A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Proceedings of a Sickle Cell Disease Ontology workshop - Towards the first comprehensive ontology for Sickle Cell Disease

Sickle cell disease (SCD) is a debilitating single gene disorder caused by a single point mutation that results in physical deformation (i.e. sickling) of erythrocytes at reduced oxygen tensions. Up to 75% of SCD in newborns world-wide occurs in sub-Saharan Africa, where neonatal and childhood mortality from sickle cell related complications is high. While SCD research across the globe is tackling the disease on multiple fronts, advances have yet to significantly impact on the health and quality of life of SCD patients, due to lack of coordination of these disparate efforts. Ensuring data across studies is directly comparable through standardization is a necessary step towards realizing this goal. Such a standardization requires the development and implementation of a disease-specific ontology for SCD that is applicable globally. Ontology development is best achieved by bringing together experts in the domain to contribute their knowledge. The SCD community and H3ABioNet members joined forces at a recent SCD Ontology workshop to develop an ontology covering aspects of SCD under the classes: phenotype, diagnostics, therapeutics, quality of life, disease modifiers and disease stage. The aim of the workshop was for participants to contribute their expertise to development of the structure and contents of the SCD ontology. Here we describe the proceedings of the Sickle Cell Disease Ontology Workshop held in Cape Town South Africa in February 2016 and its outcomes. The objective of the workshop was to bring together experts in SCD from around the world to contribute their expertise to the development of various aspects of the SCD ontology

Efficacy of c-Met inhibitor for advanced prostate cancer

<p>Abstract</p> <p>Background</p> <p>Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR) signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC). Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer.</p> <p>Methods</p> <p>We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression.</p> <p>Results</p> <p>We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration.</p> <p>Conclusions</p> <p>The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.</p

Differential Effects of Early- and Late-Life Access to Carotenoids on Adult Immune Function and Ornamentation in Mallard Ducks (Anas platyrhynchos)

Environmental conditions early in life can affect an organism’s phenotype at adulthood, which may be tuned to perform optimally in conditions that mimic those experienced during development (Environmental Matching hypothesis), or may be generally superior when conditions during development were of higher quality (Silver Spoon hypothesis). Here, we tested these hypotheses by examining how diet during development interacted with diet during adulthood to affect adult sexually selected ornamentation and immune function in male mallard ducks (Anas platyrhynchos). Mallards have yellow, carotenoid-pigmented beaks that are used in mate choice, and the degree of beak coloration has been linked to adult immune function. Using a 2×2 factorial experimental design, we reared mallards on diets containing either low or high levels of carotenoids (nutrients that cannot be synthesized de novo) throughout the period of growth, and then provided adults with one of these two diets while simultaneously quantifying beak coloration and response to a variety of immune challenges. We found that both developmental and adult carotenoid supplementation increased circulating carotenoid levels during dietary treatment, but that birds that received low-carotenoid diets during development maintained relatively higher circulating carotenoid levels during an adult immune challenge. Individuals that received low levels of carotenoids during development had larger phytohemagglutinin (PHA)-induced cutaneous immune responses at adulthood; however, dietary treatment during development and adulthood did not affect antibody response to a novel antigen, nitric oxide production, natural antibody levels, hemolytic capacity of the plasma, or beak coloration. However, beak coloration prior to immune challenges positively predicted PHA response, and strong PHA responses were correlated with losses in carotenoid-pigmented coloration. In sum, we did not find consistent support for either the Environmental Matching or Silver Spoon hypotheses. We then describe a new hypothesis that should be tested in future studies examining developmental plasticity

Experimental Infection of Cynomolgus Macaques (Macaca fascicularis) with Aerosolized Monkeypox Virus

Monkeypox virus (MPXV) infection in humans results in clinical symptoms very similar to ordinary smallpox. Aerosol is a route of secondary transmission for monkeypox, and a primary route of smallpox transmission in humans. Therefore, an animal model for aerosol exposure to MPXV is needed to test medical countermeasures. To characterize the pathogenesis in cynomolgus macaques (Macaca fascicularis), groups of macaques were exposed to four different doses of aerosolized MPXV. Blood was collected the day before, and every other day after exposure and assessed for complete blood count (CBC), clinical chemistry analysis, and quantitative PCR. Macaques showed mild anorexia, depression, and fever on day 6 post-exposure. Lymphadenopathy, which differentiates monkeypox from smallpox, was observed in exposed macaques around day 6 post-exposure. CBC and clinical chemistries showed abnormalities similar to human monkeypox cases. Whole blood and throat swab viral loads peaked around day 10, and in survivors, gradually decreased until day 28 post-exposure. Survival was not dose dependent. As such, doses of 4×104 PFU, 1×105 PFU, or 1×106 PFU resulted in lethality for 70% of the animals, whereas a dose of 4×105 PFU resulted in 85% lethality. Overall, cynomolgus macaques exposed to aerosolized MPXV develop a clinical disease that resembles that of human monkeypox. These findings provide a strong foundation for the use of aerosolized MPXV exposure of cynomolgus macaques as an animal model to test medical countermeasures against orthopoxviruses

Immigration Rates in Fragmented Landscapes – Empirical Evidence for the Importance of Habitat Amount for Species Persistence

BACKGROUND: The total amount of native vegetation is an important property of fragmented landscapes and is known to exert a strong influence on population and metapopulation dynamics. As the relationship between habitat loss and local patch and gap characteristics is strongly non-linear, theoretical models predict that immigration rates should decrease dramatically at low levels of remaining native vegetation cover, leading to patch-area effects and the existence of species extinction thresholds across fragmented landscapes with different proportions of remaining native vegetation. Although empirical patterns of species distribution and richness give support to these models, direct measurements of immigration rates across fragmented landscapes are still lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using the Brazilian Atlantic forest marsupial Gray Slender Mouse Opossum (Marmosops incanus) as a model species and estimating demographic parameters of populations in patches situated in three landscapes differing in the total amount of remaining forest, we tested the hypotheses that patch-area effects on population density are apparent only at intermediate levels of forest cover, and that immigration rates into forest patches are defined primarily by landscape context surrounding patches. As expected, we observed a positive patch-area effect on M. incanus density only within the landscape with intermediate forest cover. Density was independent of patch size in the most forested landscape and the species was absent from the most deforested landscape. Specifically, the mean estimated numbers of immigrants into small patches were lower in the landscape with intermediate forest cover compared to the most forested landscape. CONCLUSIONS/SIGNIFICANCE: Our results reveal the crucial importance of the total amount of remaining native vegetation for species persistence in fragmented landscapes, and specifically as to the role of variable immigration rates in providing the underlying mechanism that drives both patch-area effects and species extinction thresholds

BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours

BORIS (for brother of the regulator of imprinted sites), a paralogue of the transcription factor, CTCF, is a novel member of the cancer-testis antigen family. The aims of the present study were as follows: (1) to investigate BORIS expression in breast cells and tumours using immunohistochemical staining, western and real-time RT–PCR analyses and (2) assess potential correlation between BORIS levels in tumours with clinical/pathological parameters. BORIS was detected in all 18 inspected breast cell lines, but not in a primary normal breast cell culture. In 70.7% (41 of 58 cases) BORIS was observed in breast tumours. High levels of BORIS correlated with high levels of progesterone receptor (PR) and oestrogen receptor (ER). The link between BORIS and PR/ER was further confirmed by the ability of BORIS to activate the promoters of the PR and ER genes in the reporter assays. Detection of BORIS in a high proportion of breast cancer patients implies potential practical applications of BORIS as a molecular biomarker of breast cancer. This may be important for diagnosis of the condition and for the therapeutic use of BORIS. The ability of BORIS to activate promoters of the RP and ER genes points towards possible involvement of BORIS in the establishment, progression and maintenance of breast tumours

β-hairpin-mediated formation of structurally distinct multimers of neurotoxic prion peptides

Protein misfolding disorders are associated with conformational changes in specific proteins, leading to the formation of potentially neurotoxic amyloid fibrils. During pathogenesis of prion disease, the prion protein misfolds into β-sheet rich, protease-resistant isoforms. A key, hydrophobic domain within the prion protein, comprising residues 109–122, recapitulates many properties of the full protein, such as helix-to-sheet structural transition, formation of fibrils and cytotoxicity of the misfolded isoform. Using all-atom, molecular simulations, it is demonstrated that the monomeric 109–122 peptide has a preference for α-helical conformations, but that this peptide can also form β-hairpin structures resulting from turns around specific glycine residues of the peptide. Altering a single amino acid within the 109–122 peptide (A117V, associated with familial prion disease) increases the prevalence of β-hairpin formation and these observations are replicated in a longer peptide, comprising residues 106–126. Multi-molecule simulations of aggregation yield different assemblies of peptide molecules composed of conformationally-distinct monomer units. Small molecular assemblies, consistent with oligomers, comprise peptide monomers in a β-hairpin-like conformation and in many simulations appear to exist only transiently. Conversely, larger assemblies are comprised of extended peptides in predominately antiparallel β-sheets and are stable relative to the length of the simulations. These larger assemblies are consistent with amyloid fibrils, show cross-β structure and can form through elongation of monomer units within pre-existing oligomers. In some simulations, assemblies containing both β-hairpin and linear peptides are evident. Thus, in this work oligomers are on pathway to fibril formation and a preference for β-hairpin structure should enhance oligomer formation whilst inhibiting maturation into fibrils. These simulations provide an important new atomic-level model for the formation of oligomers and fibrils of the prion protein and suggest that stabilization of β-hairpin structure may enhance cellular toxicity by altering the balance between oligomeric and fibrillar protein assemblies

Advances in research on the use of biochar in soil for remediation: a review

Purpose: Soil contamination mainly from human activities remains a major environmental problem in the contemporary world. Significant work has been undertaken to position biochar as a readily-available material useful for the management of contaminants in various environmental media notably soil. Here, we review the increasing research on the use of biochar in soil for the remediation of some organic and inorganic contaminants.  Materials and methods: Bibliometric analysis was carried out within the past 10 years to determine the increasing trend in research related to biochar in soil for contaminant remediation. Five exemplar contaminants were reviewed in both laboratory and field-based studies. These included two inorganic (i.e., As and Pb) and three organic classes (i.e., sulfamethoxazole, atrazine, and PAHs). The contaminants were selected based on bibliometric data and as representatives of their various contaminant classes. For example, As and Pb are potentially toxic elements (anionic and cationic, respectively), while sulfamethoxazole, atrazine, and PAHs represent antibiotics, herbicides, and hydrocarbons, respectively.  Results and discussion: The interaction between biochar and contaminants in soil is largely driven by biochar precursor material and pyrolysis temperature as well as some characteristics of the contaminants such as octanol-water partition coefficient (KOW) and polarity. The structural and chemical characteristics of biochar in turn determine the major sorption mechanisms and define biochar’s suitability for contaminant sorption. Based on the reviewed literature, a soil treatment plan is suggested to guide the application of biochar in various soil types (paddy soils, brownfield, and mine soils) at different pH levels (4–5.5) and contaminant concentrations ( 50 mg kg−1).  Conclusions: Research on biochar has grown over the years with significant focus on its properties, and how these affect biochar’s ability to immobilize organic and inorganic contaminants in soil. Few of these studies have been field-based. More studies with greater focus on field-based soil remediation are therefore required to fully understand the behavior of biochar under natural circumstances. Other recommendations are made aimed at stimulating future research in areas where significant knowledge gaps exist