Abstract Background Neural stem cells (NSCs) have the potential to engraft and replace damaged brain tissue, repairing the damaged neonatal brain that causes cerebral palsy (CP). There are procedures that could increase engraftment of NSCs and may be critical for efficacy, but hold notable risks. Before clinical trials progress, it is important to engage with the CP community to understand their opinions. The aim of this study was to determine the acceptability of NSC therapy for CP in the CP community. Methods Australian residents with CP and parents/carers of those with CP completed a questionnaire to determine their willingness to use NSCs from three sources (fetal, embryonic and induced pluripotent stem cells) and their willingness to undergo accompanying procedures (neurosurgery, immunosuppression) that carry potential risks. To further explore their views, participants also answered free text questions about their ethical concerns regarding the source of NSCs and their perceptions of meaningful outcomes following NSC treatment. Results In total, 232 responses were analyzed. Participants were willing to use NSCs from all three cell sources and were willing to undergo NSC therapy despite the need for neurosurgery and immunosuppression. Participants identified a range of outcome domains considered important following NSC treatment including gross motor function, quality of life, independence and cognitive function. Conclusions Hypothetical NSC therapy was acceptable to the Australian CP community. This study has identified important findings from the CP community which can be used to inform future NSC research, including the design of clinical trials which may help to increase recruitment, compliance and participant satisfaction.
Introduction: In Aotearoa New Zealand the COVID-19 pandemic in 2020 resulted in a four-week lockdown in March and April of 2020 with ongoing restrictions for several weeks. Aim: To explore the experiences of women who were pregnant, giving birth and/or managing the early weeks of motherhood during the 2020 COVID-19 alert levels 3 and 4 in Aotearoa New Zealand. Method: This qualitative study used semi-structured interviews to explore childbirth experiences during the COVID-19 alert level restrictions. Reflexive, inductive, thematic analysis was used to identify codes, subthemes and themes. Findings: Seventeen women participated in the study. Analysis of the qualitative interviews revealed four themes. The first of these was: Relationship with my midwife, in which participants described the importance of the midwifery continuity of care relationship, with midwives often going above and beyond usual care and filling the gaps in service provision. In the Disruption to care theme the participants described feeling anxious and uncertain, with concerns about the hospital restrictions and changing rules. The participants also described their Isolation during postnatal care in a maternity facility due to separation from their partners/whānau; they describe receiving the bare necessities of care, feeling they were on their own, and working towards their release home; all of which took an emotional and mental toll. The final theme, Undisturbed space, describes the positive aspects of the lockdown of being undisturbed by visitors, being better able to bond with the baby and being able to breastfeed in peace. Conclusion: Midwifery continuity of care appears to have supported these women and their families/whānau during the service restrictions caused by the COVID-19 lockdown. The partner, or other primary support person, and whānau should be considered essential support and should not be excluded from early postpartum hospital care.
Abstract Creatine is a metabolite involved in cellular energy homeostasis. In this study, we examined placental creatine content, and expression of the enzymes required for creatine synthesis, transport and the creatine kinase reaction, in pregnancies complicated by low birthweight. We studied first trimester chorionic villus biopsies (CVBs) of small for gestational age (SGA) and appropriately grown infants (AGA), along with third trimester placental samples from fetal growth restricted (FGR) and healthy gestation-matched controls. Placental creatine and creatine precursor (guanidinoacetate—GAA) levels were measured. Maternal and cord serum from control and FGR pregnancies were also analyzed for creatine concentration. mRNA expression of the creatine transporter (SLC6A8); synthesizing enzymes arginine:glycine aminotransferase (GATM) and guanidinoacetate methyltransferase (GAMT); mitochondrial (mtCK) and cytosolic (BBCK) creatine kinases; and amino acid transporters (SLC7A1 & SLC7A2) was assessed in both CVBs and placental samples. Protein levels of AGAT (arginine:glycine aminotransferase), GAMT, mtCK and BBCK were also measured in placental samples. Key findings; total creatine content of the third trimester FGR placentae was 43% higher than controls. The increased creatine content of placental tissue was not reflected in maternal or fetal serum from FGR pregnancies. Tissue concentrations of GAA were lower in the third trimester FGR placentae compared to controls, with lower GATM and GAMT mRNA expression also observed. No differences in the mRNA expression of GATM, GAMT or SLC6A8 were observed between CVBs from SGA and AGA pregnancies. These results suggest placental creatine metabolism in FGR pregnancies is altered in late gestation. The relevance of these changes on placental bioenergetics should be the focus of future investigations.
Brain injury in the asphyxic newborn infant may be exacerbated by delayed restoration of cardiac output and oxygen delivery. With increasing severity of asphyxia, cerebral autoregulatory responses are compromised. Further brain injury may occur in association with high arterial pressures and cerebral blood flows following the restoration of cardiac output. Initial resuscitation aims to rapidly restore cardiac output and oxygenation whilst mitigating the impact of impaired cerebral autoregulation. Recent animal studies have indicated that the current standard practice of immediate umbilical cord clamping prior to resuscitation may exacerbate injury. Resuscitation prior to umbilical cord clamping confers several haemodynamic advantages. In particular, it retains the low-resistance placental circuit that mitigates the rebound hypertension and cerebrovascular injury. Prolonged cerebral hypoxia–ischaemia is likely to contribute to further perinatal brain injury, while, at the same time, tissue hyperoxia is associated with oxidative stress. Efforts to monitor and target cerebral flow and oxygen kinetics, for example, using near-infrared spectroscopy, are currently being evaluated and may facilitate development of novel resuscitation approaches.
Spontaneous subarachnoid hemorrhage (SAH) causes a prolonged corrected QT interval (QTc) in 25% to 90% of patients, but whether this occurs with traumatic SAH (tSAH) is unknown. This investigation was conducted to determine whether QTc prolongation occurs with tSAH and to evaluate QTc prolongation with respect to severity of tSAH.Records of 104 consecutive tSAH patients were reviewed. A QTc was calculated on posttrauma day (PTD) 0, 1, and 3. Cranial computed tomography (CT) scans were graded for severity using a previously validated scale. QTc intervals were compared based on CT scan severity.Pennsylvania level II trauma center.Trauma patients with tSAH.NoneQTc prolongation occurred in 67% of those with tSAH. Mean QTc intervals for PTD0, PTD1, and PTD3 were 470 +/- 69 ms, 467 +/- 72 ms, and 465 +/- 50 ms, respectively. As the severity of the tSAH increased, the average QTc became more prolonged (Pearson's r = 0.855, P = 0.003).tSAH is a common cause of an acquired prolonged QTc syndrome. As the tSAH becomes more severe, the QTc becomes more prolonged.