Exploring atypical manifestations and multisystem involvement of Epstein-Barr virus infection in hospitalized pediatric patients from Mexico: insights from a tertiary hospital (2012-2022).

INTRODUCTION: Epstein-Barr virus (EBV) infection, with a global prevalence exceeding 95%, typically manifests in children as infectious mononucleosis. However, clinical practice frequently encounters diverse atypical presentations characterized by multisystem involvement, often resulting in an unfavorable clinical course. Our objective is to describe the clinical manifestations and results of EBV infection in a tertiary pediatric hospital in Mexico. METHOD: An observational, transversal, retrospective, and descriptive study that included a systematic review of medical records (2012-2022) of patients under 18 years of age with detectable EBV particles in peripheral blood. RESULTS: The study included 26 patients with a median age of 5 years and a male predominance of 53.8%. Predominant symptoms were fever (85%) and lymphadenopathy (35%). Sixty-five percent had severe and atypical manifestations, including pneumonia and hepatic, hematologic-oncologic, and autoimmune diseases. Anemia, thrombocytopenia and leukopenia were common, with lymphocytosis in 19% of cases. The median EBV viral load was 2816 copies/mL (range: 555-355,500 copies/mL). Four deaths related to EBV infection were reported. Viral load in these cases also varied widely from 594 to 121,000 copies/mL. Supportive care was administered to 85% of patients, while others received antiviral treatment, steroids, and rituximab. CONCLUSION: Atypical manifestations were common, especially in children with multisystem involvement. EBV should be considered as a potential contributor to a diverse spectrum of clinical presentations, emphasizing the need for comprehensive evaluation and awareness in clinical diagnosis.

INTRODUCCIÓN: La infección por el virus de Epstein-Barr (VEB) tiene una prevalencia mundial superior al 95%. Se considera que en los niños se manifiesta principalmente como mononucleosis infecciosa; sin embargo, en la práctica clínica, a menudo encontramos numerosas manifestaciones atípicas con compromiso multisistémico que llevan a un curso desfavorable. Nuestro objetivo es describir las manifestaciones clínicas y los resultados de la infección por VEB en un hospital pediátrico de tercer nivel en México. MÉTODO: Estudio observacional, transversal, retrospectivo y descriptivo, en el cual se revisaron sistemáticamente los expedientes médicos de pacientes menores de 18 años con una detección positiva de partículas de VEB en sangre periférica en el periodo 2012-2022. RESULTADOS: Se incluyeron 26 pacientes con una mediana de edad de 5 años y predominio de varones (53.8%). El 65% presentaron manifestaciones graves y atípicas, incluyendo enfermedades respiratorias, hepáticas, hematooncológicas y autoinmunitarias. Los síntomas más frecuentes fueron fiebre (85%) y linfadenopatía (35%). El 54% presentaron manifestaciones atípicas, incluyendo linfohistiocitosis hemofagocítica, neumonía y neoplasia. La anemia, la trombocitopenia y la leucocitopenia fueron comunes, mientras que el 19% presentaron linfocitosis. La media de la carga viral fue de 2816 copias/ml (555-355,500). Se informaron cuatro muertes atribuidas a la infección por VEB, con valores de carga viral de 594 a 121,000 copias/ml. El 85% de los pacientes recibieron solo tratamiento sintomático, mientras que otros recibieron antivirales, esteroides y rituximab. CONCLUSIÓN: Las manifestaciones atípicas se observaron comúnmente, en especial en niños con compromiso multisistémico. El VEB debe considerarse como un potencial factor contribuyente en el diagnóstico de una amplia gama de manifestaciones clínicas.

Phenolic compounds profile in extracts of Smilax spp., antioxidant activity, and inhibition of advanced glycation end products.

Smilax genus possesses bioactive properties attributed to phenolic compounds, which may exhibit antioxidant effects and inhibit the advanced glycation end products (AGEs). However, identifying these phenolic compounds and AGEs has become increasingly relevant to understanding such activities. This study aimed to identify phenolic compounds in extracts of Smilax spp. and evaluate their antioxidant and AGEs inhibitory activities. To achieve this, the Smilax genus was identified via PCR, and phenolic compounds including chlorogenic acid, naringenin-6-C-glucoside, quercetin, quercetin-3-O-glucoside, and myricetin were identified using HPLC-MS/MS. Antioxidant activity was assessed by ferric reducing antioxidant power (FRAP), and radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis-[3-ethyl-benzothiazoline]-6-sulfonic acid (ABTS), while AGEs inhibition was evaluated using a model system formed by bovine serum albumin-glucose. The highest antioxidant activity was 3612.18 mM TE/g, and the inhibition of AGEs was 52.44 %. These results demonstrate that Smilax spp. can inhibit AGEs, neutralize free radicals, and reduce compounds associated with antioxidant capacity.

Mineralocorticoid receptor (MR) antagonist eplerenone and MR modulator balcinrenone prevent renal extracellular matrix remodeling and inflammation via the MR/proteoglycan/TLR4 pathway.

Excessive activation of the mineralocorticoid receptor (MR) is implicated in cardiovascular and renal disease. Decreasing MR activation with MR antagonists (MRA) is effective to slow chronic kidney disease (CKD) progression and its cardiovascular comorbidities in animal models and patients. The present study evaluates the effects of the MR modulator balcinrenone and the MRA eplerenone on kidney damage in a metabolic CKD mouse model combining nephron reduction and a 60% high-fat diet. Balcinrenone and eplerenone prevented the progression of renal damages, extracellular matrix remodeling and inflammation to a similar extent. We identified a novel mechanism linking MR activation to the renal proteoglycan deposition and inflammation via the TLR4 pathway activation. Balcinrenone and eplerenone similarly blunted this pathway activation.

Obesity-Associated Colorectal Cancer.

Colorectal cancer (CRC) affects approximately 2 million people worldwide. Obesity is the major risk factor for CRC. In addition, obesity contributes to a chronic inflammatory stage that enhances tumor progression through the secretion of proinflammatory cytokines. In addition to an increased inflammatory response, obesity-associated cancer presents accrued molecular factors related to cancer characteristics, such as genome instability, sustained cell proliferation, telomere dysfunctions, angiogenesis, and microbial alteration, among others. Despite the evidence accumulated over the last few years, the treatments for obesity-associated CRC do not differ from the CRC treatments in normal-weight individuals. In this review, we summarize the current knowledge on obesity-associated cancer, including its epidemiology, risk factors, molecular factors, and current treatments. Finally, we enumerate possible new therapeutic targets that may improve the conditions of obese CRC patients. Obesity is key for the development of CRC, and treatments resulting in the reversal of obesity should be considered as a strategy for improving antineoplastic CRC therapies.

Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism.

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone Improves Diastolic Dysfunction in Preclinical Nondiabetic Chronic Kidney Disease.

BACKGROUND: The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes. METHODS AND RESULTS: We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity. CONCLUSIONS: We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.

Improved Feedback Quantizer with Discrete Space Vector.

The use of advanced modulation and control schemes for power converters, such as a Feedback Quantizer and Predictive Control, is widely studied in the literature. This work focuses on improving the closed-loop modulation scheme called Feedback Quantizer, which is applied to a three-phase voltage source inverter. This scheme has the natural behavior of mitigating harmonics at low frequencies, which are detrimental to electrical equipment such as transformers. This modulation scheme also provides good tracking for the voltage reference at the fundamental frequency. On the other hand, the disadvantage of this scheme is that it has a variable switching frequency, creating a harmonic spectrum in frequency dispersion, and it also needs a small sampling time to obtain good results. The proposed scheme to improve the modulation scheme is based on a Discrete Space Vector with virtual vectors to obtain a better approximation of the optimal vectors for use in the algorithm. The proposal improves the conventional scheme at a high sampling time (200 µs), obtaining a THD less than 2% in the load current, decreases the noise created by the conventional scheme, and provides a fixed switching frequency. Experimental tests demonstrate the correct operation of the proposed scheme.

High Pulsed Voltage Alkaline Electrolysis for Water Splitting.

Pulsed electrolysis has become a promising research topic in recent decades due to advances in solid-state semiconductor devices. These technologies have enabled the design and construction of simpler, more efficient, and less costly high-voltage and high-frequency power converters. In this paper, we study high-voltage pulsed electrolysis considering variations in both power converter parameters and cell configuration. Experimental results are obtained for frequency variations ranging from 10 Hz to 1 MHz, voltage changes from 2 V to 500 V, and electrode separations from 0.1 to 2 mm. The results demonstrate that pulsed plasmolysis is a promising method for decomposing water for hydrogen production.

Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence.

The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells.

Benefits of the Non-Steroidal Mineralocorticoid Receptor Antagonist Finerenone in Metabolic Syndrome-Related Heart Failure with Preserved Ejection Fraction.

The mineralocorticoid receptor (MR) plays an important role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Antagonizing the overactivation of the MR with MR antagonists (MRA) is a therapeutic option, but their use in patients with CKD is limited due to the associated risk of hyperkalemia. Finerenone is a non-steroidal MRA associated with an improved benefit-risk profile in comparison to steroidal MRAs. In this study, we decided to test whether finerenone improves renal and cardiac function in male hypertensive and diabetic ZSF1 rats as an established preclinical HFpEF model. Finerenone was administered at 10 mg/kg/day for 12 weeks. Cardiac function/hemodynamics were assessed in vivo. ZSF1 rats showed classical signs of CKD with increased BUN, UACR, hypertrophy, and fibrosis of the kidney together with characteristic signs of HFpEF including cardiac fibrosis, diastolic dysfunction, and decreased cardiac perfusion. Finerenone treatment did not impact kidney function but reduced renal hypertrophy and cardiac fibrosis. Interestingly, finerenone ameliorated diastolic dysfunction and cardiac perfusion in ZSF1 rats. In summary, we show for the first time that non-steroidal MR antagonism by finerenone attenuates cardiac diastolic dysfunction and improves cardiac perfusion in a preclinical HFpEF model. These cardiac benefits were found to be largely independent of renal benefits.

Multiomics insights on the onset, progression, and metastatic evolution of breast cancer.

Breast cancer is the most common malignant neoplasm in women. Despite progress to date, 700,000 women worldwide died of this disease in 2020. Apparently, the prognostic markers currently used in the clinic are not sufficient to determine the most appropriate treatment. For this reason, great efforts have been made in recent years to identify new molecular biomarkers that will allow more precise and personalized therapeutic decisions in both primary and recurrent breast cancers. These molecular biomarkers include genetic and post-transcriptional alterations, changes in protein expression, as well as metabolic, immunological or microbial changes identified by multiple omics technologies (e.g., genomics, epigenomics, transcriptomics, proteomics, glycomics, metabolomics, lipidomics, immunomics and microbiomics). This review summarizes studies based on omics analysis that have identified new biomarkers for diagnosis, patient stratification, differentiation between stages of tumor development (initiation, progression, and metastasis/recurrence), and their relevance for treatment selection. Furthermore, this review highlights the importance of clinical trials based on multiomics studies and the need to advance in this direction in order to establish personalized therapies and prolong disease-free survival of these patients in the future.

Association of total and pancreatic serum amylase enzymatic activity with insulin resistance and the glucose and insulin responses to oral starch test in Mexican children.

BACKGROUND/OBJECTIVES: Little is known about the effect of serum amylase enzymatic activity on glucose metabolism. We investigated the association of serum amylase enzymatic activity with fasting plasma glucose, insulin resistance (IR), and the plasma glucose and insulin response to an oral starch test (OST) in Mexican children. METHODS: Anthropometric data, glucose and insulin levels, and the serum enzymatic activity of total (AMYt), salivary (AMY1), and pancreatic (AMY2) amylase were analysed in 764 children (Nnormal weight  = 427/Nobesity  = 337). After categorization into low (LA) and high (HA) AMYt, an OST with commercial white bread was performed in 39 children (Nnormal weight  = 17/Nobesity  = 22). RESULTS: A positive association between serum enzymatic activity of AMY2 and IR was observed in children with obesity (p = 0.018). Children with normal weight had lower plasma glucose and insulin response to OST than children with obesity (Pglucose  = 4.1 × 10-12 ; Pinsulin  = 2.1 × 10-15 ). Compared with the LA group, children with HA showed lower plasma glucose and insulin response to OST (Pglucose ≤ 0.040; Pinsulin ≤ 0.015). CONCLUSION: Our results suggest that AMY2 is positively associated with IR. A high level of AMYt is related to lower glucose and insulin responses to OST in Mexican children, regardless of their weight status.

The myeloid mineralocorticoid receptor regulates dermal angiogenesis and inflammation in glucocorticoid-induced impaired wound healing.

BACKGROUND AND PURPOSE: Delayed wound healing is among the deleterious consequences of over-activation of the mineralocorticoid receptor (MR) induced by topical dermocorticoids. The role of dermal inflammation and angiogenesis in the benefits of MR blockade is unknown. EXPERIMENTAL APPROACH: Skin wounds were made on C57Bl6 mice after topical pretreatment with the dermocorticoid clobetasol. The impact of topical MR blockade by canrenoate on inflammation, angiogenesis, and the wound macrophage phenotype was analysed 5 days post-wounding. Similar experiments were conducted on mice with genetic deletion of the MR in myeloid cells. KEY RESULTS: Topical inhibition of the MR with canrenoate improved delayed wound healing through the resolution of prolonged inflammation in glucocorticoid-pretreated mouse skin. This effect was associated with a higher ratio of anti-inflammatory macrophages versus pro-inflammatory macrophages in wounds treated by canrenoate. Furthermore, MR blockade led to upregulated expression of pro-angiogenic factors and improved impaired angiogenesis in wounds of glucocorticoid-pretreated skin. Finally, deletion of MR expression by myeloid cells reproduced the benefits of topical pharmacological MR blockade. CONCLUSION AND IMPLICATIONS: Topical MR antagonism facilitates the switching of macrophages towards an anti-inflammatory phenotype, which improves prolonged inflammation and induces angiogenesis to accelerate wound healing delayed by glucocorticoid treatment.

Biglycan Is a Novel Mineralocorticoid Receptor Target Involved in Aldosterone/Salt-Induced Glomerular Injury.

The beneficial effects of mineralocorticoid receptor (MR) antagonists (MRAs) for various kidney diseases are established. However, the underlying mechanisms of kidney injury induced by MR activation remain to be elucidated. We recently reported aldosterone-induced enhancement of proteoglycan expression in mitral valve interstitial cells and its association with fibromyxomatous valvular disorder. As the expression of certain proteoglycans is elevated in several kidney diseases, we hypothesized that proteoglycans mediate kidney injury in the context of aldosterone/MR pathway activation. We evaluated the proteoglycan expression and tissue injury in the kidney and isolated glomeruli of uninephrectomy/aldosterone/salt (NAS) mice. The MRA eplerenone was administered to assess the role of the MR pathway. We investigated the direct effects of biglycan, one of the proteoglycans, on macrophages using isolated macrophages. The kidney samples from NAS-treated mice showed enhanced fibrosis and increased expression of biglycan accompanying glomerular macrophage infiltration and enhanced expression of TNF-α, iNOS, Nox2, CCL3 (C-C motif chemokine ligand 3), and phosphorylated NF-κB. Eplerenone blunted these changes. Purified biglycan stimulated macrophages to express TNF-α, iNOS, Nox2, and CCL3. This was prevented by a toll-like receptor 4 (TLR4) or NF-κB inhibitor, indicating that biglycan stimulation is dependent on the TLR4/NF-κB pathway. We identified the proteoglycan biglycan as a novel target of MR involved in MR-induced glomerular injury and macrophage infiltration via a biglycan/TLR4/NF-κB/CCL3 cascade.

Mineralocorticoid Receptor Antagonism Prevents the Synergistic Effect of Metabolic Challenge and Chronic Kidney Disease on Renal Fibrosis and Inflammation in Mice.

Obesity and/or metabolic diseases are frequently associated with chronic kidney disease and several factors associated with obesity may contribute to proteinuria and extracellular matrix production. Mineralocorticoid receptor antagonists have proven their clinical efficacy in diabetic kidney disease with preclinical data suggesting that they may also be efficient in non-diabetic chronic kidney disease associated to metabolic diseases. In the present study we developed a novel mouse model combining severe nephron reduction and High Fat Diet challenge that led to chronic kidney disease with metabolic alterations. We showed that the Mineralocorticoid Receptor antagonist canrenoate improved metabolic function, reduced albuminuria and prevented the synergistic effect of high fat diet on renal fibrosis and inflammation in chronic kidney disease mice.

Análisis comparativo de la respuesta e índice glicémico, carga glicémica y saciedad de leche alta en proteínas y leche sin lactosa en sujetos sanos

RESUMEN Objetivo: Determinar el efecto del consumo de 3 tipos de leche de vaca (sin lactosa, alta en proteínas y estándar) sobre carga glicémica (CG), respuesta glicémica (RG) e índice glicémico (IG) y el nivel de saciedad en adultos sanos. Metodología: En 11 sujetos sanos se aplicó la metodología propuesta por la norma ISO 26642 para determinar índice glicémico. Se obtuvo muestra de sangre capilar a los 0, 30, 45, 60, 90 y 120 minutos. Se evaluó el nivel de hambre, saciedad y plenitud mediante escala visual análoga (EVA). El análisis estadístico se hizo mediante Test de Friedman, Wilcoxon, ajustado por Bonferroni o ANOVA de medidas repetidas. Significancia estadística con valor p0,05). Conclusión: Si bien la leche sin lactosa presentó un alto índice glicémico, ésta no afectó el nivel de saciedad. Por otro lado, la leche alta en proteínas y estándar tienen un bajo índice glicémico.

ABSTRACT Objective: To determine the effect of consumption of 3 types of cow's milk (lactose free, high in protein, and standard) on glycemic load (GL), glycemic response (GR) and glycemic index (GI) and the level of satiety in healthy adults. Methodology: Eleven healthy subjects participated. The methodology proposed by the ISO 26642 standard was applied to determine GI. Capillary blood sample was obtained at 0, 30, 45, 60, 90 and 120 minutes. The level of hunger, satiety and fullness were evaluated using a visual analog scale (VAS). Statistical analysis was done using the Friedman, Wilcoxon test, adjusted by Bonferroni or repeated measures ANOVA. Statistical significance was set as p0.05). Conclusion: Although lactose-free milk had a high GI, it did not affect satiety. On the other hand, high protein and standard milk have a low GI.

Frequency of allele variations in the CFTR gene in a Mexican population.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CF variants incidence is highly variable and even undetermined in some countries like Mexico. METHODS: In this study, the allele frequencies of 361 variants in the CFTR gene were investigated in 1455 Mexicans without a CF or CFTR-related disorders (CFTR-RD) diagnosis. We also performed a statistical comparative analysis against allele frequencies of different populations to measure genetic differences in the prevalence of CFTR variants. RESULTS: In the vast majority of cases, the allele frequencies of this cohort were comparable to those found in other populations. However, some variants displayed significant differences in their allele frequencies when compared with European and African populations. CONCLUSIONS: This study provides information about CFTR variants to predict the prevalence of CF in Mexico and uncover other unknown but frequent pathogenic variants in the country. Additionally, other CFTR-RD variants have also been studied using population data of the same CFTR variants. Studies like this could help develop a regional molecular diagnostic screen to optimize the medical care of CF patients.

Efectividad y seguridad del uso de alfa-cetoanálogos en el manejo de la enfermedad renal crónica avanzada: recomendaciones para la práctica clínica / Effectiveness and safety of the use of alpha-keto analogues in the management of advanced chronic kidney disease: clinical practice recommendations

Resumen Introducción: la dieta con restricción de proteínas parece tener un papel importante en la progresión de la enfermedad renal crónica (ERC) y la aparición anticipada de síntomas urémicos, además la suplementación de aminoácidos esenciales ofrece aparente seguridad para lograr restricciones agresivas de proteínas. Objetivo: realizar una revisión de la literatura para establecer las recomendaciones de uso práctico sobre la dieta con restricción de proteínas en la ERC avanzada. Materiales y métodos: se realizó una búsqueda estructurada rápida de la literatura en la que se incluyeron revisiones sistemáticas y metaanálisis, de los cuales se extrajeron las respuestas de las preguntas con estructura PICOT diseñadas a priori. Los resultados fueron sometidos a consenso para generar recomendaciones prácticas. Resultados: se incluyeron 6 revisiones sistemáticas de la literatura con una evaluación de calidad moderada. Según los hallazgos, una dieta muy baja en proteínas con suplementación de alfa-cetoanálogos beneficia a los pacientes que ingresan a diálisis o son sometidos a trasplante renal, además reduce la progresión de la enfermedad. No obstante, se requiere de ensayos clínicos con mejor calidad que consideren aspectos como la calidad de vida. Conclusiones: aunque la evidencia es de baja calidad, se establece que la dieta muy baja en proteínas y suplementada con alfa-cetoanálogos en pacientes adecuadamente seleccionados reduce el deterioro de la tasa de filtración glomerular y parece reducir el ingreso a diálisis. Por tanto, se recomienda hacer un seguimiento estricto y periódico en el que se vigilen las medidas antropométricas y el perfil de riesgo de desnutrición.

Abstract Introduction and objective: The protein-restricted diet appears to play an important role in the progression of chronic kidney disease and the early onset of uremic symptoms, the supplementation of essential amino acids offers apparent security in achieving aggressive protein restrictions. The objective of this document is to carry out a literature review to inform practical use recommendations on this behavior in advanced Renal Disease (CKD). Materials and methods: A quick structured search of the literature is carried out, with the selection of systematic reviews and meta-analyzes, from which the answers to the questions with a PICOT structure designed a priori are extracted. The results were submitted to consensus to generate practical recommendations. Results: six systematic reviews of the literature were included, with a moderate quality evaluation, the extraction of the information reports an apparent benefit of the very low protein diet with supplementation of alpha-keto-analogues on admission to dialysis or kidney transplantation and a consistent reduction of disease progression. Better clinical trials that integrate outcomes such as quality of life are required. Conclusions: With low quality of evidence, the very low protein diet, supplemented with alpha-keto analogues, in the properly selected patient, reduces the deterioration of the glomerular filtration rate, seems to reduce admission to dialysis. Regular strict monitoring is recommended, with monitoring of anthropometric measures and malnutrition risk profile.

Insights into functional mitral regurgitation using transillumination rendering.

Secondary mitral regurgitation has been originally explained by tethering of the structurally normal mitral leaflets or by mitral annular dilation after atrial remodeling. Advances in echocardiography have provided more insights into functional anatomy of the mitral valve leaflets as active participants in this entity.

Antimicrobial resistance and antibiotic consumption in a third level pediatric hospital in Mexico City.

INTRODUCTION: The increasing resistance to antibiotics is a public health problem and an imminent therapeutic challenge in hospitals. In this report we aimed to analyze the relationship between antimicrobial resistance and antibiotic consumption in a third-level pediatric hospital. METHODOLOGY: A cross-sectional analysis was conducted using the information from the microbiology and pharmacy databases of the Pediatric Hospital "Doctor Silvestre Frenk Freund", during the period 2015-2018. Prevalence of antimicrobial resistance by microorganisms and dispensed grams of selected antibiotics were calculated annually. Antibiotic resistance trend over the time was evaluated using the Chi-square trends test and to assess the correlation between the dispensed grams of antibiotics with their antimicrobial resistance prevalence, we calculated the Pearson's coefficient (r). RESULTS: A total of 4,327 isolated bacterial samples were analyzed (56.5% Gram-positive and 44.5% Gram-negative). Most frequently isolated microorganisms were coagulase-negative staphylococci (CoNS), E. coli, K. pneumoniae, P. aeruginosa and S. aureus. We found a significant increase in resistance to clindamycin and oxacillin for CoNS and significant decrease in nitrofurantoin and amikacin resistance for E. coli and K. pneumoniae. We observed a strong positive and statistically significant correlation between amikacin resistance prevalence and amikacin dispensed grams for P. aeruginosa (r = 0.95, p = 0.05). CONCLUSIONS: The antibiotic resistance profile showed by our study highlights the need of an appropriate antibiotic control use in the Hospital setting.