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The correct identification of variables affecting parasite diversity and assemblage composition at different spatial scales is crucial for understanding how pathogen distribution responds to anthropogenic disturbance and climate change. Here, we used a database of avian haemosporidian parasites to test how the taxonomic and phylogenetic diversity and phylogenetic structure of the genera Plasmodium , Haemoproteus and Leucocytozoon from three zoogeographic regions are related to surrogate variables of Earth's energy input, habitat heterogeneity (climatic diversity, landscape heterogeneity, host richness and human disturbance) and ecological interactions (resource use), which was measured by a novel assemblage-level metric related to parasite niche overlap (degree of generalism). We found that different components of energy input explained variation in richness for each genus. We found that human disturbance influences the phylogenetic structure of Haemoproteus while the degree of generalism explained richness and phylogenetic structure of Plasmodium and Leucocytozoon genera. Furthermore, landscape attributes related to human disturbance (human footprint) can filter Haemoproteus assemblages by their phylogenetic relatedness. Finally, assembly processes related to resource use within parasite assemblages modify species richness and phylogenetic structure of Plasmodium and Leucocytozoon assemblages. Overall, our study highlighted the genus-specific patterns with the different components of Earth's energy budget, human disturbances and degree of generalism.

Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection., Significance: For the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image. See related commentary by Cunningham and Turner, p. 2125. This article is featured in Selected Articles from This Issue, p. 2109., (©2023 The Authors; Published by the American Association for Cancer Research.)

High prevalence of placental-derived complications, such as preeclampsia and intrauterine growth restriction, has been reported in women with breast cancer (BC) treated with chemotherapy during pregnancy (PBC-CHT)., Aim: To ascertain whether PBC-CHT is associated with an imbalance of angiogenic factors, surrogate markers for placental insufficiency, that could explain perinatal outcomes., Methods: Prospective study between 2012 and 2016 in a single institution. Soluble fms-like tyrosine kinase (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) in maternal blood were assessed throughout pregnancy in 12 women with BC and 215 controls., Results: Cancer patients were treated with doxorubicin-based regimes and with taxanes. Ten PBC-CHT (83%) developed obstetrical complications. At the end of the third trimester, significantly higher levels of sFlt-1; sFlt-1/PGF ratio, and sEng levels were observed in BC women as compared to controls. Moreover; there was a significant correlation between plasma levels of sFlt-1 and the number of chemotherapy cycles administered. Besides, more chemotherapy cycles correlated with lower birthweight and head circumference at birth., Conclusions: Women with BC treated during pregnancy showed an antiangiogenic state compatible with placental insufficiency. Angiogenic factors could be useful in the clinical obstetric management of these patients; although further studies will be required to guide clinical decision-making.

Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR-]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I-III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P < 0.001). Median follow-up was 7.9 years. Second primary BC (P = 0.009) and non-BC malignancies (P = 0.02) were more frequent among mBRCA1 patients while distant recurrences were less frequent (P = 0.02). Irrespective of hormone receptor status, mBRCA1 patients had worse disease-free survival (DFS; adjusted HR = 0.76, 95% CI = 0.60-0.96), with no difference in distant recurrence-free interval (DRFI) and overall survival (OS). Patients with HR+ disease had more frequent distant recurrences (P < 0.001) and less frequent second primary malignancies (BC: P = 0.005; non-BC: P = 0.18). No differences in DFS and OS were observed according to hormone receptor status, with a tendency for worse DRFI (adjusted HR = 1.39, 95% CI = 0.94-2.05) in patients with HR+ BC. Type of mBRCA gene and hormone receptor status strongly impact BC clinical behavior and outcomes in mBRCA young patients. These results provide important information for patients' counseling on treatment, prevention, and surveillance strategies.

Purpose: Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations., Patients and Methods: This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors., Results: Of 1,252 patients with germline BRCA mutations ( BRCA1 , 811 patients; BRCA2 , 430 patients; BRCA1/2 , 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts., Conclusion: Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA -mutated breast cancer interested in future fertility.

The brown seaweed Scytosiphon lomentaria produces moderate amounts of fucoidans. By cetrimide fractionation, typical heavily sulfated galactofucans are obtained, with no major signs of chemical heterogeneity, together with fractions with higher proportions of xylose, mannose and uronic acids. Anyway, fucose is the most important monosaccharide in most of the subfractions of the subsequent extracts. The fucan moieties appear to be mostly as 3-linked α-l-fucopyranosyl units, with several patterns of sulfate and branching. Galactose is mostly 6-linked, whereas mannose appears to be 2-linked, and xylose appears mostly as terminal stubs. Small amounts of 2-O-acetylated fucose units appear. A high and selective antiviral activity against HSV-1 and HSV-2 was determined for the galactofucan fractions whereas the uronofucoidans were inactive., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: We assessed maternal and neonatal outcome in women diagnosed with breast cancer during pregnancy., Patients and Methods: Retrospective single-centre cohort study of 25 consecutive pregnant women (mean age 36 years) diagnosed and treated for breast cancer between 2000 and 2011. Management was individualized according to type of tumor and time of gestation at diagnosis., Results: Twelve patients were diagnosed during the second trimester. BI-RADS category <3 mammographic lesions were diagnosed in 7 patients. A suspicious area was detected by ultrasound in 20 of 21 women who underwent ultrasound studies. Nineteen patients had positive hormone receptors and 7 sobreexpressed HER2. One patient was in stage 0, 8 in stage I, 8 in stage II, 3 in stage III and 5 in stage IV. Four patients decided voluntarily to legally terminate their pregnancies, one had a spontaneous miscarriage and in three patients, pregnancy was interrupted at the end of the third trimester before oncological treatment. Eleven patients were treated with chemotherapy during pregnancy after the second trimester using anthracycline-based regimens. In five patients the pregnancy was ended before 34 weeks of gestation. Nine patients had gestation-related complications, including preterm labor, pneumonia, increase in velocity of the middle cerebral artery, oligohydramnios, preeclampsia, extreme prematurity, intrauterine growth restriction, dyspnea, spontaneous miscarriage and chemotherapy-related granulocytopenia. Betamethasone to stimulate fetal lung maturation was used in 6 patients., Conclusion: Breast cancer women diagnosed during pregnancy presented a high number of complications unrelated to antineoplastic treatment. A multidisciplinary team approach is necessary for satisfactory neonatal results., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: No consensus exists on optimum therapy for older cancer patients. This singlecentre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer., Methods: Data of all elderly breast cancer patients (≥80 years) with primary breast cancer treated at out institution between 1990 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the Kaplan-Meier method., Results: The study population consisted of 259 patients (median age 84 years). There were 189 (73%) patients with early stage disease (I, IIA, IIB) and 70 (27%) with locally advanced disease (IIIA, IIIB, IIIC). A total of 175 (67.7%) patients underwent surgical treatment and 84 (32.4%) received primary endocrine treatment. Patients were followed for a median of 65 months. In patients with early stages, the mean breast cancer-specific survival was 108 months (95% CI 101-115) in the surgical group and 50 months (95% CI 39-61) in the non-surgical group (P < 0.01), whereas patients with locally advanced breast cancer breast cancer-specific survival was similar for the surgical and non-surgical groups. Breast cancer-specific survival and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those with suboptimal surgery., Conclusion: In women ≥80 years with early-stage breast cancer, standard surgical treatment as compared with non-surgical therapy was associated with a better breast cancer-specific., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

We assessed whether pregnancy after breast cancer in patients younger than 36 years of age affects the prognosis. Of 115 women with breast cancer followed for a mean of 6 years, 18 became pregnant (median time between diagnosis and the first pregnancy 44.5 months). Voluntary interruption of pregnancy was decided by 8 (44.4%) women. Significant differences in prognostic factors between pregnant and non-pregnant women were not observed. Pregnant women showed a lower frequency of positive estrogen receptors (41%) than non-pregnant (64%) (P=0.06). At 5 years of follow-up, 100% of women in the pregnant group and 80% in the non-pregnant group were alive. The percentages of disease-free women were 94% and 64%, respectively (P=0.009). Breast cancer patients presented a high number of unwanted pregnancies. Pregnancy after breast cancer not only did not adversely affect prognosis of the neoplasm but also may have a protective effect., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We assessed whether axillary dissection using the electrothermal bipolar vessel sealing system (LigaSure) improved perioperative outcome when compared with conventional axillary dissection, in a prospective randomized study of 100 women with breast cancer. Those needing axillary dissection were randomized to the use of LigaSure or to conventional axillary dissection (with 50 patients in each group, all of whom had a closed suction drain in the axilla). The LigaSure patients had less intraoperative blood loss (exceeding 199 mL in 30.8% vs. 69.2%, P < 0.001), quicker axillary dissection (mean 48 vs. 63.2 min, P = 0.004), fewer days of suction drainage (4.3 vs. 5.7 days, P = 0.012), and shorter hospitalization (5.1 vs. 6.5 days, P = 0.021). No difference was found in the rate of hematomas, reoperations or infection. The use of LigaSure in axillary surgery reduced the surgical time and length of hospital stay, favoring early drain removal without increasing postoperative complications., (Copyright © 2011 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

We describe the case of a pregnant woman diagnosed with breast cancer at 26 weeks' gestation. The tumor was positive for estrogen and progesterone receptors and negative for overexpression of c-erbB-2 protein. Neoadjuvant FAC (fluorouracil, adriamycin, cytoxan) chemotherapy was started at 29 weeks' gestation. At 37 weeks, delivery was induced and the patient gave born to a healthy female baby weighing 2350 g, after which she was given a further cycle of chemotherapy and weekly paclitaxel. Clinical and radiological remission was achieved. Resection of the breast tissue showed complete pathological response and negative lymph nodes. This case illustrates how the integrated work of different specialists can obtain excellent oncological and obstetrical results in the care of pregnant women with breast cancer.

Objective: The aim of this study is to evaluate if it is necessary to remove all the radioactive sentinel lymph nodes (SLNs) not seen on lymphoscintigraphy in order to accurately stage breast cancer patients., Material and Methods: From March 1999 to March 2006, SLN biopsy was performed in 461 patients. All patients were only injected with radioisotope. Lymphoscintigraphy was performed in all the patients. The mean number of SLNs removed was 2.1 (range 1-15)., Results: The SLN was positive in 133 patients (28.8%). Lymphoscintigraphy accurately predicted the number of SLNs identified intraoperatively in 243 patients (52.7%). In 175 patients (37.9%) there were more SLNs identified intraoperatively than were seen on lymphos cintigraphy. In 11 (6.2%) of these 175 patients, additional SLNs identified intraoperatively harboured metastasis. Type of injection, need for a second injection, tumour location and age were not identified as statistically significantly associated with additional positive SLNs identified intraoperatively and not seen on lymphoscintigraphy., Conclusions: Lymphoscintigraphy does not accurately predict the number of SLNs identified intraoperatively, this number being underestimated. Surgeons should remove all radioactive SLNs to improve the detection of positive SLNs.

Three fatty acid-binding proteins (FABPs) from the liver of the shark Halaetunus bivius were isolated and characterized: one of them belongs to the liver-type FABP family and the other two to the heart-type FABP family. The complete primary structure of the first FABP, and partial primary structures of the two others, were determined. The liver-type FABP constitutes 69% of the total FABPs, and its amino acid sequence presents the highest identity with chicken, catfish, iguana and elephant fish liver basic FABPs. The L-FABP protein has low affinity for palmitic and oleic acids and high affinity for linoleic and arachidonic acids and other hydrophobic ligands, all of them important for the metabolic functions of the liver. In contrast, both heart-type FABPs have the highest affinity for palmitic acid, the principal fatty acid mobilized from fat deposits for beta-oxidation.

Five fatty-acid-binding proteins from the liver of the elephant fish (Callorhynchus callorhynchus), a chimaera fish that belongs--together with the elasmobranchs--to the ancient chondrichthyes class were isolated and characterized. The purification procedures for these proteins involved gel filtration, anion-exchange chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a last step. They were submitted to "in gel" tryptic or cyanogen bromide digestion and the resulting peptides were separated by high performance liquid chromatography and then sequenced by Edman degradation. According to their partial amino acid sequences, one of them presents the highest identity with fatty-acid-binding proteins from human and catfish liver, another three with those from mammalian heart or adipose tissue and the fifth with the mammalian intestinal fatty-acid-binding protein. The presence of various members of this protein family, as now found in elephant fish and previously in catfish (Rhamdia sapo) liver, does not occur in mammalian liver which express only one a characteristic fatty-acid-binding protein.

A fatty acid-binding protein from the cytosolic fraction of the armadillo Chaetophractus villosus Harderian gland was purified to homogeneity by a procedure based on gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein has an apparent molecular mass of 14 kDa. N-terminal sequence analysis showed that the protein has a blocked N-terminus. For internal amino acid sequencing, the protein was digested in-gel and the resulting peptides were fractionated by reverse-phase high performance liquid chromatography and subjected to automated Edman degradation. Partial amino acid sequencing suggests that it belongs to the heart type. Moreover, it cross-reacted with anti-serum to rat heart fatty acid-binding protein but not with rat intestinal and liver anti-sera. A very slow cross-reaction was also found with anti-serum to rat ALBP. This is the first time that a fatty acid-binding protein has been reported in a Harderian gland.

The fatty acid-binding protein (FABP) from armadillo liver was purified to homogeneity by a procedure involving gel filtration and two anion exchange chromatography steps. The purified protein proved to have a pI between 5.0 and 5.2 and migrated by sodium dodecyl sulfate-polyacrilamyde gel electrophoresis as a single entity of approximately 14 kDa. The armadillo FABP cross-reacted with antiserum against rat liver FABP but not against rat intestinal FABP. The same as other members of the family, it has a blocked N-terminus. Amino acid sequencing of peptides obtained by cyanogen bromide cleavage and in-gel tryptic digestion shows that the armadillo, despite being one of the less evolved mammals, has a liver FABP of the same type as that of highly evolved mammals.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) is a powerful purification technique in protein chemistry research. This procedure is frequently used as a last step in protein purification for sequencing. For proteins which are N-terminal blocked, 'in gel' digestion offers a useful approach for the generation of internal sequence data from proteins purified by SDS-PAGE. In this study, we propose a procedure where proteins purified by this method are chemically cleaved 'in gel' by using CNBr and the resulting peptides are isolated in a second SDS-PAGE. After that, electroblotting is performed onto PVDF membranes and the electroblotted and Coomassie-stained peptide, from each band is then sequenced by Edman degradation. Proteins often have a small number of methionines whose cleavage allows the obtention of long peptides suitable to sequence a good deal of residues. Three standard proteins of different molecular mass have been assayed by this procedure and the 'in situ' cleavage profile compared with direct chemical digestion in a protein solution.

The intracellular lipid-binding proteins are a group of homologous proteins which bind and facilitate the transport of fatty acids, bile acids and retinoids. The evolutionary relationship of 51 family members from vertebrates and invertebrates was analyzed. The inferred phylogeny implies the occurrence of at least 14 gene duplications and contains five regions where the branching order is statistically non-significant--this uncertainty explaining most inconsistencies between previous phylogenetic analyses. The phylogeny also suggests that the intestinal fatty acid-binding protein and the liver fatty acid-binding protein/ileal lipid-binding protein subfamilies diverged from the other subfamilies before the vertebrate-invertebrate split. Finally, results presented herein indicate that the putative fatty acid-binding domain of NMDA receptor 1 is unlikely to be a member of this family.

A case of accessory liver, located in the gallbladder is presented; the lesion was discovered incidentally. The patient was a 35 year-old female who was operated on for cholecystitis and cholelithiasis; the accessory liver tissue showed signs of cholangitis and congestion, secondary to the gallbladder pathology. We point out that this rare abnormality has no pathological significance and does not require surgical treatment except, as in this case, for the coincidental cholelithiasis or if it is the site of hepatoma or cholangiocarcinoma.