Chromosomal amplifications, 3q gain and deletions of 2q33-q37 are the frequent genetic changes in cervical carcinoma

BACKGROUND: Carcinoma of uterine cervix is the second most common cancers among women worldwide. Combined radiation and chemotherapy is the choice of treatment for advanced stages of the disease. The prognosis is poor, with a five-year survival rate ranging from about 20–65%, depending on stage of the disease. Therefore, genetic characterization is essential for understanding the biology and clinical heterogeneity in cervical cancer (CC). METHODS: We used a genome-wide screening method – comparative genomic hybridization (CGH) to identify DNA copy number changes in 77 patients with cervical cancer. We applied categorical and survival analyses to analyze whether chromosomal changes were related to clinico-pathologic characteristics and patients survival. RESULTS: The CGH analysis revealed a loss of 2q33-q37 (57.1%), gain of 3q (54.5%) and chromosomal amplifications (20.77%) as frequent genetic changes. A total of 15 amplified chromosomal sites were detected in 16 cases that include 1p31, 2q32, 7q22, 8q21.2-q24, 9p22, 10q21, 10q24, 11q13, 11q21, 12q15, 14q12, 17p11.2, 17q22, 18p11.2, and 19q13.1. Recurrent amplified sites were noted at 11q13, 11q21, and 19q13.1. The genomic alterations were further evaluated for prognostic significance in CC patients, and we did not find any correlation with a number of clinical or histological parameters. The tumors harboring HPV18 exhibited higher genomic instability compared to tumors with HPV 16. CONCLUSIONS: This study demonstrated that 2q33-q37 deletions, 3q gains and chromosomal amplifications as characteristic changes in invasive CC. These genetic alterations will aid in the identification of novel tumor suppressor gene(s) at 2q33-q37 and oncogenes at amplified chromosomal sites. Molecular characterization of these chromosomal changes utilizing the current genomic technologies will provide new insights into the biology and clinical behavior of CC

Combinations of Host Biomarkers Predict Mortality among Ugandan Children with Severe Malaria: A Retrospective Case-Control Study

Background: Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. Methodology/Findings: Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1-99.9) sensitivity and 88.8% (79.7-94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). Conclusions: We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria

A longitudinal survey of African animal trypanosomiasis in domestic cattle on the Jos Plateau, Nigeria:prevalence, distribution and risk factors

BACKGROUND: Trypanosomiasis is a widespread disease of livestock in Nigeria and a major constraint to the rural economy. The Jos Plateau, Nigeria was free from tsetse flies and the trypanosomes they transmit due to its high altitude and the absence of animal trypanosomiasis attracted large numbers of cattle-keeping pastoralists to inhabit the plateau. The Jos Plateau now plays a significant role in the national cattle industry, accommodating approximately 7% of the national herd and supporting 300,000 pastoralists and over one million cattle. However, during the past two decades tsetse flies have invaded the Jos Plateau and animal trypanosomiasis has become a significant problem for livestock keepers. METHODS: In 2008 a longitudinal two-stage cluster survey on the Jos Plateau. Cattle were sampled in the dry, early wet and late wet seasons. Parasite identification was undertaken using species-specific polymerase chain reactions to determine the prevalence and distribution bovine trypanosomiasis. Logistic regression was performed to determine risk factors for disease. RESULTS: The prevalence of bovine trypanosomiasis (Trypanosoma brucei brucei, Trypanosoma congolense savannah, Trypanosoma vivax) across the Jos Plateau was found to be high at 46.8% (39.0 – 54.5%) and significant, seasonal variation was observed between the dry season and the end of the wet season. T. b. brucei was observed at a prevalence of 3.2% (1% – 5.5%); T. congolense at 27.7% (21.8% - 33.6%) and T. vivax at 26.7% (18.2% - 35.3%). High individual variation was observed in trypanosomiasis prevalence between individual villages on the Plateau, ranging from 8.8% to 95.6%. Altitude was found to be a significant risk factor for trypanosomiasis whilst migration also influenced risk for animal trypanosomiasis. CONCLUSIONS: Trypanosomiasis is now endemic on the Jos Plateau showing high prevalence in cattle and is influenced by seasonality, altitude and migration practices. Attempts to successfully control animal trypanosomiasis on the Plateau will need to take into account the large variability in trypanosomiasis infection rates between villages, the influence of land use, and husbandry and management practices of the pastoralists, all of which affect the epidemiology of the disease

Association of the Gene Polymorphisms IFN-γ +874, IL-13 −1055 and IL-4 −590 with Patterns of Reinfection with Schistosoma mansoni

Approximately 200 million people have schistosomiasis in parts of Africa, South America, the Middle East, the Caribbean and Asia. Several studies of multiple treatments and reinfections indicate that some people develop resistance to reinfection. Of all the immunologic findings associated with such studies, the most consistent observation is that resistance (usually defined as lower levels of infection upon reinfection) correlates with high IgE and low IgG4 antibodies against schistosome antigens. Our studies test whether single nucleotide polymorphisms residing in the gene or promoter regions of cytokines pivotal in controlling production of these antibody isotypes are different amongst those that develop resistance to reinfection as opposed to those that do not. Through genotyping of these polymorphisms in a cohort of occupationally exposed car washers, we found that men with certain genotypic patterns of polymorphisms in IL-4, IFN-γ, and IL-13 were significantly more likely to be resistant to reinfection than those with different patterns. These data provide initial insights into the potential genetic foundation of propensities of people to develop resistance to reinfection by schistosomes, and offer a basis for further molecular studies of how these polymorphisms might work at the transcriptional and gene product level in cells stimulated by schistosome antigens

Correlates of opium use: retrospective analysis of a survey of tribal communities in Arunachal Pradesh, India

BACKGROUND: Household survey data of Changlang district, Arunachal Pradesh, were used in the present study to assess the prevalence of opium use among different tribes, and to examine the association between sociodemographic factors and opium use. METHODS: A sample of 3421 individuals (1795 men and 1626 women) aged 15 years and older was analyzed using a multivariate logistic regression model to determine factors associated with opium use. Sociodemographic information such as age, education, occupation, religion, ethnicity and marital status were included in the analysis. RESULTS: The prevalence of opium use was significantly higher (10.6%) among men than among women (2.1%). It varied according to age, educational level, occupation, marital status and religion of the respondents. In both sexes, opium use was significantly higher among Singpho and Khamti tribes compared with other tribes. Multivariate logistic regression indicated that opium use was significantly associated with age, occupation, ethnicity, religion and marital status of the respondents of both sexes. Multivariate rate ratios (MRR) for opium use were significantly higher (4–6 times) among older age groups (≥35 years) and male respondents. In males, the MRR was also significantly higher in respondents of Buddhist and Indigenous religion, while in females, the MRR was significantly higher in Buddhists. Most of the female opium users had taken opium for more than 5 years and were introduced to it by their husbands after marriage. Use of other substances among opium users comprised mainly tobacco (76%) and alcohol (44%). CONCLUSIONS: The study reveals the sociodemographic factors, such as age, sex, ethnicity, religion and occupation, which are associated with opium use. Such information is useful for institution of intervention measures to reduce opium use

Outcomes in pancreatic resection are negatively influenced by pre-operative hospitalization

AbstractBackgroundQuality improvement in high-acuity surgery increasingly relies on clinical pathways to streamline patient care and to maximize cost-efficiency. Yet, it remains unclear whether immediate pre-operative hospitalization (non-elective resection) influences operative performance and to what extent it alters the post-operative course.MethodsRetrospective case series, cost analysis.University tertiary care referral centre. Four hundred and twelve consecutive pancreatic resections performed for benign and malignant disease between 2001 and 2008. Outcomes for both elective and non-elective operations were scrutinized, and correlated with deviations from our clinical Carepath for Pancreatic Resection. Observed-to-expected (O/E) morbidity ratios were calculated for each.ResultsOverall, 39 patients (10%) required immediate pre-operative hospitalization, 22 (56%) of which were transferred from another hospital. The most common indications were pancreatitis, gastric outlet obstruction, intractable abdominal pain and gastrointestinal bleeding. During a 1- to 2-week hospitalization, 51% of patients underwent endoscopic retrograde cholangio-pancreatography (ERCP), 36% were administered parenteral nutrition, 20% received antibiotics and 15% were transfused blood products. Yet, this pre-operative scenario, at a median cost of $7250 per patient, had no measurable impact on operative performance. Post-operatively, non-elective patients suffered more complications and a higher (O/E) ratio (1.00 vs. 0.93). These outcomes resulted in significantly more deviations from our carepath and an additional$7000 per non-elective case.ConclusionImmediate pre-operative hospitalization has no meaningful impact on operative performance; yet, deviations from a standardized clinical pathway are far more likely after non-elective pancreatic resection, and result in more severe clinical and economic outcomes