Endothelial to Mesenchymal Transition: Role in Physiology and in the Pathogenesis of Human Diseases.

Numerous studies have demonstrated that endothelial cells are capable of undergoing endothelial to mesenchymal transition (EndMT), a newly recognized type of cellular transdifferentiation. EndMT is a complex biological process in which endothelial cells adopt a mesenchymal phenotype displaying typical mesenchymal cell morphology and functions, including the acquisition of cellular motility and contractile properties. Endothelial cells undergoing EndMT lose the expression of endothelial cell-specific proteins such as CD31/platelet-endothelial cell adhesion molecule, von Willebrand factor, and vascular-endothelial cadherin and initiate the expression of mesenchymal cell-specific genes and the production of their encoded proteins including α-smooth muscle actin, extra domain A fibronectin, N-cadherin, vimentin, fibroblast specific protein-1, also known as S100A4 protein, and fibrillar type I and type III collagens. Transforming growth factor-ß1 is considered the main EndMT inducer. However, EndMT involves numerous molecular and signaling pathways that are triggered and modulated by multiple and often redundant mechanisms depending on the specific cellular context and on the physiological or pathological status of the cells. EndMT participates in highly important embryonic development processes, as well as in the pathogenesis of numerous genetically determined and acquired human diseases including malignant, vascular, inflammatory, and fibrotic disorders. Despite intensive investigation, many aspects of EndMT remain to be elucidated. The identification of molecules and regulatory pathways involved in EndMT and the discovery of specific EndMT inhibitors should provide novel therapeutic approaches for various human disorders mediated by EndMT.

COL1A1 proximal promoter topology regulates its transcriptional response to transforming growth factor ß.

OBJECTIVE: The COL1A1 proximal promoter contains two GC-rich regions and two inverted CCAAT boxes. The transcription factors Sp1 and CBF bind to the GC sequence at -122 to -115 bp and the inverted CCAAT box at -101 to -96 bp, respectively, and stimulate COL1A1 transcriptional activity. METHODS: To further define the regulatory mechanisms controlling COL1A1 expression by Sp1 and CBF, we introduced 2, 4, 6, or 8 thymidine nucleotides (T-tracts) at position -111 bp of the COL1A1 gene promoter to increase the physical distance between these two binding sites and examined in vitro the transcriptional activities of the resulting constructs and their response to TGF-ß1.`. RESULTS: Insertion of 2 or 4 nucleotides decreased COL1A1 promoter activity by up to 70%. Furthermore, the expected increase in COL1A1 transcription in response to TGF-ß1 was abolished. Computer modeling of the modified DNA structure indicated that increasing the physical distance between the Sp1 and CBF binding sites introduces a rotational change in the DNA topology that disrupts the alignment of Sp1 and CBF binding sites and likely alters protein-protein interactions among these transcription factors or their associated co-activators. CONCLUSION: The topology of the COL1A1 proximal promoter is crucial in determining the transcriptional activity of the gene and its response to the stimulatory effects of TGF-ß1.

Dentate nucleus: a review and implications for dentatotomy.

PURPOSE: The dentate nucleus (DN) is the largest, most lateral, and phylogenetically most recent of the deep cerebellar nuclei. Its pivotal role encompasses the planning, initiation, and modification of voluntary movement but also spans non-motor functions like executive functioning, visuospatial processing, and linguistic abilities. This review aims to offer a comprehensive description of the DN, detailing its embryology, anatomy, physiology, and clinical relevance, alongside an analysis of dentatotomy. METHODS AND RESULTS: We delve into the history, embryology, anatomy, vascular supply, imaging characteristics, and clinical significance of the DN. Furthermore, we thoroughly review the dentatotomy, emphasizing its role in treating spasticity. CONCLUSIONS: Understanding the intricacies of the anatomy, physiology, vasculature, and projections of the DN has taken on increased importance in current neurosurgical practice. Advances in technology have unveiled previously unknown functions of the deep cerebellar nuclei, predominantly related to non-motor domains. Such discoveries are revitalizing older techniques, like dentatotomy, and applying them to newer, more localized targets.

Comparison of microvascular decompression, percutaneous radiofrequency rhizotomy, and stereotactic radiosurgery in the treatment of trigeminal neuralgia: A long term quasi-experimental study.

BACKGROUND: Microvascular decompression (MVD), radiofrequency rhizotomy (RFR), and stereotactic radiosurgery (SRS) are surgical techniques frequently used in the treatment of idiopathic trigeminal neuralgia (TN), although the results reported for each of these are diverse. OBJECTIVE: This study aimed to compare long-term pain control obtained by MVD, SRS, and RFR in patients with idiopathic TN. METHODS: To compare the results obtained by MVD, SRS, and RFR we chose a quasi-experimental, ambispective design with control groups but no pretest. A total of 52 participants (MVD n = 33, RFR n = 10, SRS n = 9) were included. Using standardized outcome measures, pain intensity, pain relief, quality of life, and satisfaction with treatment were assessed by an independent investigator. The TREND statement for reporting non-randomized evaluations was applied. Clinical outcomes were evaluated at the initial postoperative period and at 6 months, 1, 2, 3, 4, and 5 years postoperatively. RESULTS: MVD has shown better results in pain scales compared to ablative procedures. Significant differences between groups were found regarding pain intensity and pain relief at the initial postoperative period (p < 0.001) and 6 months (p = 0.022), 1 year (p < 0.001), 2 years (p = 0.002), and 3 years (p = 0.004) after the intervention. Those differences exceeded the thresholds of the minimal clinically important difference. A higher percentage of patients free of pain was observed in the group of patients treated by MVD, with significant differences at the initial postoperative period (p < 0.001) and 6 months (p = 0.02), 1 year (p = 0.001), and 2 years (p = 0.04) after the procedure. Also, a higher risk of pain recurrence was observed in the RFR and SRS groups (HR 3.15, 95% CI 1.33-7.46; p = 0.009; and HR 4.26, 95% CI 1.77-10.2; p = 0.001, respectively) compared to the MVD group. No significant differences were found in terms of quality of life and satisfaction with treatment. A higher incidence of complications was observed in the MVD group. CONCLUSION: Concerning pain control and risk of pain recurrence, MVD is superior to RFR and SRS, but not in terms of quality of life, satisfaction with treatment, and safety profile.

Probable role of exosomes in the extension of fibrotic alterations from affected to normal cells in systemic sclerosis.

SSc is a systemic autoimmune disease of unknown etiology characterized by frequently progressive cutaneous and internal organ fibrosis causing severe disability, organ failure and high mortality. A remarkable feature of SSc is the extension of the fibrotic alterations to nonaffected tissues. The mechanisms involved in the extension of fibrosis have remained elusive. We propose that this process is mediated by exosome microvesicles released from SSc-affected cells that induce an activated profibrotic phenotype in normal or nonaffected cells. Exosomes are secreted microvesicles involved in an intercellular communication system. Exosomes can transfer their macromolecular content to distant target cells and induce paracrine effects in the recipient cells, changing their molecular pathways and gene expression. Confirmation of this hypothesis may identify the molecular mechanisms responsible for extension of the SSc fibrotic process from affected cells to nonaffected cells and may allow the development of novel therapeutic approaches for the disease.

Effect of ß-alanine and sodium bicarbonate co-supplementation on the body's buffering capacity and sports performance: A systematic review.

Muscle acidification is one of the main factors causing fatigue during exercise, thus compromising performance. The sport supplements beta alanine (ß-A) and sodium bicarbonate (SB) are thought to enhance the effects of the body's buffer systems by reducing H+ concentrations. The aim of this systematic review was to analyze the effects of ß-A and SB co-supplementation on the organism's buffering capacity and sport performance. The databases PubMed, Web of Science, Medline, CINAHL and SPORTDiscus were searched until November 2021 following PRISMA guidelines. Randomized controlled trials, at least single-blind, performed in athletes of any age were considered. Nine studies including a total of 221 athletes were identified for review. Athletes were supplemented with ß-A and SB while they performed exercise tests to assess physical performance and buffer capacity. Five of the nine studies indicated there was some additional improvement in buffering capacity and performance with co-supplementation, while one study concluded that the effect was comparable to the added effects of the individual supplements. According to the results of the studies reviewed, we would recommend ß-A and SB co-supplementation during high intensity exercises lasting between 30 s and 10 min.

Muscle hypertrophy induced by N-3 PUFA supplementation in absence of exercise: a systematic review of randomized controlled trials.

The use of omega-3 polyunsaturated fatty acids (n-3 PUFA) has been studied in physically active population, however, there is a lack of information about the effects of n-3 PUFA supplementation on people with a sedentary behavior or who are undergoing a period of limb immobilization. This systematic review aims to examine the effect of n-3 PUFA on lean mass and muscle protein synthesis (MPS) in absence of physical training. The PubMed, Web of Science, MEDLINE, CINAHL and SPORTDiscus databases were searched following the PRISMA guidelines. Only randomized controlled trials, at least single blind, performed with sedentary humans were considered. Seven studies on a total of 192 individuals were included. Five of the six studies which measured changes in skeletal muscle volume and mass showed higher values with n-3 PUFA. Only two studies measured skeletal muscle protein expression. Both showed beneficial effects of supplementation in muscle protein fractional synthesis rate (FSR), while no effect of n-3 PUFA was observed for mechanistic target of rapamycin (mTOR) and kinase protein (Akt). In addition, ribosomal protein S6 kinase 1 (p70s6k) improved with n-3 PUFA only in one study. Finally, the two studies which measured the skeletal muscle gene expression observed no effect of supplementation.

Effects of acute caffeine intake on combat sports performance: A systematic review and meta-analysis.

The interest in the benefits of caffeine in combat sports has grown exponentially in the last few years, evidenced by the significant rise of post-competition urine caffeine concentration. We conduct a systematic review and meta-analysis on the effects of caffeine on different performance variables in combat sports athletes. In total, we included 25 studies. All studies included had blinded, and cross-over experimental designs, and we conducted a risk of bias analysis. For nonspecific outcomes, there was an ergogenic effect of caffeine on vertical jump height (SMD: 0.38; 95% CI: 0.04, 0.71) and reaction time (SMD: -0.98, 95% CI: -1.46,-0.50). For outcomes specific to combat sports, there was an increase in the number of throws with caffeine in the Special Judo Fitness Test (SMD: 0.62; 95% CI: 0.14, 1.09). Caffeine ingestion increased the number of offensive actions during combats (SMD: 0.40; 95% CI: 0.06, 0.74). Caffeine ingestion increased the duration of offensive actions during combat (SMD: 0.58; 95% CI: 0.21, 0.96). Finally, caffeine ingestion increased blood lactate concentration after bout 1 (SMD: 1.35) bout 2 (SMD: 1.43) and bout 3 (SMD: 1.98). Overall, athletes competing in combat sports may consider supplementing with caffeine for an acute increase in exercise performance.

Immunomodulatory effects of inactivated Ligilactobacillus salivarius CECT 9609 on respiratory epithelial cells.

The microbiota in humans and animals play crucial roles in defense against pathogens and offer a promising natural source for immunomodulatory products. However, the development of physiologically relevant model systems and protocols for testing such products remains challenging. In this study, we present an experimental condition where various natural products derived from the registered lactic acid bacteria Ligilactobacillus salivarius CECT 9609, known for their immunomodulatory activity, were tested. These products included live and inactivated bacteria, as well as fermentation products at different concentrations and culture times. Using our established model system, we observed no morphological changes in the airway epithelium upon exposure to Pasteurella multocida, a common respiratory pathogen. However, early molecular changes associated with the innate immune response were detected through transcript analysis. By employing diverse methodologies ranging from microscopy to next-generation sequencing (NGS), we characterized the interaction of these natural products with the airway epithelium and their potential beneficial effects in the presence of P. multocida infection. In particular, our discovery highlights that among all Ligilactobacillus salivarius CECT 9609 products tested, only inactivated cells preserve the conformation and morphology of respiratory epithelial cells, while also reversing or altering the natural immune responses triggered by Pasteurella multocida. These findings lay the groundwork for further exploration into the protective role of these bacteria and their derivatives.

Pharmacological treatment of systemic sclerosis-associated interstitial lung disease: an updated review and current approach to patient care.

Interstitial lung disease (ILD) has a high prevalence among patients with systemic sclerosis (SSc), carrying high mortality and morbidity. During the last decade, the emergence of new pharmacological therapies for SSc-associated ILD (SSc-ILD) and improved tools for its diagnosis and monitoring have changed the prevailing clinical approach, highlighting the need for early recognition and prompt treatment for SSc-ILD. Furthermore, the recent approval of multiple therapies for SSc-ILD poses challenges for the rheumatologist and pulmonologist in choosing the appropriate therapy for individual clinical scenarios. We review the pathophysiology of SSc-ILD, and the mechanisms of action and rationale behind current therapies. We also review the evidence of the efficacy and safety of immunosuppressive drugs, antifibrotic agents, and immunomodulators from cyclophosphamide and mycophenolate to novel agents such as nintedanib and tocilizumab. We also emphasise the importance of early diagnosis and monitoring and describe our approach to pharmacological therapy for SSc-ILD patients.

Effects of Concurrent Resistance and Endurance Training Using Continuous or Intermittent Protocols on Muscle Hypertrophy: Systematic Review With Meta-Analysis.

ABSTRACT: Monserdà-Vilaró, A, Balsalobre-Fernández, C, Hoffman, JR, Alix-Fages, C, and Jiménez, SL. Effects of concurrent resistance and endurance training using continuous or intermittent protocols on muscle hypertrophy: Systematic review with meta-analysis. J Strength Cond Res 37(3): 688-709, 2023-The purpose of this systematic review with meta-analysis was to explore the effects of concurrent resistance and endurance training (CT) incorporating continuous or intermittent endurance training (ET) on whole-muscle and type I and II muscle fiber hypertrophy compared with resistance training (RT) alone. Randomized and nonrandomized studies reporting changes in cross-sectional area at muscle fiber and whole-muscle levels after RT compared with CT were included. Searches for such studies were performed in Web of Science, PubMed, Scopus, SPORTDiscus, and CINAHL electronic databases. The data reported in the included studies were pooled in a random-effects meta-analysis of standardized mean differences (SMDs). Twenty-five studies were included. At the whole-muscle level, there were no significant differences for any comparison (SMD < 0.03). By contrast, RT induced greater type I and type II muscle fiber hypertrophy than CT when high-intensity interval training (HIIT) was incorporated alone (SMD > 0.33) or combined with continuous ET (SMD > 0.27), but not compared with CT incorporating only continuous ET (SMD < 0.16). The subgroup analyses of this systematic review and meta-analysis showed that RT induces greater muscle fiber hypertrophy than CT when HIIT is included. However, no CT affected whole-muscle hypertrophy compared with RT.

WHO CNS5 2021 includes specific mutations in gliomas that can be identified with MRI quantitative biomarkers.

In 2021, the latest version of the World Health Organization classification of central nervous system tumors (WHO CNS5) was published, which is considered an international standard. The first editions of this classification were based on histological characteristics and, subsequently, aspects related to new knowledge were incorporated. In the 2016 revision, molecular characteristics were implemented for the classification and staging of gliomas, such as the presence of mutations in IDH1 or IDH2. Currently, advanced magnetic resonance imaging (MRI) techniques allow assessing for the presence of 2-HG (increased oncometabolite that precedes IDH mutations), whereby IDH mutations can be indirectly identified, without invasive procedures being required. Advanced MRI is a growing field, highly useful for diagnosis and management of different pathologies. This document addresses the implications of WHO CNS5 classification in the evaluation of gliomas, as well as historical aspects, the bases of conventional MRI, and advanced MRI sequences useful in current classification.

En 2021 se publicó la última versión de la clasificación de tumores del sistema nervioso central de la Organización Mundial de la Salud (WHO CNS5 por sus siglas en inglés), considerada un estándar internacional. Las primeras ediciones se basaron en características histológicas y posteriormente se incorporaron aspectos relacionados con nuevos conocimientos. En la revisión de 2016 se implementaron características moleculares para la clasificación y estadificación de los gliomas, como la presencia de mutaciones en IDH1 y IDH2. Actualmente, las técnicas de resonancia magnética avanzada permiten valorar la presencia de 2-HG (oncometabolito incrementado ante mutaciones en IDH), de forma que indirectamente y sin procedimientos invasivos pueden identificarse las mutaciones en IDH. La resonancia magnética avanzada es un procedimiento aún en desarrollo, de gran utilidad para el diagnóstico y manejo de distintas patologías. En el presente documento se abordan las implicaciones de la WHO CNS5 en la evaluación de gliomas, así como aspectos históricos, las bases de la resonancia magnética convencional y secuencias de resonancia magnética avanzada útiles en la clasificación actual.

Visual impairment associated with diabetic retinopathy and macular edema: a hospital-based study.

BACKGROUND: Data on visual impairment (VI) in patients with diabetes are necessary in order to guide economic and human resources for reducing its prevalence. OBJECTIVE: To estimate the prevalence of diabetic retinopathy-related VI in patients with type 2 diabetes in a hospital-based setting. MATERIAL AND METHODS: Cross-sectional study carried out from 2014 to 2019 in an ophthalmology outpatient clinic. Any VI was defined as corrected pin-hole visual acuity in the better eye of ≥ 0.24 logMAR. The presence of diabetic retinopathy (DR), diabetic macular edema (DME) and cataract was evaluated. RESULTS: A total of 840 patients were included; median diabetes duration was 15 years. The prevalence of VI was 30%. DR was found in 62% of patients (30% had sight-threatening DR [STDR]), 17% had referable DME, and 3%, cataracts. The odds ratio for moderate or worse VI was 9.02 for STDR (p < 0.001), 5.89 for referable DME (p = 0.001), and 2.51 for cataract (p = 0.006). CONCLUSION: Thirty percent of participants had some degree of VI. Moderate or worse VI showed a strong association with STDR and referable DME.

ANTECEDENTES: Los datos sobre discapacidad visual (DV) en pacientes con diabetes son necesarios para orientar los recursos económicos y humanos que disminuyan su prevalencia. OBJETIVO: Estimar la prevalencia de DV relacionada con retinopatía diabética en pacientes con diabetes tipo 2 en un entorno hospitalario. MATERIAL Y MÉTODOS: Estudio transversal realizado de 2014 a 2019 en una consulta externa de oftalmología. Cualquier DV se definió como agudeza visual corregida con agujero estenopeico en el ojo con mejor visión (≥ 0.24 logMAR). Se evaluó la presencia de retinopatía diabética, edema macular diabético (EMD) y cataratas. RESULTADOS: Se incluyeron 840 pacientes; la mediana de duración de la diabetes fue de 15 años. La prevalencia de DV fue de 30 %. Se encontró retinopatía diabética en 62 % (30 % tenía retinopatía diabética que amenazaba la visión [RDAV]); 17 %, EMD y 3 %, cataratas. La razón de momios para DV moderada o de mayor gravedad fue de 9.02 para RDAV (p < 0.001), 5.89 para EMD referible (p = 0.001) y 2.51 para catarata (p = 0.006). CONCLUSIÓN: Treinta por ciento de los participantes tenía algún grado de DV. La DV moderada o de mayor gravedad mostró una fuerte asociación con RDAV y EMD referible.

PhyloMissForest: a random forest framework to construct phylogenetic trees with missing data.

BACKGROUND: In the pursuit of a better understanding of biodiversity, evolutionary biologists rely on the study of phylogenetic relationships to illustrate the course of evolution. The relationships among natural organisms, depicted in the shape of phylogenetic trees, not only help to understand evolutionary history but also have a wide range of additional applications in science. One of the most challenging problems that arise when building phylogenetic trees is the presence of missing biological data. More specifically, the possibility of inferring wrong phylogenetic trees increases proportionally to the amount of missing values in the input data. Although there are methods proposed to deal with this issue, their applicability and accuracy is often restricted by different constraints. RESULTS: We propose a framework, called PhyloMissForest, to impute missing entries in phylogenetic distance matrices and infer accurate evolutionary relationships. PhyloMissForest is built upon a random forest structure that infers the missing entries of the input data, based on the known parts of it. PhyloMissForest contributes with a robust and configurable framework that incorporates multiple search strategies and machine learning, complemented by phylogenetic techniques, to provide a more accurate inference of lost phylogenetic distances. We evaluate our framework by examining three real-world datasets, two DNA-based sequence alignments and one containing amino acid data, and two additional instances with simulated DNA data. Moreover, we follow a design of experiments methodology to define the hyperparameter values of our algorithm, which is a concise method, preferable in comparison to the well-known exhaustive parameters search. By varying the percentages of missing data from 5% to 60%, we generally outperform the state-of-the-art alternative imputation techniques in the tests conducted on real DNA data. In addition, significant improvements in execution time are observed for the amino acid instance. The results observed on simulated data also denote the attainment of improved imputations when dealing with large percentages of missing data. CONCLUSIONS: By merging multiple search strategies, machine learning, and phylogenetic techniques, PhyloMissForest provides a highly customizable and robust framework for phylogenetic missing data imputation, with significant topological accuracy and effective speedups over the state of the art.

Serine/threonine kinase inhibition as antifibrotic therapy: transforming growth factor-ß and Rho kinase inhibitors.

Serine/threonine kinases mediate the phosphorylation of intracellular protein targets, transferring a phosphorus group from an adenosine triphosphate molecule to the specific amino acid residues within the target proteins. Serine/threonine kinases regulate multiple key cellular functions. From this large group of kinases, TGF-ß through serine/threonine activity of its receptors and Rho kinase (ROCK) play an important role in the development and maintenance of fibrosis in various human diseases, including SSc. In recent years, multiple drugs targeting and inhibiting these kinases have been developed, opening the possibility of becoming potential antifibrotic agents of clinical value for treating fibrotic diseases. This review analyses the contribution of TGF-ß and ROCK-mediated serine/threonine kinase molecular pathways to the development and maintenance of pathological fibrosis and the potential clinical use of their inhibition.

p53 regulation by MDM2 contributes to self-renewal and differentiation of basal stem cells in mouse and human airway epithelium.

Proper physiological function of mammalian airways requires the differentiation of basal stem cells into secretory or multiciliated cells, among others. In addition, the self-renewal ability of these basal stem cells is crucial for developing a quick response to toxic agents in order to re-establish the epithelial barrier function of the airways. Although these epithelial missions are vital, little is known about those mechanism controlling airway epithelial regeneration in health and disease. p53 has been recently proposed as the guardian of homeostasis, promoting differentiation programs, and antagonizing a de-differentiation program. Here, we exploit mouse and human tracheal epithelial cell culture models to study the role of MDM2-p53 signaling in self-renewal and differentiation in the airway epithelium. We show that p53 protein regulation by MDM2 is crucial for basal stem cell differentiation and to keep proper cell proliferation. Therefore, we suggest that MDM2/p53 interaction modulation is a potential target to control regeneration of the mammalian airway epithelia without massively affecting the epithelium integrity and differentiation potential.

Synergy of carbohydrate and caffeine ingestion on physical performance and metabolic responses to exercise: A systematic review with meta-analysis.

Carbohydrates (CHO) and caffeine (CAF) are two ergogenic aids commonly used among athletes to enhance performance. However, there is some controversy as to whether the concurrent intake of both supplements might result in an additive and synergistic improvement in exercise performance. The aim of this systematic review and meta-analysis was to determine the effect of adding CAF to a protocol of CHO ingestion, compared with the intake of each ergogenic aid alone and with placebo, on exercise performance and metabolic responses in healthy young physically active adults. This study was conducted according to PRISMA 2020 guidelines. The PubMed, Web of Science, Medline Complete, CINAHL, SPORTDiscus and CENTRAL databases were searched including randomized controlled trials (RCT) that were at least single blind. The risk of bias assessment was performed using the Cochrane Risk-of-Bias tool 2. Meta-analysis were performed on performance variables and rating of perceived exertion (RPE) using the random-effects model. Thirteen RCT with 128 participants (117 men and 11 women) were included in this study. The ingestion of CAF and CHO reduced sprint time during repeated sprint protocols in comparison with CHO isolated ingestion (SMD: -0.45; 95% CI: -0.85, -0.05) while there was a tendency for a reduction in the time employed during time trials (SMD: -0.36; 95% CI: -0.77, 0.05). The RPE tended to be lower with CAF and CHO compared with CHO isolated ingestion during steady-state exercise (SMD: -0.43; 95% CI: -0.91, 0.05) with no differences between conditions in performance trials (SMD: -0.05, 95% CI: -0.39, 0.29). Although most of the studies showed higher values of blood glucose when CHO was co-ingested with CAF compared with PLA, only two studies observed higher values with CHO and CAF co-ingestion with respect to the isolated intake of CHO. One study observed greater fat oxidation and lower glycogen use when CAF was added to CHO. In terms of cortisol levels, one study showed an increase in cortisol levels when CAF was co-ingested with CHO compared with PLA. In summary, concurrent CHO and CAF intake may produce an additive ergogenic effect respect of the isolated ingestion of CHO. This additive effect was present when CHO was provided by a 6-9% of CHO solution (maltodextrin/dextrin + fructose) and CAF is administered in a dose of 4-6.5 mg/kg.

Substance Use, Violence, and Sexual Risk Among Young Cis-Gender Women Placed at High-Risk for Human Immunodeficiency Virus Infection.

The substance use, violence, and AIDS (SAVA) syndemic framework is used to study risk for HIV/AIDS. As a secondary analysis from a large HIV/AIDS prevention study, we categorized participants into having from zero to three SAVA conditions based on the presence or absence of self-reported substance use in the past 4 months, history of lifetime sexual abuse, and intimate partner violence. We used Poisson regression models to examine the association between the number of SAVA conditions and sexual risk behavior. Among all participants (n = 195, median age, 20), 37.9%, 19.5%, and 6.7% reported occurrence of one, two, and all three SAVA conditions, respectively. We found that more than one SAVA condition experienced by women was significantly associated with having more than one sex partner (adjusted prevalence ratio [aPR] = 1.88; 95% confidence interval [CI] = 1.28, 2.76) and with substance use before sex (aPR = 1.61 95% CI = 1.06, 2.45).

Volviéndonos mejores: necesidad de acción inmediata ante el reto de la obesidad. Una postura de profesionales de la salud.

La creciente epidemia de obesidad ha sido uno de los retos más importantes de salud pública en México durante los últimos años. Con apoyo de la Federación Mundial de Obesidad, en 2021 formamos un grupo de profesionales para identificar y resumir las acciones prioritarias en las que puede enfocarse nuestro país para hacer frente a esta epidemia. Al proceso de desarrollo y discusión de este grupo se sumaron más de 1 000 profesionales de la salud para retomar recomendaciones de documentos y guías de alto nivel previamente publicados. En conmemoración del Día Mundial de la Obesidad, en este 2022 se presenta esta postura como insumo para el desarrollo de acciones en el ámbito profesional y de los diferentes sectores, en la que se incluyen 10 recomendaciones de acción, desde la perspectiva poblacional hasta la atención individualizada, y se enfatiza en la importancia de la participación social, de las intervenciones integrales con visión centrada en la persona y de la sostenibilidad planetaria, además de mejorar la educación y las campañas de difusión, propiciar un ambiente promotor de entornos activos y blindar de conflictos de interés los esfuerzos de prevención y control. La postura hace un llamado para abordar la obesidad de manera seria, con base en la evidencia científica, oportuna e integral, con enfoque de curso de vida, de forma ética y sensible, y sin perpetuar las barreras del estigma de peso en la sociedad.

The Genomic Landscape of Corticotroph Tumors: From Silent Adenomas to ACTH-Secreting Carcinomas.

Corticotroph cells give rise to aggressive and rare pituitary neoplasms comprising ACTH-producing adenomas resulting in Cushing disease (CD), clinically silent ACTH adenomas (SCA), Crooke cell adenomas (CCA) and ACTH-producing carcinomas (CA). The molecular pathogenesis of these tumors is still poorly understood. To better understand the genomic landscape of all the lesions of the corticotroph lineage, we sequenced the whole exome of three SCA, one CCA, four ACTH-secreting PA causing CD, one corticotrophinoma occurring in a CD patient who developed Nelson syndrome after adrenalectomy and one patient with an ACTH-producing CA. The ACTH-producing CA was the lesion with the highest number of single nucleotide variants (SNV) in genes such as USP8, TP53, AURKA, EGFR, HSD3B1 and CDKN1A. The USP8 variant was found only in the ACTH-CA and in the corticotrophinoma occurring in a patient with Nelson syndrome. In CCA, SNV in TP53, EGFR, HSD3B1 and CDKN1A SNV were present. HSD3B1 and CDKN1A SNVs were present in all three SCA, whereas in two of these tumors SNV in TP53, AURKA and EGFR were found. None of the analyzed tumors showed SNV in USP48, BRAF, BRG1 or CABLES1. The amplification of 17q12 was found in all tumors, except for the ACTH-producing carcinoma. The four clinically functioning ACTH adenomas and the ACTH-CA shared the amplification of 10q11.22 and showed more copy-number variation (CNV) gains and single-nucleotide variations than the nonfunctioning tumors.