Uso de Hipotermia Induzida no Colapso Súbito Pós-Natal: um Estudo Retrospetivo

Introduction: Sudden and unexpected postnatal collapse is a rare event with potentially dramatic consequences. Intervention approaches are limited, but hypothermia has been considered after postnatal collapse. The aim of this study was to analyse sudden and unexpected postnatal collapse cases that underwent therapeutic hypothermia in the five Portuguese hypothermia centres. Material and methods: In this multicentre, retrospective and descriptive study, clinical, ultrasonography, amplitude-integrated electroencephalography and brain magnetic resonance findings of newborns with postnatal collapse that underwent therapeutic hypothermia are reported (2010 - 2018). Statistical analysis was performed by using IBM SPSS Statistics version 21. Results: Twenty-two cases of sudden and unexpected postnatal collapse were referred for therapeutic hypothermia (82% outborn), all ≥ 36 weeks, with Apgar 5´ ≥ 8. Collapse occurred during the first two hours in 73% (all < 24 hours), 50% during skin-to-skin care, 55% related to feeding and 23% during co-bedding. Moderate-severe encephalopathy and severe acidosis were observed (median: Thompson score 16, pH 6.90, base deficit 22 mmol/L). Amplitude-integrated electroencephalogram was abnormal in 95% and magnetic resonance imaging showed severe brain injury in 46%. The mortality rate was 50%. A possible cause was identified in 27%. Discussion: The incidence rate of 2.7 sudden cases of postnatal collapse per 100 000 births, is possibly under-estimated. All infants suffered the collapse in the first day, mostly within the first two hours, as reported before. Possible causes were identified in less than a third of cases, but multiple predisposing conditions were identified, suggesting that prevention may be possible. Newborn positioning and skin-to-skin care have been the most discussed practices. A significant proportion of infants had poor outcomes. Lower Thompson score, electroencephalogram amplitude normalization and normal magnetic resonance imaging seemed to indicate better outcomes. Although conclusive trials on therapeutic hypothermia after postnatal collapse are not available, its use has been considered individually. No severe adverse effects directly related to hypothermia were registered in this study, but the results do not allow drawing meaningful conclusions. Conclusion: In our national sample of 22 infants who suffered sudden and unexpected postnatal collapse and underwent therapeutic hypothermia, a significant proportion had poor outcomes. Absolute conclusions from our experience with hypothermia in postnatal collapse cannot be drawn, but systematic reporting of cases and long-term clinical evaluation would facilitate understanding of the real benefits of hypothermia. As this procedure has not been validated with clinical trials for this indication, its use should be considered on a case-by-case approach. The potentially avoidable nature of unexpected postnatal collapse is evident from its association with certain behaviours and risk factors. Surveillance practices during the first hours should be implemented, whilst the benefits of breastfeeding and skin-to-skin care should continue to be widely promoted.info:eu-repo/semantics/publishedVersio

Temperature and force dependence of nanoscale electron transport via the Cu protein Azurin

The mechanisms of solid-state electron transport (ETp) via a monolayer of immobilized Azurin (Az) was examined by conducting probe atomic force microscopy (CP-AFM), both as function of temperature (248 - 373K) and of applied tip force (6-12 nN). By varying both temperature and force in CP-AFM, we find that the ETp mechanism can alter with a change in the force applied via the tip to the proteins. As the applied force increases, ETp via Az changes from temperature-independent to thermally activated at high temperatures. This is in contrast to the Cu-depleted form of Az (apo-Az), where increasing the applied force causes only small quantitative effects, that fit with a decrease in electrode spacing. At low force ETp via holo-Az is temperature-independent and thermally activated via apo-Az. This observation agrees with macroscopic-scale measurements, thus confirming that the difference in ETp dependence on temperature between holo- and apo-Az is an inherent one that may reflect a difference in rigidity between the two forms. An important implication of these results, which depend on CP-AFM measurements over a significant temperature range, is that for ETp measurements on floppy systems, such as proteins, the stress applied to the sample should be kept constant or, at least controlled during measurement.Comment: 24 pages, 6 figures, plus Supporting Information with 4 pages and 2 figure

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Tuning electronic transport via hepta-alanine peptides junction by tryptophan doping

Charge migration for electron transfer via the polypeptide matrix of proteins is a key process in biological energy conversion and signaling systems. It is sensitive to the sequence of amino acids composing the protein and, therefore, offers a tool for chemical control of charge transport across biomaterial-based devices. We designed a series of linear oligoalanine peptides with a single tryptophan substitution that acts as a "dopant," introducing an energy level closer to the electrodes' Fermi level than that of the alanine homopeptide. We investigated the solid-state electron transport (ETp) across a self-assembled monolayer of these peptides between gold contacts. The single tryptophan "doping" markedly increased the conductance of the peptide chain, especially when its location in the sequence is close to the electrodes. Combining inelastic tunneling spectroscopy, UV photoelectron spectroscopy, electronic structure calculations by advanced density-functional theory, and dc current-voltage analysis, the role of tryptophan in ETp is rationalized by charge tunneling across a heterogeneous energy barrier, via electronic states of alanine and tryptophan, and by relatively efficient direct coupling of tryptophan to a Au electrode. These results reveal a controlled way of modulating the electrical properties of molecular junctions by tailor-made "building block" peptides