Human Papillomavirus Prevalence in a Population of Women Living in Port-au-Prince and Leogane,Haiti

Background

There have been no published studies of carcinogenic human papillomavirus (HPV)--the necessary cause of cervical cancer--in Haiti, a nation that has one of the greatest burdens of cervical cancer globally.

Objective

Characterize prevalence of carcinogenic HPV and the prevalence of individual carcinogenic HPV genotypes in women with cervical precancer or cancer, cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+).

Methods

Women (n=9,769; aged 25-60 years) were screened for carcinogenic HPV by Hybrid Capture 2 (HC2; Qiagen, Gaithersburg, MD). Carcinogenic HPV positives underwent colposcopy and visible lesions were biopsied. A subset of carcinogenic HPV positives was tested for individual HPV genotypes using a GP5+/6+ assay.

Results

The prevalence of carcinogenic HPV was 19.0% (95% confidence interval: 18.4%-19.9%) and decreased with increasing age (p_trend < 0.001). Women with 3 or more sexual partners and who started sex before the age of 18 years had twice the age-adjusted prevalence of carcinogenic HPV of women with one partner and who started sex after the age of 21 (24.3% vs. 12.9%, respectively). HPV16 and HPV35 were the most common HPV genotypes detected in CIN2+ and more common in women with CIN2+ than those without CIN2+. HPV16 and/or HPV18 were detected in 21.0% of CIN2 (n = 42), 46.2% of CIN3 (n = 52), and 80% of cancers (n = 5).

Conclusions

The prevalence of carcinogenic HPV in Haiti was much greater than the prevalence in other Latin American countries. High carcinogenic HPV prevalence and a lack of cervical cancer screening may explain the high burden of cervical cancer in Haiti.     

Response-Predictive Gene Expression Profiling of Glioma Progenitor Cells In Vitro

Background

High-grade gliomas are amongst the most deadly human tumors. Treatment results are disappointing. Still, in several trials around 20% of patients respond to therapy. To date, diagnostic strategies to identify patients that will profit from a specific therapy do not exist.

Methods

In this study, we used serum-free short-term treated in vitro cell cultures to predict treatment response in vitro. This approach allowed us (a) to enrich specimens for brain tumor initiating cells and (b) to confront cells with a therapeutic agent before expression profiling.

Results

As a proof of principle we analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Profiles from treated progenitor cells allowed to predict therapy-induced impairment of proliferation in vitro.

Conclusion

For the tyrosine kinase inhibitor Sunitinib used in this dataset, the approach revealed additional predictive information in comparison to the evaluation of classical signaling analysis.     

Visualization-Aided Classification Ensembles Discriminate Lung Adenocarcinoma and Squamous Cell Carcinoma Samples Using Their Gene Expression Profiles

Introduction

The widespread application of microarray experiments to cancer research is astounding including lung cancer, one of the most common fatal human tumors. Among non-small cell lung carcinoma (NSCLC), there are two major histological types of NSCLC, adenocarcinoma (AC) and squamous cell carcinoma (SCC).

Results

In this paper, we proposed to integrate a visualization method called Radial Coordinate Visualization (Radviz) with a suitable classifier, aiming at discriminating two NSCLC subtypes using patients'' gene expression profiles. Our analyses on simulated data and a real microarray dataset show that combining with a classification method, Radviz may play a role in selecting relevant features and ameliorating parsimony, while the final model suffers no or least loss of accuracy. Most importantly, a graphic representation is more easily understandable and implementable for a clinician than statistical methods and/or mathematic equations.

Conclusion

To conclude, using the NSCLC microarray data presented here as a benchmark, the comprehensive understanding of the underlying mechanism associated with NSCLC and of the mechanisms with its subtypes and respective stages will become reality in the near future.     

Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution

Background

Comparison of toxicogenomic data facilitates the identification of deregulated gene patterns and maximizes health risk prediction in human.

Results

Here, we performed phenotypic anchoring on the effects of acute exposure to low-grade polluted groundwater using mouse and zebrafish. Also, we evaluated two windows of chronic exposure in mouse, starting in utero and at the end of lactation. Bioinformatic analysis of livers microarray data showed that the number of deregulated biofunctions and pathways is higher after acute exposure, compared to the chronic one. It also revealed specific profiles of altered gene expression in all treatments, pointing to stress response/mitochondrial pathways as major players of environmental toxicity. Of note, dysfunction of steroid hormones was also predicted by bioinformatic analysis and verified in both models by traditional approaches, serum estrogens measurement and vitellogenin mRNA determination in mice and zebrafish, respectively.

Conclusions

In our report, phenotypic anchoring in two vertebrate model organisms highlights the toxicity of low-grade pollution, with varying susceptibility based on exposure window. The overlay of zebrafish and mice deregulated pathways, more than single genes, is useful in risk identification from chemicals implicated in the observed effects.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1067) contains supplementary material, which is available to authorized users.     

Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas

Objective

To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI).

Method

To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model.

Results

Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen.

Conclusions

The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas.     

MiRNA Expression May Account for Chronic but Not for Acute Regulation of mRNA Expression in Human Thyroid Tumor Models

Background

For thyroid tumorigenesis, two main human in vitro models are available: primary cultures of human thyrocytes treated with TSH or EGF/serum as models for autonomous adenomas (AA) or papillary thyroid carcinomas (PTC) respectively, and human thyroid tumor derived cell lines. Previous works of our group have assessed properties of those models, with a special emphasis on mRNA regulations. It is often assumed that miRNA may be one of the primary events inducing these mRNA regulations.

Methods

The purpose of this study was to investigate the representativity of those models to study microRNA regulations and their relation with mRNA expression. To achieve this aim, the miRNA expressions profiles of primary cultures treated with TSH or EGF/serum and of 6 thyroid cancer cell lines were compared to the expression profiles of 35 tumor tissues obtained by microarrays.

Results

Our data on primary cultures have shown that the TSH or EGF/serum treatment did not greatly modify the microRNA expression profiles, which is contrary to what is observed for mRNA expression profiles, although they still evolved differently according to the treatment. The analysis of miRNA and mRNA expressions profiles in the cell lines has shown that they have evolved into a common, dedifferentiated phenotype, closer to ATC than to the tumors they are derived from.

Conclusions

Long-terms TSH or EGF/serum treatments do not mimic AA or PTC respectively in terms of miRNA expression as they do for mRNA, suggesting that the regulations of mRNA expression induced by these physiological agents occur independently of miRNA. The general patterns of miRNA expression in the cell lines suggest that they represent a useful model for undifferentiated thyroid cancer. Mirna probably do not mediate the rapid changes in gene expression in rapid cell biology regulation.     

Psychological Sequelae of the Station Nightclub Fire: Comparing Survivors with and without Physical Injuries Using a Mixed-Methods Analysis

Background

Surveying survivors from a large fire provides an opportunity to explore the impact of emotional trauma on psychological outcomes.

Methods

This is a cross-sectional survey of survivors of The Station Fire. Primary outcomes were post-traumatic stress (Impact of Event Scale – Revised) and depressive (Beck Depression Inventory) symptoms. Linear regression was used to examine differences in symptom profiles between those with and without physical injuries. The free-response section of the survey was analyzed qualitatively to compare psychological sequelae of survivors with and without physical injuries.

Results

104 participants completed the study survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. The mean age of respondents was 32 years, 62% were male, and 47% experienced a physical injury. No significant relationships were found between physical injury and depressive or post-traumatic stress symptom profiles. In the qualitative analysis, the emotional trauma that survivors experienced was a major, common theme regardless of physical injury. Survivors without physical injuries were more likely to experience survivor guilt, helplessness, self-blame, and bitterness. Despite the post-fire challenges described, most survivors wrote about themes of recovery and renewal.

Conclusions

All survivors of this large fire experienced significant psychological sequelae. These findings reinforce the importance of mental health care for all survivors and suggest a need to understand factors influencing positive outcomes.     

Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

Background

It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations.

Methodology

Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites.

Principal Findings

The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption.

Conclusions

It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces.     

The Impact of Psychological Capital on Job Burnout of Chinese Nurses: The Mediator Role of Organizational Commitment

Background

Nursing has a high risk of job burnout, but only a few studies have explored its influencing factors from an organizational perspective.

Objective

The present study explores the impact of psychological capital on job burnout by investigating the mediating effect of organizational commitment on this relationship.

Methods

A total of 473 female nurses from four large general hospitals in Xi’an City of China were selected as participants. Data were collected via the Psychological Capital Questionnaire, the Maslach Burnout Inventory-General Survey, and the Organizational Commitment Scale.

Results

Both psychological capital and organizational commitment were significantly correlated to job burnout. Structural equation modelling indicated that organizational commitment partially mediated the relationship between psychological capital and job burnout.

Conclusion

The final model revealed a significant path from psychological capital to job burnout through organizational commitment. These findings extended prior reports and shed some light on the influence of psychological capital on job burnout.     

Psychopathological Profiles in Transsexuals and the Challenge of Their Special Status among the Sexes

Objective

Investigating psychopathological profiles of transsexuals raises a very basic methodological question: are control groups, which represent the biological or the phenotypic sex, most suited for an optimal evaluation of psychopathology of transsexuals?

Method

Male-to-female (MtF) (n=52) and female-to-male transsexuals (FtM) (n=32), receiving cross-sex hormone treatment, were compared with age matched healthy subjects of the same genetic sex (n=178) and with the same phenotypic sex (n=178) by means of the Symptom Check List-90-Revisited instrument (SCL-90-R). We performed analyses of covariance (ANCOVA) to test for group and sex effects. Furthermore, we used a profile analysis to determine if psychopathological symptom profiles of transsexuals more closely resemble genotypic sex or phenotypic sex controls.

Results

Transsexual patients reported more symptoms of psychopathological distress than did healthy control subjects in all subscales of the SCL-90-R (all p<0.001), regardless of whether they were compared with phenotype or genotype matched controls. Depressive symptoms were more pronounced in MtF than in FtM (SCL-90-R score 0.85 vs. 0.45, p = 0.001). We could demonstrate that FtM primarily reflect the psychopathological profile of biological males rather than that of biological females (r = 0.945), while MtF showed a slightly higher profile similarity with biological females than with biological males (r = 0.698 vs. r = 0.685).

Conclusion

Our findings suggest that phenotypic sex matched controls are potentially more appropriate for comparison with the psychopathology of transsexual patients than are genetic sex matched controls.     

GeneComps and ChemComps: a new CTD metric to identify genes and chemicals with shared toxicogenomic profiles

The Comparative Toxicogenomics Database is a public resource that promotes understanding about the effects of environmental chemicals on human health. Currently, CTD describes over 184,000 molecular interactions for more than 5,100 chemicals and 16,300 genes/proteins. We have leveraged this dataset of chemical-gene relationships to compute similarity indices following the statistical method of the Jaccard index. These scores are used to produce lists of comparable genes (“GeneComps”) or chemicals (“ChemComps”) based on shared toxicogenomic profiles. GeneComps and ChemComps are now provided for every curated gene and chemical in CTD. ChemComps are particularly significant because they provide a way to group chemicals based upon their biological effects, instead of their physical or structural properties. These metrics provide a novel way to view and classify genes and chemicals and will help advance testable hypotheses about environmental chemical-genedisease networks.

Availability

CTD is freely available at http://ctd.mdibl.org/     

Proteomic Interactions in the Mouse Vitreous-Retina Complex

Purpose

Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina.

Methods

Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software.

Results

We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor.

Conclusions

Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.     

A Study of Cytological Changes in the Bone Marrow of Patients with Severe Fever with Thrombocytopenia Syndrome

Background

Peripheral blood leucopenia and thrombocytopenia are the main manifestations in severe fever with thrombocytopenia syndrome (SFTS) patients. However, the underlying causes are poorly understood. Therefore, we aimed to investigate cytology of bone marrow samples collected from SFTS patients.

Methods

10 SFTS patients were identified by typical clinical manifestations, detection of peripheral blood leucopenia and thrombocytopenia, and nucleic acid-based detection of the newly identified bunyavirus. SFTS patients, along with 10 participants with acute aplastic anemia and 10 healthy volunteers were enrolled in this study after written informed consent to undergo bone marrow cytological examination.

Results

We observed similar bone marrow properties in SFTS patients and healthy volunteers, significantly different from the characteristics observed in acute aplastic anemia patients.

Conclusion

Similarities between bone marrow samples collected from SFTS patients and healthy volunteers suggest that peripheral blood leucopenia and thrombocytopenia do not result from bone marrow cell plasticity.     

Pharmaceutical Availability across Levels of Care: Evidence from Facility Surveys in Ghana,Kenya, and Uganda

Objective

In this study we use facility-level data from nationally representative surveys conducted in Ghana, Kenya, and Uganda to understand pharmaceutical availability within the three countries.

Methods

In 2012, we conducted a survey to capture information on pharmaceuticals and other facility indicators from over 200 facilities in each country. We analyze data on the availability of pharmaceuticals and quantify its association with various facility-level indicators. We analyze both availability of essential medicines, as defined by the various essential medicine lists (EMLs) of each respective country, and availability of all surveyed pharmaceuticals deemed important for treatment of various high-burden diseases, including those on the EMLs.

Results

We find that there is heterogeneity with respect to availability across the three countries with Ghana generally having better availability than Uganda and Kenya. To analyze the relationship between facility-level factors and pharmaceutical stock-out we use a binomial regression model. We find that the factors associated with stock-out vary by country, but across all countries both presence of a laboratory at the facility and presence of a vehicle at the facility are significantly associated with reduced stock-out.

Conclusion

The results of this study highlight the poor availability of essential medicines across these three countries and suggest more needs to be done to strengthen the supply system so that stock remains uninterrupted.     

Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare,Zimbabwe, 2012

Background

Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare.

Methods

A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff''s spatial scan statistic.

Principal Findings

We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff''s spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic.

Conclusions

This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.     

When Local Extinction and Colonization of River Fishes Can Be Predicted by Regional Occupancy: the Role of Spatial Scales

Background

Predicting which species are likely to go extinct is perhaps one of the most fundamental yet challenging tasks for conservation biologists. This is particularly relevant for freshwater ecosystems which tend to have the highest proportion of species threatened with extinction. According to metapopulation theories, local extinction and colonization rates of freshwater subpopulations can depend on the degree of regional occupancy, notably due to rescue effects. However, relationships between extinction, colonization, regional occupancy and the spatial scales at which they operate are currently poorly known.

Methods

And Findings: We used a large dataset of freshwater fish annual censuses in 325 stream reaches to analyse how annual extinction/colonization rates of subpopulations depend on the regional occupancy of species. For this purpose, we modelled the regional occupancy of 34 fish species over the whole French river network and we tested how extinction/colonization rates could be predicted by regional occupancy described at five nested spatial scales. Results show that extinction and colonization rates depend on regional occupancy, revealing existence a rescue effect. We also find that these effects are scale dependent and their absolute contribution to colonization and extinction tends to decrease from river section to larger basin scales.

Conclusions

In terms of management, we show that regional occupancy quantification allows the evaluation of local species extinction/colonization dynamics and reduction of local extinction risks for freshwater fish species implies the preservation of suitable habitats at both local and drainage basin scales.     

Relative Mortality among Criminals in Norway and the Relation to Drug and Alcohol Related Offenses

Background

Registered offenders are known to have a higher mortality rate, but given the high proportion of offenders with drug-addiction, particularly among offenders with a custodial sentence, higher mortality is expected. While the level of overall mortality compared to the non-criminal population is of interest in itself, we also estimate the risk of death by criminal records related to substance abuse and other types of criminal acts, and separate between those who receive a prison sentence or not.

Methods

Age-adjusted relative risks of death for 2000–2008 were studied in a population based dataset. Our dataset comprise the total Norwegian population of 2.9 million individuals aged 15–69 years old in 1999, of whom 10% had a criminal record in the 1992–1999 period.

Results

Individuals with a criminal record have twice the relative risk (RR) of death of the control group (non-offenders). Males with a record of use/possession of drugs and a prison record have an 11.9 RR (females, 15.6); males with a drug record but no prison record have a 6.9 RR (females 10.5). Males imprisoned for driving under the influence of substances have a 4.4 RR (females 5.6); males with a record of driving under the influence but no prison sentence have a 3.2 RR (females 6.5). Other male offenders with a prison record have a 2.8 RR (females 3.7); other male offenders with no prison record have a 1.7 RR (females 2.3).

Conclusion

Significantly higher mortality was found for people with a criminal record, also for those without any record of drug use. Mortality is much higher for those convicted of substance-related crimes: more so for drug- than for alcohol-related crimes and for women.