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Length-weight relationships (LWRs) are pivotal for comparative life-history studies, conservation strategies and ecosystem modelling among regions. They provide essential information on the growth, fitness and wellbeing of a population in an ecosystem. Length and weight relationships and descriptive statistics for eight Chondrichthyes, caught off the Madeira archipelago between 2004 and 2019 from depths ranging from 350 to 2500 m, are herein reported. A total of 767 specimens was studied and it was observed that the parameter b (relative growth rate) oscillated between 2.558 for males of Centrophorus squamosus and 3.494 for females of Etmopterus princeps. This study is the first to include the LWRs for these 8 Chondrichthyes species in Madeira waters. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.dsr.2009.03.009 Byline: Florian Peine (a), Robert Turnewitsch (b), Christian Mohn (c), Theresa Reichelt (d), Barbara Springer (a), Manfred Kaufmann (e) Keywords: Thorium-234/uranium-238 disequilibria; Sediment dynamics; Bottom boundary layer; Topography; Seamounts; Internal tides; Northeast Atlantic; Eastern Mediterranean Abstract: Key aspects of deep-ocean fluid dynamics such as basin-scale (residual) and tidal flow are believed to have changed over glacial/interglacial cycles, with potential relevance for climatic change. To constrain the mechanistic links, magnitudes and temporal succession of events analyses of sedimentary paleo-records are of great importance. Efforts have been underway for some time to reconstruct residual-flow patterns from sedimentary records. Attempts to reconstruct tidal flow characteristics from deep-sea sediment deposits, however, are at a very early stage and first require a better understanding of the reflection of modern tides in sediment dynamics. In this context internal (baroclinic) tides, which are formed by the surface (barotropic) tide interacting with seafloor obstacles, are believed to play a particularly important role. Here we compare two modern deep-sea environments with respect to the effect of tides on sediment dynamics. Both environments are influenced by kilometre-scale topographic features but with vastly different tidal forcing: (1) two sites in the Northeast Atlantic (NEA) being surrounded by, or located downstream of, fields of short seamounts (maximum barotropic tidal current velocities [approximately equal to]5cms.sup.-1); and (2) a site next to the Anaximenes seamount in the Eastern Mediterranean (EMed) (maximum barotropic tidal current velocities [approximately equal to]0.5cms.sup.-1). With respect to other key fluid-dynamical parameters both environments are very similar. Signals of sedimentary particle dynamics, as influenced by processes taking place in the bottom boundary layer, were traced by the vertical water-column distribution of radioactive disequilibria (daughter/parent activity ratios[not equal to]1) between the naturally occurring, short-lived (half-life: 24.1d) particulate-matter tracer.sup.234Th relative to its very long-lived and non-particle-reactive parent nuclide.sup.238U. Activity ratios of.sup.234Th/.sup.238U1). The results of this study, therefore, add to the evidence suggesting that tides in the deep sea of the open oceans are more important for sediment dynamics than previously thought. It is hypothesised that (a) tide/seamount interactions in the deep open ocean control the local distribution of erosivity proxies (e.g., distributions of sediment grain sizes, heavy minerals and particle-reactive radionuclides) in sedimentary deposits and (b) the aforementioned topographically controlled sedimentary imprints of (internal) tides are useful in the reconstruction of past changes of tidal forcing in the deep sea. Author Affiliation: (a) Department of Marine Biology, Biosciences, University of Rostock, Albert-Einstein-Str. 3, 18051 Rostock, Germany (b) The Scottish Association for Marine Science, Dunstaffnage Marine Laboratory, Oban PA37 1QA, UK (c) Department of Earth and Ocean Sciences, Martin Ryan Institute, National University of Ireland Galway, Ireland (d) Institute of Oceanography, University of Hamburg, Bundesstr. 53, 20146 Hamburg, Germany (e) Department of Biology & Centre of Macaronesian Studies, University of Madeira, Marine Biology Station of Funchal, Cais do Carvao 9000-107 Funchal, Madeira Island, Portugal Article History: Received 21 October 2008; Revised 6 March 2009; Accepted 23 March 2009

Plastic additives, such as phthalates, are ubiquitous contaminants that can have detrimental impacts on marine organisms and overall ecosystems' health. Valuable information about the status and resilience of marine ecosystems can be obtained through the monitoring of key indicator species, such as cetaceans. In this study, fatty acid profiles and phthalates were examined in blubber biopsies of free-ranging individuals from two delphinid species (short-finned pilot whale – Globicephala macrorhynchus , n = 45; common bottlenose dolphin – Tursiops truncatus , n = 39) off Madeira Island (NE Atlantic). This investigation aimed to explore the relations between trophic niches (epipelagic vs. mesopelagic), contamination levels, and the health status of individuals within different ecological and biological groups (defined by species, residency patterns and sex). Multivariate analysis of selected dietary fatty acids revealed a clear niche segregation between the two species. Di-n-butylphthalate (DBP), diethyl phthalate (DEP), and bis(2-ethylhexyl) phthalate (DEHP) were the most prevalent among the seven studied phthalates, with the highest concentration reached by DEHP in a bottlenose dolphin (4697.34 ± 113.45 ng/g). Phthalates esters (PAEs) concentration were higher in bottlenose dolphins (Mean ∑ PAEs: 947.56 ± 1558.34 ng/g) compared to pilot whales (Mean ∑ PAEs: 229.98 ± 158.86 ng/g). In bottlenose dolphins, DEHP was the predominant phthalate, whereas in pilot whales, DEP and DBP were more prevalent. Health markers suggested pilot whales might suffer from poorer physiological conditions than bottlenose dolphins, although high metabolic differences were seen between the two species. Phthalate levels showed no differences by ecological or biological groups, seasons, or years. This study is the first to assess the extent of plastic additive contamination in free-ranging cetaceans from a remote oceanic island system, underscoring the intricate relationship between ecological niches and contaminant exposure. Monitoring these chemicals and their potential impacts is vital to assess wild population health, inform conservation strategies, and protect critical species and habitats. [Display omitted] • Dietary fatty acids (FAs) analysis confirmed distinct trophic niches between the two species. • Phthalates (PAEs) were detected in all analyzed individuals. • PAE concentrations did not differ by sex, residency patterns, or over time. • Bottlenose dolphins exhibited notably higher levels of PAEs, particularly DEHP. • FA health markers may indicate poorer health conditions in pilot whales. [ABSTRACT FROM AUTHOR]

The ingestion of microplastics (MPs - plastic particles <5 mm) by planktivorous organisms represents a significant threat to marine food webs. To investigate how seasonality might affect plastic intake in oceanic islands' ecosystems, relative abundances and composition of MPs and mesozooplankton samples collected off Madeira Island (NE Atlantic) between February 2019 and January 2020 were analysed. MPs were found in all samples, with fibres accounting for 89 % of the particles. MPs and zooplankton mean abundance was 0.262 items/m3 and 18.137 individuals/m3, respectively. Their monthly variations follow the seasonal fluctuation of environmental parameters, such as currents, chlorophyll- a concentration, sea surface temperature and precipitation intensity. A higher MPs/zooplankton ratio was recorded in the warm season (May-Oct), reaching 0.068 items/individual when considering large-sized particles (1000–5000 μm). This is the first study to assess the seasonal variability of MPs in an oceanic island system providing essential information respecting its ecological impact in pelagic environments. [Display omitted] • Abundance and composition of microplastics and zooplankton were analysed monthly. • Oceanographic processes and precipitation significantly affect these traits. • Fibres were the most abundant microplastic type found. • The microplastics/zooplankton ratio is greater in the warm season. • Seasonal variability might influence microplastics' ecological hazard. [ABSTRACT FROM AUTHOR]

Seagrasses are experiencing fragmentation and regression globally; thus, protection and recovery of meadows are a preservation priority. However, conservation actions must consider inherent regional conditions, since certain coastal areas are not suitable for the settlement of extensive meadows. Likewise, small oceanic archipelagos are not always able to fulfil the habitat requirements of seagrass habitats but can harbour small patches that in turn provide unique research opportunities. In this study, we focused on the seagrass Cymodocea nodosa in the archipelago of Madeira (NE Atlantic Ocean). Here we compile historical and contemporary records of this species along with characterization of associated communities (fish and invertebrates). A bionomic map with potentially suitable areas for the establishment and settlement of this species is also included. Lastly, we highlight coastal management and restoration actions and future research directions to preserve this species in Madeira Island. [ABSTRACT FROM AUTHOR]

Abstract: Recently it has been shown that the genome organizer SATB1 plays an important role in breast cancer progression and predicts a poor prognosis. However its prognostic value compared to markers as the estrogen receptor is currently unclear. The expression levels of SATB1 mRNA from Affymetrix microarray in a cohort of 2058 breast cancer samples and its prognostic impact were analyzed. There was no significant difference in disease-free survival among ER negative cancers but instead a benefit for high SATB1 expression among ER positive tumors (p = 0.042). However, even in ER positive cancer no independent prognostic value in multivariate analysis with standard parameters was observed. Thus the use of SATB1 as target or prognostic marker for breast cancer should be viewed with caution and a possible confounding effect of the estrogen receptor status of the tumor should be taken into account when analysing new markers as SATB1. [Copyright &y& Elsevier]

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Abstract: GABG-IV B-93 is a prospective, randomised study comparing goserelin (n =384) with no further treatment (n =392) in hormone receptor (HR)-negative breast cancer patients (n =465) after 3 cycles cyclophosphamide, methotrexate, 5-fluorouracil (CMF) for patients with 0–3 positive lymph nodes (LN) or 4 cycles epirubicin, cyclophosphamide (EC) followed by 3 cycles CMF for patients with 4–9 positive LN. After completion of the ZEBRA trial the study was amended to enrol also HR-positive patients with 1–9+LN (n =311). After a median follow-up of 4.7 years neither HR-negative nor HR-positive patients showed a benefit for goserelin. The adjusted estimated hazard ratio for event-free survival in HR-negative patients was 1.01 (goserelin versus control, 95% confidence interval [CI] 0.72–1.42, P =0.97) and 0.77 in HR-positive patients (95% CI 0.47–1.24, P =0.27). These results do not support the general use of goserelin after adjuvant chemotherapy in this group of premenopausal patients. [Copyright &y& Elsevier]

Abstract: Breast cancer remains a leading cause of cancer death in women worldwide, and the risk for disease recurrence continues despite improvements in screening and treatment and the use of prophylactic estrogen-inhibiting therapies such as tamoxifen. A number of long-term studies now indicate a significant risk for breast cancer recurrence among patients who have undergone the currently recommended five years of tamoxifen adjuvant therapy following successful treatment of their initial disease. This ongoing recurrence risk extends even to patients commonly considered at low risk for relapse, that is, those with low-grade, small tumors, and/or node-negative disease. Treatment with tamoxifen for more than five years appears detrimental rather than beneficial and, therefore, tamoxifen is not indicated for use beyond the initial five years. Endometrial cancer and thromboembolism are among the serious adverse events that have been observed with long-term tamoxifen treatment. The aromatase inhibitors are able to reduce overall estrogen levels and appear to be better tolerated over a long term. Letrozole is the most potent aromatase inhibitor and has been available in Europe since 1996 and in the United States since 1997. Letrozole has been approved for first-line treatment of postmenopausal women with hormone-receptor – positive or hormone-receptor – unknown, advanced or metastatic breast cancer in the United States and Europe, as well as for neoadjuvant treatment (primary systemic therapy) of early breast cancer prior to surgery in many countries. The results of the pivotal MA-17 trial demonstrate that letrozole is unique in its ability to improve disease-free survival in breast cancer patients who have undergone tamoxifen therapy for five years. The MA-17 results indicate that extended adjuvant therapy with letrozole reduces risk of recurrence in this setting by 42%, reduces risk of distant recurrence (metastasis), and may improve patient survival in the node-positive patient population. The results also show letrozole to be well tolerated and safe over the length of follow-up. The trial outcomes have led to the approval of letrozole for the extended adjuvant indication in more than 40 countries worldwide. Re-randomization of letrozole-treated patients from this pivotal trial is underway to investigate if ten years of extended adjuvant endocrine therapy leads to further improvement, and the results of this extension study should aid in resolving several open questions regarding extended adjuvant therapy, including who should be treated and for how long. [Copyright &y& Elsevier]

Summary: The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)–α, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT gene was performed to analyze the hot spot mutational regions in representative cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth pattern (P = .001). Furthermore, c-KIT expression was strongly associated with HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive cases (P = .001 and P = .006, respectively). C-KIT expression alone or co-expression with HER-2 in pure DCIS did not differ significantly from DCIS with invasive component (P = .09). Mutational analysis in 6 c-KIT–positive DCIS revealed no activating mutations in exons 9 or 11. Our findings suggest that the expression of c-KIT protein might define a subset of poorly differentiated, HER-2–positive DCIS with decreased expression of steroid hormone receptors, comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2 co-expression for breast carcinogenesis should be further evaluated. [Copyright &y& Elsevier]

Summary: Preoperative systemic treatment (PST) is a valid option not only for advanced breast cancer stages but also for operable breast cancer. We know that disease-free and overall survival after PST are equivalent to those after adjuvant therapy. Furthermore, PST is able to improve surgical treatment by increasing the rate of breast conservation surgery, which minimises psychological distress for patients fearing mastectomy. Response to PST is a predictor of long-term outcome and gives prognostic information after a short-term interval in contrast to adjuvant trials, which do not show their results until after a 5- to 10-year follow-up. More often, endocrine non-responsive tumours demonstrate a pathological complete response (pCR). Thus, PST can change the formerly bad prognostic marker into one that indicates a favourable prognosis if pCR is achieved by PST. If PST is performed outside clinical trials, anthracycline/taxane-based regimens should be used, especially in sequential prolonged schedules. The use of aromatase inhibitors in preoperative endocrine therapy in elderly postmenopausal patients with endocrine-responsive breast cancer yields a larger proportion of local response than tamoxifen. The duration of PST is not well established, but at least four cycles of chemotherapy should be administered and endocrine therapy needs a minimal time to show greatest benefit when given for at least 3–4 months . The concurrent use of chemotherapy and endocrine drugs did not show any benefit, even in endocrine-responsive tumours and should therefore be avoided. Sentinel node biopsy is a reasonable approach, but this technique should be reserved for experienced surgeons. PCR is the most important surrogate marker of PST, demonstrating an improved disease-free and overall survival. But even if pCR of the primary tumour is achieved, the detection of lymph node metastases is the most important prognostic factor, indicating a substantial risk of cancer recurrence. PST will lead to individualised (tailored) treatment in patients with primary breast cancer. [Copyright &y& Elsevier]

In the last decades, due to monitoring programs and strict legislation poisoning incidents occurrence provoked by ingestion of naturally contaminated marine organisms has decreased. However, climate change and anthropogenic interference contributed to the expansion and establishment of toxic alien species to more temperate ecosystems. In this work, the coasts of Madeira, São Miguel islands and the northwestern Moroccan coast were surveyed for four groups of lipophilic toxins (yessotoxins, azaspiracids, pectenotoxins, and spirolides), searching for new vectors and geographical tendencies. Twenty-four species benthic organisms were screened using UHPLC-MS/MS technique. We report 19 new vectors for these toxins, six of them with commercial interest (P. aspera , P. ordinaria , C. lampas , P. pollicipes , H. tuberculata and P. lividus). Regarding toxin uptake a south-north gradient was detected. This study contributes to the update of monitoring routines and legislation policies, comprising a wider range of vectors, to better serve consumers and ecosystems preservation. Unlabelled Image • 19 new vectors were detected for the screened toxins in edible and commercial interest species. • Monitoring practices regarding lipophilic toxins should comprise a wider range of vectors. • Geographical tendencies regarding lipophilic toxins distribution were unravelled. [ABSTRACT FROM AUTHOR]

The anthracyclines doxorubicin and epirubicin, and the taxanes paclitaxel and docetaxel, are effective chemotherapeutic agents for the first-line and second-line treatment of metastatic breast cancer, and their clinical use is widespread. However, for women whose disease has progressed despite receiving these drugs, treatment options are limited. These women often have a good performance status, and may survive for many months or even years, so they should be given the opportunity to benefit from further chemotherapy. The goals of chemotherapy in these patients are to obtain maximum control of symptoms, prevent serious complications, and increase survival without diminishing quality of life. Several agents are used for this purpose, including fluorouracil, docetaxel (in patients who have already received paclitaxel), vinorelbine, and mitomycin c, but because data from controlled trials are limited, a standard regimen has not yet been established. Moreover, these agents may be inconvenient to administer and can be associated with adverse events requiring hospitalisation. Therefore, there is a clear need for additional therapeutic options for patients with metastatic breast cancer. Ideally, agents should have a convenient method of administration, eg, oral, and should be suitable for home-based rather than hospital-based therapy. Treatment should control disease in at least 20–30% of patients with an acceptable side-effect profile. Novel oral therapies have now been developed and are being used increasingly in patients whose disease has progressed following taxane therapy. [Copyright &y& Elsevier]

• Bacterial cellulose (BC) biopolymers are promising solutions to MPs pollution. • Fully hydrated BC biopolymers remove up to 99% of MPs from contaminated waters. • BC biopolymers maintain high efficiency and resistance through filtration cycles. • BC biopolymers show ability to substitute fossil-based filters in water filtration. Microplastics (MPs) pollution has become one of our time's most consequential issue. These micropolymeric particles are ubiquitously distributed across all natural and urban ecosystems. Current filtration systems in wastewater treatment plants (WWTPs) rely on non-biodegradable fossil-based polymeric filters whose maintenance procedures are environmentally damaging and unsustainable. Following the need to develop sustainable filtration frameworks for MPs water removal, years of R&D lead to the conception of bacterial cellulose (BC) biopolymers. These bacterial-based naturally secreted polymers display unique features for biotechnological applications, such as straightforward production, large surface areas, nanoporous structures, biodegradability, and utilitarian circularity. Diligently, techniques such as flow cytometry, scanning electron microscopy and fluorescence microscopy were used to evaluate the feasibility and characterise the removal dynamics of highly concentrated MPs-polluted water by BC biopolymers. Results show that BC biopolymers display removal efficiencies of MPs of up to 99%, maintaining high performance for several continuous cycles. The polymer's characterisation showed that MPs were both adsorbed and incorporated in the 3D nanofibrillar network. The use of more economically- and logistics-favourable dried BC biopolymers preserves their physicochemical properties while maintaining high efficiency (93–96%). These polymers exhibited exceptional structural preservation, conserving a high water uptake capacity which drives microparticle retention. In sum, this study provides clear evidence that BC biopolymers are high performing, multifaceted and genuinely sustainable/circular alternatives to synthetic water treatment MPs-removal technologies. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: In recent years, the global distribution of phytoplankton functional types (PFT) and phytoplankton size classes (PSC) has been determined by remote sensing. Many of these methods rely on interpretation of phytoplankton size or type from pigment data, but independent validation has been difficult due to lack of appropriate in situ data on cell size. This work uses in situ data (photosynthetic pigments concentration and cell abundances) from the north-east Atlantic, along a trophic gradient, sampled from 2005 to 2010, as well as Atlantic Meridional Transect (AMT) data for the same region, to test a previously developed conceptual model, which calculates the fractional contributions of pico-, nano- and micro-plankton to total phytoplankton chlorophyll biomass (Brewin et al., 2010). The application of the model proved to be successful, as shown by low mean absolute error between data and model fit. However, regional values obtained for the model parameters had some effect on the relative distribution of size classes as a function of chlorophyll-a, compared with the results according to the original model. The regional parameterisation yielded a dominance of micro-plankton contribution for chlorophyll-a concentrations greater than 0.5mgm−3, rather than from 1.3mgm−3 in the original model. Intracellular chlorophyll-a (Chla) per cell, for each size class, was computed from the cell enumeration results (microscope counts and flow cytometry) and the chlorophyll-a concentration for that size class given by the model. The median intracellular chlorophyll-a values computed were 0.004, 0.224 and 26.78pg Chlacell−1 for pico-, nano-, and micro-plankton respectively. This is generally consistent with the literature, thereby providing an indirect validation of the method based on pigments to assign size classes. Using a satellite-derived composite image of chlorophyll-a for the study area, a map of cell abundance was generated based on the computed intracellular chlorophyll-a for each size-class, thus extending the remote-sensing method for mapping size classes of phytoplankton from chlorophyll-a concentration to mapping cell numbers in each class. The map reveals the ubiquitous presence of pico-plankton, and shows that all size classes are more abundant in more productive areas. [Copyright &y& Elsevier]

Summary: Background: Worldwide, many patients with HER2-positive early stage breast cancer do not receive trastuzumab—the standard adjuvant treatment. We investigated the efficacy and safety of adjuvant lapatinib for patients with trastuzumab-naive HER2-positive early-stage breast cancer, started at any time after diagnosis. Methods: This study was a placebo-controlled, multicentre, randomised phase 3 trial. Women outpatients from 33 centres with HER2-positive early-breast cancer who had previously received adjuvant chemotherapy but not trastuzumab were randomly assigned (1:1) to receive daily lapatinib (1500 mg) or daily placebo for 12 months. Randomisation was done with a computer-generated sequence, stratified by time since diagnosis, lymph node involvement at diagnosis, and tumour hormone-receptor status. Investigators, site staff, and patients were masked to treatment assignment. The primary endpoint was disease-free survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00374322. Findings: Between August, 2006, and May, 2008, 3161 women were enrolled and 3147 were assigned to lapatinib (n=1571) or placebo (n=1576). After a median follow-up of 47·4 months (range 0·4–60·0) in the lapatinib group and 48·3 (0·7–61·3) in the placebo group, 210 (13%) disease-free survival events had occurred in the lapatinib group versus 264 (17%) in the placebo group (hazard ratio [HR] 0·83, 95% CI 0·70–1·00; p=0·053). Central review of HER2 status showed that only 2490 (79%) of the randomised women were HER2-positive. 157 (13%) of 1230 confirmed HER2-positive patients in the lapatinib group and in 208 (17%) of 1260 in the placebo group had a disease-free survival event (HR 0·82, 95% 0·67–1·00; p=0·04). Serious adverse events occurred in 99 (6%) of 1573 patients taking lapatinib and 77 (5%) of 1574 patients taking placebo, with higher incidences of grade 3–4 diarrhoea (97 [6%] vs nine [<1%]), rash (72 [5%] vs three [<1%]), and hepatobiliary disorders (36 [2%] vs one [<1%]). Interpretation: Our data show that there was no significant difference in disease-free survival between groups when analysed in the intention-to-treat population. However, exploratory analyses restricted to patients who had HER2-positive disease confirmed by central fluorescence in-situ hybridisation review suggested marginal benefit with lapatinib in terms of disease-free survival. Thus lapatinib might be an option for women with HER2-positive breast cancer who do not or cannot receive adjuvant trastuzumab. Funding: GlaxoSmithKline. [Copyright &y& Elsevier]

Summary: Background: Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child. Methods: We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833. Findings: From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22–51). At the time of diagnosis, median gestational age was 24 weeks (range 5–40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1–105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76–1·69]; p=0·539). Interpretation: Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance. Funding: BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium. [Copyright &y& Elsevier]

Summary: Background: We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. Methods: In the GeparQuinto randomised phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pNSLN+). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin [90 mg/m2 intravenously] plus cyclophosphamide [600 mg/m2 intravenously], every 3 weeks), and four cycles of docetaxel (100 mg/m2 intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000–1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1–3 cN0–2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov, number NCT00567554. Findings: Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio [OR] 0·68 [95%CI 0·47–0·97]; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 [39·1%] vs 88 [28·7%]) and dyspnoea (90 [29·6%] vs 66 [21·4%]), and ECL-TL with more diarrhoea (231 [75·0%] vs 144 [47·4%]) and skin rash (169 [54·9%] vs 97 [31·9%]). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. Interpretation: This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. Funding: GlaxoSmithKline, Roche, and Sanofi-Aventis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Molecular markers displaying bimodal expression distribution can reveal distinct disease subsets and may serve as prognostic or predictive markers or represent therapeutic targets. Oestrogen (ER) and human epidermal growth factor receptor 2 (HER2) receptors are strongly bimodally expressed genes in breast cancer. Material and methods: We applied a novel method to identify bimodally expressed genes in 394 triple negative breast cancers (TNBC). We identified 133 bimodally expressed probe sets (128 unique genes), 69 of these correlated to previously reported metagenes that define molecular subtypes within TNBC including basal-like, molecular-apocrine, claudin-low and immune cell rich subgroups but 64 probe sets showed no correlation with these features. Results: The single most prominent functional group among these uncorrelated genes was the X chromosome derived Cancer/Testis Antigens (CT-X) including melanoma antigen family A (MAGE-A) and Cancer/Testis Antigens (CTAG). High expression of CT-X genes correlated with worse survival in multivariate analysis (HR 2.02, 95% CI 1.27–3.20; P =0.003). The only other significant variable was lymph node status. The poor prognosis of patients with high MAGE-A expression was ameliorated by the concomitant high expression of immune cell metagenes (HR 1.87, 95% CI 0.96–3.64; P =0.060), whereas the same immune metagene had lesser prognostic value in TNBC with low MAGE-A expression. Conclusions: MAGE-A antigen defines a very aggressive subgroup of TNBC; particularly in the absence of immune infiltration in the tumour microenvironment. These observations suggest a therapeutic hypothesis; TNBC with MAGE-A expression may benefit the most from further augmentation of the immune response. Novel immune stimulatory drugs such as (anti-cytotoxic T-lymphocyte antigen-4 CTLA-4) directed therapies provide a realistic opportunity to directly test this hypothesis in the clinic. [Copyright &y& Elsevier]

Abstract: To compare dose-intensified epirubicin monotherapy with a standard sequential regimen, patients with primary breast cancer and ⩾10 involved axillary nodes were randomised to either four 21-day cycles of epirubicin 120mg/m2 (E120; n =202) or four 21-day cycles of epirubicin 90mg/m2 plus cyclophosphamide 600mg/m2 (EC) followed by three 28-day cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF; n =209). Simultaneous hormonal treatment was applied in both arms. At 5years’ median follow-up, the 5-year event-free survival (EFS) rates were 47.7% (95% confidence interval [CI], 40.2–55.2%) for E120 and 45.9% (38.5–53.3%) for EC-CMF. E120 was as effective as EC-CMF with regard to EFS (hazard ratio [HR] for E120 versus EC-CMF 1.04; 95% CI, 0.79–1.36; p =0.79) and overall survival (HR 1.06; 95% CI 0.77–1.46; p =0.72). The data demonstrate that 4 cycles of dose-intensified epirubicin monotherapy can be as effective as 7 cycles of standard sequential polychemotherapy in high-risk breast cancer patients with ⩾10 positive lymph nodes, despite treatment with a single agent and a shorter treatment duration. [Copyright &y& Elsevier]

Abstract: Key aspects of deep-ocean fluid dynamics such as basin-scale (residual) and tidal flow are believed to have changed over glacial/interglacial cycles, with potential relevance for climatic change. To constrain the mechanistic links, magnitudes and temporal succession of events analyses of sedimentary paleo-records are of great importance. Efforts have been underway for some time to reconstruct residual-flow patterns from sedimentary records. Attempts to reconstruct tidal flow characteristics from deep-sea sediment deposits, however, are at a very early stage and first require a better understanding of the reflection of modern tides in sediment dynamics. In this context internal (baroclinic) tides, which are formed by the surface (barotropic) tide interacting with seafloor obstacles, are believed to play a particularly important role. Here we compare two modern deep-sea environments with respect to the effect of tides on sediment dynamics. Both environments are influenced by kilometre-scale topographic features but with vastly different tidal forcing: (1) two sites in the Northeast Atlantic (NEA) being surrounded by, or located downstream of, fields of short seamounts (maximum barotropic tidal current velocities ∼5cms−1); and (2) a site next to the Anaximenes seamount in the Eastern Mediterranean (EMed) (maximum barotropic tidal current velocities ∼0.5cms−1). With respect to other key fluid-dynamical parameters both environments are very similar. Signals of sedimentary particle dynamics, as influenced by processes taking place in the bottom boundary layer, were traced by the vertical water-column distribution of radioactive disequilibria (daughter/parent activity ratios≠1) between the naturally occurring, short-lived (half-life: 24.1d) particulate-matter tracer 234Th relative to its very long-lived and non-particle-reactive parent nuclide 238U. Activity ratios of 234Th/238U<1 in water samples collected near the seafloor indicate fast 234Th scavenging onto particles followed by fast settling of these particles from the sampled parcel of water and, therefore, imply active sediment resuspension and dynamics on time scales of up to several weeks. In the Northeast Atlantic study region tides (in particular internal tides) are very likely to locally push total current velocities near the seafloor across the critical current velocity threshold for sediment erosion or resuspension whereas in the Eastern Mediterranean the tides are much too weak for this to happen. This difference in tidal forcing is reflected in a difference of the frequency of the occurrence of radioactive disequilibria <1 between total 234Th and 238U: In the near-bottom water column of the Northeast Atlantic region 59% of samples had detectable 234Th/238U disequilibria whereas at the Eastern Mediterranean site this fraction was only 7% (including a few disequilibria >1). The results of this study, therefore, add to the evidence suggesting that tides in the deep sea of the open oceans are more important for sediment dynamics than previously thought. It is hypothesised that (a) tide/seamount interactions in the deep open ocean control the local distribution of erosivity proxies (e.g., distributions of sediment grain sizes, heavy minerals and particle-reactive radionuclides) in sedimentary deposits and (b) the aforementioned topographically controlled sedimentary imprints of (internal) tides are useful in the reconstruction of past changes of tidal forcing in the deep sea. [Copyright &y& Elsevier]

Abstract: Plexins, cell-surface receptors for semaphorins, are involved in cell adhesion and migration. In the previous work, we demonstrated that the loss of Plexin B1 expression is associated with poor outcome in breast cancer patients. The goal of the present study was a validation of Plexin B1 expression in a large scale microarray dataset from n =1086 breast cancer patients. Plexin B1 correlates with ER status (p <0.001) and is of prognostic significance only in ER positive (p =0.024) but not in ER negative samples (p =0.85). Among ER positive tumours, the loss of Plexin B1 expression is associated with a positive ErbB2 status (p =0.05) and a high Ki67 expression (p =0.016) in univariate analysis. Multivariate Cox regression including all standard parameters among ER positive tumours revealed that Plexin B1 (HR 1.59, 95% confidence interval (CI) 1.03–2.47, p =0.036) remains a significant prognostic marker besides tumour size (HR 2.27, 95% CI 1.33–3.89, p =0.0028) and Ki67 (HR 1.78, 95% CI 1.12–2.84, p =0.0149). Interestingly, the prognostic value of Plexin B1 was pronounced in low proliferating ER positive tumours otherwise characterised by a low risk of recurrence. In conclusion, this study confirms our previous observations suggesting Plexin B1 as a new prognostic marker in ER positive breast cancers. [Copyright &y& Elsevier]

Objective: To characterize the expression of WNT7A in human eutopic and ectopic endometrium. Design: Experimental study using real-time polymerase chain reaction, laser microdissection, in situ hybridization, and immunofluorescence. Setting: University-based laboratory. Patient(s): Patients with and without endometriosis undergoing surgery for benign indications. Intervention(s): None. Main Outcome Measure(s): Relative expression values compared with housekeeping genes using real-time polymerase chain reaction. Detection of positive cells by immunofluorescence and in situ hybridization. Result(s): In endometriosis, statistically significant higher WNT7A mRNA expression was observed compared with eutopic endometrium. Expression of WNT7A was found in the luminal and glandular epithelial cells as well as stroma cells in endometrium and endometriosis by immunofluorescence, in situ hybridization, and polymerase chain reaction of laser microdissected tissue. Conclusion(s): The results of the present study suggest that WNT7A plays a role in the pathophysiology of endometriosis. [Copyright &y& Elsevier]

Abstract: Primary systemic therapy (PST) allows the observation of tumour response under treatment, but little is known regarding the typical course of clinical response during such therapy. The aim of this study is to support decision making in case of insufficient clinical response. Tumour response was assessed by palpation at different times in 436 patients with operable breast cancer from the dose-dense biweekly therapy arm of the GEPARDUO phase III trial. The predictive value of clinical response for pathologic complete response (pCR), prognostic models to assess the prognosis and individual courses of clinical response were investigated. Sensitivity and positive predictive value were low, but comparatively highest after the 3rd cycle. The predictive value of clinical response by palpation for pCR was subsequently limited. The majority of patients (68.1%) experienced a consistent decrease in tumour size during PST. The results indicate that decisions about further treatment should take place at the earliest after the 3rd cycle or 6 weeks of dose-dense PST. [Copyright &y& Elsevier]

Objective: To compare the expression of genes playing a decisive role during the embryonic development of the female genital tract (WNT4, WNT5A, WNT7A, PAX8) in the peritoneum of patients with endometriosis and control patients. Design: Experimental study using real-time polymerase chain reaction and in situ hybridization. Setting: University-based laboratory. Patient(s): Patients with and without endometriosis undergoing surgery for benign indications. Intervention(s): None. Main Outcome Measure(s): Percentage of samples positive for gene expression by using real-time polymerase chain reaction, as well as relative expression values compared with housekeeping genes. Confirmation of results by in situ hybridization. Result(s): Expression of WNT7A and PAX8 was found in the normal peritoneum in approximately half of the patients with endometriosis in contrast to the controls. In patients with endometriosis WNT7A and PAX8 in histologically normal peritoneum (with no evidence of endometriosis, endosalpingiosis, or other changes) were confirmed by in situ hybridization. Conclusion(s): The expression of these genes in the normal peritoneum suggests that endometriosis can arise through metaplasia and can in the process make use of the developmental steps involved in the embryonic development of the female genital tract. [ABSTRACT FROM AUTHOR]

Background: For more than 20 years, tamoxifen has been the mainstay of adjuvant endocrine therapy for women with hormone-sensitive early-stage breast cancer. However, not only does tamoxifen have potential side-effects such as an increased risk of endometrial cancer and thromboembolic events, but patients can also develop resistance to the drug. We aimed to investigate whether switching treatment of postmenopausal women with such breast cancer to anastrozole after 2-3 years of tamoxifen would be more effective than continuing on tamoxifen for a total of 5 years.Methods: We did a meta-analysis of three clinical trials--the Austrian Breast and Colorectal Cancer Study Group (ABCSG 8), Arimidex-Nolvadex (ARNO 95), and the Italian Tamoxifen Anastrozole (ITA) studies--in which postmenopausal women with histologically confirmed, hormone-sensitive early-stage breast cancer were randomised to 1 mg/day anastrozole (n=2009) after 2-3 years of tamoxifen treatment or to continued 20 or 30 mg/day tamoxifen (n=1997). We analysed the data with a stratified Cox proportional hazards model with the covariates of age, tumour size, nodal status, grade, surgery, and chemotherapy.Findings: Patients who switched to anastrozole had fewer disease recurrences (92 vs 159) and deaths (66 vs 90) than did those who remained on tamoxifen, resulting in significant improvements in disease-free survival (hazard ratio 0.59 [95% CI 0.48-0.74]; p<0.0001), event-free survival (0.55 [0.42-0.71]; p<0.0001), distant recurrence-free survival (0.61 [0.45-0.83]; p=0.002), and overall survival (0.71 [0.52-0.98]; p=0.04).Interpretation: Our results show that the clinical benefits in terms of event-free survival seen in individual trials for those patients who switched to anastrozole translate into a benefit in overall survival. These findings confirm that clinicians should consider switching postmenopausal women who have taken adjuvant tamoxifen for 2-3 years to anastrozole. [ABSTRACT FROM AUTHOR]

Abstract: Gonadotrophin-releasing hormone analogues were investigated as adjuvant treatment for patients with node-negative, hormone-sensitive, premenopausal breast cancer. Patients were randomised to either three cycles of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy (n =378) or goserelin every 28d for 2years (n =393). During a median follow-up of 4.9 years, 123 events were observed. The first-failure event of CMF versus goserelin, respectively, was ipsilateral locoregional recurrence (18 versus 20), contralateral breast cancer (7 versus 6), distant failure (35 versus 24) and death without recurrence (2 versus 2). Forty-two (23 versus 19) deaths of any cause occurred. The estimated adjusted hazard ratio for goserelin versus CMF (intention-to-treat analysis) was 0.79 (95% CI=0.54–1.14; P =0.19). It is concluded that medical ovarian ablation with goserelin represents a valid option for premenopausal patients with node-negative breast cancer. [Copyright &y& Elsevier]

Abstract: As a model for hormone-dependent breast cancer, we studied the MCF-7 cell line to examine differences in the stimulation of the inducible (i) and endothelial (e) nitric oxide synthase (NOS) and the role of 17β-estradiol (E2). MCF-7 cells were stimulated with (a) E2 (10−8 M) and (b) a combination of different cytokines such as interleukin-1 beta (Il-1β), tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ), and lipopolysaccharide (LPS). e-NOS and i-NOS proteins were measured using Western blot analysis. Using the Griess method nitric oxide (NO) was estimated by assessing the stable product nitrite (NO2−) in the culture medium, and a direct method, employing EPR spin trapping also was used. Western blot analysis revealed the presence of e-NOS and i-NOS in MCF-7 cells. In Western blot analysis, e-NOS, but not i-NOS, expression could be stimulated by E2. An increase in NO2− was noted after stimulation of MCF-7 using different combinations of cytokines Il-1β, TNFα and INFγ, and LPS, but not after E2. In conclusion, e-NOS and i-NOS are weakly expressed in the MCF-7 cell line, but are stimulated differently. The MCF-7 cell may contain both a constitutive NOS and an inducible NOS. [Copyright &y& Elsevier]

The Polo-like kinase 1 (Plk1) is a key regulator of mitosis. It is reported that the human peptidyl-prolyl cis/trans-isomerase Pin1 binds to Plk1 from mitotic cell extracts in vitro. Here we demonstrate that Ser-65 in Pin1 is the major site for Plk1-specific phosphorylation, and the polo-box domain of Plk1 is required for this phosphorylation. Interestingly, the phosphorylation of Pin1 by Plk1 does not affect its isomerase activity but rather is linked to its protein stability. Pin1 is ubiquitinated in HeLa S3 cells, and substitution of Glu for Ser-65 reduces the ubiquitination of Pin1. Furthermore, inhibition of Plk1 activity by expression of a dominant negative form of Plk1 or by transfection of small interfering RNA targeted to Plk1 enhances the ubiquitination of Pin1 and subsequently reduces the amount of Pin1 in human cancer cells. Since previous reports suggested that Plk1 is a substrate of Pin1, our work adds a new dimension to this interaction of two important mitotic regulators. [ABSTRACT FROM AUTHOR]

Abstract: Nitric oxide synthases are expressed in breast cancer. To elucidate the clinical role of the inducible NOS (i-NOS) in human breast cancer, 161 primary breast cancer tissues were stained immunohistochemically. Staining patterns for i-NOS were correlated with classical prognostic factors such as lymph node status, age, hormonal receptor status, tumour size and tumour differentiation. With classical prognostic factors such as lymph node status, age, hormonal receptor status, tumour size and tumour differentiation. Patients survival was also analysed. Sixty-one percent of the tumours stained positively for i-NOS. Detection of i-NOS was positively correlated with increasing tumour size and decreasing tumour differentiation (P=0.018 and P=0.039, respectively). However, in the ⩽50 year age group, i-NOS staining also correlated with lymph node status. Patients with i-NOS-positive breast carcinomas had a significantly worse overall survival rate versus those with negative stains (5-year survival rate 84.8% versus 67.1%; P=0.049; log-rank test). To date, this is the largest analysis of i-NOS expression in breast cancer patients and the only study to assess survival. [Copyright &y& Elsevier]

In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SK-BR-3 and BT474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neu-overexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses. [ABSTRACT FROM AUTHOR]

Presents a study that investigated whether growth arrest of tumors treated with anti-epidermal growth factor-receptor (EGF-R) MAb was dependent on EGF-R expression and distinct histopathologic criteria of those neoplasms. Background on EGF; Role of growth factors and their receptors in regulating the growth of malignant cells; Implications of the results.

• PS and PMMA microplastics (MPs) exposure effects on P. tricornutum biochemistry was studied over its full growth cycle. • Biochemical response to the presence of MPs was shown to be two-staged. • Biomass production was severely decreased upon MPs exposure. • Longer exposure to high MPs pollution levels decreased pigments and carbohydrates. • MPs pollution has potential impact on the microalgal-based industry. Microplastics (MPs) are widely spread throughout aquatic systems and water bodies. Given that water quality is one of the most important parameters in the microalgal-based industry, it is critical to assess the biochemical impact of short- and long-term exposure to MPs pollution. Here, the microalga Phaeodactylum tricornutum was exposed to water contaminated with 0.5 and 50 mg L−1 of polystyrene (PS) and/or polymethyl methacrylate (PMMA). Results show that the microalgal cultures exposed to lower concentrations of PS displayed a growth enhancement of up to 73% in the first stage (days 3-9) of the exponential growth phase. Surprisingly, and despite the fact that long-term exposure to MPs contamination did not impair microalgal growth, a steep decrease in biomass production (of up to 82%) was observed. The production of photosynthetic pigments was shown to be pH-correlated during the full growth cycle, but cell density-independent in later stages of culturing. The extracellular carbohydrates production exhibited a major decrease during long-term exposure. Still, the production of extracellular proteins was not affected by the presence of MPs. This pilot laboratory-scale study shows that the microalgal exposure to water contaminated with MPs disturbs its biochemical equilibrium in a time-dependent manner, decreasing biomass production. Thus, microalgal industry-related consequences derived from the use of MPs-contaminated water are a plausible possibility. Image, graphical abstract [ABSTRACT FROM AUTHOR]

• Dibutyl phthalate (DBP) is a phthalate derived from plastic pollution that is widely found in aquatic environments. • DBP effect on Scenedesmus sp. growth is dose-dependent, with a more negative effect within the first 48 h of exposure. • Environmental concentrations of DBP decreased the microalgal growth and carbohydrates but did not change the pigment and protein concentration. • DBP environmental concentrations decrease the microalgal growth and carbohydrates but did not change the pigment and protein. Phthalate esters are highly present in aquatic plastic litter, which can interfere with the biological processes in the wildlife. In this work, the commonly found freshwater microalga Scenedesmus sp. was exposed to environmental concentrations (0.02, 1 and 100 μg L−1) and to a higher concentration (500 μg L−1) of dibutyl phthalate (DBP), which is an environmental pollutant. The growth, pH variation, production of photosynthetic pigments, proteins and carbohydrates were evaluated. The main inhibition effect of DBP on the microalgal growth was observed in the first 48 h of the exposure (EC 50 : 41.88 μg L-1). A reduction in the photosynthetic pigment concentration was observed for the 0.02, 1 and 100 μg L-1 conditions indicating that the DBP downregulated the growth rate and affected the photosynthetic process. A significant increase in protein production was only observed under 500 μg L−1 DBP exposure. The extracellular carbohydrates production slightly decreased with the presence of DBP, with a stronger decrease occurring in the 500 μg L-1 condition. These results highlight the environmental risk evaluation and ecotoxicological effects of DBP on the production of biovaluable compounds by microalgae. The results also emphasize the importance of assessing the consequences of the environmental concentrations exposure as a result of the DBP dose-dependent correlation effects. [ABSTRACT FROM AUTHOR]

Objective: To report a successful pregnancy after transfer of embryos derived from oocytes after calcium ionophore correction of the pronuclei localization after intracytoplasmic sperm injection (ICSI). Design: Case report. Setting: University hospital. Patient(s): A 30-year-old patient and her 30-year-old husband, diagnosed with asthenoteratozoopermia, underwent ICSI because of three unsuccessful IUI attempts. Intervention(s): Thirteen metaphase II oocytes were injected with morphologically normal spermatozoa and immediately divided into two groups. Group 1 (n = 7) was the untreated control and in group 2 (n = 6), the oocytes were treated with 10 μM calcium ionophore solution for 20 minutes at 37°C in 6% CO2. The fertilization was checked 18 hours later and location of pronuclei in cytoplasm was assessed. Transfer of two embryos was performed on the third day after oocyte retrieval. Main Outcome Measure(s): Pregnancy after transfer of embryos after calcium ionophore correction of pronuclei localization. Result(s): Fertilized zygotes from calcium ionophore-treated oocytes with physiologically normal central localization of pronuclei were chosen for ET. Clinical pregnancy was confirmed at 7 weeks of gestation. Conclusion(s): Post-ICSI calcium ionophore activation of oocytes can be used for correction of the pronuclei localization, which can increase developmental rate of embryos. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the influence of pregnancy on primary umbilical endometriosis. Design: Case report. Setting: Gynecologic endocrinology outpatient department of a university hospital. Patient(s): 27-year-old nulliparous woman. Intervention(s): Surgical treatment with total excision of the umbilicus during early pregnancy. Main Outcome Measure(s): Progressive enlargement of endometriotic umbilical lesions during pregnancy. Result(s): At 3-month follow-up evaluation, there were no signs of recurrence of the disease. Conclusion(s): Spontaneous umbilicus endometriosis is a rare disease that can worsen during pregnancy. [Copyright &y& Elsevier]