Management of late-preterm and term infants with hyperbilirubinaemia in resource-constrained settings.

Hyperbilirubinaemia is a ubiquitous transitional morbidity in the vast majority of newborns and a leading cause of hospitalisation in the first week of life worldwide. While timely and effective phototherapy and exchange transfusion are well proven treatments for severe neonatal hyperbilirubinaemia, inappropriate or ineffective treatment of hyperbilirubinaemia, at secondary and tertiary hospitals, still prevails in many poorly-resourced countries accounting for a disproportionately high burden of bilirubin-induced mortality and long-term morbidity. As part of the efforts to curtail the widely reported risks of frequent but avoidable bilirubin-induced neurologic dysfunction (acute bilirubin encephalopathy (ABE) and kernicterus) in low and middle-income countries (LMICs) with significant resource constraints, this article presents a practical framework for the management of late-preterm and term infants (≥ 35 weeks of gestation) with clinically significant hyperbilirubinaemia in these countries particularly where local practice guidelines are lacking. Standard and validated protocols were followed in adapting available evidence-based national guidelines on the management of hyperbilirubinaemia through a collaboration among clinicians and experts on newborn jaundice from different world regions. Tasks and resources required for the comprehensive management of infants with or at risk of severe hyperbilirubinaemia at all levels of healthcare delivery are proposed, covering primary prevention, early detection, diagnosis, monitoring, treatment, and follow-up. Additionally, actionable treatment or referral levels for phototherapy and exchange transfusion are proposed within the context of several confounding factors such as widespread exclusive breastfeeding, infections, blood group incompatibilities and G6PD deficiency, which place infants at high risk of severe hyperbilirubinaemia and bilirubin-induced neurologic dysfunction in LMICs, as well as the limited facilities for clinical investigations and inconsistent functionality of available phototherapy devices. The need to adjust these levels as appropriate depending on the available facilities in each clinical setting and the risk profile of the infant is emphasised with a view to avoiding over-treatment or under-treatment. These recommendations should serve as a valuable reference material for health workers, guide the development of contextually-relevant national guidelines in each LMIC, as well as facilitate effective advocacy and mobilisation of requisite resources for the optimal care of infants with hyperbilirubinaemia at all levels

Comparison of membrane proteins of Mycobacterium tuberculosis H37Rv and H37Ra strains

Background: The potential causes for variation in virulence between distinct M. tuberculosis strains are still not fully known. However, differences in protein expression are probably an important factor. In this study we used a labelfree quantitative proteomic approach to estimate differences in protein abundance between two closely related M. tuberculosis strains; the virulent H37Rv strain and its attenuated counterpart H37Ra. Results: We were able to identify more than 1700 proteins from both strains. As expected, the majority of the identified proteins had similar relative abundance in the two strains. However, 29 membrane-associated proteins were observed with a 5 or more fold difference in their relative abundance in one strain compared to the other. Of note, 19 membrane- and lipo-proteins had higher abundance in H37Rv, while another 10 proteins had a higher abundance in H37Ra. Interestingly, the possible protein-export membrane protein SecF (Rv2586c), and three ABCtransporter proteins (Rv0933, Rv1273c and Rv1819c) were among the more abundant proteins in M. tuberculosis H37Rv. Conclusion: Our data suggests that the bacterial secretion system and the transmembrane transport system may be important determinants of the ability of distinct M. tuberculosis strains to cause disease

Definition of novel cell envelope associated proteins in Triton X-114 extracts of Mycobacterium tuberculosis H37Rv

<p>Abstract</p> <p>Background</p> <p>Membrane- and membrane-associated proteins are important for the pathogenicity of bacteria. We have analysed the content of these proteins in virulent <it>Mycobacterium tuberculosis </it>H37Rv using Triton X-114 detergent-phase separation for extraction of lipophilic proteins, followed by their identification with high resolution mass spectrometry.</p> <p>Results</p> <p>In total, 1417 different proteins were identified. <it>In silico </it>analysis of the identified proteins revealed that 248 proteins had at least one predicted trans-membrane region. Also, 64 of the identified proteins were predicted lipoproteins, and 54 proteins were predicted as outer membrane proteins. Three-hundred-and-ninety-five of the observed proteins, including 91 integral membrane proteins were described for the first time. Comparison of abundance levels of the identified proteins was performed using the exponentially modified protein abundance index (emPAI) which takes into account the number of the observable peptides to the number of experimentally observed peptide ions for a given protein. The outcome showed that among the membrane-and membrane-associated proteins several proteins are present with high relative abundance. Further, a close examination of the lipoprotein LpqG (Rv3623) which is only detected in the membrane fractions of <it>M. tuberculosis </it>but not in <it>M. bovis</it>, revealed that the homologous gene in <it>M. bovis </it>lack the signal peptide and lipobox motif, suggesting impaired export to the membrane.</p> <p>Conclusions</p> <p>Altogether, we have identified a substantial proportion of membrane- and membrane-associated proteins of <it>M. tuberculosis </it>H37Rv, compared the relative abundance of the identified proteins and also revealed subtle differences between the different members of the <it>M. tuberculosis </it>complex.</p

Produtividade de plantações de eucalipto intercaladas com espécies nativas em áreas de pastagens degradadas no noroeste do Estado do Paraná.

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Numerical simulations of the decay of primordial magnetic turbulence

We perform direct numerical simulations of forced and freely decaying 3D magnetohydrodynamic turbulence in order to model magnetic field evolution during cosmological phase transitions in the early Universe. Our approach assumes the existence of a magnetic field generated either by a process during inflation or shortly thereafter, or by bubble collisions during a phase transition. We show that the final configuration of the magnetic field depends on the initial conditions, while the velocity field is nearly independent of initial conditions.Comment: 10 pages, 6 figures, references added, PRD accepte

Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series

Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13 years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the “Abnormal Involuntary Movement Scale” (AIMS) as well as the motor part of the “Burke Fahn Marsden Dystonia Rating Scale” (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80–90%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13 years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term

Analysis of animal serum proteins using antisera against human analogous proteins: A study of immunological cross reaction between human and animal serum proteins

In the present rocket immunoelectrophoretic analysis commercially available antisera against human serum proteins were screened for their usability in the analysis of analogous proteins in a number of animal species.The result appears as a table which demonstrates to what extent antibodies raised against a human protein can be used in the quantitative and/or qualitative study of an analogous animal protein

High accuracy mass spectrometry analysis as a tool to verify and improve gene annotation using Mycobacterium tuberculosis as an example

Background: While the genomic annotations of diverse lineages of the Mycobacterium tuberculosis complex are available, divergences between gene prediction methods are still a challenge for unbiased protein dataset generation. M. tuberculosis gene annotation is an example, where the most used datasets from two independent institutions (Sanger Institute and Institute of Genomic Research-TIGR) differ up to 12% in the number of annotated open reading frames, and 46% of the genes contained in both annotations have different start codons. Such differences emphasize the importance of the identification of the sequence of protein products to validate each gene annotation including its sequence coding area. Results: With this objective, we submitted a culture filtrate sample from M. tuberculosis to a highaccuracy LTQ-Orbitrap mass spectrometer analysis and applied refined N-terminal prediction to perform comparison of two gene annotations. From a total of 449 proteins identified from the MS data, we validated 35 tryptic peptides that were specific to one of the two datasets, representing 24 different proteins. From those, 5 proteins were only annotated in the Sanger database. In the remaining proteins, the observed differences were due to differences in annotation of transcriptional start sites. Conclusion: Our results indicate that, even in a less complex sample likely to represent only 10% of the bacterial proteome, we were still able to detect major differences between different gene annotation approaches. This gives hope that high-throughput proteomics techniques can be used to improve and validate gene annotations, and in particular for verification of high-throughput, automatic gene annotations.publishedVersio