The association between living conditions and health among Syrian refugee children in informal tented settlements in Lebanon

BACKGROUND: This cross-sectional study explores the relationship between housing, social wellbeing, access to services and health among a population of Syrian refugee children in Lebanon. METHODS: We surveyed 1902 Syrian refugee households living in informal tented settlements in Lebanon in 2017. Logistic regressions assessed relationships between housing problems, socioeconomic deprivation, social environment and health. RESULTS: Of the 8284 children in the study, 33.0% had at least one health problem. A considerable number of households (43.1%) had > 8 housing problems. Children in these households had higher odds to have three or more health problems compared to children in households with < 6 housing problems (adjusted odds ratio [AOR], 2.39; confidence interval [CI], 1.50-3.81). Nearly three-quarters (74.3%) of households were severely food insecure. Children in these households had higher odds to have one health problem than those in food secure households (AOR, 1.75; CI, 1.11-2.76). There was a significant positive association between households that reported being unhappy with their neighbourhood and the number of children with health problems in those households. CONCLUSIONS: This study highlights the association between the physical and social living conditions and refugee children's health. Without multidimensional interventions that consider improvements to living conditions, the health of young Syrian refugees will continue to worsen

Mechanical tests and definition of new indexes of grape berry firmness. Evolution of berry skin hardness during alcoholic fermentation

The mechanical strength or firmness of a fruit is considered an important parameter to characterise its state of ripeness or conservation, as well as other parameters such as sugar level or color. The mechanical hardness of grapes influences the integrity and sanitary quality of the harvest. In this study, the mechanical characteristics of grapevine berries were studied at harvest time in order to determine their rheological properties (firmness and hardness of the berry skin) during alcoholic fermentation. Special indexes were defined measuring the energy needed to crush the berries to 50 % of their initial diameter, and applied successively to two different varieties. The entire berry firmness and the skin hardness were both different. Mechanical indexes linked to grape firmness were defined. Using these indexes, a significant effect on the firmness behavior due to variety was recorded: the skin of 'Grenache Noir' was found firmer and harder than 'Carignan Noir'. Furthermore, during the alcoholic fermentation, no change in skin hardness was observed for both varieties, despite changes in the composition of the must. These results give new information on mechanical properties of berries and could be used as an aid in the winemaking process. Indeed, they would probably help the winemaker to better choose the type of fermentation and maceration adapted to his grapes according to the type of wine he wishes to produce

Phospho-MEK1/2 and uPAR Expression Determine Sensitivity of AML Blasts to a Urokinase-Activated Anthrax Lethal Toxin (PrAgU2/LF)

In this study, we attempt to target both the urokinase plasminogen activator and the mitogen-activated protein kinase pathway in acute myeloid leukemia (AML) cell lines and primary AML blasts using PrAgU2/LF, a urokinase-activated anthrax lethal toxin. PrAgU2/LF was cytotoxic to five out of nine AML cell lines. Cytotoxicity of PrAgU2/LF appeared to be nonapoptotic and was associated with MAPK activation and urokinase activity because all the PrAgU2/LF-sensitive cell lines showed both uPAR expression and high levels of MEK1/2 phosphorylation. Inhibition of uPAR or desensitization of cells to MEK1/2 inhibition blocked toxicity of PrAgU2/LF, indicating requirement for both uPAR expression and MAPK activation for activity. PrAgU2/LF was also cytotoxic to primary blasts from AML patients, with blasts from four out of five patients showing a cytotoxic response to PrAgU2/LF. Cytotoxicity of primary AML blasts was also dependent on uPAR expression and phos-MEK1/2 levels. CD34+ bone marrow blasts and peripheral blood mononuclear cells lacked uPAR expression and were resistant to PrAgU2/LF, demonstrating the lack of toxicity to normal hematological cells and, therefore, the tumor selectivity of this approach. Dose escalation in mice revealed that the maximal tolerated dose of PrAgU2/LF is at least 5.7-fold higher than that of the wild-type anthrax lethal toxin, PrAg/LF, further demonstrating the increased safety of this molecule. We have shown, in this study, that PrAgU2/LF is a novel, dual-specific molecule for the selective targeting of AML

Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function

Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the µg/mL range with half-lives of 10–20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the µg/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections

Efficient Targeting of Head and Neck Squamous Cell Carcinoma by Systemic Administration of a Dual uPA and MMP-Activated Engineered Anthrax Toxin

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although considerable progress has been made in elucidating the etiology of the disease, the prognosis for individuals diagnosed with HNSCC remains poor, underscoring the need for development of additional treatment modalities. HNSCC is characterized by the upregulation of a large number of proteolytic enzymes, including urokinase plasminogen activator (uPA) and an assortment of matrix metalloproteinases (MMPs) that may be expressed by tumor cells, by tumor-supporting stromal cells or by both. Here we explored the use of an intercomplementing anthrax toxin that requires combined cell surface uPA and MMP activities for cellular intoxication and specifically targets the ERK/MAPK pathway for the treatment of HNSCC. We found that this toxin displayed strong systemic anti-tumor activity towards a variety of xenografted human HNSCC cell lines by inducing apoptotic and necrotic tumor cell death, and by impairing tumor cell proliferation and angiogenesis. Interestingly, the human HNSCC cell lines were insensitive to the intercomplementing toxin when cultured ex vivo, suggesting that either the toxin targets the tumor-supporting stromal cell compartment or that the tumor cell requirement for ERK/MAPK signaling differs in vivo and ex vivo. This intercomplementing toxin warrants further investigation as an anti-HNSCC agent

EMQN best practice guidelines for the molecular genetic testing and reporting of chromosome 11p15 imprinting disorders: Silver–Russell and Beckwith–Wiedemann syndrome

Molecular genetic testing for the 11p15-associated imprinting disorders Silver–Russell and Beckwith–Wiedemann syndrome (SRS, BWS) is challenging because of the molecular heterogeneity and complexity of the affected imprinted regions. With the growing knowledge on the molecular basis of these disorders and the demand for molecular testing, it turned out that there is an urgent need for a standardized molecular diagnostic testing and reporting strategy. Based on the results from the first external pilot quality assessment schemes organized by the European Molecular Quality Network (EMQN) in 2014 and in context with activities of the European Network of Imprinting Disorders (EUCID.net) towards a consensus in diagnostics and management of SRS and BWS, best practice guidelines have now been developed. Members of institutions working in the field of SRS and BWS diagnostics were invited to comment, and in the light of their feedback amendments were made. The final document was ratified in the course of an EMQN best practice guideline meeting and is in accordance with the general SRS and BWS consensus guidelines, which are in preparation. These guidelines are based on the knowledge acquired from peer-reviewed and published data, as well as observations of the authors in their practice. However, these guidelines can only provide a snapshot of current knowledge at the time of manuscript submission and readers are advised to keep up with the literature

Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci.

Congenital imprinting disorders (IDs) are characterised by molecular changes affecting imprinted chromosomal regions and genes, i.e. genes that are expressed in a parent-of-origin specific manner. Recent years have seen a great expansion in the range of alterations in regulation, dosage or DNA sequence shown to disturb imprinted gene expression, and the correspondingly broad range of resultant clinical syndromes. At the same time, however, it has become clear that this diversity of IDs has common underlying principles, not only in shared molecular mechanisms, but also in interrelated clinical impacts upon growth, development and metabolism. Thus, detailed and systematic analysis of IDs can not only identify unifying principles of molecular epigenetics in health and disease, but also support personalisation of diagnosis and management for individual patients and families.All authors are members of the EUCID.net network, funded by COST (BM1208). TE is funded by the German Ministry of research and education (01GM1513B). GPdN is funded by I3SNS Program of the Spanish Ministry of Health (CP03/0064; SIVI 1395/09), Instituto de Salud Carlos III (PI13/00467) and Basque Department of Health (GV2014/111017).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13148-015-0143-

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways