The S100B protein was identified in the mid-1960s as a protein fraction which -on the basis of chromatographic and electrophoretic methods available at that time -was detectable in the brain but not in non-neural extracts, and was named S100 because of its solubility in a 100% saturated solution with ammonium sulphate (Moore 1965). At present, owing to the discovery of a series of proteins exhibiting structural similarities, the term S100 is used to embrace a multigenic family of mostly dimeric calcium-binding proteins comprising more than 20 members with different degrees of homology to each other at the amino acid level, and representing the largest subgroup within the EF-hand superfamily. The genes encoding the majority of human S100 proteins are organized in a cluster within the chromosomal region 1q21, while some genes coding individual S100 proteins are located in other chromosomal regions, including 21q22 where, in particular, the gene for the S100B protein is located. Each monomer is approximately 10-12 kDa and is characterized by two calcium-binding regions, each comprising two alpha helices with an intervening calcium-binding loop forming a conserved pentagonal arrangement around the calcium ion (EF-hand motif).The binding of calcium to EF-hand domains triggers conformational changes that allow interactions with other proteins, so Abstract S100B is a calcium-binding protein concentrated in glial cells, although it has also been detected in definite extra-neural cell types. Its biological role is still debated. When secreted, S100B is believed to have paracrine/autocrine trophic effects at physiological concentrations, but toxic effects at higher concentrations. Elevated S100B levels in biological fluids (CSF, blood, urine, saliva, amniotic fluid) are thus regarded as a biomarker of pathological conditions, including perinatal brain distress, acute brain injury, brain tumors, neuroinflammatory/neurodegenerative disorders, psychiatric disorders. In the majority of these conditions, high S100B levels offer an indicator of cell damage when standard diagnostic procedures are still silent. The key question remains as to whether S100B is merely leaked from injured cells or is released in concomitance with both physiological and pathological conditions, participating at high concentrations in the events leading to cell injury. In this respect, S100B levels in biological fluids have been shown to increase in physiological conditions characterized by stressful physical and mental activity, suggesting that it may be physiologically regulated and raised during conditions of stress, with a putatively active role. This possibility makes this protein a candidate not only for a biomarker but also for a potential therapeutic target.

, for the SLI Trial Investigators abstract BACKGROUND: Studies suggest that giving newly born preterm infants sustained lung inflation (SLI) may decrease their need for mechanical ventilation (MV) and improve their respiratory outcomes.

ObjectivesTo evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19.MethodsSecondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI).ResultsMean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8–0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09–1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3–7.9; p=0.001) were independently associated with composite adverse fetal outcome.ConclusionsEarly gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying "disorders" in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at -80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.

The purpose of this article is to study one of the most significant causes of neonatal morbidity and mortality: neonatal sepsis. This pathology is due to a bacterial or fungal infection acquired during the perinatal period. Neonatal sepsis has been categorized into two groups: early onset if it occurs within 3-6 days and late onset after 4-7 days. Due to the not-specific clinical signs, along with the inaccuracy of available biomarkers, the diagnosis is still a major challenge. In this regard, the use of a combined approach based on both nuclear magnetic resonance ( 1 H-NMR) and gas-chromatography-mass spectrometry (GC-MS) techniques, coupled with a multivariate statistical analysis, may help to uncover features of the disease that are still hidden. The objective of our study was to evaluate the capability of the metabolomics approach to identify a potential metabolic profile related to the neonatal septic condition. The study population included 25 neonates (15 males and 10 females): 9 (6 males and 3 females) patients had a diagnosis of sepsis and 16 were healthy controls (9 males and 7 females). This study showed a unique metabolic profile of the patients affected by sepsis compared to non-affected ones with a statistically significant difference between the two groups (p = 0.05).

To determine whether S100␤, an acidic calcium-binding protein previously demonstrated as a reliable indicator of a brain lesion, could be helpful in the detection of brain distress in intrauterine growth-retarded (IUGR) fetuses, we studied, by a case-control study, the correlation between S100B protein and the degree of fetoplacental blood flow impairment. Maternal and umbilical blood samples and placental tissue specimens were collected at delivery from IUGR pregnancies with normal (n ϭ 10) or abnormal (n ϭ 10) umbilical artery Doppler findings and from 40 uncomplicated pregnancies. S100␤ protein levels were measured by means of a specific RIA, and flow velocimetry waveforms were recorded from uterine, umbilical, and fetal middle cerebral arteries. Overall mean S100␤ proteins in umbilical plasma levels were higher (p Ͻ 0.05) in IUGR patients (121.8 Ϯ 70.4 fmol/mL) than in control patients (54.7 Ϯ 21.9 fmol/mL). IUGR fetuses with redistribution of blood flow showed the higher concentration of the protein (163.7 Ϯ 55.2 fmol/mL).Fetal S100␤ concentrations correlated with middle cerebral artery pulsatility index (r ϭ Ϫ0.536, p Ͻ 0.03) and with umbilical artery pulsatility index to middle cerebral artery pulsatility index ratio (r ϭ 0.469, p Ͻ 0.03). No difference in the localization or intensity of S100␤ staining in the placental tissues or cord between uncomplicated and IUGR pregnancies was found. This study provides evidence that circulating S100␤ protein is increased in IUGR fetuses and correlates with cerebral hemodynamics, suggesting that it may represent an index of cerebral cell damage in the perinatal period. The S100 family of calcium-binding proteins, first isolated in 1965 by Moore (1) in a subcellular fraction from bovine brain, contains approximately 16 members, each of which exhibits a unique pattern of tissue-or cell type-specific expression. Although the distribution of these proteins is not restricted to the nervous system, the involvement of several members of this family in nervous system development, function, and disease has sparked new interest in these proteins. S100␤, one of the original two members of this family, is an acidic calcium-binding protein with a molecular weight of 21 kD. It is present extracellularly, intracellularly, and in the cytosol; its half-life is approximately 2 h, and it is mainly eliminated by the kidney (2). S100␤ is present in CNS and is concentrated in the glial cells, astrocytes, Schwann cells, and neurons. It regulates several cellular functions (cell-cell communication, cell growth, cell structure, energy metabolism, contraction, and intracellular signal transduction). Elevated plasma levels are found in patients with brain damage (3). Abnormal S100␤ levels have been associated with neurobehavioral abnormalities and microcephaly caused by in utero cocaine exposure (4), and abnormal S100␤ immunoreactivity cells in anencephalic fetuses have been shown (5).The S100␤ concentration in blood and in cerebrospinal fluid is increased as result of brain damage in adults a...

Significance: Many physiological effects of natural antioxidants, their extracts or their major active components, have been reported in recent decades. Most of these compounds are characterized by a phenolic structure, similar to that of a-tocopherol, and present antioxidant properties that have been demonstrated both in vitro and in vivo. Polyphenols may increase the capacity of endogenous antioxidant defenses and modulate the cellular redox state. Such effects may have wide-ranging consequences for cellular growth and differentiation. Critical Issues: The majority of in vitro and in vivo studies conducted so far have attributed the protective effect of bioactive polyphenols to their chemical reactivity toward free radicals and their capacity to prevent the oxidation of important intracellular components. One possible protective molecular mechanism of polyphenols is nuclear factor erythroid 2-related factor (Nrf2) activation, which in turn regulates a number of detoxification enzymes. Recent Advances: Among the latter, the heme oxygenase-1 (HO-1) pathway is likely to contribute to the established and powerful antioxidant/anti-inflammatory properties of polyphenols. In this context, it is interesting to note that induction of HO-1 expression by means of natural compounds contributes to prevention of cardiovascular diseases in various experimental models. Future Directions: The focus of this review is on the role of natural HO-1 inducers as a potential therapeutic strategy to protect the cardiovascular system against various stressors in several pathological conditions. Antioxid. Redox Signal. 18, 000-000.

nisolone produced a weak signal at a slightly different retention time. At the evaluated concentration of 5000 g/L, prednisolone produced a signal equivalent to 20 g/L cortisol, representing a 0.4% interference. Fenofibrate generated parent ions at m/z 361 and 363 in an abundance ratio of 3:1, a distinctive pattern related to the presence of chlorine in the chemical composition. In MS/MS mode, fenofibrate produced a m/z 3633121 transition that interfered with the quantitative transition of cortisol, but it did not produce the m/z 363397 transition. Thus, switching to the secondary transition for quantification eliminated interference from this drug. In addition, the elution time of the drug was ϳ30 s longer than that of cortisol.Taylor et al.(1 ) noted isotopic exchange between the deuterated IS and hydrogen-containing vapors in an APCI ion source. Unlike the observations of Taylor et al., we have not observed isotopic exchange with our APCI interface. The reason for this difference is unclear, but it may be related to ion source conditions. The good agreement obtained between our method and the comparison LC-MS/MS method suggests that isotopic exchange did not affect the proposed method.Apparently healthy adult volunteers (25 males and 25 females; age range, 19 -53 years) collected 24-h urine samples without preservative. The volunteers were asked to keep samples under refrigeration during the collection. Statistical results for this study are presented in Table 1.To evaluate agreement between the established reference interval with UFC values in the population, we evaluated results for 2089 random 24-h urine specimens analyzed with the proposed method (Fig. 1). The mean (SD) value for log-transformed UFC excretion in 24 h was 1.26 (0.24) log g/24 h (minimum and maximum, 0.3 and 3.84 log g/24 h, respectively), and skewness and kurtosis for the distribution were 1.51 and 5.57, respectively.The stability of cortisol in urine was evaluated in the presence of acetic (15 mmol/L), boric (15 mmol/L), and hydrochloric (30 mmol/L) acid. Two samples without added acid were stored and analyzed under the same conditions as the samples stored with the acids. Samples were stored at room temperature, 4°C, and Ϫ20°C and analyzed every 4 -7 days during 1 month of storage. Cortisol concentrations in samples stored with the acids were higher by ϳ30% than in samples stored without acid, possibly as a result of partial hydrolysis of sulfate and glucuronide conjugates.In conclusion, the rapid LC-MS/MS method for UFC analysis appears to be free from interference and agrees closely with a HPLC-MS/MS method that uses sample extraction. The method has been demonstrated reliable in a high-volume clinical laboratory environment.