Clinical practice guidelines for diagnostic and treatment of the chronic heart failure.

Chronic heart failure continues to be one of the main causes of impairment in the functioning and quality of life of people who suffer from it, as well as one of the main causes of mortality in our country and around the world. Mexico has a high prevalence of risk factors for developing heart failure, such as high blood pressure, diabetes, and obesity, which makes it essential to have an evidence-based document that provides recommendations to health professionals involved in the diagnosis and treatment of these patients. This document establishes the clinical practice guide (CPG) prepared at the initiative of the Mexican Society of Cardiology (SMC) in collaboration with the Iberic American Agency for the Development and Evaluation of Health Technologies, with the purpose of establishing recommendations based on the best available evidence and agreed upon by an interdisciplinary group of experts. This document complies with international quality standards, such as those described by the US Institute of Medicine (IOM), the National Institute of Clinical Excellence (NICE), the Intercollegiate Network for Scottish Guideline Development (SIGN) and the Guidelines International Network (G-I-N). The Guideline Development Group was integrated in a multi-collaborative and interdisciplinary manner with the support of methodologists with experience in systematic literature reviews and the development of CPG. A modified Delphi panel methodology was developed and conducted to achieve an adequate level of consensus in each of the recommendations contained in this CPG. We hope that this document contributes to better clinical decision making and becomes a reference point for clinicians who manage patients with chronic heart failure in all their clinical stages and in this way, we improve the quality of clinical care, improve their quality of life and reducing its complications.

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad.

Highly multiplexed design of an allosteric transcription factor to sense novel ligands.

Allosteric transcription factors (aTF), widely used as biosensors, have proven challenging to design for detecting novel molecules because mutation of ligand-binding residues often disrupts allostery. We developed Sensor-seq, a high-throughput platform to design and identify aTF biosensors that bind to non-native ligands. We screened a library of 17,737 variants of the aTF TtgR, a regulator of a multidrug exporter, against six non-native ligands of diverse chemical structures - four derivatives of the cancer therapeutic tamoxifen, the antimalarial drug quinine, and the opiate analog naltrexone - as well as two native flavonoid ligands, naringenin and phloretin. Sensor-seq identified novel biosensors for each of these ligands with high dynamic range and diverse specificity profiles. The structure of a naltrexone-bound design showed shape-complementary methionine-aromatic interactions driving ligand specificity. To demonstrate practical utility, we developed cell-free detection systems for naltrexone and quinine. Sensor-seq enables rapid, scalable design of new biosensors, overcoming constraints of natural biosensors.

Urinary concentration of Cathepsin D as a relievable marker of preeclampsia.

BACKGROUND: The early and accurate diagnosis of preeclampsia is crucial to avoid serious complications for both the mother and baby. However, the current diagnostic methods are limited, and there is a need for new diagnostic biomarkers. Previous studies have shown that cathepsin D (CTD) participates in the pathophysiology of preeclampsia and is present in urine samples, making it a potential biomarker for the disease. This study aimed to compare urinary and serum levels of CTD in preeclamptic and normotensive women and analyze its potential role as a diagnostic biomarker in preeclampsia. METHODS: The study included thirty-nine patients with preeclampsia and twelve normotensive pregnant women as controls. Biomarkers were determined using Multiplex Assay kit, and serum prolactin (Prl) and urinary TNF-α levels were also evaluated. Statistical analysis was conducted using the Mann-Whitney U test. RESULTS: We found that urinary and serum CTD levels were significantly higher in the preeclampsia group than in the normotensive group, suggesting that CTD could be a diagnostic biomarker for preeclampsia. No significant differences were found in the levels of serum prolactin or urinary TNF-α between the two groups. CONCLUSIONS: The study provides evidence that non-invasive biological samples such as urine can be used to improve new therapeutic strategies for the early management of preeclampsia.

Noninvasive Diabetes Detection through Human Breath Using TinyML-Powered E-Nose.

Volatile organic compounds (VOCs) in exhaled human breath serve as pivotal biomarkers for disease identification and medical diagnostics. In the context of diabetes mellitus, the noninvasive detection of acetone, a primary biomarker using electronic noses (e-noses), has gained significant attention. However, employing e-noses requires pre-trained algorithms for precise diabetes detection, often requiring a computer with a programming environment to classify newly acquired data. This study focuses on the development of an embedded system integrating Tiny Machine Learning (TinyML) and an e-nose equipped with Metal Oxide Semiconductor (MOS) sensors for real-time diabetes detection. The study encompassed 44 individuals, comprising 22 healthy individuals and 22 diagnosed with various types of diabetes mellitus. Test results highlight the XGBoost Machine Learning algorithm's achievement of 95% detection accuracy. Additionally, the integration of deep learning algorithms, particularly deep neural networks (DNNs) and one-dimensional convolutional neural network (1D-CNN), yielded a detection efficacy of 94.44%. These outcomes underscore the potency of combining e-noses with TinyML in embedded systems, offering a noninvasive approach for diabetes mellitus detection.

Rational Approach to Optimizing Conformation-Switching Aptamers for Biosensing Applications.

The utilization of structure-switching aptamers (SSAs) has enabled the development of novel sensing platforms for the sensitive and continuous detection of molecules. De novo development of SSAs, however, is complex and laborious. Here we describe a rational approach to SSA optimization that simultaneously improves aptamer binding affinity and introduces target-dependent conformation-switching for compatibility with real-world biosensor applications. Key structural features identified from NMR and computational modeling were used to optimize conformational switching in the presence of target, while large-scale, microarray-based mutation analysis was used to map regions of the aptamer permissive to mutation and identify combinations of mutations with stronger binding affinity. Optimizations were carried out in a relevant biofluid to ensure a seamless transition of the aptamer to a biosensing platform. Initial proof-of-concept for this approach is demonstrated with a cortisol binding aptamer but can easily be translated to other relevant aptamers. Cortisol is a hormone correlated with the stress response that has been associated with various medical conditions and is present at quantifiable levels in accessible biofluids. The ability to continuously track levels of stress in real-time via cortisol monitoring, which can be enabled by the aptamers reported here, is crucial for assessing human health and performance.

The Incidence, Impact, and Techniques of Commissural Alignment in Transcatheter Aortic Valve Implantation: A Review.

In current clinical practice, commissural alignment of the transcatheter heart valve (THV) during transcatheter aortic valve implantation (TAVI) is seldom achieved. Orientation of the THV within the aortic root and the subsequent influence upon leaflet haemodynamic function, coronary blood flow, and ease of access to the coronary ostia are gaining significant interest. Herein, we review the incidence and clinical implications of commissural misalignment in TAVI and offer thorough descriptions of how optimal alignment can be achieved with several different contemporary THV devices.

Transcutaneous Spinal Cord Stimulation to Stabilize Seated Systolic Blood Pressure in Persons With Chronic Spinal Cord Injury: Protocol Development.

Transcutaneous spinal cord stimulation (tSCS) is an emerging therapeutic strategy to target spinal autonomic circuitry to normalize and stabilize blood pressure (BP) in hypotensive persons living with chronic spinal cord injury (SCI). Our aim is to describe our current methodological approach to identify individual tSCS parameters that result in the maintenance of seated systolic blood pressure (SBP) within a pre-defined target range. The parent study is a prospective, randomized clinical trial in which eligible participants will undergo multiple mapping sessions to optimize tSCS parameter settings to promote stable SBP within a target range of 110-120 mm Hg for males and 100-120 mm Hg for females. Parameter mapping includes cathode electrode placement site (T7/8, T9/10, T11/12, and L1/2), stimulation frequency (30, 60 Hz), current amplitudes (0-120 mA), waveform (mono- and biphasic), pulse width (1000 µs), and use of carrier frequency (0, 10 kHz). Each participant will undergo up to 10 mapping sessions involving different electrode placement sites and parameter settings. BP will be continuously monitored throughout each mapping session. Stimulation amplitude (mA) will be increased at intervals of between 2 and 10 mA until one of the following occurs: 1) seated SBP reaches the target range; 2) tSCS intensity reaches 120 mA; or 3) the participant requests to stop. Secondary outcomes recorded include 1) symptoms related to autonomic dysreflexia and orthostatic hypotension, 2) Likert pain scale, and 3) skin appearance after removal of the tSCS electrode. Clinical Trials Registration: NCT05180227.

El conocimiento y cumplimiento de las normas de protección sobre la radiación ionizante en una clínica dental docente

Introducción: El uso de radiografías como elemento complementario para el diagnóstico es fundamental para la práctica profesional de todo cirujano dentista. Por tanto, es importante conocer no solo los beneficios de la radiología oral y los fundamentos de protección radiológica, sino también determinar su nivel de aplicación o la adherencia frente al cumplimiento de los aspectos normativos que regulan el uso de la radiación ionizante en odontología. Objetivo: Relacionar el conocimiento sobre los cuidados en radiología bucal, las ventajas y los peligros en la toma de radiografías con el cumplimiento de las normas de protección radiológica y radiación ionizante en estudiantes de odontología de una clínica dental docente. Métodos: La población de estudio estuvo constituida por 180 estudiantes del cuarto año de la carrera de odontología, que emplearon los equipos radiológicos en la clínica docente asistencial durante los años 2019 (segundo semestre) y 2020 (primer trimestre). Se tomó como muestra representativa a 104 estudiantes, incorporados al estudio mediante muestreo aleatorio simple. Se aplicaron dos instrumentos de recolección de datos, uno para evaluar el conocimiento (cuestionario) y otro para verificar el cumplimiento de normas (lista de chequeo) sobre la protección radiológica y el diagnóstico por imágenes en la práctica odontológica. Para el análisis estadístico se aplicó la prueba estadística chi cuadrado con un nivel de significancia del 95 %. Resultados: No se encontró relación estadísticamente significativa (p = 0,30) entre el conocimiento teórico sobre la protección radiológica y el diagnóstico por imágenes, respecto el cumplimiento de las normas que regulan su aplicación (p > 0,05). El 90 % de participantes tienen conocimientos entre regulares y excelentes. Sin embargo, solo el 32 % cumple las normas técnicas de protección sobre radiación ionizante en su práctica clínica. Conclusión: Los estudiantes de odontología tienen suficiente conocimiento sobre protección radiológica y diagnóstico por imágenes. Sin embargo, este conocimiento no se refleja en prácticas adheridas a las normas.

Introduction: The use of radiographs as a complementary element for diagnosis is fundamental to the professional practice of every dental surgeon. Therefore, it is important to know not only the benefits of oral radiology and the fundamentals of radiological protection, but also to determine their level of application or adherence to compliance with the regulatory aspects that regulate the use of ionizing radiation in dentistry. Objective: To relate the knowledge of oral radiology care, the advantages and dangers in taking radiographs with compliance with the norms of radiological protection and ionizing radiation in dental students of a dental teaching clinic. Methods: The study population consisted of 180 fourth year dental students who used the radiological equipment in the teaching dental clinic during 2019 (second semester) and 2020 (first quarter). A representative sample of 104 students was taken, incorporated into the study by simple random sampling. Two data collection instruments were applied, one to evaluate knowledge (questionnaire) and the other to verify compliance with standards (checklist) on radiological protection and diagnostic imaging in dental practice. For the statistical analysis the chi-square statistical test was applied with a significance level of 95 %. Results: No statistically significant relationship was found (p = 0.30) between theoretical knowledge of radiological protection and diagnostic imaging with respect to compliance with the norms that regulate its application (p > 0.05). Ninety percent of participants have fair to excellent knowledge. However, only 32 % comply with the technical norms of ionizing radiation protection in their clinical practice. Conclusion: Dental students have sufficient knowledge of radiation protection and diagnostic imaging. However, this knowledge is not reflected in practices that adhere to the standards.

Actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata sobre células de adenocarcinoma mamario murino 4T1

Introducción. Los tumores neoplásicos se caracterizan por su invasividad y metástasis. Las células neoplásicas tienen heterogeneidad genética, por lo cual pueden desarrollar resistencia a los quimioterápicos. Por esta razón, las plantas continúan siendo una fuente importante de nuevos productos anticancerígenos. Objetivo. Evaluar la actividad citotóxica y antiproliferativa de un extracto rico en fucoidan de Lessonia trabeculata nativa (EFLt) sobre la línea celular de adenocarcinoma mamario murino, triple negativo 4T1. Métodos. La citotoxicidad y la IC50 se determinaron en monocapas de 4T1 empleando el reactivo MTT. Para demostrar la actividad antiproliferativa se aplicaron los métodos de cierre de herida y anticlonogénico utilizando las IC50 del EFLt y Dox (doxorubicina). El cierre de herida fue evaluado mediante barrido de tiempos discretos; el efecto anticlonogénico fue evaluado 7 días postratamiento mediante el conteo de colonias y se determinó la fracción de sobrevivencia. Adicionalmente, se evaluaron la citotoxicidad y actividad antiproliferativa combinando las IC50 de EFLt y Dox. El porcentaje de migración y conteo de colonias se realizó con el programa ImageJ. Resultados. La IC50 del EFLt (950 μg/mL) produjo 56% de citotoxicidad, 80,3% de inhibición de la migración celular, 68% de inhibición en la formación de colonias. La IC50 de Dox fue 0,5 μg/mL. Conclusiones. El EFLt ejerce citotoxicidad dependiente de la concentración y tiene efecto antiproliferativo sobre 4T1. Se requiere continuar los ensayos en modelos de mayor complejidad que permitan esclarecer el potencial antitumoral del EFLt.

Introduction. Neoplastic tumors are characterized by invasiveness and metastasis. Neoplastic cells are genetically heterogeneous and can develop resistance to chemotherapeutic agents. For this reason, plants continue to be an important source of new anticancer products. Objective. To determine the cytotoxic and antiproliferative activity of a fucoidan-rich extract of native Lessonia trabeculata (EFLt) on the tripe negative murine mammary adenocarcinoma cell line 4T1. Methods. Cytotoxicity and IC50 were determined in 4T1 monolayers using the MTT reagent. To demonstrate antiproliferative activity, "wound" closure and anticlonogenic methods were applied using the IC50 of EFLt and Doc (doxorubicin). "Wound" closure was evaluated by discrete times sweep to determine percentage inhibition of cell migration; the anticlonogenic effect was evaluated by colony counting 7 days after treatment and the survival fraction was determined. In addition, cytotoxicity and antiproliferative activity were evaluated by combining the IC50 of EFLt and Dox. Percent migration and colony counts were performed using ImageJ software. Results. The IC50 (950 μg/mL) of EFLt was 56% cytotoxicity, 80,3% inhibition of cell migration, 68% inhibition of colony formation.The ICof Dox was 0,5 μg/mL. Conclusions. EFLt exerts concentration-dependent cytotoxicity and antiproliferative effect on 4T1. Further studies in more complex models are needed to elucidate the anti-tumor potential of EFLt.

Analysis of gene expression related to polyamine concentration and dimorphism induced in ornithine decarboxylase (odc) and spermidine synthase (spd) Ustilago maydis mutants.

Polyamines are ubiquitous small organic cations, and their roles as regulators of several cellular processes are widely recognized. They are implicated in the key stages of the fungal life cycle. Ustilago maydis is a phytopathogenic fungus, the causal agent of common smut of maize and a model system to understand dimorphism and virulence. U. maydis grows in yeast form at pH 7 and it can develop its mycelial form in vitro at pH 3. Δodc mutants that are unable to synthesize polyamines, grow as yeast at pH 3 with a low putrescine concentration, and to complete its dimorphic transition high putrescine concentration is require. Δspd mutants require spermidine to grow and cannot form mycelium at pH 3. In this work, the increased expression of the mating genes, mfa1 and mfa2, on Δodc mutants, was related to high putrescine concentration. Global gene expression analysis comparisons of Δodc and Δspd U. maydis mutants indicated that 2,959 genes were differentially expressed in the presence of exogenous putrescine at pH 7 and 475 genes at pH 3. While, in Δspd mutant, the expression of 1,426 genes was affected by exogenous spermine concentration at pH 7 and 11 genes at pH 3. Additionally, we identified 28 transcriptional modules with correlated expression during seven tested conditions: mutant genotype, morphology (yeast, and mycelium), pH, and putrescine or spermidine concentration. Furthermore, significant differences in transcript levels were noted for genes in modules relating to pH and genotype genes involved in ribosome biogenesis, mitochondrial oxidative phosphorylation, N-glycan synthesis, and Glycosylphosphatidylinositol (GPI)-anchor. In summary, our results offer a valuable tool for the identification of potential factors involved in phenomena related to polyamines and dimorphism.

COVID-19: presentación clínica inicial y su correlación con la gravedad de la enfermedad / COVID-19: initial clinical presentation and its correlation with the severity of the disease

Los pacientes con COVID-19 tienen un amplio espectro de presentación clínica y las tasas de mortalidad en los casos graves son relativamente altas. La identificación tem prana de los factores de riesgo que se relacionan con la gravedad de la enfermedad es de vital importancia. Con el objetivo de correlacionar los síntomas iniciales de COVID-19 con la gravedad de la enfermedad, se realizó el presente estudio de cohorte transversal retrospectivo y observacional de 413 pacientes con diagnóstico de COVID-19 entre enero y marzo 2021. De todos los síntomas iniciales estudiados, la disnea (p < 001), fiebre (p 0,001), tos (p 0,002), odinofagia (p 0,01), cefalea (p 0,01) y síntomas gastrointestinales (p 0,03), se asociaron con el desarrollo de una enfermedad grave. Las comorbilidades que se asociaron con peor pronóstico fueron: hipertensión arterial (p < 0,001), obesidad (p < 0,001), EPOC (p < 0,001), extabaquismo (p < 0,001), diabetes (p 0,01), enfermedad cardiovascular previa (p 0,03), y enfermedad oncológica activa (p 0,04). En conclusión, los pacientes con diagnóstico de COVID-19, cuya manifestación inicial es disnea, fiebre, tos, odinofagia, cefalea y síntomas gastrointestinales, deben ser monitoreados de cerca para prevenir el deterioro de la enfermedad.

Patients with COVID-19 have a broad spectrum of clinical presentations, and mortal ity rates are relatively high in severe cases. Early identification of risk factors that are related to the severity of the disease is of vital importance. In order to correlate the initial symptoms of COVID-19 with disease severity, the present retrospective, cross-sectional, observational cohort study was conducted, including 413 patients diagnosed with COVID-19 between January and March, 2021. Of all the initial symptoms that were studied, dyspnea (p < 001), fever (p 0.001), cough (p 0.002), odynophagia (p 0.01), headache (p 0.01), and gastrointestinal symptoms (p 0.03) were associated with the development of severe illness. The comorbidities that were associated with the worst prognoses were: arterial hypertension (p < 0.001), obesity (p < 0.001), COPD (chronic obstructive pulmonary disease) (p < 0.001), former smoking (p < 0.001), diabetes (p 0.01), previous cardiovascular disease (p 0.03), and active oncological disease (p 0.04). In conclusion, patients diagnosed with COVID-19 whose initial manifestations include dyspnea, fever, cough, odynophagia, headache, and gastrointestinal symptoms should be closely monitored to prevent disease deterioration.

Incoherent merger network for robust ratiometric gene expression response.

A ratiometric response gives an output that is proportional to the ratio between the magnitudes of two inputs. Ratio computation has been observed in nature and is also needed in the development of smart probiotics and organoids. Here, we achieve ratiometric gene expression response in bacteria Escherichia coli with the incoherent merger network. In this network, one input molecule activates expression of the output protein while the other molecule activates an intermediate protein that enhances the output's degradation. When degradation rate is first order and faster than dilution, the output responds linearly to the ratio between the input molecules' levels over a wide range with R2 close to 1. Response sensitivity can be quantitatively tuned by varying the output's translation rate. Furthermore, ratiometric responses are robust to global perturbations in cellular components that influence gene expression because such perturbations affect the output through an incoherent feedforward loop. This work demonstrates a new molecular signal processing mechanism for multiplexed sense-and-respond circuits that are robust to intra-cellular context.

A multiplexed, paired-pooled droplet digital PCR assay for detection of SARS-CoV-2 in saliva.

In response to the SARS-CoV-2 pandemic, we developed a multiplexed, paired-pool droplet digital PCR (MP4) screening assay. Key features of our assay are the use of minimally processed saliva, 8-sample paired pools, and reverse-transcription droplet digital PCR (RT-ddPCR) targeting the SARS-CoV-2 nucleocapsid gene. The limit of detection was determined to be 2 and 12 copies per µl for individual and pooled samples, respectively. Using the MP4 assay, we routinely processed over 1,000 samples a day with a 24-h turnaround time and over the course of 17 months, screened over 250,000 saliva samples. Modeling studies showed that the efficiency of 8-sample pools was reduced with increased viral prevalence and that this could be mitigated by using 4-sample pools. We also present a strategy for, and modeling data supporting, the creation of a third paired pool as an additional strategy to employ under high viral prevalence.

Candida auris Discovery through Community Wastewater Surveillance during Healthcare Outbreak, Nevada, USA, 2022.

Candida auris transmission is steadily increasing across the United States. We report culture-based detection of C. auris in wastewater and the epidemiologic link between isolated strains and southern Nevada, USA, hospitals within the sampled sewershed. Our results illustrate the potential of wastewater surveillance for containing C. auris.