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Human and animal EEG data demonstrate that focal seizures start with low-voltage fast activity, evolve into rhythmic burst discharges and are followed by a period of suppressed background activity. This suggests that processes with dynamics in the range of tens of seconds govern focal seizure evolution. We investigate the processes associated with seizure dynamics by complementing the Hodgkin-Huxley mathematical model with the physical laws that dictate ion movement and maintain ionic gradients. Our biophysically realistic computational model closely replicates the electrographic pattern of a typical human focal seizure characterized by low voltage fast activity onset, tonic phase, clonic phase and postictal suppression. Our study demonstrates, for the first time in silico, the potential mechanism of seizure initiation by inhibitory interneurons via the initial build-up of extracellular K+ due to intense interneuronal spiking. The model also identifies ionic mechanisms that may underlie a key feature in seizure dynamics, i.e., progressive slowing down of ictal discharges towards the end of seizure. Our model prediction of specific scaling of inter-burst intervals is confirmed by seizure data recorded in the whole guinea pig brain in vitro and in humans, suggesting that the observed termination pattern may hold across different species. Our results emphasize ionic dynamics as elementary processes behind seizure generation and indicate targets for new therapeutic strategies.

Background And Objective:Gastric acidity is a major nonimmune defense mechanism against infections. The objective of this study was to investigate whether ranitidine treatment in very low birth weight (VLBW) infants is associated with an increased risk of infections, necrotizing enterocolitis (NEC), and fatal outcome.Methods:Newborns with birth weight between 401 and 1500 g or gestational age between 24 and 32 weeks, consecutively observed in neonatal intensive care units, were enrolled in a multicenter prospective observational study. The rates of infectious diseases, NEC, and death in enrolled subjects exposed or not to ranitidine were recorded.Results:We evaluated 274 VLBW infants: 91 had taken ranitidine and 183 had not. The main clinical and demographic characteristics did not differ between the 2 groups. Thirty-four (37.4%) of the 91 children exposed to ranitidine and 18 (9.8%) of the 183 not exposed to ranitidine had contracted infections (odds ratio 5.5, 95% confidence interval 2.9–10.4, P < .001). The risk of NEC was 6.6-fold higher in ranitidine-treated VLBW infants (95% confidence interval 1.7–25.0, P = .003) than in control subjects. Mortality rate was significantly higher in newborns receiving ranitidine (9.9% vs 1.6%, P = .003).Conclusions:Ranitidine therapy is associated with an increased risk of infections, NEC, and fatal outcome in VLBW infants. Caution is advocated in the use of this drug in neonatal age.

Necrotising enterocolitis (NEC) is a leading cause of mortality in preterm neonates.1 ,2 Despite the central role of innate immune inflammatory components in the pathogenesis of NEC,2 the potential diagnostic utility of these mediators remain largely uninvestigated. Measurement of serum levels of S100 myeloid-related proteins A8/A9 (S100 A8/A9), one of the principal mediators of innate immune response, has been proposed as diagnostic marker for several inflammatory conditions including neonatal sepsis.3 In the present study we aimed to evaluate the diagnostic accuracy of S100 A8/A9 in neonates with NEC. In a prospective multicentre study we enrolled neonates with gestational age (GA)

Aims: To analyze all evidence on the possible increase in morbidity and mortality determined by the use of inhibitors of gastric acid secretion (IGAS) drugs. Materials and Methods: We review all evidence exploring the adverse events associated with IGAS use in neonates. Results: Despite being prescribed in an off-label manner because of the perceived safety and potential benefit demonstrated for older populations, IGAS are being increasingly used in the neonatal period with much evidence derived from adults and children. Few data are available for neonates and indicate an association between IGAS use with infections and necrotizing enterocolitis (NEC), and with an increased mortality. Delayed gastric emptying, increased gastric mucus viscosity, modification in microbiota, and impairment of neutrophils functions are possible mechanisms of adverse events associated with IGAS use. Conclusions: A careful prescription of IGAS is crucial in order to reduce iatrogenic damage in neonates.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement.

This study was undertaken to assess to what extent estimated energy content of 13 infant formulas was related to gross energy measured by bomb calorimetry. Measured gross energy exceeded significantly metabolizable energy as claimed by the manufacturers by applying the classical Atwater's factors by about 12% (range, 6-17%). Measured gross energy also exceeded significantly gross energy calculated by applying either FAO/WHO or our own values of heat combustion of nutrient by 6% (range, 3-9%) and 3.5% (range, 1-6%), respectively. It is concluded that for reasons of symmetry and simplicity, the labeling of the energy content of infant formulas should continue to be calculated by applying the classical Atwater's factors to the nutrient composition. However, when accurate energy balance studies are carried out, the energy content of the diet should be measured by bomb calorimetry rather than be estimated by applying conversion factors to claimed or determined nutrient composition.

Vain et al1 have recently reported that the use of the exchange transfusion (ET) with fresh blood in addition to antibiotics and other supportive care therapies, had brought about a decreased mortality in a series of ten newborn infants suffering from severe septicemia with sclerema. They ascribe this effect more to the removal of endotoxins and the improvement of perfusion and tissue oxygenation than to the enhancement of an inflammatory response on the basis of two factors. First, although fresh blood transfusions are postulated to increase humoral immunity depending on the opsonic activity of blood from the donors, many patients had failed to show a significant clinical response after receiving large fresh blood transfusions; but after ET with blood from the same donors a clear improvement had been obtained.

Objective Clinical care of rare and complex epilepsies is challenging, because evidence‐based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web‐based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht‐like diseases. A consensus‐based questionnaire was generated for each disease. Results Twenty‐six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht‐like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers.

The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia.

Statins have since long been reported to exert acute neuroprotection in experimental stroke models. However, crucial questions still need to be addressed as far as the timing of their cerebral effects after intravascular administration and the role played by the blood brain barrier (BBB) crossing properties. We tested the effects of an hydrophilic statin (pravastatin, 100 nM), which poorly crosses BBB under physiological conditions. Pravastatin was administered either 90 min before or immediately after transient middle cerebral artery occlusion in the in vitro isolated Guinea pig brain preparation. A multi-modal outcome assessment was performed, through electrophysiological and cerebral vascular tone recordings, MAP-2 immunohistochemistry, BBB evaluation via ZO-1/FITC-albumin analysis, AKT and ERK activation and whole-cell antioxidant capacity. Pravastatin pre-ischemic administration did not produce any significant effect. Pravastatin post-ischemic administration significantly prevented MAP-2 immunoreactivity loss in ischemic areas, increased ERK phosphorylation in the ischemic hemisphere and enhanced whole-cell antioxidant capacity. Electrophysiological parameters, vascular tone and AKT signaling were unchanged. In all tested ischemic brains, ZO-1 fragmentation and FITC albumin extravasation was observed, starting 30 min from ischemia onset, indicating loss of BBB integrity. Our findings indicate that the rapid anti-ischemic effects of intravascular pravastatin are highly dependent on BBB increased permeability after stroke.

Commentary on: Terrin G, Passariello A, De Curtis M, et al. Ranitidine is associated with infections, necrotizing enterocolitis, and fatal outcome in newborns. Pediatrics 2012;129:e40–5.[OpenUrl][1][Abstract/FREE Full Text][2] Gastroesophageal reflux (GER) is the retrograde movement of stomach contents into the oesophagus. Pharmacotherapy aimed at reducing problems attributed to GER includes histamine receptor blockers (H2 blockers), such as ranitidine, which reduce stomach acidity. Extremely preterm infants often exhibit clinical signs consistent with GER,1 and GER medications are among the most commonly prescribed medications in neonatal intensive care units (NICUs).2 Approximately one third of extremely premature (

The incidence of inflammatory bowel disease (IBD) is progressively increasing in children in Western countries (1). At present, IBD diagnosis and staging is based on a combination of clinical, endoscopic, histological, and radiographic criteria, and there is no simple, noninvasive reliable individual marker for evaluating disease activity and topographical involvement, to predict relapses, and to select distinct treatment strategies (2, 3). Increased nitric oxide (NO) levels have been detected in the stools and plasma of children with IBD (4). This is the likely result of an upregulation of inducible NO synthase activity, which has been detected in intestinal mucosal segments of patients with active ulcerative colitis (UC) and, with lower intensity, of those with Crohn's disease (CD), suggesting a role of NO in IBD pathophysiology . The aim of this study was to determine whether rectal NO production, measured by a simple and noninvasive technique, reflects local inflammatory changes and disease activity in children with IBD. Forty children were included in the study: diagnosis, disease activity, and topographical involvement were obtained in all subjects by endoscopy and mucosal biopsy. Mean NO concentration was significantly higher in children with active UC than in control subjects. In nonactive UC patients and in active CD patients with rectal involvement, an overproduction of NO was also detected, but its magnitude was significantly lower than that observed in active UC children. On the contrary, in active CD children with rectal sparing NO production was similar to that of controls

During a five years period 8 newborns on 2035 admissions developed septic arthritis representing a very low incidence of 4%. Umbilical catheters were used in 3 patients. Staphylococcus aureus was the most frequent etiologic agent and in 6/8 cases blood cultures were positive for the same pathogen agent. Because of the paucity of clinical signs in the first period in the sick neonate, detection of the disorder by the radiologist assumes great importance in the neonatal intensive care unit, as early recognition and therapy may prevent residual deformity.