Redox cycling-based signal amplification at alkanethiol modified nanoporous gold interdigitated microelectrodes.

Interdigitated electrodes (IDEs) enable electrochemical signal enhancement through repeated reduction and oxidation of the analyte molecule. Porosity on these electrodes is often used to lower the impedance background. However, their high capacitive current and signal interferences with oxygen reduction limit electrochemical detection ability. We present utilization of alkanethiol modification on nanoporous gold (NPG) electrodes to lower their background capacitance and chemically passivate them from interferences due to oxygen reduction, while maintaining their fast electron transfer rates, as validated by lower separation between anodic and cathodic peaks (ΔE) and lower charge transfer resistance (Rct) values in comparison to planar gold electrodes. Redox amplification based on this modification enables sensitive detection of various small molecules, including pyocyanin, p-aminophenol, and selective detection of dopamine in the presence of ascorbic acid. Alkanethiol NPG arrays are applied as a multiplexed sensor testbed within a well plate to screen binding of various peptide receptors to the SARS COV2 S-protein by using a sandwich assay for conversion of PAPP (4-aminophenyl phosphate) to PAP (p-aminophenol), by the action of AP (alkaline phosphatase), which is validated against optical ELISA screens of the peptides. Such arrays are especially of interest in small volume analytical settings with complex samples, wherein optical methods are unsuitable.

Complete mitochondrial genome of the introduced Indian walking stick Carausius morosus (Lonchodidae, Insecta) from California.

We present the complete mitochondrial genome of Carausius morosus from Salinas, CA. The mitochondrial genome of C. morosus is circular, AT rich (78.1%), and 16,671 bp in length. It consists of 13 protein-coding, 22 transfer RNA, and 2 ribosomal RNA genes and is identical in gene content to Carausius sp.

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.

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.

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.

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 / Knowledge and compliance with ionizing radiation protection standards in a teaching dental clinic

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.

Lesiones en tejidos dentarios y trastornos de la salud bucal en el examen médico ocupacional de trabajadores del sector construcción de Lima, Perú / Lesions in dental tissues and oral health disorders in the occupational medical examination of workers in the construction sector in Lima, Peru / Lesões nos tecidos dentários e perturbações da saúde oral no exame médico ocupacional dos trabalhadores do sector da construção em Lima, Peru

RESUMEN Objetivo: Describir las lesiones en tejidos dentarios y trastornos de la salud bucal encontradas durante el examen médico ocupacional en trabajadores del sector construcción de Lima, Perú. Material y métodos: Estudio epidemiológico transversal realizado en 150 trabajadores del sector construcción, seleccionados mediante muestreo aleatorio simple. Se realizó una evaluación estomatológica mediante observación directa y se empleó un instrumento de evaluación odontológico-ocupacional con índices para caries dental, severidad de caries y traumatismos dentales e indicadores de consecuencias clínicas de caries no tratada (patología pulpar) y lesiones no cariosas. Resultados: La experiencia de caries de los operadores sin estudio superior (CPOD = 14,99) y con estudio superior (CPOD = 13,06) fue superior frente a los supervisores (CPOD = 8,23) y administrativos (CPOD = 5,08). Los trabajadores operadores sin estudio superior (SiC = 18,04) y con estudio superior (SiC = 17,17) presentaron peores indicadores de significancia de caries frente a los supervisores (SiC = 13,67) y administrativos (SiC = 8,25). Además, los operadores sin estudio superior presentaron mayor carga de consecuencias clínicas de caries no tratada (PUFA = 2,35; severidad = 9,2%) en comparación con los operativos con estudio superior (PUFA = 1,91; severidad = 8,4%), los supervisores (PUFA = 0,53; severidad = 2,1%) y los administrativos (PUFA = 0,46; severidad = 1,8%), así como mayor frecuencia de lesiones no cariosas (47,3 %) y traumatismos dentales (21,3 %). Conclusiones: La salud dental, sus consecuencias clínicas y la estructura de los tejidos dentarios de los trabajadores operativos de una empresa constructora se encuentran más afectadas en comparación con los otros grupos laborales de la misma empresa.

ABSTRACT Objective: To describe the lesions in dental tissues and oral health disorders found during the occupational medical examination of workers in the construction sector in Lima, Peru. Material and methods: A cross-sectional epidemiological study was carried out on 150 workers in the construction sector, selected by simple random sampling. A stomatological evaluation was carried out by direct observation, and a dental-occupational evaluation instrument was used with indexes for dental caries, caries severity and dental trauma, and indicators of clinical consequences of untreated caries (pulp pathology) and non-carious lesions. Results: The caries experience of operators without higher education (CPOD = 14.99) and with higher education (CPOD = 13.06) was higher than that of supervisors (CPOD = 8.23) and administrative workers (CPOD = 5.08). The operators without higher education (SiC = 18.04) and with higher education (SiC = 17.17) presented worse caries significance indicators compared to supervisors (SiC = 13.67) and administrative workers (SiC = 8.25). In addition, operators without higher education had a higher burden of clinical consequences of untreated caries (PUFA = 2.35; severity = 9.2%) compared to operators with higher education (PUFA = 1.91; severity = 8.4%), supervisors (PUFA = 0.53; severity = 2.1%) and administrators (PUFA = 0.46; severity = 1.8%), as well as a higher frequency of non-carious lesions (47.3%) and dental trauma (21.3%). Conclusions: Dental health, its clinical consequences, and the structure of the dental tissues of the operative workers of a construction company are more affected compared to the other labor groups of the same company.

RESUMO Objetivo: Descrever as lesões nos tecidos dentários e os distúrbios de saúde oral encontrados durante o exame médico ocupacional em trabalhadores do sector da construção em Lima, Peru. Material e métodos: Foi realizado um estudo epidemiológico transversal em 150 trabalhadores do sector da construção, selecionados por amostragem aleatória simples. Foi realizada uma avaliação de estomatologia por observação direta e foi utilizado um instrumento de avaliação dentária ocupacional com índices de cárie dentária, gravidade da cárie e traumatismo dentário e indicadores das consequências clínicas da cárie não tratada (patologia pulpar) e lesões não cariosas. Resultados: A experiência de cárie dos operadores sem ensino superior (CPOD = 14,99) e com ensino superior (CPOD = 13,06) foi maior em comparação com os supervisores (CPOD = 8,23) e trabalhadores administrativos (CPOD = 5,08). Os operadores sem ensino superior (SiC = 18,04) e com ensino superior (SiC = 17,17) apresentaram piores indicadores de significância da cárie quando comparados aos supervisores (SiC = 13,67) e aos funcionários administrativos (SiC = 8,25). Além disso, os operadores sem ensino superior apresentaram maior carga de consequências clínicas da cárie não tratada (PUFA = 2,35; severidade = 9,2%) em relação aos operadores com ensino superior (PUFA = 1,91; severidade = 8,4%), supervisores (PUFA = 0,53; severidade = 2,1%) e administradores (PUFA = 0,46; severidade = 1,8%), bem como maior frequência de lesões não cariosas (47,3%) e traumatismos dentários (21,3%). Conclusões: A saúde dentária, as suas consequências clínicas e a estrutura dos tecidos dentários dos operários de uma empresa de construção civil são mais afetadas em comparação com os outros grupos de trabalho da mesma empresa.

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.