Exploring the link between hedonic overeating and prefrontal cortex dysfunction in the Ts65Dn trisomic mouse model.

Individuals with Down syndrome (DS) have a higher prevalence of obesity compared to the general population. Conventionally, this has been attributed to endocrine issues and lack of exercise. However, deficits in neural reward responses and dopaminergic disturbances in DS may be contributing factors. To investigate this, we focused on a mouse model (Ts65Dn) bearing some triplicated genes homologous to trisomy 21. Through detailed meal pattern analysis in male Ts65Dn mice, we observed an increased preference for energy-dense food, pointing towards a potential "hedonic" overeating behavior. Moreover, trisomic mice exhibited higher scores in compulsivity and inflexibility tests when limited access to energy-dense food and quinine hydrochloride adulteration were introduced, compared to euploid controls. Interestingly, when we activated prelimbic-to-nucleus accumbens projections in Ts65Dn male mice using a chemogenetic approach, impulsive and compulsive behaviors significantly decreased, shedding light on a promising intervention avenue. Our findings uncover a novel mechanism behind the vulnerability to overeating and offer potential new pathways for tackling obesity through innovative interventions.

Effectiveness, Toxicity, and Survival Predictors of Regorafenib in Metastatic Colorectal Cancer: A Multicenter Study of Routinely Collected Data.

OBJECTIVES: To assess the effectiveness and toxicity of regorafenib in patients with metastatic colorectal cancer (mCRC) in routine clinical practice, as well as predictive factors of effectiveness. METHODS: This was a retrospective multicenter study in patients with mCRC who received regorafenib from November 2013 to May 2020. Effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method. Cox regression was performed to determine survival predictors. RESULTS: Ninety patients were enrolled (median age, 64.3 years). Fifty-two patients (57.8%) were male, and 57 (63.3%) had an ECOG performance status (PS) of 0 to 1. Median follow-up was 2.80 months. Median OS was 8.03 months (95% CI, 5.90-10.17), and median PFS was 2.90 months (95% CI, 2.59-3.21). Eighty-eight patients (97.8%) experienced drug-related adverse events. The most frequent were fatigue in 66 patients (73.3%), followed by palmar-plantar erythrodysesthesia in 40 (44.4%). Low liver tumor burden score (LTBS) and good ECOG PS were independent OS predictive factors. CONCLUSIONS: Patients taking regorafenib had OS and PFS rates similar to those reported in previous randomized trials; the agent had a poor toxicity profile. We identified low LTBS and good ECOG PS as possible predictive factors of better OS, useful in selecting patients with mCRC who might benefit from regorafenib.

Exclusively Breastfed Infant Microbiota Develops over Time and Is Associated with Human Milk Oligosaccharide Intakes.

Temporal development of maternal and infant microbiomes during early life impacts short- and long-term infant health. This study aimed to characterize bacterial dynamics within maternal faecal, human milk (HM), infant oral, and infant faecal samples during the exclusive breastfeeding period and to document associations between human milk oligosaccharide (HMO) intakes and infant oral and faecal bacterial profiles. Maternal and infant samples (n = 10) were collected at 2−5, 30, 60, 90 and 120 days postpartum and the full-length 16S ribosomal RNA (rRNA) gene was sequenced. Nineteen HMOs were quantitated using high-performance liquid chromatography. Bacterial profiles were unique to each sample type and changed significantly over time, with a large degree of intra- and inter-individual variation in all sample types. Beta diversity was stable over time within infant faecal, maternal faecal and HM samples, however, the infant oral microbiota at day 2−5 significantly differed from all other time points (all p < 0.02). HMO concentrations and intakes significantly differed over time, and HMO intakes showed differential associations with taxa observed in infant oral and faecal samples. The direct clinical relevance of this, however, is unknown. Regardless, future studies should account for intakes of HMOs when modelling the impact of HM on infant growth, as it may have implications for infant microbiota development.

Human Milk Oligosaccharides and Bacterial Profile Modulate Infant Body Composition during Exclusive Breastfeeding.

Human milk is a complex and variable ecosystem fundamental to the development of newborns. This study aimed to investigate relationships between human milk oligosaccharides (HMO) and human milk bacterial profiles and infant body composition. Human milk samples (n = 60) were collected at two months postpartum. Infant and maternal body composition was measured with bioimpedance spectroscopy. Human milk bacterial profiles were assessed using full-length 16S rRNA gene sequencing and 19 HMOs were quantitated using high-performance liquid chromatography. Relative abundance of human milk bacterial taxa were significantly associated with concentrations of several fucosylated and sialylated HMOs. Individual human milk bacteria and HMO intakes and concentrations were also significantly associated with infant anthropometry, fat-free mass, and adiposity. Furthermore, when data were stratified based on maternal secretor status, some of these relationships differed significantly among infants born to secretor vs non-secretor mothers. In conclusion, in this pilot study the human milk bacterial profile and HMO intakes and concentrations were significantly associated with infant body composition, with associations modified by secretor status. Future research designed to increase the understanding of the mechanisms by which HMO and human milk bacteria modulate infant body composition should include intakes in addition to concentrations.

Antibacterial activity of Morinda citrifolia Linneo seeds against Methicillin-Resistant Staphylococcus spp.

In traditional medicine, Morinda citrifolia (Noni) is used to treat various ailments, including skin and respiratory-tract infections. In this work, a bio-directed study (seed extracts) with five bacteria was carried out against four clinical isolates of Methicillin-Resistant Staphylococcus (MRS) and Staphylococcus aureus ATCC 29213 strain to find molecules capable of inhibiting them. Three organic extracts were obtained by maceration of the noni seeds with ascending polarity solvents (n-hexane, dichloromethane and methanol) that were evaluated as antibacterial in the model of bioautography and broth microdilution techniques. The results showed that the methanolic extract was the most active against all bacteria (MIC = 16 mg/mL). The chromatographic fractionation performed on this extract allowed obtaining six fractions (EMF1-EMF6), of which F1, F2 and F5 exhibited activity against some of the bacteria. EMF1 fraction reached an MIC of 25 µg/mL against S. haemolyticus twice as much as the positive control, in which the chemical content is mainly composed of a mixture of γ-butyrolactones (1-2) and esterified fatty acids (3-9); chemical characterization of the nine compounds was carried out based on gas chromatography coupled to masses. EMF2 fraction, presented an MIC of 200 µg/mL against S. aureus 0198 and S. haemolyticus 562B, where a coumarin known as scopoletin (10) was isolated and active against S. aureus 0198 (MIC = 100 µg/mL). EMF5 fraction demonstrated an MIC of 200 µg/mL against S. aureus 0198, S. haemolyticus 562B and S. epidermidis 1042, in which a neolignan known as americanin A (11) was identified, showing activity against S. haemolyticus 562B and S. epidermidis 1042 (MIC = 100 µg/mL). The chemical characterization of isolated compounds 10 and 11 was performed by the analysis of 1H and 13C NMR. Therefore, the methanolic extract, identified and isolated compounds showed important antibacterial activity against the MRS, validating its use in traditional medicine.

Sociodemographic correlates and family aggregation of leukocyte telomere length in adults and children from Mesoamerica.

OBJECTIVE: Telomere length is a biomarker of cumulative stress and inflammation related to chronic disease risk. We examined the associations of leukocyte telomere length (LTL) with sociodemographic and anthropometric variables and estimated LTL family aggregation in Central America, a region with a high burden of chronic disease where LTL has not been studied. METHODS: We conducted a cross-sectional study of 174 school age children and their parents in the capital cities of Belize, Honduras, Nicaragua, Costa Rica, Panama, and the city of Tuxtla-Gutierrez in Mexico. We measured LTL by quantitative PCR in DNA extracted from whole blood. We compared the distribution of LTL by categories of sociodemographic and anthropometric characteristics using linear regression. Family aggregation was estimated with correlation coefficients and intraclass correlations. RESULTS: In mothers, LTL was inversely associated with age (P, trend < .0001) and positively associated with height (P = .0002). Among fathers, LTL was inversely associated with food insecurity (P, trend = .0004). In children, boys had 0.10 log units shorter LTL than girls (95% CI: -0.17, -0.03; P = .004). LTL was inversely associated with parental education (P, trend = .01) and positively associated with paternal age at birth (P, trend < .0001), maternal LTL (P, trend = .007), and paternal LTL (P, trend = .02). LTL varied significantly by country of origin among all family members. Aggregation was greatest between children and their mothers, and mostly occurred at the country, rather than family, level. CONCLUSION: LTL is associated with age and height in women; food insecurity in men; and sex, parental education, parental LTL, and paternal age at birth among children.

Correlates and family aggregation of vitamin D concentrations in school-aged children and their parents in nine Mesoamerican countries.

OBJECTIVE: To determine the associations of sociodemographic characteristics, diet and outdoor activity as an indicator of sun exposure with serum 25-hydroxyvitamin D (25(OH)D) concentrations in children and their parents from Mesoamerica. We also quantified family aggregation of serum 25(OH)D. DESIGN: Cross-sectional study. Serum 25(OH)D concentrations were quantified using immunoassay. We compared the distribution of 25(OH)D concentrations in adults and children by levels of each correlate with the use of linear regression. Family aggregation was estimated using Pearson and intraclass correlation coefficients. SETTING: Capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Costa Rica, Panama and Belize, and Tuxtla Gutiérrez in Mexico. SUBJECTS: Children (n 223) aged 7-12 years and 492 parents. RESULTS: Mean (sd) 25(OH)D concentrations in adults and children were 81·3 (21·1) and 79·5 (18·1) nmol/l, respectively. Prevalence of vitamin D deficiency (VDD; 25(OH)D <50 nmol/l) was 3·9 % among adults and 3·6 % among children. In adults, adjusted mean 25(OH)D concentrations were highest in Nicaragua (P<0·0001). Serum 25(OH)D was positively related to time spent gardening (P=0·03). Among children, 25(OH)D concentrations were positively associated with male sex (P=0·005), dairy intake (P=0·03) and mother's serum 25(OH)D concentrations (P<0·0001); and inversely associated with mother's BMI (P=0·02) and number of home assets (P=0·04). Family membership explained 31 % of the variability in 25(OH)D concentrations; aggregation was highest between mothers and children. CONCLUSIONS: VDD prevalence was low in this study. Sociodemographic characteristics, diet and outdoor activity predict serum 25(OH)D. Family aggregation of serum 25(OH)D is high between mothers and children.

Prevalence and sociodemographic correlates of metabolic syndrome in school-aged children and their parents in nine Mesoamerican countries.

OBJECTIVE: To ascertain the prevalence and sociodemographic correlates of cardiometabolic risk factors in adults and school-aged children from Mesoamerica. DESIGN: Cross-sectional study with convenience sampling. In adults, metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III (ATP III) criteria. In children, we calculated a continuous sex- and age-standardized metabolic risk score using variables corresponding to adult ATP III criteria. Metabolic syndrome prevalence in adults and risk score distribution in children were compared across levels of sociodemographic characteristics with use of Poisson and linear regression, respectively. SETTING: Capital cities of Guatemala, El Salvador, the Dominican Republic, Honduras, Nicaragua, Panama, Costa Rica, the Mexican State of Chiapas (Tuxtla Gutiérrez city) and Belize. SUBJECTS: Families (n 267), comprising one child aged 7-12 years and their biological parents. RESULTS: The prevalence of metabolic syndrome was 37·9 % among women and 35·3 % among men. The most common component was low HDL cholesterol, 83·3 % in women and 78·9 % in men. Prevalence was positively associated with age. In women, metabolic syndrome was inversely related to education level whereas in men it was positively associated with household food security and height, after adjustment. The metabolic risk score in children was inversely related to parental height, and positively associated with height-for-age and with having parents with the metabolic syndrome. CONCLUSIONS: Metabolic syndrome is highly prevalent in Mesoamerica. The burden of metabolic risk factors disproportionately affects women and children of lower socio-economic status and men of higher socio-economic status.

Investigations on the Degradation Behavior of Processed FeMnSi-xCu Shape Memory Alloys.

A new functional Fe-30Mn-5Si-xCu (x = 1.5 and 2 wt%) biomaterial was obtained from the levitation induction melting process and evaluated as a biodegradable material. The degradation characteristics were assessed in vitro using immersion tests in simulated body fluid (SBF) at 37 ± 1 °C, evaluating mass loss, pH variation that occurred in the solution, open circuit potential (OCP), linear and cyclic potentiometry (LP and CP), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS) and nano-FTIR. To obtain plates as samples, the cast materials were thermo-mechanically processed by hot rolling. Dynamic mechanical analysis (DMA) was employed to evaluate the thermal properties of the smart material. Atomic force microscopy (AFM) was used to show the nanometric and microstructural changes during the hot rolling process and DMA solicitations. The type of corrosion identified was generalized corrosion, and over the first 3-5 days, an increase in mass was observed, caused by the compounds formed at the metal-solution interface. The formed compounds were identified mainly as oxides that passed into the immersion liquid. The degradation rate (DR) was obtained as a function of mass loss, sample surface area and immersion duration. The dynamic mechanical behavior and dimensions of the sample were evaluated after 14 days of immersion. The nanocompounds found on the surface after atmospheric corrosion and immersion in SBF were investigated with the Neaspec system using the nano-FTIR technique.

Livestock and environmental characterization of Colombian municipalities: study of vesicular stomatitis.

Amid the surge in data volume generated across various fields of knowledge, there is an increasing necessity for advanced analytical methodologies to effectively process and utilize this information. Particularly in the field of animal health, this approach is pivotal for enhancing disease understanding, surveillance, and management. The main objective of the study was to conduct a comprehensive livestock and environmental characterization of Colombian municipalities and examine their relationship with the distribution of vesicular stomatitis (VS). Utilizing satellite imagery to delineate climatic and land use profiles, along with data from the Colombian Agricultural Institute (ICA) concerning animal populations and their movements, the research employed Principal Component Analysis (PCA) to explore the correlation between environmental and livestock-related variables. Additionally, municipalities were grouped through a Hierarchical Clustering process. The assessment of risk associated with VS was carried out using a Generalized Linear Model. This process resulted in the formation of four distinct clusters: three primarily characterized by climatic attributes and one predominantly defined by livestock characteristics. Cluster 1, identified as "Andino" due to its climatic and environmental features, exhibited the highest odds ratio for VS occurrence. The adopted methodology not only provides a deeper understanding of the local population and its context, but also offers valuable insights for enhancing disease surveillance and control programs.

Sterilization of free-ranging female capybaras (Hydrochoerus hydrochaeris): a comparison between two surgical techniques.

This study evaluated two surgical sterilization techniques in free-ranging female capybaras (n = 21). The first group underwent uterine horn ligature (HL; n = 11), while the second was subjected to partial salpingectomy (S; n = 10). We assessed total operative time, incision length, the ease of identifying reproductive structures, the adequacy of exposure for surgical performance through flank or midline approaches, and the extent of abdominal viscera manipulation for each method. The HL method emerged as faster, with an average operative time difference of 16 minutes. In the S group, a flank mini-laparotomy over the ovarian topography facilitated easy exposure of the ipsilateral ovary and uterine tube, enabling ligature and partial resection of the uterine tube but not the uterine horn exposure. However, accessing the contralateral uterine tube without a bilateral incision was impractical, thus prolonging the total operative time due to the need for patient repositioning and new antisepsis procedures. Conversely, a post-umbilical approach for the HL method necessitated only one mini-laparotomy incision, offering ample uterine exposure for hysterotomy in pregnant females. Both methods involved minimal abdominal viscera manipulation and resulted in no fatalities or postoperative complications. Although direct comparison is limited by the distinct sterilization techniques and surgical approaches, this study underscores the challenges and surgical access of each method. Our findings endorse the HL technique as an effective contraception method for female capybaras to prevent the birth of seronegative offspring that could amplify Rickettsia sp., the causative agent of Brazilian spotted fever.

Ultra-high performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry for the identification of non-volatile compounds migrating from 'natural' dishes.

Although most new biomaterials for food industry applications are labelled '100% natural fabrication' and 'chemical-free', certain compounds may migrate from those materials to the food, compromising the organoleptic characteristics and safety of the product. In this work, the degree of compound migration from dishes made with four different biomaterials: bamboo, palm leaf, wood and wheat pulp was investigated. Migration tests were carried out using three food simulants, 10% ethanol (simulant A), 3% acetic acid (simulant B), and 95% ethanol (simulant D2). Unequivocal identification of non-intentionally added substances (NIAS) is challenging even when using high-resolution mass spectrometry techniques however, a total of 25 different non-volatile compounds from the migration tests were identified and quantified using Ultra-high performance liquid chromatography coupled to ion mobility quadrupole time-of-flight mass spectrometry (UPLC-IMS-MS). In the bamboo samples three oligomers, cyclic diethylene glycol adipate, 3,6,9,16,19,22-hexaoxabicyclo[22.3.1]-octacosa-1(28),24,26-triene-2,10,15,23-tetrone and 1,4,7,14,17,20-hexaoxacyclohexacosane-8,13,21,26-tetrone exceeded the specified limits of migration.

Analysis of Degradation Products of Biodegradable ZnMgY Alloy.

Biodegradable metallic materials are increasingly gaining ground in medical applications. Zn-based alloys show a degradation rate between those recorded for Mg-based materials with the fastest degradation rate and Fe-based materials with the slowest degradation rate. From the perspective of medical complications, it is essential to understand the size and nature of the degradation products developed from biodegradable materials, as well as the stage at which these residues are eliminated from the body. This paper presents investigations conducted on the corrosion/degradation products of an experimental material (ZnMgY alloy in cast and homogenized state) after immersion tests in three physiological solutions (Dulbecco's, Ringer's and simulated body fluid (SBF)). Scanning electron microscopy (SEM) was used to highlight the macroscopic and microscopic aspects of corrosion products and their effects on the surface. An X-ray energy dispersive detector (EDS), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) provided general information about the compounds based on their non-metallic character. The pH of the electrolyte solution was recorded for 72 h during immersion. The pH variation of the solution confirmed the main reactions proposed for the corrosion of ZnMg. The agglomerations of corrosion products were on the micrometer scale, mainly oxides, hydroxides and carbonates or phosphates. The corrosion effects on the surface were homogeneously spread, with a tendency to connect and form cracks or larger corrosion zones, transforming the pitting corrosion pattern into a generalized one. It was noticed that the alloy's microstructure strongly influences the corrosion characteristics.

Impact of mini-driver genes in the prognosis and tumor features of colorectal cancer samples: a novel perspective to support current biomarkers.

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths, and its development is associated with the gains and/or losses of genetic material, which leads to the emergence of main driver genes with higher mutational frequency. In addition, there are other genes with mutations that have weak tumor-promoting effects, known as mini-drivers, which could aggravate the development of oncogenesis when they occur together. The aim of our work was to use computer analysis to explore the survival impact, frequency, and incidence of mutations of possible mini-driver genes to be used for the prognosis of CRC. Methods: We retrieved data from three sources of CRC samples using the cBioPortal platform and analyzed the mutational frequency to exclude genes with driver features and those mutated in less than 5% of the original cohort. We also observed that the mutational profile of these mini-driver candidates is associated with variations in the expression levels. The candidate genes obtained were subjected to Kaplan-Meier curve analysis, making a comparison between mutated and wild-type samples for each gene using a p-value threshold of 0.01. Results: After gene filtering by mutational frequency, we obtained 159 genes of which 60 were associated with a high accumulation of total somatic mutations with Log2 (fold change) > 2 and p values < 10-5. In addition, these genes were enriched to oncogenic pathways such as epithelium-mesenchymal transition, hsa-miR-218-5p downregulation, and extracellular matrix organization. Our analysis identified five genes with possible implications as mini-drivers: DOCK3, FN1, PAPPA2, DNAH11, and FBN2. Furthermore, we evaluated a combined classification where CRC patients with at least one mutation in any of these genes were separated from the main cohort obtaining a p-value < 0.001 in the evaluation of CRC prognosis. Conclusion: Our study suggests that the identification and incorporation of mini-driver genes in addition to known driver genes could enhance the accuracy of prognostic biomarkers for CRC.

Influence of Dynamic Strain Sweep on the Degradation Behavior of FeMnSi-Ag Shape Memory Alloys.

Iron-based SMAs can be used in the medical field for both their shape memory effect (SME) and biodegradability after a specific period, solving complicated chirurgical problems that are partially now addressed with shape-memory polymers or biodegradable polymers. Iron-based materials with (28-32 wt %) Mn and (4-6 wt %) Si with the addition of 1 and 2 wt % Ag were obtained using levitation induction melting equipment. Addition of silver to the FeMnSi alloy was proposed in order to enhance its antiseptic property. Structural and chemical composition analyses of the newly obtained alloys were performed by X-ray diffraction (confirming the presence of ε phase), scanning electron microscopy (SEM) and energy-dispersive spectroscopy. The corrosion resistance was evaluated through immersion tests and electrolyte pH solution variation. Dynamic mechanical solicitations were performed with amplitude sweep performed on the FeMnSi-1Ag and FeMnSi-2Ag samples, including five deformation cycles at 40 °C, with a frequency of 1 Hz, 5 Hz and 20 Hz. These experiments were meant to simulate the usual behavior of some metallic implants subjected to repetitive mechanical loading. Atomic force microscopy was used to analyze the surface roughness before and after the dynamic mechanical analysis test followed by the characterization of the surface profile change by varying dynamic mechanical stress. Differential scanning calorimetry was performed in order to analyze the thermal behavior of the material in the range of -50-+200 °C. X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) along with Neaspec nano-FTIR experiments were performed to identify and confirm the corrosion compounds (oxides, hydroxides or carbonates) formed on the surface.

The lipidomic and inflammatory profiles of visceral and subcutaneous adipose tissues are distinctly regulated by the SGLT2 inhibitor empagliflozin in Zucker diabetic fatty rats.

The pharmacological inhibition of sodium-glucose cotransporter 2 (SGLT2) has emerged as a treatment for patients with type 2 diabetes mellitus (T2DM), cardiovascular disease and/or other metabolic disturbances, although some of the mechanisms implicated in their beneficial effects are unknown. The SGLT2 inhibitor (SGLT2i) empagliflozin has been suggested as a regulator of adiposity, energy metabolism, and systemic inflammation in adipose tissue. The aim of our study was to evaluate the impact of a 6-week-empagliflozin treatment on the lipidome of visceral (VAT) and subcutaneous adipose tissue (SAT) from diabetic obese Zucker Diabetic Fatty (ZDF) rats using an untargeted metabolomics approach. We found that empagliflozin increases the content of diglycerides and oxidized fatty acids (FA) in VAT, while in SAT, it decreases the levels of several lysophospholipids and increases 2 phosphatidylcholines. Empagliflozin also reduces the expression of the cytokines interleukin-1 beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNFα), monocyte-chemotactic protein-1 (MCP-1) and IL-10, and of Cd86 and Cd163 M1 and M2 macrophage markers in VAT, with no changes in SAT, except for a decrease in IL-1ß. Empagliflozin treatment also shows an effect on lipolysis increasing the expression of hormone-sensitive lipase (HSL) in SAT and VAT and of adipose triglyceride lipase (ATGL) in VAT, together with a decrease in the adipose content of the FA transporter cluster of differentiation 36 (CD36). In conclusion, our data highlighted differences in the VAT and SAT lipidomes, inflammatory profiles and lipolytic function, which suggest a distinct metabolism of these two white adipose tissue depots after the empagliflozin treatment.

Examining the Role of Histaminergic, Orexinergic, and Cannabinergic Systems in Redox Regulation in Gastric Adenocarcinoma.

Histaminergic, orexinergic, and cannabinoid systems play a role in both physiologic and oncogenic mechanisms in digestive tissues. These three systems are important mediators of tumor transformation, as they are associated with redox alterations, which are key aspects in oncological disorders. The three systems are known to promote alterations in the gastric epithelium through intracellular signaling pathways, such as oxidative phosphorylation, mitochondrial dysfunction, and increased Akt, which might promote tumorigenesis. Histamine promotes cell transformation through redox-mediated alterations in the cell cycle, DNA repair, and immunological response. The increase in histamine and oxidative stress generates angiogenic and metastatic signals through the VEGF receptor and H2R-cAMP-PKA pathway. Immunosuppression in the presence of histamine and ROS is linked to a decrease in dendritic and myeloid cells in gastric tissue. These effects are counteracted by histamine receptor antagonists, such as cimetidine. Regarding orexins, overexpression of the Orexin 1 Receptor (OX1R) induces tumor regression through the activation of MAPK-dependent caspases and src-tyrosine. OX1R agonists are candidates for the treatment of gastric cancer by stimulating apoptosis and adhesive interactions. Lastly, cannabinoid type 2 (CB2) receptor agonists increase ROS, leading to the activation of apoptotic pathways. In contrast, cannabinoid type 1 (CB1) receptor agonists decrease ROS formation and inflammation in gastric tumors exposed to cisplatin. Overall, the repercussion of ROS modulation through these three systems on tumor activity in gastric cancer depends on intracellular and/or nuclear signals associated with proliferation, metastasis, angiogenesis, and cell death. Here, we review the role of these modulatory systems and redox alterations in gastric cancer.

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

In-Vitro Analysis of FeMn-Si Smart Biodegradable Alloy.

Special materials are required in many applications to fulfill specific medical or industrial necessities. Biodegradable metallic materials present many attractive properties, especially mechanical ones correlated with good biocompatibility with vivant bodies. A biodegradable iron-based material was realized through electric arc-melting and induction furnace homogenization. The new chemical composition obtained presented a special property named SME (shape memory effect) based on the martensite transformation. Preliminary results about this special biodegradable material with a new chemical composition were realized for the chemical composition and structural and thermal characterization. Corrosion resistance was evaluated in Ringer's solution through immersion tests for 1, 3, and 7 days, the solution pH was measured in time for 3 days with values for each minute, and electro-corrosion was measured using a potentiostat and a three electrode cell. The mass loss of the samples during immersion and electro-corrosion was evaluated and the surface condition was studied by scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). SME was highlighted with differential scanning calorimetry (DSC). The results confirm the possibility of a memory effect of the materials in the wrought case and a generalized corrosion (Tafel and cyclic potentiometry and EIS) with the formation of iron oxides and a corrosion rate favorable for applications that require a longer implantation period.

Implementation of a methodology to assess patient reported outcomes in lung cancer patients: The PeOpLe (Patient-reported Outcomes in Lung cancer ) study protocol.

OBJECTIVE: The purpose of this article is to describe the PeOpLe study protocol, developed to assess patient-reported health outcomes in  advanced or metastatic non-small-cell lung cancer in routine clinical practice using the methodology provided by the International Consortium for Health Outcomes Measurement tool. METHOD: The study envisaged will be multicenter, longitudinal, ambispective and observational. Two groups will be compared: a control group (followed up according to standard clinical practice) and an experimental group (followed up using the International Consortium for Health  Outcomes Measurement methodology adapted to the Spanish setting for 6  months). The variables collected will be related to demography (age, sex,  degree of family support), clinical factors (smoking, comorbidities, lung  capacity), the neoplasm (histology, staging, mutations), pharmacotherapy  (treatment schedule, modifications, and complications), health status  (functional status, quality of life, satisfaction and overall survival) and resource consumption (emergency visits, hospital admissions and time spent by health providers). The PeOpLe study protocol has been approved by the Ethics Committee for Research into Medicinal Products of the Gregorio Marañón General University Hospital and will be conducted in compliance with prevailing ethical principles and standards. CONCLUSIONS: The PeOpLe study will explore how patient-reported outcomes collection can be developed and integrated with the clinical processes used in  the management of patients with locally advanced or metastatic nonsmall cell  lung cancer what patient-reported outcomes can be measured with systems  that can conveniently be used both by patients and by healthcare providers.  Systematic evaluation of patient-reported outcomes will help determine their  impact in terms of effectiveness (survival), safety (complications of systemic  therapy), and quality of life and patient satisfaction. The multidisciplinary and  multicenter nature of the study will facilitate a comprehensive view of the  subject analyzed and allow external reproducibility.

OBJETIVO: El objetivo es describir el protocolo del estudio PeOpLe, cuyo fin es  evaluar los resultados en salud centrados en el paciente con cáncer de pulmón  no microcítico avanzado o metastásico en la práctica clínica habitual mediante  una metodología adaptada de la herramienta del International Consortium for  Health Outcomes Measurement.Método: Estudio observacional, ambispectivo, longitudinal y multicéntrico. Se  compararán dos grupos: grupo control (seguimiento según práctica clínica  habitual) frente a un grupo intervención (seguimiento mediante la metodología  del International Consortium for Health Outcomes Measurement adaptada al entorno español) durante un período de 6 meses.  Las variables recogidas incluirán aspectos demográficos (edad, sexo, apoyo familiar), clínicos (hábito tabáquico, comorbilidades, capacidad   pulmonar), del tumor (histología, estadiaje, mutaciones), farmacoterapéutico (esquema de tratamiento, modificaciones y  complicaciones), grado de salud (estado funcional, calidad de vida, satisfacción y supervivencia global) y consumo de recursos (visitas a urgencias, ingresos  hospitalarios y tiempo dedicado por los profesionales sanitarios). El protocolo  del estudio PeOpLe ha sido aprobado por el Comité de Ética de la Investigación con medicamentos y se realizará respetando los principios y las normas éticas  básicas. CONCLUSIONES: El estudio PeOpLe explorará cómo se pueden desarrollar e  integrar los procesos de medición de resultados en salud centrados en los  pacientes, especialmente los patient-reported outcomes, en pacientes con  cáncer de pulmón no microcítico localmente avanzado o metastásico en la  práctica clínica. La evaluación sistemática de estos patient-reported outcomes  permitirá conocer su impacto en términos de efectividad (supervivencia),  seguridad (complicaciones de la terapia sistémica) y calidad de vida y  satisfacción. El carácter multidisciplinar y multicéntrico facilitará una visión  integral y su reproducibilidad externa.