An improvement of the conceptual system of the sequential events model of road crashes (i-MOSES).

Background: The circulation of vehicles, motorized or not, is a risky activity that can lead to a traffic accident in which all road users can be affected. Road accidents generate high personal, labor, health and economic costs, as well as civil, administrative and even criminal responsibilities. Therefore, it is necessary to carry out a correct investigation of these road accidents. This paper reviews one of the models used for this investigation, the sequential events model for road crashes called MOSES. This model simplifies into a single sequential analysis the actions and conditions that have generated the occurrence and correlation of events that have led to a collision between two bodies, at least one of which is a vehicle, with harmful consequences for the environment, people and things. Methods: Analyzing the road accidents that occurred in the city of Badajoz between 2018 and 2022, this work proposes a new position of the sequential events in road accidents. This new position is present in more than fifty percent of the analyzed road accidents. How this new position can improve the description of traffic accidents is tested by analyzing an actual traffic accident recorded in the city of Badajoz between a motorcycle and a car. Results: The new position has been called Trust Position (TP) and is located between the Real Perception Position (RPP) and the Decision Enforcement Position (DEP) in the sequential events model for road crashes (i-MOSES). Furthermore, in this improvement of the MOSES model (i-MOSES), the reaction time (RT) is analyzed in more depth with the PIEV (Perception, Intellection, Emotion and Volition) theory, establishing that between RPP and TP are present the phases of perception and intellection, and between TP and DEP are present the phases of emotion and volition. Conclusions: This analysis shows how the proposed i-MOSES model allows for a deeper and more effective analysis of the causes that generated the traffic accident and all its circumstances. Moreover, it provides conclusions closer to the reality of how the accident actually happened and why it could have happened, ultimately leading to preventive measures to avoid future accidents.

Emittance preservation in a plasma-wakefield accelerator.

Radio-frequency particle accelerators are engines of discovery, powering high-energy physics and photon science, but are also large and expensive due to their limited accelerating fields. Plasma-wakefield accelerators (PWFAs) provide orders-of-magnitude stronger fields in the charge-density wave behind a particle bunch travelling in a plasma, promising particle accelerators of greatly reduced size and cost. However, PWFAs can easily degrade the beam quality of the bunches they accelerate. Emittance, which determines how tightly beams can be focused, is a critical beam quality in for instance colliders and free-electron lasers, but is particularly prone to degradation. We demonstrate, for the first time, emittance preservation in a high-gradient and high-efficiency PWFA while simultaneously preserving charge and energy spread. This establishes that PWFAs can accelerate without degradation-an essential step toward energy boosters in photon science and multistage facilities for compact high-energy particle colliders.

Bacterial endometritis-induced changes in the endometrial proteome in mares: Potential uterine biomarker for bacterial endometritis.

Equine endometritis is one of the main causes of subfertility in the mare. Unraveling the molecular mechanisms involved in this condition and pinpointing proteins with biomarker potential could be crucial in both diagnosing and treating this condition. This study aimed to identify the endometritis-induced changes in the endometrial proteome in mares and to elucidate potential biological processes in which these proteins may be involved. Secondly, biomarkers related to bacterial endometritis (BE) in mares were identified. Uterine lavage fluid samples were collected from 28 mares (14 healthy: negative cytology and culture, and no clinical signs and 14 mares with endometritis: positive cytology and culture, in addition to clinical signs). Proteomic analysis was performed with a UHPLC-MS/MS system and bioinformatic analysis was carried out using Qlucore Omics Explorer. Gene Ontology enrichment and pathway analysis (PANTHER and KEGG) of the uterine proteome were performed to identify active biological pathways in enriched proteins from each group. Quantitative analysis revealed 38 proteins differentially abundant in endometritis mares when compared to healthy mares (fold changes >4.25, and q-value = 0.002). The proteins upregulated in the secretome of mares with BE were involved in biological processes related to the generation of energy and REDOX regulation and to the defense response to bacterium. A total of 24 biomarkers for BE were identified using the biomarker workbench algorithm. Some of the proteins identified were related to the innate immune system such as isoforms of histones H2A and H2B involvement in neutrophil extracellular trap (NET) formation, complement C3a, or gelsolin and profilin, two actin-binding proteins which are essential for dynamic remodeling of the actin cytoskeleton during cell migration. The other group of biomarkers were three known antimicrobial peptides (lysosome, equine cathelicidin 2 and myeloperoxidase (MPO)) and two uncharacterized proteins with a high homology with cathelicidin families. Findings in this study provide the first evidence that innate immune cells in the equine endometrium undergo reprogramming of metabolic pathways similar to the Warburg effect during activation. In addition, biomarkers of BE in uterine fluid of mares including the new proteins identified, as well as other antimicrobial peptides already known, offer future lines of research for alternative treatments to antibiotics.

First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Non-invasive assessment of hormonal fluctuations during pregnancy in guanacos (Lama guanicoe) and its application in a wild population.

Obtaining endocrinological profiles using non-invasive methodologies by the measurement of hormone fecal metabolites is a widely used method to monitor ovarian activity and pregnancy in wild species. These tools allow the obtention of physiological information without causing capture-related stress on the individuals. In this research, we aimed to 1) biologically validate a non-invasive method to assess fecal progestagens and estrogens fluctuations during gestation in guanacos (Lama guanicoe) and 2) apply this technique to assess pregnancy in a wild free-ranging population. Fecal samples were collected through the gestation period (~12 months) of female guanacos in a 6.5-ha paddock. An increase in fecal metabolites of both hormones was detected. Progestagens increased gradually, in contrast to estrogens, which remained at basal values for most of the gestation period and peaked only a few days before calving. To assess pregnancy in wild free-ranging animals, fecal samples were collected from a population of La Payunia provincial reserve (Mendoza, Argentina) during the beginning of gestation and at the end of gestation. Through the first months of possible gestation, pregnant females represented between 40 and 80% of the population; at the end of gestation, only 20-40% of the females had confirmed pregnancies. Our results demonstrated that the polyclonal antisera and sexual hormone metabolite assays used here detect variations in the metabolites excreted through feces in guanacos and provide the possibility of non-invasive hormone monitoring of female reproductive status. Also, the findings in wild conditions suggest that natural abortions could have occurred during the first months of gestation. Although some abortions may be natural, the harsh environmental conditions that challenge the support of such a long gestational process may be another relevant factor to consider. The results obtained here enhance our understanding of the reproductive physiology of one of the most emblematic ungulates in South America.

Fetal circular shunt in Ebstein's anomaly and non-steroidal anti-inflammatory treatment.

A circular shunt is a poor prognostic factor associated with Ebstein's anomaly. Targeting the constriction of the ductus arteriosus (DA) in order to limit or resolve the circular shunt, has been shown to improve fetal outcomes. Prenatal non-steroidal anti-inflammatory drugs (NSAIDs) have been known to constrict the DA. Recently, prenatal NSAIDs have been used for that purpose in the treatment of circular shunt. Limited research shows that it may be an effective treatment leading to improved fetal outcomes. In this article, we did an extensive review of literature to describe this therapy's effectiveness and outcomes. 82% of fetuses were able to achieve ductal constriction with prenatal NSAID therapy. For fetuses who achieved ductal constriction, fetal demise was less likely (6%) when compared to those who were unable to achieve the same (50%). Of all the fetuses with hydrops, 50% had resoluation of hydrops with prenatal NSAID treatment.

Agrobiodiversity and smallholder resilience: A scoping review.

Agrobiodiversity is often touted as a crucial adaptation strategy to mitigate risks linked to climate change by increasing the response capability of a system to external shocks and, consequently, the smallholder's resilience. This scoping review, conducted following the PRISMA protocol, aims to elucidate how agrobiodiversity's effect on resilience has been conceptualized, analyzed, and reported in the literature and to identify knowledge gaps. We systematically examined 193 articles, with 63 selected for full review based on predefined criteria. Notably, only 16 studies featured actual measurements of the effect of agrobiodiversity on resilience. Our findings indicate that articles often operationalize these complex theoretical concepts using limited variables. Agrobiodiversity is typically measured by crop count, while resilience is assessed through economic, ecological, and/or social dimensions. We identified key attributes expected in resilient systems and found that agrobiodiversity's impact on resilience was positive in 10 cases, negative in 9, and contingent on production types and system shocks in others. This review emphasizes the context-dependent agrobiodiversity-resilience relationship and the need for tailored agricultural diversification strategies. We discuss how inconsistencies between theoretical concepts and practical measures may compromise study validity and comparability and how smallholder context can influence resilience conceptualization. Based on our findings, we propose guidelines for future research and emphasize the need for improved metrics, empirical evidence generation, and mixed-method approaches. Our findings prompt further exploration of key questions to advance our understanding of agrobiodiversity's role in fostering agricultural resilience.

Effects of serum albumin on the photophysical characteristics of synthetic and endogenous protoporphyrin IX.

The study of the interaction of synthetic protoporphyrin IX (PpIXs) and protoporphyrin IX extracted from Harderian glands of ssp Rattus novergicus albinus rats (PpIXe) with bovine serum albumin (BSA) was conducted in water at pH 7.3 and pH 4.5 by optical absorption and fluorescence spectroscopies. PpIXs is present as H- and J-aggregates in equilibrium with themselves and with monomers. The PpIXs charge is 2- at pH 7.3 and 1- at pH 4.5. This increases its aggregation at pH 4.5 and shifts the equilibrium in favor of J-aggregates. In spite of electrostatic attraction at pH 4.5, where BSA is positive, the binding constant (Kb) of PpIXs to BSA is 20% less than that at pH 7.3, where BSA is negative. This occurs because higher aggregation of PpIXs at pH 4.5 reduces the observed Kb value. At both pHs, water-soluble PpIXe exists in the monomeric form with the charge of 1- and its Kb exceeds that of PpIXs. At pH 4.5, its Kb is 12 times higher than that at pH 7.3 due to electrostatic attraction between the positively charged BSA and the negatively charged PpIXe. The higher probability of PpIXe binding to BSA makes PpIXe more promising as a fluorescence probe for fluorescence diagnostics and as a photosensitizer for photodynamic therapy. The existence of PpIXe in the monomeric form can explain its faster cell internalization. Aggregation reduces quantum yields and lifetimes of the PpIXs excited states, which explains higher phototoxicity of PpIXe toward malignant cells compared with PpIXs.

Proteomics reveal the protective effects of chlorogenic acid on Enterococcus faecium Q233 in a simulated pro-oxidant colonic environment.

Certain phytochemicals have been found to promote the beneficial effects of probiotic bacteria although the molecular mechanisms of such interactions are poorly understood. The objective of the present study was to evaluate the impact of the exposure to 0.5 mM chlorogenic acid (CA) on the redox status and proteome of Enterococcus faecium isolated from cheese and challenged with 2.5 mM hydrogen peroxide (H2O2). The bacterium was incubated in anaerobic conditions for 48 h at 37 °C. CA exposure led to a more intense oxidative stress and accretion of bacterial protein carbonyls than those induced by H2O2. The oxidative damage to bacterial proteins was even more severe in the bacterium treated with both CA and H2O2, yet, such combination led to a strengthening of the antioxidant defenses, namely, a catalase-like activity. The proteomic study indicated that H2O2 caused a decrease in energy supply and the bacterium responded by reinforcing the membrane and wall structures and counteracting the redox and pH imbalance. CA stimulated the accretion of proteins related to translation and transcription regulators, and hydrolases. This phytochemical was able to counteract certain proteomic changes induced by H2O2 (i.e. increase of ATP binding cassete (ABC) transporter complex) and cause the increase of Rex, a redox-sensitive protein implicated in controlling metabolism and responses to oxidative stress. Although this protection should be confirmed under in vivo conditions, such effects point to benefits in animals or humans affected by disorders in which oxidative stress plays a major role.

Protein oxidation marker, α-amino adipic acid, impairs proteome of differentiated human enterocytes: Underlying toxicological mechanisms.

Protein oxidation and oxidative stress are involved in a variety of health disorders such as colorectal adenomas, inflammatory bowel's disease, neurological disorders and aging, among others. In particular, the specific final oxidation product from lysine, the α-amino adipic acid (α-AA), has been found in processed meat products and emphasized as a reliable marker of type II diabetes and obesity. Currently, the underlying mechanisms of the biological impairments caused by α-AA are unknown. To elucidate the molecular basis of the toxicological effect of α-AA, differentiated human enterocytes were exposed to dietary concentrations of α-AA (200 µM) and analyzed by flow cytometry, protein oxidation and proteomics using a Nanoliquid Chromatography-Orbitrap MS/MS. Cell viability was significantly affected by α-AA (p < 0.05). The proteomic study revealed that α-AA was able to alter cell homeostasis through impairment of the Na+/K+-ATPase pump, energetic metabolism, and antioxidant response, among other biological processes. These results show the importance of dietary oxidized amino acids in intestinal cell physiology and open the door to further studies to reveal the impact of protein oxidation products in pathological conditions.

Evaluation of testicular echotexture with Ecotext as a diagnostic method of testicular dysfunction in stallions.

This study aimed to assess if Ecotext, a new software for evaluation of testicular echotexture, is a good method for diagnosis of stallions with testicular dysfunction (TD). Relationships between Ecotext parameters and sperm motility and production, testicular volume, and testicular blood flow were also studied. Ecotext provides a total of six echotexture parameters: Ecotext 1 (black pixels), 2 (white pixels) and 3 (grey pixels), and another 3 parameters related to hypoechogenic areas: Ecotext tubular density (ETD), Ecotext tubular diameter (ETd), and Ecotext tubular area (ETA). Stallions (n = 33) were assessed using proven diagnostic techniques (spermiogram, B-mode and Pulse Doppler ultrasound), and subsequent analysis with Ecotext. Animals were classified as "control stallions" (n:21, acceptable semen quality), and "stallions with TD" (n:12, poor semen quality (TM < 60%, PM < 45% and total nº of sperm with PM < 2000 × 106 spz), that were subdivided into "induced TD group" (immunized, anti-GnRH vaccine) and "acquired TD group". The acquired TD group showed differences in all Ecotext parameters in relation to controls (Ecotext 1:0.11 ± 0.17 vs 2.82 ± 2.52, Ecotext 2:1584.0 ± 575.8 vs 388 ± 368.2, Ecotext 3:134.2 ± 9.26; ETA: 2.14 ± 0.59 vs 5.40 ± 1.90; ETd: 65.66 ± 6.27 vs 86.93 ± 10.65 and ETD: 92.35 ± 11.24 vs 132.10 ± 16.35, p ≤ 0.001). Results suggest acquired TD stallions were suffering testicular degeneration with loss of architecture and function as all Ecotext parameters were altered in relation to controls. Induced TD horses only showed a reduction in ETD (116.2 ± 8.59 vs 132.10 ± 16.35, p ≤ 0.001), despite all sperm parameters being worse. These findings suggested immunized stallions probably only experience an acute loss of testicular functionality and parenchyma architecture is likely not affected since differences in Ecotext parameters with control stallions were not detected. ETD was the best parameter to identify animals with TD (AUC: 0.84, optimal cut-off value of 124.3 seminiferous tubules/cm2). Correlations were found between ETD and Doppler indices (PI: 0.60; RI: 0.47 p ≤ 0.001), total testicular volume (r: 0.48; p ≤ 0.05) and sperm motility (TM:0.51; and PM:0.54; p ≤ 0.001) and production (r:0.51; p ≤ 0.001). In summary, Ecotext could identify changes in testicular echotexture of stallions with TD. Results open the possibility for new research focused on establishing the relationship between Ecotext parameters and histomorphometry features in stallion testes.

Sociodemographic and clinical characteristics related with hyperprolactinaemia in psychiatric clinical population.

BACKGROUND: Hyperprolactinaemia (HyperPRL) induced by psychotropic drugs is a high-prevalence consequence which has repercussions in psychical and mental health in the psychiatric population, so this research had the objective to expand which sociodemographic and clinical features are associated with prolactin (PRL) elevation in patients treated with antidepressant and/or antipsychotic drugs. METHODS: An observational, cross-sectional, comparative and retrolective study was conducted on 300 patients who received clinical attention in a third level of psychiatric care unit in Mexico during 2017. These patients have been reported to show PRL levels greater than 25 ng/mL among women and greater than 20 ng/mL among men. In the same way, sociodemographic and clinical variables were collected, as well as psychiatric diagnosis and type of psychopharmacological treatment used by the patients. RESULTS: HyperPRL was more frequent in women (80.7%) than men (19.3%). The mean levels of PRL were 68.94 ± 62.28 ng/mL with higher levels in women (71.9 ± 67.3, p=.02). Regarding the treatment, 78.3%, 71.3% and 49.7% consumed antipsychotics, antidepressants, and both drugs, respectively. The relationship between hyperPRL (>100 n/mL) and typical antipsychotics was dose-dependent (33.23 ± 13.24 mg, p=.01). In the multivariate regression models according to the type of treatment, as well as the demographic and clinical features, hyperPRL was associated independently with the use of antipsychotic treatment, pituitary adenoma and hypertension (R2=0.05). CONCLUSIONS: HyperPRL is a complex clinical syndrome frequent in the psychiatric population with detrimental long-term consequences, as well as its relationship with the use of psychotropic drugs as in the case of antipsychotics. Effective actions should be implemented in the prevention, approach and treatment of this condition paying special attention to the accompanying medical comorbidities.

Indicadores de fuerza en mujeres jóvenes con diferente tasa de fuerza relativa / Force Indicators in Young Women with Different Relative Force Rate

Objetivo: Comparar la tasa de fuerza relativa (TFR) con distintos indicadores de fuerza en mujeres jóvenes. Métodos: Se evaluaron a 146 mujeres que se distribuyeron en tres grupos de acuerdo con los resultados de la TFR obtenida en el ejercicio de sentadilla y se compararon los resultados obtenidos en las pruebas de Fuerza prensil de la mano derecha e izquierda (FPMD- FPMI), Fuerza isométrica miembros inferiores (FIMI), Fuerza máxima de pecho (FMP), Fuerza máxima en sentadilla (FMS) Velocidad de desplazamiento sobre treinta metros (V30), altura del salto en (CMJ), potencia de pedaleo (PP) y la velocidad media propulsiva de miembros superiores e inferiores (VMPMS-VMPMI) obtenida al 50%, 60%, 70% y 80% de una repetición máxima en sentadilla. Resultados: Se observaron diferencias significativas (p≤0,01) entre los grupos en la FMS, CMJ, V30, VMP y PP, y la mayoría de las variables presentaban la diferencia entre el G1 y G3 (p≤0,01). (AU)

Objective: To compare the relative strength ratio (RSR) and other strength indicators between young women. Methods 146 women were evaluated which were distributed in three groups according to the results of the TFR obtained in the squat exercise and compared the results obtained in the tests of prehensile strength of the right and left hand (PSRH-PSLH), Isometric strength lower limbs (ISLL), maximum chest strength (MCS), maximum squat strength (MSS), velocity over thirty meters (V30), jump height in (CMJ), pedaling power (PP) and mean propulsive velocity of upper and lower limbs (MPVUL-MPVLL) obtained at 50%, 60%, 70% and 80% of a maximum squat repetition. Results_ Significant differences (p≤0.01) were observed between the groups in the MCS, CMJ, V30, MPV and PP, and most of the variables presented the difference between G1 and G3 (p≤0.01). (AU)

A prognostic model to identify short survival expectancy of medical oncology patients at the time of hospital discharge.

BACKGROUND: Hospitalization of cancer patients is associated with poor overall survival, but prognostic misclassification may lead to suboptimal therapeutic decisions and transitions of care. No model is currently available for stratifying the heterogeneous population of oncological patients after a hospital admission to a general Medical Oncology ward. We developed a multivariable prognostic model based on readily available and objective clinical data to estimate survival in oncological patients after hospital discharge. METHODS: A multivariable model and nomogram for overall survival after hospital discharge was developed in a retrospective training cohort and prospectively validated in an independent set of adult patients with solid tumors and a first admission to a unit of medical oncology. Performance of the model was assessed by C-index and Kaplan-Meier survival curves stratified by risk categories. RESULTS: From a population of 1089 patients with a first hospitalization, 757 patients were included in the training group [median survival, 43 weeks; 95% confidence interval (CI), 37-51 weeks] and 200 patients in the validation cohort (median survival, 44 weeks; 95% CI, 34 weeks-not reached). An accelerated failure time log-normal model was built, including five variables (primary tumor, stage, cause of admission, active treatment, and age). The C-index was 0.71 (95% CI, 0.69-0.73), with a good calibration, and adequate validation in the prospective cohort (C-index: 0.69; 95% CI, 0.65-0.74). Median survival in three predefined model-based risk groups was 10.7 weeks (high), 27.0 weeks (intermediate), and 3 years (low) in the training cohort, with comparable values in the validation cohort. CONCLUSIONS: In oncological patients, individualized predictions of survival after hospitalization were provided by a simple and validated model. Further evaluation of the model might determine whether its use improves shared decision making at discharge.

Effects of serum albumin on the photophysical characteristics of synthetic and endogenous protoporphyrin IX

The study of the interaction of synthetic protoporphyrin IX (PpIXs) and protoporphyrin IX extracted from Harderian glands of ssp Rattus novergicus albinus rats (PpIXe) with bovine serum albumin (BSA) was conducted in water at pH 7.3 and pH 4.5 by optical absorption and fluorescence spectroscopies. PpIXs is present as H- and J-aggregates in equilibrium with themselves and with monomers. The PpIXs charge is 2− at pH 7.3 and 1− at pH 4.5. This increases its aggregation at pH 4.5 and shifts the equilibrium in favor of J-aggregates. In spite of electrostatic attraction at pH 4.5, where BSA is positive, the binding constant (Kb) of PpIXs to BSA is 20% less than that at pH 7.3, where BSA is negative. This occurs because higher aggregation of PpIXs at pH 4.5 reduces the observed Kb value. At both pHs, water-soluble PpIXe exists in the monomeric form with the charge of 1− and its Kb exceeds that of PpIXs. At pH 4.5, its Kb is 12 times higher than that at pH 7.3 due to electrostatic attraction between the positively charged BSA and the negatively charged PpIXe. The higher probability of PpIXe binding to BSA makes PpIXe more promising as a fluorescence probe for fluorescence diagnostics and as a photosensitizer for photodynamic therapy. The existence of PpIXe in the monomeric form can explain its faster cell internalization. Aggregation reduces quantum yields and lifetimes of the PpIXs excited states, which explains higher phototoxicity of PpIXe toward malignant cells compared with PpIXs.

Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer

The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs (AU)

The inhibition of spermatic cystine/glutamate antiporter xCT (SLC7A11) influences the ability of cryopreserved stallion sperm to bind to heterologous zonae pellucidae.

Sperm are redox-regulated cells, and deregulation of their redox status is considered to affect male fertility and to reduce their fertilizing ability following biotechnological procedures, such as cryopreservation. Cystine (CysS), after incorporation in sperm via SLC7A11 antiporter, has been demonstrated to increase intracellular GSH content, the most important non enzymatic antioxidant. This study was aimed at investigating the role of SLC7A11 antiporter on frozen-thawed stallion sperm ability to respond to in vitro capacitating environment after post-thaw incubation with CysS and/or Sulfasalazine (SS), a specific inhibitor of SLC7A11 antiporter. Viability, motility, immunolocalization of tyrosine phosphorylated proteins and the ability to bind to heterologous zonae pellucidae were evaluated. Thawed sperm from seven stallions (2 ejaculates/stallion) was washed and resuspended in Tyrodes media; each thawed ejaculate was divided in Control (CTR) and 3 samples supplemented with: 0.5 mM Cystine (CysS), 500 µM Sulfasalazine (SS) and 0.5 mM CysS + 500 µM SS (CysS + SS). After 1 h of incubation at 37 °C, samples were washed twice, resuspended in capacitating BWW medium and incubated at 38 °C under 5% CO2. After 30 and 60 min, sperm motility, viability and tyrosine phosphorylated protein immunolocalization, used as capacitation status index, were evaluated. After 30 min of capacitation, 4 × 105 sperm were co-incubated with denuded pig oocytes in capacitation medium for 30 min for the heterologous binding assay. None of the sperm parameters studied (motility, viability and tyrosine phosphorylation) showed any difference respective to control. The number of sperm bound per oocyte (mean ± SEM) tended to increase in CysS group (44.0 ± 12.3) respect CTR (40.8 ± 10.8) while decreased in SS group (32.4 ± 7.8) (p < 0.01). Moreover, CysS + SS group showed a lower binding rate (32.0 ± 10.0) compared to CysS (p < 0.001). Our results suggest that CysS supplementation of thawed stallion sperm can influence their ability to bind to heterologous zona pellucidae as the inhibition of CysS incorporation by SLC7A11 reduced the number of sperm bound per oocyte. This effect does not seem to be ascribed to a modification of sperm motility, membrane integrity and tyrosine phosphorylation.

Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer.

The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

Exposure to 2.45 GHz radiofrequency modulates calcitonin-dependent activity and HSP-90 protein in parafollicular cells of rat thyroid gland.

In this study we analyzed the response of parafollicular cells in rat thyroid gland after exposure to radiofrequency at 2.45 GHz using a subthermal experimental diathermy model. Forty-two Sprague Dawley rats, divided into two groups of 21 rats each, were individually exposed at 0 (control), 3 or 12 W in a Gigahertz Transverse Electro-Magnetic (GTEM) chamber for 30 min. After radiation, we used simple or fluorescence immunohistochemistry to measure calcitonin cells or cellular stress levels, indicated by the presence hyperplasia of parafollicular cells, heat shock protein (HSP) 90. Immunomarking of calcitonin-positive cells was statistically significant higher in the thyroid tissue of rats exposed to 2.45 GHz radiofrequency and cell hyperplasia appeared 90 min after radiation at the SAR levels studied. At the same time, co-localized expression of HSP-90 and calcitonin in parafollicular cells was statistically significant attenuated 90 min after radiation and remained statistically significantly low 24 h after radiation, even though parafollicular cell levels normalized. These facts indicate that subthermal radiofrequency (RF) at 2.45 GHz constitutes a negative external stress stimulus that alters the activity and homeostasis of parafollicular cells in the rat thyroid gland. However, further research is needed to determine if there is toxic action in human C cells.

Noxious effects of selected food-occurring oxidized amino acids on differentiated CACO-2 intestinal human cells.

The harmful effects of food-occurring oxidized amino acids, namely, aminoadipic acid (AAA), dityrosine (DTYR), L-kynurenine (KN), kynurenic acid (KA) and 3-nitrotyrosine (3NT), were studied on differentiated CACO-2 cells by flow cytometry and quantification of glutathione (GSH), and allysine. Cells were exposed to food-relevant doses (200 µM) of each compound for 4 or 72h and compared to a control (no stimulated cells). All oxidized amino acids induced apoptosis and results indicated that underlying mechanisms depended on the chemical nature of the species. AAA, KN and KA caused ROS generation and severe oxidative stress in 96%, 98% and 89% of exposed cells (77% in control cells), leading to significant GSH depletion and allysine accretion (1.5, 1.5 and 1.6 nmol allysine/mg protein, respectively at 4h; control: 0.22 nmol/mg protein; p < 0.05). DTYR and 3NT induced significant apoptosis to 29% and 25% of cells (control: 16%; p < 0.05) and necrosis to 28% and 26% of cells (control: 23%) at 72h by ROS-independent mechanisms. KN and KA were found to induce a cycle arrest effect on CACO-2 cells. These findings emphasize the potential harmful effects of the intake of oxidized proteins and amino acids and urge the necessity of carrying out further molecular studies.