Preliminary Metabolomics Study Suggests Favorable Metabolic Changes in the Plasma of Breast Cancer Patients after Surgery and Adjuvant Treatment.

Background/Objectives: The management of early breast cancer (BC) includes surgery, followed by adjuvant radiotherapy, chemotherapy, hormone therapy, or immunotherapy. However, the influence of these interventions in metabolic reprogramming remains unknown. This study explored alterations in the plasma metabolome of BC patients following distinct treatments to deepen our understanding of BC pathophysiology, outcomes, and the identification of potential biomarkers. Methods: We included 52 women diagnosed with BC and candidates for surgery as primary oncological treatment. Blood samples were collected at diagnosis, two weeks post-surgery, and one month post-radiotherapy. Plasma samples from 49 healthy women served as controls. Targeted metabolomics assessed 74 metabolites spanning carbohydrates, amino acids, lipids, nucleotide pathways, energy metabolism, and xenobiotic biodegradation. Results: Before treatment, the BC patients exhibited notable changes in carbohydrate, nucleotide, lipid, and amino acid metabolism. We noticed a gradual restoration of specific metabolite levels (hypoxanthine, 3-phosphoglyceric acid, xylonic acid, and maltose) throughout different treatments, suggesting a normalization of the nucleotide and carbohydrate metabolic pathways. Moreover, we observed increased dodecanoic acid concentrations, a metabolite associated with cancer protection. These variations distinguished patients from controls with high specificity and sensitivity. Conclusions: Our preliminary study suggests that oncological treatments modify the metabolism of patients towards a favorable profile with a decrease in the pathways that favor cell proliferation and an increase in the levels of anticancer molecules. These findings emphasize the pivotal role of metabolomics in recognizing the biological pathways influenced by each cancer treatment and the resulting metabolic consequences. Furthermore, it aids in identifying potential biomarkers for disease onset and progression.

Combining Metabolomics and Machine Learning to Identify Diagnostic and Prognostic Biomarkers in Patients with Non-Small Cell Lung Cancer Pre- and Post-Radiation Therapy.

Lung cancer is the leading cause of cancer-related deaths globally, with non-small cell lung cancer (NSCLC) accounting for over 85% of cases and poor prognosis in advanced stages. This study explored shifts in circulating metabolite levels in NSCLC patients versus healthy controls and examined the effects of conventionally fractionated radiation therapy (CFRT) and stereotactic body radiation therapy (SBRT). We enrolled 91 NSCLC patients (38 CFRT and 53 SBRT) and 40 healthy controls. Plasma metabolite levels were assessed using semi-targeted metabolomics, revealing 32 elevated and 18 reduced metabolites in patients. Key discriminatory metabolites included ethylmalonic acid, maltose, 3-phosphoglyceric acid, taurine, glutamic acid, glycocolic acid, and d-arabinose, with a combined Receiver Operating Characteristics curve indicating perfect discrimination between patients and controls. CFRT and SBRT affected different metabolites, but both changes suggested a partial normalization of energy and amino acid metabolism pathways. In conclusion, metabolomics identified distinct metabolic signatures in NSCLC patients with potential as diagnostic biomarkers. The differing metabolic responses to CFRT and SBRT reflect their unique therapeutic impacts, underscoring the utility of this technique in enhancing NSCLC diagnosis and treatment monitoring.

Evaluation of vascular changes in cavernous arteries by penile doppler ultrasound in patients undergoing laparoscopic radical prostatectomy.

Patients undergoing radical prostatectomy for prostate cancer may experience erectile dysfunction (ED). Age of patients, experience of the surgeons and existence of ED before surgery are factors related to its appearance. The objective of the study was to assess the hemodynamic changes produced in the cavernous arteries in patients undergoing laparoscopic radical prostatectomy (LRP) measured with penile Doppler ultrasound (PDUS). A prospective database of 83 patients undergoing LRP was analysed. PDUS were performed at baseline and twelve months after surgery. International Index of Erectile Function (IIEF) and Erectile Hardness Score (EHS) questionnaires were also evaluated. A 12-month decrease in all hemodynamic parameters of both cavernous arteries was found except for the end diastolic velocity (EDV) on the left cavernous artery. Only changes between baseline and twelve-months mean values of the diameter (0.725 vs. 0.67 mm; p= 0.033) and peak systolic velocity (PSV) of the right cavernous artery (32.6 vs. 27.22 cm/s; p = 0.004) presented significant variations. The rest of the parameters were close to statistical significance, except for EDV of the right cavernous artery (p = 0.887). The erectile function domain of the IIEF showed a significant decrease (median at baseline: 26 vs. post-surgery: 7; p < 0.0001) as well as the EHS test (grade I at baseline: 2.4% vs. 12-months: 31.3%; p < 0.0001). Our study supports the idea that LRP produces local vascular injuries. A decrease in the PSV and in the diameter of both cavernous arteries was observed with PDUS and it may explain the vascular origin of ED.

Serum Levels of Arachidonic Acid, Interleukin-6, and C-Reactive Protein as Potential Indicators of Pulmonary Viral Infections: Comparative Analysis of Influenza A, Respiratory Syncytial Virus Infection, and COVID-19.

Acute respiratory tract infections, including influenza A (FluA), respiratory syncytial virus (RSV) infection, and COVID-19, can aggravate to levels requiring hospitalization, increasing morbidity and mortality. Identifying biomarkers for an accurate diagnosis and prognosis of these infections is a clinical need. We performed a cross-sectional study aimed to investigate the changes in circulating levels of arachidonic acid, interleukin 6 (IL-6), and C-reactive protein (CRP) in patients with FluA, RSV, or COVID-19, and to analyze the potential of these parameters as diagnosis or prognosis biomarkers. We analyzed serum samples from 172 FluA, 80 RSV, and 217 COVID-19 patients, and 104 healthy volunteers. Individuals with lung viral diseases showed reduced arachidonic acid concentrations compared to healthy people, with these differences being most pronounced in the order COVID-19 > RSV > FluA. Conversely, IL-6 and CRP levels were elevated across diseases, with IL-6 emerging as the most promising diagnostic biomarker, with areas under the curve (AUC) of the receiver operating characteristics plot higher than 0.85 and surpassing arachidonic acid and CRP. Moreover, IL-6 displayed notable efficacy in distinguishing between FluA patients who survived and those who did not (AUC = 0.80). These findings may provide useful tools for diagnosing and monitoring the severity of acute viral respiratory tract infections, ultimately improving patient outcomes.

Metabolomics and triple-negative breast cancer: A systematic review.

Triple-negative breast cancer stands out as the most aggressive subtype of breast malignancy and is characterized by an unfavourable prognosis. Objective: This systematic review summarizes the insights gleaned from metabolomic analyses of individuals afflicted with this cancer variant. The overarching goal was to delineate the molecular alterations associated with triple-negative breast cancer, pinpointing potential therapeutic targets and novel biomarkers. Methods: We systematically searched for evidence using the PubMed database and followed the PRISMA and STARLITE guidelines. The search parameters were delimited to articles published within the last 13 years. Results: From an initial pool of 148 scrutinized articles, 17 studies involving 1686 participants were deemed eligible for inclusion. The current body of research shows a paucity of studies, and the available evidence presents conflicting outcomes. Notwithstanding, Pathway Enrichment Analysis identified the urea and glucose-alanine cycles as the most affected metabolic pathways, followed by arginine, proline, and aspartate metabolism. Conclusion: Future investigations need to focus on elucidating which of those metabolites and/or pathways might be reliable candidates for novel therapeutic interventions or reliable biomarkers for diagnosis and prognosis of this subtype of breast cancer.

Metabolic adaptations in severe obesity: Insights from circulating oxylipins before and after weight loss.

BACKGROUND: The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss. METHODS: In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays. RESULTS: We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity. CONCLUSIONS: Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.

Galectin-9 interacts with Vamp-3 to regulate cytokine secretion in dendritic cells.

Intracellular vesicle transport is essential for cellular homeostasis and is partially mediated by SNARE proteins. Endosomal trafficking to the plasma membrane ensures cytokine secretion in dendritic cells (DCs) and the initiation of immune responses. Despite its critical importance, the specific molecular components that regulate DC cytokine secretion are poorly characterised. Galectin-9, a ß-galactoside-binding protein, has emerged as a novel cellular modulator although its exact intracellular roles in regulating (immune) cell homeostasis and vesicle transport are virtually unknown. We investigated galectin-9 function in primary human DCs and report that galectin-9 is essential for intracellular cytokine trafficking to the cell surface. Galectin-9-depleted DCs accumulate cytokine-containing vesicles in the Golgi complex that eventually undergo lysosomal degradation. We observed galectin-9 to molecularly interact with Vamp-3 using immunoprecipitation-mass-spectrometry and identified galectin-9 was required for rerouting Vamp-3-containing endosomes upon DC activation as the underlying mechanism. Overall, this study identifies galectin-9 as a necessary mechanistic component for intracellular trafficking. This may impact our general understanding of vesicle transport and sheds new light into the multiple roles galectins play in governing cell function.

Factors related to the development of health-promoting community activities in Spanish primary healthcare: two case-control studies.

OBJECTIVE: Spanish primary healthcare teams have the responsibility of performing health-promoting community activities (CAs), although such activities are not widespread. Our aim was to identify the factors related to participation in those activities. DESIGN: Two case-control studies. SETTING: Performed in primary care of five Spanish regions. SUBJECTS: In the first study, cases were teams that performed health-promoting CAs and controls were those that did not. In the second study (on case teams from the first study), cases were professionals who developed these activities and controls were those who did not. MAIN OUTCOME MEASURES: Team, professional and community characteristics collected through questionnaires (team managers/professionals) and from secondary sources. RESULTS: The first study examined 203 teams (103 cases, 100 controls). Adjusted factors associated with performing CAs were percentage of nurses (OR 1.07, 95% CI 1.01 to 1.14), community socioeconomic status (higher vs lower OR 2.16, 95% CI 1.18 to 3.95) and performing undergraduate training (OR 0.44, 95% CI 0.21 to 0.93). In the second study, 597 professionals responded (254 cases, 343 controls). Adjusted factors were professional classification (physicians do fewer activities than nurses and social workers do more), training in CAs (OR 1.9, 95% CI 1.2 to 3.1), team support (OR 2.9, 95% CI 1.5 to 5.7), seniority (OR 1.06, 95% CI 1.03 to 1.09), nursing tutor (OR 2.0, 95% CI 1.1 to 3.5), motivation (OR 3.7, 95% CI 1.8 to 7.5), collaboration with non-governmental organisations (OR 1.9, 95% CI 1.2 to 3.1) and participation in neighbourhood activities (OR 3.1, 95% CI 1.9 to 5.1). CONCLUSIONS: Professional personal characteristics, such as social sensitivity, profession, to feel team support or motivation, have influence in performing health-promoting CAs. In contrast to the opinion expressed by many professionals, workload is not related to performance of health-promoting CAs.

The effect of ventilation protocols on airborne particulate matter in subway systems.

As part of the European-funded IMPROVE LIFE project work programme experiments were performed in the Barcelona Metro system with the objective of better understanding the relationship between ventilation and air quality. The results demonstrate that tunnel ventilation plays an extremely important role in maintaining cleaner air and is capable of reducing both inhalable particulate matter (PM) mass and particle number concentration (>0.3µm) on platforms by over 50%, even in the presence of full-length platform screen doors. Another key influence on platform air quality is the chosen combination of fan power and forced air flow direction (impulsion of outdoor ambient air or extraction of subway indoor air): cleaner platform air was achieved using platform impulsion at higher power settings designed to ameliorate high summer temperatures underground. Reversing platform air flow from impulsion to extraction produced an immediate deterioration in PM air quality, most notably if the higher power setting was maintained, when an especially marked increase in numbers of very fine (submicron) particles was observed and attributed to tunnel air being drawn into the platform. At night, in the absence of trains and platform ventilation, platform air quality improves when tunnel fans are working at reduced power, whatever the flow direction (impulsion/extraction). Inside the air conditioned Barcelona Metro trains (where underground commuters spend most of their time) air quality is markedly better than on the platform, and unchanged A/C filters were observed capable of maintaining a similar reduction in inside train PM for at least three months.

Factors controlling air quality in different European subway systems.

Sampling campaigns using the same equipment and methodology were conducted to assess and compare the air quality at three South European subway systems (Barcelona, Athens and Oporto), focusing on concentrations and chemical composition of PM2.5 on subway platforms, as well as PM2.5 concentrations inside trains. Experimental results showed that the mean PM2.5 concentrations widely varied among the European subway systems, and even among different platforms within the same underground system, which might be associated to distinct station and tunnel designs and ventilation systems. In all cases PM2.5 concentrations on the platforms were higher than those in the urban ambient air, evidencing that there is generation of PM2.5 associated with the subway systems operation. Subway PM2.5 consisted of elemental iron, total carbon, crustal matter, secondary inorganic compounds, insoluble sulphate, halite and trace elements. Of all metals, Fe was the most abundant, accounting for 29-43% of the total PM2.5 mass (41-61% if Fe2O3 is considered), indicating the existence of an Fe source in the subway system, which could have its origin in mechanical friction and wear processes between rails, wheels and brakes. The trace elements with the highest enrichment in the subway PM2.5 were Ba, Cu, Mn, Zn, Cr, Sb, Sr, Ni, Sn, Co, Zr and Mo. Similar PM2.5 diurnal trends were observed on platforms from different subway systems, with higher concentrations during subway operating hours than during the transport service interruption, and lower levels on weekends than on weekdays. PM2.5 concentrations depended largely on the operation and frequency of the trains and the ventilation system, and were lower inside the trains, when air conditioning system was operating properly, than on the platforms. However, the PM2.5 concentrations increased considerably when the train windows were open. The PM2.5 levels inside the trains decreased with the trains passage in aboveground sections.

Origin of inorganic and organic components of PM2.5 in subway stations of Barcelona, Spain.

The present work assesses indoor air quality in stations of the Barcelona subway system. PM2.5 concentrations on the platforms of 4 subway stations were measured during two different seasons and the chemical composition was determined. A Positive Matrix Factorization analysis was performed to identify and quantify the contributions of major PM2.5 sources in the subway stations. Mean PM2.5 concentrations varied according to the stations design and seasonal periods. PM2.5 was composed of haematite, carbonaceous aerosol, crustal matter, secondary inorganic compounds, trace elements, insoluble sulphate and halite. Organic compounds such as PAHs, nicotine, levoglucosan and aromatic musk compounds were also identified. Subway PM2.5 source comprised emissions from rails, wheels, catenaries, brake pads and pantographs. The subway source showed different chemical profiles for each station, but was always dominated by Fe. Control actions on the source are important for the achievement of better air quality in the subway environment.

Spanish (Spain) validation of a specific symptomatic questionnaire for male patients with nocturia.

OBJECTIVES: To validate in Spanish (Spain) a self-administered questionnaire on the quality of life (QoL) specific to nocturia in an older adult male population. MATERIAL AND METHODS: We analysed the Spanish version of the ICIQ-Nqol questionnaire (provided by ICIQ who owns the copyright), which meets the translation criteria required by the validation protocol. The study included 69 male patients older than 60 years of age with 1 or more nocturia episodes. The participants completed the questionnaire on two occasions, along with other Spanish-validated questionnaires that measure the QoL related to urinary symptoms. We analysed the internal reliability and consistency, reproducibility, convergent validity and discriminant validity. RESULTS: The study included 69 men, with a mean age of 70.64 years (range, 60-87 years). Both the overall scale and the energy/sleep subscale met the minimum criteria for internal reliability and consistency. A good correlation has been demonstrated between the overall index of the ICIQ-Nqol questionnaire and the other questionnaires included in the study. The reproducibility (test-retest reliability) of both the overall scale and subscales of the ICIQ-Nqol and the other questionnaires was demonstrated. Conclusions The ICIQ-Nqol questionnaire has been shown to be an appropriate instrument for assessing the symptomatic intensity and impact on the QoL of patients with nocturia. This study confirms its validity for a Spanish-speaking male population. Neurourol. Urodynam. 35:847-850, 2016. © 2015 Wiley Periodicals, Inc.

Urban air quality comparison for bus, tram, subway and pedestrian commutes in Barcelona.

Access to detailed comparisons in air quality variations encountered when commuting through a city offers the urban traveller more informed choice on how to minimise personal exposure to inhalable pollutants. In this study we report on an experiment designed to compare atmospheric contaminants inhaled during bus, subway train, tram and walking journeys through the city of Barcelona. Average number concentrations of particles 10-300 nm in size, N, are lowest in the commute using subway trains (N<2.5×10(4) part. cm(-3)), higher during tram travel and suburban walking (2.5×10(4) cm(-3)5.0×10(4) cm(-3)), with extreme transient peaks at busy traffic crossings commonly exceeding 1.0×10(5) cm(-3) and accompanied by peaks in Black Carbon and CO. Subway particles are coarser (mode 90 nm) than in buses, trams or outdoors (<70 nm), and concentrations of fine particulate matter (PM2.5) and Black Carbon are lower in the tram when compared to both bus and subway. CO2 levels in public transport reflect passenger numbers, more than tripling from outdoor levels to >1200 ppm in crowded buses and trains. There are also striking differences in inhalable particle chemistry depending on the route chosen, ranging from aluminosiliceous at roadsides and near pavement works, ferruginous with enhanced Mn, Co, Zn, Sr and Ba in the subway environment, and higher levels of Sb and Cu inside the bus. We graphically display such chemical variations using a ternary diagram to emphasise how "air quality" in the city involves a consideration of both physical and chemical parameters, and is not simply a question of measuring particle number or mass.

Exposure to airborne particulate matter in the subway system.

The Barcelona subway system comprises eight subway lines, at different depths, with different tunnel dimensions, station designs and train frequencies. An extensive measurement campaign was performed in this subway system in order to characterise the airborne particulate matter (PM) measuring its concentration and investigating its variability, both inside trains and on platforms, in two different seasonal periods (warmer and colder), to better understand the main factors controlling it, and therefore the way to improve air quality. The majority of PM in the underground stations is generated within the subway system, due to abrasion and wear of rail tracks, wheels and braking pads caused during the motion of the trains. Substantial variation in average PM concentrations between underground stations was observed, which might be associated to different ventilation and air conditioning systems, characteristics/design of each station and variations in the train frequency. Average PM2.5 concentrations on the platforms in the subway operating hours ranged from 20 to 51 and from 41 to 91 µg m(-3) in the warmer and colder period, respectively, mainly related to the seasonal changes in the subway ventilation systems. The new subway lines with platform screen doors showed PM2.5 concentrations lower than those in the conventional system, which is probably attributable not only to the more advanced ventilation setup, but also to the lower train frequency and the design of the stations. PM concentrations inside the trains were generally lower than those on the platforms, which is attributable to the air conditioning systems operating inside the trains, which are equipped with air filters. This study allows the analysis and quantification of the impact of different ventilation settings on air quality, which provides an improvement on the knowledge for the general understanding and good management of air quality in the subway system.

A new look at inhalable metalliferous airborne particles on rail subway platforms.

Most particles breathed on rail subway platforms are highly ferruginous (FePM) and extremely small (nanometric to a few microns in size). High magnification observations of particle texture and chemistry on airborne PM10 samples collected from the Barcelona Metro, combined with published experimental work on particle generation by frictional sliding, allow us to propose a general model to explain the origin of most subway FePM. Particle generation occurs by mechanical wear at the brake-wheel and wheel-rail interfaces, where magnetic metallic flakes and splinters are released and undergo progressive atmospheric oxidation from metallic iron to magnetite and maghemite. Flakes of magnetite typically comprise mottled mosaics of octahedral nanocrystals (10-20 nm) that become pseudomorphed by maghemite. Continued oxidation results in extensive alteration of the magnetic nanostructure to more rounded aggregates of non-magnetic hematite nanocrystals, with magnetic precursors (including iron metal) still preserved in some particle cores. Particles derived from steel wheel and rails contain a characteristic trace element chemistry, typically with Mn/Fe=0.01. Flakes released from brakes are chemically very distinctive, depending on the pad composition, being always carbonaceous, commonly barium-rich, and texturally inhomogeneous, with trace elements present in nanominerals incorporated within the crystalline structure. In the studied subway lines of Barcelona at least there appears to be only a minimal aerosol contribution from high temperature processes such as sparking. To date there is no strong evidence that these chemically and texturally complex inhalable metallic materials are any more or less toxic than street-level urban particles, and as with outdoor air, the priority in subway air quality should be to reduce high mass concentrations of aerosol present in some stations.

Propofol and thiopental as anesthetic agents in electroconvulsive therapy: a retrospective study in major depression.

OBJECTIVE: To determine the influence of propofol and thiopental as anesthetics in electroconvulsive therapy (ECT), as regards, seizure duration, electrical charge, clinical efficacy, cardiovascular profile, and presence of adverse cognitive effects. METHODS: A retrospective design including 127 patients who received bilateral ECT for the treatment of a major depressive episode. RESULTS: The mean seizure duration in the propofol group was significantly shorter than in the thiopental group (21.23±6.09 versus 28.24±6.6 7s, P<.001). The mean stimulus charge was 348.22 mC in the propofol group, and 238 mC in the thiopental group (P<.001). Propofol was associated with a lower increase in blood pressure. There were no differences between groups in treatment response or presence of adverse effects. CONCLUSIONS: The anesthetic agent used in ECT might determine differences in parameters such as seizure duration or electrical charge. However, this does not seem to be translated into differences in clinical efficacy or the pattern of adverse effects observed.

Observational study on factors related to health-promoting community activity development in primary care (frAC Project): a study protocol.

INTRODUCTION: According to Spanish health regulations, primary care professionals have the responsibility to carry out health-promoting community activities (CAs). However, in practice, their implementation is not as widespread as it should be. The aims of this study were to identify factors within the team, the community and the professionals that influence the development of these activities and to describe the community interventions in progress. METHODS AND ANALYSIS: This study is an observational analytical retrospective study. The information will be collected from five Spanish regions: Catalonia, Madrid, the Balearic Islands, Navarra and Aragón. The authors will contact primary care teams (PCTs) and identify the CAs from the previous year. The research team will conduct a peer review whether the inclusion criteria are met. In the health centres where CAs are implemented, the authors will select professionals carrying them out and randomly select an identical number of professionals not doing these activities. In the centres where no CA is implemented, three professionals will be randomly selected. The selected professionals will complete the questionnaires for individual-level variables. Information about the registered population and the PCTs will be collected through questionnaires and secondary sources. OUTCOMES: Variables will be collected from the community, the PCTs, the individual professionals and CAs. ANALYSIS: A descriptive analysis of all the variables will be carried out, along with a bivariate and a logistic regression analysis, with CAs being the primary outcome. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of the Jordi Gol y Gurina Foundation in Barcelona and area 11 in Madrid. The questionnaire distributed to the professionals will be anonymous.