The effect of pond dyes on oviposition and survival in wild UK Culex mosquitoes

British Culex pipiens complex [Culex pipiens sensu lato) mosquito distribution, abundance, and potential for disease transmission are intimately linked to their environment. Pond and lake dyes that block light to restrict algal photosynthesis are a relatively new product assumed to be an environmentally friendly since they are based on food dyes. Their use in urban garden ponds raises questions linked to mosquito oviposition, since coloured water can be an attractant. Culex (mostly pipiens) is commonly found in UK gardens and is a potential vector of viruses including the West Nile Virus (WNV). Any factors that significantly change the distribution and population of Cx pipiens could impact future risks of disease transmission. A gravid trap was used to catch female Cx pipiens mosquitoes for use in oviposition choice tests in laboratory and semi-field conditions. Two types of pond dye, blue and shadow (which looks slightly red), were tested for their impact on oviposition and survival of wild caught Cx pipiens. There were no significant differences in the number of egg batches laid when gravid mosquitoes were given a choice between either blue dye and clear water or shadow dye and clear water indicating that these dyes are not attractants. Larvae hatched from egg batches laid by wild-caught gravid females were used to measure survival to adulthood with or without dye, , in a habitat controlled to prevent further colonisation. The experiment was run twice, once in the summer and again in the autumn, whereas the dyes had no impact on emergence in the summer, there were highly significant reductions in emergence of adults in both dye treated habitats in the autumn. Containers with or without shadow dye were placed outside to colonise naturally and were sampled weekly for larvae and pupae over a 6 month period through summer and autumn. There was a significant negative effect of shadow dye on pupal abundance in a three week period over the summer, but otherwise there was no effect. It is likely that population abundance and food was a more powerful factor for mosquito survival than the dye

Neoadjuvant endocrine therapy in primary breast cancer: indications and use as a research tool

Neoadjuvant endocrine therapy has been increasingly employed in clinical practice to improve surgical options for postmenopausal women with bulky hormone receptor-positive breast cancer. Recent studies indicate that tumour response in this setting may predict long-term outcome of patients on adjuvant endocrine therapy, which argues for its broader application in treating hormone receptor-positive disease. From the research perspective, neoadjuvant endocrine therapy provides a unique opportunity for studies of endocrine responsiveness and the development of novel therapeutic agents

Treatment options for patients with triple-negative breast cancer

Breast cancer is a heterogeneous disease composed of different subtypes, characterized by their different clinicopathological characteristics, prognoses and responses to treatment. In the past decade, significant advances have been made in the treatment of breast cancer sensitive to hormonal treatments, as well as in patients whose malignant cells overexpress or amplify HER2. In contrast, mainly due to the lack of molecular targets, little progress has been made in the treatment of patients with triple-negative breast cancer. Recent improved understanding of the natural history, pathophysiology, and molecular features of triple-negative breast cancers have provided new insights into management and therapeutic strategies for women affected with this entity. Ongoing and planned translational clinical trials are likely to optimize and improve treatment of women with this disease

Outcomes and incidence of PF-ILD according to different definitions in a real-world setting

Background: Almost one-third of fibrosing ILD (fILDs) have a clinical disease behavior similar to IPF, demonstrating a progressive phenotype (PF-ILD). However, there are no globally accepted criteria on the definition of a progressive phenotype in non-IPF fILD yet. Four different definitions have been used; however, no internationally accepted definition currently exists. Research Question: To compare the clinical and functional characteristics of progressive fILD according to the currently available definitions. Study design and methods: Cases of fILD were identified retrospectively from the database of the tertiary referral center for ILD in Heidelberg. Lung function, clinical signs of progression, and radiological changes were evaluated. Patients with fILD were considered to have progression according to each of the four available definitions: Cottin (CO), RELIEF (RE), INBUILD (IN), and UILD study. Lung function changes, expressed as mean absolute decline of FVC%, were reported every 3 months following diagnosis and analyzed in the context of each definition. Survival was also analyzed. Results: A total of 566 patients with non-IPF fILD were included in the analysis. Applying CO-, RE-, IN-, and UILD-definitions, 232 (41%), 183 (32%), 274 (48%), and 174 (31%) patients were defined as PF-ILD, respectively. RE- and UILD-criteria were the most stringent, with only 32 and 31% patients defined as progressive, while IN- was the most broad, with almost 50% of patients defined as progressive. CO- definition was in-between, classifying 41% as progressive. PF ILD patients with a UILD definition had worse prognosis. Interpretation: Depending on the definition used, the existing criteria identify different groups of patients with progressive fILD, and this may have important prognostic and therapeutic implications

An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers

BACKGROUND: Stromal tumor-infiltrating lymphocytes (TILs) are a robust prognostic factor in triple-negative breast cancer (TNBC). However, the clinical significance of TILs may be influenced by the complex landscape of the tumor immune microenvironment. In this study, we aimed to evaluate the composition and the functionality of lymphocytic infiltration and checkpoint receptors in TNBC. METHODS: Formalin-fixed, paraffin-embedded tissues were retrospectively collected from a cohort of patients with early-stage TNBC treated with adjuvant anthracycline-based chemotherapy (n = 259). Results were validated in an independent cohort of patients with TNBC (n = 104). Stromal TILs were evaluated on hematoxylin-and-eosin-stained sections. The density of CD4+, CD8+, and FOXP3+ lymphocytes, and the expression of the immune checkpoints PD-1 and LAG-3, were assessed by immunohistochemical analysis. RESULTS: The presence of elevated TILs positively correlated with the density of all T cell subtypes, especially cytotoxic CD8+ lymphocytes. We showed that increasing stromal TILs assessed as a continuous variable is an independent prognostic marker of prolonged relapse-free survival and overall survival in TNBC. Among immune subpopulations, CD8+ lymphocytes are the main effectors of anti-tumor immune responses. In two independent cohorts, we found that PD-1 and LAG-3 were concurrently expressed in approximately 15% of patients with TNBC. The expression of both checkpoint receptors positively correlated with the presence of TILs, but was not significantly associated with patient outcome. CONCLUSIONS: Overall, our data indicate that the evaluation of stromal TILs remains the most reliable immune prognostic marker in TNBC, and support the clinical evaluation of anti-PD-1/PD-L1 and anti-LAG-3 in a subset of patients with TNBC who have concurrent expression of both checkpoint receptors