Clavicle fracture nonunion in the paediatric population: a systematic review of the literature.

Aims: Clavicle fracture nonunions are extremely rare in children. The aim of this systematic review was to assess what factors may predispose children to form clavicle fracture nonunions and evaluate the treatment methods and outcomes. Methods: We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, aiming to find papers reporting clavicle fracture nonunion in children under the age of 18 years. Data was collected on patient demographics, fracture type, mechanism of injury (MOI), surgical intervention and reported outcome. Two independent reviewers evaluated all the data. Results: A total of 13 articles reporting 21 cases of clavicle fracture nonunion were identified. The mean age at time of injury was 11.4 years (4 to 17). Falls were the most common MOI. The majority of nonunions occurred after displaced fractures on the right side. Six were refractures. Mean time of presentation following injury was 13.5 months (4 to 60). In all, 16 were treated surgically. Radiographic union was eventually achieved in 12 cases, with functional outcome satisfactory in all cases. Conclusion: Clavicle nonunion is an extremely rare but possible complication in children. The majority occur after displaced right-sided fractures or refractures and present around one year after injury. Surgical fixation provides good radiographic healing and functional outcomes. Level of evidence: IV

99pharnessing copper in cancer to enhance anti tumor immune response

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f(R)f(R) theory and geometric origin of the dark sector in Horava-Lifshitz gravity

Inclusion of $f(R)$ term in the action of Horava-Lifshitz quantum gravity with projectability but without detailed balance condition is investigated, where $R$ denotes the 3-spatial dimensional Ricci scalar. Conditions for the spin-0 graviton to be free of ghosts and instability are studied. The requirement that the theory reduce to general relativity in the IR makes the scalar mode unstable in the Minkowski background but stable in the de Sitter. It is remarkable that the dark sector, dark matter and dark energy, of the universe has a naturally geometric origin in such a setup. Bouncing universes can also be constructed. Scalar perturbations in the FRW backgrounds with non-zero curvature are presented.Comment: Mod. Phys. Lett. A26, 387-398 (2011

Lessons from the decoupling limit of Horava gravity

We consider the so-called "healthy" extension of Horava gravity in the limit where the Stuckelberg field decouples from the graviton. We verify the alleged strong coupling problem in this limit, under the assumption that no large dimensionless parameters are put in by hand. This follows from the fact that the dispersion relation for the Stuckelberg field does not have the desired z = 3 anisotropic scaling in the UV. To get the desired scaling and avoid strong coupling one has to introduce a low scale of Lorentz violation and retain some coupling between the graviton and the Stuckelberg field. We also make use of the foliation preserving symmetry to show how the Stuckelberg field couples to some violation of energy conservation. We source the Stuckelberg field using a point particle with a slowly varying mass and show that two such particles feel a constant attractive force. In this particular example, we see no Vainshtein effect, and violations of the Equivalence Principle. The latter is probably generic to other types of source and could potentially be used to place lower bounds on the scale of Lorentz violation.Comment: 18 pages, 1 figure. Version to appear in JHEP. Conclusions with respect to strong coupling modified - our strong coupling analysis does not apply to a low scale of Lorentz violation. Expanded Equivalence Principle violation discussion, noting it presents a challenge to low scale Lorentz violation, exactly the scenario designed to cure strong coupling. Other minor corrections and references adde

In vivo [64Cu]CuCl2 PET imaging reveals activity of Dextran-Catechin on tumor copper homeostasis

Given the strong clinical evidence that copper levels are significantly elevated in a wide spectrum of tumors, copper homeostasis is considered as an emerging target for anticancer drug design. Monitoring copper levels in vivo is therefore of paramount importance when assessing the efficacy of copper-targeting drugs. Herein, we investigated the activity of the copper-targeting compound Dextran-Catechin by developing a [64Cu]CuCl2 PET imaging protocol to monitor its effect on copper homeostasis in tumors. Methods: Protein expression of copper transporter 1 (CTR1) in tissue microarrays representing 90 neuroblastoma patient tumors was assessed by immunohistochemistry. Western blotting analysis was used to study the effect of Dextran-Catechin on the expression of CTR1 in neuroblastoma cell lines and in tumors. A preclinical human neuroblastoma xenograft model was used to study anticancer activity of Dextran-Catechin in vivo and its effect on tumor copper homeostasis. PET imaging with [64Cu]CuCl2 was performed in such preclinical neuroblastoma model to monitor alteration of copper levels in tumors during treatment. Results: CTR1 protein was found to be highly expressed in patient neuroblastoma tumors by immunohistochemistry. Treatment of neuroblastoma cell lines with Dextran-Catechin resulted in decreased levels of glutathione and in downregulation of CTR1 expression, which caused a significant decrease of intracellular copper. No changes in CTR1 expression was observed in normal human astrocytes after Dextran-Catechin treatment. In vivo studies and PET imaging analysis using the neuroblastoma preclinical model revealed elevated [64Cu]CuCl2 retention in the tumor mass. Following treatment with Dextran-Catechin, there was a significant reduction in radioactive uptake, as well as reduced tumor growth. Ex vivo analysis of tumors collected from Dextran-Catechin treated mice confirmed the reduced levels of CTR1. Interestingly, copper levels in blood were not affected by treatment, demonstrating potential tumor specificity of Dextran-Catechin activity. Conclusion: Dextran-Catechin mediates its activity by lowering CTR1 and intracellular copper levels in tumors. This finding further reveals a potential therapeutic strategy for targeting copper-dependent cancers and presents a novel PET imaging method to assess patient response to copper-targeting anticancer treatments

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Current trends in nursing informatics: Results of an international survey

© 2016 IMIA and IOS Press. Nursing informatics (NI) can help provide effective and safe healthcare. This study aimed to describe current research trends in NI. In the summer 2015, the IMIA-NI Students Working Group created and distributed an online international survey of the current NI trends. A total of 402 responses were submitted from 44 countries. We identified a top five NI research areas: standardized terminologies, mobile health, clinical decision support, patient safety and big data research. NI research funding was considered to be difficult to acquire by the respondents. Overall, current NI research on education, clinical practice, administration and theory is still scarce, with theory being the least common. Further research is needed to explain the impact of these trends and the needs from clinical practice

Advancing nursing informatics in the next decade: Recommendations from an international survey

© 2016 IMIA and IOS Press. In the summer of 2015, the International Medical Informatics Association Nursing Informatics Special Interest Group (IMIA NISIG) Student Working Group developed and distributed an international survey of current and future trends in nursing informatics. The survey was developed based on current literature on nursing informatics trends and translated into six languages. Respondents were from 31 different countries in Asia, Africa, North and Central America, South America, Europe, and Australia. This paper presents the results of responses to the survey question: "What should be done (at a country or organizational level) to advance nursing informatics in the next 5-10 years?" (n responders=272). Using thematic qualitative analysis, responses were grouped into five key themes: 1) Education and training; 2) Research; 3) Practice; 4) Visibility; and 5) Collaboration and integration. We also provide actionable recommendations for advancing nursing informatics in the next decade

Delivery of PEGylated liposomal doxorubicin by bispecific antibodies improves treatment in models of high-risk childhood leukemia

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia

Genetic diversity and differentiation among populations of the Indian eri silkworm, Samia cynthia ricini, revealed by ISSR markers

Samia cynthia ricini (Lepidoptera:Saturniidae), the Indian eri silkworm, contributes significantly to the production of commercial silk and is widely distributed in the Brahmaputra river valley in North-Eastern India. Due to over exploitation coupled with rapid deforestation, most of the natural populations of S. cynthia ricini are dwindling rapidly and its preservation has become an important goal. Assessment of the genetic structure of each population is a prerequisite for a sustainable conservation program. DNA fingerprinting to detect genetic variation has been used in different insect species not only between populations, but also between individuals within a population. Since, information on the genetic basis of phenotypic variability and genetic diversity within the S. cynthia ricini populations is scanty, inter simple sequence repeat (ISSR) system was used to assess genetic diversity and differentiation among six commercially exploited S. cynthia ricini populations. Twenty ISSR primers produced 87% of inter population variability among the six populations. Genetic distance was lowest between the populations Khanapara (E5) and Mendipathar (E6) (0.0654) and highest between Dhanubhanga (E4) and Titabar (E3) (0.3811). Within population, heterozygosity was higher in Borduar (E2) (0.1093) and lowest in Titabar (E3) (0.0510). Highest gene flow (0.9035) was between E5 and E6 and the lowest (0.2172) was between E3 and E5. Regression analysis showed positive correlation between genetic distance and geographic distance among the populations. The high GST value (0.657) among the populations combined with low gene flow contributes significantly to the genetic differentiation among the S. cynthia ricini populations. Based on genetic diversity, these populations can be considered as different ecotypes and in situ conservation of them is recommended