Underground speciation: Unraveling the systematics and evolution of the highly diverse tuco-tucos (genus Ctenomys) with genomic data.

Subterranean rodents of the genus Ctenomys (tuco-tucos) are endemic to South America and have experienced relatively recent radiation. There are about 67 recognized species that originated in approximately 1-2 MY. They stand out for their species richness, extraordinary chromosomal diversity, and wide range of habitat they occupy in the continent. Phylogenetic relationships among species of tuco-tucos have been challenging to resolve. Groups of closely-related species have been suggested, but their relationships must be resolved. This study estimates the phylogeny of the genus using massive sequencing, generating thousands of independent molecular markers obtained by RADseq, with a taxonomic sampling that includes 66% of the recognized species. The sequences obtained were mapped against the C. sociabilis genome, recovering up to 1,215 widely shared RAD loci with more than 19,000 polymorphic sites. Our new phylogenetic hypothesis corroborated the species groups previously proposed with cytochrome b gene sequences and provided a much greater resolution of the relationships among species groups. The frater group is sister to all other tuco-tucos, whereas some of the earlierliest proposals placed the sociabilis group as sister to all other tuco-tucos. Ctenomys leucodon, previously proposed as an independent lineage, is associated with the frater group with moderate statistical support. The magellanicus and mendocinus are sister groups in a major clade formed by the boliviensis, talarum, tucumanus, torquatus, and opimus groups. Ctenomys viperinus, included in the phylogeny for the first time, belongs to the tucumanus group. This multi-locus phylogenetic hypothesis provides insights into the historical biogeography of understanding this highly diverse genus.

Scaling properties of the action in the Riemann-Liouville fractional standard map.

The Riemann-Liouville fractional standard map (RL-fSM) is a two-dimensional nonlinear map with memory given in action-angle variables (I,θ). The RL-fSM is parameterized by K and α∈(1,2], which control the strength of nonlinearity and the fractional order of the Riemann-Liouville derivative, respectively. In this work we present a scaling study of the average squared action 〈I^{2}〉 of the RL-fSM along strongly chaotic orbits, i.e., for K≫1. We observe two scenarios depending on the initial action I_{0}, I_{0}≪K or I_{0}≫K. However, we can show that 〈I^{2}〉/I_{0}^{2} is a universal function of the scaled discrete time nK^{2}/I_{0}^{2} (n being the nth iteration of the RL-fSM). In addition, we note that 〈I^{2}〉 is independent of α for K≫1. Analytical estimations support our numerical results.

Good clinical practice recommendations for the diagnosis and treatment of gastroesophageal reflux disease. An expert review from the Asociación Mexicana de Gastroenterología.

INTRODUCTION: Gastroesophageal reflux disease (GERD) is very prevalent in the general population, with a broad spectrum of clinical manifestations, requiring accurate diagnosis and treatment. AIM: The aim of this expert review is to establish good clinical practice recommendations for the diagnosis and personalized treatment of GERD. METHODS: The good clinical practice recommendations were produced by a group of experts in GERD, members of the Asociación Mexicana de Gastroenterología (AMG), after carrying out an extensive review of the published literature and discussing each recommendation at a face-to-face meeting. This document does not aim to be a clinical practice guideline with the methodology such a document requires. RESULTS: Fifteen experts on GERD formulated 27 good clinical practice recommendations for recognizing the symptoms and complications of GERD, the rational use of diagnostic tests and medical treatment, the identification and management of refractory GERD, the overlap with functional disorders, endoscopic and surgical treatment, and GERD in the pregnant woman, older adult, and the obese patient. CONCLUSIONS: An accurate diagnosis of GERD is currently possible, enabling the prescription of a personalized treatment in patients with this condition. The goal of the good clinical practice recommendations by the group of experts from the AMG presented in this document is to aid both the general practitioner and specialist in the process of accurate diagnosis and treatment, in the patient with GERD.

Lyophilized Avocado Paste Improves Corn Chips' Nutritional Properties and Sensory Acceptability.

Avocado paste (AP) is an industrial byproduct and a potential source of bioactive compounds, so there is great interest in its valorization. The objective of the present study was to evaluate the effects of adding AP to corn chips regarding their nutritional profile and sensory acceptability. Three AP-supplemented corn chip samples were prepared (C-2%, C-6%, and C-10%), along with a control chip (C), whose total phenolics, flavonoids, antioxidant capacity, proximate composition, minerals, fatty acids, and sensory acceptability were evaluated. Regarding the content of phenolic compounds and flavonoids, significant increases were found between all samples (p < 0.05), particularly between C and C-10% (from 0.93 to 3.56 mg GAE/g dw and 1.17 to 6.61 mg QE/g dw, respectively). Their antioxidant capacity also increased significantly (p < 0.05) with all methods used (FRAP, DPPH, ORAC, and TEAC). Regarding the sensory analysis, no significant differences were found (p > 0.05) between C and C-2% in the parameters of smell, color, flavor, and overall acceptability; however, the texture of C-2% was better evaluated. The C-2% sample also had the highest acceptability; 82% of the participants mentioned that they would buy the C-2%, higher than the rest of the samples. These results suggest the feasibility of adding 2% AP as a strategy to improve the nutritional properties of corn chips without compromising their sensory acceptability; therefore, AP may be used as a food ingredient.

Comparison of the use of blood pressure telemonitoring versus standard medical care in the achievement of short-term therapeutic goals in blood pressure in patients with uncontrolled hypertension: An open-label clinical trial.

Background: In Mexico less than half of the treated hypertensive patients reach blood pressure (BP) targets. Most hypertensive individuals rely on the standard medical care (SMC) to achieve the BP control goals; however, the efficacy of BP telemonitoring (BPT) to achieve BP targets has been poorly studied. Aim: To compare the efficacy of BPT versus SMC to achieve BP goals in patients with uncontrolled hypertension. Methods: A two-arm, open-label clinical trial was conducted in patients ≥18 years with uncontrolled hypertension. The participants were randomized to 2 arms (BPT vs SMC) and followed for 12 weeks. For the statistical analysis, the chi-squared test and covariance were used. Results: One hundred and seventy-eight participants were included, BPT (n = 94) and SMC (n = 84), after 12 weeks of follow up, we observed a baseline-adjusted reduction in systolic BP with both BPT (-13.5 [1.3] mmHg) and the SMC (-5.9 [1.4] mmHg; p < 0.001) but a greater decrease with BPT (p < 0.001). Likewise, we found a baseline-adjusted reduction of diastolic BP with BPT (-6.9 [0.9] mmHg) and SMC (-2.7 [0.9] mmHg) (p = 0.007) with a more significant percentage change from baseline with BPT (-6.8% [1.0] vs 2.5% [1.1]; p = 0.007). In the BPT arm, a larger proportion of patients achieved the BP target versus SMC (30.5% vs 12.8%; p = 0.005). Conclusion: BPT showed a greater proportion of patients achieving office BP control goals (<140/90 mmHg), compared to standard medical care.

Intermittent fasting combined with exercise training reduces body mass and alleviates hypothalamic disorders induced by high-fat diet intake.

High-fat diet consumption causes hypothalamic inflammation, dysregulating the leptin pathway, which, in turn, compromises the modulation of hypothalamic neuronal activities and predisposes obesity development. Intermittent fasting (IF) and exercise training (ET) have been demonstrated as efficient interventions to modulate hypothalamic inflammation and neuronal activity. However, no studies have evaluated whether combining these interventions could induce better results in reestablishing hypothalamic homeostasis disrupted by high-fat diet intake. The 8-week-old male C57BL/6 mice were randomly assigned into 2 groups: sedentary mice fed a standard diet (CT), and sedentary mice fed a high-fat diet (HF). After 8 weeks of an HF diet, part of the HF group (now 16 weeks old) was randomly subjected to different interventions for 6 weeks: HF-IF = HF diet mice submitted to IF; HF-T = HF diet mice submitted to ET; HF-IFT = HF diet mice submitted to IF and ET. All interventions decreased the body weight gain induced by high-fat diet intake, associated with reduced calorie consumption in week 14. Only the HF-IFT group presented improved serum insulin, leptin, resistin, and Tnf-alpha levels concomitantly with decreased hypothalamic inflammation. The HF-IFT group also demonstrated increased Pomc mRNA expression associated with enhanced pSTAT3 expression in the hypothalamic arcuate and ventromedial hypothalamic nuclei. Our data indicate that the beneficial effects of the combination of IF and ET on energy homeostasis are associated with increased leptin sensitivity in the hypothalamic arcuate nucleus and ventromedial hypothalamic nucleus, which is likely due to an improvement in hypothalamic inflammatory pathways in these nuclei.

Cáncer de mama Her2-positivo: Terapias sistémicas actuales y experiencia local

El cáncer de mama (CM) es la primera causa de muerte por cáncer en mujeres tanto a nivel mundial como en Chile. Basados en características clínicas, histológicas y moleculares, múltiples estudios han identificado cuatro subtipos básicos de CM, los cuales están asociados a estrategias de tratamiento específicas y diferenciadas. El CM HER2-positivo representa un 15%-25% de todas las neoplasias mamarias y se caracteriza por su agresividad, recurrencia temprana y mayor tendencia a presentar compromiso del sistema nervioso central. En las últimas décadas, nuevas terapias dirigidas se han posicionado como el estándar de tratamiento y han cambiado la historia natural de esta enfermedad, transformándola en una enfermedad potencialmente curable incluso en etapas avanzadas. Esta revisión busca entregar un resumen de las bases biológicas de esta enfermedad. Por otro lado, dada la aparición de un creciente número de nuevas estrategias de manejo sistémico, nos proponemos revisar sus mecanismos de acción analizando reportes de datos clínicos publicados y la experiencia de nuestro grupo.

Breast cancer (BC) is the leading cause of cancer death for women both worldwide and in Chile. Based on clinical, histological, and molecular features, studies have identified four BC subtypes that correlate with treatment sensitivity. Human Epidermal growth factor Receptor type 2-positive (HER2+) BC represents 15%-25% of newly diagnosed breast neoplasms; HER2+ BC is characterized by its aggressive behavior, early recurrence, and higher risk of brain metastasis. In recent years, HER2-targeted therapies have become the mainstay of treatment and have redefined the natural history of this subtype, reducing relapse rates for early-stage patients and increasing survival in advanced-stage patients. Herein we review novel treatment strategies and their mechanisms of action, along with clinical and real-world data. We also provide a summary of currently available treatments for this subtype and our local experience regarding the management of this disease.

Quality assessment of Clinical Practice Guidelines (CPG) for the diagnosis and treatment of inflammatory bowel disease using the AGREE II instrument: a systematic review.

BACKGROUND: The incidence and diagnosis of inflammatory bowel disease (IBD) has increased considerably in recent years. Many clinical practice guidelines (CPG) have been developed for the management of this disease across different clinical contexts, however, little evidence exists on their methodological quality. Therefore, we aimed to systematically evaluate the quality of CPGs for the diagnosis and treatment of IBD using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. METHODS: We identified CPGs by searching databases (MEDLINE - PubMed, EMBASE, CINAHL, LILACS) and other sources of gray literature on January 2022. We included guidelines with specific recommendations for the diagnosis and treatment of IBD and evaluated them with the AGREE II instrument to assess their methodological quality. Six independent reviewers assessed the quality of the guidelines and resolved conflicts by consensus. We assessed the degree of agreement using the intraclass correlation coefficient (ICC) and change in quality over time was appraised in two periods: from 2012 to 2017 and from 2018 to 2022. RESULTS: We analyzed and evaluated 26 CPGs that met the inclusion criteria. The overall agreement among reviewers was moderate (ICC: 0.74; 95% CI 0.36 - 0.89). The mean scores of the AGREE II domains were: "Scope and purpose" 84.51%, "Stakeholder involvement" 60.90%, "Rigor of development" 69.95%, "Clarity of presentation" 85.58%, "Applicability" 26.60%, and "Editorial independence" 62.02%. No changes in quality were found over time. CONCLUSIONS: The quality of the CPGs evaluated was generally good, with a large majority of the assessed guidelines being "recommended" and "recommended with modifications"; despite this, there is still room for improvement, especially in terms of stakeholder involvement and applicability. Efforts to develop high quality CPGs for IBD need to be further optimized.

Single-Cell Protein Production as a Strategy to Reincorporate Food Waste and Agro By-Products Back into the Processing Chain.

Food waste is a serious problem with negative environmental and economic consequences. Unused food (either as waste or by-products and referred to as food residues in the present work) is a source of carbohydrates, lipids, proteins, vitamins, minerals and bioactive compounds that could be used in an alternate or secondary life cycle to avoid discarding it. The present work reviews the potential use of food residues for the bioengineering of single-cell protein (SCP), addressing aspects of production, nutrition and safety, as well as the main challenges and perspectives. SCP is obtained from various microorganisms, including fungi, bacteria, yeasts and algae, in pure or mixed form. SCP generally contains a higher percentage of protein (30-80%) compared to soy (38.6%), fish (17.8%), meat (21.2%) and whole milk (3.28%). SCP is a source of essential amino acids, including methionine, threonine and lysine. The use of food residues as substrates for the production of SCP would reduce production costs (35-75%); however, optimization and industrial scaling are some of the main challenges to its sustainable production. The use food waste and agro by-products from the food industry could be a promising alternative to obtain protein according to a circular production scheme.

Lesser-Consumed Tropical Fruits and Their by-Products: Phytochemical Content and Their Antioxidant and Anti-Inflammatory Potential.

Açaí, lychee, mamey, passion fruit and jackfruit are some lesser-consumed tropical fruits due to their low commercial production. In 2018, approximately 6.8 million tons of these fruits were harvested, representing about 6.35% of the total world production of tropical fruits. The present work reviews the nutritional content, profile of bioactive compounds, antioxidant and anti-inflammatory capacity of these fruits and their by-products, and their ability to modulate oxidative stress due to the content of phenolic compounds, carotenoids and dietary fiber. Açaí pulp is an excellent source of anthocyanins (587 mg cyanidin-3-glucoside equivalents/100 g dry weight, dw), mamey pulp is rich in carotenoids (36.12 mg ß-carotene/100 g fresh weight, fw), passion fruit peel is rich in dietary fiber (61.16 g/100 dw). At the same time, jackfruit contains unique compounds such as moracin C, artocarpesin, norartocarpetin and oxyresveratrol. These molecules play an important role in the regulation of inflammation via activation of mitogen-activated protein kinases (including p38, ERK and JNK) and nuclear factor κB pathways. The properties of the bioactive compounds found in these fruits make them a good source for use as food ingredients for nutritional purposes or alternative therapies. Research is needed to confirm their health benefits that can increase their marketability, which can benefit the primary producers, processing industries (particularly smaller ones) and the final consumer, while an integral use of their by-products will allow their incorporation into the circular bioeconomy.

[Structural changes to the brain in drug-resistant juvenile myoclonic epilepsy]. / Cambios estructurales cerebrales en la epilepsia mioclónica juvenil farmacorresistente.

INTRODUCTION: The aim of this research is to determine the changes in brain structures, both cortical and subcortical, in patients with drug-resistant juvenile myoclonic epilepsy (JME), in order to contribute to the understanding of the characteristics of the drug-resistant syndrome and to offer possible answers and hypotheses for further studies and more adequate treatments. SUBJECTS AND METHODS: Observational case-control study. A convenience sample size of four cases and 16 healthy controls was defined to ensure the feasibility of the project (ratio of 4:1). The data collected for patients with drug-resistant JME came from 1.5T MRI equipment. FreeSurfer software was used to determine cortical and subcortical areas in both drug-resistant JME patients and healthy controls. RESULTS: A total of 20 participants were included in the study, of whom four (20%) were drug-resistant JME patients and 16% (80%) were healthy controls. The clusters with statistically significant differences in cortical thickness are located in the precentral gyrus, superior temporal gyrus, transverse temporal gyrus, medial temporal gyrus and supramarginal gyrus, predominantly in the left hemisphere. CONCLUSIONS: Structural brain changes are observed in patients with drug-resistant JME that may go undetected by the conventional processing techniques used in magnetic resonance imaging.

TITLE: Cambios estructurales cerebrales en la epilepsia mioclónica juvenil farmacorresistente.Introducción. El objetivo de la investigación es determinar los cambios en las estructuras cerebrales, tanto corticales como subcorticales, de pacientes con epilepsia mioclónica juvenil (EMJ) farmacorresistente, para aportar al conocimiento de las características del síndrome farmacorresistente y brindar posibles respuestas e hipótesis para nuevos estudios y tratamientos más adecuados. Sujetos y métodos. Estudio observacional de casos y controles. Se define un tamaño de muestra a conveniencia de cuatro casos y 16 controles sanos para garantizar la viabilidad del proyecto (relación 4:1). Los datos recolectados para los pacientes con EMJ farmacorresistentes provienen de un equipo de resonancia magnética de 1,5 T. Para determinar las áreas corticales y subcorticales, tanto en la EMJ farmacorresistente como en los controles sanos, se usó el software FreeSurfer. Resultados. Se incluyó a un total de 20 participantes en el estudio, de los cuales cuatro (20%) corresponden a EMJ farmacorresistentes y 16 (80 %) a controles sanos. La localización de los clústeres con diferencias estadísticamente significativas en el grosor cortical se encuentra en el giro precentral, el giro temporal superior, el giro temporal transverso, el giro temporal medial y el giro supramarginal, con predominancia en el hemisferio izquierdo. Conclusiones. Se evidencian cambios estructurales cerebrales en pacientes con EMJ farmacorresistente, cambios que pueden pasar desapercibidos por las técnicas convencionales en el procesamiento de las imágenes de resonancia magnética.

Using Intermittent Fasting as a Non-pharmacological Strategy to Alleviate Obesity-Induced Hypothalamic Molecular Pathway Disruption.

Intermittent fasting (IF) is a popular intervention used to fight overweight/obesity. This condition is accompanied by hypothalamic inflammation, limiting the proper signaling of molecular pathways, with consequent dysregulation of food intake and energy homeostasis. This mini-review explored the therapeutic modulation potential of IF regarding the disruption of these molecular pathways. IF seems to modulate inflammatory pathways in the brain, which may also be correlated with the brain-microbiota axis, improving hypothalamic signaling of leptin and insulin, and inducing the autophagic pathway in hypothalamic neurons, contributing to weight loss in obesity. Evidence also suggests that when an IF protocol is performed without respecting the circadian cycle, it can lead to dysregulation in the expression of circadian cycle regulatory genes, with potential health damage. In conclusion, IF may have the potential to be an adjuvant treatment to improve the reestablishment of hypothalamic responses in obesity.

Adaptación transcultural de la versión colombiana de la Escala de Soledad de UCLA en pacientes con diagnóstico de cáncer / Transcultural adaptation of the Colombian version of the UCLA Loneliness Scale in patients diagnosed with cancer

Resumen Introducción: La soledad no deseada es un constructo que se ha relacionado con desenlaces negativos en diferentes aspectos de la salud, incluidos aquellos de los pacientes con cáncer. La escala de soledad de UCLA es un instrumento ampliamente utilizado en el contexto de investigación en salud para medir dicho constructo, y en Colombia la versión 03 de dicho instrumento no se encuentra traducida, ni adaptada transculturalmente. Objetivo: Traducir y adaptar transculturalmente la escala de soledad de UCLA, versión 03 para su uso en pacientes con cáncer en Colombia. Métodos: El proceso de traducción y adaptación transcultural siguió la metodología propuesta por el grupo EORTC, con el objetivo de lograr la equivalencia semántica con la versión original de la escala disponible en inglés. Se realizó una prueba piloto con 20 pacientes colombianos diagnosticados con diferentes tipos de cáncer, que asistieron al Instituto Nacional de Cancerología de Colombia. Resultados: No hubo cambios ni en la traducción de instrucciones ni en las opciones de respuesta. En la versión conciliada se modificó el ítem UC1. En la prueba piloto, dos de 20 pacientes informaron que los ítems UC6, UC7, UC11 y UC19 deberían ser modificados y un paciente mencionó que el ítem UC8 era difícil de entender; sin embargo, no se hicieron cambios dado el bajo número de pacientes que reportaron estos hallazgos, y las sugerencias planteadas podían cambiar el sentido y la equivalencia de los ítems de la escala original. Ninguno de los ítems fue ofensivo para los pacientes. Conclusión: Se generó una versión traducida y adaptada transculturalmente para ser validada en pacientes con cáncer en Colombia.

Abstract Introduction: Unwanted loneliness is a construct that has shown relationships with different negative outcomes of health, including those of patients with cancer. In the context of health research, the UCLA loneliness scale is a widely used instrument for measuring this construct. In Colombia, the 03 version of this instrument has still not been neither translated, nor transculturally adapted. Objective: To translate and perform transcultural adaptation of the UCLA loneliness scale, version 03 for its use in patients having cancer in Colombia. Methods: The process of translation and transcultural adaptation followed the methodology proposed by the EORTC group, aimed at achieving semantic equivalence with the original version of the scale. A pilot test has been made with 20 Colombian patients diagnosed with different types of cancer, attending the Instituto Nacional de Cancerología, Colombia. Results: In the reconciliated version, item UC1 has been modified. There has been not changes neither in translation of instructions, nor in response options. In pilot testing two out of 20 patients reported that items UC6, UC7, UC11 y UC19 should be modified and one patient mentioned that item UC8 was difficult to understand; however, no changes were made taking into account the low number of patients describing similar findings, and because these suggestions could change the semantic equivalence of these items. No items were deemed offensive. Conclusion: It is available a transculturally adapted version of the UCLA loneliness scale, version 03 for its validation in patients with cancer in Colombia.

Effects of mesenchymal stem cell culture on radio sterilized human amnion or radio sterilized pig skin in burn wound healing.

Deep second and third degree burns treatment requires fibroblasts, keratinocytes and other skin cells in order to grow new dermis and epidermis. Cells can proliferate, secrete growth factors and extracellular matrix required to repair the damaged tissue. Radiosterilized human amnion and radiosterilized pig skin have been used as natural origin skin dressings for burned patients. Adipose-derived mesenchymal stem cells can differentiate into fibroblasts and keratinocytes and improve wound-healing progress. These cells can stimulate vascular tissue formation, release growth factors, synthetize new extracellular matrix and immunoregulate other cells. In this study, we developed mesenchymal stem cells-cellularized skin substitutes based from radiosterilized human amnion or pig skin. Third-degree burns were induced in mice animal models to evaluate the effect of cellularized skin substitutes on burn wound healing. Mesenchymal phenotype was immunophenotypically confirmed by flow cytometry and cell viability was close to 100%. Skin recovery was evaluated in burned mice after seven and fourteen days post-coverage with cellularized and non-cellularized sustitutes. Histological techniques and immunofluorescence were used to evaluate re-epithelization and type I collagen deposition. We determined that cellularized-human amnion or cellularized-pig skin in combination with mesenchymal stem cells improve extracellular matrix deposition. Both cellularized constructs increase detection of type I collagen in newly formed mouse skin and can be potentially used as skin coverage for further clinical treatment of burned patients.