In situ measurement of PCB pore water concentration profiles in activated carbon-amended sediment using passive samplers.

Vertical pore water profiles of in situ PCBs were determined in a contaminated mudflat in San Francisco Bay, CA, 30 months after treatment using an activated carbon amendment in the upper layer of the sediment. Pore water concentrations were derived from concentrations of PCBs measured in two passive samplers; polyethylene (PE, 51 μm thick) and polyoxymethylene (POM, 17 μm thick) at different sediment depths. To calculate pore water concentrations from PCB contents in the passive samplers, an equilibrium approach and a first-order uptake model were applied, using five performance reference compounds to estimate pore water sampling rates.

The impact of epithelial biomarkers, local immune response and human papillomavirus genotype in the regression of cervical intraepithelial neoplasia grades 2-3.

Background And Aims: 15-30% of cases of cervical intraepithelial neoplasia grades 2-3 (CIN2-3) detected in punch biopsies regress spontaneously (ie, show CIN1 or less in the follow-up cone). Epithelial retinoblastoma protein (pRb), tumour suppressor protein (p53), HPV genotype and immunoreactive cells have been reported to be helpful in predicting regression but their interaction in regression prediction is unknown.

Material And Methods: 55 cases of CIN2-3 in cervical biopsies with subsequent cervical cones were studied retrospectively to assess how epithelial biomarkers, immunoreactive cells (with immunohistochemistry) and high-risk (hr) HPV genotypes (by the AMPLICOR and linear array tests) prognostically interact with epithelial pRb and p53.

Marital satisfaction and communication behaviors during sexual and nonsexual conflict discussions in newlywed couples: a pilot study.

The way couples communicate during conflict discussions has been found to be a reliable predictor of marital satisfaction. However, in previous research, there has been little experimental control over the selection of topics. The present study examined, in a sample of 15 newlywed couples, whether affective displays during the discussion of a sexual and a nonsexual conflict topic differentially predict current marital satisfaction.

Sexual arousal in men: a review and conceptual analysis.

Sexual arousal is an emotional/motivational state that can be triggered by internal and external stimuli and that can be inferred from central (including verbal), peripheral (including genital), and behavioral (including action tendencies and motor preparation) responses. This article, while focusing on sexual arousal in men, provides a conceptual analysis of this construct, reviews models of sexual arousal, and discusses the usefulness of perspectives derived from motivation and emotion research in improving our understanding of its determinants and behavioral correlates. In this, it considers the role of genital feedback in men's subjective sexual arousal and the connections between sexual arousal and sexual desire.

Patterns of sexual arousal in homosexual, bisexual, and heterosexual men.

The purpose of this study was to determine if self-identified bisexual, heterosexual, and homosexual men show differential genital and subjective arousal patterns to video presentations of bisexual, heterosexual, male homosexual, and lesbian sexual interactions. It was predicted that, relative to heterosexual and homosexual stimuli, bisexual men would show the highest levels of sexual arousal to bisexual erotic material, while this stimulus would induce relatively low levels of response in heterosexual and homosexual men. A sample of 59 men (19 homosexual, 13 bisexual, and 27 heterosexual) were presented with a series of 4-min sexual videos while their genital and subjective sexual responses were measured continuously.

The prognostic value of the orphan nuclear receptor DAX-1 (NROB1) in node-negative breast cancer.

Background: DAX-1 inhibits oestrogen receptor (ER) activities and aromatase P450 expression. The prognostic effect of DAX-1 expression in breast cancer was investigated.

Patients And Methods: DAX-1, apolipoprotein D (ApoD), mitotic activity index (MAI) and other prognosticators were evaluated, by quantitative immunohistochemistry (IHC) and/or real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis, in 103 invasive node-negative breast carcinomas.

Molecular biomarkers in endometrial hyperplasias predict cancer progression.

Objective: The purpose of this study was to assess the value of the 2003 World Health Organization (WHO) and endometrial intraepithelial neoplasia (EIN) classifications, D-score, and molecular biomarkers in endometrial hyperplasia (EH) for cancer progression.

Study Design: We conducted a review of 307 endometrial hyperplasias for WHO and EIN classifications and an analysis of biomarkers, D-score, and cancer progression-free survival.

Results: The WHO, EIN, D-score, and many biomarkers were prognostic; 7.

Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis.

Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors.

D2-40/p63 defined lymph vessel invasion has additional prognostic value in highly proliferating operable node negative breast cancer patients.

Phosphohistone H3 assessed proliferation has strong prognostic value. Lymph vessel invasion by D2-40 is also prognostic, but D2-40+ myoepithelial expression in small ducts completely filled by solid-pattern ductal carcinoma in situ can mimic lymphovascular invasion. As myoepithelial cells are also p63 positive, we have investigated whether lymph vessel invasion identified by combined D2-40/p63 is stronger prognostically than by D2-40 alone, and whether it has independent prognostic value to phosphohistone H3.

Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series.

Objective: To examine the safety and efficacy of the interleukin-1 (IL-1) receptor antagonist anakinra as first-line therapy for systemic juvenile idiopathic arthritis (JIA).

Methods: Patients with systemic JIA receiving anakinra as part of initial disease-modifying antirheumatic drug (DMARD) therapy were identified from 11 centers in 4 countries. Medical records were abstracted using a standardized instrument, and resulting data were analyzed to characterize concomitant therapies, clinical course, adverse events, and predictors of outcome.

Selective expansion of merocytic dendritic cells and CD8DCs confers anti-tumour effect of Fms-like tyrosine kinase 3-ligand treatment in vivo.

Vaccination with autologous cancer cells aims to enhance adaptive immune responses to tumour-associated antigens. The incorporation of Fms-like tyrosine kinase 3-ligand (FLT3L) treatment to the vaccination scheme has been shown previously to increase the immunogenicity of cancer vaccines, thereby enhancing their therapeutic potential. While evidence has been provided that FLT3L confers its effect through the increase of absolute dendritic cell (DC) numbers, it is currently unknown which DC populations are responsive to FLT3L and which effect FLT3L treatment has on DC functions.

Measuring risk perceptions of skin cancer: reliability and validity of different operationalizations.

Objective: Risk perceptions play a pivotal role in health behaviour theories. Accurate measurement is essential in order to investigate the explanatory value and effectiveness of interventions influencing these beliefs. This study investigated the reliability and predictive validity of different risk perception operationalizations related to skin cancer and sunscreen use in order to explain the inconsistent findings in literature regarding the relationship between risk perceptions and (cancer related) behaviours.

Harnessing dendritic cells for tumor antigen presentation.

Dendritic cells (DC) are professional antigen presenting cells that are crucial for the induction of anti-tumor T cell responses. As a consequence, research has focused on the harnessing of DCs for therapeutic interventions. Although current strategies employing ex vivo-generated and tumor-antigen loaded DCs have been proven feasible, there are still many obstacles to overcome in order to improve clinical trial successes and offset the cost and complexity of customized cell therapy.

In patients younger than age 55 years with lymph node-negative breast cancer, proliferation by mitotic activity index is prognostically superior to adjuvant!

Purpose: In breast cancer, different tools are used for prognostication and adjuvant systemic therapy selection. We compared the accuracy of the online program Adjuvant!, the Norwegian Breast Cancer Group (NBCG) guidelines, and the proliferation factor mitotic activity index (MAI) in patients with lymph node (LN) -negative disease (pN0).

Patients And Methods: Adjuvant! and MAI thresholds were set to 90% to 95% breast cancer-specific survival (BCSS) rates.

High frequency microsatellite instability has a prognostic value in endometrial endometrioid adenocarcinoma, but only in FIGO stage 1 cases.

Objectives: to analyze the prognostic value of microsatellite instability (MSI) in a population-based study of FIGO stage 1-4 endometrial endometrioid adenocarcinomas.

Study Design: survival analysis in 273 patients of MSI status and clinico-pathologic features. Using a highly sensitive pentaplex polymerase chain reaction to establish MSI status, cases were divided into microsatellite stable (MSS), MSI-low (MSI-L, 1 marker positive) and MSI-high (MSI-H, 2-5 markers positive).

B7-mediated costimulation of CD4 T cells constrains cytomegalovirus persistence.

Cytomegalovirus (CMV) utilizes multiple strategies to modulate immunity and promote lifelong, persistent/latent infection, including suppressing T cell activation pathways. Here we examined the role of B7 costimulatory ligands in establishing immune détente from both the host and virus perspectives. Mice lacking both B7.

Incorporating emotions specific to the sexual response into theories of emotion using the Indiana Sexual and Affective Word Set.

The sexual response includes an emotional component, but it is not clear whether this component is specific to sex and whether it is best explained by dimensional or discrete emotion theories. To determine whether the emotional component of the sexual response is distinct from other emotions, participants (n = 1099) rated 1450 sexual and non-sexual words according to dimensional theories of emotion (using scales of valence, arousal, and dominance) and according to theories of basic emotion (using scales of happiness, anger, sadness, fear, and disgust). In addition, ratings were provided for newly developed scales of sexual valence, arousal, and energy.

Assessment of field-related influences on polychlorinated biphenyl exposures and sorbent amendment using polychaete bioassays and passive sampler measurements.

Field-related influences on polychlorinated biphenyl (PCB) exposure were evaluated by employing caged deposit-feeders, Neanthes arenaceodentata, along with polyoxymethylene (POM) samplers using parallel in situ and ex situ bioassays with homogenized untreated or activated carbon (AC) amended sediment. The AC amendment achieved a remedial efficiency in reducing bioaccumulation by 90% in the laboratory and by 44% in the field transplants. In situ measurements showed that PCB uptake by POM samplers was greater for POM placed in the surface sediment compared with the underlying AC amendment, suggesting that tidal exchange of surrounding material with similar PCB availability as untreated sediment was redeposited in the cages.

Asymmetric synthesis of synthetic alkaloids by a tandem biocatalysis/Ugi/Pictet-Spengler-type cyclization sequence.

We have combined the biocatalytic desymmetrization of 3,4-cis-substituted meso-pyrrolidines with an Ugi-type multicomponent reaction followed in situ by a Pictet-Spengler-type cyclization reaction sequence for the rapid asymmetric synthesis of alkaloid-like polycyclic compounds.

The effects of impulsivity, sexual arousability, and abstract intellectual ability on men's and women's go/no-go task performance.

While a number of studies have assessed the role of personality traits, situational variables, and drug use on sexual risk behaviors, fewer studies have employed experimental methods to examine cognitive processes that may underlie risky sexual decision making. This study used a go/no-go paradigm to examine how individual difference variables and sexual arousal influence discrimination learning and sexual and nonsexual decision making. A total of 28 men (M age = 20 years) and 25 women (M age = 19 years) completed self-report measures of impulsivity, abstract intellectual ability, and sexual excitation and inhibition and participated in a laboratory experiment.

A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions.

A very short and efficient synthesis of the important drug candidate telaprevir, featuring a biocatalytic desymmetrization and two multicomponent reactions as the key steps, is presented. The classical issue of lack of stereoselectivity in Ugi- and Passerini-type reactions is circumvented. The atom economic and convergent nature of the synthetic strategy require only very limited use of protective groups.

Biologic profiling of lymph node negative breast cancers by means of microRNA expression.

Breast cancer is a heterogeneous disease. Different subgroups can be recognized on the basis of the steroid receptors, HER-2, cytokeratin expression and proliferation patterns. As a result of mRNA-profiling studies, five major groups can be recognized, of which the triple-negative and basal-like tumors have the worst prognosis.

Prolonged antigen storage endows merocytic dendritic cells with enhanced capacity to prime anti-tumor responses in tumor-bearing mice.

Tumor cell vaccination with irradiated autologous tumor cells is a promising approach to activate tumor-specific T cell responses without the need for tumor Ag identification. However, uptake of dying cells by dendritic cells (DCs) is generally a noninflammatory or tolerizing event to prevent the development of autoreactive immune responses. In this study, we describe the mechanisms that confer the potent T cell priming capacity of a recently identified a population of DCs (merocytic DCs [mcDCs]) that potently primes both CD8(+) and CD4(+) T cells to cell-associated Ags upon uptake of apoptotic cells.

Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes.

In type 1 diabetes, the breach of central and peripheral tolerance results in autoreactive T cells that destroy insulin-producing, pancreatic beta cells. In this study, we identify a critical subpopulation of dendritic cells responsible for mediating both the cross-presentation of islet Ags to CD8(+) T cells and the direct presentation of beta cell Ags to CD4(+) T cells. These cells, termed merocytic dendritic cells (mcDCs), are more numerous in the NOD mouse and, when Ag-loaded, rescue CD8(+) T cells from peripheral anergy and deletion while stimulating islet-reactive CD4(+) T cells.