Cardiometabolic health, diet and the gut microbiome: a meta-omics perspective

Cardiometabolic diseases have become a leading cause of morbidity and mortality globally. They have been tightly linked to microbiome taxonomic and functional composition, with diet possibly mediating some of the associations described. Both the microbiome and diet are modifiable, which opens the way for novel therapeutic strategies. High-throughput omics techniques applied on microbiome samples (meta-omics) hold the unprecedented potential to shed light on the intricate links between diet, the microbiome, the metabolome and cardiometabolic health, with a top-down approach. However, effective integration of complementary meta-omic techniques is an open challenge and their application on large cohorts is still limited. Here we review meta-omics techniques and discuss their potential in this context, highlighting recent large-scale efforts and the novel insights they provided. Finally, we look to the next decade of meta-omics research and discuss various translational and clinical pathways to improving cardiometabolic health

A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

BACKGROUND: Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. METHODS: A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. RESULTS: Twenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1–14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%). CONCLUSION: The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

<p>Abstract</p> <p>Background</p> <p>Aromatase (<it>CYP19A1</it>) regulates estrogen biosynthesis. Polymorphisms in <it>CYP19A1 </it>have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of <it>CYP19A1 </it>and their effect on response to neoadjuvant letrozole in early BC.</p> <p>Methods</p> <p>We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4^thmonth by World Health Organization (WHO) criteria. Three polymorphisms of <it>CYP19A1</it>, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.</p> <p>Results</p> <p>Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).</p> <p>Conclusions</p> <p>Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.</p

HER-2/neu diagnostics in breast cancer

HER-2/neu status of the primary breast cancer (PBC) is determined by immunohistochemistry and fluorescent in situ hybridization. Because of a variety of technical factors, however, the PBC may not accurately reflect the metastatic tumor in terms of HER-2/neu status. Recently published guidelines recommend that tumors be defined as HER-2/neu positive if 30% or more of the cells are 3+. Circulating levels of the HER-2 extracellular domain can be measured in serum using a test cleared by the US Food and Drug Administration, and increased serum HER-2/neu levels to above 15 ng/ml can reflect tumor progression. Studies comparing tissue HER-2/neu status of the PBC and HER-2/neu levels above 15 ng/ml in metastatic breast cancer patients are also reviewed

Role of dietary fatty acids in mammary gland development and breast cancer

Breast cancer is the most common cancer among women worldwide. Estimates suggest up to 35% of cases may be preventable through diet and lifestyle modification. Growing research on the role of fats in human health suggests that early exposure in life to specific fatty acids, when tissues are particularly sensitive to their environment, can have long-term health impacts. The present review examines the role of dietary fat in mammary gland development and breast cancer throughout the lifecycle. Overall, n-3 polyunsaturated fatty acids have promising cancer-preventive effects when introduced early in life, and warrant further research to elucidate the mechanisms of action

Standardization of molecular monitoring of CML: results and recommendations from the European treatment and outcome study

Standardized monitoring of BCR::ABL1 mRNA levels is essential for the management of chronic myeloid leukemia (CML) patients. From 2016 to 2021 the European Treatment and Outcome Study for CML (EUTOS) explored the use of secondary, lyophilized cell-based BCR::ABL1 reference panels traceable to the World Health Organization primary reference material to standardize and validate local laboratory tests. Panels were used to assign and validate conversion factors (CFs) to the International Scale and assess the ability of laboratories to assess deep molecular response (DMR). The study also explored aspects of internal quality control. The percentage of EUTOS reference laboratories (n = 50) with CFs validated as optimal or satisfactory increased from 67.5% to 97.6% and 36.4% to 91.7% for ABL1 and GUSB, respectively, during the study period and 98% of laboratories were able to detect MR4.5 in most samples. Laboratories with unvalidated CFs had a higher coefficient of variation for BCR::ABL1(IS) and some laboratories had a limit of blank greater than zero which could affect the accurate reporting of DMR. Our study indicates that secondary reference panels can be used effectively to obtain and validate CFs in a manner equivalent to sample exchange and can also be used to monitor additional aspects of quality assurance.</p

Affective computing in virtual reality: emotion recognition from brain and heartbeat dynamics using wearable sensors

[EN] Affective Computing has emerged as an important field of study that aims to develop systems that can automatically recognize emotions. Up to the present, elicitation has been carried out with nonimmersive stimuli. This study, on the other hand, aims to develop an emotion recognition system for affective states evoked through Immersive Virtual Environments. Four alternative virtual rooms were designed to elicit four possible arousal-valence combinations, as described in each quadrant of the Circumplex Model of Affects. An experiment involving the recording of the electroencephalography (EEG) and electrocardiography (ECG) of sixty participants was carried out. A set of features was extracted from these signals using various state-of-the-art metrics that quantify brain and cardiovascular linear and nonlinear dynamics, which were input into a Support Vector Machine classifier to predict the subject's arousal and valence perception. The model's accuracy was 75.00% along the arousal dimension and 71.21% along the valence dimension. Our findings validate the use of Immersive Virtual Environments to elicit and automatically recognize different emotional states from neural and cardiac dynamics; this development could have novel applications in fields as diverse as Architecture, Health, Education and Videogames.This work was supported by the Ministerio de Economia y Competitividad. Spain (Project TIN2013-45736-R).Marín-Morales, J.; Higuera-Trujillo, JL.; Greco, A.; Guixeres Provinciale, J.; Llinares Millán, MDC.; Scilingo, EP.; Alcañiz Raya, ML.... (2018). Affective computing in virtual reality: emotion recognition from brain and heartbeat dynamics using wearable sensors. Scientific Reports. 8:1-15. https://doi.org/10.1038/s41598-018-32063-4S1158Picard, R. W. Affective computing. (MIT press, 1997).Picard, R. W. Affective Computing: Challenges. Int. J. Hum. Comput. 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Study of carbon nitride compounds synthesised by co-implantation of C and N in copper at different temperatures

Carbon nitride compounds have been synthesised in copper by simultaneous high fluence (10 at. cm) implantation of C and N ions. During the implantation process, the substrate temperature was maintained at 25, 250, 350 or 450 °C. Depth profiles of C and N were determined using the non-resonant nuclear reactions (NRA) induced by a 1.05 MeV deuteron beam. The retained doses were deduced from NRA measurements and compared to the implanted fluence. The chemical bonds between carbon and nitrogen were studied as a function of depth and temperature by X-ray photoelectron spectroscopy (XPS). The curve fitting of C 1s and N 1s core level photoelectron spectra reveal different types of C-N bonds and show the signature of N molecules. The presence of nitrogen gas bubbles in copper was highlighted by mass spectroscopy. The structure of carbon nitride compounds was characterised by transmission electron microscopy (TEM). For that purpose, cross-sectional samples were prepared using a focused ion beam (FIB) system. TEM observations showed the presence of small amorphous carbon nitride "nano-capsules" and large gas bubbles in copper. Based on our observations, we propose a model for the growth of these nano-objects. Finally, the mechanical properties of the implanted samples were investigated by nano-indentation. © 2010 Elsevier B.V. All rights reserved

A Bioinspired Computing Approach to Model Complex Systems

The use of models is intrinsic to any scientific activity. In particular, formal/mathematical models provide a relevant tool for scientific investigation. This paper presents a new Membrane Computing based computational paradigm as a framework for modelling processes and real-life phenomena. P systems, devices in Membrane Computing, are not used as a computing paradigm, but rather as a formalism for describing the behaviour of the system to be modelled. They offer an approach to the development of models for biological systems that meets the requirements of a good modelling framework: relevance, understandability, extensibility and computability.Ministerio de Economía y Competitividad TIN2012-3743