An anomalous case of S-ICD malfunctioning: A big trouble or a soap bubble?

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Hyperhomocysteinemia and MTHFR Polymorphisms as Antenatal Risk Factors of White Matter Abnormalities in Two Cohorts of Late Preterm and Full Term Newborns

Higher total homocysteine (tHcy) levels, and C677T and A1298C methylenetetrahydrofolate (MTHFR) polymorphisms, have been reported in preterm or full term newborns with neonatal encephalopathy following perinatal hypoxic-ischemic insult. This study investigated the causal role of tHcy and MTHFR polymorphisms together with other acquired risk factors on the occurrence of brain white matter abnormalities (WMA) detected by cranial ultrasound scans (cUS) in a population of late preterm and full term infants. A total of 171 newborns (81 M, 47.4%), 45 (26.3%) born <37 wks, and 126 (73.7%) born ≥37 wks were recruited in the study. cUS detected predominant WMA pattern in 36/171 newborns (21.1%) mainly characterized by abnormal periventricular white matter signal and mild-to-moderate periventricular white matter volume loss with ventricular dilatation (6/36, 16.6%). WMA resulted in being depending on tHcy levels (P<0.014), lower GA (P<0.000), lower Apgar score at 1 minutes (P<0.000) and 5 minutes (P<0.000), and 1298AC and 677CT/1298AC genotypes (P<0.000 and P<0.000). In conclusion, both acquired and genetic predisposing antenatal factors were significantly associated with adverse neonatal outcome and WMA. The role of A1298C polymorphism may be taken into account for prenatal assessment and treatment counseling

SP576ASSESSMENT OF INTRADIALYTIC HYPOTENSION : A NEW METHOD DERIVED FROM INTRADIALYTIC BLOOD PRESSURE VARIABILITY

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Cognitive Empowerment with New Technologies Improves Neuropsychological and Neurophysiological Parameters in Rett Syndrome

The aim of the present study is to investigate if cognitive empowerment through Eye Tracker technologies increases both neuropsychological and neurophysiological measures in patients with RS. Since the residual capacity of the girls with Rett Syndrome to move the eye to communicate, eye tracker is a new technology that helps researchers to better study attention and cognitive processes in RS girls and can supply the lack of appropriate tests. Rett Syndrome (RS) is ain severe mental retardation and neuro-behavioral disability. Currently there are several attempts to improve RS cognitive processes through new technologies. The aim of this study is to investigate whether cognitive empowerment through eye tracking technology increases neuropsychological and neurophysiological measures in patients with RS. 12 girls with Rett Syndrome were trained to discriminate five stimuli of different semantic categories. Results show that all the parameters of discrimination task became more efficient. Neurophysiological parameters show an enhancement of vigilant state. Results were discussed in terms of the efficacy of cognitive empowerment

Predictive role of early milestones-related psychomotor profiles and long-term neurodevelopmental pitfalls in preterm infants

Background Developmental milestones are useful signposts developed to assess the pace and the trajectory of maturation occurring during specific time-windows called critical periods. The predictive role of their clinical assessment in premature infants is challenging, however, it actually represents an easy and reliable tool at follow-up. Aim and study design Relying on a milestone-based neurological examination, we aimed to detect the interdependence between time of achievement of each milestone with long-term neuropsychological and neurodevelopmental outcomes. The influence of pre-perinatal events was also considered. Patients &amp; methods Two-hundred-eighty patients (53.2% M) were serially assessed by classic neurological examination during the first 18 months and subsequently evaluated by Griffiths Developmental Mental Scale. Children were sorted by ranges of gestational age and compared according to their different profiles. Results The Extremely PreTerms appeared to have a globally delayed development with subsequent attentional and behavioral troubles. Differently, the older peers, from Moderately to Full Term ones, although did not show significant differences in achievement of gross motor skills, had a stable delay of visual and social skills across the age ranges. This gap was not evidenced at the long-term evaluation, except for the Extremely PreTerm children. Pre-perinatal factors played a significant role on short and long term neurodevelopmental outcome. Conclusions Early assessed classic neurological examination might address neurodevelopmental trajectories in PreTerm children in which visual and social skills appear to be the mostly affected. It remains the easiest and most reliable tool of evaluation throughout the follow-up programs

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS. The nuclear scaffold protein promyelocytic leukemia (PML), a regulator of forebrain development, promotes neural progenitor/stem cell (NPC) and neuroblast migration in the adult mouse brain. The PML pro-migratory role is active also in transformed mouse NPCs and in human primary GBM cells. In both normal and neoplastic settings, PML controls cell migration via Polycomb repressive complex 2 (PRC2)-mediated repression of Slits, key regulators of axon guidance. Finally, a PML/SLIT1 axis regulates sensitivity to the PML-targeting drug arsenic trioxide in primary GBM cells. Taken together, these findings uncover a drug-targetable molecular axis controlling cell migration in both normal and neoplastic cells

Targeting autophagy potentiates tyrosine kinase inhibitor–induced cell death in Philadelphia chromosome–positive cells, including primary CML stem cells

Imatinib mesylate (IM), a potent inhibitor of the BCR/ABL tyrosine kinase, has become standard first-line therapy for patients with chronic myeloid leukemia (CML), but the frequency of resistance increases in advancing stages of disease. Elimination of BCR/ABL-dependent intracellular signals triggers apoptosis, but it is unclear whether this activates additional cell survival and/or death pathways. We have shown here that IM induces autophagy in CML blast crisis cell lines, CML primary cells, and p210BCR/ABL-expressing myeloid precursor cells. IM-induced autophagy did not involve c-Abl or Bcl-2 activity but was associated with ER stress and was suppressed by depletion of intracellular Ca2+, suggesting it is mechanistically nonoverlapping with IM-induced apoptosis. We further demonstrated that suppression of autophagy using either pharmacological inhibitors or RNA interference of essential autophagy genes enhanced cell death induced by IM in cell lines and primary CML cells. Critically, the combination of a tyrosine kinase inhibitor (TKI), i.e., IM, nilotinib, or dasatinib, with inhibitors of autophagy resulted in near complete elimination of phenotypically and functionally defined CML stem cells. Together, these findings suggest that autophagy inhibitors may enhance the therapeutic effects of TKIs in the treatment of CML