Predischarge transcutaneous bilirubin screening reduces readmission rate for hyperbilirubinaemia in diverse South African newborns: A randomised controlled trial

Background. In South Africa (SA), healthy term newborns are usually discharged ˂72 hours after delivery. Discharged babies remain at risk for severe hyperbilirubinaemia if it is not identified early. Hyperbilirubinaemia is an important cause of readmission, and also leads to neonatal mortality and morbidity. Use of transcutaneous bilirubin (TcB) screening before hospital discharge has been controversial.Objectives. To test the clinical benefits of TcB screening of healthy newborns before discharge for the outcomes of readmission for jaundice and severe hyperbilirubinaemia in a randomised controlled trial (RCT).Methods. This was a RCT. We compared predischarge TcB screening with visual assessment (alone) for jaundice in apparently healthy newborns at a public tertiary hospital in Cape Town, SA. Patients or study participants were not involved in the study design and implementation.Results. Of the 1 858 infants, 63% were black, 35% of mixed race and 1% white. There was a significant reduction in the rate of readmission for jaundice (risk ratio (RR) 0.25; 95% confidence interval (CI) 0.14 - 0.46; p<0.0001) and in the incidence of severe hyperbilirubinaemia (RR 0.27; 95% CI 0.08 - 0.97; p=0.05) with the use of TcB screening compared with visual inspection.Conclusions. Predischarge TcB screening is superior in identifying newborns at risk of severe hyperbilirubinaemia compared with visual inspection. We recommend that every newborn, regardless of skin pigmentation, should receive objective bilirubin screening before hospital discharge. Universal bilirubin screening in newborns could potentially reduce hyperbilirubinaemia-related morbidity and mortality

The Patient's Guide to Psoriasis Treatment. Part 2: PUVA Phototherapy.

BackgroundPUVA treatment is photochemotherapy for psoriasis that combines psoralen with UVA radiation. Although PUVA is a very effective treatment option for psoriasis, there is an absence of patient resources explaining and demonstrating the process of PUVA. Studies have shown that patients who viewed videos explaining the treatment procedures for various medical conditions had a greater understanding of their treatment and were more active participants in their health.ObjectiveTo present a freely available online guide and video on PUVA treatment designed for patient education on PUVA.MethodsThe PUVA treatment protocol used at the University of California-San Francisco Psoriasis and Skin Treatment Center as well as available information from the literature was reviewed to design a comprehensive guide for patients receiving PUVA treatment.ResultsWe created a printable guide and video resource that reviews the benefits and risks of PUVA, discusses the three types of PUVA (hand-foot soak, full body soak, and systemic), demonstrates the PUVA process, and provides practical tips for safe use.ConclusionOnline media and video delivers material in a way that is flexible and often familiar to patients. This new format is beneficial for prospective patients planning to undergo PUVA treatment, health-care providers, and trainees who want to learn more about this treatment

Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns

CITATION: Okwundu, C. I., et al. 2017. Transcutaneous bilirubinometry versus total serum bilirubin measurement for newborns. Cochrane Database of Systematic Reviews, 5:1-12, Art. CD012660, doi:10.1002/14651858.CD012660.The original publication is available at https://www.cochranelibrary.comThis is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows: - To determine the diagnostic accuracy of TcB as: i) a diagnostic test for hyperbilirubinaemia in newborns suspected to have hyperbilirubinaemia on visual inspection; ii) a diagnostic test for monitoring bilirubin levels in newborns receiving treatment (e.g. phototherapy) for hyperbilirubinaemia. - To determine whether the gestational age, postnatal age, body weight, race and site of TcB measurement have any influence on the accuracy of TcB measurement for hyperbilirubinaemia in newborns.https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012660/fullPublisher's versio

Report of the Task Force on Enhancing technology use in agriculture insurance

Pradhan Mantri Fasal Bima Yojana (PMFBY) is a flagship scheme of the Government of India to provide insurance coverage and financial support to farmers in the event of failure of any of the notified crops, unsown area and damage to harvest produce as a result of natural calamities, pests and diseases to stabilise the income of farmers, and to encourage them to adopt modern agricultural practices. The scheme is a considerable improvement over all previous insurance schemes in India and is heavily subsidised by the state and central governments. The scheme aims to cover 50 percent of the farming households within next 3 years. During its implementation in the last one season, several challenges relating to enrolment, yield estimation, loss assessment, and claim settlement were reported by farmers, insurance companies as well as the state governments. It was also noted that several technological opportunities existed for possibly leveraging support to the Indian crop insurance program for enhanced efficiency and effectiveness. NITI Aayog of the Government of India, therefore, constituted a Task Force to deliberate on this subject and identify such potential opportunities. This report summarises the recommendations of the Task Force. The Task Force constituted to address the issue of technology support to crop insurance comprised the following 5 sub-groups: (1) Remote Sensing & Drones; (2) Decision Support Systems, Crop Modelling & Integrated Approaches; (3) IT/ICT in Insurance; (4) Crop Cutting Experiments (CCEs); and (5) Technologies for Livestock and Aquaculture Insurance. Each sub-group had several discussions with experts in the respective areas, and submitted draft reports. More than 100 experts related to professional research agencies, insurance industry, banks, and the government contributed to these discussions. Technological options available in the country and abroad were considered by all groups. The Task Force together with the sub-groups then deliberated on key issues and formulated its recommendations as presented in this report. During the discussions it was realised that there were many administrative and institutional issues that needed to be addressed in PMFBY. However, the focus of the Task Force was on its main mandate, technology use in crop insurance. We hope these recommendations would help the Indian crop insurance sector take full advantage of the technological options suggested so as to increase its efficacy and effectiveness leading to reduced agrarian distress in the country

Quantitative model of R-loop forming structures reveals a novel level of RNA–DNA interactome complexity

R-loop is the structure co-transcriptionally formed between nascent RNA transcript and DNA template, leaving the non-transcribed DNA strand unpaired. This structure can be involved in the hyper-mutation and dsDNA breaks in mammalian immunoglobulin (Ig) genes, oncogenes and neurodegenerative disease related genes. R-loops have not been studied at the genome scale yet. To identify the R-loops, we developed a computational algorithm and mapped R-loop forming sequences (RLFS) onto 66 803 sequences defined by UCSC as ‘known’ genes. We found that ∼59% of these transcribed sequences contain at least one RLFS. We created R-loopDB (http://rloop.bii.a-star.edu.sg/), the database that collects all RLFS identified within over half of the human genes and links to the UCSC Genome Browser for information integration and visualisation across a variety of bioinformatics sources. We found that many oncogenes and tumour suppressors (e.g. Tp53, BRCA1, BRCA2, Kras and Ptprd) and neurodegenerative diseases related genes (e.g. ATM, Park2, Ptprd and GLDC) could be prone to significant R-loop formation. Our findings suggest that R-loops provide a novel level of RNA–DNA interactome complexity, playing key roles in gene expression controls, mutagenesis, recombination process, chromosomal rearrangement, alternative splicing, DNA-editing and epigenetic modifications. RLFSs could be used as a novel source of prospective therapeutic targets

Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells

Background: Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC). Methods: We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells. Results: Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol. Conclusions: Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade

The Oncoprotein EVI1 and the DNA Methyltransferase Dnmt3 Co-Operate in Binding and De Novo Methylation of Target DNA

EVI1 has pleiotropic functions during murine embryogenesis and its targeted disruption leads to prenatal death by severely affecting the development of virtually all embryonic organs. However, its functions in adult tissues are still unclear. When inappropriately expressed, EVI1 becomes one of the most aggressive oncogenes associated with human hematopoietic and solid cancers. The mechanisms by which EVI1 transforms normal cells are unknown, but we showed recently that EVI1 indirectly upregulates self-renewal and cell-cycling genes by inappropriate methylation of CpG dinucleotides in the regulatory regions of microRNA-124-3 (miR-124-3), leading to the repression of this small gene that controls normal differentiation and cell cycling of somatic cells. We used the regulatory regions of miR-124-3 as a read-out system to investigate how EVI1 induces de novo methylation of DNA. Here we show that EVI1 physically interacts with DNA methyltransferases 3a and 3b (Dnmt3a/b), which are the only de novo DNA methyltransferases identified to date in mouse and man, and that it forms an enzymatically active protein complex that induces de novo DNA methylation in vitro. This protein complex targets and binds to a precise region of miR-124-3 that is necessary for repression of a reporter gene by EVI1. Based on our findings, we propose that in cooperation with Dnmt3a/b EVI1 regulates the methylation of DNA as a sequence-specific mediator of de novo DNA methylation and that inappropriate EVI1 expression contributes to carcinogenesis through improper DNA methylation

Aerosol delivery to ventilated newborn infants: historical challenges and new directions

There are several aerosolized drugs which have been used in the treatment of neonatal respiratory illnesses, such as bronchodilators, diuretics, and surfactants. Preclinical in vitro and in vivo studies identified a number of variables that affect aerosol efficiency, including particle size, aerosol flows, nebulizer choice, and placement. Nevertheless, an optimized aerosol drug delivery system for mechanically ventilated infants still does not exist. Increasing interest in this form of drug delivery requires more controlled and focused research of drug/device combinations appropriate for the neonatal population. In the present article, we review the research that has been conducted thus far and discuss the next steps in developing the optimal aerosol delivery system for use in mechanically ventilated neonates

Epigenetic modifications in cardiovascular disease

Epigenetics represents a phenomenon of altered heritable phenotypic expression of genetic information occurring without changes in DNA sequence. Epigenetic modifications control embryonic development, differentiation and stem cell (re)programming. These modifications can be affected by exogenous stimuli (e.g., diabetic milieu, smoking) and oftentimes culminate in disease initiation. DNA methylation has been studied extensively and represents a well-understood epigenetic mechanism. During this process cytosine residues preceding a guanosine in the DNA sequence are methylated. CpG-islands are short-interspersed DNA sequences with clusters of CG sequences. The abnormal methylation of CpG islands in the promoter region of genes leads to a silencing of genetic information and finally to alteration of biological function. Emerging data suggest that these epigenetic modifications also impact on the development of cardiovascular disease. Histone modifications lead to the modulation of the expression of genetic information through modification of DNA accessibility. In addition, RNA-based mechanisms (e.g., microRNAs and long non-coding RNAs) influence the development of disease. We here outline the recent work pertaining to epigenetic changes in a cardiovascular disease setting