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The impact of stressful events is especially important during early life, because certain cortical regions, especially the prefrontal cortex (PFC), are still developing. Consequently, aversive experiences that occur during the peripubertal period can cause long-term alterations in neural connectivity, physiology and related behaviors. Although sex influences the stress response and women are more likely to develop stress-related psychiatric disorders, knowledge about the effects of stress on females is still limited. In order to analyze the long-term effects of peripubertal stress (PPS) on the excitatory and inhibitory circuitry of the adult PFC, and whether these effects are sex-dependent, we applied an unpredictable chronic PPS protocol based on psychogenic stressors. Using two strains of transgenic mice with specific fluorescent cell reporters, we studied male and diestrus females to know how PPS affects the structure and connectivity of parvalbumin expressing (PV+) interneurons and pyramidal neurons. We also studied the expression of molecules related to excitatory and inhibitory neurotransmission, as well as alterations in the expression of plasticity-related molecules. The structure of pyramidal neurons was differentially affected by PPS in male and female mice: while the former had a decreased dendritic spine density, the latter displayed an increase in this parameter. PPS affected the density of puncta expressing excitatory and inhibitory synaptic markers exclusively in the female mPFC. Similarly, only in female mice we observed an increased complexity of the dendritic tree of PV+ neurons. Regarding the perisomatic innervation on pyramidal and PV+neurons by basket cells, we found a significant increase in the density of puncta in stressed animals, with interesting differences between the sexes and the type of basket cell analyzed. Finally, the PPS protocol also altered the total number of somata expressing the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) when we analyzed both sexes together. These results highlight the strong programming effects of aversive experiences during early life for the establishment of cortical circuitry and the special impact of these stressful events on females.

BackgroundMany older patients don't receive appropriate oncological treatment. Our aim was to analyse whether there are age differences in the use of adjuvant chemotherapy and preoperative radiotherapy in patients with colorectal cancer.MethodsA prospective cohort study was conducted in 22 hospitals including 1157 patients with stage III colon or stage II/III rectal cancer who underwent surgery. Primary outcomes were the use of adjuvant chemotherapy for stage III colon cancer and preoperative radiotherapy for stage II/III rectal cancer. Generalised estimating equations were used to adjust for education, living arrangements, area deprivation, comorbidity and clinical tumour characteristics.ResultsIn colon cancer 92% of patients aged under 65years, 77% of those aged 65 to 80years and 27% of those aged over 80years received adjuvant chemotherapy (chi(2)(trends)

Purpose To identify and validate risk factors that contribute to prolonged length of hospital stay (LOS) in patients undergoing resection for colorectal cancer. Methods This prospective cohort study included 1955 patients admitted to 22 hospitals for primary resection of colorectal cancer. Multivariate analyses were used to identify and validate risk factors, randomizing patients into a derivation and a validation cohort. Multiple correspondence and cluster analysis were performed to identify clinical subtypes based on LOS. Results The strongest independent predictors of prolonged LOS were postoperative reintervention, surgical site infection, open surgery, and distant metastasis. The multiple correspondence and cluster analysis provided three groups of patients in relation to prolonged LOS: patients with the longest LOS included the highest percentage of patients with open surgery, distant metastasis, deep surgical site infections, emergency admissions, additional diagnostic factors, and highly contaminated surgical sites. Patients with prolonged LOS (> 14 days) were more likely to develop adverse outcomes within 30 days after discharge. Conclusions Patients undergoing resection of colorectal cancer cluster into different groups based on LOS of the index admission. Those with prolonged LOS were more likely to develop adverse outcomes within 30 days after discharge. Some of the strongest independent predictors of prolonged LOS, such as surgical infections or open surgery, could be modified to reduce LOS and, in turn, other adverse outcomes.

[Purpose] In the VELOUR study, aflibercept + FOLFIRI regimen resulted in improved survival in metastatic colorectal cancer (mCRC) patients who progressed after oxaliplatin. The use of aflibercept outside the clinical trial framework needs to be further assessed in terms of effectiveness and tolerability. [Methods] Early access to aflibercept through a named patient programme (NPP) was provided to mCRC patients receiving FOLFIRI as second-line treatment in Spain. The effectiveness of aflibercept was assessed as progression-free survival (PFS) achieved within the NPP population. Post hoc analyses on PFS were done according to certain baseline characteristics (K-RAS mutation, prior targeted therapy) or prognostic factors. [Results] Registries from 71 mCRC patients included in the NPP were reviewed retrospectively. The median age for the NPP population was 64 years (19.7 % aged ≥70 years) and 63.4 % patients had ≥2 metastases. A median PFS of 5.3 months (95 % CI, 3.6–8.5 months) was achieved, which did not depend on K-RAS mutation status or prior targeted therapy received. The risk of progression or death increased in patients with a poor prognosis as per the GERCOR score (performance status [PS] 1–2 and increased baseline lactate dehydrogenase [LDH] level) compared with patients with a good prognosis (PS 0 and normal LDH level) (median PFS: 2.6 vs. 8.3 months, respectively; p = 0.0124). Aflibercept was well tolerated, with a manageable toxicity profile. [Conclusions] Bearing in mind the differences in sample size, the PFS achieved with the aflibercept + FOLFIRI regimen in the real-life practice setting is comparable to that observed in the clinical trial setting. This study was supported by Sanofi. A. Del Campo (Pivotal SL) provided medical writing services on behalf of Sanofi Pharmaceuticals.

This article discusses experimental data on the flexural and compressive strength of Portland cement mortars containing additions or cement replacements consisting in petroleum or coal tar, by-products of the oil and coal industries. The materials studied were two coal (BACA and BACB) and two petroleum (BPP and BPT) tars. The results show that it is feasible to use such materials as a partial replacement for cement in mortar manufacture. This should lead to the design of a new sustainable product that will contribute to lowering the environmental impact of construction materials while at the same time opening up an avenue for the re-use of this type of industrial by-products., En este artículo se presentan datos experimentales de resistencia a flexión y a compresión de morteros de cemento Portland con adición y sustitución de breas de petróleo y de alquitrán de carbón, que son subproductos de la industria del carbón o del petróleo. Los materiales estudiados son breas de alquitrán de carbón A (BACA) y B (BACB), y dos breas de petróleo (BPP) y (BPT). Los datos demuestran la viabilidad del uso de estas breas en la fabricación de morteros con menores contenidos de cemento, permitiendo diseñar un nuevo material sostenible con el medio ambiente y que contribuya a reducir el impacto ambiental de los materiales de construcción, hecho que permite abrir una nueva vía de valorización de estos subproductos.

Advances in the care of patients with metastatic colorectal cancer arise from well-designed clinical trials. In the present document we address specific challenges in the design of clinical trials for metastatic colorectal cancer regarding staging and standard of care according to prognosis, as well as some relevant methodological issues.

10.1371/journal.pone.0031280 De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes.

10.1371/journal.pone.0033264 Zinc-α2 glycoprotein (ZAG) stimulates lipid loss by adipocytes and may be involved in the regulation of adipose tissue metabolism. However, to date no studies have been made in the most extreme of obesity. The aims of this study are to analyze ZAG expression levels in adipose tissue from morbidly obese patients, and their relationship with lipogenic and lipolytic genes and with insulin resistance (IR).

Durante la última década, se ha producido un rápido desarrollo en la nefroscopia y la ureterorrenoscopia flexible, litotricia láser y diferentes instrumentos para manejar las litiasis. Realizaremos una revisión del empleo del láser en distintas situaciones. Se deben hacer esfuerzos para minimizar el daño renal y el láser juega un papel importante en el tratamiento de pacientes con urolitiasis y riñones en herradura, insuficiencia renal crónica, pacientes neurológicos. During the last decade there has been a rapid development in flexible nephroscopy, flexible ureterorenoscopy, laser lithotripsy and instruments for stone manipulation. We are going to review the use of Laser in the management of lithiasis in different situations. Efforts should be made to minimize renal injury and lasers play a significant role in patients with urolithiasis and horseshoe kidneys, chronic renal failure, neurological patients.

The paper describes the effect of carbon fibre on alkaliactivated slag mortar (AAS) mechanical strength, volume stability and reinforcing steel corrosion, compared to its effect on the same properties in Portland cement (PC) properties. Mechanical strength and volume stability tests were performed as set out in the respective Spanish UNE standards. The corrosion rate of steel embedded in the specimens studied was determined from polarization resistance analysis. One of the findings of the study performed was that carbon fibre failed to improve AAS or CP mortar strength. As far as volume stability is concerned, the inclusion of carbon fibres in AAS with a liquid/solid ratio of 0.5 reduced drying shrinkage by about 50%. The effect of carbon fibre on PC mortars differed from its effect on AAS mortars. Studies showed that in the presence of carbonation, steel corrosion reached higher levels in carbon-fibre reinforced AAS mortars; the inclusion of 1% carbon fibre improved corrosion resistance perceptibly in these same mortars, however, when exposed to chloride attack., Se ha estudiado el efecto de la incorporación de fibras de carbón en el comportamiento mecánico, estabilidad de volumen y nivel de corrosión de la armadura en morteros de escorias activadas alcalinamente (AAS). Se evalúa la influencia de las fibras de carbón en el comportamiento de morteros alcalinos en comparación con el efecto que producen en morteros de Portland (CP). Los ensayos mecánicos y de estabilidad de volumen se han realizado según lo establecido en la norma UNE que los regula. Se ha utilizado la técnica de la Resistencia a la Polarización para determinar la velocidad de corrosión del acero embebido en las muestras estudiadas. Como consecuencia del estudio realizado, se ha podido concluir que la adición de fibras de carbón a morteros de AAS y CP no mejora las características resistentes de los mismos. En relación con la estabilidad de volumen, la incorporación de fibras de carbón a los morteros de AAS, preparados con una relación líquido/sólido de 0,5, reduce alrededor del 50% su retracción al secado. En los morteros de CP, la influencia de las fibras de carbón difiere de la observada para los morteros de AAS. Los estudios de corrosión han demostrado que en condiciones de carbonatación, los morteros de AAS con fibras de carbón incrementan el nivel de corrosión del acero embebido en los mismos; mientras que mejora sensiblemente el comportamiento de los morteros AAS con un 1% de fibra de carbón frente a la corrosión ante el ataque por cloruros.

Primary signet-ring cell adenocarcinoma of the urinary bladder is a rare tumor. We report in this study the case of a 53 year old man consulting for gross hematuria. Computed tomography imaging demonstrated right hydronephrosis and an invasive bladder tumor. The bladder biopsy showed a signet-ring cell carcinoma; the exploration of the gastrointestinal tract did nor reveal any other tumor localization. A total cystoprostatectomy was performed followed by adjuvant chemotherapy with cisplatin and gemcitabine. The aim of this study is to determine the anatomoclinical, therapeutic and evolutionary characteristics of this rare tumor. El adenocarcinoma de células en anillo de sello primario de vejiga es un tumor raro. Describimos un caso de un varón de 53 años que consultó por hematuria macroscópica. La imagen de la tomografía axial computerizada mostró un hidronefrosis derecha y un tumor invasivo de la vejiga urinaria. La biopsia mostró un carcinoma de células en anillo de sello. No se detectó localización primaria digestiva en la exploración del tracto grastrointestinal. El paciente se trató con cistoprostatectomía total y quimioterapia adyuvante con cisplatino y gemcitabina. El objetivo de este caso es presentar las características anatomoclínicas, tratamiento y evolución de este infrecuente tumor.

Objective: To assess the impact of HIV/AIDS on the incidence of tuberculosis (TB) and to analyse the determinants of TB presenting as the first indicative disease of AIDS. Design: Analysis of TB and AIDS surveillance data. Setting: Catalonia, north-east Spain. Patients: Two separate sources were used: (i) TB cases reported to the Catalan TB registry diagnosed between January 1982 and December 1993; (ii) AIDS cases reported to the AIDS Catalan registry diagnosed between January 1982 and December 1994. Main outcome measures: Expected and observed TB cases, and number and characteristics of AIDS cases presenting with TB. Results: From 1987 to 1993 the annual TB crude incidence rate increased by 50% to a rate of 49.7 per 100 000, with at least 60% of the increase directly due to AIDS. During that period specific rates among children aged 0-4 years remained high at around 40 per 100 000. A total of 7010 AIDS cases were diagnosed between 1988 and 1994, ot whom 24.3% had TB. Multivariate analysis from those AIDS cases showed that besides male sex, young age, and urban residence, the strongest predictors of TB among AIDS cases were history of imprisonment (odds ratio, 2.16, P < 0.001) and intravenous drug use [odds ratio, 1.65; P < 0.001). Conclusions: The high rates of TB among children and young adults suggest that TB transmission has increased during this period, especially among people at high risk of AIDS. The determinants of individual risk of TB among AIDS patients act together, especially in prisons. The HIV/TB coepidemic is an emerging threat potentially for all and requires expanding targeted measures to prevent and control both diseases in our setting.

Diagnosis; Esophageal cancer; Treatment Diagnóstico; Cáncer de esófago; Tratamiento Diagnòstic; Càncer d'esòfag; Tractament Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.

Bariatric surgery is the only procedure to obtain and maintain weight loss in the long term, although the mechanisms driving these benefits are not completely understood. In the last years, gut microbiota has emerged as one of the drivers through its metabolites, especially secondary bile acids. In the current study, we have compared the gut microbiota and the bile acid pool, as well as anthropometric and biochemical parameters, of patient with morbid obesity who underwent bariatric surgery by two different techniques, namely Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Gut microbiota populations differed after the respective procedures, particularly with respect to the Enterobacteriaceae family. Both techniques resulted in changes in the bile acids pool, but RYGB was the procedure which suffered the greatest changes, with a reduction in most of their levels. Blautia and Veillonella were the two genera that more relationships showed with secondary bile acids, indicating a possible role in their formation and inhibition, respectively. Correlations with the anthropometric and biochemical variables showed that secondary bile acids could have a role in the amelioration of the glucose and HDL-cholesterol levels. Thus, we have observed a possible relationship between the interaction of the bile acids pool metabolized by the gut microbiota in the metabolic improvements obtained by bariatric surgery in the frame of morbid obesity, deserving further investigation in greater cohorts to decipher the role of each bile acid in the homeostasis of the host for their possible use in the development of microbiota-based therapeutics, such as new drugs, postbiotics or probiotics.

Journal Article; Aflibercept is a recombinant fusion protein that acts by inhibiting tumoural angiogenesis. Efficacy data obtained in the VELOUR randomised study has contributed to the approval of aflibercept as a second-line metastatic colorectal cancer (mCRC) treatment following an oxaliplatin-based regimen. The present study reports a case series of five patients with mCRC, who were treated in two centres since 2011 in the Compassionate Use Program for aflibercept. All patients had a KRAS mutation and previously received palliative fluoropyrimidine-oxaliplatin-based chemotherapy with bevacizumab. A doublet with irinotecan combined with aflibercept was administered until progression of disease. The majority of patients received a greater number of aflibercept cycles than the median reported in the VELOUR study (12 vs. 7 cycles), with manageable and reversible toxicity. The most frequent adverse events observed were diarrhoea, neutropenia, fatigue, proteinuria and hypertension. Most cases obtained a progression-free survival greater than the median reported in the VELOUR study (11 vs. 6.9 months) and, in a subgroup of patients previously treated with bevacizumab, and a median survival time of ~47 months was reached from the initial treatment of the disease. The present study contrasts the efficacy and safety results obtained from the pivotal VELOUR trial, and confirms that aflibercept, used in routine clinical practice outside of the clinical trial environment, is active and well-tolerated following bevacizumab treatment. Medical writing assistance, supported financially by Sanofi Spain (Barcelona, Spain). Yes

Journal Article; Abstract A prospective 1-year follow-up study in ear, nose, and throat (ENT) cancer patients was carried out one year after radiotherapy to assess the effect of varying consumption of ω3 fatty acid according to whether they consumed more or less than the 50th percentile of ω3 fatty acids. Clinical, analytical, inflammatory (CRP and IL-6), and oxidative variables (TAC, GPx, GST, and SOD) were evaluated. The study comprised 31 patients (87.1% men), with a mean age of 61.3 ± 9.1 years. Hematological variables showed significant differences in the patients with a lower consumption of ω3 fatty acids. A lower mortality and longer survival were found in the group with ω3 fatty acid consumption ≥50th percentile but the differences were not significant. No significant difference was reached in toxicity, inflammation, and oxidative stress markers. The group with ω3 fatty acid consumption

Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. METHODS We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). RESULTS When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression ≥ P50 before bariatric surgery had a lower percentage hip circumference loss (

Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; OBJECTIVE Zinc-α(2) glycoprotein (ZAG) stimulates lipid loss by adipocytes and may be involved in the regulation of adipose tissue metabolism. However, to date no studies have been made in the most extreme of obesity. The aims of this study are to analyze ZAG expression levels in adipose tissue from morbidly obese patients, and their relationship with lipogenic and lipolytic genes and with insulin resistance (IR). METHODS mRNA expression levels of PPARγ, IRS-1, IRS-2, lipogenic and lipolytic genes and ZAG were quantified in visceral (VAT) and subcutaneous adipose tissue (SAT) of 25 nondiabetic morbidly obese patients, 11 with low IR and 14 with high IR. Plasma ZAG was also analyzed. RESULTS The morbidly obese patients with low IR had a higher VAT ZAG expression as compared with the patients with high IR (p = 0.023). In the patients with low IR, the VAT ZAG expression was greater than that in SAT (p = 0.009). ZAG expression correlated between SAT and VAT (r = 0.709, p

BACKGROUND: A key role for HIF-1α in the promotion and maintenance of dietary obesity has been proposed. We analyzed the association between hypoxia and de novo lipogenesis in human adipose tissue. METHODS: We studied HIF-1α mRNA and protein expression in fasting status in visceral adipose tissue (VAT) from non-obese and morbidly obese subjects, and in VAT from wild-type and ob/ob C57BL6J mice in both fasting and feeding status. We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis. RESULTS: HIF-1α was increased in VAT from morbidly obese subjects. In fasting status, C57BL6J ob/ob mice had a higher VAT HIF-1α mRNA expression than C57BL6J wild-type mice. In feeding status, VAT HIF-1α mRNA expression significantly increased in C57BL6J wild-type, but not in C57BL6J ob/ob mice. In humans, HIF-1α mRNA expression correlated positively with body mass index and insulin resistance. VAT HIF-1α mRNA expression correlated negatively with ACC1, PDHB and SIRT3 mRNA expression, and positively with PPAR-γ. VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression. CONCLUSIONS: Morbidly obese subjects have a higher level of VAT HIF-1α. Postprandial status is associated with an increase in HIF-1α mRNA expression in C57BL6J wild-type mice. Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT. Yes

[This corrects the article DOI: 10.3389/fimmu.2024.1415804.]., (Copyright © 2024 Garcia-Flores, Dawid De Vera, Pilo, Rego, Gomez-Casado, Arranz-Salas, Martín, Alcaide, Torres, Ortega-Gomez, Boughanem and Macias-Gonzalez.)