Postnatal Age Research Articles

High-Resolution Computed Tomography Scores in Cases of Bronchopulmonary Dysplasia.

Background Bronchopulmonary dysplasia (BPD) carries a risk of long-term pulmonary sequelae. High-resolution computed tomography (HRCT) is a method of detecting such structural changes. This study is aimed at characterizing structural abnormalities associated with BPD and at evaluating the clinical findings in the newborn period associated with HRCT scores. Methods 28 patients born with a mean gestation age of 30 ± 2.9 weeks and diagnosed as BPD in their neonatal period were reevaluated when they were between the postnatal ages of 6 and 12 months. HRCT was performed in 20 patients with a history of moderate and severe BPD. Scans were interpreted by one radiologist using a scoring system. Results Patients were 9.8 ± 2.3 months at the time of reevaluation. The average HRCT score of patients was, respectively, 7.20 ± 4.05 with moderate and 7.40 ± 2.84 with severe BPD. The difference between them was not significant (p = 0.620). When moderate and severe groups were collected as a whole on the basis of physical findings and drug treatment, 6 had normal physical examination findings, no oxygen and no drug requirement; 14 had at least one finding at the time of reevaluation. No significant difference was detected in terms of HRCT score between the two groups (6.50 ± 3.83 versus 7.64 ± 3.30). Conclusions More studies are needed in terms of the role of HRCT in the assessment of BPD prognosis. A contemporary definition of BPD that correlates with respiratory morbidity in childhood is needed. Also, a new lung ultrasound technique for predicting the respiratory outcome in patients with BPD can be used instead of HRCT.

Influence of NAT2 Genotype and Maturation on Isoniazid Exposure in Low-Birth-Weight and Preterm Infants With or Without Human Immunodeficiency Virus (HIV) Exposure.

Isoniazid (INH) metabolism depends on the N-acetyl transferase 2 (NAT2) enzyme, whose maturation process remains unknown in low birth weight (LBW) and preterm infants. We aimed to assess INH exposure and safety in infants receiving oral tuberculosis prevention. This population pharmacokinetics (PK) analysis used INH and N-acetyl-isoniazid (ACL) concentrations in infants (BW ≤ 4kg), including preterm, with follow-up for 6 months. PK parameters were described using nonlinear mixed effects modeling. Simulations were performed to assess INH exposure and optimal dosing regimens, using 2 targets: Cmax at 3-6mg/L and area under the curve (AUC) ≥ 10.52mg h/L. We included 57 infants (79% preterm, 84% LBW) in the PK analysis, with a median (range) gestational age of 34 (28.7-39.4) weeks. At the time of sampling, postnatal age was 2.3 (0.2-7.3) months and weight (WT) was 3.7 (0.9-9.3) kg. NAT2 genotype was available in 43 (75.4%) patients (10 slow, 26 intermediate, and 7 fast metabolizers). Ninety percent of NAT2 maturation was attained by 4.4 post-natal months. WT, postmenstrual age, and NAT2 genotype significantly influenced INH exposure, with a 5-fold difference in AUC between slow and fast metabolizers for the same dose. INH appeared safe across the broad range of exposure for 61 infants included in the safety analysis. In LBW/preterm infants, INH dosing needs frequent adjustment to account for growth and maturation. Pharmacogenetics-based dosing regimens is the most powerful approach to deliver safe and equalized exposures for all infants, because NAT2 genotype highly impacts INH pharmacokinetic variability.

The short-term effects of RBC transfusions on intestinal injury in preterm infants.

BackgroundAnemic preterm infants may require red blood cell (RBC) transfusions to maintain sufficient oxygen supply to vital organs. Transfusion treatment, however, may have adverse intestinal effects. We aimed to investigate the short-term effects of RBC transfusions, hypothesizing to find signs of oxidative stress and intestinal injury, possibly related to levels of splanchnic (re-)oxygenation.MethodsWe prospectively included preterm infants (gestational age < 32 weeks). We measured urinary biomarkers for oxidative stress (8-isoprostane) and intestinal cell injury (intestinal fatty acid-binding protein, I-FABP) shortly before and after RBC transfusion. Splanchnic oxygen saturation (rsSO2) and rsSO2 variability were assessed simultaneously.ResultsTwenty-nine preterm infants received 58 RBC transfusions at various postnatal ages. Six of them developed necrotizing enterocolitis (NEC) after transfusion. Urinary 8-isoprostane and I-FABP increased following RBC transfusion (median 282–606 pg/ml and 4732–6968 pg/ml, p < 0.01), more pronounced in infants who developed NEC. Change in I-FABP correlated with change in 8-isoprostane (rho = 0.623, p < 0.01). Lower rsSO2 variability, but not higher mean rsSO2 was associated with higher 8-isoprostane and I-FABP levels after transfusion.ConclusionsPreterm RBC transfusions are associated with concomitant signs of oxidative stress and intestinal injury, parallel with lower variability in splanchnic oxygenation. This may represent the early pathogenetic process of transfusion-associated NEC.Impact Red blood cell (RBC) transfusions in preterm infants are associated with a near 2-fold increase in urinary biomarkers for oxidative stress (8-isoprostane) and intestinal cell injury (intestinal fatty acid-binding protein, I-FABP).Magnitude of change in I-FABP strongly correlated with the magnitude of 8-isoprostane change, suggesting a role for oxidative stress in the pathogenesis of intestinal injury.Lower splanchnic oxygen saturation variability following RBC transfusion was associated with higher 8-isoprostane and I-FABP levels.Loss of splanchnic variability after RBC transfusion may result from increased oxidative stress and its concomitant intestinal injury, possibly representing the early pathogenetic process of transfusion-associated necrotizing enterocolitis.

Dynamic Spatiotemporal Expression Pattern of the Senescence-Associated Factor p16Ink4a in Development and Aging.

A plethora of factors have been attributed to underly aging, including oxidative stress, telomere shortening and cellular senescence. Several studies have shown a significant role of the cyclin-dependent kinase inhibitor p16ink4a in senescence and aging. However, its expression in development has been less well documented. Therefore, to further clarify a potential role of p16 in development and aging, we conducted a developmental expression study of p16, as well as of p19ARF and p21, and investigated their expression on the RNA level in brain, heart, liver, and kidney of mice at embryonic, postnatal, adult, and old ages. P16 expression was further assessed on the protein level by immunohistochemistry. Expression of p16 was highly dynamic in all organs in embryonic and postnatal stages and increased dramatically in old mice. Expression of p19 and p21 was less variable and increased to a moderate extent at old age. In addition, we observed a predominant expression of p16 mRNA and protein in liver endothelial cells versus non-endothelial cells of old mice, which suggests a functional role specifically in liver endothelium of old subjects. Thus, p16 dynamic spatiotemporal expression might implicate p16 in developmental and physiological processes in addition to its well-known function in the build-up of senescence.

The Utility of Cerebral Autoregulation Indices in Detecting Severe Brain Injury Varies by Cooling Treatment Phase in Neonates with Hypoxic-Ischemic Encephalopathy

Identifying the hemodynamic range that best supports cerebral perfusion using near infrared spectroscopy (NIRS) autoregulation monitoring is a potential physiologic marker for neonatal hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia. However, an optimal autoregulation monitoring algorithm has not been identified for neonatal clinical medicine. We tested whether the hemoglobin volume phase (HVP), hemoglobin volume (HVx), and pressure passivity index (PPI) identify changes in autoregulation that are associated with brain injury on MRI or death. The HVP measures the phase difference between a NIRS metric of cerebral blood volume, the total hemoglobin (THb), and mean arterial blood pressure (MAP) at the frequency of maximum coherence. The HVx is the correlation coefficient between MAP and THb. The PPI is the percentage of coherent MAP-DHb (difference between oxygenated and deoxygenated hemoglobin, a marker of cerebral blood flow) epochs in a chosen time period. Neonates cooled for HIE were prospectively enrolled in an observational study in two neonatal intensive care units. In analyses adjusted for study site and encephalopathy level, all indices detected relationships between poor autoregulation in the first 6 h after rewarming with a higher injury score on MRI. Only HVx and PPI during hypothermia and the PPI during rewarming identified autoregulatory dysfunction associated with a poor outcome independent of study site and encephalopathy level. Our findings suggest that the accuracy of mathematical autoregulation algorithms in detecting the risk of brain injury or death may depend on temperature and postnatal age. Extending autoregulation monitoring beyond the standard 72 h of therapeutic hypothermia may serve as a method to provide personalized care by assessing the need for and efficacy of future therapies after the hypothermia treatment phase.

Incubator humidity and temperature control in infants born at 22–23 weeks' gestation

BackgroundPreterm infants, especially those born at ≤23 gestational weeks (GW), present with extremes in insensible water loss (IWL) and changes in water balance. AimsTo prevent water loss from the skin and achieve skin maturation without infection, we investigated transepidermal water loss (TEWL), IWL from the skin (IWL-s), and electrolyte balance with differences in high incubator humidity and temperature control from birth to postnatal 1 month in 22–23 GW and 24–25 GW infants. Study designProspective cohort study. SubjectsExtremely preterm infants born at 22–23 GW (n = 11) and 24–25 GW (n = 11), admitted to the neonatal intensive care unit between September 2018 and October 2019. Outcome measuresTotal fluid intake (TFI), fluid output volume, TEWL, IWL-s, and electrolyte balance were compared between the two groups with controlled incubator humidity and temperature, gradually decreasing the humidity and ambient temperature from 95% to 50% and from 37.0 to 34.0 °C, respectively, while maintaining the central body temperature at 36.5–37.5 °C. ResultsTEWL and IWL-s between the 22–23 and 24–25 GW was not significantly different for infants at postnatal age. No significant difference in electrolyte imbalance was noted between the two groups, within the first 7 days. Differences in TEWL and IWL-s were eliminated with corresponding humidity and temperature adjustments. ConclusionsIncubator humidity and temperature control should aid management of 22–23 GW infants to reduce IWL, facilitate skin maturation, and prevent infection.

Differential age-dependent development of inter-area brain connectivity in term and preterm neonates

BackgroundAmong preterm infants, higher morbidities of neurological disturbances and developmental delays are critical issues. Resting-state networks (RSNs) in the brain are suitable measures for assessing higher-level neurocognition. Since investigating task-related brain activity is difficult in neonates, assessment of RSNs provides invaluable insight into their neurocognitive development.MethodsThe participants, 32 term and 71 preterm neonates, were divided into three groups based on gestational age (GA) at birth. Cerebral hemodynamic activity of RSNs was measured using functional near-infrared spectroscopy in the temporal, frontal, and parietal regions.ResultsHigh-GA preterm infants (GA ≥ 30 weeks) had a significantly stronger RSN than low-GA preterm infants and term infants. Regression analyses of RSNs as a function of postnatal age (PNA) revealed a steeper regression line in the high-GA preterm and term infants than in the low-GA infants, particularly for inter-area brain connectivity between the frontal and left temporal areas.ConclusionsSlower PNA-dependent development of the frontal–temporal network found only in the low-GA group suggests that significant brain growth optimal in the intrauterine environment takes place before 30 weeks of gestation. The present study suggests a likely reason for the high incidence of neurodevelopmental impairment in early preterm infants.ImpactResting-state fNIRS measurements in three neonate groups differing in gestational age (GA) showed stronger networks in the high-GA preterm infants than in the term and low-GA infants, which was partly explained by postnatal age (PNA).Regression analyses revealed a similar PNA-dependence in the development of the inter-area networks in the frontal and temporal lobes in the high-GA and term infants, and significantly slower development in the low-GA infants.These results suggest that optimal intrauterine brain growth takes place before 30 weeks of gestation. This explains one of the reasons for the high incidence of neurodevelopmental impairment in early preterm infants.

Randomized Trial on Echocardiography-Guided Ductus Arteriosus Treatment to Reduce Necrotizing Enterocolitis.

ObjectivePatent ductus arteriosus (PDA) approach remains controversial. We aim to evaluate whether echocardiography-guided (EchoG) PDA closure (to reduce drug exposure) and 24-h continuous ibuprofen infusion (24 h-IB) (to reduce peak concentration), compared with EchoG PDA closure plus conventional bolus (bolus-IB), reduces severe bowel adverse event rate in preterm infants with hemodynamically significant (hs) PDA.Study DesignThe study design is a multicenter, blinded, randomized controlled trial. Infants with <28 weeks of gestation underwent routine echocardiographic assessment (18–72 h of birth); infants with 28–33 weeks were screened only in cases where PDA was clinically suspected. HsPDA was considered if ductal diameter >1.5 mm and indicators of pulmonary overflow, systemic hypoperfusion, or both were present. Pharmacodynamic effect of CYP450 genotypes was also analyzed.ResultsOne hundred forty-six infants [median gestational age 26 (25–28) weeks; median birth weight 881 (704–1,100) g] were randomized to 24 h-IB (n = 70) or bolus-IB (n = 76) study group at 86 (58–140) h from birth. Groups were comparable regarding perinatal and neonatal clinical data, but higher prevalence of male sex in the bolus-IB group was found. Neither severe bowel adverse event rate [10% (24 h-IB) and 2.6% (bolus-IB), p = 0.1] nor ductal closure rate was different between the study groups. Postnatal age and peripheral SaO2 at treatment start and pulmonary hemorrhage were associated with severe bowel events, independent of treatment group allocation. CYP2C8 genetic polymorphisms were associated with ibuprofen efficacy (p = 0.03).ConclusionsIbuprofen intravenous continuous infusion compared with bolus infusion in preterm infants with hsPDA shows similar rates of success and does not reduce the prevalence of severe bowel events.

Oral versus intravenous paracetamol for patent ductus arteriosus closure in preterm infants.

To examine whether oral administration of paracetamol as a first-line agent had a greater effect on the closure of a patent ductus arteriosus than the intravenous route. We performed a retrospective study of preterm infants (<37 weeks of gestation) between 2012 and 2020 treated with oral or intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction and compared rates of ductal closure, course duration, cumulative dose, PDA characteristics, and serum levels. Over the study period, 80 preterm infants received paracetamol, of which 50 received paracetamol as first-line treatment to augment constriction of the PDA. Closure rate was higher in the oral group (n = 15/19, 79%) compared to the intravenous group (n = 8/20, 40%, p < 0.01), and remained significant after adjusting for gestational age, length of treatment, and postnatal age (OR 0.14, 95% CI 0.03-0.67, p = 0.014, RR 0.51, 95% CI 0.28-0.91). Eleven preterm infants received a combination of both oral and intravenous paracetamol with a closure rate of 45% (n = 5). Oral administration of paracetamol as a first-line agent is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. Our retrospective study comparing the use of oral versus intravenous paracetamol as the first line for patent ductus arteriosus (PDA) constriction in preterm infants demonstrates that oral administration of paracetamol is more efficacious to constrict the PDA than the intravenous route, irrespective of gestational age or course duration. To our knowledge, this is the first published study (prospective or retrospective) to compare the efficacy of oral versus intravenous paracetamol as a first-line treatment for PDA closure in preterm infants. Our finding may improve the rate of PDA closure when paracetamol is used as a first-line agent.

Cystatin C Concentration During the First Three Postnatal Days in Healthy Term Newborns.

Cystatin C (Cys-C) concentration has not been examined sufficiently among healthy newborn population, particularly in terms of reference values. This study aimed to establish gender-, postnatal age- and birth weight-specific Cys-C concentration for healthy term newborns. Its objective was also to examine if there were any differences between our measured concentration and the reference interval established by the CALIPER study. Serum samples from a total of 90 healthy term newborns were used to determine Cys-C concentration. Cys-C was measured within first three days of birth using particle-enhanced turbidimetric immunoassay (PETIA) on the Architect plus ci8200 analyzer. Median concentration of the Cys-C was 2.05 mg/L. There were no statistically significant differences in Cys-C concentration regarding gender (p=0.779), birth weight (p=0.505), postnatal age (p=0.512) or Apgar score (p=0.799). The value of the 2.5th and 97.5th percentile for Cys-C concentrations for girls was 0.93-3.15 mg/L and for boys it was 1.5-3.36 mg/L. Cys-C concentration in healthy term newborns does not depend on gender, birth weight, postnatal age, or Apgar score. Our measured concentration range of CyS-C in healthy newborns turned out to be slightly wider than the interval determined in the CALIPER study.

Evaluation and modification of French screening guidelines for retinopathy of prematurity

To evaluate the current French screening guidelines for retinopathy of prematurity (ROP) and to suggest modifications to it. In this multicentric retrospective, noncomparative, interventional case series we included infants with a gestational age (GA) ≤32 weeks who were screened for ROP by fundus examination between 2011 and 2018. Main Outcome Measures were the presence of ROP and the need for treatment. A total of 2246 children with a mean GA of 28.9 ± 2.0 weeks and mean birth weight (BW) of 1141.1 ± 332.0 g were screened. Retinopathy of prematurity (ROP) was found in 683 infants (30.4%), of whom 145 (6.5%) had type 2 ROP and 58 (2.6%) had type 1 ROP. Mean GA of infants with type 1 ROP needing treatment was 25.9 + 1.5 weeks (range: 23.6-30) and mean BW was 774.1 ± 173.7 g (range: 540-1400). Both GA and BW had an impact on the development of type 1 and 2 ROP. None of the infants needing treatment had a GA of 31 weeks or more. None of the children needed treatment before 33 weeks of postmenstrual age (PMA) or 6 weeks of postnatal age (PNA). It seems possible to decrease the screening of premature infants to ≤31 weeks of GA and to start screening at 31 weeks PMA for infants having a GA < 26 weeks and at 6 weeks PNA for more mature children.

Optimisation of fluconazole therapy for the treatment of invasive candidiasis in preterm infants

IntroductionFluconazole is an important antifungal in the prevention and treatment of invasive Candida infections in neonates, even though its use in preterm infants is still off-label. Here, we performed a...

Age-At-Injury Influences the Glial Response to Traumatic Brain Injury in the Cortex of Male Juvenile Rats.

Few translational studies have examined how age-at-injury affects the glial response to traumatic brain injury (TBI). We hypothesized that rats injured at post-natal day (PND) 17 would exhibit a greater glial response, that would persist into early adulthood, compared to rats injured at PND35. PND17 and PND35 rats (n = 75) received a mild to moderate midline fluid percussion injury or sham surgery. In three cortical regions [peri-injury, primary somatosensory barrel field (S1BF), perirhinal], we investigated the glial response relative to age-at-injury (PND17 or PND35), time post-injury (2 hours, 1 day, 7 days, 25 days, or 43 days), and post-natal age, such that rats injured at PND17 or PND35 were compared at the same post-natal-age (e.g., PND17 + 25D post-injury = PND42; PND35 + 7D post-injury = PND42). We measured Iba1 positive microglia cells (area, perimeter) and quantified their activation status using skeletal analysis (branch length/cell, mean processes/cell, cell abundance). GFAP expression was examined using immunohistochemistry and pixel analysis. Data were analyzed using Bayesian multivariate multi-level models. Independent of age-at-injury, TBI activated microglia (shorter branches, fewer processes) in the S1BF and perirhinal cortex with more microglia in all regions compared to uninjured shams. TBI-induced microglial activation (shorter branches) was sustained in the S1BF into early adulthood (PND60). Overall, PND17 injured rats had more microglial activation in the perirhinal cortex than PND35 injured rats. Activation was not confounded by age-dependent cell size changes, and microglial cell body sizes were similar between PND17 and PND35 rats. There were no differences in astrocyte GFAP expression. Increased microglial activation in PND17 brain-injured rats suggests that TBI upregulates the glial response at discrete stages of development. Age-at-injury and aging with an injury are translationally important because experiencing a TBI at an early age may trigger an exaggerated glial response.

Regional cerebral and splanchnic tissue oxygen saturation in preterm infants – Longitudinal normative measurements

BackgroundTo investigate regional splanchnic and cerebral tissue oxygen saturation in preterm infants <30 weeks gestation. MethodsCerebral (cTOI) and splanchnic (sTOI) Tissue Oxygenation Index were measured weekly in 5 min epochs for a total period of 60 min using NIRS (NIRO-300) for the first 8 weeks of life, in 48 appropriately grown preterm infants born at <30 weeks gestation. Infants who developed HPI and/or NEC (n = 12) and those that died (n = 1) were excluded from our main outcome measure of regional gut and cerebral tissue oxygenation in healthy preterm infants <30 weeks gestation. ResultsMedian birthweight 789 g (460–1486), gestational age 25+6 weeks (23+0–29+1) and 51.4% female. 217 NIRS measurements were completed across the first 8 weeks of life. Mean weekly cTOI ranged from 56.8–65.4% and sTOI ranged from 36.7–46.0%. Mean cTOI was significantly higher than mean sTOI (p < 0.001) throughout the first 8 weeks of life. Mean cTOI decreased significantly with increasing postnatal age [−0.59% each week (−1.26% to −0.07%) p = 0.04]. None of the examined confounding factors had a significant effect. ConclusionsThis is the first report of regional cerebral and splanchnic tissue oxygen saturation ranges during the first 8 weeks of life for preterm infants born at <30 weeks gestation.

High-risk phenotypes of genetic disease in a Neonatal Intensive Care Unit population.

High-risk phenotypes of genetic disease in a Neonatal Intensive Care Unit population.

Cognitive impairment persists at least 1 year after juvenile rats are treated with methotrexate

Methotrexate (MTX) is widely employed for children with cancer, but is also associated with persistent cognitive deficits among survivors. The present study investigated the mechanisms behind long-term cognitive dysfunction after juvenile animals are treated with MTX. Male and female Long-Evans rats were treated with a combination of 6 systemic doses (0.5 mg/kg/dose intraperitoneally) and 4 intrathecal doses (1 mg/kg) beginning at post-natal age 3 weeks, a schedule designed to mimic repeated exposure given to children with leukemia. Behavioral testing was conducted at 60–61 weeks of age, followed by analysis of brain histolopathology. This MTX regimen had no acute toxicity and no effect on growth. The spatial memory and visual memory deficits observed at 13 and 17 weeks of age persisted 1 year after MTX exposure in both females and males. Significantly decreased cell proliferation and increased hippocampal microglial activation were observed in MTX-treated females when compared to the controls, with a similar trend in the male groups. In addition, MTX treatment significantly increased the number of TUNEL positive cells in the periventricular area. Our study demonstrates that a clinically relevant regimen of systemic and intrathecal MTX induces persistent deficits in cognition, lasting approximately 1 year after the last injection. The mechanisms behind MTX-induced deficits are likely multifactorial, including suppression of neurogenesis, microglial activation, and increased brain cell apoptosis. Our study suggests female and male animals differ in susceptibility to MTX-induced neurotoxicity and provides insights for developing therapeutic approaches to prevent treatment related cognitive impairment among children with ALL.

Physiological QT Interval Changes in Early Infancy Using Post-Menstrual and Post-Natal Age Calculation for Electrocardiogram Long QT Interval Screening in Taiwan.

Prolongation of the QT interval is associated with the risk of sudden infant death syndrome. QT interval differs depending on age at the time of screening. Screening protocols have yet to be established for Taiwanese patients. To construct QT interval reference values during early infancy, to investigate whether QT interval change differs according to age calculation methods, and to identify an optimal QT correction method and associated infant factors. Electrocardiographic readings and QT intervals were recorded cross-sectionally in 595 healthy infants and screened prospectively for long QT interval. Corrected QT intervals with Bazett's (QTc-B) and Fridericia's (QTc-F) formulas were compared by post-natal and post-menstrual screening age, sex, body mass index (BMI), heart rate (HR), birth and family history. QTc-B and QTc-F decreased in the second month (31-60 days), and peaked in the third month (61-90 days). QT interval length was similar between post-menstrual and post-natal ages for QTc-B. Simple linear regression showed that post-menstrual age, post-natal age, HR and BMI were associated with QTc-F, while only sex and HR were associated with QTc-B. Although both QTc-B and QTc-F were significantly associated with HR, QTc-B was less affected by HR than QTc-F (β = -0.1, p < 0.05 for QTc-B vs. β = -0.3, p < 0.001 for QTc-F). Female infants tended to have slightly longer QTc intervals. QT interval in early infancy changed physiologically, peaking in the third month. The rate of QT change was not affected by different age correction methods. QTc-B was less affected by age, BMI and HR, although differences in sex should be noted.

Age-dependent viscoelastic characterization of rat brain cortex

Recent efforts in biomaterial-assisted brain tissue engineering suggest that match of mechanical properties of biomaterials to those of native brain tissue may be crucial for brain regeneration. In particular, the mechanical properties of native brain tissue vary as a function of age. To date, detailed characterization of age-dependent viscoelastic properties of brain tissue throughout the postnatal development to adulthood is only available at sparse age points in animal studies. To fill this gap, we have characterized the linear viscoelastic properties of the cerebral cortex in rats at well-spaced ages from postnatal day 4 to 4 months old, the age range that is widely used in neural regeneration studies. Using an oscillatory rheometer, the viscoelastic properties of rat cortical slices were measured independently by storage moduli (G′) and loss moduli (G″). The data demonstrated increases in both the storage moduli and the loss moduli of cortex tissue over post-natal age in rats. At all ages, the damping factor (G″/G′ ratio) remained constant at low oscillatory strain frequencies (<10 rad/s) before it started to decline at medium frequency range (10-100 rad/s). Such changes were not age-dependent. The stress-relaxation response increased over post-natal age, consistent with the increasing tissue stiffness. Taken together, our study demonstrates that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. This data may provide the guidelines for age-specific biomechanics study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration studies. Statement of significanceStudies about age-dependent viscoelastic properties of rat brain tissue throughout the postnatal development to adulthood is sparsely available. To fill up the gap of knowledge, in this study, we have characterized the age-dependent viscoelastic properties and the linear viscoelastic properties of the cerebral cortex throughout the postnatal development stage to adulthood in rats by measuring storage moduli (G′), loss moduli (G″), damping factor (G″/G′ ratio) and stress-relaxation response. We have found that age is a crucial factor determining the mechanical properties of the cerebral cortex in rats during early postnatal development. The findings of this study could provide guidelines for age-specific biomechanical study of brain tissue and help to define the mechanical properties of biomaterials for biomaterial-assisted brain tissue regeneration in experimental models in rats.

The first fungi: mode of delivery determines early life fungal colonization in the intestine of preterm infants

Aim: The role of intestinal fungi in human health and disease is becoming more evident. The mycobiota composition and diversity of preterm infants is affected by interactions with bacteria and clinical variables. In this study, we aimed to characterize the composition and the diversity of the preterm infant mycobiota and the effect of clinical variables on it in the first six postnatal weeks. Methods: Preterm infants (n = 50) and full-term infants (n = 6) admitted to Isala Women and Children’s hospital (Zwolle, The Netherlands) who were born during 24-36 or 37-40 weeks of gestation, respectively, were included in this study. Feces were collected during the first six postnatal weeks (n = 109) and their mycobiota composition and diversity were characterized by ITS2 amplicon sequencing. Results: Composition analyses identified fungi and other eukaryotic kingdoms, of which Viridiplantae was most abundant. Of the fungal kingdom, Ascomycota and Basidiomycota were the first and second most prominent phyla in early life of all infants. Candida was the most abundant genus in the first six weeks of life and increased with gestational and postnatal age. Fungal phylogenetic diversity remained stable in the first six postnatal weeks. The individuality and the mode of delivery were identified as significant predictors for the variation in the mycobiota composition. Vaginally delivered infants were enriched in Candida spp., whereas infants delivered through emergency C-section were characterized by Malassezia spp. Conclusion: These results indicate that fungi and other eukaryotic kingdoms are detected in the intestine of preterm and full-term infants in the first six postnatal weeks. Similar to the microbiota, colonization of the preterm intestine with fungi is determined by clinical variables including individuality and mode of delivery.

Infant mortality in the Greek community of Odessa (1860–1920)

The article examines infant mortality – the mortality of children aged from 0 to 364 days in the Greek community of Odessa during the period from 1860 to 1920. It aims at the demographic analysis of infant mortality in the Greek population of Odessa that, in general, involves the discussion of statistical figures demonstrating the development of the phenomenon in question including trends, frequency, seasonality and social structure of infant mortality. The work is based on data derived from the records of birth registers of the Greek Church of the Holy Trinity in Odessa. It addresses a number of demographic characteristics such as the seasonality of infant deaths, times of their peaks, the causes of deaths, and the social belonging of the deceased. In particular, the highest mortality rate in the 60-year period is observed during the winter and summer months. This shows the regional urban specificity, where the peaks of the deaths clearly reflect the living conditions in Odessa. The infant mortality rate in Odessa appears not very high when compared to that in other cities of Europe and Russia. This indicates a quite favorable situation in the urban environment of the time. The prevalence of mortality among boys, both in the perinatal and postnatal ages, is indicative, and the percentage of the latter age group continued to increase at the expense of boys. The high percentage of the church funeral services for the Greek children of formally foreign subjects emphasizes the complex composition of the Greek population of Odessa and, at the same time, the economic activity of the townspeople.