Factors that Influence Treatment Delay for Patients with Breast Cancer.

INTRODUCTION: The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. METHODS: This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery. RESULTS: Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. CONCLUSIONS: Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.

Sequence Identification of Bioactive Peptides from Amaranth Seed Proteins (Amaranthus hypochondriacus spp.).

Amaranthus hypochondriacus spp. is a commonly grown cereal in Latin America, known for its high protein content. The objective of this study was to separate and identify bioactive peptides found in amaranth seeds through enzymatically-assisted hydrolysis using alcalase and flavourzyme. Hydrolysis was carried out for each enzyme separately and compared to two-step continuous process where both enzymes were combined. The biological activity of the resulting three hydrolysates was analyzed, finding, in general, higher bioactive potential of the hydrolysate obtained in a continuous process (combined enzymes). Its fractions were separated by RP-HPLC, and their bioactivity was analyzed. In particular, two fractions showed the highest biological activity as ACE inhibitors with IC50 at 0.158 and 0.134, thrombin inhibitors with IC50 of 167 and 155, and antioxidants in ABTS assay with SC50 at 1.375 and 0.992 mg/L, respectively. Further sequence analysis of the bioactive peptides was carried out using MALDI-TOF, which identified amino acid chains that have not been reported as bioactive so far. Bibliographic survey allowed identification of similarities between peptides reported in amaranth and other proteins. In conclusion, amaranth proteins are a potential source of peptides with multifunctional activity.

Bioactivity of Peptides Released During Lactic Fermentation of Amaranth Proteins with Potential Cardiovascular Protective Effect: An In Vitro Study.

Fermentation has shown to be an effective technique in bioactive peptides release. That is why in this study antihypertensive, antithrombotic, and antioxidant activity was evaluated during amaranth proteins fermentation with Lactobacillus casei Shirota and Streptococcus thermophilus 54102 in mono and combined culture. During fermentation an increase of free amine groups was observed, and no statistical differences among monocultures were shown, getting higher concentration in combined culture. This was related to antihypertensive and antioxidant activities, where the highest values were also found in the combined process (45% of angiotensin-converting enzyme inhibition, and 168 µmol Trolox equivalents per liter [TE/L] for 2,2-diphenyl-1-picrylhydrazyl, 268 µmol TE/L for 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid, and 381 µmol Fe2E/L for ferric reducing ability of plasma). On the contrary, antithrombotic activity was not related to free amine groups during fermentation, having the highest bioactivity in different moments in each experiment. L. casei Shirota and S. thermophilus 54102 are strains that are able to release bioactive peptides from amaranth protein, although amaranth is not a common matrix for the development of lactic acid bacteria. In addition, in this study it was observed for the first time that lactic acid strains are able to release bioactive peptides from amaranth protein. In addition, this methodology could be part for the development of fermented beverages, different from fermented milk, to diversify matrix to obtain a novel functional food.

Evolutionary history of Na,K-ATPases and their osmoregulatory role.

The Na/K pump, or Na,K-ATPase, is a key enzyme to the homeostasis of osmotic pressure, cell volume, and the maintenance of electrochemical gradients. Its alpha subunit, which holds most of its functions, belongs to a large family of ATPases known as P-type, and to the subfamily IIC, which also includes H,K-ATPases. In this study, we attempt to describe the evolutionary history of IIC ATPases by doing phylogenetic analysis with most of the currently available protein sequences (over 200), and pay special attention to the relationship between their diversity and their osmoregulatory role. We include proteins derived from many completed or ongoing genome projects, many of whose IIC ATPases have not been phylogenetically analyzed previously. We show that the most likely origin of IIC proteins is prokaryotic, and that many of them are present in non-metazoans, such as algae, protozoans or fungi. We also suggest that the pre-metazoan ancestor, represented by the choanoflagellate Monosiga brevicollis, whose genome has been sequenced, presented at least two IIC-type proteins. One of these proteins would have given rise to most current animal IIC ATPases, whereas the other apparently evolved into a lineage that, so far, has only been found in nematodes. We also propose that early deuterostomes presented a single IIC gene, from which all the extant diversity of vertebrate IIC proteins originated by gene and genome duplications.

Dietary regulation of hypodermal polyploidization in C. elegans.

BACKGROUND: Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. RESULTS: Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. CONCLUSION: We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

Regulation of growth by ploidy in Caenorhabditis elegans.

Some animals, such as the larvae of Drosophila melanogaster, the larvae of the Appendicularian chordate Oikopleura, and the adults of the nematode Caenorhabditis elegans, are unusual in that they grow largely by increases in cell size. The giant cells of such species are highly polyploid, having undergone repeated rounds of endoreduplication. Since germline polyploid strains tend to have large cells, it is often assumed that endoreduplication drives cell growth, but this remains controversial. We have previously shown that adult growth in C. elegans is associated with the endoreduplication of nuclei in the epidermal syncitium, hyp 7. We show here that this relationship is causal. Manipulation of somatic ploidy both upwards and downwards increases and decreases, respectively, adult body size. We also establish a quantitative relationship between ploidy and body size. Finally, we find that TGF-beta (DBL-1) and cyclin E (CYE-1) regulate body size via endoreduplication. To our knowledge, this is the first experimental evidence establishing a cause-and-effect relationship between somatic polyploidization and body size in a metazoan.