Ibrahim Rabie, Ahmed E. Altyar, Rania M. Sarhan, Marian S. Boshra and Doaa M. Khalil
Healthcare 2025, 13(13), 1591; https://doi.org/10.3390/healthcare13131591 - 3 Jul 2025
Viewed by 424
Abstract
Background/Objectives: Using healthcare vouchers mitigates the financial burdens of low-income individuals, therefore enhancing mothers’ satisfaction and encouraging service utilization. In Yemen, reducing financial barriers results in marked improvement in reproductive health services utilization for mothers and their newborns. Such financial strain can be [...] Read more.
Background/Objectives: Using healthcare vouchers mitigates the financial burdens of low-income individuals, therefore enhancing mothers’ satisfaction and encouraging service utilization. In Yemen, reducing financial barriers results in marked improvement in reproductive health services utilization for mothers and their newborns. Such financial strain can be addressed through reproductive health vouchers, which reduce out-of-pocket expenses of family planning, pregnancy, birth, postnatal care and neonatal care. This study compares the Safe Motherhood and Family Planning Voucher Program in the Lahj governorate to the non-voucher program in the Abyan governorate in terms of enhancement of reproductive healthcare accessibility and use. Methods: This facility-based, quantitative, comparative, cross-sectional study was conducted in the Lahj governorate, which supports the Safe Motherhood and Family Planning Voucher Program, and the Abyan governorate, which does not. Results: The voucher-supported program has greatly improved mothers’ satisfaction, access, and use of all reproductive health services by covering transportation, covering lodging during hospitalization, and providing free reproductive treatments. Compared to Abyan mothers, Lahj governorate mothers more frequently used rental vehicles (paid for by the voucher program) and free reproductive health services (p-value < 0.001). Lahj governorate mothers (who used the vouchers) used family planning, prenatal care, facility-based delivery, home delivery by competent birth staff, cesarean section, postnatal care, and neonatal care more frequently than Abyan governorate mothers. A health institution which supported the Safe Motherhood and Family Planning Voucher Program (SMHFPVP) provided prenatal care (98.5%), competent birth services (99.0%), and modern contraceptive use (92.3%)—oral contraceptive pills, implants, injectables, contraceptive patches, vaginal rings, and intrauterine devices—for mothers who were interviewed and attended the targeted HFs in the Lahj governorate, compared with (77.6%), (80.3%), and (67.8%), respectively, for mothers in Abyan governorate who were not supported by the SMHFPVP. This study demonstrates substantially higher satisfaction levels among voucher-using mothers in the Lahj governorate compared to those in the Abyan governorate, across all satisfaction domains and overall satisfaction scores. Conclusions: This study found that women without access to maternal health vouchers experienced worse prenatal, natal, and postnatal care and were less satisfied with healthcare services compared with women who used vouchers. Full article
(This article belongs to the Section Family Medicine)
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10 pages, 232 KiB  
Article
Impact of the COVID-19 Pandemic on Emergency Air Medical Transport of Pediatric Patients in the Penghu Islands
by Hung-Hsiang Fang, Chuang-Yen Huang, Po-Chang Hsu, Chia-Cheng Sung, Sheng-Ping Li and Chung-Yu Lai
Healthcare 2025, 13(12), 1450; https://doi.org/10.3390/healthcare13121450 - 17 Jun 2025
Viewed by 438
Abstract
Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted healthcare systems worldwide. As a result, remote areas such as the Penghu Islands have encountered unique challenges related to pediatric care. This study examined the effects of the pandemic on the emergency [...] Read more.
Background and Objectives: The coronavirus disease 2019 (COVID-19) pandemic significantly impacted healthcare systems worldwide. As a result, remote areas such as the Penghu Islands have encountered unique challenges related to pediatric care. This study examined the effects of the pandemic on the emergency air medical transport (EAMT) of pediatric patients from the Penghu Islands to Taiwan. Materials and Methods: This retrospective study analyzed 40 pediatric patients who received EAMT from the Penghu Islands to Taiwan between January 2017 and December 2022. This study compared patients before and during the COVID-19 pandemic and focused on patient demographics, reasons for EAMT, and clinical outcomes. Due to the small sample size, non-parametric statistical methods were applied, including the Mann–Whitney U-test for continuous variables and Fisher’s exact test for categorical variables. Results: Among the 40 pediatric patients analyzed, the median age decreased from 3 years (IQR, 0–5 years) before the pandemic to 1 year (IQR, 0–5 years) during the pandemic. While the overall increase in hospital length of stay during the pandemic was not statistically significant, a significant prolongation was observed in preschool-aged children and neonates without trauma (20 days vs. 9 days; p < 0.05). The lack of specialist physicians became an increasingly prominent factor for EAMT during the pandemic (p = 0.056). The most common medical reasons for EAMT were critical illness (35%), neonatal diseases (30%), and neurological conditions (27.5%), with similar distributions across both time periods. Conclusions: The COVID-19 pandemic heightened existing healthcare disparities in the Penghu Islands, particularly by increasing reliance on EAMT due to a shortage of pediatric specialists. Hospital stays for preschool children and neonates significantly increased during the pandemic, suggesting delayed or prolonged care. These findings underscore the need to strengthen local pediatric infrastructure, decentralize specialist services, and improve emergency preparedness to better support vulnerable populations in remote areas during future public health emergencies. Full article
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21 pages, 2080 KiB  
Article
The Individual Variations in Sperm Quality of High-Fertility Boars Impact the Offspring Production and Early Physiological Functions
by Santa María Toledo-Guardiola, Chiara Luongo, Felipe Martínez-Pastor, Cristina Soriano-Úbeda and Carmen Matás
Vet. Sci. 2025, 12(6), 582; https://doi.org/10.3390/vetsci12060582 - 13 Jun 2025
Viewed by 1153
Abstract
Artificial insemination (AI) is essential in intensive pig production, which significantly depends on semen quality from boars selected for health, genetics, and fertility. While AI aims to improve productivity, larger litters often result in smaller and less resistant piglets. Beyond fertility and genetic [...] Read more.
Artificial insemination (AI) is essential in intensive pig production, which significantly depends on semen quality from boars selected for health, genetics, and fertility. While AI aims to improve productivity, larger litters often result in smaller and less resistant piglets. Beyond fertility and genetic traits, boars also influence offspring health. This study investigated the relationship between sperm parameters of highly fertile boars and both reproductive outcomes and piglet physiological indicators. Multivariate analysis revealed significant paternal effects on blood markers reflecting organ function, including those of the pancreas, liver, and kidneys, as well as on glucose homeostasis, lipid metabolism, oxidative stress, protein and carbohydrate metabolism, muscle contraction, and neural signaling. Notably, sperm velocity was correlated with mitochondrial function, which is crucial for sperm motility, capacitation, DNA integrity, and embryo development—factors likely linked to healthier, more resilient offspring. Boars transmitting superior sperm velocity, erythropoiesis efficiency, and oxygen transport capacities produced piglets with better glucose regulation, growth, and resistance to neonatal hypoglycemia. These findings underscore the broader impact of sperm quality on offspring vitality and suggest that advanced sperm analysis could improve boar selection and enable more effective, health-oriented breeding strategies. Full article
(This article belongs to the Special Issue Sperm Biotechnology in Animals Reproduction—2nd Edition)
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18 pages, 758 KiB  
Review
Clinical Implications and Preventive Strategies for Neonatal and Infant Hypovitaminosis D: Analysis and Comparison of Current Evidence
by Vittorio Ferrari, Giacomo Biasucci, Egidio Candela, Rita Ortolano, Federico Baronio and Marcello Lanari
Endocrines 2025, 6(2), 21; https://doi.org/10.3390/endocrines6020021 - 7 May 2025
Viewed by 910
Abstract
Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and [...] Read more.
Background: Vitamin D is essential for neonatal health, with maternal vitamin D status crucial in fetal development and neonatal outcomes. During pregnancy, vitamin D is transferred to the fetus via the placenta, forming an initial reserve. Postnatally, neonates rely on maternal levels and supplementation due to limited sunlight exposure and immature skin synthesis. Objectives: This review evaluates neonatal vitamin D deficiency’s causes and clinical consequences, emphasizing its impact on newborn and infant health. Results: Maternal vitamin D levels strongly correlate with neonatal 25(OH)D concentrations, influencing birth weight, bone development, and overall health. Supplementation during pregnancy reduces the risk of severe deficiencies and rickets, particularly in exclusively breastfed infants who require daily supplementation of 400 IU. Formula-fed infants typically meet requirements through fortified formulas. Preterm infants are at a higher risk of complications like osteopenia and rickets, with mixed evidence on the effectiveness of higher supplementation doses. Vitamin D is critical in skeletal development, immune function, and protection against respiratory infections such as bronchiolitis and pneumonia. Deficiency is associated with respiratory distress syndrome (RDS), atopic dermatitis, and impaired bone mineralization due to reduced placental calcium transport. Conclusions: Vitamin D deficiency during pregnancy and infancy has significant clinical implications, including impaired skeletal and immune development. Maternal and neonatal supplementations are critical to prevent deficiencies, particularly in high-risk groups such as preterm and breastfed infants. Targeted strategies are essential to improve neonatal health outcomes and prevent complications. Full article
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15 pages, 539 KiB  
Review
Reducing Neonatal Mortality in Nepal’s Remote Regions: A Narrative Review of Challenges, Disparities, and the Role of Helping Babies Breathe (HBB)
by Victoria Jane Kain, Ranjan Dhungana and Animesh Dhungana
Pediatr. Rep. 2025, 17(2), 48; https://doi.org/10.3390/pediatric17020048 - 17 Apr 2025
Viewed by 710
Abstract
Background: Nepal’s diverse geography creates significant challenges for healthcare accessibility, particularly for neonatal care. Rural areas, especially in the mountainous regions, face severe healthcare gaps due to isolation, inadequate infrastructure, and a shortage of skilled staff. Strengthening healthcare in these underserved regions is [...] Read more.
Background: Nepal’s diverse geography creates significant challenges for healthcare accessibility, particularly for neonatal care. Rural areas, especially in the mountainous regions, face severe healthcare gaps due to isolation, inadequate infrastructure, and a shortage of skilled staff. Strengthening healthcare in these underserved regions is essential to reducing neonatal mortality. Helping Babies Breathe (HBB) is a neonatal resuscitation training program designed to reduce neonatal mortality due to birth asphyxia in low-resource settings. Methods: A comprehensive literature search identified studies on neonatal mortality and interventions, particularly HBB, which were analyzed using a narrative synthesis approach. This review examines disparities in neonatal health outcomes, regional differences, and barriers to healthcare access. Findings: This review identifies key themes related to healthcare disparities, neonatal mortality, and birth outcomes in Nepal’s remote regions. Geographical isolation, inadequate healthcare infrastructure, and cultural barriers contribute to persistently high neonatal mortality, particularly in mountainous areas such as Jumla and Dolpa, where rates exceed 60 per 1000 live births. HBB has shown a significant impact, reducing neonatal mortality by up to 60% when effectively implemented. However, infrastructural gaps, lack of emergency transport, and the uneven distribution of skilled birth attendants (SBAs) remain critical challenges. Addressing these disparities requires expanded training, increased availability of neonatal resuscitation equipment, and culturally sensitive healthcare strategies. Full article
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8 pages, 1739 KiB  
Case Report
Neonatal Air Transport of Thoraco-Omphalopagus Conjoined Twins: A Case of Adaptation and Multidisciplinary Coordination
by Bogdan Oprita, Teodor Nicolae Berea and Ruxandra Oprita
Children 2025, 12(4), 423; https://doi.org/10.3390/children12040423 - 28 Mar 2025
Viewed by 450
Abstract
Background: The emergency transport of thoraco-omphalopagus conjoined twins is a rare occurrence in the medical field of emergency medicine with no specific guidelines on which medical personnel can rely upon. We present to you the case of the transport of thoraco-omphalopagus conjoined [...] Read more.
Background: The emergency transport of thoraco-omphalopagus conjoined twins is a rare occurrence in the medical field of emergency medicine with no specific guidelines on which medical personnel can rely upon. We present to you the case of the transport of thoraco-omphalopagus conjoined twins. Methods: Important changes were made to the configuration of the aircraft as to provide adequate ventilation (one twin ventilated manually with an ABV while the other benefiting from mechanical ventilation) and hemodynamic stability. Results: The team successfully orchestrated the transfer with no complications arriving during the transfer with the twins benefiting from specialized care in the intended tertiary care center. Conclusions: Our paper highlights the importance for innovative approaches in adapting neonatal transport equipment, including ventilation and monitoring for two critically ill patients in a space designed for one, all that underscores the importance of tailored neonatal transport solutions. Full article
(This article belongs to the Section Pediatric Neonatology)
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11 pages, 662 KiB  
Brief Report
ECMO Support in Pediatric Populations with the Newborn ECMOLife Centrifugal Pump
by Carlo Pace Napoleone, Ignazio Condello, Maria Teresa Cascarano, Enrico Aidala, Licia Peruzzi, Isabella Molinari, Cristina Rivoldini, Maria Stella Di Carlo, Stefania Iannandrea and Enrico Bonaveglio
Medicina 2025, 61(3), 493; https://doi.org/10.3390/medicina61030493 - 13 Mar 2025
Viewed by 854
Abstract
Background and Objectives: Pediatric ECMO is a valid support mechanism for refractory cardiac and/or respiratory failure. Magnetic levitation technology applied to the centrifugal pump has reduced the hemolysis caused by this procedure, which can be particularly dangerous, especially in neonates and small [...] Read more.
Background and Objectives: Pediatric ECMO is a valid support mechanism for refractory cardiac and/or respiratory failure. Magnetic levitation technology applied to the centrifugal pump has reduced the hemolysis caused by this procedure, which can be particularly dangerous, especially in neonates and small children. ECMOLife, a new magnetic levitation centrifugal pump, has been introduced for these patients. Materials and Methods: Four patients were supported with the ECMOLife System in a newborn setting, with veno-venous application in two cases and veno-arterial in the other two. All parameters related to pump functioning, anticoagulation, hemolysis, and inflammation were recorded for the duration of the support. Results: All patients survived the procedure, in three cases achieving recovery, while one veno-arterial ECMO was switched to VAD, and then the patient underwent heart transplantation. All recorded parameters were compatible with clinical conditions. In particular, free haemoglobin was close to 0 g/L in all recorded samples. The possibility of monitoring pump functioning parameters, venous and arterial O2 saturation, and venous and arterial pressures creates an opportunity to check the adequacy of mechanical support for the clinical condition of the patient. Conclusions: This is the first reported experiment in a newborn setting with ECMOLife mechanical support. At present, ECMOLife represents the only system with a newborn and pediatric pump, allowing for the continuous monitoring of perfusion and hemodynamic parameters, with a large number of facilities for transportation available. Full article
(This article belongs to the Section Pediatrics)
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22 pages, 2256 KiB  
Article
Mild Zika Virus Infection in Mice Without Motor Impairments Induces Working Memory Deficits, Anxiety-like Behaviors, and Dysregulation of Immunity and Synaptic Vesicle Pathways
by Jaime Alexander Chivatá-Ávila, Paola Rojas-Estevez, Alejandra M. Muñoz-Suarez, Esthefanny Caro-Morales, Aura Caterine Rengifo, Orlando Torres-Fernández, Jose Manuel Lozano and Diego A. Álvarez-Díaz
Viruses 2025, 17(3), 405; https://doi.org/10.3390/v17030405 - 12 Mar 2025
Viewed by 1092
Abstract
Background: The Zika virus (ZIKV) is an arbovirus linked to “Congenital Zika Syndrome” and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go [...] Read more.
Background: The Zika virus (ZIKV) is an arbovirus linked to “Congenital Zika Syndrome” and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go unnoticed in neonates, resulting in long-term social and academic difficulties. Murine models of ZIKV infection can be used to mimic part of the spectrum of motor and cognitive deficits observed in humans. These can be evaluated through behavioral tests, enabling comparison with gene expression profiles and aiding in the characterization of ZIKV-induced NDDs. Objectives: This study aimed to identify genes associated with behavioral changes following a subtle ZIKV infection in juvenile BALB/c mice. Methods: Neonatal mice were subcutaneously inoculated with ZIKV (MH544701.2) on postnatal day 1 (DPN) at a dose of 6.8 × 103 PFU. Viral presence in the cerebellum and cortex was quantified at 10- and 30-days post-infection (DPI) using RT-qPCR. Neurobehavioral deficits were assessed at 30 DPI through T-maze, rotarod, and open field tests. Next-Generation Sequencing (NGS) was performed to identify differentially expressed genes (DEGs), which were analyzed through Gene Ontology (GO) and KEGG enrichment. Gene interaction networks were then constructed to explore gene interactions in the most enriched biological categories. Results: A ZIKV infection model was successfully established, enabling brain infection while allowing survival beyond 30 DPI. The infection induced mild cognitive behavioral changes, though motor and motivational functions remained unaffected. These cognitive changes were linked to the functional repression of synaptic vesicles and alterations in neuronal structure, suggesting potential disruptions in neuronal plasticity. Conclusions: Moderate ZIKV infection with circulating strains from the 2016 epidemic may cause dysregulation of genes related to immune response, alterations in cytoskeletal organization, and modifications in cellular transport mediated by vesicles. Despite viral control, neurocognitive effects persisted, including memory deficits and anxiety-like behaviors, highlighting the long-term neurological consequences of ZIKV infection in models that show no apparent malformations. Full article
(This article belongs to the Special Issue Arboviral Lifecycle 2025)
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21 pages, 2755 KiB  
Review
The Triad of Blood–Brain Barrier Integrity: Endothelial Cells, Astrocytes, and Pericytes in Perinatal Stroke Pathophysiology
by Tania Garcia-Martínez, Denise G. Gornatti, Marina Ortiz, Guillem Cañellas, Damià Heine-Suñer and Cristòfol Vives-Bauzà
Int. J. Mol. Sci. 2025, 26(5), 1886; https://doi.org/10.3390/ijms26051886 - 22 Feb 2025
Cited by 1 | Viewed by 3721
Abstract
Pediatric stroke, a significant cause of long-term neurological deficits in children, often arises from disruptions within neurovascular unit (NVU) components. The NVU, a dynamic ensemble of astrocytes, endothelial cells, pericytes, and microglia, is vital for maintaining cerebral homeostasis and regulating vascular brain development. [...] Read more.
Pediatric stroke, a significant cause of long-term neurological deficits in children, often arises from disruptions within neurovascular unit (NVU) components. The NVU, a dynamic ensemble of astrocytes, endothelial cells, pericytes, and microglia, is vital for maintaining cerebral homeostasis and regulating vascular brain development. Its structural integrity, particularly at the blood–brain barrier (BBB), depends on intercellular junctions and the basement membrane, which together restrict paracellular transport and shield the brain from systemic insults. Dysfunction in this intricate system is increasingly linked to pediatric stroke and related cerebrovascular conditions. Mutations disrupting endothelial cell adhesion or pericyte–endothelial interactions can compromise BBB stability, leading to pathological outcomes such as intraventricular hemorrhage in the germinal matrix, a hallmark of vascular brain immaturity. Additionally, inflammation, ferroptosis, necroptosis, and autophagy are key cellular processes influencing brain damage and repair. Excessive activation of these mechanisms can exacerbate NVU injury, whereas targeted therapeutic modulation offers potential pathways to mitigate damage and support recovery. This review explores the cellular and molecular mechanisms underlying NVU dysfunction, BBB disruption, and subsequent brain injury in pediatric stroke. Understanding the interplay between genetic mutations, environmental stressors, and NVU dynamics provides new insights into stroke pathogenesis. The susceptibility of the germinal matrix to vascular rupture further emphasizes the critical role of NVU integrity in early brain development. Targeting inflammatory pathways and cell death mechanisms presents promising strategies to preserve NVU function and improve outcomes for affected neonates. Full article
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12 pages, 1947 KiB  
Article
Neonatal Emergency Transport Organisation and Activities in Italy—The Nationwide 2023 Survey by the Neonatal Transport Study Group of the Italian Society of Neonatology
by Carlo Bellini, Maurizio Gente, Diego Minghetti and on behalf of the Neonatal Transport Study Group of the Italian Society of Neonatology
Children 2025, 12(2), 162; https://doi.org/10.3390/children12020162 - 29 Jan 2025
Cited by 1 | Viewed by 972
Abstract
Background: The regionalisation of perinatal care emphasises the importance of transferring high-risk pregnancies “in utero” to minimise risks; yet, neonatal inter-facility transport remains necessary. Neonatal Emergency Transport Services (NETSs) play a crucial role in reducing transportation risks, especially for very preterm infants. [...] Read more.
Background: The regionalisation of perinatal care emphasises the importance of transferring high-risk pregnancies “in utero” to minimise risks; yet, neonatal inter-facility transport remains necessary. Neonatal Emergency Transport Services (NETSs) play a crucial role in reducing transportation risks, especially for very preterm infants. Italy’s healthcare system, which is decentralised in nature, leads to variations in NETS organisation and resources across the country, resulting in disparities in access and quality of care. Methods: A questionnaire regarding neonatal transfer practices and NETS activity was sent to the 55 NETSs operating in twenty Italian regions. Demographic data were obtained from the Italian National Statistical Institute (ISTAT). Results: Survey Overview. A 2022 national survey by the Italian Society of Neonatology aimed to assess the status of NETS in Italy, achieving a 100% response rate from the 55 NETS. The 2022 data highlighted the transport of 6494 neonatal, of which 92% were primary transports (transferred to higher-level care) and 553 were back-transports (returning stabilised neonates to lower-level care). Subgroup analysis identified 544 transports of neonates born at 30–34 weeks of gestation and 305 transports of neonates born at under 30 weeks of gestation. This was shown to have regional variability. NETS coverage: 18 regions have full NETS coverage. Sicily offers partial coverage. Sardinia, despite an approved plan, lacks an operational NETS. Operational models: all NETS provide a 24/7 service; 50 NETSs rely on an on-call basis using NICU staff for transport. Only five NETS have dedicated teams exclusively for neonatal transport. This decentralisation results in heterogeneity in service availability, access, and quality. Conclusions: This study highlights that although differences still exist, the NETS in Italy is adequately structured and effective. The presence of NETS operating with limited transport volumes puts a strain on maintaining skilled staff and cost-effective operations. Regional disparities: inequities in NETS access (e.g., in Sicily and Sardinia regions) underline the need to improve regional collaboration. While Italy has made progress in organising NETS, regional discrepancies persist in access and service quality, reflecting the decentralised nature of its healthcare system. Full article
(This article belongs to the Section Pediatric Neonatology)
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22 pages, 5316 KiB  
Article
Impaired Molecular Mechanisms Contributing to Chronic Pain in Patients with Hidradenitis Suppurativa: Exploring Potential Biomarkers and Therapeutic Targets
by Uppala Radhakrishna, Murali R. Kuracha, Iltefat Hamzavi, Nazia Saiyed, Jignesh Prajapati, Rakesh M. Rawal, Lavanya V. Uppala, Giovanni Damiani, Uppala Ratnamala and Swapan K. Nath
Int. J. Mol. Sci. 2025, 26(3), 1039; https://doi.org/10.3390/ijms26031039 - 25 Jan 2025
Cited by 1 | Viewed by 2355
Abstract
Hidradenitis suppurativa (HS) is a chronic skin condition that primarily affects areas with dense hair follicles and apocrine sweat glands, such as the underarms, groin, buttocks, and lower breasts. Intense pain and discomfort in HS have been commonly noted, primarily due to the [...] Read more.
Hidradenitis suppurativa (HS) is a chronic skin condition that primarily affects areas with dense hair follicles and apocrine sweat glands, such as the underarms, groin, buttocks, and lower breasts. Intense pain and discomfort in HS have been commonly noted, primarily due to the lesions’ effects on nearby tissues. Pain is a factor that can influence DNA methylation patterns, though its exact role in HS is not fully understood. We aim to identify molecular markers of chronic pain in HS patients. We performed DNA methylome of peripheral blood DNA derived from a group of 24 patients with HS and 24 healthy controls, using Illumina methylation array chips. We identified 253 significantly differentially methylated CpG sites across 253 distinct genes regulating pain sensitization in HS, including 224 hypomethylated and 29 hypermethylated sites. Several genes with pleiotropic roles include transporters (ABCC2, SLC39A8, SLC39A9), wound healing (MIR132, FGF2, PDGFC), ion channel regulators (CACNA1C, SCN1A), oxidative stress mediators (SCN8A, DRD2, DNMT1), cytochromes (CYP19A, CYP1A2), cytokines (TGFB1, IL4), telomere regulators (CSNK1D, SMAD3, MTA1), circadian rhythm (IL1R2, ABCG1, RORA), ultradian rhythms (PHACTR1, TSC2, ULK1), hormonal regulation (PPARA, NR3C1, ESR2), and the serotonin system (HTR1D, HTR1E, HTR3C, HTR4, TPH2). They also play roles in glucose metabolism (POMC, IRS1, GNAS) and obesity (DRD2, FAAH, MMP2). Gene ontology and pathway enrichment analysis identified 43 pathways, including calcium signaling, cocaine addiction, and nicotine addiction. This study identified multiple differentially methylated genes involved in chronic pain in HS, which may serve as biomarkers and therapeutic targets. Understanding their epigenetic regulation is crucial for personalized pain management and could enhance the identification of high-risk patients, leading to better preventative therapies and improved maternal and neonatal outcomes. Full article
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22 pages, 3131 KiB  
Review
Fetal Red Blood Cells: A Comprehensive Review of Biological Properties and Implications for Neonatal Transfusion
by Claudio Pellegrino, Elizabeth F. Stone, Caterina Giovanna Valentini and Luciana Teofili
Cells 2024, 13(22), 1843; https://doi.org/10.3390/cells13221843 - 7 Nov 2024
Cited by 2 | Viewed by 6638
Abstract
Transfusion guidelines worldwide include recommendations regarding the storage length, irradiation, or even donor cytomegalovirus serostatus of red blood cell (RBC) units for anemic neonates. Nevertheless, it is totally overlooked that RBCs of these patients fundamentally differ from those of older children and adults. [...] Read more.
Transfusion guidelines worldwide include recommendations regarding the storage length, irradiation, or even donor cytomegalovirus serostatus of red blood cell (RBC) units for anemic neonates. Nevertheless, it is totally overlooked that RBCs of these patients fundamentally differ from those of older children and adults. These differences vary from size, shape, hemoglobin composition, and oxygen transport to membrane characteristics, cellular metabolism, and lifespan. Due to these profound dissimilarities, repeated transfusions of adult RBCs in neonates deeply modify the physiology of circulating RBC populations. Unsurprisingly, the number of RBC transfusions in preterm neonates, particularly if born before 28 weeks of gestation, predicts morbidity and mortality. This review provides a comprehensive description of the biological properties of fetal, cord blood, and neonatal RBCs, including the implications that neonatal RBCs, and their replacement by adult RBCs, may have for perinatal disease pathophysiology. Full article
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14 pages, 1505 KiB  
Review
Influence of Maternal Adipokines on Anthropometry, Adiposity, and Neurodevelopmental Outcomes of the Offspring
by Jorge Valencia-Ortega, Andrea Castillo-Santos, Miranda Molerés-Orduña, Juan Mario Solis-Paredes, Renata Saucedo, Guadalupe Estrada-Gutierrez and Ignacio Camacho-Arroyo
Int. J. Mol. Sci. 2024, 25(21), 11655; https://doi.org/10.3390/ijms252111655 - 30 Oct 2024
Cited by 2 | Viewed by 1313
Abstract
Pregnancy is distinguished by a multitude of intricate interactions between the mother and the new individual, commencing at implantation and persisting until the maturation and integration of the fetal apparatus and systems. The physiological increase in fat mass during pregnancy and the association [...] Read more.
Pregnancy is distinguished by a multitude of intricate interactions between the mother and the new individual, commencing at implantation and persisting until the maturation and integration of the fetal apparatus and systems. The physiological increase in fat mass during pregnancy and the association of maternal obesity with adverse neonatal outcomes have directed attention to the study of maternal adipokines as participants in fetal development. Interestingly, maternal concentrations of certain adipokines such as adiponectin, leptin, tumor necrosis factor-alpha, and interleukin-6 have been found to be associated with offspring anthropometry and adiposity at birth and at three months of age, even with neurodevelopmental alterations later in life. This is partly explained by the functions of these adipokines in the regulation of maternal metabolism and placental nutrient transport. This review compiles, organizes, and analyzes the most relevant studies on the association between maternal adipokines with anthropometry, adiposity, and neurodevelopmental outcomes of the offspring. Furthermore, it proposes the underlying mechanisms involved in this association. Full article
(This article belongs to the Special Issue Adipose Tissue in Human Health and Disease 2.0)
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24 pages, 6053 KiB  
Article
Gestational Diabetes-like Fuels Impair Mitochondrial Function and Long-Chain Fatty Acid Uptake in Human Trophoblasts
by Kyle M. Siemers, Lisa A. Joss-Moore and Michelle L. Baack
Int. J. Mol. Sci. 2024, 25(21), 11534; https://doi.org/10.3390/ijms252111534 - 27 Oct 2024
Cited by 1 | Viewed by 2482
Abstract
In the parent, gestational diabetes mellitus (GDM) causes both hyperglycemia and hyperlipidemia. Despite excess lipid availability, infants exposed to GDM are at risk for essential long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Isotope studies have confirmed less LCPUFA transfer from the parent to the [...] Read more.
In the parent, gestational diabetes mellitus (GDM) causes both hyperglycemia and hyperlipidemia. Despite excess lipid availability, infants exposed to GDM are at risk for essential long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Isotope studies have confirmed less LCPUFA transfer from the parent to the fetus, but how diabetic fuels impact placental fatty acid (FA) uptake and lipid droplet partitioning is not well-understood. We evaluated the effects of high glucose conditions, high lipid conditions, and their combination on trophoblast growth, viability, mitochondrial bioenergetics, BODIPY-labeled fatty acid (FA) uptake, and lipid droplet dynamics. The addition of four carbons or one double bond to FA acyl chains dramatically affected the uptake in both BeWo and primary isolated cytotrophoblasts (CTBs). The uptake was further impacted by media exposure. The combination-exposed trophoblasts had more mitochondrial protein (p = 0.01), but impaired maximal and spare respiratory capacities (p < 0.001 and p < 0.0001), as well as lower viability (p = 0.004), due to apoptosis. The combination-exposed trophoblasts had unimpaired uptake of BODIPY C12 but had significantly less whole-cell and lipid droplet uptake of BODIPY C16, with an altered lipid droplet count, area, and subcellular localization, whereas these differences were not seen with individual high glucose or lipid exposure. These findings bring us closer to understanding how GDM perturbs active FA transport to increase the risk of adverse outcomes from placental and neonatal lipid accumulation alongside LCPUFA deficiency. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Treatment of Pregnancy Complications)
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8 pages, 503 KiB  
Article
Neonatal Hypoxic Respiratory Failure: Referral for ECMO
by Tracey Lutz, Andrew Berry, Angela McGillivray and Kathryn Browning-Carmo
Emerg. Care Med. 2024, 1(3), 304-311; https://doi.org/10.3390/ecm1030031 - 21 Sep 2024
Viewed by 1505
Abstract
Background: Neonatal hypoxic respiratory failure (HRF) secondary to PPHN (persistent pulmonary hypertension of the newborn) is an uncommon but life-threatening complication. Despite advances in therapeutic interventions, there are neonates who may require ECMO (extracorporeal membrane oxygenation), which improves survival. In establishing the [...] Read more.
Background: Neonatal hypoxic respiratory failure (HRF) secondary to PPHN (persistent pulmonary hypertension of the newborn) is an uncommon but life-threatening complication. Despite advances in therapeutic interventions, there are neonates who may require ECMO (extracorporeal membrane oxygenation), which improves survival. In establishing the capability of ECMO in transport in New South Wales, significant variation in referral thresholds and management of PPHN in referring hospitals has been noted. Aim: To review cases referred to the Newborn and paediatric Emergency Transport Service (NETS) for consideration of ECMO due to HRF in neonates. The aetiology of HRF, the number of retrievals and their short-term outcomes were reported. Methods: A retrospective audit of referrals to NETS (January 2019 to December 2022) of infants aged <28 days with HRF for ECMO. Patient demographics, management, advice at the time of call and the outcome are described. Results: The mean weight was 3511 g, mean gestation was 37.1 weeks and 69% of the patients were male. The main diagnoses were MAS/PPHN (50%), and there was variation in inotropes and ventilation strategies at the time of the referral. Six (25%) of the fifteen babies who were transported by NETS to paediatric intensive care were placed on ECMO at the referring hospital. A further six babies were stabilised at the referral centre following NETS co-ordinated specialist advice and did not require retrieval or ECMO. All the babies who received ECMO and survived had normal early development (<6 months) with normal head US or MRI imaging. Conclusions: Optimising ventilation and inotrope management can eliminate the need for ECMO prior to or following retrieval. Early referral for the consideration of ECMO and a collaborative discussion can assist in optimising conventional therapy, thus eliminating the need for ECMO. Neonates requiring ECMO for HRF have good survival rates with good short-term neurological outcomes. Full article
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