Education, Age and Gender: Critical Factors in Determining Interventions for Child Brick Workers in Pakistan and Afghanistan.

Working in factories fashioning bricks by hand seems the epitome of hazardous child labor. Yet, efforts to remove children from this work have shown little success; impoverished families balance the value of their children's contribution against the risks they see. Unfortunately, psychosocial impacts are often not visible, and are rarely taken into consideration when designing interventions. A comprehensive occupational health study of children working in brick factories included a module on psychosocial risks and impacts. This analysis reports on the Pakistan and Afghanistan portion of the study which was administered to 450 child brick workers and 486 controls, aged 11-17. Factorial ANOVAs confirmed that working in brick factories was the strongest predictor of respondent's psychosocial health. However, they also identified subgroups of children that escape this prediction. Older girls, for example, actually felt better when working, compared with staying at home. Schooling had positive associations, especially in younger boys and adolescent girls. In fact, the results of this study showed that those who are at greatest psychosocial risk were girls who do not go to school. These findings underscore the importance of assessing psychosocial impacts and tailoring policy and interventions to specific gender and age categories of young workers.

Circulating Biomarkers for Early Stage Non-Small Cell Lung Carcinoma Detection: Supplementation to Low-Dose Computed Tomography.

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients' overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low-dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

An Educational Bioinformatics Project to Improve Genome Annotation.

Scientific advancement is hindered without proper genome annotation because biologists lack a complete understanding of cellular protein functions. In bacterial cells, hypothetical proteins (HPs) are open reading frames with unknown functions. HPs result from either an outdated database or insufficient experimental evidence (i.e., indeterminate annotation). While automated annotation reviews help keep genome annotation up to date, often manual reviews are needed to verify proper annotation. Students can provide the manual review necessary to improve genome annotation. This paper outlines an innovative classroom project that determines if HPs have outdated or indeterminate annotation. The Hypothetical Protein Characterization Project uses multiple well-documented, freely available, web-based, bioinformatics resources that analyze an amino acid sequence to (1) detect sequence similarities to other proteins, (2) identify domains, (3) predict tertiary structure including active site characterization and potential binding ligands, and (4) determine cellular location. Enough evidence can be generated from these analyses to support re-annotation of HPs or prioritize HPs for experimental examinations such as structural determination via X-ray crystallography. Additionally, this paper details several approaches for selecting HPs to characterize using the Hypothetical Protein Characterization Project. These approaches include student- and instructor-directed random selection, selection using differential gene expression from mRNA expression data, and selection based on phylogenetic relations. This paper also provides additional resources to support instructional use of the Hypothetical Protein Characterization Project, such as example assignment instructions with grading rubrics, links to training videos in YouTube, and several step-by-step example projects to demonstrate and interpret the range of achievable results that students might encounter. Educational use of the Hypothetical Protein Characterization Project provides students with an opportunity to learn and apply knowledge of bioinformatic programs to address scientific questions. The project is highly customizable in that HP selection and analysis can be specifically formulated based on the scope and purpose of each student's investigations. Programs used for HP analysis can be easily adapted to course learning objectives. The project can be used in both online and in-seat instruction for a wide variety of undergraduate and graduate classes as well as undergraduate capstone, honor's, and experiential learning projects.

Systems and strategies for identifying and enumerating children outside of family care.

Methodologies to identify and enumerate children outside of family care vary as do the vulnerability categories of the children themselves. Children outside of family care is a broad term encompassing children absent of permanent family care, e.g., institutionalized children, children on/of the street, child-headed households, separated or unaccompanied children, trafficked children, children working in exploitive labor situations, etc. This paper reviews the various methodologies applied to identify and enumerate these often hidden and/or mobile populations. Methodologies that identify and enumerate children outside of family strive to meet two objectives: (1) to estimate the number and characteristics of a specific vulnerability category and (2) to determine eligibility to receive services. The paper reviews eight methodologies; six are categorized as survey sample methods (time-location sampling, capture recapture sampling, respondent driven sampling, the neighborhood method, household surveys, and establishment surveys) while two were labeled as data management systems (child labor management system, and databases of institutions). Each review includes a concise description of the methodology, its strengths and limitations, the most appropriate population it is suited to identify and/or enumerate, and any necessary conditions. Conclusions from these reviews advocate for tailoring a methodology (or a combination of methodologies) to the specific circumstances under which it is meant to identify or enumerate children outside of family care. In addition, further research and validation studies are needed to identify the conditions under which the strategies described here can be used and to develop appropriate protocols for utilization.

In vitro modeling of the clinical interactions between octreotide and 111In-pentetreotide: is there evidence of somatostatin receptor downregulation?

UNLABELLED: Some authors have suggested that chronic octreotide use enhances the efficiency of radiolabeled somatostatin receptor (sst) imaging. Conversely, desensitization of sst on tumor tissue (tachyphylaxis) may occur occasionally in patients on chronic octreotide therapy. Assuming that chronic exposure to octreotide induces tachyphylaxis, we hypothesized that chronic exposure of sst subtype 2 (sst2)-expressing cells to octreotide would downregulate binding of 111In-pentetreotide to sst and that this downregulation would be due to a reduction in the gene copy number for sst2. METHODS: The clinical scenarios of acute (24 h) and chronic (2 wk) octreotide use, followed by either nuclear imaging exposure (8.6 pmol/L) or therapeutic exposure (510 pmol/L) to (111)In-pentetreotide, were modeled in vitro. Receptor binding in IMR-32 human neuroblastoma cells (high sst2 expression) and PANC-1 human pancreatic cancer cells (no detectable sst2 expression) was evaluated. Gene copy numbers for sst subtypes 1-5 in IMR-32 cells were determined by quantitative polymerase chain reaction. RESULTS: Acute or chronic octreotide exposure at low or high doses did not significantly alter sst2 gene copy numbers or binding of either the diagnostic dose or the therapeutic dose of 111In-pentetreotide. CONCLUSION: In vitro exposure of cells to low or high doses of octreotide for 1-14 d does not result in the development of either tachyphylaxis or upregulation of sst as assessed by changes in gene expression or in high-affinity binding.