Interorganellar calcium signaling in the regulation of cell metabolism: A cancer perspective.

Organelles were originally considered to be individual cellular compartments with a defined organization and function. However, recent studies revealed that organelles deeply communicate within each other via Ca2+ exchange. This communication, mediated by specialized membrane regions in close apposition between two organelles, regulate cellular functions, including metabolism and cell fate decisions. Advances in microscopy techniques, molecular biology and biochemistry have increased our understanding of these interorganelle platforms. Research findings suggest that interorganellar Ca2+ signaling, which is altered in cancer, influences tumorigenesis and tumor progression by controlling cell death programs and metabolism. Here, we summarize the available data on the existence and composition of interorganelle platforms connecting the endoplasmic reticulum with mitochondria, the plasma membrane, or endolysosomes. Finally, we provide a timely overview of the potential function of interorganellar Ca2+ signaling in maintaining cellular homeostasis.

[Management of children with headache in a Pediatric Emergency Department before and after the introduction of the Second International Classification of Headache Disorders (ICHD-II)]. / Il percorso dei pazienti con cefalea in Pronto Soccorso pediatrico prima e dopo la seconda classificazione internazionale delle cefalee.

The aim of this study was to evaluate how the management of children admitted with headache to a Pediatric Emergency Department, was modified by the introduction of the Second International Classification of Headache Disorders ( ICHD-II) published in 2004. The complexity and average costs of the services provided to patients in 2002 and 2011 were compared. The results revealed a decrease in the number of tests performed and in-hospital admissions. However, tests were more complex, and an increase in requests of specialist advice was observed. We hypothesized that this change may be related to the introduction of ICHD-II, which suggests a more rational approach to the child with headache and a better use of hospital resources.

Amplitude-integrated EEG recorded at 32 weeks postconceptional age. Correlation with MRI at term.

OBJECTIVE: The study aims to establish the role of late aEEG (scored by Burdjalov) in predicting brain maturation as well as abnormalities evaluated at term equivalent age (TEA) by brain MRI. METHODS: 91 infants born before 30 wks gestation underwent an aEEG monitoring at 32 wks postconceptional age (PCA). aEEG, was correlated with TEA MRI, scored by Kidokoro. RESULTS: A significant correlation between the aEEG score and the MRI scores was found. The same results were obtained for the aEEG continuity score; cyclicity and bandwidth scores were associated with grey matter and cerebellar MRI items. Moreover, a correlation between aEEG and cEEG recorded both at 32 and 40 wks PCA, was found. CONCLUSIONS: aEEG monitoring can be predictive of MRI findings at TEA, suggesting that it could be implemented as a useful tool to support ultrasound to help identify neonates who will benefit from early intervention services.

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy.

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Mitophagy in Cardiovascular Diseases.

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.

Melatonin as a master regulator of cell death and inflammation: molecular mechanisms and clinical implications for newborn care.

Melatonin, more commonly known as the sleep hormone, is mainly secreted by the pineal gland in dark conditions and regulates the circadian rhythm of the organism. Its intrinsic properties, including high cell permeability, the ability to easily cross both the blood-brain and placenta barriers, and its role as an endogenous reservoir of free radical scavengers (with indirect extra activities), confer it beneficial uses as an adjuvant in the biomedical field. Melatonin can exert its effects by acting through specific cellular receptors on the plasma membrane, similar to other hormones, or through receptor-independent mechanisms that involve complex molecular cross talk with other players. There is increasing evidence regarding the extraordinary beneficial effects of melatonin, also via exogenous administration. Here, we summarize molecular pathways in which melatonin is considered a master regulator, with attention to cell death and inflammation mechanisms from basic, translational and clinical points of view in the context of newborn care.

Universal Head Ultrasound Screening in Full-term Neonates: A Retrospective Analysis of 6771 Infants.

BACKGROUND: Full-term neonates may have asymptomatic cranial injuries at birth and head ultrasound screening could be useful for early diagnosis. The aim of this study was to assess the prevalence and type of intracranial abnormalities and the usefulness of head ultrasound screening in these infants. METHODS: Head ultrasound screening was performed on all full-term neonates (gestational age between 37 and 42 weeks), born at Sant'Anna University Hospital of Ferrara, Italy, from June 1, 2008 through May 31, 2013. Ultrasound findings were categorized into three groups: normal, minor, and major anomalies. RESULTS: All full-term neonates (6771) born at our hospital underwent head ultrasound screening. One hundred fourteen of 6771 (1.7%) presented ultrasound abnormalities, whereas 6657 were normal or exhibited insignificant findings. In 101 of 114 (88.6%), abnormalities were minor, and only 13 infants had major abnormalities (0.19% of all full-term newborns). All neonates with major abnormalities presented with either microcephaly or abnormal neurological evaluations. Only one individual with major abnormalities was detected exclusively by ultrasound. CONCLUSIONS: The number of significant anomalies detected by head ultrasound screening in asymptomatic full-term neonates born during the study period was low. Therefore, there is no indication for routine general head ultrasound screening in these patients. However, even if low, in neonates who have neurological abnormalities, risk factors or suspected brain malformations, head ultrasound screening may play an important role in the early diagnosis of intracranial anomalies.

Two mutations in surfactant protein C gene associated with neonatal respiratory distress.

Multiple mutations of surfactant genes causing surfactant dysfunction have been described. Surfactant protein C (SP-C) deficiency is associated with variable clinical manifestations ranging from neonatal respiratory distress syndrome to lethal lung disease. We present an extremely low birth weight male infant with an unusual course of respiratory distress syndrome associated with two mutations in the SFTPC gene: C43-7G>A and 12T>A. He required mechanical ventilation for 26 days and was treated with 5 subsequent doses of surfactant with temporary and short-term efficacy. He was discharged at 37 weeks of postconceptional age without any respiratory support. During the first 16 months of life he developed five respiratory infections that did not require hospitalization. Conclusion. This mild course in our patient with two mutations is peculiar because the outcome in patients with a single SFTPC mutation is usually poor.

Corrigendum to "Two Mutations in Surfactant Protein C Gene Associated with Neonatal Respiratory Distress".

[This corrects the article DOI: 10.1155/2015/591783.].

Use of ketamine in a newborn with refractory status epilepticus: a case report.

BACKGROUND: Brain malformations represent a major cause of refractory seizures. Standardized protocols to treat status epilepticus of newborn are not available in the literature. PATIENT: We present a case report of use of ketamine administered to a late preterm with Pierre Robin sequence, lissencephaly, polymicrogyria, and severe epilepsy. RESULTS: The infusion of ketamine permitted resolution of status epilepticus, cardiorespiratory stabilization, and improved parental care for 15 days. No significant side effects were noted. CONCLUSION: In the literature there are few studies regarding the use of ketamine for refractory status epilepticus, and only in nine of these described the use of, ketamine in children (2 months-18 years). This is the first report to document the effective use of ketamine in the newborn with status epilepticus.

Universal cranial ultrasound screening in preterm infants with gestational age 33-36 weeks. A retrospective analysis of 724 newborns.

BACKGROUND: Cranial ultrasonography is a useful tool to detect intracranial lesions in premature neonates at risk. Our primary aim was to determine the number of patients with abnormal cranial ultrasonography. Secondary aims were to evaluate the usefulness of universal cranial ultrasonography screening in moderately preterm infants. METHODS: All infants born from 2007 to 2012 at the University Hospital of Ferrara (Italy), with gestational age of 33-36 weeks, were included in the study. Cranial ultrasonography findings were retrospectively classified into nonsignificant and significant. RESULTS: All the 724 babies born were screened. Intracranial lesions were in 13% of neonates (3.7% at 36 weeks to 27.1% at 33 weeks of gestational age). Babies born at 33-34 weeks of gestational age were four times more likely to have an abnormal cranial ultrasonography than those at 35-36 weeks. Statistical analysis revealed no association between cranial ultrasonography abnormalities and being small for gestational age or mode of delivery. A significant association was present between the presence of head circumference less than the third percentile, the need for ventilation or surfactant, low Apgar index at fifth minute, and neurological abnormalities. The presence of at least one considered risk factor increases the probability of cranial ultrasonography abnormalities twice in infants born at 33-34 weeks and 15 times in born at 35-36 weeks. CONCLUSIONS: A considerable number of infants born between 33 and 36 weeks have cranial ultrasonography abnormalities. We suggest that screening should be performed or at least that a uniform protocol should be developed for the early detection of all significant cranial ultrasonography abnormalities.

Universal neonatal screening for sickle cell disease and other haemoglobinopathies in Ferrara, Italy.

BACKGROUND: Sickle cell disease is the commonest haemoglobinopathy in Africa, the Middle East and India. In recent years, its incidence has increased dramatically also in Europe and North America because of the high rate of migration of people from endemic areas. From January 2009 to January 2010 the number of foreign residents in the province of Ferrara (Italy) increased by 12.2%: most of the immigrants were from countries at high risk of sickle cell disease. Since neonatal screening and prophylactic penicillin in early childhood could reduce mortality by 10 years of age to less than 2%, the aim of this study was to establish a neonatal screening programme for haemoglobinopathies in Ferrara. MATERIALS AND METHODS: First we assessed how many pregnant women underwent haemoglobin analysis by high performance liquid chromatography before or during pregnancy and how many of them were carriers of haemoglobinopathies. Subsequently, we verified the feasibility of neonatal screening for sickle cell disease and other haemoglobinopathies, analysing cord blood by high performance liquid chromatography. Neonates found to be positive were managed by a multidisciplinary team to implement all the appropriate prophylactic and therapeutic measures. RESULTS: We found that 59% of women who delivered at the University Hospital of Ferrara, from 2007 to 2009, had undergone high performance liquid chromatography. Of the 41% who were not tested, many were from areas in which sickle cell disease is common. Between September 26th 2010 and January 31st 2012, 1992 neonatal tests were performed and 24 carriers of haemoglobinopathies were identified (16 with HbS, 4 with HbC, 2 with HbE, 1 with HbD Punjab and 1 with HbD-Ouled Rabah); 42.6% of the mothers of these 1,992 neonates had not undergone high performance liquid chromatography during pregnancy. DISCUSSION: Currently prevention of haemoglobinopathies in Italy is provided during the pre-conception period but only to patients with abnormal blood counts. Neonatal screening is useful and cost-effective to ensure early diagnosis and appropriate treatment for infants with sickle cell disease or other haemoglobinopathies.