Next-generation sequencing for endocrine cancers : Recent advances and challenges

Contemporary molecular biology research tools have enriched numerous areas of biomedical research that address challenging diseases, including endocrine cancers (pituitary, thyroid, parathyroid, adrenal, testicular, ovarian, and neuroendocrine cancers). These tools have placed several intriguing clues before the scientific community. Endocrine cancers pose a major challenge in health care and research despite considerable attempts by researchers to understand their etiology. Microarray analyses have provided gene signatures from many cells, tissues, and organs that can differentiate healthy states from diseased ones, and even show patterns that correlate with stages of a disease. Microarray data can also elucidate the responses of endocrine tumors to therapeutic treatments. The rapid progress in next-generation sequencing methods has overcome many of the initial challenges of these technologies, and their advantages over microarray techniques have enabled them to emerge as valuable aids for clinical research applications (prognosis, identification of drug targets, etc.). A comprehensive review describing the recent advances in next-generation sequencing methods and their application in the evaluation of endocrine and endocrine-related cancers is lacking. The main purpose of this review is to illustrate the concepts that collectively constitute our current view of the possibilities offered by next-generation sequencing technological platforms, challenges to relevant applications, and perspectives on the future of clinical genetic testing of patients with endocrine tumors. We focus on recent discoveries in the use of next-generation sequencing methods for clinical diagnosis of endocrine tumors in patients and conclude with a discussion on persisting challenges and future objectives

Decrease in water clarity of the southern and central North Sea during the 20th century

Light in the marine environment is a key environmental variable coupling physics to marine biogeochemistry and ecology. Weak light penetration reduces light available for photosynthesis, changing energy fluxes through the marine food web. Based on published and unpublished data, this study shows that the central and southern North Sea has become significantly less clear over the second half of the 20th century. In particular, in the different regions and seasons investigated, the average Secchi depth pre-1950 decreased between 25% and 75% compared to the average Secchi depth post-1950. Consequently, in summer pre-1950, most (74%) of the sea floor in the permanently mixed area off East Anglia was within the photic zone. For the last 25+ years, changes in water clarity were more likely driven by an increase in the concentration of suspended sediments, rather than phytoplankton. We suggest that a combination of causes have contributed to this increase in suspended sediments such as changes in sea-bed communities and in weather patterns, decreased sink of sediments in estuaries, and increased coastal erosion. A predicted future increase in storminess (Beniston et al., 2007; Kovats et al., 2014) could enhance the concentration of suspended sediments in the water column and consequently lead to a further decrease in clarity, with potential impacts on phytoplankton production, CO2 fluxes, and fishery production

embCAB Sequence Variation Among Ethambutol-Resistant Mycobacterium Tuberculosis Isolates Without embB306 Mutation

Mechanisms of resistance to ethambutol in Mycobacterium tuberculosis remain inadequately described. Although there is mounting evidence that mutations of codon 306 in embB play a key role, a significant number of phenotypically ethambutol-resistant strains do not carry mutations in this codon. Here, other mutations in the embCAB operon are suggested to be involved in resistance development

Multi-analyte profiling of ten cytokines in South African HIV-infected patients with Immune Reconstitution Inflammatory Syndrome (IRIS)

Abstract Background Immune reconstitution inflammatory syndrome (IRIS) is an important complication of HAART in sub-Saharan Africa, where opportunistic infections (OIs) including mycobacteria and cryptococcus are common. The immune system's role in HIV infected patients is complex with cytokine expression strongly influencing HIV infection and replication. Methods We determined the expression patterns of 10 cytokines by Luminex multi-analyte profiling in 17 IRIS nested case-control pairs participating in a prospective South African cohort initiating anti-retroviral therapy. Results Interferon-gamma (IFN-γ) expression was significantly elevated in IRIS cases compared to controls (median 9.88 pg/ml versus 2.68 pg/ml, respectively, P = 0.0057), while other cytokines displayed non-significant differences in expression. Significant correlation was observed between IL-6, IL-10, and IFN-γ expression in the IRIS patients. Conclusions Significantly increased expression levels of IFN-γ suggest that this cytokine possibly plays a role in IRIS pathology and is a potential diagnostic marker

Effects of Family Literacy Programs : the role of implementation quality

Enhancing literacy skills in children who are at risk of lagging behind in school is an international policy priority, as these skills are of key importance for children’s academic careers. Recognizing the strong and long lasting influence of parents as first educators of their children, family literacy programs aim to promote children’s literacy development by stimulating the home literacy environment, particularly in at-risk families. Previously established disappointing program effects for these families stress the need for insight into how programs are implemented. Starting from a comprehensive framework for measuring i

Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance.

BACKGROUND: Data on the performance of standardized short-course directly observed treatment (DOTS) of tuberculosis (TB) in areas with high levels of drug resistance and on the potential impact of DOTS on amplification of resistance are limited. Therefore, we analyzed treatment results from a cross-sectional sample of patients with TB enrolled in a DOTS program in an area with high levels of drug resistance in Uzbekistan and Turkmenistan in Central Asia. METHODS: Sputum samples for testing for susceptibility to 5 first-line drugs and for molecular typing were obtained from patients starting treatment in 8 districts. Patients with sputum smear results positive for TB at the end of the intensive phase of treatment and/or at 2 months into the continuation phase were tested again. RESULTS. Among 382 patients with diagnoses of TB, 62 did not respond well to treatment and were found to be infected with an identical Mycobacterium tuberculosis strain when tested again; 19 of these patients had strains that developed new or additional drug resistance. Amplification occurred in only 1.2% of patients with initially susceptible or monoresistant TB strains, but it occurred in 17% of those with polyresistant strains (but not multidrug-resistant strains, defined as strains with resistance to at least isoniazid and rifampicin) and in 7% of those with multidrug-resistant strains at diagnosis. Overall, 3.5% of the patients not initially infected with multidrug-resistant TB strains developed such strains during treatment. Amplification of resistance, however, was found only in polyresistant Beijing genotype strains. CONCLUSIONS: High levels of amplification of drug resistance demonstrated under well-established DOTS program conditions reinforce the need for implementation of DOTS-Plus for multidrug-resistant TB in areas with high levels of drug resistance. The strong association of Beijing genotype and amplification in situations of preexisting resistance is striking and may underlie the strong association between this genotype and drug resistance

Multiple fragmented habitat-patch use in an urban breeding passerine, the Short-toed Treecreeper

Individual responses of wild birds to fragmented habitat have rarely been studied, despite large-scale habitat fragmentation and biodiversity loss resulting from widespread urbanisation. We investigated the spatial ecology of the Short-toed Treecreeper Certhia brachydactyla, a tiny, resident, woodland passerine that has recently colonised city parks at the northern extent of its range. High resolution spatiotemporal movements of this obligate tree-living species were determined using radio telemetry within the urbanized matrix of city parks in Copenhagen, Denmark. We identified regular edge crossing behaviour, novel in woodland birds. While low numbers of individuals precluded a comprehensive characterisation of home range for this population, we were able to describe a consistent behaviour which has consequences for our understanding of animal movement in urban ecosystems. We report that treecreepers move freely, and apparently do so regularly, between isolated habitat patches. This behaviour is a possible driver of the range expansion in this species and may contribute to rapid dispersal capabilities in certain avian species, including Short-toed Treecreepers, into northern Europe. Alternatively, these behaviours might be common and/or provide an adaptive advantage for birds utilising matrix habitats, for example within urban ecosystems