Wernerowen0045

To evaluate whether extremely preterm infants regulate iron status via hepcidin.

A retrospective analysis of infants from the Preterm Epo Neuroprotection (PENUT) Trial. Urine hepcidin (Uhep) normalized to creatinine (Uhep/UCr) was evaluated among infants randomized to erythropoietin (Epo) or placebo.

The correlation (r) between Uhep/UCr and serum markers of iron status (ferritin and zinc protoporphyrin-to-heme ratio (ZnPP/H)) and iron dose was assessed. A total of 243 urine samples from 76 infants born at 24-27 6/7 weeks gestation were analyzed. Median Uhep/UCr was 0.3, 1.3, 0.4 and 0.1 ng/mg at baseline, 2, 4 and 12 weeks, respectively, in placebo-treated infants. Median Uhep/UCr values in Epo-treated infants were not significantly different, with the exception of the 2-week time point (median Uhep/UCr 0.1 ng/mg, p<0.001). A significant association was seen between Uhep/UCr and ferritin at 2 and 4 weeks (r= 0.63, p<0.001 at 2 weeks, r=0.41, p=0.01 at 4 weeks) and ZnPP/H at 2 weeks (r=-0.49, P = .002).

Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that EP neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in EP neonates, particularly those treated with Epo.

Uhep/UCr values correlate with serum iron markers. Uhep/UCr values vary over time and are affected by treatment with Epo, suggesting that EP neonates can regulate hepcidin and therefore their iron status. Uhep is suppressed in EP neonates, particularly those treated with Epo.

To describe birth prevalence of rare craniofacial anomalies and associations with antenatal and perinatal factors.

All live and stillbirths in Western Australia between 1980 and 2010 were identified from the Western Australian Birth Registrations and the Midwives Notification System (also provides information on antenatal and perinatal factors). Rare CFA [Craniosynostosis, craniofacial microsomia and others (Pierre Robin, Van der Woude and Treacher Collins syndrome)] were ascertained from the Western Australian Register of Developmental Anomalies and linked to other data sources. Trends in prevalence, adjusted for sex and Indigenous status were investigated by Poisson regression presented as annual percent change (APC). Strengths of association of related factors were assessed using multivariable log-binomial regression adjusted for sex, Indigenous status, birth year, socioeconomic disadvantage and remoteness and reported as risk ratios with 95% confidence intervals.

There was a temporal increase in prevalence of metopic synostosis [APC5.59(2.32,8.96)] and CFM (Goldenhar syndrome) [APC4.43(1.94,6.98)]. Rare CFA were more likely among infants born preterm, as twins or higher order multiples, with growth restriction, to older parents, to mothers undertaking fertility treatments and with pre-existing medical conditions specifically epilepsy, diabetes or hypothyroidism. Prenatal identification of rare CFA was uncommon (0.6%).

Our findings indicate a steady increase over time in prevalence of metopic synostosis and CFM (Goldenhar syndrome). Possible associations of fertility treatments and pre-existing maternal medical conditions with rare CFA require further investigation.

Our findings indicate a steady increase over time in prevalence of metopic synostosis and CFM (Goldenhar syndrome). Possible associations of fertility treatments and pre-existing maternal medical conditions with rare CFA require further investigation.

To develop and face-validate population-level indicators for potential appropriateness of end-of-life care, for children with cancer, neurological conditions, and genetic/congenital conditions, to be applied to administrative health data containing medication and treatment variables.

Modified RAND/University of California at Los Angeles (RAND/UCLA) appropriateness method. We identified potential indicators per illness group through systematic literature review, scoping review, and expert interviews. Three unique expert panels, a cancer (n=19), neurology (n=21), and genetic/congenital (n=17) panel, participated in interviews and rated indicators in individual ratings, group discussions, and second individual ratings. find protocol Each indicator was rated on a scale from 1 to 9 for suitability. Consensus was calculated with Interpercentile Range Adjusted for Symmetry formula. Indicators with consensus about unsuitability were removed, those with consensus about suitability were retained, those with lack of consensus delf-life care. Differences from adults' indicators stress the specificity of children's end-of-life care. Individual care and remaining aspects, such as family support, can be evaluated with complementary tools.We investigated the microbiology, management, and orthopedic outcome of osteoarticular infections in infants ≤ 1 year of age at our institution. Among 87 patients, Staphylococcus aureus was the most common pathogen (44.8%) followed by group B Streptococcus. Twenty-nine patients (33%), with a median age of 9.2 months, were transitioned to oral antibiotic therapy after less then 14 days of parenteral therapy; orthopedic outcomes were similar to those with prolonged parenteral therapy.

To assess the impact of the time to treatment of the first electrographic seizure on subsequent seizure burden; secondary aim was to describe overall seizure management in a large neonatal cohort.

Newborns (36-44 weeks' gestation) requiring electroencephalographic (EEG) monitoring recruited to two multicentre European studies were included. Infants who received anti-seizure medication exclusively after electrographic seizure onset, were grouped based on time to treatment of the first seizure ASM within 1-hour, ASM between 1-2 hours and ASM after 2-hours. Outcomes measured were seizure burden, maximum seizure burden, status epilepticus, number of seizures and ASM dose over 24-hours following seizure onset.

Out of 472 newborns recruited, 154(32.6%) infants had confirmed electrographic seizures. Sixty-nine infants were exclusively treated after onset of electrographic seizures 21 infants received ASM within 1 hour, 15 infants between 1-2 hours and 33 infants after 2 hours of seizure onset. Significantly lower seizure burden and less seizures were noted in infants treated with ASM within 1 hour from seizure onset (p value=0.029 and 0.035, respectively). Overall, 258/472(54.7%) infants received ASM throughout the study period, of which 40 infants without electrographic seizures had treatment during EEG monitoring and 11 infants with electrographic seizures had no treatment.

Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment.

Treatment of neonatal seizures may be time-critical, but more research is required to confirm this. We also need to improve neonatal seizure diagnosis and treatment.Parkinson's disease (PD) is defined as a complex disorder with multifactorial pathogenesis, yet a more accurate definition could be that PD is not a single entity, but rather a mixture of different diseases with similar phenotypes. Attempts to classify subtypes of PD have been made based on clinical phenotypes or biomarkers. However, the most practical approach, at least for a portion of the patients, could be to classify patients based on genes involved in PD. GBA and LRRK2 mutations are the most common genetic causes or risk factors of PD, and PRKN is the most common cause of autosomal recessive form of PD. Patients carrying variants in GBA, LRRK2 or PRKN differ in some of their clinical characteristics, pathology and biochemical parameters. Thus, these three PD-associated genes are of special interest for drug development. Existing therapeutic approaches in PD are strictly symptomatic, as numerous clinical trials aimed at modifying PD progression or providing neuroprotection have failed over the last few decades. The lack of precision medicine approach in most of these trials could be one of the reasons why they were not successful. In the current review we discuss novel therapeutic approaches targeting GBA, LRRK2 and PRKN and discuss different aspects related to these genes and clinical trials.Ibudilast is a non-selective phosphodiesterase (PDE) inhibitor and glial cell modulator which has shown great promise for the treatment of drug and alcohol use disorders in recent clinical studies. However, it is unknown whether and how ibudilast affects cocaine seeking behavior. Here we show that systemic administration of ibudilast dose-dependently reduced cocaine self-administration under fixed- and progressive-ratio reinforcement schedules in rats and shifted cocaine dose-response curves downward. In addition, ibudilast decreased cocaine prime- and cue-induced reinstatement of cocaine seeking. These results indicate that ibudilast was effective in reducing the reinforcing effects of cocaine and relapse to cocaine seeking. Chronic cocaine exposure induces cAMP-related neuroadaptations in the reward circuitry of the brain. To investigate potential mechanisms for ibudilast-induced attenuation of cocaine self-administration, we recorded from ventral tegmental area (VTA) dopamine neurons in ex vivo midbrain slices prepared from rats that had undergone saline and cocaine self-administration. We found cocaine self-administration led to a decrease in inhibitory postsynaptic currents (IPSCs), an increase in the AMPAR/NMDAR ratio, and an increase in the excitation to inhibition (E/I) ratio. Ibudilast pretreatments enhanced GABAergic inhibition and did not further change cocaine-induced potentiation of excitation, leading to normalization of the E/I ratio. Restoration of the balance between excitation and inhibition in VTA dopamine neurons may contribute to the attenuation of cocaine self-administration by ibudilast.Passive uptake of contaminants of emerging concern (CECs) and its relationship with physicochemical properties, such as lipophilicity (LogKow), ionization behavior (pKa), distribution coefficient (LogDow) and transpiration rate are scarcely studied. In the current study, hydroponically grown corn (Zea mays) was exposed to carbamazepine (CBZ), fluoxetine (FLX), gemfibrozil (GBZ), triclosan (TRI) and atrazine (ATZ)) at environmentally relevant concentrations (20 μg/L each one). Plant tissue concentrations of CECs were determined several times over 21 days. Eighteen plants were used, nine exposed to the CECs and nine untreated. Whole plants were harvested at 7, 14 and 21 days and separated into roots, stem, leaf and male bud flower (only at 21 days). Hydroponic solution was maintained at pH 5.5 throughout the study. CECs concentrations in the exposure solution and tissues were determined by LC-MS/MS. ATZ metabolites desisopropylatrazine (DIA) and desethylatrazine (DEA) were determined by LC-DAD. In shoot tissues, CBZ, FLX and ATZ were detected, while TRI and GBZ were detected only in roots. Root concentrations were related with LogKow (R2ROOT = 0.415). Leaf and stem concentrations of CBZ, FLX and ATZ were linked with LogKow and strongly linked with pKa. Transpiration was related with CBZ and ATZ in shoot, but not related with FLX shoot levels. Neutral compounds such as CBZ (pKa = 13.94; 100% neutral) and ATZ (pKa = 1.6; 85% neutral) were taken up passively with transpiration. Root accumulation was related with CECs lipophilicity, while translocation and bioaccumulation in shoot were not only related with lipophilicity, but also with CECs ionization behavior and transpiration.