Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury

There is a need for a method of real-time assessment of brain metabolism during neonatal hypoxic-ischaemic encephalopathy (HIE). We have used broadband near-infrared spectroscopy (NIRS) to monitor cerebral oxygenation and metabolic changes in 50 neonates with HIE undergoing therapeutic hypothermia treatment. In 24 neonates, 54 episodes of spontaneous decreases in peripheral oxygen saturation (desaturations) were recorded between 6 and 81 h after birth. We observed differences in the cerebral metabolic responses to these episodes that were related to the predicted outcome of the injury, as determined by subsequent magnetic resonance spectroscopy derived lactate/N-acetyl-aspartate. We demonstrated that a strong relationship between cerebral metabolism (broadband NIRS-measured cytochrome-c-oxidase (CCO)) and cerebral oxygenation was associated with unfavourable outcome; this is likely to be due to a lower cerebral metabolic rate and mitochondrial dysfunction in severe encephalopathy. Specifically, a decrease in the brain tissue oxidation state of CCO greater than 0.06 µM per 1 µM brain haemoglobin oxygenation drop was able to predict the outcome with 64% sensitivity and 79% specificity (receiver operating characteristic area under the curve = 0.73). With further work on the implementation of this methodology, broadband NIRS has the potential to provide an early, cotside, non-invasive, clinically relevant metabolic marker of perinatal hypoxic-ischaemic injury

Многофункциональное сельское хозяйство и его влияние на развитие сельских территорий

The paper deals with the main conceptual approaches to the definition of agriculture multifunctionality, indicates positive changes towards multifunctionality of rural territories in Ukraine and substantiates the main restraining factors such as low level of innovation activity of economic entities operating in this sphere, related sectors of economy, moral ageing of social and communal infrastructure of the village, lack of relations with universities which are the main generators of knowledge. The paper proposes to establish the Regional Coordination Centers for Rural Development in the structure of the Agro-industrial Development Departments. The main function of the centers should be obtaining multifunctional agriculture due to interaction of enterprises and the state shifting the emphasis from production to rural development. It is noted that the establishment of such centers in the conditions of decentralization will allow ensuring interaction of enterprises, state and population and implementing properly multifunctionality of agriculture. It is proved that forming the conceptual foundations of rural development, it should be borne in mind that sustainable multifunctional development should be based on effective rural economy, extended reproduction of human capital and productive employment of rural population, on improvement of people’s quality of life, rational use of natural resources and their reproduction.В статье рассматриваются основные концептуальные подходы к определению многофункциональности сельского хозяйства, констатированы положительные сдвиги в направлении многофункциональности сельских территорий в Украине и обоснованы основные сдерживающие факторы, среди которых: низкий уровень инновационной активности субъектов хозяйствования, работающих в этой сфере и смежных с ней секторах экономики; моральное старение социальной и коммунальной инфраструктуры сельской местности; отсутствие связи с университетами – основными генераторами знаний. Предложено создание в структуре департаментов агропромышленного развития региональных координационных центров развития села, основной функцией которых должно стать достижение многофункциональности сельского хозяйства путем взаимодействия предприятий и государства со смещением акцента от производственной функции к сельскому развитию. Отмечено, что в условиях децентрализации создание таких центров позволит обеспечить взаимодействие предприятий, государства и населения и в должной мере реализовать многофункциональность сельского хозяйства. Доказано, что при формировании концептуальных основ развития сельских территорий необходимо иметь в виду, что устойчивое многофункциональное их развитие должно быть основано на эффективной сельской экономике, расширенном воспроизводстве человеческого капитала и продуктивной занятости сельского населения, повышении уровня и качества его жизни, рациональном использовании и воспроизводстве природных ресурсов

Proton Magnetic Resonance Spectroscopy Lactate/N-Acetylaspartate Within 48 h Predicts Cell Death Following Varied Neuroprotective Interventions in a Piglet Model of Hypoxia–Ischemia With and Without Inflammation-Sensitization

Despite therapeutic hypothermia, survivors of neonatal encephalopathy have high rates of adverse outcome. Early surrogate outcome measures are needed to speed up the translation of neuroprotection trials. Thalamic lactate (Lac)/N-acetylaspartate (NAA) peak area ratio acquired with proton (1H) magnetic resonance spectroscopy (MRS) accurately predicts 2-year neurodevelopmental outcome. We assessed the relationship between MR biomarkers acquired at 24–48 h following injury with cell death and neuroinflammation in a piglet model following various neuroprotective interventions. Sixty-seven piglets with hypoxia–ischemia, hypoxia alone, or lipopolysaccharide (LPS) sensitization were included, and neuroprotective interventions were therapeutic hypothermia, melatonin, and magnesium. MRS and diffusion-weighted imaging (DWI) were acquired at 24 and 48 h. At 48 h, experiments were terminated, and immunohistochemistry was assessed. There was a correlation between Lac/NAA and overall cell death [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] [mean Lac/NAA basal ganglia and thalamus (BGT) voxel r = 0.722, white matter (WM) voxel r = 0.784, p < 0.01] and microglial activation [ionized calcium-binding adapter molecule 1 (Iba1)] (BGT r = −0.786, WM r = −0.632, p < 0.01). Correlation with marker of caspase-dependent apoptosis [cleaved caspase 3 (CC3)] was lower (BGT r = −0.636, WM r = −0.495, p < 0.01). Relation between DWI and TUNEL was less robust (mean diffusivity BGT r = −0.615, fractional anisotropy BGT r = 0.523). Overall, Lac/NAA correlated best with cell death and microglial activation. These data align with clinical studies demonstrating Lac/NAA superiority as an outcome predictor in neonatal encephalopathy (NE) and support its use in preclinical and clinical neuroprotection studies

Impact of myocardial injury on regional left ventricular function in the course of acute myocarditis with preserved ejection fraction: insights from segmental feature tracking strain analysis using cine cardiac MRI

The aim of this study was to provide insights into myocardial adaptation over time in myocyte injury caused by acute myocarditis with preserved ejection fraction. The effect of myocardial injury, as defined by the presence of late gadolinium enhancement (LGE), on the change of left ventricular (LV) segmental strain parameters was evaluated in a longitudinal analysis. Patients with a first episode of acute myocarditis were enrolled retrospectively. Peak radial (PRS), longitudinal (PLS) and circumferential (PCS) LV segmental strain values at baseline and at follow-up were computed using feature tracking cine cardiac magnetic resonance imaging. The change of segmental strain values in LGE positive (LGE+) and LGE negative (LGE−) segments was compared over a course of 89 ± 20 days. In 24 patients, 100 LGE+ segments and 284 LGE− segments were analysed. Between LGE+ and LGE− segments, significant differences were found for the change of segmental PCS (p < 0.001) and segmental PRS (p = 0.006). LGE + segments showed an increase in contractility, indicating recovery, and LGE− segments showed a decrease in contractility, indicating normalisation after a hypercontractile state or impairment of an initially normal contracting segment. No significant difference between LGE+ and LGE− segments was found for the change in segmental PLS. In the course of acute myocarditis with preserved ejection fraction, regional myocardial function adapts inversely in segments with and without LGE. As these effects seem to counterbalance each other, global functional parameters might be of limited use in monitoring functional recovery of these patients

An optical biomarker of hypoxic-ischaemic injury severity in the neonatal brain

We present a new optical platform that combines broadband near-infrared spectroscopy and diffuse correlation spectroscopy for identification of brain injury severity in a preclinical model of hypoxic-ischemic encephalopathy of the neonatal brain

First-principles study on the energetics and vibrational properties of the S2 - impurity in alkali-halide crystals

金沢大学大学院自然科学研究科計算科学金沢大学理学部We have performed first-principles electronic structure calculations for the S2 and S2- molecules in the vacuum and found that the calculated equilibrium bond lengths and vibrational spectroscopic constants are in good agreement with the experiments as well as the previous calculations. Based on this conformation we extended these calculations to the substitutional S2- molecule in the alkali halides, such as NaCl, NaBr, NaI, KCI, KBr, KI, RbCl, RbBr, and RbI. It is found from these calculations that the S2- center aligned to [110] direction is generally favorable over those with the [100] and [111] orientations, in agreement with the experiments. We also found that the vibrational frequencies of the S2- anion in the alkali halides shift to higher energies with decreasing lattice parameters. These results suggest that the change in the bond length of the S2- anion in the matrices depends on the species of halogen atom, while the frequencies are influenced by the species of alkali atom

An optical biomarker of hypoxic-ischaemic injury severity in the neonatal brain

We present a new optical platform that combines broadband near-infrared spectroscopy and diffuse correlation spectroscopy for identification of brain injury severity in a preclinical model of hypoxic-ischemic encephalopathy of the neonatal brain

Heart failure in COVID-19: the multicentre, multinational PCHF-COVICAV registry.

AIMS: We assessed the outcome of hospitalized coronavirus disease 2019 (COVID-19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. METHODS AND RESULTS: International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID-19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF-COVICAV). The primary endpoint was in-hospital mortality. Of 1974 patients hospitalized with COVID-19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62-81] years, 58% male), with HF being present in 256 [20%] patients. Overall in-hospital mortality was 25% (n = 323/1282 deaths). In-hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non-HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44-2.59], P < 0.001). After adjusting, HF remained associated with in-hospital mortality (OR 1.45 [95% confidence interval: 1.01-2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in-hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24-4.29], P < 0.001). CONCLUSIONS: Hospitalized COVID-19 patients with HF are at increased risk for in-hospital death. In-hospital worsening of HF or acute HF de novo are common and associated with a further increase in in-hospital mortality