Phase-Changing Glauber Salt Solution for Medical Applications in the 28-32 °C Interval

(1) Background: The field of medicine requires simple cooling materials. However, there is little knowledge documented about phase change materials (PCM) covering the range of 28 to 40 degrees Celsius, as needed for medical use. Induced mild hypothermia, started within 6 h after birth, is an emerging therapy for reducing death and severe disabilities in asphyxiated infants. Currently, this hypothermia is accomplished with equipment that needs a power source and a liquid supply. Neonatal cooling is more frequent in low-resource settings, where ~1 million deaths are caused by birth-asphyxia. (2) Methods: A simple and safe cooling method suitable for medical application is needed for the 28 to 37.5 °C window. (3) Results: Using empirical experiments in which the ingredients in Glauber salt were changed, we studied the effects of temperature on material in the indicated temperature range. The examination, in a controlled manner, of different mixtures of NaCl, Na2SO4 and water resulted in a better understanding of how the different mixtures act and how to compose salt solutions that can satisfy clinical cooling specifications. (4) Conclusions: Our Glauber salt solution is a clinically suited PCM in the temperature interval needed for the cooling of infants suffering from asphyxia

Developmental motor problems and health-related quality of life in 5-year-old children born extremely preterm: A European cohort study

Aim To measure the association between cerebral palsy (CP) and non-CP-related movement difficulties and health-related quality of life (HRQoL) among 5-year-old children born extremely preterm (<28 weeks gestational age). Method We included 5-year-old children from a multi-country, population-based cohort of children born extremely preterm in 2011 to 2012 in 11 European countries (n = 1021). Children without CP were classified using the Movement Assessment Battery for Children, Second Edition as having significant movement difficulties (<= 5th centile of standardized norms) or being at risk of movement difficulties (6th-15th centile). Parents reported on a clinical CP diagnosis and HRQoL using the Pediatric Quality of Life Inventory. Associations were assessed using linear and quantile regressions. Results Compared to children without movement difficulties, children at risk of movement difficulties, with significant movement difficulties, and CP had lower adjusted HRQoL total scores (beta [95% confidence interval] = -5.0 [-7.7 to -2.3], -9.1 [-12.0 to -6.1], and - 26.1 [-31.0 to -21.2]). Quantile regression analyses showed similar decreases in HRQoL for all children with CP, whereas for children with non-CP-related movement difficulties, reductions in HRQoL were more pronounced at lower centiles. Interpretation CP and non-CP-related movement difficulties were associated with lower HRQoL, even for children with less severe difficulties. Heterogeneous associations for non-CP-related movement difficulties raise questions for research about mitigating and protective factors.Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Grant/Award Number: SFRH/BPD/117597/2016; Horizon 2020 Framework Programme, Grant/Award Number: No 633724 and No 733280; Seventh Framework Programme, Grant/Award Number: No 25988

Linkage between fitness of yeast cells and adenylate kinase catalysis

Enzymes have evolved with highly specific values of their catalytic parameters kcat and KM. This poses fundamental biological questions about the selection pressures responsible for evolutionary tuning of these parameters. Here we are address these questions for the enzyme adenylate kinase (Adk) in eukaryotic yeast cells. A plasmid shuffling system was developed to allow quantification of relative fitness (calculated from growth rates) of yeast in response to perturbations of Adk activity introduced through mutations. Biophysical characterization verified that all variants studied were properly folded and that the mutations did not cause any substantial differences to thermal stability. We found that cytosolic Adk is essential for yeast viability in our strain background and that viability could not be restored with a catalytically dead, although properly folded Adk variant. There exist a massive overcapacity of Adk catalytic activity and only 12% of the wild type kcat is required for optimal growth at the stress condition 20°C. In summary, the approach developed here has provided new insights into the evolutionary tuning of kcat for Adk in a eukaryotic organism. The developed methodology may also become useful for uncovering new aspects of active site dynamics and also in enzyme design since a large library of enzyme variants can be screened rapidly by identifying viable colonies

Variation in follow-up for children born very preterm in Europe

Background: Children born very preterm (<32 weeks of gestation) face high risks of neurodevelopmental and health difficulties compared with children born at term. Follow-up after discharge from the neonatal intensive care unit is essential to ensure early detection and intervention, but data on policy approaches are sparse. Methods: We investigated the characteristics of follow-up policy and programmes in 11 European countries from 2011 to 2022 using healthcare informant questionnaires and the published/grey literature. We further explored how one aspect of follow-up, its recommended duration, may be reflected in the percent of parents reporting that their children are receiving follow-up services at 5 years of age in these countries using data from an area-based cohort of very preterm births in 2011/12 (N = 3635). Results: Between 2011/12 and 22, the number of countries with follow-up policies or programmes increased from 6 to 11. The policies and programmes were heterogeneous in eligibility criteria, duration and content. In countries that recommended longer follow-up, parent-reported follow-up rates at 5 years of age were higher, especially among the highest risk children, born <28 weeks’ gestation or with birthweight <1000 g: between 42.1% and 70.1%, vs. <20% in most countries without recommendations. Conclusions: Large variations exist in follow-up policies and programmes for children born very preterm in Europe; differences in recommended duration translate into cross-country disparities in reported follow-up at 5 years of age

Long Lasting Local and Systemic Inflammation after Cerebral Hypoxic ischemia in Newborn Mice

Background: Hypoxic ischemia (HI) is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice. Methodology/Principal Findings: We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune responses in the brain 24 h to 7 months after HI brain injury. In addition, functional studies of ex vivo splenocytes after cerebral hypoxic ischemia were performed. Both central and peripheral activation of CD11b + and CD11c + antigen presenting cells were seen with expression of the costimulatory molecule CD86 and MHC-II, indicating active antigen presentation in the damaged hemisphere and in the spleen. After one week, naïve CD45rb + T-lymphocytes were demonstrated in the damaged brain hemisphere. In a second phase after three months, pronounced activation of CD45rb 2 T-lymphocytes expressing CD69 and CD25 was seen in the damaged hemisphere. Brain homogenate induced proliferation in splenocytes after HI but not in controls. Conclusions/Significance: Our findings demonstrate activation of both local and systemic immune responses months after hypoxic ischemic neonatal brain injury. The long term immune activation observed is of general importance for future studies of the inflammatory response after brain injury as most previous studies have focused on the first few weeks afte

High healthcare use at age five in a European cohort of children born very preterm

Objectives To describe parent-reported healthcare service use at five years of age in children born very preterm and investigate whether perinatal and social factors and the use of very preterm follow-up services are associated with high service use. Study design We used data from an area-based cohort of births at <32 weeks of gestation from 11 European countries, collected from birth records and parental questionnaires at five years of age. Using the published literature, we defined high use of outpatient/inpatient care (≥4 sick visits to general practitioners, pediatricians, or nurses, ≥3 emergency room visits, or ≥1 overnight hospitalization) and specialist care (≥2 different specialists or ≥3 visits). We also categorized countries as having either high or low rates of children using very preterm follow-up services at five years. Results Overall, 43% of children had high outpatient/inpatient care use, and 48% had high specialist care use during the previous year. Perinatal factors were associated with high outpatient/inpatient and specialist care use, with a more significant association with specialist services. Associations with intermediate parental educational level and unemployment were stronger for outpatient/inpatient services. Living in a country with higher rates of very preterm follow-up service use was associated with lower use of outpatient/inpatient services. Conclusions Children born very preterm had high healthcare service use at five years of age, with different patterns for outpatient/inpatient and specialist care by perinatal and social factors. Longer follow-up of children born very preterm may improve care coordination and help avoid undesirable health service use

Follow-up after very preterm birth in Europe

International audienc