“It Is Me Who Endures but My Family That Suffers”: Social Isolation as a Consequence of the Household Cost Burden of Buruli Ulcer Free of Charge Hospital Treatment

Despite free of charge biomedical treatment, the cost burden of Buruli ulcer disease (Bu) hospitalisation in Central Cameroon accounts for 25% of households' yearly earnings, surpassing the threshold of 10%, which is generally considered catastrophic for the household economy, and calling into question the sustainability of current Bu programmes. The high non-medical costs and productivity loss for Bu patients and their households make household involvement in the healing process unsustainable. 63% of households cease providing social and financial support for patients as a coping strategy, resulting in the patient's isolation at the hospital. Social isolation itself was cited by in-patients as the principal cause for abandonment of biomedical treatment. These findings demonstrate that further research and investment in Bu are urgently needed to evaluate new intervention strategies that are socially acceptable and appropriate in the local context

Regulation of the High Affinity IgE Receptor (FcεRI) in Human Neutrophils: Role of Seasonal Allergen Exposure and Th-2 Cytokines

The high affinity IgE receptor, FcεRI, plays a key role in the immunological pathways involved in allergic asthma. Previously we have demonstrated that human neutrophils isolated from allergic asthmatics express a functional FcεRI, and therefore it was of importance to examine the factors regulating its expression. In this study, we found that neutrophils from allergic asthmatics showed increased expression of FcεRI-α chain surface protein, total protein and mRNA compared with those from allergic non asthmatics and healthy donors (p<0.001). Interestingly, in neutrophils isolated from allergic asthmatics, FcεRI-α chain surface protein and mRNA expression were significantly greater during the pollen season than outside the pollen season (n = 9, P = 0.001), an effect which was not observed either in the allergic non asthmatic group or the healthy donors (p>0.05). Allergen exposure did not affect other surface markers of neutrophils such as CD16/FcγRIII or IL-17R. In contrast to stimulation with IgE, neutrophils incubated with TH2 cytokines IL-9, GM-CSF, and IL-4, showed enhanced FcεRI-α chain surface expression. In conclusion, these results suggest that enhanced FcεRI expression in human neutrophils from allergic asthmatics during the pollen season can make them more susceptible to the biological effects of IgE, providing a possible new mechanism by which neutrophils contribute to allergic asthma

BioInfer: a corpus for information extraction in the biomedical domain

BACKGROUND: Lately, there has been a great interest in the application of information extraction methods to the biomedical domain, in particular, to the extraction of relationships of genes, proteins, and RNA from scientific publications. The development and evaluation of such methods requires annotated domain corpora. RESULTS: We present BioInfer (Bio Information Extraction Resource), a new public resource providing an annotated corpus of biomedical English. We describe an annotation scheme capturing named entities and their relationships along with a dependency analysis of sentence syntax. We further present ontologies defining the types of entities and relationships annotated in the corpus. Currently, the corpus contains 1100 sentences from abstracts of biomedical research articles annotated for relationships, named entities, as well as syntactic dependencies. Supporting software is provided with the corpus. The corpus is unique in the domain in combining these annotation types for a single set of sentences, and in the level of detail of the relationship annotation. CONCLUSION: We introduce a corpus targeted at protein, gene, and RNA relationships which serves as a resource for the development of information extraction systems and their components such as parsers and domain analyzers. The corpus will be maintained and further developed with a current version being available at

Interfacial Chemistry in Al/CuO Reactive Nanomaterial and Its Role in Exothermic Reaction.

Interface layers between reactive and energetic materials in nanolaminates or nanoenergetic materials are believed to play a crucial role in the properties of nanoenergetic systems. Typically, in the case of Metastable Interstitial Composite nanolaminates, the interface layer between the metal and oxide controls the onset reaction temperature, reaction kinetics, and stability at low temperature. So far, the formation of these interfacial layers is not well understood for lack of in situ characterization, leading to a poor control of important properties. We have combined in situ infrared spectroscopy and ex situ X-ray photoelectron spectroscopy, differential scanning calorimetry, and high resolution transmission electron microscopy, in conjunction with firstprinciples calculations to identify the stable configurations that can occur at the interface and determine the kinetic barriers for their formation. We find that (i) an interface layer formed during physical deposition of aluminum is composed of a mixture of Cu, O, and Al through Al penetration into CuO and constitutes a poor diffusion barrier (i.e., with spurious exothermic reactions at lower temperature), and in contrast, (ii) atomic layer deposition (ALD) of alumina layers using trimethylaluminum (TMA)produces a conformal coating that effectively prevents Al diffusion even for ultrathin layer thicknesses (∼0.5 nm), resulting in better stability at low temperature and reduced reactivity. Importantly, the initial reaction of TMA with CuO leads to the extraction of oxygen from CuO to form an amorphous interfacial layer that is an important component for superior protection properties of the interface and is responsible for the high system stability. Thus, while Al e-beam evaporation and ALD growth of an alumina layer on CuO both lead to CuO reduction, the mechanism for oxygen removal is different, directly affecting the resistance to Al diffusion. This work reveals that it is the nature of the monolayer interface between CuO and alumina/Al rather than the thickness of the alumina layer that controls the kinetics of Al diffusion, underscoring the importance of the chemical bonding at the interface in these energetic materials

Gender and HIV-associated pulmonary tuberculosis: presentation and outcome at one year after beginning antituberculosis treatment in Uganda

BACKGROUND: Tuberculosis is responsible for more female deaths around the earth than any other infectious disease. Reports have suggested that responses to tuberculosis may differ between men and women. We investigated gender related differences in the presentation and one year outcomes of HIV-infected adults with initial episodes of pulmonary tuberculosis in Uganda. METHODS: We enrolled and followed up a cohort of 105 male and 109 female HIV-infected adults on treatment for initial episodes of culture-confirmed pulmonary tuberculosis between March 1993 and March 1995. A favorable outcome was defined as being cured and alive at one year while an unfavorable outcome was not being cured or dead. Subjects were followed-up by serial medical examinations, complete blood counts, serum β(2) microglobulin, CD4+ cell counts, sputum examinations, and chest x-rays. RESULTS: Male patients were older, had higher body mass indices, and lower serum β(2) microglobulin levels than female patients at presentation. At one year, there was no difference between male and female patients in the likelihood of experiencing a favorable outcome (RR 1.02, 95% CI 0.89–1.17). This effect persisted after controlling for symptoms, serum β(2) microglobulin, CD4+ cell count, and severity of disease on chest x-ray (OR 1.07, 95% CI 0.54–2.13) with a repeated measures model. CONCLUSIONS: While differences existed between males and females with HIV-associated pulmonary tuberculosis at presentation, the outcomes at one year after the initiation of tuberculosis treatment were similar in Uganda. Women in areas with a high HIV and tuberculosis prevalence should be encouraged to present for screening at the first sign of tuberculosis symptoms

Transient Alteration of Cellular Redox Buffering before Irradiation Triggers Apoptosis in Head and Neck Carcinoma Stem and Non-Stem Cells

Background: Head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy owing to intrinsic radioresistance and lack of induction of apoptosis. The major focus of this work was to design a transient glutathione depleting strategy during the course of irradiation of HNSCC in order to overcome their radioresistance associated with redox adaptation. Methodology/Principal Findings: Treatment of SQ20B cells with dimethylfumarate (DMF), a GSH-depleting agent, and L-Buthionine sulfoximine (BSO), an inhibitor of GSH biosynthesis 4 h before a 10 Gy irradiation led to the lowering of the endogenous GSH content to less than 10 % of that in control cells and to the triggering of radiation-induced apoptotic cell death. The sequence of biochemical events after GSH depletion and irradiation included ASK-1 followed by JNK activation which resulted in the triggering of the intrinsic apoptotic pathway through Bax translocation to mitochondria. Conclusions: This transient GSH depletion also triggered radiation-induced cell death in SQ20B stem cells, a key event to overcome locoregional recurrence of HNSCC. Finally, our in vivo data highlight the relevance for further clinical trials o

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Corpus annotation for mining biomedical events from literature

<p>Abstract</p> <p>Background</p> <p>Advanced Text Mining (TM) such as semantic enrichment of papers, event or relation extraction, and intelligent Question Answering have increasingly attracted attention in the bio-medical domain. For such attempts to succeed, text annotation from the biological point of view is indispensable. However, due to the complexity of the task, semantic annotation has never been tried on a large scale, apart from relatively simple term annotation.</p> <p>Results</p> <p>We have completed a new type of semantic annotation, event annotation, which is an addition to the existing annotations in the GENIA corpus. The corpus has already been annotated with POS (Parts of Speech), syntactic trees, terms, etc. The new annotation was made on half of the GENIA corpus, consisting of 1,000 Medline abstracts. It contains 9,372 sentences in which 36,114 events are identified. The major challenges during event annotation were (1) to design a scheme of annotation which meets specific requirements of text annotation, (2) to achieve biology-oriented annotation which reflect biologists' interpretation of text, and (3) to ensure the homogeneity of annotation quality across annotators. To meet these challenges, we introduced new concepts such as Single-facet Annotation and Semantic Typing, which have collectively contributed to successful completion of a large scale annotation.</p> <p>Conclusion</p> <p>The resulting event-annotated corpus is the largest and one of the best in quality among similar annotation efforts. We expect it to become a valuable resource for NLP (Natural Language Processing)-based TM in the bio-medical domain.</p

Ceramides bind VDAC2 to trigger mitochondrial apoptosis

Ceramides draw wide attention as tumor suppressor lipids that act directly on mitochondria to trigger apoptotic cell death. However, molecular details of the underlying mechanism are largely unknown. Using a photoactivatable ceramide probe, we here identify the voltage-dependent anion channels VDAC1 and VDAC2 as mitochondrial ceramide binding proteins. Coarse-grain molecular dynamics simulations reveal that both channels harbor a ceramide binding site on one side of the barrel wall. This site includes a membrane-buried glutamate that mediates direct contact with the ceramide head group. Substitution or chemical modification of this residue abolishes photolabeling of both channels with the ceramide probe. Unlike VDAC1 removal, loss of VDAC2 or replacing its membrane-facing glutamate with glutamine renders human colon cancer cells largely resistant to ceramide-induced apoptosis. Collectively, our data support a role of VDAC2 as direct effector of ceramide-mediated cell death, providing a molecular framework for how ceramides exert their anti-neoplastic activity

Detecting Foci of Malaria Transmission with School Surveys: A Pilot Study in the Gambia.

BACKGROUND: In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community. METHODS: The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schools in the Upper River Region of The Gambia were selected with probability proportional to size; in each school approximately 100 children were randomly chosen for inclusion in the study. Each child had a finger prick blood sample collected for the determination of antimalarial antibodies by ELISA, malaria infection by microscopy and PCR, and for haemoglobin measurement. In addition, a simple questionnaire on socio-demographic variables and the use of insecticide-treated bed nets was completed. The cut-off for positivity for antimalarial antibodies was obtained using finite mixture models. The clustered nature of the data was taken into account in the analyses. RESULTS: A total of 3,277 children were included in the survey. The mean age was 10 years (SD = 2.7) [range 4-21], with males and females evenly distributed. The prevalence of malaria infection as determined by PCR was 13.6% (426/3124) [95% CI = 12.2-16.3] with marked variation between schools (range 3-25%, p<0.001), while the seroprevalence was 7.8% (234/2994) [95%CI = 6.4-9.8] for MSP119, 11.6% (364/2997) [95%CI = 9.4-14.5] for MSP2, and 20.0% (593/2973) [95% CI = 16.5-23.2) for AMA1. The prevalence of all the three antimalarial antibodies positive was 2.7% (79/2920). CONCLUSIONS: This survey shows that malaria prevalence and seroprevalence before the transmission season were highly heterogeneous