Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines.

BACKGROUND: Metformin, a widely prescribed antidiabetic drug, has shown several promising effects for cancer treatment. These effects have been shown to be mediated by dual modulation of the AMPK-mTORC1 axis, where AMPK acts upstream of mTORC1 to decrease its activity. Nevertheless, alternative pathways have been recently discovered suggesting that metformin can act through of different targets regulation. METHODS: We performed a transcriptome screening analysis using HeLa xenograft tumors generated in NOD-SCID mice treated with or without metformin to examine genes regulated by metformin. Western Blot analysis, Immunohistochemical staining, and RT-qPCR were used to confirm alterations in gene expression. The TNMplot and GEPIA2 platform were used for in silico analysis of genes found up-regulated by metformin, in cervical cancer patients. We performed an AMPK knock-down using AMPK-targeted siRNAs and mTOR inhibition with rapamycin to investigate the molecular mechanisms underlying the effect of metformin in cervical cancer cell lines. RESULTS: We shown that metformin decreases tumor growth and increased the expression of a group of antitumoral genes involved in DNA-binding transcription activator activity, hormonal response, and Dcp1-Dcp2 mRNA-decapping complex. We demonstrated that ZFP36 could act as a new molecular target increased by metformin. mTORC1 inhibition using rapamycin induces ZFP36 expression, which could suggest that metformin increases ZFP36 expression and requires mTORC1 inhibition for such effect. Surprisingly, in HeLa cells AMPK inhibition did not affect ZFP36 expression, suggesting that additional signal transducers related to suppressing mTORC1 activity, could be involved. CONCLUSIONS: These results highlight the importance of ZFP36 activation in response to metformin treatment involving mTORC1 inhibition.

Correction: Prevalence and factors associated with self-reported anxiety in adults during the COVID-19 pandemic in Argentina, Brazil, Peru, Mexico, and Spain: A cross-sectional Ibero-American study.

[This corrects the article DOI: 10.1371/journal.pone.0280528.].

Using interoperable nursing care data to improve outcomes for multiple traumas patients with Impaired Physical Mobility.

AIM(S): To demonstrate how interoperable nursing care data can be used by nurses to create a more holistic understanding of the healthcare needs of multiple traumas patients with Impaired Physical Mobility. By proposing and validating linkages for the nursing diagnosis of Impaired Physical Mobility in multiple trauma patients by mapping to the Nursing Outcomes Classification (NOC) and Nursing Interventions Classification (NIC) equivalent terms using free-text nursing documentation. DESIGN: A descriptive cross-sectional design, combining quantitative analysis of interoperable data sets and the Kappa's coefficient score with qualitative insights from cross-mapping methodology and nursing professionals' consensus. METHODS: Cross-mapping methodology was conducted in a Brazilian Level 1 Trauma Center using de-identified records of adult patients with a confirmed medical diagnosis of multiple traumas and Impaired Physical Mobility (a nursing diagnosis). The hospital nursing free-text records were mapped to NANDA-I, NIC, NOC and NNN linkages were identified. The data records were retrieved for admissions from September to October 2020 and involved medical and nursing records. Three expert nurses evaluated the cross-mapping and linkage results using a 4-point Likert-type scale and Kappa's coefficient. RESULTS: The de-identified records of 44 patients were evaluated and then were mapped to three NOCs related to nurses care planning: (0001) Endurance; (0204) Immobility Consequences: Physiological, and (0208) Mobility and 13 interventions and 32 interrelated activities: (6486) Environmental Management: Safety; (0840) Positioning; (3200) Aspiration Precautions; (1400) Pain Management; (0940) Traction/Immobilization Care; (3540) Pressure Ulcer Prevention; (3584) Skincare: Topical Treatment; (1100) Nutrition Management; (3660) Wound Care; (1804) Self-Care Assistance: Toileting; (1801) Self-Care Assistance: Bathing/Hygiene; (4130) Fluid Monitoring; and (4200) Intravenous Therapy. The final version of the constructed NNN Linkages identified 37 NOCs and 41 NICs. CONCLUSION: These valid NNN linkages for patients with multiple traumas can serve as a valuable resource that enables nurses, who face multiple time constraints, to make informed decisions efficiently. This approach of using evidence-based linkages like the one developed in this research holds high potential for improving patient's safety and outcomes. NO PATIENT OR PUBLIC CONTRIBUTION: In this study, there was no direct involvement of patients, service users, caregivers or public members in the design, conduct, analysis and interpretation of data or preparation of the manuscript. The study focused solely on analysing existing de-identified medical and nursing records to propose and validate linkages for nursing diagnoses.

Mutant p53 gain-of-function stimulates canonical Wnt signaling via PI3K/AKT pathway in colon cancer.

Aberrant canonical Wnt signaling is a hallmark of colon cancer. The TP53 tumor suppressor gene is altered in many solid tumors, including colorectal cancer, resulting in mutant versions of p53 (mut-p53) that lose their tumor suppressor capacities and acquire new-oncogenic functions (GOFs) critical for disease progression. Although the mechanisms related to mut-p53 GOF have been explored extensively, the relevance of mut-p53 in the canonical Wnt pathway is not well defined. This work investigated the influence of mut-p53 compared to wt-p53 in ß-catenin-dependent Wnt signaling. Using the TCGA public data from Pan-Cancer and the GEPIA2 platform, an in silico analysis of wt-p53 versus mut-p53 genotyped colorectal cancer patients showed that TP53 (p53) and CTNNB1 (ß-catenin) are significantly overexpressed in colorectal cancer, compared with normal tissue. Using p53 overexpression or p53 knockdown assays of wt-p53 or mut-p53, we found that while wt-p53 antagonizes canonical Wnt signaling, mut-p53 induces the opposite effect, improving the ß-catenin-dependent transcriptional activity and colony formation ability of colon cancer cells, which were both decreased by mut-p53 knockdown expression. The mechanism involved in mut-p53-induced activation of canonical Wnt appears to be via AKT-mediated phosphorylation of Ser 552 of ß-catenin, which is known to stabilize and enhance its transcriptional activity. We also found that while wt-p53 expression contributes to 5-FU sensitivity in colon cancer cells, the RITA p53 reactivating molecule counteracted the resistance against 5-FU in cells expressing mut-p53. Our results indicate that mut-p53 GOF acts as a positive regulator of canonical Wnt signaling and participates in the induction of resistance to 5-FU in colon cancer cells.

Postmastectomy analgesia with subcutaneous infiltration of ketamine with lidocaine in surgical wound. / Analgesia postmastectomía con infiltración subcutánea en herida quirúrgica de ketamina con lidocaína

Background: Ketamine is an analgesic adjuvant useful in acute pain preventive treatment. However, there are few studies evaluating its efficacy in local administration for postoperative pain management. Objective: To compare ketamine´s efficacy plus 2% lidocaine versus placebo plus 2% lidocaine infiltrated into surgical wound as postoperative analgesia in patients undergoing mastectomy. Material and methods: An experimental, randomized, single-blind study was carried out in 18 patients older than 18 years scheduled for mastectomy under general anesthetic technique. The surgical wound was infiltrated before to its closure with 0.5 mg/kg of ketamine plus 10 mL of simple 2% lidocaine volumetric to 20 mL with saline solution (group 1) or 10 mL saline solution + 10 mL of simple 2% lidocaine (group 2). Each patient was randomly assigned to one of the two intervention groups by draw (from which a piece of paper was drawn indicating the group to which they would belong). The pain intensity was assessed by Analog Numerical Scale (ANS) at 2, 8 and 12 hours after surgery and the need for analgesic rescue doses. Results: The scores on the ANS scale in both groups were similar at leaving (p 0.26) and 2 hours later (p 0.05). The ENA value was lower with 2% ketamine/lidocaine infiltration at 8 hours (ketamine 2.5 [2-3]; placebo 4 [3-7], p 0.01) and 12 hours (ketamine 3 [1-5]; placebo 5 [4-6], p < 0.001). Conclusions: Ketamine infiltrated into the surgical wound provides superior analgesia and improves ENA scores in the post-surgical period.

Introducción: la ketamina es un fármaco ahorrador de opioides y adyuvante analgésico, útil en el tratamiento preventivo del dolor agudo postoperatorio. Sin embargo, existen pocos estudios que evalúen su eficacia en su administración local para el manejo de dolor postoperatorio. Objetivo: comparar la eficacia de la ketamina más lidocaína al 2% frente a placebo más lidocaína al 2% infiltrada en herida quirúrgica como analgesia postoperatoria en pacientes sometidas a cirugía de mama. Material y métodos: se realizó un estudio experimental, prospectivo y aleatorizado en 18 pacientes mayores de 18 años programadas para mastectomía bajo técnica anestésica general. El sitio quirúrgico se infiltró con 0.5 mg/kg de ketamina más 10 mL de lidocaína al 2% aforado a 20 mL con solución salina (grupo 1) o solución salina 10 mL + 10 mL de lidocaína simple al 2% (grupo 2). Se valoró la intensidad del dolor mediante la Escala Numérica Análoga (ENA) a las 2, 8, y 12 horas posteriores a la cirugía y la necesidad de dosis de rescate analgésico. Resultados: las puntuaciones en la ENA en ambos grupos fueron similares al salir (p 0.26) y 2 horas posteriores (p 0.05). El valor de la ENA fue menor con la infiltración de ketamina/lidocaína 2% a las 8 horas (ketamina 2.5 [2-3]; placebo 4 [3-7], p 0.01) y 12 horas (ketamina 3 [1-5]; placebo 5 [4-6], p < 0.001). Conclusiones: la ketamina infiltrada en la herida quirúrgica provee analgesia superior, brinda seguridad y mejora las puntuaciones de la ENA en el periodo postquirúrgico.

Clinical, imaging, and laboratory characteristics of patients with COVID-19 according to ICU admission requirement in Cali, Colombia / Características clínicas, imagenológicas y de laboratorio de pacientes con COVID-19 según requerimiento de ingreso a UCI en Cali, Colombia

Abstract Introduction: At present, few studies conducted in Latin America have addressed the demographic, clinical, and laboratory characteristics of patients with COVID-19 and intensive care unit (ICU) admission requirement. Objective: To compare the sociodemographic, clinical, imaging, and laboratory characteristics of patients diagnosed with COVID -19 and treated in the emergency department of a hospital in Cali, Colombia, based on ICU admission requirement. Materials and methods: Retrospective and descriptive single cohort study conducted in 49 adults with COVID-19 treated in the emergency department of a quaternary care hospital in Cali (Colombia) between March and April 2020. Patients were divided into two groups: ICU admission requirement (n=24) and non-ICU admission requirement (n=25). Bivariate analyses were performed to determine differences between groups (chi-square, Fisher's exact, Student's t, and Mann-Whitney U tests), with a significance level of p<0.05. Results: Participants' mean age was 53 years (SD=13) and 29 patients were men. Significant differences were found between groups in the following variables: mean age (ICU x̅ =58 vs. Non-ICU x̅ =49; p=0.020), presence of diabetes (8 vs. 1; p=0.010); presence of respiratory distress (20 vs. 11; p=0.007) ; unilateral or bilateral presence of areas of consolidation (12 vs. 3; p=0.005); median leukocyte (Med=7 570/mm3 vs. Med=5 130/mm3; p=0.0013), neutrophil (Med=5 980/mm3 vs. Med=3 450/mm3; p=0.0001) and lymphocyte (Med=865/mm3 vs. Med=1 400/mm3; p<0.0001) count; median C-reactive protein (Med=141,25mg/L vs. Med=27.95mg/L; p<0.001), ferritin (Med=1038ng/L vs. Med=542.5ng/L; p=0.0073) and lactate dehydrogenase (Med=391U/L vs. Med=248.5U/L, p=0.0014) levels. Finally, 15 patients required invasive mechanical ventilation, 2 presented with extubation failure, and 5 died. Conclusions. Significant differences were observed in the values of several inflammatory markers, cellular damage and complete blood count parameters between patients who required admission to the ICU and those who did not, so these variables could be used to develop tools that contribute to establishing the prognosis of this disease.

Resumen Introducción. Actualmente hay pocos estudios en Latinoamérica sobre las características demográficas, clínicas y de laboratorio de pacientes con COVID-19 y con requerimiento de ingreso a la unidad de cuidados intensivos (UCI). Objetivo. Comparar las características sociodemográficas, clínicas, imagenológicas y de laboratorio de pacientes diagnosticados con COVID-19 atendidos en el servicio de urgencias de una clínica en Cali, Colombia, según requerimiento de ingreso a UCI. Materiales y métodos. Estudio retrospectivo descriptivo de cohorte única realizado en 49 adultos con COVID-19 atendidos en el servicio de urgencias de un hospital de cuarto nivel de atención de Cali entre marzo y abril de 2020, los cuales se dividieron en dos grupos: requerimiento de ingreso a UCI (n=24) y no requerimiento de ingreso a UCI (n=25). Se realizaron análisis bivariados para determinar las diferencias entre ambos grupos (pruebas de chi-cuadrado, exacta de Fisher, t de Student y U de Mann-Whitney), con un nivel de significancia de p<0.05. Resultados. La edad promedio fue 53 años (DE=13) y 29 pacientes fueron hombres. Se encontraron diferencias significativas entre ambos grupos en las siguientes variables: edad promedio (UCI x̅ =58 vs. No UCI x̅=49; p=0.020); presencia de diabetes (8 vs. 1; p=0.010); presencia de dificultad respiratoria (20 vs. 11; p=0.007); presencia uni o bilateral de áreas de consolidación (12 vs. 3; p=0.005), y mediana del conteo de leucocitos (Med=7 570/mm3 vs. Med=5 130/mm3; p=0.0013), neutrófilos (Med=5 980/mm3 vs. Med=3 450/mm3; p=0.0001), linfocitos (Med=865/mm3 vs. Med=1 400/mm3; p<0.0001), proteína C reactiva (Med=141.25 mg/L vs. Med=27.95 mg/L; p<0.001), ferritina (Med=1038 ng/L vs. Med=542.5 ng/L; p=0.0073) y lactato-deshidroge-nasa (Med=391 U/L vs. Med=248.5 U/L; p=0.0014). Finalmente, 15 pacientes requirieron ventilación mecánica invasiva, 2 presentaron extubación fallida y 5 fallecieron. Conclusiones. Se observaron diferencias significativas en los valores de varios marcadores inflamatorios, daño celular y parámetros del hemograma entre los pacientes que requirieron admisión a la UCI y los que no, por lo que estas variables podrían emplearse para desarrollar herramientas que contribuyan a establecer el pronóstico de esta enfermedad.

Pyrethroid genetic resistance in the dengue vector (Aedes aegypti) in Posadas, Argentina.

Pyrethroids are extensively used to control adult populations of the arboviral vector Aedes aegypti, raising concerns regarding the increasing frequency and distribution of insecticide resistance mutations (kdr: knock-down resistance) in the voltage-gated sodium channel gene (Nav). The widespread use of pyrethroids imposes a threat to the success of mosquito control and the environment. In this study, we investigated the presence of two kdr mutations (V1016I and F1534C) in the Nav gene and their distribution across four neighborhoods in Posadas, Argentina, with different Ae. aegypti abundance and contrasting socioeconomic status (SES). Alleles at each locus were interrogated using TaqMan SNP genotyping assays in DNA extracted from adult females collected in a longitudinal study. We report the presence of both pyrethroid resistance alleles (kdr 1016I = 29.08%; kdr 1534C = 70.70%) among adult females. The frequency of combined kdr genotypes reveals that approximately 70% of local adult females have enhanced resistance to pyrethroids. Both, the proportion of resistant adult females (with at least one kdr allele in each locus) and Ae. aegypti abundance showed an uneven distribution between neighborhoods with different SES (p < 0.001). In high-SES neighborhoods, we found more mosquitoes and a higher frequency of pyrethroid resistance, possibly as a consequence of different public health interventions, social habits, and insecticide use. This is the first report of kdr mutations in Ae. Aegypti in the northeast region of Argentina. Our results focus on the need for within-population (city) distribution analyses of kdr mutations and highlight the relevance of incorporating insecticide resistance monitoring within the Integrated Vector Management initiative.

Prevalence and factors associated with self-reported anxiety in adults during the COVID-19 pandemic in Argentina, Brazil, Peru, Mexico, and Spain: A cross-sectional Ibero-American study.

The present study evaluated the factors associated with the perception of anxiety during the first wave of covid-19 in Ibero-American countries. This cross-sectional study was carried out with 5.845 participants of both sexes, over 18 years of age, and residents of four Latin American countries-Argentina (16.7%), Brazil (34.5%), Mexico (11.1%), and Peru (17.5%), and one European country-Spain (20.1%). Data were collected in 2020, between April 1st and June 30th in Spain and between July 13th and September 26th in the Latin American countries. We used an online questionnaire with sociodemographic, lifestyle, self-reported anxiety, and covid-19 related questions. The chi-square statistical test and Multivariate logistic regressions were performed to analyze the factors associated with self-reported anxiety. The presence of self-reported anxiety was found in 63.8% of the participants during the isolation period. The association occurred mainly in women (OR:1.52; CI: 1.3-1.7), those aged 18 to 29 years (OR: 1.51; CI: 1.2-1.9) and 30 to 49 years (OR: 1.56; CI: 1.3-1.9), residents of Argentina (OR: 1.55 CI: 1.2-1.9), Brazil (OR: 2.38; CI: 2.0-2.8) and Mexico (OR: 1.52; CI: 1.2-1.9), those who gained weight (OR:1.71 CI: 1.5-1.9) or lost weight (OR: 1.40; CI: 1.2-1.6), and those who reported having slept more (OR: 1.56; CI: 1.3-1.8) or less (OR: 2.89; CI: 2.5-3.4). We conclude that the prevalence of self-reported anxiety in Ibero-American countries was high during the period studied, highlighting a higher likelihood of its occurrence in Brazil, in those who began to sleep less and gained weight.

Identification of RP1 as the genetic cause of retinitis pigmentosa in a multi-generational pedigree using Extremely Low-Coverage Whole Genome Sequencing (XLC-WGS).

MOTIVATION: Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. RESULTS: We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.

Evaluation of the effectiveness of nursing interventions in research from Brazilian postgraduation programs.

PURPOSE: The purpose of this study was to evaluate research from Brazilian postgraduate students who provide evidence of effectiveness for Nursing Interventions Classification (NIC). METHODS: We conducted a literature review study of thesis and dissertations available in the Brazilian Digital Library of Dissertations and Theses (D/T) in May 2021 regardless of the year they were conducted. In those studies that did not utilize the NIC in the effectiveness evaluation, the cross-mapping methodology was employed between NIC and the interventions used by the authors of the studies. RESULTS: Using a systematic process, we identified 91 studies. Twenty-seven met a priori inclusion and exclusion criteria. We found an increase in studies that focused on nursing interventions in the last 10 years (n = 19), a large proportion of clinical trials (n = 16), and the majority of articles from the Southeast region of Brazil (n = 20). The areas of focus were adult and elderly care, and with a special interest in the behavioral domain (n = 11). Two sensitivity criteria were identified in all D/T (n = 27), and each study presented evidence of effectiveness of a minimum of three criteria simultaneously. CONCLUSIONS: Based on the effectiveness criteria, the Brazilian scientific production in postgraduate programs carried out by nurses provides evidence of the effectiveness for NIC nursing interventions. IMPLICATIONS FOR NURSING PRACTICE: It is recommended to conduct further research that uses the NIC in the planning, conduct, and evaluation of interventions, based on effectiveness criteria of nursing sensitivity.

Quality of Life of Chilean Breast Cancer Survivors: Multicentric Study / Qualidade de Vida de Sobreviventes de Câncer de Mama do Chile: Estudo Multicêntrico / Calidad de Vida de Sobrevivientes de Cáncer de Mama de Chile: Estudio Multicentrico

Introduction: As breast cancer survivorship rates increase, so does the necessity to improve survivors' health-related quality of life (HRQoL). Objective: To analyze HRQoL among Chilean breast cancer survivors, in general and considering geographic location. In addition, to correlate HRQoL with age, education level and body mass index (BMI). Method: Cross-sectional observational study which included 125 female breast cancer survivors from three public hospitals in three Chilean Macroregions: Central, North Central, and South. The EORTC Questionnaires, QLQ-C30 and QLQ-BR23, and sociodemographic and clinical records were applied. Results: The mean age was 56.1 (±11.9) years with a HRQoL summary score of 67.6 (21.9). HRQoL was reduced mainly in emotional functioning, pain, and insomnia. Fatigue, dyspnea, appetite loss, constipation, financial difficulties, breast and arm symptoms were also reported. The women from the South Macroregion Hospital presented the worst HRQoL scores for most of the domains [general health, functioning (physical, emotional, cognitive and social), fatigue, and nausea], p<0.001. The summary score of HRQoL was correlated to age (Spearman ́s rho=0.202, p=0.033), BMI (rho=-0.341, p<0.001), and education level (rho=0.310, p=0.001). Conclusion: Women from three Macroregions showed differences in HRQoL. The latter correlated to age, BMI, and education level. Considering the high presence of symptoms, it is necessary to improve survivorship care plans, providing access to rehabilitation in the continuum of care.

Introdução: À medida que as taxas de sobrevivência do câncer de mama aumentam, também aumenta a necessidade de melhorar a qualidade de vida relacionada à saúde (QVRS) dos sobreviventes. Objetivo: Analisar a QVRS em geral e considerando a localização geográfica entre sobreviventes de câncer de mama chilenas. Além disso, correlacionar a QVRS com idade, nível educacional e índice de massa corporal (IMC). Método: Estudo observacional transversal que incluiu 125 mulheres sobreviventes de câncer de mama de três hospitais públicos em três Macrorregiões chilenas: Central, Norte-Central e Sul. Foram utilizados os Questionários EORTC QLQ-C30 e QLQ-BR23 e os registros sociodemográficos e clínicos. Resultado: A média de idade foi de 56,1 (±11,9) anos com escore resumido de QVRS de 67,6 (21,9). A QVRS estava reduzida principalmente no funcionamento emocional, dor e insônia. Fadiga, dispneia, perda de apetite, constipação, dificuldades financeiras, sintomas de braço e mama também foram mencionados. As mulheres do hospital da Macrorregião Sul apresentaram os piores escores de QVRS para a maioria dos domínios [saúde geral, funcionamento (físico, emocional, cognitivo e social), fadiga e náusea], p<0,001. A pontuação geral de QVRS esteve correlacionada com idade (rho de Spearman=0,202, p=0,033), IMC (rho=-0,341, p<0,001) e nível educacional (rho=0,310, p=0,001). Conclusão: As mulheres das três Macrorregiões apresentaram diferenças na QVRS.Esta última se correlacionou com idade, IMC e nível educacional. Considerando a alta presença de sintomas, há necessidade de aprimoramento dos planos de atenção à sobrevivência, possibilitando acesso à reabilitação no contínuo do cuidado

Introducción: A medida que aumentan las tasas de supervivencia al cáncer de mama, también aumenta la necesidad de mejorar la calidad de vida relacionada con la salud (CdV) de las sobrevivientes. Objetivo: Analizar la CdV entre supervivientes chilenas de cáncer de mama, en general y considerando ubicación geográfica. Además, correlacionar CdV con edad, nivel educacional e índice de masa corporal (IMC). Método: Estudio observacional transversal que incluyó a 125 mujeres sobrevivientes de cáncer de mama de tres Hospitales públicos de tres Macrorregiones de Chile: Centro, Centro Norte y Sur. Se utilizaron los Cuestionarios EORTC QLQ-C30 y QLQ-BR23, historias sociodemográficas y clínicas. Resultados: La edad media fue de 56,1 (±11,9) años con una puntuación resumida de CdV de 67,6 (21,9). La CdV estuvo disminuida principalmente en funcionamiento emocional, dolor e insomnio. Fatiga, disnea, pérdida de apetito, estreñimiento, dificultades financieras, síntomas de brazo y mama también fueron reportados. Las mujeres del hospital de la Macrorregión Sur presentaron las peores puntuaciones de calidad de vida en la mayoría de los dominios [salud general, funcionamiento (físico, emocional, cognitivo y social), fatiga y nausea], p<0,001. El puntaje de CdV estuvo correlacionado con edad (rho de Spearman =0,202, p=0,033), IMC (rho=-0,341, p<0,001) y nivel educacional (rho=0,310, p=0,001). Conclusión: Las mujeres pertenecientes a tres regiones presentaron diferencias en la CdV.Esta última se correlacionó con edad, IMC y nivel educacional. Considerando la elevada presencia de síntomas, es necesario mejorar los planes de atención a las sobrevivientes, posibilitando acceso a rehabilitación en el continuo de los cuidados.

Extracellular vesicles from blood of breast cancer women induce angiogenic processes in HUVECs.

Breast cancer is the most frequent malignancy among women in developed countries and the main cause of death related to cancer in women worldwide. Extracellular vesicles (EVs) are vesicles with a variable size enclosed within a phospholipid bilayer that contain a variety of molecules with biological activity. Cancer cells release EVs that induce proliferation, escape from apoptosis, reprogramming energy metabolism, invasion and metastasis. In this study we studied whether EV fractions deprived of platelet EVs from breast cancer women (BC EVs) can mediate cell processes related with angiogenesis in human umbilical vein endothelial cells (HUVECs). Our findings demonstrate that BC EVs enhance migration, invasion and formation of new tubules in HUVECs, compared with EV fractions deprived of platelet EVs from healthy women (Ctrl EVs). In summary, we demonstrate, for the first time, that BC EVs induce cellular processes in HUVECs that participate in angiogenesis.

Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways.

Polyphenols constitute an important group of natural products that are traditionally associated with a wide range of bioactivities. These are usually found in low concentrations in natural products and are now available in nutraceuticals or dietary supplements. A group of polyphenols that include apigenin, quercetin, curcumin, resveratrol, EGCG, and kaempferol have been shown to regulate signaling pathways that are central for cancer development, progression, and metastasis. Here, we describe novel mechanistic insights on the effect of this group of polyphenols on key elements of the signaling pathways impacting cancer. We describe the protein modifications induced by these polyphenols and their effect on the central elements of several signaling pathways including PI3K, Akt, mTOR, RAS, and MAPK and particularly those affecting the tumor suppressor p53 protein. Modifications of p53 induced by these polyphenols regulate p53 gene expression and protein levels and posttranslational modifications such as phosphorylation, acetylation, and ubiquitination that influence stability, subcellular location, activation of new transcriptional targets, and the role of p53 in response to DNA damage, apoptosis control, cell- cycle regulation, senescence, and cell fate. Thus, deep understanding of the effects that polyphenols have on these key players in cancer-driving signaling pathways will certainly lead to better designed targeted therapies, with less toxicity for cancer treatment. The scope of this review centers on the regulation of key elements of cancer signaling pathways by the most studied polyphenols and highlights the importance of a profound understanding of these regulations in order to improve cancer treatment and control with natural products.

Analysis of Caloric and Noncaloric Sweeteners Present in Dairy Products Aimed at the School Market and Their Possible Effects on Health.

Over the past decades, Mexico has become one of the main sweetener-consuming countries in the world. Large amounts of these sweeteners are in dairy products aimed at the children's market in various presentations such as yogurt, flavored milk, flan, and cheeses. Although numerous studies have shown the impact of sweeteners in adults, the current evidence for children is insufficient and discordant to determine if these substances have any risk or benefit on their well-being. Therefore, this study aimed to describe the sweeteners present in 15 dairy products belonging to the school-age children's market in Mexico and their impact on health. These dairy products were selected through a couple of surveys directed at parents of school-age children. After that, the list of ingredients of each product was analyzed to identify their sweetener content. From there, exhaustive bibliographic research on sweeteners and their possible health effects was carried out, which included 109 articles and 18 studies. The results showed that at a neurological, endocrinological, cardiovascular, metabolic, osseous, renal, hepatic, dental, reticular, carcinogenic, and gut microbiota level; sucrose, fructose, high-fructose corn syrup, maltodextrins, sucralose, and acesulfame K, have a negative effect. While maltodextrins, stevia, polydextrose, and modified starch have a positive one. For these reasons, it is necessary to evaluate the advantages and disadvantages that the consumption of each sweetener entails, as well as a determination of the appropriate acceptable daily intake (ADI).

Determinants of Aedes mosquito density as an indicator of arbovirus transmission risk in three sites affected by co-circulation of globally spreading arboviruses in Colombia, Ecuador and Argentina.

BACKGROUND: The global impact of Zika virus in Latin America has drawn renewed attention to circulating mosquito-borne viruses in this region, such as dengue and chikungunya. Our objective was to assess socio-ecological factors associated with Aedes mosquito vector density as a measure of arbovirus transmission risk in three cities of potentially recent Zika virus introduction: Ibagué, Colombia; Manta, Ecuador; and Posadas, Argentina, in order to inform disease mitigation strategies. METHODS: We sampled Aedes mosquito populations in a total of 1086 households, using indoor and peridomestic mosquito collection methods, including light traps, resting traps, traps equipped with chemical attractant and aspirators. For each sampled household, we collected socio-economic data using structured questionnaires and data on microenvironmental conditions using iButton data loggers. RESULTS: A total of 3230 female Aedes mosquitoes were collected, of which 99.8% were Aedes aegypti and 0.2% were Aedes albopictus. Mean female Aedes mosquito density per household was 1.71 (standard deviation: 2.84). We used mixed-effects generalized linear Poisson regression analyses to identify predictors of Aedes density, using month, neighborhood and country as random-effects variables. Across study sites, the number of household occupants [incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 1.01-1.14], presence of entry points for mosquitoes into the household (IRR: 1.51, 95% CI: 1.30-1.76) and presence of decorative vegetation (IRR: 1.52, 95% CI: 1.22-1.88) were associated with higher Aedes density; while being in the highest wealth tertile of household wealth (IRR: 0.78, 95% CI: 0.66-0.92), knowledge of how arboviruses are transmitted (IRR: 0.94, 95% CI: 0.89-1.00) and regular emptying of water containers by occupants (IRR: 0.79, 95% CI: 0.67-0.92) were associated with lower Aedes density. CONCLUSIONS: Our study addresses the complexities of arbovirus vectors of global significance at the interface between human and mosquito populations. Our results point to several predictors of Aedes mosquito vector density in countries with co-circulation of multiple Aedes-borne viruses, and point to modifiable risk factors that may be useful for disease prevention and control.

Diet and Lifestyle Changes During the COVID-19 Pandemic in Ibero-American Countries: Argentina, Brazil, Mexico, Peru, and Spain.

This study aimed to evaluate changes in dietary and lifestyle habits during the period of confinement due to the first wave of the COVID-19 pandemic in Ibero-American countries. A cross-sectional investigation was conducted with 6,325 participants of both genders (68% women), over 18 years of age and from five countries: Brazil (N = 2,171), Argentina (N = 1,111), Peru (N = 1,174), Mexico (N = 686), and Spain (N = 1,183). Data were collected during the year 2020, between April 01 and June 30 in Spain and between July 13 and September 26, in the other countries studied using a self-administered online survey designed for the assessment of sociodemographic, employment, physical activity, health status, and dietary habits changes. Most participants (61.6%), mainly those from Spain, remained constant, without improving or worsening their pattern of food consumption. Among those who changed, a pattern of better eating choices prevailed (22.7%) in comparison with those who changed toward less healthy choices (15.7%). Argentina and Brazil showed the highest proportion of changes toward a healthier pattern of food consumption. Peruvians and Mexicans were less likely to make healthy changes in food consumption (OR: 0.51; 95% CI: 0.4-0.6 and OR: 0.69; 95% CI: 0.4-0.8, respectively), when compared to Argentinians. Most respondents did not change their pattern of meal consumption, but those who did reduced their consumption of main meals and increased intake of small meals and snacks. Although most participants affirmed to be doing physical activity at home, about one-half reported perception of weight gain. Individuals with alterations in sleep pattern (either by increasing or decreasing sleep time) were more likely to change their diets to a healthier pattern. In contrast, individuals with confirmed diagnosis of COVID-19 and those who reported feeling anxious were more likely to perform changes to a less healthy eating pattern (OR: 1.72; 95% CI: 1.2-2.3 and OR: 1.21; 95% CI: 1.1-1.4, respectively). In conclusion, although most participants remained constant in their eating habits, lifestyle changes and anxiety feelings were reported. Among those who changed patterns of food consumption, healthier choices prevailed, with differences between countries. However, there were alterations in the distribution of meals, with higher consumption of snacks and small meals. These results can be used to guide policies to prevent deleterious consequences that may affect the incidence of chronic diseases.

Nutritional Guideline for the Management of Mexican Patients with CKD and Hyperphosphatemia.

Chronic kidney disease (CKD) represents a serious concern for the Mexican population since the main predisposing diseases (diabetes, hypertension, etc.) have a high prevalence in the country. The development of frequent comorbidities during CKD such as anemia, metabolic disorders, and hyperphosphatemia increases the costs, symptoms, and death risks of the patients. Hyperphosphatemia is likely the only CKD comorbidity in which pharmaceutical options are restricted to phosphate binders and where nutritional management seems to play an important role for the improvement of biochemical and clinical parameters. Nutritional interventions aiming to control serum phosphate levels need to be based on food tables, which should be specifically elaborated for the cultural context of each population. Until now, there are no available food charts compiling a high amount of Mexican foods and describing phosphorus content as well as the phosphate to protein ratio for nutritional management of hyperphosphatemia in CKD. In this work, we elaborate a highly complete food chart as a reference for Mexican clinicians and include charts of additives and drug phosphate contents to consider extra sources of inorganic phosphate intake. We aim to provide an easy guideline to contribute to the implementation of more nutritional interventions focusing on this population in the country.

Utility of biomarkers in traumatic brain injury: a narrative review / Utilidad de los biomarcadores en trauma craneoencefálico: una revisiOn narrativa

Abstract Introduction: With the evolution of diagnostic techniques in traumatic brain injury (TBI), the study of neurological injury has made progress based on the concepts of primary and secondary injury, leading to the era of proteomics to understand the complex molecular events involved in the process. Objectives: This narrative review is intended to discuss the state of the art of the most frequently used biomarkers in TBI, their clinical utility, and the implications for therapeutic decision-making protocols. Materials and methods: In order to fulfill the objective of this paper, a literature review was conducted of the most important databases. Results: Several biomarkers have been studied as prognostic factors in patients with TBI. Learning about their sensitivity and specificity in neurological injury, and its post-trauma evolution over time, has been the goal of various papers in the past few years. Conclusion: Breakthroughs in the study of protein degradation make it necessary to broaden the spectrum and knowledge of new diagnostic methods in TBI. Further studies are needed to define the role of biomarkers and to promote protocols integrating specific values.

Resumen Introducción: Con la evolución de las técnicas diagnósticas en el trauma craneoencefálico, el estudio de la lesión neurológica ha progresado sobre los conceptos de lesión primaria y secundaria, para entrar así en la era de la proteómica y, con ella, entender los complejos eventos moleculares existentes en su proceso. Objetivos: En esta revisión narrativa se pretende presentar el estado actual de los biomarcadores que más se usan en lesión cerebral traumática, su utilidad clínica y las implicaciones en protocolos de decisión terapéutica. Materiales y métodos: Para dar respuesta al objetivo de este trabajo, se realizó una revisión de la literatura en las principales bases de datos. Resultados: Se han estudiado varios biomarcadores como factor pronóstico en pacientes con trauma craneoencefálico. Conocer su sensibilidad y especificidad para la lesión neurológica, así como su evolución en el tiempo tras el traumatismo, ha sido el objetivo de diversos trabajos en los últimos años. Conclusión: El avance en el estudio de los productos de degradación de las proteínas hace necesario ampliar el espectro y el conocimiento en el campo de los nuevos métodos diagnósticos en el trauma craneoencefálico. Se requieren más estudios para definir la función de los biomarcadores y proponer protocolos que integren valores específicos.

Mutant p53 Gain-of-Function: Role in Cancer Development, Progression, and Therapeutic Approaches.

Frequent p53 mutations (mutp53) not only abolish tumor suppressor capacities but confer various gain-of-function (GOF) activities that impacts molecules and pathways now regarded as central for tumor development and progression. Although the complete impact of GOF is still far from being fully understood, the effects on proliferation, migration, metabolic reprogramming, and immune evasion, among others, certainly constitute major driving forces for human tumors harboring them. In this review we discuss major molecular mechanisms driven by mutp53 GOF. We present novel mechanistic insights on their effects over key functional molecules and processes involved in cancer. We analyze new mechanistic insights impacting processes such as immune system evasion, metabolic reprogramming, and stemness. In particular, the increased lipogenic activity through the mevalonate pathway (MVA) and the alteration of metabolic homeostasis due to interactions between mutp53 and AMP-activated protein kinase (AMPK) and Sterol regulatory element-binding protein 1 (SREBP1) that impact anabolic pathways and favor metabolic reprograming. We address, in detail, the impact of mutp53 over metabolic reprogramming and the Warburg effect observed in cancer cells as a consequence, not only of loss-of-function of p53, but rather as an effect of GOF that is crucial for the imbalance between glycolysis and oxidative phosphorylation. Additionally, transcriptional activation of new targets, resulting from interaction of mutp53 with NF-kB, HIF-1α, or SREBP1, are presented and discussed. Finally, we discuss perspectives for targeting molecules and pathways involved in chemo-resistance of tumor cells resulting from mutp53 GOF. We discuss and stress the fact that the status of p53 currently constitutes one of the most relevant criteria to understand the role of autophagy as a survival mechanism in cancer, and propose new therapeutic approaches that could promote the reduction of GOF effects exercised by mutp53 in cancer.