Neonatal neurobehavioral abnormalities and MRI brain injury in encephalopathic newborns treated with hypothermia

Background Neonatal Encephalopathy (NE) is a prominent cause of infant mortality and neurodevelopmental disability. Hypothermia is an effective neuroprotective therapy for newborns with encephalopathy. Post-hypothermia functional–anatomical correlation between neonatal neurobehavioral abnormalities and brain injury findings on MRI in encephalopathic newborns has not been previously described. Aim To evaluate the relationship between neonatal neurobehavioral abnormalities and brain injury on magnetic resonance imaging (MRI) in encephalopathic newborns treated with therapeutic hypothermia. Study design Neonates with hypoxic ischemic encephalopathy (HIE) referred for therapeutic hypothermia were prospectively enrolled in this observational study. Neurobehavioral functioning was assessed with the NICU network neurobehavioral scale (NNNS) performed at target age 14 days. Brain injury was assessed by MRI at target age 7–10 days. NNNS scores were compared between infants with and without severe MRI injury. Subjects & outcome measures Sixty-eight term newborns (62% males) with moderate to severe encephalopathy underwent MRI at median 8 days (range 5–16) and NNNS at median 12 days of life (range 5–20). Fifteen (22%) had severe injury on MRI. Results Overall Total Motor Abnormality Score and individual summary scores for Non-optimal Reflexes and Asymmetry were higher, while Total NNNS Z-score across cognitive/behavioral domains was lower (reflecting poorer performance) in infants with severe MRI injury compared to those without (p \u3c 0.05). Conclusions Neonatal neurobehavioral abnormalities identified by the NNNS are associated with MRI brain injury in encephalopathic newborns post-hypothermia. The NNNS can provide an early functional assessment of structural brain injury in newborns, which may guide rehabilitative therapies in infants after perinatal brain injury

Molecular cloning and characterization of the porcine prostaglandin transporter (SLCO2A1): evaluation of its role in F4 mediated neonatal diarrhoea

<p>Abstract</p> <p>Background</p> <p>Because prostaglandins are involved in many (patho)physiological processes, <it>SLCO2A1 </it>was already characterized in several species in an attempt to unravel specific processes/deficiencies. Here, we describe the molecular cloning and characterization of the porcine ortholog in order to evaluate its possible involvement in F4 enterotoxigenic <it>E. coli </it>mediated neonatal diarrhoea, based on a positional candidate gene approach study.</p> <p>Results</p> <p>Porcine <it>SLCO2A1 </it>is organized in 14 exons, containing an open reading frame of 1935 bp, encoding a 12-transmembrane organic anion cell surface transporter of 644 aa. The -388 to -5 upstream region comprises a (CpG)₄₈island containing a number of conserved promoter elements, including a TATA box. A potential alternative promoter region was found in the conserved -973 to -700 upstream region. No consensus polyadenylation signal was discovered in the 3' UTR. Repeat sequences were found in 15% of all the non coding sequences.</p> <p>As expected for a multifunctional protein, a wide tissue distribution was observed. mRNA expression was found in the adrenal gland, bladder, caecum, colon (centripetal coil/centrifugal coil), diaphragm, duodenum, gallbladder, heart, ileum, jejunum, kidney, liver, longissimus dorsi muscle, lung, lymph node, mesenterium, rectum, spleen, stomach, tongue and ureter, but not in the aorta, oesophagus and pancreas.</p> <p>The promoter region and the exons (including the splice sites) of <it>SLCO2A1 </it>were resequenced in 5 F4ab/ac receptor positive and 5 F4ab/ac receptor negative pigs. Two silent and 2 missense (both S → L at position 360 and 633) mutations were found, but none was associated with the F4ab/ac receptor phenotype. In addition, no phenotype associated differential mRNA expression or alternative/abberant splicing/polyadenylation was found in the jejunum.</p> <p>Conclusion</p> <p>The molecular cloning and characterization of porcine <it>SLCO2A1 </it>not only contributes to the already existing knowledge about the transporter in general, but enables studies on porcine prostaglandin related processes/deficiencies as patient and/or model. Here we examined its possible involvement as receptor in F4 enterotoxigenic <it>E. coli </it>mediated neonatal diarrhoea. Because no phenotype associated differences could be found in the gene sequence nor in its jejunal transcription profile of F4ab/ac receptor positive/negative pigs, SLCO2A1 can most likely be excluded as receptor for F4 bacteria.</p

Notulae to the Italian native vascular flora: 2

In this contribution new data concerning the Italian distribution of native vascular flora are presented. It includes new records, exclusions, and confirmations to the Italian administrative regions for taxa in the genera Arctostaphylos, Artemisia, Buglossoides, Convolvulus, Crocus, Damasonium, Epipogium, Ficaria, Filago, Genista, Heptaptera, Heracleum, Heteropogon, Hieracium, Myosotis, Ononis, Papaver, Pilosella, Polygonum, Pulmonaria, Scorzonera, Silene, Trifolium, Vicia and Viola

Will Democracy Endure Private School Choice? The Effect of the Milwaukee Parental Choice Program on Adult Voting Behavior

We employ probit regression analysis to compare the adult voting activity of students who participated in the Milwaukee Parental Choice Program (MPCP) to their matched public school counterparts. We use a sophisticated matching algorithm to create a traditional public school student comparison group using data from the state-mandated evaluation of the MPCP. By the time the students are 19-26 years old, we do not find evidence that private school voucher students are more or less likely to vote in 2012 or 2016 than students educated in public schools. These results are robust to all models and are consistent for all subgroups

Earthquake rupture forecasts for the mps19 seismic hazard model of Italy

In recent years, new approaches for developing earthquake rupture forecasts (ERFs) have been proposed to be used as an input for probabilistic seismic hazard assessment (PSHA). Zone-based approaches with seismicity rates derived from earthquake catalogs are commonly used in many countries as the standard for national seismic hazard models. In Italy, a single zone-based ERF is currently the basis for the official seismic hazard model. In this contribution, we present eleven new ERFs, including five zone-based, two smoothed seismicity-based, two fault-based, and two geodetic-based, used for a new PSH model in Italy. The ERFs were tested against observed seismicity and were subject to an elicitation procedure by a panel of PSHA experts to verify the scientific robustness and consistency of the forecasts with respect to the observations. Tests and elicitation were finalized to weight the ERFs. The results show a good response to the new inputs to observed seismicity in the last few centuries. The entire approach was a first attempt to build a community-based set of ERFs for an Italian PSHA model. The project involved a large number of seismic hazard practitioners, with their knowledge and experience, and the development of different models to capture and explore a large range of epistemic uncertainties in building ERFs, and represents an important step forward for the new national seismic hazard model

GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.

Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. NG2-expressing oligodendrocyte precursor cells (NG2 cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2 cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2 cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. Conversely, blockade of GABA catabolism or GABA uptake reduced NG2 cell numbers and increased the formation of mature oligodendrocytes both in control and hypoxic mice. Our results indicate that GABAergic signaling regulates NG2 cell differentiation and proliferation in vivo, and suggest that its perturbation is a key factor in DWMI

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior