Need for timely paediatric HIV treatment within primary health care in rural South Africa

<p>Background: In areas where adult HIV prevalence has reached hyperendemic levels, many infants remain at risk of acquiring HIV infection. Timely access to care and treatment for HIV-infected infants and young children remains an important challenge. We explore the extent to which public sector roll-out has met the estimated need for paediatric treatment in a rural South African setting.</p> <p>Methods: Local facility and population-based data were used to compare the number of HIV infected children accessing HAART before 2008, with estimates of those in need of treatment from a deterministic modeling approach. The impact of programmatic improvements on estimated numbers of children in need of treatment was assessed in sensitivity analyses.</p> <p>Findings: In the primary health care programme of HIV treatment 346 children <16 years of age initiated HAART by 2008; 245(70.8%) were aged 10 years or younger, and only 2(<1%) under one year of age. Deterministic modeling predicted 2,561 HIV infected children aged 10 or younger to be alive within the area, of whom at least 521(20.3%) would have required immediate treatment. Were extended PMTCT uptake to reach 100% coverage, the annual number of infected infants could be reduced by 49.2%.</p> <p>Conclusion: Despite progress in delivering decentralized HIV services to a rural sub-district in South Africa, substantial unmet need for treatment remains. In a local setting, very few children were initiated on treatment under 1 year of age and steps have now been taken to successfully improve early diagnosis and referral of infected infants.</p&gt

Radical palliative surgery: new limits to pursue

This case report describes the radical subtotal palliative resection of a massive recurrent desmoid tumor encompassing the abdomen, pelvis, and groin in a child who was 13 years old at the time of initial resection. Given the extensive distribution of the tumor en bloc resection, which is the standard treatment of desmoid tumors, would have meant performing a hemipelvectomy and repair of a large abdominal wall defect, likely with skin grafts and mesh. The patient’s personal goals however were to alleviate the pain and limited mobility that would allow her to re-attend high school and appear normal to her peers. Therefore, palliative surgery was pursued and currently the patient is 5 years out from her last surgery doing well. We believe that the option of surgical palliation in this case was warranted and should be an option for similar cases in the future

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

Peer reviewedPublisher PD

Genome-wide identification of NBS-encoding resistance genes in Brassica rapa

Nucleotide-binding site (NBS)-encoding resistance genes are key plant disease-resistance genes and are abundant in plant genomes, comprising up to 2% of all genes. The availability of genome sequences from several plant models enables the identification and cloning of NBS-encoding genes from closely related species based on a comparative genomics approach. In this study, we used the genome sequence of Brassica rapa to identify NBS-encoding genes in the Brassica genome. We identified 92 non-redundant NBS-encoding genes [30 CC-NBS-LRR (CNL) and 62 TIR-NBS-LRR (TNL) genes] in approximately 100 Mbp of B. rapa euchromatic genome sequence. Despite the fact that B. rapa has a significantly larger genome than Arabidopsis thaliana due to a recent whole genome triplication event after speciation, B. rapa contains relatively small number of NBS-encoding genes compared to A. thaliana, presumably because of deletion of redundant genes related to genome diploidization. Phylogenetic and evolutionary analyses suggest that relatively higher relaxation of selective constraints on the TNL group after the old duplication event resulted in greater accumulation of TNLs than CNLs in both Arabidopsis and Brassica genomes. Recent tandem duplication and ectopic deletion are likely to have played a role in the generation of novel Brassica lineage-specific resistance genes

Evaluation of Indirect Fluorescent Antibody Assays Compared to Rapid Influenza Diagnostic Tests for the Detection of Pandemic Influenza A (H1N1) pdm09

Performance of indirect fluorescent antibody (IFA) assays and rapid influenza diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with the relative effects of age and illness severity on test accuracy. Clinicians and laboratories submitted specimens on patients with respiratory illness to public health from April to mid October 2009 for polymerase chain reaction (PCR) testing as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT were performed in clinical settings. Sensitivity and specificity for detection of the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs tested by PCR were falsely negative (sensitivity 71% and 69%, respectively). Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT (84%). Specificity of tests performed on hospitalized children was 94% for IFA and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to previously published studies on pandemic H1N1 influenza and sensitivity of IFA was similar to what has been reported in children for seasonal influenza. Both diagnostic tests produced a high number of false negatives and should not be used to rule out influenza infection

Computational Fitness Landscape for All Gene-Order Permutations of an RNA Virus

How does the growth of a virus depend on the linear arrangement of genes in its genome? Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. We used a mathematical model for vesicular stomatitis virus (VSV), a prototype RNA virus that encodes five genes (N-P-M-G-L), to simulate the intracellular growth of all 120 possible gene-order variants. Simulated yields of virus infection varied by 6,000-fold and were found to be most sensitive to gene-order permutations that increased levels of the L gene transcript or reduced levels of the N gene transcript, the lowest and highest expressed genes of the wild-type virus, respectively. Effects of gene order on virus growth also depended upon the host-cell environment, reflecting different resources for protein synthesis and different cell susceptibilities to infection. Moreover, by computationally deleting intergenic attenuations, which define a key mechanism of transcriptional regulation in VSV, the variation in growth associated with the 120 gene-order variants was drastically narrowed from 6,000- to 20-fold, and many variants produced higher progeny yields than wild-type. These results suggest that regulation by intergenic attenuation preceded or co-evolved with the fixation of the wild type gene order in the evolution of VSV. In summary, our models have begun to reveal how gene functions, gene regulation, and genomic organization of viruses interact with their host environments to define processes of viral growth and evolution

A Novel Resource Polymorphism in Fish, Driven by Differential Bottom Environments: An Example from an Ancient Lake in Japan

Divergent natural selection rooted in differential resource use can generate and maintain intraspecific eco-morphological divergence (i.e., resource polymorphism), ultimately leading to population splitting and speciation. Differing bottom environments create lake habitats with different benthos communities, which may cause selection in benthivorous fishes. Here, we document the nature of eco-morphological and genetic divergence among local populations of the Japanese gudgeon Sarcocheilichthys (Cyprinidae), which inhabits contrasting habitats in the littoral zones (rocky vs. pebbly habitats) in Lake Biwa, a representative ancient lake in East Asia. Eco-morphological analyses revealed that Sarcocheilichthys variegatus microoculus from rocky and pebbly zones differed in morphology and diet, and that populations from rocky environments had longer heads and deeper bodies, which are expected to be advantageous for capturing cryptic and/or attached prey in structurally complex, rocky habitats. Sarcocheilichthys biwaensis, a rock-dwelling specialist, exhibited similar morphologies to the sympatric congener, S. v. microoculus, except for body/fin coloration. Genetic analyses based on mitochondrial and nuclear microsatellite DNA data revealed no clear genetic differentiation among local populations within/between the gudgeon species. Although the morphogenetic factors that contribute to morphological divergence remain unclear, our results suggest that the gudgeon populations in Lake Biwa show a state of resource polymorphism associated with differences in the bottom environment. This is a novel example of resource polymorphism in fish within an Asian ancient lake, emphasizing the importance and generality of feeding adaptation as an evolutionary mechanism that generates morphological diversification

Virtual reality as a recovering environment - Implications for design principles

Peer reviewe

Suppression of Allograft Rejection by Tim-1-Fc through Cross-Linking with a Novel Tim-1 Binding Partner on T Cells

Engagement of T-cell immunoglobulin mucin (Tim)-1 on T cells with its ligand, Tim-4, on antigen presenting cells delivers positive costimulatory signals to T cells. However, the molecular mechanisms for Tim-1-mediated regulation of T-cell activation and differentiation are relatively poorly understood. Here we investigated the role of Tim-1 in T-cell responses and allograft rejection using recombinant human Tim-1 extracellular domain and IgG1-Fc fusion proteins (Tim-1-Fc). In vitro assays confirmed that Tim-1-Fc selectively binds to CD4+ effector T cells, but not dendritic cells or natural regulatory T cells (nTregs). Tim-1-Fc was able to inhibit the responses of purified CD4+ T cells that do not express Tim-4 to stimulation by anti-CD3/CD28 mAbs, and this inhibition was associated with reduced AKT and ERK1/2 phosphorylation, but it had no influence on nTregs. Moreover, Tim-1-Fc inhibited the proliferation of CD4+ T cells stimulated by allogeneic dendritic cells. Treatment of recipient mice with Tim-1-Fc significantly prolonged cardiac allograft survival in a fully MHC-mismatched strain combination, which was associated with impaired Th1 response and preserved Th2 and nTregs function. Importantly, the frequency of Foxp3+ cells in splenic CD4+ T cells was increased, thus shifting the balance toward regulators, even though Tim-1-Fc did not induce Foxp3 expression in CD4+CD25− T cells directly. These results indicate that Tim-1-Fc can inhibit T-cell responses through an unknown Tim-1 binding partner on T cells, and it is a promising immunosuppressive agent for preventing allograft rejection