Management and investigation of neonatal encephalopathy: 2017 update.

This review discusses an approach to determining the cause of neonatal encephalopathy, as well as current evidence on resuscitation and subsequent management of hypoxic-ischaemic encephalopathy (HIE). Encephalopathy in neonates can be due to varied aetiologies in addition to hypoxic-ischaemia. A combination of careful history, examination and the judicious use of investigations can help determine the cause. Over the last 7 years, infants with moderate to severe HIE have benefited from the introduction of routine therapeutic hypothermia; the number needed to treat for an additional beneficial outcome is 7 (95% CI 5 to 10). More recent research has focused on optimal resuscitation practices for babies with cardiorespiratory depression, such as delayed cord clamping after establishment of ventilation and resuscitation in air. Around a quarter of infants with asystole at 10 min after birth who are subsequently cooled have normal outcomes, suggesting that individualised decision making on stopping resuscitation is needed, based on access to intensive treatment unit and early cooling. The full benefit of cooling appears to have been exploited in our current treatment protocols of 72 hours at 33.5°C; deeper and longer cooling showed adverse outcome. The challenge over the next 5-10 years will be to assess which adjunct therapies are safe and optimise hypothermic brain protection in phase I and phase II trials. Optimal care may require tailoring treatments according to gender, genetic risk, injury severity and inflammatory status

The subthreshold-active KV7 current regulates neurotransmission by limiting spike-induced Ca2+ influx in hippocampal mossy fiber synaptic terminals

Little is known about the properties and function of ion channels that affect synaptic terminal-resting properties. One particular subthreshold-active ion channel, the Kv7 potassium channel, is highly localized to axons, but its role in regulating synaptic terminal intrinsic excitability and release is largely unexplored. Using electrophysiological recordings together with computational modeling, we found that the KV7 current was active at rest in adult hippocampal mossy fiber synaptic terminals and enhanced their membrane conductance. The current also restrained action potential-induced Ca2+ influx via N- and P/Q-type Ca2+ channels in boutons. This was associated with a substantial reduction in the spike half-width and afterdepolarization following presynaptic spikes. Further, by constraining spike-induced Ca2+ influx, the presynaptic KV7 current decreased neurotransmission onto CA3 pyramidal neurons and short-term synaptic plasticity at the mossy fiber–CA3 synapse. This is a distinctive mechanism by which KV7 channels influence hippocampal neuronal excitability and synaptic plasticity

Pollution from uncontrolled coal fires: Continuous gaseous emissions and nanoparticles from coal mines

In this investigation, the coal fires in different Colombian coal mines were studied using advanced electron beam and X-ray diffraction techniques. The results were compared with information from highresolution transmission electron microscopy (HR-TEM) equipped with a dispersive X-ray detector (EDS). Amorphous phases, salammoniac, anatase, muscovite, goethite, jarosite, calcite, gypsum, kaolinite, illite, and quartz are the dominant mineral matter constituents in almost all of the coal fires, with minute quantities of native sulfur, magnetite, siderite, pyrite, pickeringite, epsomite, hexahydrite, halotrichite being present in around half of the investigated coal fire samples. Other minerals that are present in some particular samples are chlorite, ankerite, and dolomite. Fe-sulfides were also detected particularly in the pyrite-bearing coal fires, possibly indicating oxidation of the Fe-sulfides occurring with coal fires. Exhaust discharge data indicate an overall trend of reducing carbon dioxide (CO2) and carbon monoxide (CO) releases (between 1.5 and 34%) from the coal fires. This is the first report on Colombian coal fires, which would be important for different perspectives of the research in the area

River dynamics and nanopaticles formation: A comprehensive study on the nanoparticle geochemistry of suspended sediments in the Magdalena River, Caribbean Industrial Area

The coastal zones on continental shelves are the main channels for the distribution of fluvial-sourced suspended sediments (SSs). In the current research, the monthly average amount of SS draining into the Caribbean Sea from the Magdalena River in northern Colombia was analyzed to detect nanoparticle (NPs) containing potential hazardous elements (PHEs). The ecological authorities of Colombia claimed that the climate change is the key reason behind land erosion and floods occurred in the last years; therefore, an elaborate understanding of NP dynamics between the Magdalena River body and streambed is an essential issue in SS research. In this work, the NP geochemistry of SS in the Magdalena River estuary was studied from the perspective of water quality controls on SS sorting. The morphologies and the structures of NPs (<100 nm) were examined by field emission scanning electron microscopy (FESEM), high-resolution transmission electron microscopy (HR-TEM), and selected area electron diffraction (SAED)/micro-beam diffraction (MBD)/energy dispersive X-ray spectroscopy (EDS) techniques. The average size of NPs was found to be greater than 2 nm and Al, Ti, Fe oxides, and other hazardous elements were also detected in the SS. The obtained data confirmed that these typical categories of NPs caused the occurrence-dependent intensification of a conjugative transmission rate associated with the regulators. The advanced electron beam technique provided a clear insight into SS transportation; therefore, it could be used as an essential instrument for river supervision/dynamics

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment

Melatonin and/or erythropoietin combined with hypothermia in a piglet model of perinatal asphyxia

AAs therapeutic hypothermia is only partially protective for neonatal encephalopathy, safe and effective adjunct therapies are urgently needed. Melatonin and erythropoietin show promise as safe and effective neuroprotective therapies. We hypothesized that melatonin and erythropoietin individually augment 12-h hypothermia (double therapies) and hypothermia + melatonin + erythropoietin (triple therapy) leads to optimal brain protection. Following carotid artery occlusion and hypoxia, 49 male piglets (<48 h old) were randomized to: (i) hypothermia + vehicle (n = 12), (ii) hypothermia + melatonin (20 mg/kg over 2 h) (n = 12), (iii) hypothermia + erythropoietin (3000 U/kg bolus) (n = 13) or (iv) tripletherapy (n = 12). Melatonin, erythropoietin or vehicle were given at 1, 24 and 48 h after hypoxia–ischaemia. Hypoxia–ischaemia severity was similar across groups. Therapeutic levels were achieved 3 hours after hypoxia–ischaemia for melatonin (15–30 mg/l) and within 30 min of erythropoietin administration (maximum concentration 10 000 mU/ml). Compared to hypothermia + vehicle, we observed faster amplitude-integrated EEG recovery from 25 to 30 h with hypothermia + melatonin (P = 0.02) and hypothermia + erythropoietin (P = 0.033) and from 55 to 60 h with tripletherapy (P = 0.042). Magnetic resonance spectroscopy lactate/N-acetyl aspartate peak ratio was lower at 66 h in hypothermia + melatonin (P = 0.012) and tripletherapy (P = 0.032). With hypothermia + melatonin, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells were reduced in sensorimotor cortex (P = 0.017) and oligodendrocyte transcription factor 2 labelled-positive counts increased in hippocampus (P = 0.014) and periventricular white matter (P = 0.039). There was no reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells with hypothermia + erythropoietin, but increased oligodendrocyte transcription factor 2 labelled-positive cells in 5 of 8 brain regions (P < 0.05). Overall, melatonin and erythropoietin were safe and effective adjunct therapies to hypothermia. Hypothermia + melatonin double therapy led to faster amplitude-integrated EEG recovery, amelioration of lactate/N-acetyl aspartate rise and reduction in terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelled-positive cells in the sensorimotor cortex. Hypothermia + erythropoietin doubletherapy was in association with EEG recovery and was most effective in promoting oligodendrocyte survival. Tripletherapy provided no added benefit over the double therapies in this 72-h study. Melatonin and erythropoietin influenced cell death and oligodendrocyte survival differently, reflecting distinct neuroprotective mechanisms which may become more visible with longer-term studies. Staggering the administration of therapies with early melatonin and later erythropoietin (after hypothermia) may provide better protection; each therapy has complementary actions which may be time critical during the neurotoxic cascade after hypoxia–ischaemia