Impact of concomitant thyroid pathology on preoperative workup for primary hyperparathyroidism

BACKGROUND: The former standard surgical treatment in patients with primary hyperparathyroidism (pHPT) has been bilateral cervical exploration. New localization techniques and the possibility of intraoperative measurement of intact parathormone (iPTH) permit a focused, minimally invasive parathyroidectomy (MIP). The introduction of MIP without complete neck exploration leads to the potential risk of missing thyroid pathology. The aim of the present study is to evaluate the value of MIP in respect to coexisting thyroid findings and their impact on preoperative workup for primary hyperparathyroidism. METHODS: This is a prospective study including 30 consecutive patients with pHPT (median age 65 years; 17 females, 13 males). In all patients preoperative localization was performed by ultrasonography and 99m Tc-MIBI scintigraphy- Intraoperative iPTH monitoring was routinely done. RESULTS: Ten patients (33%) had a concurrent thyroid finding requiring additional thyroid surgery, and two patients (7%) with negative localization results underwent bilateral neck exploration. Therefore, MIP was attempted in 18 (60%) patients. The conversion rate to a four gland exploration was 6% (1/18). The sensitivities of 99m Tc-MIBI scanning and ultrasonography were 83.3% and 76.6%, respectively. The respective accuracy rates were 83.3% and 76.6%. Of note, the combination of the two modalities did not improve the sensitivity and accuracy in our patient population. During a median follow-up of 40 months, none of the patients developed persistent or recurrent hypocalcaemia, resulting in a 100% cure rate. CONCLUSION: Coexisting thyroid pathology is relatively frequent in patients with pHPT in our region. Among patients having pHPT without any thyroid pathology, the adenoma localization is correct with either ultrasonography or 99m Tc-MIBI scintigraphy in the majority of cases. MIP with iPTH monitoring are highly successful in this group of patients and this operative technique should be the method of choice

The Sound Generated by Mid-Ocean Ridge Black Smoker Hydrothermal Vents

Hydrothermal flow through seafloor black smoker vents is typically turbulent and vigorous, with speeds often exceeding 1 m/s. Although theory predicts that these flows will generate sound, the prevailing view has been that black smokers are essentially silent. Here we present the first unambiguous field recordings showing that these vents radiate significant acoustic energy. The sounds contain a broadband component and narrowband tones which are indicative of resonance. The amplitude of the broadband component shows tidal modulation which is indicative of discharge rate variations related to the mechanics of tidal loading. Vent sounds will provide researchers with new ways to study flow through sulfide structures, and may provide some local organisms with behavioral or navigational cues

Constraints on 6D Supergravity Theories with Abelian Gauge Symmetry

We study six-dimensional N=(1,0) supergravity theories with abelian, as well as non-abelian, gauge group factors. We show that for theories with fewer than nine tensor multiplets, the number of possible combinations of gauge groups - including abelian factors - and non-abelian matter representations is finite. We also identify infinite families of theories with distinct U(1) charges that cannot be ruled out using known quantum consistency conditions, though only a finite subset of these can arise from known string constructions.Comment: 49 pages, latex; v2: minor corrections, references added; v3: minor correction

Real-Time Definition of Non-Randomness in the Distribution of Genomic Events

Features such as mutations or structural characteristics can be non-randomly or non-uniformly distributed within a genome. So far, computer simulations were required for statistical inferences on the distribution of sequence motifs. Here, we show that these analyses are possible using an analytical, mathematical approach. For the assessment of non-randomness, our calculations only require information including genome size, number of (sampled) sequence motifs and distance parameters. We have developed computer programs evaluating our analytical formulas for the real-time determination of expected values and p-values. This approach permits a flexible cluster definition that can be applied to most effectively identify non-random or non-uniform sequence motif distribution. As an example, we show the effectivity and reliability of our mathematical approach in clinical retroviral vector integration site distribution

Quality of life among Latina breast cancer patients: a systematic review of the literature

Introduction The Latino population is the most rapidly growing ethnic minority in the United States and Latinas have higher rates of advanced breast cancer and more rigorous treatments than White women. However, the literature lacks reviews on quality of life among this population of breast cancer patients. Methods A systematic review of the breast cancer quality of life (QOL) literature was conducted among studies that provided a comparison of mental, physical, social, or sexual QOL between Latinas and other racial/ethnic groups. Of the 375 studies reviewed, 20 quantitative studies and two qualitative studies met criteria for inclusion. Results Latinas were more likely to report poor mental, physical, and social QOL, relative to non-Latinas. Only four studies assessed sexual QOL, making it difficult to draw any conclusions. Of these four QOL domains, the largest disparity was found in the area of mental health in which Latinas reported poorer QOL compared to non-Latina Whites and Blacks. Discussion/conclusions Most quantitative studies revealed either that Latinas consistently evidenced significantly lower QOL than non-Latinas on all measures (6 studies) or reported mixed findings in which Latinas generally demonstrated significantly worse QOL on most, but not all, measures (12 studies) included in the study. Explanatory mechanisms including socio-demographic, treatment-related, and culturally-relevant factors are discussed. Implications for research design, measurement, and clinical work are also included. Implications for cancer survivors Although not entirely consistent, data suggest that Latina breast cancer survivors on average experience worse QOL than non-Latina Whites. Understanding ethnic differences in QOL among breast cancer survivors can inform interventions targeted at improving health status for Latinas

Virtual pathway explorer (viPEr) and pathway enrichment analysis tool (PEANuT): creating and analyzing focus networks to identify cross-talk between molecules and pathways

BACKGROUND: Interpreting large-scale studies from microarrays or next-generation sequencing for further experimental testing remains one of the major challenges in quantitative biology. Combining expression with physical or genetic interaction data has already been successfully applied to enhance knowledge from all types of high-throughput studies. Yet, toolboxes for navigating and understanding even small gene or protein networks are poorly developed. RESULTS: We introduce two Cytoscape plug-ins, which support the generation and interpretation of experiment-based interaction networks. The virtual pathway explorer viPEr creates so-called focus networks by joining a list of experimentally determined genes with the interactome of a specific organism. viPEr calculates all paths between two or more user-selected nodes, or explores the neighborhood of a single selected node. Numerical values from expression studies assigned to the nodes serve to score identified paths. The pathway enrichment analysis tool PEANuT annotates networks with pathway information from various sources and calculates enriched pathways between a focus and a background network. Using time series expression data of atorvastatin treated primary hepatocytes from six patients, we demonstrate the handling and applicability of viPEr and PEANuT. Based on our investigations using viPEr and PEANuT, we suggest a role of the FoxA1/A2/A3 transcriptional network in the cellular response to atorvastatin treatment. Moreover, we find an enrichment of metabolic and cancer pathways in the Fox transcriptional network and demonstrate a patient-specific reaction to the drug. CONCLUSIONS: The Cytoscape plug-in viPEr integrates –omics data with interactome data. It supports the interpretation and navigation of large-scale datasets by creating focus networks, facilitating mechanistic predictions from –omics studies. PEANuT provides an up-front method to identify underlying biological principles by calculating enriched pathways in focus networks. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2017-z) contains supplementary material, which is available to authorized users

Location-Specific Responses to Thermal Stress in Larvae of the Reef-Building Coral Montastraea faveolata

The potential to adapt to a changing climate depends in part upon the standing genetic variation present in wild populations. In corals, the dispersive larval phase is particularly vulnerable to the effects of environmental stress. Larval survival and response to stress during dispersal and settlement will play a key role in the persistence of coral populations.To test the hypothesis that larval transcription profiles reflect location-specific responses to thermal stress, symbiont-free gametes from three to four colonies of the scleractinian coral Montastraea faveolata were collected from Florida and Mexico, fertilized, and raised under mean and elevated (up 1 to 2 degrees C above summer mean) temperatures. These locations have been shown to exchange larvae frequently enough to prevent significant differentiation of neutral loci. Differences among 1,310 unigenes were simultaneously characterized using custom cDNA microarrays, allowing investigation of gene expression patterns among larvae generated from wild populations under stress. Results show both conserved and location-specific variation in key processes including apoptosis, cell structuring, adhesion and development, energy and protein metabolism, and response to stress, in embryos of a reef-building coral.These results provide first insights into location-specific variation in gene expression in the face of gene flow, and support the hypothesis that coral host genomes may house adaptive potential needed to deal with changing environmental conditions

Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review

The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells

Novel Small-Molecule Inhibitors of Hepatitis C Virus Entry Block Viral Spread and Promote Viral Clearance in Cell Culture

Combinations of direct-acting anti-virals offer the potential to improve the efficacy, tolerability and duration of the current treatment regimen for hepatitis C virus (HCV) infection. Viral entry represents a distinct therapeutic target that has been validated clinically for a number of pathogenic viruses. To discover novel inhibitors of HCV entry, we conducted a high throughput screen of a proprietary small-molecule compound library using HCV pseudoviral particle (HCVpp) technology. We independently discovered and optimized a series of 1,3,5-triazine compounds that are potent, selective and non-cytotoxic inhibitors of HCV entry. Representative compounds fully suppress both cell-free virus and cell-to-cell spread of HCV in vitro. We demonstrate, for the first time, that long term treatment of an HCV cell culture with a potent entry inhibitor promotes sustained viral clearance in vitro. We have confirmed that a single amino acid variant, V719G, in the transmembrane domain of E2 is sufficient to confer resistance to multiple compounds from the triazine series. Resistance studies were extended by evaluating both the fusogenic properties and growth kinetics of drug-induced and natural amino acid variants in the HCVpp and HCV cell culture assays. Our results indicate that amino acid variations at position 719 incur a significant fitness penalty. Introduction of I719 into a genotype 1b envelope sequence did not affect HCV entry; however, the overall level of HCV replication was reduced compared to the parental genotype 1b/2a HCV strain. Consistent with these findings, I719 represents a significant fraction of the naturally occurring genotype 1b sequences. Importantly, I719, the most relevant natural polymorphism, did not significantly alter the susceptibility of HCV to the triazine compounds. The preclinical properties of these triazine compounds support further investigation of entry inhibitors as a potential novel therapy for HCV infection