Metformin in combination with chemotherapy increases apoptosis in gastric cancer cells and counteracts senescence induced by chemotherapy.

Gastric cancer (GC) is the fourth leading cause of cancer death in the world, and there is a demand for new therapeutic agents to treat GC. Metformin has been demonstrated to be an antineoplastic agent in some types of cancer; however, it has not been sufficiently valued in treating GC because the effect of metformin in combination with chemotherapy regimens has not yet been evaluated. The present study aimed to evaluate the mechanisms underlying cell death induced by metformin alone or when combined with chemotherapy. The cytogenetic characteristics of the NCI-N87 cell line were determined by fluorescence in situ hybridization (FISH). To determine viability, the cells were treated with metformin, epirubicin, cisplatin, docetaxel and 5-fluorouracil (individually and at different concentrations). Subsequently, the cells were treated with metformin alone, and in combination with the chemotherapeutic drugs and the epirubicin + cisplatin + 5-fluorouracil, docetaxel + cisplatin + 5-fluorouracil, and cisplatin + 5-fluorouracil regimens. Cell viability, proliferation and mitochondrial membrane potential (ΔΨm) were analyzed by spectrophotometry. Apoptosis, caspase activity and cell cycle progression were assessed by flow cytometry. Finally, light microscopy was used to evaluate senescence and clonogenicity. The results revealed that metformin, alone and when combined with chemotherapy, increased the proportion of apoptotic cells, promoted the loss of ΔΨm, and induced apoptosis through caspase activity in GC cells. Moreover, metformin decreased cell proliferation. In addition, metformin alone did not induce senescence and it counteracted the effects of chemotherapy-induced senescence in GC cells. Additionally, metformin, alone and when combined with chemotherapy, decreased the clonogenic capacity of NCI-N87 GC cells. In conclusion, metformin may increase the effects of chemotherapy on NCI-N87 cell death and could represent an option to improve the treatment of GC.

Impact of sex on clinical and laboratory parameters in patients with heart failure: insights from the Colombian Heart Failure Registry (RECOLFACA).

INTRODUCTION: Heart failure (HF) is one of the leading causes of morbidity and mortality worldwide. This study aimed to assess the impact of sex on sociodemographic, clinical, and laboratory parameters in patients with HF who were included in the Colombian Heart Failure Registry (RECOLFACA). METHODS: This was a cross-sectional analytical research. All 2528 patients included in RECOLFACA were analysed. The Mann-Whitney U test was used to compare median values as well as first and third quartiles (Q1-Q3). The age-related trend of NT-proBNP levels for both men and women groups was statistically evaluated. RESULTS: The study included 2528 patients with HF (1072 women and 1456 men). The echocardiographic evidence showed that men presented reduced left ventricular ejection fraction (LVEF) (79.63 vs. 69.75%, respectively; p < 0.001) more often than women, which had a significantly higher proportion of preserved LVEF (20.46 vs.11.24%, respectively; p < 0.001). Women displayed a higher value of systolic blood pressure (p < 0.001) and heart rate (p = 0.014) compared to men. Haemoglobin, creatinine, and sodium levels were significantly higher in men. Men had a considerably lower glomerular filtration rate value, with the median reaching a G3a value for chronic renal failure. According to age, the levels of NT-proBNP in each sex increased equivalently with age. CONCLUSION: Sex differences presented in this study are comparable to those discovered in other nations. However, certain variations show that these sex differences may differ by geographical area, which should encourage further investigations to describe them.

Eligibility of sodium-glucose cotransporter-2 inhibitors in heart failure with preserved ejection fraction: Insights from the Colombian heart failure registry (RECOLFACA).

Background: The value of Sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitor) therapy in individuals with heart failure with preserved EF (HFpEF) was unknown until the EMPEROR-Preserved trial. We aimed to assess the proportion of patients with HFpEF that are eligible for empagliflozin therapy within the Colombian Heart Failure Registry (RECOLFACA). Methods: RECOLFACA enrolled adult patients with a HF diagnosis during 2017-2019 from 60 medical centers in Colombia. Criteria of the EMPEROR-Preserved Trial were used to recruit participants. The main outcome was individual eligibility with N-terminal pro-B-type natriuretic peptide (NT-proBNP) criteria, while the secondary outcome was eligibility without NT-proBNP data. Results: RECOLFACA had 799 patients with HFpEF (mean age70.7 ± 13.5; 50.7 % males). According to the major selection criteria of the EMPEROR Preserved Trial, 73.7 % patients would be eligible for empagliflozin therapy initiation when considering the NT-proBNP threshold. The NT-proBNP threshold represented the main determinant of ineligibility in patients with this biomarker measure (13.6 %; n = 16). In patients without NT-proBNP data, the main reasons for exclusion were the diagnosis of symptomatic hypotension or a systolic blood pressure below 100 mmHg (7.5 %), having an eGFR < 20 ml/min/1.73 m2 (4.3 %), and haemoglobin < 9 g/dl (3.1 %). Excluding NT-proBNP criteria increased empagliflozin eligibility to 80.6 %. Conclusion: Most patients with HFpEF from RECOLFACA are potential candidates for empagliflozin therapy initiation according to the EMPEROR-Preserved trial criteria. These findings favor the utilization of SGLT-2 inhibitor medications in daily medical practice, which may further decrease morbidity and mortality in HF patients, regardless of their EF classification.

Salmonellosis in adult cattle in Central Argentina: case series.

Salmonellosis is an infectious disease caused by bacteria belonging to the Salmonella genus. Bovine salmonellosis is more frequent in young cattle under intensive overcrowd husbandry conditions, and therefore uncommon in adults. We report four outbreaks of clinical salmonellosis due to Salmonella Typhimurium, Salmonella Newport and Salmonella Dublin provoking outbreaks of diarrheic/septicemic disease in adult cattle of Central Argentina. Anamnesis information, clinical, pathological, and bacteriological findings were retrospective analyzed. This report emphasizes the importance to include salmonellosis among the differential diagnosis of clinical enteric/septicemic disease in adult cattle under different husbandry conditions in Argentina. The source of Salmonella could not be established in these outbreaks.

Comparative Genomics of the First Resistant Candida auris Strain Isolated in Mexico: Phylogenomic and Pan-Genomic Analysis and Mutations Associated with Antifungal Resistance.

Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes (ERG11 and FKS1) associated with drug resistance in C. auris, a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.

Engineering principles for rationally design therapeutic strategies against hepatocellular carcinoma.

The search for new therapeutic strategies against cancer has favored the emergence of rationally designed treatments. These treatments have focused on attacking cell plasticity mechanisms to block the transformation of epithelial cells into cancerous cells. The aim of these approaches was to control particularly lethal cancers such as hepatocellular carcinoma. However, they have not been able to control the progression of cancer for unknown reasons. Facing this scenario, emerging areas such as systems biology propose using engineering principles to design and optimize cancer treatments. Beyond the possibilities that this approach might offer, it is necessary to know whether its implementation at a clinical level is viable or not. Therefore, in this paper, we will review the engineering principles that could be applied to rationally design strategies against hepatocellular carcinoma, and discuss whether the necessary elements exist to implement them. In particular, we will emphasize whether these engineering principles could be applied to fight hepatocellular carcinoma.

Acute atrazine intoxication in heifers: Case report and toxicological studies.

Atrazine is a triazine organochloride herbicide, frequently used in different agricultural activities. Rare acute intoxication with atrazine is reported in production animals, and its metabolism in mammals is unknown. We report a spontaneous case of atrazine acute intoxication in 16.1% animals of a 168-beef heifer herd exposed to the herbicide at a farm located in Buenos Aires province, Argentina. Affected heifers showed different neurological signs and died suddenly, similar to the previous natural atrazine intoxication report. During autopsy, no gross lesions were observed. Different body fluids and tissues samples were collected during postmortem examination. No relevant histopathological findings were observed. High levels of atrazine and its metabolites were detected in different fluids and tissues by ultra-liquid chromatography high performance coupled to triple quadrupole mass spectrometry. These findings suggest ruminal or hepatic metabolization of atrazine in the exposed cattle. This is the first report of quantification and distribution of atrazine and its metabolites in intoxicated mammals providing relevant information for diagnostic purposes.

Differential modulation of cell morphology, migration, and Neuropilin-1 expression in cancer and non-cancer cell lines by substrate stiffness.

Physical changes in the tumor microenvironment, such as increased stiffness, regulate cancer hallmarks and play an essential role in gene expression, cell morphology, migration, and malignancy. However, the response of cancer cells to stiffness is not homogeneous and varies depending on the cell type and its mechanosensitivity. In this study, we investigated the differential responses of cervical (HeLa) and prostate (PC-3) cancer cell lines, as well as non-tumoral cell lines (HEK293 and HPrEC), to stiffness using polyacrylamide hydrogels mimicking normal and tumoral tissues. We analyzed cell morphology, migration, and the expression of neuropilin 1 (NRP1), a receptor involved in angiogenesis, cell migration, and extracellular matrix remodeling, known to be associated with cancer progression and poor prognosis. Our findings reveal that NRP1 expression increases on substrates mimicking the high stiffness characteristic of tumoral tissue in the non-tumoral cell lines HPrEC and HEK293. Conversely, in tumoral PC-3 cells, stiffness resembling normal prostate tissue induces an earlier and more sustained expression of NRP1. Furthermore, we observed that stiffness influences cell spreading, pseudopodia formation, and the mode of cell protrusion during migration. Soft substrates predominantly trigger bleb cell protrusion, while pseudopodia protrusions increase on substrates mimicking normal and tumor-like stiffnesses in HPrEC cells compared to PC-3 cells. Stiffer substrates also enhance the percentage of migratory cells, as well as their velocity and total displacement, in both non-tumoral and tumoral prostate cells. However, they only improve the persistence of migration in tumoral PC-3 cells. Moreover, we found that NRP1 co-localizes with actin, and its suppression impairs tumoral PC-3 spreading while decreasing pseudopodia protrusion mode. Our results suggest that the modulation of NRP1 expression by the stiffness can be a feedback loop to promote malignancy in non-tumoral and cancer cells, contingent upon the mechanosensitivity of the cells.

Síndrome de Sjögren: identificación de nuevos biomarcadores y mecanismos moleculares implicados en su fisiopatogénesis

Introducción: El Síndrome de Sjögren (SS) es una enfermedad autoinmune de carácter sistémico, que afecta principalmente al sistema glandular exocrino, generando un funcionamiento anormal de las glándulas lacrimales y salivales. Objetivo: proporcionar una actualización sobre la identificación de nuevos biomarcadores y mecanismos moleculares implicados en la fisiopatogénesis del SS. Método: Revisión narrativa de la literatura en diferentes bases de datos, mediante la búsqueda de términos descritos incluidos en los tesauros MESH y DeCs, para artículos publicados a partir del año 2018. Resultados: presentamos evidencia que destaca la identificación de nuevos biomarcadores y mecanismos implicados en la fisiopatogénesis del SS, describiendo las vías de: linfocitos B, catepsina S, cistatina C, quimioquina C-X3-C modificada de ligando 1, quimiocina regulada por activación del timo, células T, proteína morfogenética ósea 6, estimulación del receptor de oxitocina, receptor de zinc, calponina-3. Conclusión: los avances en la tecnología facilita el análisis detallado de la genética y fisiopatogénesis del SS, impulsando el desarrollo de terapias específicas. La búsqueda de biomarcadores no invasivos responde a las limitaciones de los métodos existentes y la invasividad de las biopsias salivales, prometiendo mejoras diagnósticas y terapéuticas.

Introduction: Sjögren's Syndrome (SS) is a systemic autoimmune disease that primarily affects the exocrine glandular system, leading to abnormal lacrimal and salivary gland function. Objective: To provide an update on identifying new biomarkers and molecular mechanisms involved in the pathogenesis of SS. Method: Narrative review of the literature in various databases, searching for terms included in the MESH and DeCs thesauri, for articles published since 2018. Results: We present evidence highlighting the identification of new biomarkers and mechanisms involved in the pathogenesis of SS, describing pathways of B lymphocytes, cathepsin S, cystatin C, modified C-X3-C chemokine ligand 1, thymus activation-regulated chemokine, T cells, bone morphogenetic protein 6, oxytocin receptor stimulation, zinc receptor, and calponin-3. Conclusion: Advances in technology facilitate detailed analysis of the genetics and pathogenesis of SS, driving the development of specific therapies. The search for non-invasive biomarkers is driven by the limitations of existing methods and the invasiveness of salivary gland biopsies, promising diagnostic and therapeutic improvements.

Spontaneous intoxication of sheep by the pollen beetle Astylus atromaculatus: 4 outbreaks in Uruguay and Argentina.

Astylus atromaculatus Blanchard is a native beetle of South America that feeds on pollen. During the summer of 2022-2023 in Argentina and Uruguay, an explosive infestation of these insects occurred in pastures in which ruminants were grazing. This was believed to be associated with a severe drought, which had significantly reduced the flowering of crops. Three farms in Uruguay and one in Argentina were visited to examine the flocks and perform autopsies. Affected sheep had watery diarrhea, anorexia, depression, and ruminal atony. The average morbidity, mortality, and case fatality rates were 7.5%, 4.3%, and 68%, respectively. The main gross findings in all animals were in the jejunum; the serosa had multifocal hemorrhages, and the mucosa was necrotic and covered by a pseudomembrane. Microscopically, the mucosa had partial-to-complete necrosis of the lamina propria, as well as loss of villus and crypt epithelium with neutrophilic infiltration. Overlying the necrotic mucosa was a pseudomembrane of fibrin, cell debris, desquamated epithelial cells, degenerate neutrophils, and bacteria. Many specimens of A. atromaculatus were in all paddocks in which sheep grazed, as well as in the ruminal content of the autopsied animals.

Infected Post-traumatic Bone Defect of the Knee using Bipolar Osteochondral Allograft and 3D Printing: A Case Report.

Introduction: Transplantation with fresh cadaveric osteochondral allograft (FOCA) is frequently used in defects of the femoral condyle and tibial plateau to preserve the knee joint. However, the use of FOCA in bipolar lesions remains controversial in cases with bipolar defects and a history of infection. Case Report: We present a 21-year-old male patient with a massive post-traumatic osteochondral defect of the lateral compartment of the knee and a history of infection, treated by a two-stage approach. In stage 1, infection was eradicated, and joint function recovered with aggressive debridement, polymethyl methacrylate beads, bone cement spacers, and Judet's quadricepsplasty. In stage 2, transplantation was performed with a bipolar FOCA. All treatments were planned using 3D-printed models. Conclusion: The two-stage approach and 3D planning can increase the chances of transplant success by preparing the future allograft bed and obtaining an optimal match between the cadaveric allograft and the patient's defect in cases with potential contraindications, such as a bipolar lesion in the femoral condyle and tibial plateau and a history of infection. A combined approach may lead to a more beneficial outcome for the patient to preserve joint function and improve quality of life.

Feasibility, acceptability and preliminary effectiveness of a community-based group psychosocial support model for conflict survivors in Colombia: An assessment of in-person and remote intervention modalities during the COVID-19 pandemic.

Background: Community-based psychosocial support (CB-PSS) interventions utilizing task sharing and varied (in-person, remote) modalities are essential strategies to meet mental health needs, including during the COVID-19 pandemic. However, knowledge gaps remain regarding feasibility and effectiveness. Methods: This study assesses feasibility, acceptability and preliminary effectiveness of a CB-PSS intervention for conflict-affected adults in Colombia through parallel randomized controlled trials, one delivered in-person (n = 165) and the other remotely (n = 103), implemented during the COVID-19 pandemic and national protests. Interventions were facilitated by nonspecialist community members and consisted of eight problem-solving and expressive group sessions. Findings: Attendance was moderate and fidelity was high in both modalities. Participants in both modalities reported high levels of satisfaction, with in-person participants reporting increased comfort expressing emotions and more positive experiences with research protocols. Symptoms of depression, anxiety and posttraumatic stress disorder improved among in-person participants, but there were no significant changes for remote participants in comparison to waitlist controls. Implications: This CB-PSS intervention appears feasible and acceptable in both in-person and remote modalities and associated with reduction in some forms of distress when conducted in-person but not when conducted remotely. Methodological limitations and potential explanations and areas for future research are discussed, drawing from related studies.

[Impact of a cardiac rehabilitation program on adherence to the mediterranean diet and physical activity in acute coronary syndrome]. / Impacto de un programa de rehabilitación cardiaca en la adherencia a la dieta mediterránea y la actividad física en el síndrome coronario agudo.

Objective: To evaluate the efficacy of a cardiac rehabilitation program (CRP) in improving adherence to non-pharmacological secondary prevention in patients with acute coronary syndrome (ACS). Method: Retrospective study of patients with ACS referred to CRP in a tertiary hospital from 2018 to 2021. Pre-post differences in adherence to physical activity, Mediterranean diet, smoking, and motivation to change were analyzed. Age, sex, and baseline motivation were analyzed in predicting change in adherence. Results: 418 patients were included. At the end of the CRP, the adherence to the mediterranean diet increased (p < 0.05; d = 0.83), frequency of physical activity increased by 2.16 (p < 0.05), and motivation to change remained constant (p = 0.94). Both women and men improved their adherence to the mediterranean diet. Both sexes performed more physical activity at the end of the CRP (1.89 times more in men and 4 times more in women; p < 0.05). An association was found between initial motivation and greater changes in adherence to the mediterranean diet (p < 0.05). An inversely proportional difference was observed between age and adherence to the mediterranean diet (p < 0.05). Conclusions: The CRP, in our hospital environment, has an effect of improving adherence to the mediterranean diet and physical exercise in patients with ACS. The change in adherence to the diet increases as the motivation to change the baseline increases, and age is inversely related to the change in adherence.

Objetivo: Evaluar la eficacia de un programa de rehabilitación cardiaca (PRC) sobre la mejora de la adherencia a las medidas de prevención secundaria no farmacológicas en pacientes con síndrome coronario agudo (SCA). Método: Estudio retrospectivo con pacientes con SCA derivados a PRC en un hospital terciario de 2018 a 2021. Se analizaron diferencias pre-post de adherencia a actividad física, dieta mediterránea, tabaquismo y motivación al cambio. Se analizaron la edad, el sexo y la motivación basal en la predicción del cambio de adherencia. Resultados: Se incluyeron 418 pacientes. Al final del PRC aumentó la adherencia a la dieta mediterránea (p < 0.05; d = 0.83), la frecuencia de actividad física aumentó 2,16 (p < 0.05) y la motivación al cambio se mantuvo constante (p = 0.94). Tanto las mujeres como los hombres mejoraron la adherencia a la dieta mediterránea. Ambos sexos realizaron más ejercicio físico al final del PRC (1.89 veces más los hombres y 4 las mujeres; p < 0.05). Se encontró una asociación entre motivación inicial y mayores cambios en la adherencia a la dieta mediterránea (p < 0.05). Se observó una diferencia inversamente proporcional entre la edad y la adherencia a la dieta mediterránea (p < 0.05). Conclusiones: El PRC, en nuestro medio hospitalario, mejora la adherencia a la dieta mediterránea y al ejercicio físico en los pacientes con SCA. La adherencia a la dieta mediterránea aumenta a medida que lo hace la motivación al cambio basal, mientras que la edad está inversamente relacionada con el cambio de adherencia.

Evaluation of the Effectiveness of Geogrids Manufactured from Recycled Plastics for Slope Stabilization-A Case Study.

This study aimed to investigate the sustainable use of recycled plastics, specifically polypropylene (PP) and high-density polyethylene (HDPE), in the manufacture of geogrids for geotechnical and civil engineering applications. Plastics were collected from a recycling center, specifically targeting containers used for food, cleaning products, and other domestic packaging items. These plastics were sorted according to the Möbius triangle classification system, with HDPE (#2) and PP (#5) being the primary categories of interest. The research methodologically evaluates the mechanical properties of PP/HDPE (0/100, 25/75, 50/50, 75/25 and 100/0% w/w) composites through tensile and flexural tests, exploring various compositions and configurations of geogrids. The results highlight the superiority of pure recycled HDPE processed into 1.3 mm thick laminated yarns and hot air welded for 20 to 30 s, exhibiting a deformation exceeding 60% in comparison to the PP/HDPE composites. Through SolidWorks® Simulation, it was shown that the adoption of a trigonal geogrid geometry optimizes force distribution and tensile strength, significantly improving slope stabilization efficiency. Based on the results obtained, a laboratory-scale prototype geogrid was developed using an extrusion process. The results underscore the importance of careful composite design and yarn configuration selection to achieve the desired mechanical properties and performance in geogrid applications. It emphasizes the potential of recycled plastics as a viable and environmentally friendly solution for stabilizing slopes, contributing to the reduction in plastic waste and promoting sustainable construction practices.

Chemotherapy-induced tubulopathy: a case report series.

Acquired tubulopathies are frequently underdiagnosed. They can be characterized by the renal loss of specific electrolytes or organic solutes, suggesting the location of dysfunction. These tubulopathies phenotypically can resemble Bartter or Gitelman syndrome). These syndromes are infrequent, they may present salt loss resembling the effect of thiazides (Gitelman) or loop diuretics (Bartter). They are characterized by potentially severe hypokalemia, associated with metabolic alkalosis, secondary hyperaldosteronism, and often hypomagnesemia. Tubular dysfunction has been described as nephrotoxic effects of platinum-based chemotherapy. We present 4 cases with biochemical signs of tubular dysfunction (Bartter-like/Gitelman-like phenotype) related to chemotherapy.

The Effect of Ultrasound on the Extraction and Functionality of Proteins from Duckweed (Lemna minor).

The inclusion of protein in the regular human diet is important for the prevention of several chronic diseases. In the search for novel alternative protein sources, plant-based proteins are widely explored from a sustainable and ecological point of view. Duckweed (Lemna minor), also known as water lentil, is an aquatic plant with potential applications for human consumption due to its protein content and carbohydrate contents. Among all the conventional and novel protein extraction methods, the utilization of ultrasound has attracted the attention of scientists because of its effects on improving protein extraction and its functionalities. In this work, a Box-Behnken experimental design was proposed to optimize the alkaline extraction of protein from duckweed. In addition, an exploration of the effects of ultrasound on the morphological, structural, and functional properties of the extracted protein was also addressed. The optimal extraction parameters were a pH of 11.5 and an ultrasound amplitude and processing time of 60% and 20 min, respectively. These process conditions doubled the protein content extracted in comparison to the value from the initial duckweed sample. Furthermore, the application of ultrasound during the extraction of protein generated changes in the FTIR spectra, color, and structure of the duckweed protein, which resulted in improvements in its solubility, emulsifying properties, and foaming capacity.

High risk of coronary artery obstruction during TAVR, how to avoid it?

BACKGROUND: Coronary artery obstruction after percutaneous aortic replacement is a complication with high short-term mortality secondary to the lack of timely treatment. There are various predictors of coronary obstruction prior to valve placement such as the distance from the ostia, the degree of calcification, the distance from the sinuses; In such a situation some measures must be taken to prevent and treat coronary obstruction. CASE PRESENTATION: An 84-year-old male, with severe aortic stenosis and high surgical risk, who was treated with TAVR. However, during the deployment of the valve he presented hemodynamic instability secondary to LMCA obstruction. The intravascular image showed obstruction of the ostium secondary to the displacement of calcium that he was successfully treated with a chimney stent technique. CONCLUSIONS: The high degree of calcification and the left ostium near the annulus are conditions for obstruction of the ostium at the time of valve release; In this context, provisional stenting prior to TAVR in patients at high risk of obstruction should be considered as a safe prevention strategy to achieve the success of the procedure.