The Use of Amniotic Membrane in the Management of Complex Chronic Wounds

Chronic wounds do not follow the usual wound healing process; instead, they are stuck in the inflammatory or proliferative phase. This is particularly evident in large, massive wounds with considerable tissue loss, which become senescent and do not epithelialize. In these wounds, we need to remove all the factors that prevent or delay normal wound healing. After that, soft tissue granulation is stimulated by local negative pressure therapy. Lastly, after the granulation is completed, the epithelialization process must be activated. Although a plethora of wound dressings and devices are available, chronic wounds persist as a unresolved medical concern. We have been using frozen amniotic membrane (AM) to treat this type of wounds with good results. Our studies have shown that AM is able to induce epithelialization in large wounds that were unable to epithelialize. AM induces several signaling pathways involved in cell migration and/or proliferation. Among those, we can highlight the mitogen‐activated protein kinase (MAPK) and Jun N‐terminal kinase (JNK) signaling pathways. Additionally, AM is able to selectively antagonise the anti-proliferative effect of TGFß by modifying its genetic program on keratinocytes. The combined effect of AM on keratinocytes, promoting cell proliferation/migration and antagonising TGFß-effect, is the perfect combination allowing chronic wounds to progress into epithelialization

Serological Findings in a Child with Paroxysmal Cold Haemoglobinuria

PCH is a rare autoimmune hemolytic anemia (AIHA) but is one of the most common causes of AIAH in children. For the diagnosis, it is important to perform the appropriate methods of serological investigation and show the typical biphasic reaction. This is a case report of a child who presented with features of haemolysis and was diagnosed with PCH of this way

Quinoxalinetacrine QT78, a cholinesterase inhibitor as a potential ligand for Alzheimer’s disease therapy

We report the synthesis and relevant pharmacological properties of the quinoxalinetacrine (QT) hybrid QT78 in a project targeted to identify new non-hepatotoxic tacrine derivatives for Alzheimer\u2019s disease therapy. We have found that QT78 is less toxic than tacrine at high concentrations (from 100 \ub5M to 1 mM), less potent than tacrine as a ChE inhibitor, but shows selective BuChE inhibition (IC50 (hAChE) = 22.0 \ub1 1.3 \ub5M; IC50 (hBuChE) = 6.79 \ub1 0.33 \ub5M). Moreover, QT78 showed effective and strong neuroprotection against diverse toxic stimuli, such as rotenone plus oligomycin-A or okadaic acid, of biological significance for Alzheimer\u2019s disease

The Myxococcus xanthus Two-Component System CorSR Regulates Expression of a Gene Cluster Involved in Maintaining Copper Tolerance during Growth and Development

Myxococcus xanthus is a soil-dwelling member of the δ–Proteobacteria that exhibits a complex developmental cycle upon starvation. Development comprises aggregation and differentiation into environmentally resistant myxospores in an environment that includes fluctuations in metal ion concentrations. While copper is essential for M. xanthus cells because several housekeeping enzymes use it as a cofactor, high copper concentrations are toxic. These opposing effects force cells to maintain a tight copper homeostasis. A plethora of paralogous genes involved in copper detoxification, all of which are differentially regulated, have been reported in M. xanthus. The use of in-frame deletion mutants and fusions with the reporter gene lacZ has allowed the identification of a two-component system, CorSR, that modulates the expression of an operon termed curA consisting of nine genes whose expression slowly increases after metal addition, reaching a plateau. Transcriptional regulation of this operon is complex because transcription can be initiated at different promoters and by different types of regulators. These genes confer copper tolerance during growth and development. Copper induces carotenoid production in a ΔcorSR mutant at lower concentrations than with the wild-type strain due to lack of expression of a gene product resembling subunit III of cbb3-type cytochrome c oxidase. This data may explain why copper induces carotenoid biosynthesis at suboptimal rather than optimal growth conditions in wild-type strains.This work has been funded by the Spanish Government (grants CSD2009-00006 and BFU2012-33248, 70% funded by FEDER). This work was also supported by the National Institute of General Medical Science of the National Institutes of Health under award number R01GM095826 to LJS, and by the National Science Foundation under award number MCB0742976 to LJS. JMD and JP received a fellowship from Junta de Andalucía to do some work at University of Georgia

CorE from Myxococcus xanthus Is a Copper-Dependent RNA Polymerase Sigma Factor

The dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. Consequently, many genes have previously been reported to participate in copper detoxification in bacteria. Myxococcus xanthus, a prokaryote, encodes many proteins involved in copper homeostasis that are differentially regulated by this metal. A σ factor of the ECF (extracytoplasmic function) family, CorE, has been found to regulate the expression of the multicopper oxidase cuoB, the P1B-type ATPases copA and copB, and a gene encoding a protein with a heavy-metal-associated domain. Characterization of CorE has revealed that it requires copper to bind DNA in vitro. Genes regulated by CorE exhibit a characteristic expression profile, with a peak at 2 h after copper addition. Expression rapidly decreases thereafter to basal levels, although the metal is still present in the medium, indicating that the activity of CorE is modulated by a process of activation and inactivation. The use of monovalent and divalent metals to mimic Cu(I) and Cu(II), respectively, and of additives that favor the formation of the two redox states of this metal, has revealed that CorE is activated by Cu(II) and inactivated by Cu(I). The activation/inactivation properties of CorE reside in a Cys-rich domain located at the C terminus of the protein. Point mutations at these residues have allowed the identification of several Cys involved in the activation and inactivation of CorE. Based on these data, along with comparative genomic studies, a new group of ECF σ factors is proposed, which not only clearly differs mechanistically from the other σ factors so far characterized, but also from other metal regulators

Large-scale database mining reveals hidden trends and future directions for cancer immunotherapy

LLC Cancer immunotherapy has fundamentally changed the landscape of oncology in recent years and significant resources are invested into immunotherapy research. It is in the interests of researchers and clinicians to identify promising and less promising trends in this field in order to rationally allocate resources. This requires a quantitative large-scale analysis of cancer immunotherapy related databases. We developed a novel tool for text mining, statistical analysis and data visualization of scientific literature data. We used this tool to analyze 72002 cancer immunotherapy publications and 1469 clinical trials from public databases. All source codes are available under an open access license. The contribution of specific topics within the cancer immunotherapy field has markedly shifted over the years. We show that the focus is moving from cell-based therapy and vaccination towards checkpoint inhibitors, with these trends reaching statistical significance. Rapidly growing subfields include the combination of chemotherapy with checkpoint blockade. Translational studies have shifted from hematological and skin neoplasms to gastrointestinal and lung cancer and from tumor antigens and angiogenesis to tumor stroma and apoptosis. This work highlights the importance of unbiased large-scale database mining to assess trends in cancer research and cancer immunotherapy in particular. Researchers, clinicians and funding agencies should be aware of quantitative trends in the immunotherapy field, allocate resources to the most promising areas and find new approaches for currently immature topics

Robot Mapping and Localisation for Feature Sparse Water Pipes Using Voids as Landmarks

Robotic systems for water pipe inspection do not generally include navigation components for mapping the pipe network and locating damage. Such navigation systems would be highly advantageous for water companies because it would allow them to more effectively target maintenance and reduce costs. In water pipes, a major challenge for robot navigation is feature sparsity. In order to address this problem, a novel approach for robot navigation in water pipes is developed here, which uses a new type of landmark feature - voids outside the pipe wall, sensed by ultrasonic scanning. The method was successfully demonstrated in a laboratory environment and showed for the first time the potential of using voids for robot navigation in water pipes

Body composition changes after a weight loss intervention: A 3-year follow-up study

Studies comparing different types of exercise-based interventions have not shown a consistent effect of training on long-term weight maintenance. The aim of this study was to compare the effects of exercise modalities combined with diet intervention on body composition immediately after intervention and at 3 years’ follow-up in overweight and obese adults. Two-hundred thirty-nine people (107 men) participated in a 6-month diet and exercise-based intervention, split into four randomly assigned groups: strength group (S), endurance group (E), combined strength and endurance group (SE), and control group (C). The body composition measurements took place on the first week before the start of training and after 22 weeks of training. In addition, a third measurement took place 3 years after the intervention period. A significant interaction effect (group × time) (p = 0.017) was observed for the fat mass percentage. It significantly decreased by 5.48 ± 0.65%, 5.30 ± 0.65%, 7.04 ± 0.72%, and 4.86 ± 0.65% at post-intervention for S, E, SE, and C, respectively. Three years after the intervention, the fat mass percentage returned to values similar to the baseline, except for the combined strength and endurance group, where it remained lower than the value at pre-intervention (p < 0.05). However, no significant interaction was discovered for the rest of the studied outcomes, neither at post-intervention nor 3 years later. The combined strength and endurance group was the only group that achieved lower levels of fat mass (%) at both post-intervention and 3 years after intervention, in comparison with the other groups.This work received financial support from the Ministerio de Ciencia e Innovación, Convocatoria de Ayudas I+D 2008, Proyectos de Investigación Fundamental No Orientada, del VI Plan de Investigación Nacional 2008–2011 (Contract: DEP2008-06354-C04-01). This study is registered at www.clinicaltrials.gov (ID: NCT0111685

Spanish Cell Therapy Network (TerCel) : 15 years of successful collaborative translational research

In the current article we summarize the 15-year experience of the Spanish Cell Therapy Network (TerCel), a successful collaborative public initiative funded by the Spanish government for the support of nationwide translational research in this important area. Thirty-two research groups organized in three programs devoted to cardiovascular, neurodegenerative and immune-inflammatory diseases, respectively, currently form the network. Each program has three working packages focused on basic science, pre-clinical studies and clinical application. TerCel has contributed during this period to boost the translational research in cell therapy in Spain, setting up a network of Good Manufacturing Practice-certified cell manufacturing facilities- and increasing the number of translational research projects, publications, patents and clinical trials of the participating groups, especially those in collaboration. TerCel pays particular attention to the public-private collaboration, which, for instance, has led to the development of the first allogeneic cell therapy product approved by the European Medicines Agency, Darvadstrocel. The current collaborative work is focused on the development of multicenter phase 2 and 3 trials that could translate these therapies to clinical practice for the benefit of patients

Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study

Background: The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31-gene expression profile (DecisionDx-Melanoma) test has shown promising results. Objectives: To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. Methods: Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease-free survival was determined using Kaplan-Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). Results: Median follow-up time was 26 months (IQR 22-30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. Conclusions: This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31-gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow-up strategies