Postnatal Day Research Articles

Role of aminophylline in prevention of acute kidney injury in term neonates with severe perinatal asphyxia: a randomized open-label controlled trial.

Acute kidney injury (AKI) is one of the frequently observed complications in neonates with severe perinatal asphyxia. The efficacy of aminophylline in preventing or alleviating renal dysfunction in these neonates remains controversial. The current study aimed to explore whether treatment with aminophylline as adjunctive therapy is superior to standard care alone in preventing AKI in severely asphyxiated term neonates and to delineate the changes in other renal parameters. In this open-label randomized clinical trial, term neonates with severe asphyxia (n = 41) received a 5 mg/kg intravenous dose of aminophylline within the first hour after birth, in addition to standard care for birth asphyxia. The control group (n = 40) received standard care alone. Their daily urine output, weight, serum creatinine, renal functional status, and complications during the first 5 days of life were monitored and compared. The statistical package for social sciences version 25 was used for analysis. Approximately 24.39% of neonates in the aminophylline group developed AKI, compared to 35.0% in the control group (P = .088). Although urine output was generally higher in aminophylline-treated newborns than in the control group, this increase was not statistically significant (P > .05), with the most notable differences observed on the second and third postnatal days. Also, the changes in plasma creatinine levels between the two groups during this time were not statistically significant. Administering a single dose of aminophylline (5 mg/kg) within the first hour of life to severely asphyxiated term neonates might temporarily enhance urine output, but does not reduce the overall incidence of AKI.

Heterozygous variants in USP25 cause genetic generalized epilepsy.

USP25 encodes ubiquitin-specific protease 25, a key member of the deubiquitinating enzyme family that is involved in neural fate determination. Although abnormal expression in Down's syndrome was reported previously, the specific role of USP25 in human diseases has not been defined. In this study, we performed trio-based whole exome sequencing in a cohort of 319 cases (families) with generalized epilepsy of unknown aetiology. Five heterozygous USP25 variants, including two de novo and three co-segregated variants, were determined in eight individuals affected by generalized seizures and/or febrile seizures from five unrelated families. The frequency of USP25 variants showed a significantly high aggregation in this cohort compared with the East Asian population and all populations in the gnomAD database. The mean age at onset of febrile and afebrile seizures were 10 months (infancy) and 11.8 years (juvenile), respectively. The patients achieved seizure freedom, except that one had occasional nocturnal seizures at the last follow-up. Two patients exhibited intellectual disability. Usp25 was expressed ubiquitously in mouse brain with two peaks, on embryonic Days 14-16 and postnatal Day 21, respectively. In human brain, likewise, USP25 is expressed in the fetus/early childhood stage and with a second peak at ∼12-20 years old, consistent with the seizure onset age in patients during infancy and in juveniles. To investigate the functional impact of USP25 deficiency in vivo, we established Usp25 knockout mice, which showed increased seizure susceptibility compared with wild-type mice in a pentylenetetrazol-induced seizure test. To explore the impact of USP25 variants, we used multiple functional detections. In HEK293 T cells, the variant associated with a severe phenotype (p.Gln889Ter) led to a significant reduction of mRNA and protein expressions but formed stable truncated dimers with an increment of deubiquitinating enzyme activities and abnormal cellular aggregations, indicating a gain-of-function effect. The p.Gln889Ter and p.Leu1045del variants increased neuronal excitability in mouse brain, with a higher firing ability in p.Gln889Ter. These functional impairments align with the severity of the observed phenotypes, suggesting a genotype-phenotype correlation. Hence, a moderate association between USP25 and epilepsy was noted, indicating that USP25 is potentially a predisposing gene for epilepsy. Our results from Usp25 null mice and the patient-derived variants indicated that USP25 would play an epileptogenic role via loss-of-function or gain-of-function effects. The truncated variant p.Gln889Ter would have a profoundly different effect on epilepsy. Together, our results underscore the significance of USP25 heterozygous variants in epilepsy, thereby highlighting the critical role of USP25 in the brain.

Combined developmental exposure to estrogenic endocrine disruptor and nutritional imbalance induces long term adult prostate inflammation through inflammasome activation

Increasing number of studies suggested that environmental deleterious impacts (such as estrogen-like endocrine disruptors, EDCs, unhealthy diet) during early human development affect the risk of developing non-communicable diseases including prostate cancer (PCa) later in life. To test if the combination of EDCs and unhealthy induces adult prostate lesions, we developed an experimental model of adult male Sprague Dawley rats exposed during gestation (from day 7) to weaning to high fat diet (HFD 60 % fat), or to a xenoestrogen (estradiol benzoate, EB, 2.5 µg/d) from post-natal days 1–5, or to a combination of both. EB and EB+HFD exposures induced decreased prostate weight in adult rats along with inflammatory status. A white blood cell infiltrate was observed after EB exposure and more dramatic lesions were observed with the combined exposure, along with a gland destruction. The lesions, following EB or EB+HFD exposure, are associated with elevated mRNA levels for TNFa, IL6 and CCL2/MCP1 pro-inflammatory cytokines while the levels of the anti-inflammatory IL10 cytokine remained unchanged. This activation of NLRP3 and elevated levels of CASP1 were observed following EB or EB+HFD exposures associated with elevated mRNA levels for IL1b, substrates for the NLRP3 complex. HFD exposure alone has mild if not pro-inflammatory effects in adult prostate. In conclusion, we showed that developmental combined exposure to EB and HFD programmed prostate inflammatory lesions in adult prostate. Since proliferative inflammatory atrophy and chronic inflammation of prostate may drive cell to become cancer cells, our model might be useful for study onset of PCa.

Temporary sensory separation of ewes from lambs effects stress-related behaviours and hormones of Small-tailed Han ewes

Context Different individuals within a group can form strong links through auditory, visual, and tactile senses. Temporarily separating sheep into subflocks, although not involving complete social isolation of individuals, can be stressful, especially when ewes are separated from lambs. Aims This study aimed to explore the effects of 1-h temporary ewe–lamb sensory separations on stress-related behaviours during separation, as well as its effect on stress-related hormones of ewes. Methods Small-tailed Han ewes were randomly assigned to the following four groups (six each): the auditory + visual + tactile separation (A + V + T group), visual + tactile separation (V + T group), tactile separation (T group), and the control (C group). Then, the ewes were separated from their lambs for 1 h on Postnatal Days 14, 21, 28, 35 and 42. Ewe behaviours during the separations were observed using focal animal-sampling methods. Key results Results showed that the separated ewes (A + V + T, V + T, and T groups) spent more time looking and exploring and less time lying (P < 0.05). Ewes showed more exploring behaviour in T group (P < 0.05). Ewes that gave birth to two lambs showed more urinating behaviour (P < 0.05). There was no significant difference in the level of stress-related hormones in ewes among the four different separation-method groups (A + V + T, V + T, T, and C groups). Conclusions One hour ewe-lamb sensory separation affected the stress related behaviours of Small-tailed Han ewes during separation, but it did not cause differences in stress-related hormones in ewes after the separation. Ewes showed increased exploring or urinating behaviour when they were separated through lack of tactile contact only with lambs, or when ewes give birth to two lambs. Implications Ewes temporarily separated from their lambs are less stressed if they are unable to hear or see the lambs, thereby improving ewe welfare. These effects appear more pronounced in ewes with multiple lambs and provides new perspectives for further studies on the effect of litter size on ewe-lamb bonding.

Two distinct enriched housings differentially ameliorate object and place recognition deficits in a rat model of schizophrenia

Schizophrenia is a psychiatric disorder characterized by cognitive dysfunctions. These dysfunctions significantly impact the daily lives of schizophrenic patients, yet effective interventions remain scarce. In this study, we explored the effects of two enriched housing types—cognitive and physical—on cognitive dysfunctions in a rat model of schizophrenia. Male neonatal Wistar-Imamichi rats were administered MK-801, a noncompetitive NMDAR antagonist, twice daily from postnatal day (PND) 7 to PND 20. Physical enrichment ameliorated memory deficits in both object and place recognition tests, while cognitive enrichment primarily improved object recognition performance. Our findings suggest that exercise therapy could be a potential approach to address cognitive dysfunctions in schizophrenia patients.

Radiosensitivity-related Variation in MicroRNA-34a-5p Levels and Subsequent Neuronal Loss in the Hilus of the Dentate Gyrus after Irradiation at Postnatal Days 10 and 21 in Mice.

The radiosensitivity of mice differs between postnatal days 10 (P10) and 21(P21); these days mark different stages of brain development. In the present study, Ki67 and doublecotin (DCX) immunostaining and hematoxylin staining was performed, which showed that acute radiation exposure at postnatal day 10 induced higher cell apoptosis and loss in the hilus of the dentate gyrus at day 1 postirradiation than postnatal day 21. MicroRNA (miRNA) sequencing and real-time quantitative reverse transcription PCR (qRT-PCR) analysis indicated the upregulation of miRNA-34a-5p at days 1 and 7 after irradiation at postnatal day 10, but not at postnatal day 21. Down-regulation of T-cell intracytoplasmic antigen-1 pathway (Tia1) was indicated by qRT-PCR at day 1 day but not day 7 after irradiation at postnatal day 10. Neurobehavioral testing in mature mice irradiated at postnatal day 10 demonstrated the impairment of short-term memory in novel object recognition and spatial memory, compared to those irradiated at postnatal day 21. Combined with our previous luciferase assay showing the direct interaction of miRNA34a-5p and Tia1, these findings suggest that radiation-induced abnormal miR-34a-5p/Tial interaction at day 1 after irradiation at postnatal day 10 may be involved in apoptosis of the dentate gyrus hilar, impairment of neurogenesis and subsequent short-term memory loss as observed in the novel object recognition and Barnes maze tests.

Retrospective analysis of volumes of manually expressed colostrum among healthy postnatal mothers at a tertiary care referral unit in South India. Not enough milk or not enough patience?

IntroductionThe volumes of colostrum have been quantified as 5 mL and 25 mL per feed on days 1 and 3, respectively, as per the data described about 20 years ago....

Effects of serotonergic manipulation in the brainstem and hypothalamus of overnourished rats during lactation

Previous studies suggest that being overweight and obese is capable of altering brain function during critical periods due to the higher plasticity of the brain during development. However, more literature still needs to be on the immediate effect of overnutrition and serotonin modulation in brain areas. In this study, we aimed to evaluate the effects of serotoninergic manipulation on oxidative stress and pro-inflammatory markers in the brainstem and hypothalamus of overnourished rats. The fluoxetine treatment was performed from postnatal day 3 (PND3) to postnatal day 21 (PND21) to evaluate mitochondrial function, oxidative balance, and the mRNA levels of monoaminergic molecules such as serotonin and dopamine, pro-inflammatory cytokines, and BDNF. Neonatal overnutrition induces molecular and biochemical changes in the brainstem and hypothalamus. These nutritional disturbances during lactation dysregulate energy balance and cellular redox, inducing oxidative stress. Conversely, modulation of the serotoninergic system through pharmacological use of fluoxetine was able to reverse the deleterious effects of overnutrition during lactation, enabling better brain development and delaying the development of pathologies and oxidative stress.

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study.Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3–10. AT1 antagonist losartan or water was given orally postnatal days 8–10. Blood pressure, autonomic function, left ventricular sympathetic innervation, β-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats.Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased β1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in β1-adrenergic-receptor expression.In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

Conductance properties of the α9α10 nicotinic acetylcholine receptor of neonatal mouse inner and outer hair cells

In the developing cochlea, just before the onset of hearing on postnatal day 12, the medial olivocochlear efferent axons in synaptic contact with the inner hair cells (IHCs) start withdrawing and new efferent synaptic connections are formed on the outer hair cells (OHCs), thereby progressing towards the adult pattern of medial olivocochlear efferent innervation. The synapses are inhibitory, calcium influx through the α9α10 nicotinic acetylcholine receptors (nAChRs) driving opening of calcium-dependent potassium channels. The nAChRs appear to function similarly in IHCs and OHCs, although with probable kinetic differences. Our aim was to assess their functional similarity in the neonatal mouse cochlea by making whole-cell recordings from both hair cell types between postnatal day 7 and 10 when nAChRs are expressed. ACh was applied to voltage-clamped hair cells by pressure-ejection from a pipette. The cells were dialysed with a Cs+-based solution designed to eliminate calcium-dependent potassium currents. There were differences in amplitude, voltage-sensitivity and reversal potential of the nAChR currents between IHCs and OHCs. There was also some indication that IHC nAChRs have slower activation and desensitization kinetics, although the relatively slow ACh application limited interpretation of this result. These differences, particularly concerning the reversal potential, might indicate the presence of different auxiliary protein subunits of the α9α10 receptor in neonatal IHCs and OHCs.

Prenatal exposure to di-n-butyl phthalate promotes RIPK1-regulated necroptosis of uroepithelial cells and induces hypospadias through the epithelial-mesenchymal transition process in newborn male rats

Maternal exposure to di-n-butyl phthalate (DBP) has been linked to the induction of hypospadias; however, the underlying mechanism remains unclear. Necroptosis is reported to be implicated in developmental malformations. This study aimed to investigate the underlying mechanism of necroptosis in the development of hypospadias. DBP was dissolved in corn oil, and pregnant rats were administered a precisely measured dose of DBP (750mg/kg/day) via gastric intubation from gestation day 14 to 18. Control rats received only corn oil. The day of birth was considered postnatal day (PND) 1. Male hypospadias rats were identified on PND 7. Genital tubercle tissues were collected and stored at −80°C for subsequent PCR analysis, cryopreserved in liquid nitrogen for western blot, or fixed in formalin for immunohistochemistry (IHC) staining. IHC staining and western blot analysis revealed increased expression of RIPK1 and necroptosis markers in genital tubercle (GT) tissue compared to the control group. Additionally, higher levels of EMT and impaired androgen receptor expression were observed in GT tissue. Exposure to increased DBP concentrations in rat primary uroepithelial cells (PUCs) led to elevated ROS production. Necroptosis markers and EMT expression levels were upregulated in PUCs following DBP incubation. Notably, treatment with DBP combined with necrostatin-1, a necroptosis inhibitor, reduced the expression of EMT markers and ROS production compared to DBP treatment alone. In vitro studies further revealed that DBP-induced necroptosis promoted the degradation of E-cadherin through the ubiquitin-proteasome pathway in PUCs. Our findings suggest that maternal exposure to DBP promotes necroptosis in uroepithelial cells by elevating ROS level and EMT status. Thus, necroptosis may play an essential role in the development of hypospadias.

Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats

Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood. This study aimed to investigate the impact of myelination on motor improvement following neonatal HI injury. We employed a modified Rice-Vannucci model; the right common carotid artery of postnatal day 7 (P7) Wistar rats was isolated and divided, and the rats were then exposed to hypoxic condition (90 min, 8 % O2). A total of 101 rats (66 males) were divided into four groups: trained-HI (n = 38), trained-Sham (n = 16), untrained-HI (n = 31), and untrained-Sham (n = 16). The trained groups underwent rotarod-based exercise training from P22 to P41 (3 days per week). Structural analysis using magnetic resonance imaging and immunohistochemistry (n = 6 per group) revealed increased fractional anisotropy and myelin density in the primary somatosensory cortex of the trained-HI group. We further evaluated the effect of myelination promotion on rotarod performance by administering clemastine, a myelination-promoting drug, via daily intraperitoneal injections. Clemastine did not enhance motor improvement in untrained-HI rats. However, clemastine-administered trained-HI rats (n = 7) exhibited significantly improved motor performance compared to both saline-administered trained-HI rats (n = 11) and clemastine-administered untrained-HI rats (n = 7). These findings suggest that myelination may be a key mechanism in motor improvement after HI injury and that combining exercise training with clemastine administration could be an effective therapeutic strategy for motor improvement following HI injury.

Particulate matter induced cognitive impairments via endoplasmic reticulum stress-mediated damage to mitochondria-associated endoplasmic reticulum membranes in immature rats

Particulate matter (PM) exposure has been increasingly recognized as detrimental to cognitive function and is associated with neurodevelopmental disorders. Mitochondria-associated endoplasmic reticulum membranes (MAMs) form an integrated interface between mitochondria and the endoplasmic reticulum (ER), facilitating crucial cellular functions. Prolonged ER stress (ERS) is implicated in various pathological states in the nervous system. MAMs and ERS may play vital roles in adverse effects of early-life PM exposure on cognitive abilities. This study investigated whether ERS plays a role in PM-induced MAMs dysfunction, leading to neuronal damage and cognitive impairments in early postnatal rats. Using a rat model with PM exposure concentrations of 2 and 10 mg/kg from postnatal Day 3 (PND3) to PND28, we observed that PM exposure resulted in anxiety-like behavior and impaired spatial working memory. The protein levels of ERS markers, including GRP78 and CHOP, were significantly increased in response to PM exposure. Western blot, transmission electron microscopy (TEM), and immunofluorescence analyses revealed decreased MAMs-related proteins and disrupted MAM structure and function caused by PM exposure. Administration of the ERS inhibitor 4-phenylbutyric acid (4-PBA) ameliorated these effects, restoring MAMs integrity and improving cognitive deficits. These findings highlighted the key role of ERS-MAMs dysfunction in PM-induced neurotoxicity and cognitive impairments, providing a new perspective and strategy for the prevention of cognitive deficits in early age with PM exposure.

Maternal depressed mood and serotonergic antidepressant treatment during pregnancy differentially shape the continuity between fetal–newborn neurobehaviour

BackgroundPrenatal serotonin reuptake inhibitor (SRI) antidepressant exposure is associated with newborn neurobehavioural disturbances, but it remains unclear whether this reflects a transient pharmacologic condition or an altered neurodevelopmental trajectory emerging in utero from sustained gestational SRI exposure. AimThis study explored longitudinal relationships between third-trimester fetal physiology and newborn neurobehaviour, and determined whether early neurobehavioural continuity is shaped by prenatal SRI or depression exposure. MethodsParticipants were 127 pregnant mothers and their fetal-newborn offspring. Four groups were defined based on antenatal depressive symptoms and SRI treatment: Control (n = 51), Depressed (unmedicated; n = 35), SRI-Depressed (n = 26) and SRI-Non-Depressed (n = 15). Doppler measures of fetal heart rate (fHR), motor activity and vascular hemodynamics were obtained at 36-weeks' gestation, then newborn neurobehavioural maturity was evaluated at postnatal day-7. Partial least squares analysis was used to identify latent correlations between fetal-newborn measures; associations were further studied with hierarchical regression testing group moderation. ResultsTwo dimensions described 74 % of the covariance between fetal physiologic and newborn neurobehavioural measures (permuted p < 0.05). Three latent fetal-newborn relationships were significantly moderated by group: (1) lower fHR variability, and (2) greater fHR decelerations, predicted lower alertness/orientation scores but only in SRI-Depressed-group newborns; and (3) lower fetal cerebrovascular resistance predicted lower motor scores in Depressed-group newborns. SRI treatment to euthymia was not associated with fetal-newborn neurobehavioural disturbances. ConclusionsMaternal depression, both unmedicated and SRI-treated with persistent/poorly-managed mood symptoms, differentially shaped fetal-newborn neurobehavioural continuity. These findings suggest that neurobehavioural disturbances may predate birth, and underscore the importance of effective mental health management during pregnancy.

Lifelong Changes in the Choroidal Thickness, Refractive Status, and Ocular Dimensions in C57BL/6J Mouse.

To investigate the changes in choroidal thickness (ChT), refractive status, and ocular dimensions in the mouse eye in vivo using updated techniques and instrumentation. High-resolution swept-source optical coherence tomography (SS-OCT), eccentric infrared photoretinoscopy, and custom real-time optical coherence tomography were used to analyze choroidal changes, refractive changes and ocular growth in C57BL/6J mice from postnatal day (P) 21 to month 22. The ChT gradually increased with age, with the thickest region in the para-optic nerve head and thinning outward, and the temporal ChT was globally thicker than the nasal ChT. Retinal thickness remained stable until 4months and subsequently decreased. The average spherical equivalent refraction error was -4.81 ± 2.71 diopters (D) at P21, which developed into emmetropia by P32, reached a hyperopic peak (+5.75±1.38D) at P82 and returned to +0.66 ± 1.86 D at 22months. Central corneal thickness, anterior chamber depth, lens thickness, and axial length (AL) increased continuously before 4months, but subsequently exhibited subtle changes. Vitreous chamber depth decreased with lens growth. ChT was correlated significantly with the ocular parameters (except for retinal thickness) before the age of 4months, but these correlations diminished after 4months. Furthermore, for mice younger than 4months, the difference in the ChT, especially temporal ChT, between the two eyes contributed most to that of axial length and spherical equivalent refraction error. Four months could be a watershed age in the growth of mouse eyes. Large-span temporal recordings of refraction, ocular dimensions, and choroidal changes provided references for the study of the physiological and pathological mechanisms responsible for myopia.

Padsevonil suppresses seizures without inducing cell death in neonatal rats.

Padsevonil (PSL) is a rationally designed anti-seizure medication (ASM) which has overlapping mechanisms of action with the two most common ASMs used for neonatal seizures, phenobarbital (PB) and levetiracetam (LEV). Here we evaluated the anti-seizure properties of PSL across the neonatal and adolescent period in rats in the pentlyenetetrazole (PTZ) induced seizures model. Postnatal day (P)7, P14 and P21 Sprague-Dawley rat pups were pre-treated with PSL (1-30mg/kg), and assessed for seizure latency and severity 30min later following injection of PTZ. A separate cohort of P7 pups were treated with neonatal ASMs and euthanized 24h later (on P8) to assess induction of cell death, a feature common to many ASMs when given to P7 rodents. This effect has been extensively reported with PB, but not with LEV. Cell death was assessed by PathoGreen staining. PSL suppressed PTZ-evoked seizures across multiple age groups, particularly at higher doses, without producing increased cell death compared to vehicle. The effects of PSL were particularly notable at suppressing tonic-clonic seizure manifestations (82% of P7 and 100% of P14 and P21 animals were protected from tonic-clonic seizures with the 30mg/kg dose). PSL displayed dose-dependent anti-seizure effects in immature rodents in the PTZ model of seizures in immature rats. While many ASMs, including PB, induce cell death in neonatal rats, PSL does not. This suggests that PSL may offer therapeutic benefit and a favorable safety profile for the treatment of neonatal seizures.

Decreased Liver Kinase B1 Expression and Impaired Angiogenesis in a Murine Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is characterized by impaired lung alveolar and vascular growth. We investigated the hypothesis that neonatal exposure to hyperoxia leads to persistent BPD phenotype caused by decreased expression of liver kinase B1 (LKB1), a key regulator of mitochondrial function. We exposed mouse pups from Postnatal Day (P)1 through P10 to 21% or 75% oxygen. Half of the pups in each group received metformin or saline intraperitoneally from P1 to P10. Pups were killed at P4 or P10 or recovered in 21% O2 until euthanasia at P21. Lung histology and morphometry, immunofluorescence, and immunoblots were performed to detect changes in lung structure and expression of LKB1; downstream targets AMPK, PGC-1α, and electron transport chain (ETC) complexes; and Notch ligands Jagged 1 and delta-like 4. LKB1 signaling and invitro angiogenesis were assessed in human pulmonary artery endothelial cells (exposed to 21% or 95% O2 for 36 hours. Levels of LKB1, phosphorylated AMPK, PGC-1α, and ETC complexes were decreased in lungs at P10 and P21 in hyperoxia. Metformin increased LKB1, phosphorylated AMPK, PGC-1α, and ETC complexes at P10 and P21 in pups exposed to hyperoxia. Radial alveolar count was decreased, and mean linear intercept increased in pups exposed to hyperoxia at P10 and P21; these were improved by metformin. Lung capillary density was decreased in hyperoxia at P10 and P21 and was increased by metformin. In vitro angiogenesis was decreased in human pulmonary artery endothelial cells by 95% O2 and was improved by metformin. Decreased LKB1 signaling may contribute to decreased alveolar and vascular growth in a mouse model of BPD.

Multidisciplinary care to optimise pregnancy outcomes among Jehovah’s Witness: Case series over fifteen years in a tertiary teaching hospital

ObjectiveTo assess the obstetric and neonatal outcomes of Jehovah’s Witness (JW) mothers and the willingness to accept blood products after multidisciplinary management. Study DesignA retrospective case-control study was conducted at Queen Mary Hospital from 2005 to 2020. Delivery records of pregnant women who identified themselves as JW were reviewed. The immediate next age-matched non-JW patient in the booking register was assigned as control. ResultsA total of 96 subjects were identified within the study period (48 JW and 48 non-JW age-matched patients). The haemoglobin levels of JW and non-JW were similar at booking, 28 weeks of gestation, pre-delivery and postnatal day 2. JW mothers were more likely to receive iron supplements in the antenatal period than the control group (27.1 % vs. 6.3 %, p = 0.01) despite the similar rate of antenatal anemia in both groups (4.2 % vs. 4.2 %, p = 1.00). There were no differences in mode of delivery, total blood loss at delivery, rate of primary postpartum haemorrhage, gestational age at delivery, birth weight, and Apgar score at 1 and 5 min between JW and non-JW. There were no maternal deaths, hysterectomy or admissions to the adult intensive care unit in either group. Six JW women accepted packed cell transfusion at the initial consultation and did not receive multidisciplinary care. The remaining 42 JW women had consultant obstetric and anesthesiologist review before delivery. After multidisciplinary consultation, two (4.8 %, 2/42) accepted blood transmission and 11 (26.2 %, 11/42) accepted some components of blood. The remaining 29 (69 %, 29/42) women refused all blood products. ConclusionJW patients who received multidisciplinary care achieved comparable pregnancy and neonatal outcomes to the normal population. Antenatal iron supplement was more common among pregnant JW despite the similar rate of antenatal anemia compared with the non-JW women. 12.5% of JW women agreed packed cell transfusion at the initial consultation and a further 27.1% of JW women agreed to some forms of blood products after multidisciplinary counseling.

The effects of moderate alcohol and THC co-use during male and female rat adolescence on AKT-GSK3ß signaling in adulthood

Alcohol and cannabis are often taken in combination, and extensive co-use has been linked to enduring changes in cognitive and metabolic functioning. The underlying mechanisms for these effects are unclear, but we recently demonstrated that co-administration of ethanol and delta-9-tetrahydrocannbinol (THC) to adolescent rats caused lasting adaptations in GABA and glycogen synthase kinase 3ß (GSK3ß) signaling in the medial prefrontal cortex (mPFC). As a ubiquitous protein kinase, GSK3ß is downstream to the protein kinase B (also known as AKT) pathway that is activated by insulin receptor signaling in a main control center for metabolism and energy homeostasis, the mediobasal hypothalamus (MBH). Our goal here was to investigate if volitional co-use of low to moderate levels of ethanol and THC would impact the total and phosphorylated levels (p) of AKT and GSK3ß in the mPFC and MBH. Peri-adolescent Long Evans rats [postnatal day (P) 30–47] consumed 10 % ethanol, cookies laced with THC (3–10 mg/kg/day), both drugs, or vehicle controls. On P114, we modeled re-exposure to a behaviorally relevant dose of THC by challenging rats (i.p.) with 5 mg/kg THC (or vehicle) and sacrificed them 30 min later. Western blot analysis revealed that THC challenge increased pAKT and pGSK3ß compared to control similarly across all treatment groups, sexes, and brain regions; no effects on total levels of AKT or GSK3ß were found. Previously reported behavioral results from these rats showed no differences in working memory assessed in adulthood. Although future studies will be necessary to determine the role of exposure dose on drug-induced adaptations in AKT and GSK3ß signaling, the current findings suggest that moderate volitional co-use of alcohol and THC may not produce long-term deficits that persist into adulthood.

Ultrastructural Features of Left Ventricle Cardiomyocytes in Preterm Newborn Rats.

The structure of left ventricular cardiomyocytes of 1 day preterm newborn rats was studied using transmission electron microscopy. It was shown that the relative area of the nucleus in cardiomyocytes of preterm rats is lower, and the relative area of the cytoplasm is higher than in full-term rats, while the relative areas of myofibrils and mitochondria do not differ. In cardiomyocytes of preterm rats damaged mitochondria, subsegmental myofibrillar contracture, and cytoplasmic swelling were found on the first postnatal day. Preterm birth in rats, in contrast to birth at term, is accompanied by the development of a number of ultrastructural damages in cardiomyocytes.