Measuring transcutaneous bilirubin: a comparative analysis of three devices on a multiracial population

BACKGROUND: Hyperbilirubinemia can lead to potentially irreversible bilirubin-induced neurotoxicity. Transcutaneous bilirubin (TcB) determination has become a valuable aid in non invasive screening of neonatal jaundice. The aim of this study is to compare the performance of three most widespread transcutaneous bilirubinometers on a multiracial population of term and late pre-term neonates. METHODS: Bilirubin concentration was determined using traditional photometric determination and transcutaneously with Bilicheck, BiliMed and JM-103, in random order. Total serum bilirubin (TSB) was determined over a wide concentration range (15,8–0,7 mg/dl) with a mean of 9,5 mg/dl. Related TcB values using Bilicheck (TcB-BC), BiliMed (TcB-BM), and JM-103 (TcB-JM) are reported in Table 1. RESULTS: A multiracial population of 289 neonates was enrolled with a gestational age ranging from 35 to 41 weeks; birth weight ranging from 1800to 4350 grams; hours of life ranging from 4 to 424. In the total study population correlation analysis using Pearson coefficients showed good results for Bilicheck (r = 0.86) and JM-103 (r = 0.85) but poor for BiliMed (r = 0,70). Similar results were found for the non-Caucasian neonates subgroup. Bilicheck and JM-103 had a greater area under the curve than BiliMed when TSB =14 mg/dl was chosen as a threshold value both for the total study population and the non-Caucasian subgroup. CONCLUSIONS: Bilicheck and JM-103, but not BiliMed, are equally reliable screening tools for hyperbilirubinemia in our multiracial neonatal population

Is lenticulostriated vasculopathy an unfavorable prognostic finding in infants with congenital cytomegalovirus infection?

Lenticulostriated vasculopathy (LSV) detected in head ultrasound (HUS) has been related to neurological and hearing sequelae in infants with congenital cytomegalovirus (cCMV) infection

Outcomes of congenital cytomegalovirus disease following maternal primary and non-primary infection

BACKGROUND: Natural history and long term prognosis of congenital cytomegalovirus (CMV) disease according to maternal primary versus non-primary infection are not clearly documented. OBJECTIVE: To investigate clinical, laboratory and neuroimaging features at onset and long term outcome of congenitally CMV-infected patients born to mothers with non-primary infection compared with a group of patients born to mothers with primary infection. STUDY DESIGN: Consecutive neonates born from 2002 to 2015 were considered eligible for the study. Patients underwent clinical, laboratory and instrumental investigation, and audiologic and neurodevelopmental evaluation at diagnosis and during the follow up. RESULTS: A cohort of 158 congenitally infected children was analyzed. Ninety-three were born to mothers with primary CMV infection (Group 1) and 65 to mothers with a non-primary infection (Group 2). Eighty-eight infants had a symptomatic congenital CMV disease: 49 (46.2%) in Group 1 and 39 (60%) in Group 2. Maternal and demographic characteristics of patients of Group 1 and Group 2 were comparable, with the exception of prematurity and a 1-min Apgar score less than 7, which were more frequent in Group 2 compared to Group 1. Prevalence of neuroimaging findings did not significantly differ between the two groups. An impaired neurodevelopmental outcome was observed in 23.7% of patients of Group 1 and in 24.6% cases of Group 2. Similarly, the frequency of hearing loss did not differ between the two groups (25.8% versus 26.2%, respectively). CONCLUSIONS: Neurodevelopmental and hearing sequelae are not affected by the type of maternal CMV infection. Preventing strategies should be developed for both primary and non-primary infections

Reverse transcriptase inhibitors promote the remodeling of nuclear architecture and induce autophagy in prostate cancer cells

Emerging data indicate that the reverse transcriptase (RT) protein encoded by LINE-1 transposable elements is a promising cancer target. Nonnucleoside RT inhibitors, e.g. efavirenz (EFV) and SPV122.2, reduce proliferation and promote differentiation of cancer cells, concomitant with a global reprogramming of the transcription profile. Both inhibitors have therapeutic anticancer efficacy in animal models. Here we have sought to clarify the mechanisms of RT inhibitors in cancer cells. We report that exposure of PC3 metastatic prostate carcinoma cells to both RT inhibitors results in decreased proliferation and concomitantly induces genome damage, associated with rearrangements of the nuclear architecture, particularly at peripheral chromatin, with disruption of the nuclear lamina and budding of micronuclei. These changes are reversible upon discontinuation of the RT-inhibitory treatment, with reconsititution of the lamina and resumption of the cancer cell original features. The use of pharmacological autophagy inhibitors proves that autophagy is largely responsible for the antiproliferative effect of RT inhibitors. These alterations are not induced in non-cancer cell lines exposed to RT inhibitors. These data provide novel insight in the molecular pathways targeted by RT inhibitors in cancer cells

Synthesis and Biochemical Evaluation of Δ2-Isoxazoline Derivatives as DNA Methyltransferase 1 Inhibitors

A series of Δ2-isoxazoline constrained analogues of procaine/procainamide (7a–k and 8a–k) were prepared and their inhibitory activity against DNA methyltransferase 1 (DNMT1) was tested. Among them, derivative 7b is far more potent in vitro (IC50 = 150 μM) than other non-nucleoside inhibitors and also exhibits a strong and dose-dependent antiproliferative effect against HCT116 human colon carcinoma cells. The binding mode of 7b with the enzyme was also investigated by means of a simple competition assay as well as of docking simulations conducted using the recently published crystallographic structure of human DNMT1. On the basis of the findings, we assessed that the mode of inhibition of 7b is consistent with a competition with the cofactor and propose it as a novel lead compound for the development of non-nucleoside DNMT inhibitors