Virtual reality versus low level simulation in newborn care teaching in Turkey.

The aim of this study is a virtual reality versus low level simulation in newborn care teaching in Turkey. Data were collected in 2019-2020 academic year in midwifery students in Turkey. In the first stage, virtual reality simulation software was developed. In the second stage, newborn care was provided with a virtual reality simulator to the experimental group and a low-fidelity simulator to the control group. Students' practice, self-confidence and satisfaction levels were compared using two different simulators. There was a difference between the two groups in terms of their skills, satisfaction and self-confidence. The simulator, which was developed and evaluated in the research, increased the students' satisfaction, self-confidence and skills. It was also found to be more effective than the classical method.

Le but de cette étude est une réalité virtuelle versus simulation de bas niveau dans l'enseignement des soins aux nouveau-nés en Turquie. Les données ont été collectées au cours de l'année universitaire 2019-2020 auprès d'étudiantes sages-femmes en Turquie. Dans un premier temps, un logiciel de simulation de réalité virtuelle a été développé. Dans la deuxième étape, les soins aux nouveau-nés ont été fournis avec un simulateur de réalité virtuelle pour le groupe expérimental et un simulateur basse fidélité pour le groupe témoin. Les niveaux de pratique, de confiance en soi et de satisfaction des étudiants ont été comparés à l'aide de deux simulateurs différents. Il existe une différence entre les deux groupes en termes de compétences, de satisfaction et de confiance en soi. Le simulateur développé et évalué dans le cadre de la recherche a accru la satisfaction, la confiance en soi et les compétences des étudiants. Elle s'est également révélée plus efficace que la méthode classique.

Maintenance intravenous fluid therapy in infants with sepsis and hyponatremia: a clinical trial.

BACKGROUND: This study aimed to compare the effect of two methods of maintenance intravenous fluid therapy on hyponatremia in hospitalized infants with sepsis. METHODS: In a double-blinded randomized clinical trial, 60 term infants with sepsis were enrolled. Blood samples were taken to determine sodium, potassium, Creatinine, and BUN levels before the initiation of treatment. Urine samples were taken to assess specific gravity and urinary output. Infants in the intervention group received half saline in 10% dextrose and infants in the control group were assigned to receive the conventional solution as maintenance. The above indicators were re-evaluated 24 and 48 h after the initiation of treatment. Two groups were compared concerning the incidence of hyponatremia, and other criteria such as urinary output and urinary specific gravity, blood urea nitrogen (BUN), and creatinine levels. RESULTS: Hyponatremia was more common in the control group. Sodium levels were significantly higher in half saline recipients 24 h (137.83 ± 2.86 vs. 134.37 ± 1.91 mmol/L), and 48 h (138.10 ± 2.41 vs. 133.66 ± 1.98 mmol/L) after treatment (P < 0.001). Although BUN in the intervention group was significantly higher in comparison to the control group, the difference in urinary output, urine specific gravity, potassium, and Creatinine levels were not significant in the two groups. CONCLUSIONS: The use of a half-saline solution as maintenance fluid reduces the risk of hyponatremia after 48 h when compared to 0.18%NaCl. TRIAL REGISTRATION: This has been registered at Iranian Registry of Clinical Trials (Retrospectively registered, Registration date: 2017-10-12, identifier: IRCT2017053034223N1, https://irct.behdasht.gov.ir/trial/26204 ).

Assessing the human factors involved in chest compression with superimposed sustained inflation during neonatal and paediatric resuscitation: A randomized crossover study.

Background: A new cardiopulmonary resuscitation technique, chest compressions with sustained inflation (CC + SI) might be an alternative to both the neonatal [3:1compressions to ventilations (3:1C:V)] and paediatric [chest compression with asynchronous ventilation (CCaV)] approaches. The human factors associated with this technique are unknown. We aimed to compare the physical, cognitive, and team-based human factors for CC + SI to standard CPR (3:1C:V or CCaV). Methods: Randomized crossover simulation study including 40 participants on 20 two-person teams. Workload [National Aeronautics and Space Administration Task Load Index (NASA-TLX)], crisis resource management skills (CRM) [Ottawa Global Rating Scale (OGRS)], and debrief analysis were compared. Results: There was no difference in paired NASA-TLX scores for any dimension between the CC + SI and standard, adjusting for CPR order. There was no difference in CRM scores for CC + SI compared to standard. Participants were less familiar with CC + SI although many found it simpler to perform, better for transitions/switching roles, and better for communication. Conclusions: The human factors are no more physically or cognitively demanding with CC + SI compared to standard CPR (NASA-TLX and participant debrief) and team performance was no different with CC + SI compared to standard CPR (OGRS score).

Neonatal tachypnea caused by diaphragmatic paralysis: A case report.

BACKGROUND: Diaphragmatic paralysis is typically associated with phrenic nerve injury. Neonatal diaphragmatic paralysis diagnosis is easily missed because its manifestations are variable and usually nonspecific. CASE SUMMARY: We report a 39-week-old newborn delivered via vaginal forceps who presented with tachypnea but without showing other birth-trauma-related manifestations. The infant was initially diagnosed with pneumonia. However, the newborn still exhibited tachypnea despite effective antibiotic treatment. Chest radiography revealed right diaphragmatic elevation. M-mode ultrasonography revealed decreased movement of the right diaphragm. The infant was subsequently diagnosed with diaphragmatic paralysis. After 4 weeks, tachypnea improved. Upon re-examination using M-mode ultrasonography, the difference in bilateral diaphragmatic muscle movement was smaller than before. CONCLUSION: Appropriate use of M-mode ultrasound to quantify diaphragmatic excursions could facilitate timely diagnosis and provide objective evaluation.

Lung ultrasound to predict the duration of respiratory support in newborn infants with respiratory distress.

AIM: Lung ultrasound (LU) and clinical parameters evaluated during the first postnatal hour potentially predict the length of CPAP therapy in newborns with respiratory distress. METHODS: In a single-centre, prospective observational pilot study, 130 newborns ≥36 weeks gestational age were assessed using standardised LU at 30 and 60 min postnatally. Various clinical parameters were evaluated influencing CPAP duration (<1 vs. ≥1 h) using univariate and multivariate analyses. RESULTS: Lung ultrasound score >5, FiO2 > 0.21 and respiratory acidosis 30 min postnatally were associated with CPAP ≥1 h. Our model showed good diagnostic quality (ROC AUC = 0.87) and was confirmed by classification and regression tree (CART) analysis. Additional LU findings like double lung point and pleural line abnormalities were frequently observed, with good interrater reliability for LU interpretation (ICC = 0.76-0.77). CONCLUSION: Newborns with postnatal respiratory distress at risk for prolonged CPAP therapy can be identified based on specific LU and clinical parameters assessed 30 min postnatally. Despite the need for validation in an independent sample, these findings may lay the groundwork for a prediction tool. LU proved feasible and reliable for assessing respiratory status in this population, highlighting potential utility in clinical practice.

Evaluation of vitamin D in the diagnosis of infants with respiratory distress, the clinical value: A systematic review and meta-analysis.

INTRODUCTION: Respiratory distress (RD) is the most common cause of admission to the Neonatal Intensive Care Unit (NICU). The role of Vitamin D in the development and fortification of fetal pulmonary architecture and the synthesis of surfactants is well-documented. While different serum levels of 25-hydroxyvitamin D (Vit. D) have been studied for their diagnostic significance in RD, there is limited research on how it specifically affects the development of respiratory problems in infants and their mothers. The purpose of the present study is a systematic review and meta-analysis to evaluate the correlation between serum levels of Vit. D in mothers and newborns with RD, and to determine the impact of treating either population on the clinical outcomes of afflicted infants. METHODS: A comprehensive literature search was conducted across various databases, including PubMed, ScienceDirect, Cochrane Library, ISI, and Google Scholar, using a combination of keywords such as RD, diagnosis, vitamin D, mothers, infants, vitamin D supplementation, Respiratory distress syndrome(RDS), and Transient Tachypnea of Newborn (TTN). The search was carried out until March 2024.The level of vitamin D in both mothers and their infants was systematically extracted and analyzed to determine the diagnostic efficacy of Vit. D levels. The mean difference (MD) was calculated along with a 95% confidence interval to determine the association between the Vit. D levels in newborns and their mothers and the likelihood of RD, RDS and TTN in infants. To assess potential publication bias, a funnel plot was generated and Egger's regression test was applied, utilizing a random-effects model. RESULTS: Initially a total of 298 relevant articles was retrieved. Among them, 17 articles with a total of 1,582 infants (745 cases and 837 healthy controls) met the criteria as eligible studies. Of these six were prospective cohort studies, four retrospective case-control studies, four randomized controlled trials (RCTs), and three descriptive-analytical studies. The meta-results revealed a significant association between Vit. D levels and risk of RD in infants (MD = 6.240, 95 %CI: 4.840-7.840, P < 0.001) and mothers (MD = 8.053, 95 %CI: 4.920-11.186, P < 0.001). Furthermore, a strong association was found for risk of RDS (MD = 5.493, 95 %CI: 3.356-7.631, P < 0.001) in infants and TTN (MD = 6.672, 95 %CI: 4.072-9.272, P < 0.001), (MD = 8.595, 95%CI: 4.604-12.586, P < 0.001) both in infants and mothers. Administering 50,000 units of vitamin D to mothers (MD = 8.595, 95 %CI: 4.604-12.586, P < 0.001) prior to childbirth was observed to reduce the likelihood of RD in newborns by 64 % (RR = 0.36, 95 %CI: 0.23-0.57, P < 0.001). Supplemental vitamin D provided to infants was associated with several clinical benefits. CONCLUSION: Our meta-results indicated a significant correlation between serum levels of Vit. D and the risk of RD, RDS and TTN in infants. Prophylactic maternal administration of vitamin D plays a protective role against neonatal RD. Additionally, providing vitamin D to premature infants has shown a significant impact in reducing the incidence of respiratory complications.

EXPRESS: Acute Respiratory Distress Syndrome: A Review of ARDS Across the Life Course.

Acute respiratory distress syndrome (ARDS) is a multifactorial, inflammatory lung disease with significant morbidity and mortality that predominantly requires supportive care in its management. Although initially described in adult patients, the diagnostic definitions for ARDS have evolved over time to accurately describe this disease process in pediatric and, more recently, neonatal patients. The management of ARDS in each age demographic has converged in the application of lung protective ventilatory strategies to mitigate the primary disease process and prevent its exacerbation by limiting ventilator induced lung injury. However, differences arise in the preferred ventilatory strategies or adjunctive pulmonary therapies used to mitigate each type of ARDS. In this review, we compare and contrast the epidemiology, common etiologies, pathophysiology, diagnostic criteria, and outcomes of ARDS across the lifespan. Additionally, we discuss in detail the different management strategies used for each subtype of ARDS and spotlight how these strategies were applied to mitigate poor outcomes during the COVID-19 pandemic. This review is geared toward both clinicians and clinician-scientists as it not only summarizes the latest information on disease pathogenesis and patient management in ARDS across the lifespan but also highlights knowledge gaps for further investigative efforts. We conclude by projecting how future studies can fill these gaps in research and what improvements may be envisioned in the management of NARDS and PARDS based on the current breadth of literature in adult ARDS treatment strategies.

Newborn concurrent hearing and genetic screening for hearing impairment: A systematic review and meta­analysis.

Hearing loss is the most prevalent neurosensory disorder in humans, with significant implications for language, social and cognitive development if not diagnosed and treated early. The present systematic review and meta-analysis aimed to determine the rate of hearing screening pass and genetic screening failure [universal newborn hearing screening (UNHS) pass/genetic failure] and to investigate the advantages of combining newborn hearing and genetic screening for newborn hearing impairment. The PubMed, Embase and Cochrane databases were searched from inception to September 2023 to identify studies reporting the combination of neonatal hearing screening with genetic screening. Duplicate literature, unpublished literature, studies with incomplete data, animal experiments, literature reviews and systematic studies were excluded. All the data were processed by STATA15.1 statistical software. A total of nine cross-sectional studies were included in this meta-analysis. The sample sizes ranged from 1,716 to 180,469, and there were a total of 377,688 participants. The pooled results revealed that the prevalence of passing the UNHS while failing genetic screening was 0.31% (95% CI, 0.22-0.41%). The prevalence of UNHS pass and gap junction protein beta 2 and solute carrier family 26 member 4 variant screen failure was 0.01% (95% CI, 0.00-0.02%) and 0.00% (95% CI, 0.00%), respectively, while the prevalence of mitochondrially encoded 12S RRNA variant screening failure and UNHS pass was 0.21% (95% CI, 0.18-0.26%). Combined screening has a significant advantage over pure hearing screening, especially in terms of identifying newborns with mitochondrial gene mutations that render them sensitive to certain medications. In clinical practice, decision-makers can consider practical circumstances and leverage the benefits of combined newborn hearing and genetic screening for early diagnosis, early counseling, and early intervention in patients with hearing loss.

A case report of newborn with Klippel-Trenaunay syndrome from mother currently infected by COVID-19.

Background: Coronavirus disease 2019 (COVID-19) novel severe acute respiratory syndrome affected the world population with an infectious condition for which therapeutic forms are limited and vascular sequelae are major challenges. Pregnant women are physiologically immunocompromised and can be more affected by the pandemic than the general population. Extra precaution measures against COVID-19 during and after the outbreak are essential to ensure the safety of the newborn. The aim of the present study was to report the cesarean birth of a female child with Klippel-Trenaunay of a mother currently infected by COVID-19. Case Description: A newborn of a 21-year-old mother with COVID-19 in the final stage of the disease was born through a cesarean section at full term. The physical examination at birth revealed substantial edema of the left lower limb associated with port-wine stains on the limb and left torso. The ultrasound revealed venous-lymphatic malformation affecting the entire left lower limb, suprapubic region and ipsilateral abdominal region. Two evaluations for COVID-19 were performed and both were negative. Infants of mothers with active COVID-19 infection during the birth period have a low probability of being positive for the disease, but precautions should be taken. Conclusions: The association with malformations, such as the rare Klippel-Trenaunay syndrome (KTS), constitutes another challenge regarding the diagnosis and proper conduct to be taken with these children.

Impacts of COVID-19 on mothers' and newborns' health outcomes in regional Canada: A cross-sectional analysis.

Background: COVID-19 infection and pandemic-related stressors (e.g., socioeconomic challenges, isolation) resulted in significant concerns for the health of mothers and their newborns during the perinatal period. Therefore, the primary objective of this study was to compare the health outcomes of pregnant mothers and their newborns one year prior to and one year into the pandemic period in Alberta, Canada. Secondary objectives included investigating: 1) predictors of admission to neonatal intensive care units (NICU) and to compare NICU-admitted newborn health outcomes between the two time periods; 2) hospital utilization between the two time periods; and 3) the health outcomes of mothers and their newborns following infection with COVID-19. Methods: This analytical cross-sectional study used a large administrative dataset (n = 32,107) obtained from provincial regional hospitals and homebirths in Alberta, Canada, from April 15, 2019, to April 14, 2021. Descriptive statistics characterized the samples. Chi-squares and two-sample t-tests statistically compared samples. Multivariable logistic regression identified predictor variables. Results: General characteristics, pregnancy and labor complications, and infant outcomes were similar for the two time periods. Preterm birth and low birthweight predicted NICU admission. During the pandemic, prevalence of hospital visits and rehospitalization after discharge decreased for all infants and hospital visits after discharge decreased for NICU-admitted neonates. The odds of hospital revisits and rehospitalization after discharge were higher among newborns with COVID-19 at birth. Conclusions: Most of the findings are contextualized on pandemic-related stressors (rather than COVID-19 infection) and are briefly compared with other countries. Hospitals in Alberta appeared to adapt well to COVID-19 since health conditions were comparable between the two time periods and COVID-19 infection among mothers or newborns resulted in few observable impacts. Further investigation is required to determine causal reasons for changes in hospital utilization during the pandemic and greater birthweight among pandemic-born infants.

Per Os to Protection - targeting the oral route to enhance immune-mediated protection from disease of the human newborn.

Insight into the mechanisms that guide the host immune response towards either immunogenicity or tolerance is crucial for the success of many biomedical interventions, including vaccination1-10. In this regard, early life is of particular interest as young infants not only suffer the highest burden of infectious disease across the human lifespan, but also receive the highest number of vaccinations11-14. Vaccines preventing infections or disease are amongst the most cost-effective life-saving medical interventions in history15. The young (< 2 years of age), including newborns, receive most of the vaccines given globally16. For example, the World Health Organization (WHO) Expanded Program on Immunization (EPI) recommends up to 9 different types of vaccines (e.g. live attenuated, subunit, adjuvanted etc.) in the first 2 years of life, but only 4 and 3 to adolescents and adults, respectively; and between 21-24 doses of vaccines are recommended for children under 2 years of age, vs. only 7 for adolescents and 5 for adults17. In this Perspective, we highlight how the uniqueness of orally (per os (p.o.) = by mouth) induced immunity in early life offers highly promising approaches to enhance immune-mediated protection at the start of life . The oral route also presents a more feasible thus scalable approach to public health interventions, especially in resource constrained settings18-21. An increased focus on investigating p.o. administration of immune modulating interventions (e.g. vaccines) thus appears prudent.

Assessment of newborn neuropsychomotor development born with exposure to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age.

OBJECTIVE: This study aimed to evaluate the Neuropsychomotor Development (NPMD) of newborns exposed to SARS-CoV-2 in the perinatal period using the Bayley III scale at 6 months of age. METHODS: Childcare appointments were scheduled for the included newborns in the study. During the 6-month consultation, the Screening Test for Bayley III Scale and, based on it, children were classified as "low risk", "moderate risk" or "high risk" in the domains: of cognitive, receptive language, expressive language, fine motor, and gross motor. Those classified as "moderate risk"; or "high risk" received guidance about NPMD stimuli and were instructed to maintain follow-up. RESULTS: Only 13 (37.1 %) of the newborns were classified as low risk in receptive language and 18 (51.4 %) in gross motor skills, with the domains most affected. Prematurity was a risk for cognitive incompetence (moderate risk/high-risk classification) (coefficient: 1.89, Odds Ratio = 6.7, 95 % CI 1.3‒35, p = 0.02). Lower birth weight that 2.500g had a similar effect on cognitive incompetence (coefficient: 1.9, Odds Ratio = 6.2, 95 % CI 1.2‒32.2, p = 0.02). Exclusive breastfeeding at hospital discharge (n = 8) was protective for incompetence (high risk/moderate risk) in the language domain (coefficient -2.14, OR = 0.12, 95 % CI 0.02‒0.71, p = 0.02). CONCLUSIONS: The children included in the study must be monitored and their development monitored in order to clarify whether there is a relationship between the delay in NPMD and perinatal exposure to COVID-19, as delays were observed in these preliminary results.

A Case Report of Pulmonary Alveolar Proteinosis Masquerading as Respiratory Distress Syndrome in Preterm Neonates.

A rare and challenging case of a preterm neonate with clinical and radiological signs of respiratory distress syndrome (RDS) since the first hour of life but was refractory to its standard treatment regimes like surfactant therapy and ventilation. Postmortem lung biopsy led us to the diagnosis of congenital pulmonary alveolar proteinosis (PAP). It occurs due to the aggregation of abnormal surfactant proteins and lipids in the alveoli, which hampers gas diffusion across the alveoli. It presents as respiratory distress at birth, and its diagnosis is often missed due to its resemblance with RDS. Although the exact etiology remains elusive, mutations in genes encoding surfactant and granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway components have been implicated in the pathogenesis of PAP. Treatment options are limited and only supportive. Among all these, whole-lung lavage is the most widely used management modality but with limited success in neonates.

Link between gut microbiota dysbiosis and childhood asthma: Insights from a systematic review.

Asthma, a chronic inflammatory disorder of the airways, is a prevalent childhood chronic disease with a substantial global health burden. The complex etiology and pathogenesis of asthma involve genetic and environmental factors, posing challenges in diagnosis, severity prediction, and therapeutic strategies. Recent studies have highlighted the significant role of the gut microbiota and its interaction with the immune system in the development of asthma. Dysbiosis, an imbalance in microbial composition, has been associated with respiratory diseases through the gut-lung axis. This axis is an interaction between the gut and lungs, allowing microbial metabolites to influence the host immune system. This systematic review examines the association between gut microbiota composition, measured using 16S rRNA sequencing, during infancy and childhood, and the subsequent development of atopic wheeze and asthma. The results suggest that higher alpha diversity of bacteria such as Bifidobacterium, Faecalibacterium, and Roseburia may have protective effects against asthmatic outcomes. Conversely, lower relative abundances of bacteria like Bacteroides and certain fungi, including Malassezia, were associated with asthma. These findings highlight the potential of early screening and risk assessment of gut microbiota to identify individuals at risk of asthma. Furthermore, investigations targeting gut microbiota, such as dietary modifications and probiotic supplementation, may hold promise for asthma prevention and management. Future research should focus on identifying specific microbial signatures associated with asthma susceptibility and further investigate approaches like fecal microbiota transplantation. Understanding the role of gut microbiota in asthma pathogenesis can contribute to early detection and development of interventions to mitigate the risk of asthmatic pathogenesis in childhood.

Comparing the effectiveness of a breastfeeding arm sling with the normal cross-cradle hold position: A quasi-experimental study in Thailand.

INTRODUCTION: In Thailand, the exclusive breastfeeding rate remains low at 14% in 2019, despite the World Health Organization's recommendation of exclusive breastfeeding for the first six months. Many mothers experience challenges such as lack of confidence, fatigue, and discomfort while breastfeeding. To address these issues, the novel arm sling innovation device was developed to provide support during breastfeeding. This study aimed to compare the effectiveness of breastfeeding using the arm sling versus the normal cross-cradle hold among first-time mothers and to evaluate their satisfaction with the breastfeeding arm sling. METHODS: A quasi-experimental crossover design was employed in the postpartum unit at Ramathibodi Hospital, Thailand, in 2022. Forty-six first-time mothers breastfed using both a breastfeeding arm sling and the normal cross-cradle hold, with a washout period in between. Breastfeeding effectiveness was measured by mothers and nurse-midwives using questionnaires, and mothers' satisfaction with the sling was assessed. Data were evaluated using descriptive statistics and t-tests. RESULTS: The breastfeeding arm sling innovation significantly improved breastfeeding effectiveness compared to the normal cross-cradle hold, reported by both mothers (t=4.32, p<0.001) and nurse-midwives (t=8.93, p<0.001). Most mothers expressed satisfaction with the arm sling, though some design aspects, such as ease of use, require improvement. CONCLUSIONS: This study suggests that the breastfeeding arm sling can potentially improve breastfeeding experiences for first-time mothers. Further research is needed on a larger scale and in more diverse settings to confirm these findings and to improve the sling's design for user-friendliness.

An Implementation Science Study of a Heat-Producing Wrap to Complement KMC in Rwanda.

Background: Neonatal hypothermia is a major cause of preventable morbidity and mortality, especially among the world's poorest newborns. A heat-producing wrap is necessary when kangaroo mother care (KMC) is insufficient or unavailable, yet there is little published research on such wraps. The Dream Warmer is a wrap designed to complement KMC and has been extensively studied in formal research settings but not in real-world conditions. Objectives: We used implementation science methodology to understand the safety, effectiveness, and functionality of the Dream Warmer (hereafter, "Warmer"); its effect on clinical workflows; its interaction with other aspects of care such as KMC; and the Warmer's reception by healthcare providers (HCPs) and parents. Methods: We conducted a prospective, interventional, one-arm, open-label, mixed-methods study in 6 district hospitals and 84 associated health centers in rural Rwanda. Our intervention was the provision of the Warmer and an educational curriculum on thermoregulation. We compared pre and post intervention data using medical records, audits, and surveys. Findings: The Warmer raised no safety concerns. It was used correctly in the vast majority of cases. The mean admission temperature rose from slightly hypothermic (36.41 °C) pre, to euthermic (36.53 °C) post intervention (p = 0.002). Patients achieved a temperature ≥36.5 °C in 86% of uses. In 1% of audits, patients were hyperthermic (37.6-37.9 °C). Both HCPs and parents reported a generally positive experience with the Warmer. HCPs were challenged to prepare it in advance of need. Conclusions: The Warmer functions similarly well in research and real-world conditions. Ongoing education directed toward both HCPs and parents is critical to ensuring the provision of a continuous heat chain. Engaging families in thermoregulation could ease the burden of overtaxed HCPs and improve the skill set of parents. Hypothermia is a preventable condition that must be addressed to optimize neonatal survival and outcome.

Determination of Normal Range of Acylcarnitine in Neonatal Dried Blood Spots using LC-MS/MS.

Background: Acylcarnitine is one of the crucial markers of fatty acid metabolism, and examination of their level in infants can reveal several Inherited Metabolic Disorders (IDM) or Inborn errors of Metabolism (IEM). Because of the great importance of hereditary, metabolic, and other inherited disorders early diagnosis before the appearance of clinical symptoms, this study was carried out to establish a reference range for carnitine analytes and to identify acylcarnitine profiles in normal weight neonatal dried blood spots (DBS) specimens. Methods: By using liquid chromatography tandem mass spectrometry (LC-MS/MS) for neonatal screening and eventually the examination and analysis of LC-MS/MS results, 34 acylcarnitine derivatives were identified. Results: The normal range for acylcarnitine analytes with carbon numbers ranging from zero to 18, both main and the branched ones, were ultimately measured. Afterward, they were compared with the results of some other diagnostic laboratories to be verified. Conclusions: This study differed from the other findings, which could be due to diversity in population and work methods. However, the reference range of most acylcarnitine derivatives in Tehran closely aligned with this study's findings.

Performance Validation of the NeoBase 2 Non-Derivatized MSMS Assay Kit and Cutoff Values Establishment of Term and Preterm Neonates.

OBJECTIVE: NeoBase 2 Non-derivatized MSMS assay kit (NeoBase 2 kit) was used for newborn screening, the performance of the NeoBase 2 kit should be validated before its implementation in clinical diagnostic laboratories. METHODS: Leftover dried blood spot samples, quality control materials in the NeoBase 2 kit, and proficiency testing materials received from the NSQAP were used. Precision, accuracy, LOD, LLOQ, recovery, and stability were carried out to verify the performance of the Waters ACQUITY TQD MS/MS system with the NeoBase 2 kit for newborn screening. Cutoffs were determined and analytes requiring different cutoffs in preterm neonates were investigated. RESULTS: Within-run and between-run precisions ranged from 3.95% to 14.41%. The accuracy and stability were within 15%. All analytes demonstrated acceptable LOD, LLOQ, and recoveries. Cutoffs for term and preterm neonates were established. CONCLUSIONS: The performance of the NeoBase 2 kit is acceptable and can be implemented in clinical diagnostic laboratories.

Adenylyl Cyclase Isoform 6 in the Pulmonary Artery Is Inhibited by Hypoxia via Cysteine Nitrosylation.

Persistent pulmonary hypertension of the newborn (PPHN) is a hypoxic disorder of pulmonary vascular relaxation, mediated in part by adenylyl cyclase (AC). Neonatal pulmonary arteries (PA) express mainly AC6 isoform, followed by AC3, 7 and 9. AC6 expression is upregulated in hypoxia. We reported AC enzyme inhibition due to S-nitrosylation in PPHN PA, and in PA myocytes exposed to hypoxia. We hypothesize that hypoxia promotes cysteine thiol nitrosylation of AC6, impairing cAMP production. HEK293T cells stably expressing AC isoforms (AC3, 5, 6, 7, 9), or cysteine-to-alanine mutants AC6_C1004A, AC6_C1145A or AC6_C447A were cultured in normoxia (21% O2) or hypoxia (10% O2) for 72 hours, or challenged with nitroso donor S-nitrosocysteine (CysNO). AC activity was determined by real-time live-cell cAMP measurement (cADDis assay) or terbium-norfloxacin AC catalytic assay, with or without challenge by allosteric agonist forskolin; protein S-nitrosylation detected by biotin switch method and quantified by affinity precipitation. Only AC6 catalytic activity is inhibited in hypoxia or by S-nitrosylating agent, in presence or absence of forskolin; impaired cAMP production in hypoxia correlates with increased cysteine nitrosylation of AC6. Selective AC6 inhibition in pulmonary artery myocytes extinguishes AC sensitivity to inhibition by hypoxia. Alanine substitution of C1004, but not of other cysteines, decreases S-nitrosylation of AC6. AC activity is diminished in AC6_C1004A compared to AC6 wild type. Substitution of C1004 also extinguishes the inhibition of AC6 by hypoxia. We conclude AC6 is uniquely S-nitrosylated in hypoxia, inhibiting its activity and cAMP generation. We speculate that S-nitrosylation at C1004 may inhibit AC6 interaction with Gαs, playing a role in PPHN pathophysiology.

Birth's transformative shift: a response to Waleszczynski.

Waleszczynski critiques my argument for why the relationship between a pregnant person and any fetus they carry is not a relationship between a parent and a child. I argue Waleszczynski does not show that my 'argument from potentiality' is inadequate, and I provide further justification for why birth marks a transformative shift into a moral relationship.