Electrochemical biotool for the dual determination of epithelial mucins associated to prognosis and minimal residual disease in colorectal cancer.

This work reports a dual immunoplatform for the simultaneous detection of two epithelial glycoproteins of the mucin family, mucin 1 (MUC1) and mucin 16 (MUC16), whose expression is related to adverse prognosis and minimal residual disease (MRD) in colorectal cancer (CRC). The developed immunoplatform involves functionalised magnetic microparticles (MBs), a set of specific antibody pairs (a capture antibody, cAb, and a biotinylated detector antibody b-dAb labelled with a streptavidin-horseradish peroxidase, Strep-HRP, polymer) for each target protein and amperometric detection at dual screen-printed carbon electrodes (SPdCEs) using the hydroquinone (HQ)/horseradish peroxidase (HRP)/H2O2 system. This dual immunoplatform allows, under the optimised experimental conditions, to achieve LOD values of 50 and 1.81 pg mL-1 (or mU mL-1) for MUC1 and MUC16, respectively, and adequate selectivity for the determination of the two targets in the clinic. The developed immunoplatform was employed to analyse CRC cell protein extracts (1.0 µg/determination) with different metastatic potential providing results in agreement with those obtained by blotting technologies but using affordable and applicable point-of-care instruments. This new biotool also emerges competitive in state-of-the-art electrochemical immunoplatforms seeking a compromise among simplicity, reduction of test time and analytical characteristics.

First bioelectronic immunoplatform for quantitative secretomic analysis of total and metastasis-driven glycosylated haptoglobin.

The glycosylation status of proteins is increasingly used as biomarker to improve the reliability in the diagnosis and prognosis of diseases as relevant as cancer. This feeds the need for tools that allow its simple and reliable analysis and are compatible with applicability in the clinic. With this objective in mind, this work reports the first bioelectronic immunoplatforms described to date for the determination of glycosylated haptoglobin (Hp) and the simultaneous determination of total and glycosylated Hp. The bioelectronic immunoplatform is based on the implementation of non-competitive bioassays using two different antibodies or an antibody and a lectin on the surface of commercial magnetic microcarriers. The resulting bioconjugates are labeled with the horseradish peroxidase (HRP) enzyme, and after their magnetic capture on disposable electroplatforms, the amperometric transduction using the H2O2/hydroquinone (HQ) system allows the single or multiple detection. The developed immunoplatform achieves limits of detection (LODs) of 0.07 and 0.46 ng mL-1 for total and glycosylated Hp in buffer solution, respectively. The immunoplatform allows accurate determination using simple and relatively short protocols (approx. 75 min) of total and glycosylated Hp in the secretomes of in vitro-cultured colorectal cancer (CRC) cells with different metastatic potentials, which is not feasible, due to lack of sensitivity, by means of some commercial ELISA kits and Western blot methodology.

Interventions for preventing keratinocytic cancer in patients with a history of a previous keratinocytic carcinoma: A systematic review.

Keratinocyte cancer (KC) is the most common cancer worldwide. It is important to analyze the actual interventions that are available for the prevention of patients with a previous history of a KC. We aim to review the existent literature to assess the efficacy and safety of interventions to prevent KC in patients with a history of previous KC. We searched clinical trials in which the main outcome was the prevention of KC in patients with a previous history of KC using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. We analyzed 18 clinical trials from which eight reported a benefit with their respective intervention but had methodological flaws and a variable risk of bias. Two clinical trials (regarding celecoxib and oral supplementation with nicotinamide) seemed to have the most beneficial results reducing the incidence of KC in treated groups. However, all of the studies are highly heterogeneous, which does not allow a meta-analysis to be performed. New studies with greater epidemiological value should be conducted.

¿Cuál es la calidad de vida de los adultos con vitiligo en México? / What is the quality of life of adults with vitiligo in Mexico?

Resumen Introducción: El vitiligo es incurable, lentamente progresivo, su prevalencia varía de 0.4 a 2.0 %. La calidad de vida relacionada con la salud (CVRS) se refiere al bienestar autopercibido asociado a la presencia de una enfermedad y su tratamiento. Métodos: Estudio transversal en un centro dermatológico. Se incluyeron adultos con vitiligo no segmentario (VNS), en tanto que se excluyeron pacientes con otros trastornos pigmentarios y otros tipos de vitiligo. Se aplicó el cuestionario VitiQoL (0 = sin afectación, 90 = máxima afectación), el Vitiligo Extent Score (VES) y el Vitiligo Area Scoring Index (VASI). Resultados: Participaron 492 pacientes, 63 % mujeres. Se obtuvieron 32.6 puntos de promedio en el VitiQoL (IC 95 % = 30.6-34.5). La autopercepción de gravedad y la CVRS se correlacionaron (r = 0.568, p < 0.001). La edad, el sexo femenino, la menor educación y la mayor gravedad autopercibida se asociaron a peor CVRS. La proporción de personas que reportaron una adicción fue similar en los grupos con peor y mejor CVRS (28 % versus 32 %, p = 0.23). Conclusión: La peor CVRS se explica por la autopercepción de gravedad, preocupación por la progresión de la enfermedad, aspecto de la piel y acciones necesarias para evitar la exposición al sol durante la recreación.

Abstract Introduction: Vitiligo is an incurable, slowly progressive skin condition, the prevalence of which ranges from 0.4 to 2.0%. Health-related quality of life (HRQoL) refers to self-perceived well-being associated with the presence of a disease and its treatment. Methods: Cross-sectional study at a dermatological center. Adults with non-segmental vitiligo (NSV) were included, while patients with other pigmentary disorders and other types of vitiligo were excluded. The VitiQoL questionnaire (0 = no skin involvement, 90 = maximum skin involvement), the Vitiligo Extent Score (VES) and the Vitiligo Area Scoring Index (VASI) were applied. Results: 492 patients did participate; 63% were women. An average score of 32.6 was obtained on VitiQoL (95% CI = 30.6-34.5). Self-perception of severity and HRQoL were correlated (r = 0.568, p < 0.001). Age, the female gender, lower education and higher self-perceived severity were associated with poorer HRQoL. The proportion of subjects who reported an addiction was similar in the worst and best HRQoL groups (28% vs. 32%, p = 0.23). Conclusion: Poorer HRQoL is explained by severity self-perception, concern about disease progression, appearance of the skin and necessary actions to avoid sun exposure during recreation.

Developing a core outcome set for anthropometric evaluation for presurgical infant orthopaedics for unilateral cleft lip and palate: e-Delphi consensus.

INTRODUCTION: Presurgical infant orthopaedics (PSIO) in infants with cleft lip and palate focuses on improving the anatomical conditions of the lip, palate and nose before the first lip surgery; however, its effectiveness has not been proven. OBJECTIVE: To develop a core outcome set for reporting anthropometry-based outcomes in studies appraising the PSIO before primary cleft lip repair in unilateral cleft lip palate (UCLP). METHOD: Literature search to identify anthropometric measures. The operational definition and schematic representation of each were elaborated, grouping those apparently the same. By using Delphi methodology with a consensus of 10 subject-matter experts, three rounds were conducted to select a core outcome set of anthropometric measures with a validity V coefficient ≥80% among considered necessary to evaluate the PSIO in UCLP. RESULTS: A total of 101 anthropometric measures were identified in the literature to evaluate PSIO in UCLP. Of these, consensus validated the content of the core outcome set, which comprises 18 anthropometric measures, including columella height, nasal tip projection, projection alar length, width of nostril, nasal basal width, angle of columella, cleft lip segment, height of the non-cleft lip, height of the cleft lip, intersegment distance, arch length, greater segment length, lesser segment length, lateral deviation of the incisal point, posterior width of palatal cleft, arch width, grater segment rotation and lesser segment rotation. CONCLUSIONS: Standardised outcome measures are necessary to evaluate and ensure the quality of treatment in CLP. The core outcome set for anthropometric evaluation validated by consensus subject-matter experts is a clinically useful and low-cost tool for PSIO effectiveness studies.

Keratosis Pilaris Treatment: Evidence from Intervention Studies.

Keratosis pilaris is a common dermatosis observed in daily dermatologic practice. The diagnosis is clinical and usually asymptomatic, although sometimes patients may complain of mild pruritus and its cosmetic appearance. Few reports exist about its treatment. There are clinical trials assessing topical treatments and laser surgery, but no systematic reviews on its management were found in literature. An online research was conducted to identify evidence-based recommendations. Lactic acid, salicylic acid, and the 1064-nm Nd:YAG laser seem to be the most effective and safe treatment options for keratosis pilaris among patients aged 12 years and older; however, high-quality randomized controlled trials with long-term outcomes are required. (SKINmed. 2022;20:258-271).

Anticipating metastasis through electrochemical immunosensing of tumor hypoxia biomarkers.

Metastasis is responsible for about 90% of cancer-associated deaths. In the context of solid tumors, the low oxygen concentration in the tumor microenvironment (hypoxia) is one of the key factors contributing to metastasis. Tumor cells adapt to these conditions by overexpressing certain proteins such as programmed death ligand 1 (PD-L1) and hypoxia-inducible factor 1 alpha (HIF-1α). However, the determination of these tumor hypoxia markers that can be used to follow-up tumor progression and improve the efficiency of therapies has been scarcely addressed using electrochemical biosensors. In this work, we report the first electrochemical bioplatform for the determination of PD-L1 as well as the first one allowing its simultaneous determination with HIF-1α. The target proteins were captured and enzymatically labeled on magnetic microbeads and amperometric detection was undertaken on the surface of screen-printed dual carbon electrodes using the hydrogen peroxide/peroxidase/hydroquinone system. Sandwich immunoassays were implemented for both the HIF-1α and PD-L1 sensors and the analytical characteristics were evaluated providing LOD values of 86 and 279 pg mL-1 for the amperometric determination of PD-L1 and HIF-1α standards, respectively. The developed electrochemical immunoplatforms are competitive versus the only electrochemical immunosensor reported for the determination of HIF-1α and the "gold standard" ELISA methodology for the single determination of both proteins in terms of assay time, compatibility with the simultaneous determination of both proteins making their use suitable for untrained users at the point of attention. The dual amperometric immunosensor was applied to the simultaneous determination of HIF-1α and PD-L1 in cancer cell lysates. The analyses lasted only 2 h and just 0.5 µg of the sample was required.

Multiplexed magnetic beads-assisted amperometric bioplatforms for global detection of methylations in nucleic acids.

This work reports the first electrochemical bioplatform developed for the multidetection of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in DNA, DNA N6-methyladenine (6mA) and RNA N6-methyladenosine (m6A) methylations at global level. Direct competitive immunoassays were implemented on the surface of magnetic beads (MBs) and optimized for the single amperometric determination of different targets varying in length, sequence and number of methylations on screen-printed carbon electrodes. After evaluating the sensitivity and selectivity of such determinations and the confirmation of no cross-reactivity, a multiplexed disposable platform allowing the simultaneous determination of the mentioned four methylation events in only 45 min has been prepared. The multiplexed bioplatform was successfully applied to the determination of m6A in cellular total RNA and of 5-mC, 5-hmC and 6mA in genomic DNA extracted from tissues. The developed bioplatform showed its usefulness to discriminate the aggressiveness of cancerous cells and between healthy and tumor tissues of colorectal cancer patients.

Electrochemical Immunosensing of ST2: A Checkpoint Target in Cancer Diseases.

A magnetic beads (MB)-involved amperometric immunosensor for the determination of ST2, a member of the IL1 receptor family, is reported in this work. The method utilizes a sandwich immunoassay and disposable screen-printed carbon electrodes (SPCEs). Magnetic immunoconjugates built on the surface of carboxylic acid-microsized magnetic particles (HOOC-MBs) were used to selectively capture ST2. A biotinylated secondary antibody further conjugated with a streptavidin peroxidase conjugate (Strep-HRP) was used to accomplish the sandwiching of the target protein. The immune platform exhibits great selectivity and a low limit of detection (39.6 pg mL-1) for ST2, allowing the determination of soluble ST2 (sST2) in plasma samples from healthy individuals and patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) in only 45 min once the immunoconjugates have been prepared. The good correlation of the obtained results with those provided by an ELISA kit performed using the same immunoreagents demonstrates the potential of the developed strategy for early diagnosis and/or prognosis of the fatal PDAC disease.

Magnetic microbeads-based amperometric immunoplatform for the rapid and sensitive detection of N6-methyladenosine to assist in metastatic cancer cells discrimination.

This work describes the preparation of an immunoplatform for the sensitive and selective determination of N6-methyladenosine (m6A). The simple and fast protocol involves for the first time the use of micromagnetic immunoconjugates to establish a direct competitive assay between the m6A target and a biotinylated RNA oligomer bearing a single m6A enzymatically labelled with a commercial conjugate of streptavidin-peroxidase (Strep-HRP) as tracer. The cathodic current change measured in the presence of H2O2/hydroquinone (HQ) at screen-printed carbon electrodes (SPCEs) upon surface capturing the magnetic bioconjugates is inversely proportional to the m6A target concentration. After evaluating the effect of key variables, the analytical characteristics were established for the determination of three different targets: the N6-methyladenosine-5'-triphosphate (m6ATP) ribonucleotide, a short synthetic RNA oligomer bearing a single m6A and the positive control provided in a commercial colorimetric kit for m6A-RNA quantification. The obtained results show that this immunoplatform is competitive with other methods reported to date, achieving an improved sensitivity (limit of detection of 0.9 pM for the short synthetic oligomer) using a much simpler and faster protocol (~1 h) and disposable electrodes for the transduction. Furthermore, the applicability for discriminating the metastatic potential of cancer cells by directly analyzing a small amount of raw total RNA without enriching or fragmenting was also preliminary assessed.

Diagnostic Accuracy of Dermoscopy of Actinic Keratosis: A Systematic Review.

INTRODUCTION: Dermoscopy is a tool that aids clinicians in the diagnosis of actinic keratosis; however, few diagnostic accuracy studies have determined its sensitivity and specificity for this diagnosis. OBJECTIVE: Determine the diagnostic accuracy of dermoscopy on actinic keratosis. METHODS: A systematic review was conducted on EMBASE, PubMed, Scopus and the Cochrane Central Registry of Controlled Trials from inception to August 2019. RESULTS: We screened 485 titles and abstracts. Two studies comprising 219 actinic keratoses were eligible for qualitative analysis. The number and heterogeneity of included studies limited a quantitative analysis. CONCLUSIONS: Studies that focus specifically on the diagnostic accuracy of dermoscopy for actinic keratosis are lacking.

Quality of clinical trials for the prevention of keratinocyte cancer.

Keratinocyte cancer (KC) is the most common form of cancer in humans. To our knowledge, no previous publications assessing the methodological quality of clinical trials for the prevention of KC have been recently published. We aim to assess the methodological quality of clinical trials focused on the prevention of KC in high-risk groups not receiving immunosuppressive therapy (NRIT) and propose solutions to improve the design of future trials. We searched clinical trials in which the main outcome was the prevention of KC in high-risk NRIT groups using the strategy published in the International Prospective Register of Systematic Reviews (PROSPERO registry), CRD42016045981. Consolidated Standards of Reporting Trials (CONSORT) criteria and the Cochrane Collaboration risk of bias tool were used to assess methodological quality. We analyzed 23 clinical trials. We found a high risk of attrition and reporting bias in 86.9% and 60.9% of the trials, respectively. Regarding the CONSORT criteria, in at least 40% of the trials, the authors omitted the following information: a description of the trial design, the number of losses and exclusions after randomization, the results of subgroup and adjusted analysis, the estimated effect size and the precision of primary and secondary outcomes. Methodological quality was improved in the recently published clinical trials compared to those published before the CONSORT criteria development. All clinical trials should report in detail the information used to assess potential risks of bias.

Intervención educativa para la evaluación de la simetría nasal en pacientes operados de labio y paladar hendido / Educational intervention for the evaluation of nasal symmetry in cleft lip and palate operated patients

Resumen Introducción: La asimetría nasal es una de las características más frecuentes de los pacientes con labio y paladar hendido; la medición antropométrica (MA) es un método accesible y confiable que puede ser utilizado por los especialistas para evaluarlo. El objetivo de este estudio fue evaluar la efectividad de una intervención educativa aplicada a especialistas que tratan pacientes con labio y paladar hendido para incrementar la precisión en las MA en la evaluación de la asimetría nasal. Métodos: Estudio cuasiexperimental. Resultados: En la primera fase del estudio, 5 de las 13 medidas antropométricas reportaron una diferencia de medias (DM) > 1.5 mm, y 12 de las 13 MA mostraron resultados mayores a dos desviaciones estándar (DE). Los resultados en la segunda fase evidenciaron 11 de las 13 MA con DM < 1 mm, y 9 de las 13 MA fueron menores a dos DE. Conclusiones: La intervención realizada con el Manual de medidas antropométricas aumentó los conocimientos de los especialistas sobre la anatomía, puntos y MA que se pueden utilizar para evaluar la asimetría nasal en pacientes con labio y paladar hendido. La intervención educativa ayuda a aumentar el acuerdo entre los evaluadores para realizar una evaluación confiable de la asimetría nasal en pacientes con estos padecimientos.

Abstract Background: Nasal asymmetry is one of the most frequent characteristics of patients with cleft lip and palate. The anthropometric measurement (AM) is an accessible and reliable method that can be used by specialists to evaluate nasal asymmetry in patients with cleft lip and palate. The aim of this study was to evaluate the effectiveness of an educational intervention applied to cleft lip and palate specialists to increase the accuracy of AM in the evaluation of nasal asymmetry. Methods: Quasi-experimental study. Results: In the first phase of the study, five of the 13 AM reported a mean difference (MD) > 1.5 mm, and 12 of the 13 AM showed results greater than 2 SD (standard deviations). In the second phase, the results showed 11 of the 13 AM with MD < 1 mm, and 9 of the 13 AM were less than 2 SD. Conclusions: The intervention carried out with the manual of AMs increased the knowledge of the specialists on the anatomy points and AM that can be used to evaluate the nasal asymmetry in patients with cleft lip and palate. Educational intervention help to increase the agreement between examiners to perform a reliable evaluation of nasal asymmetry in patients with these conditions.

Content validity of psoriatic arthritis screening questionnaires: systematic review.

BACKGROUND: Psoriatic arthritis (PsA) is the main entity associated with psoriasis (PsO). Consequently, several PsA screening instruments have been developed, most of them are self-administered questionnaires, known as patient-reported outcome measures (PROMs). OBJECTIVE: To identify, summarize, and systematically evaluate the evidence of the content validity of PsA screening PROMs, in patients with PsO, by the dermatologist, based on COSMIN methodology. METHODS: A structured literature search was performed, until June 2019, that included development and/or validation studies of a questionnaire for the screening of PsA in patients with PsO. The evaluation was based on the PROMs' development, relevance, comprehensiveness, and comprehensibility. RESULTS: Eleven PROMs were included in the systematic review with four additional validation studies of the included instruments. Only ToPAS2 (Toronto Psoriatic Arthritis Screen) questionnaire had an adequate content validity. CONTEST (Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis), CEPPA (Center of Excellence for Psoriasis sand Psoriatic Arthritis), and SiPAS (Simple Psoriatic Arthritis Screening questionnaire) qualified as inadequate. CONCLUSIONS: Despite the existence of eleven validated PsA screening PROMs, none were supported by very high-quality evidence of their content validity, which brings the opportunity for the creation of a new proposal PROM for the screening of PsA.

Amperometric Bioplatforms To Detect Regional DNA Methylation with Single-Base Sensitivity.

This work reports the first bioplatform able to determine electrochemically 5-hydroxymethylcytosine (5-hmC) methylation events at localized sites and single-base sensitivity. The described bioplatform relies on a specific antibody (anti-5-hmC), further conjugated with commercial bioreagents loaded with multiple horseradish peroxidase (HRP) molecules, recognizing the epimark in a target DNA, captured through hybridization onto streptavidin-magnetic microbeads (Strep-MBs) modified with a complementary DNA capture probe. The electrochemical detection is performed by amperometry (-0.20 V vs Ag pseudoreference electrode) at disposable screen-printed carbon electrodes (SPCEs) in the presence of H2O2/hydroquinone (HQ) upon magnetic capture of the modified MBs onto the SPCE. The use of the commercial bioreagents ProtA-polyHRP80 and Histostar, very scarcely explored so far in electrochemical biosensors, provides high sensitivities for a synthetic target DNA sequence with a unique 5-hmC in the promoter region of MGMT tumor suppressor gene. Amplification factors of 43.6 and 55.2 were achieved using ProtA-polyHRP80 or Histostar, respectively, compared to the conventional secondary antibody labeling. This amplification was crucial to detect methylation events at single-nucleotide resolution achieving limits of detection (LODs) of 23.0 and 13.2 pM, respectively, without any target DNA amplification. The ProtA-polyHRP80-based bioplatform, selected as a compromise between sensitivity and cost per determination, exhibited full discrimination toward the target 5-hmC against the closely related 5-mC. In addition, the bioplatform detected 5-hmC at the regional level (MGMT promoter region) in just 10 ng of genomic DNA (gDNA, ∼2700 genomes) extracted from cancer cells and tissues from colorectal cancer (CRC) patients within 60 min.

A novel peptide-based electrochemical biosensor for the determination of a metastasis-linked protease in pancreatic cancer cells.

Proteases are involved in cancer' taking part in immune (dis)regulation, malignant progression and tumour growth. Recently, it has been found that expression levels of one of the members of the serine protease family, trypsin, is upregulated in human cancer cells of several organs, being considered as a specific cancer biomarker. Considering the great attention that electrochemical peptide sensors have nowadays, in this work, we propose a novel electroanalytical strategy for the determination of this important biomolecule. It implies the immobilization of a short synthetic peptide sequence, dually labelled with fluorescein isothiocyanate (FITC) and biotin, onto neutravidin-modified magnetic beads (MBs), followed by the peptide digestion with trypsin. Upon peptide disruption, the modified MBs were incubated with a specific fluorescein Fab fragment antibody labelled with horseradish peroxidase (HRP-antiFITC) and magnetically captured on the surface of a screen-printed carbon electrode (SPCE), where amperometric detection was performed using the hydroquinone (HQ)/HRP/H2O2 system. The biosensor exhibited a good reproducibility of the measurements (RSD 3.4%, n = 10), and specificity against other proteins and proteases commonly found in biological samples. This work reports the first quantitative data so far on trypsin expression in human cell lysates. The developed bioplatform was used for the direct determination of this protease in lysates from pancreatic cancer, cervix carcinoma and kidney cells in only 3 h and 30 min using low amounts (~ 0.1 µg) of raw extracts. Graphical abstract.

A novel zinc finger protein-based amperometric biosensor for miRNA determination.

This paper reports a simple electrochemical strategy for the determination of microRNAs (miRNAs) using a commercial His-Tag-Zinc finger protein (His-Tag-ZFP) that binds preferably (but non-sequence specifically) RNA hybrids over ssRNAs, ssDNAs, and dsDNAs. The strategy involves the use of magnetic beads (His-Tag-Isolation-MBs) as solid support to capture the conjugate formed in homogenous solution between His-Tag-ZFP and the dsRNA homohybrid formed between the target miRNA (miR-21 selected as a model) and a biotinylated synthetic complementary RNA detector probe (b-RNA-Dp) further conjugated with a streptavidin-horseradish peroxidase (Strep-HRP) conjugate. The electrochemical detection is carried out by amperometry at disposable screen-printed carbon electrodes (SPCEs) (- 0.20 V vs Ag pseudo-reference electrode) upon magnetic capture of the resultant magnetic bioconjugates and H2O2 addition in the presence of hydroquinone (HQ). The as-prepared biosensor exhibits a dynamic concentration range from 3.0 to 100 nM and a detection limit (LOD) of 0.91 nM for miR-21 in just ~ 2 h. An acceptable discrimination was achieved between the target miRNA and other non-target nucleic acids (ssDNA, dsDNA, ssRNA, DNA-RNA, miR-122, miR-205, and single central- or terminal-base mismatched sequences). The biosensor was applied to the analysis of miR-21 from total RNA (RNAt) extracted from epithelial non-tumorigenic and adenocarcinoma breast cells without target amplification, pre-concentration, or reverse transcription steps. The versatility of the methodology due to the ZFP's non-sequence-specific binding behavior makes it easily extendable to determine any target RNA only by modifying the biotinylated detector probe.

Opportunities, Challenges, and Prospects in Electrochemical Biosensing of Circulating Tumor DNA and its Specific Features.

Nowadays, analyzing circulating tumor DNA (ctDNA), a very small part of circulating free DNA (cfDNA) carried by blood, is considered to be an interesting alternative to conventional single-site tumor tissue biopsies, both to assess tumor burden and provide a more comprehensive snapshot of the time-related and spatial heterogeneity of cancer genetic/epigenetic scenery. The determination of ctDNA and/or mapping its characteristic features, including tumor-specific mutations, chromosomal aberrations, microsatellite alterations, and epigenetic changes, are minimally invasive, powerful and credible biomarkers for early diagnosis, follow-up, prediction of therapy response/resistance, relapse monitoring, and tracking the rise of new mutant subclones, leading to improved cancer outcomes This review provides an outline of advances published in the last five years in electrochemical biosensing of ctDNA and surrogate markers. It emphasizes those strategies that have been successfully applied to real clinical samples. It highlights the unique opportunities they offer to shift the focus of cancer patient management methods from actual decision making, based on clinic-pathological features, to biomarker-driven treatment strategies, based on genotypes and customized targeted therapies. Also highlighted are the unmet hurdles and future key points to guide these devices in the development of liquid biopsy cornerstone tools in routine clinical practice for the diagnosis, prognosis, and therapy response monitoring in cancer patients.

Versatile Electroanalytical Bioplatforms for Simultaneous Determination of Cancer-Related DNA 5-Methyl- and 5-Hydroxymethyl-Cytosines at Global and Gene-Specific Levels in Human Serum and Tissues.

This paper reports the preparation of versatile electrochemical biosensing platforms for the simple, rapid, and PCR-independent detection of the most frequent DNA methylation marks (5-methylcytosine, 5-mC, and/or 5-hydroxymethylcytosine, 5-hmC) both at global and gene-specific levels. The implemented strategies, relying on the smart coupling of immuno-magnetic beads (MBs), specific DNA probes and amperometric detection at screen-printed carbon electrodes (SPCEs), provided sensitive and selective determination of the target methylated DNAs in less than 90 min with a great reproducibility and demonstrated feasibility for the simultaneous detection of the same or different cytosine epimarks both at global level and in different loci of the same gene or in different genes. The bioplatforms were applied to determine global methylation events in paraffin-embedded colorectal tissues and specific methylation at promoters of tumor suppressor genes in genomic DNA extracted from cancer cells and paraffin-embedded colorectal tissues, and in serum without previous DNA extraction from cancer patients.

Validation and Adaptation of the Spanish Version of the STRONGkids Nutrition Screening Tool.

BACKGROUND: The use of malnutrition screening tools (MSTs) among hospitalized pediatric patients is a simple practice that may allow the identification of patients at nutrition risk. There are different tools developed in the English language, but there are limited data available on their validity when translated into other languages. The aim of this study was to construct a Spanish version (SV) of the STRONGkids MST and determine its validity and reliability in a pediatric population. METHODS: The translation and cross-cultural adaptation of the tool was performed, followed by the reliability, feasibility, and validity of the SV of the STRONGkids MST. Anthropometric assessment was used as the reference standard to evaluate the criterion validity of the MST. The length of hospital stay was used to determine predictive validity. RESULTS: A total 400 children were included in the study, 90 of whom took part in the reliability phase. The interrater agreement between dietitians and nursing staff was kappa (κ) = 0.67, while the intrarater agreement among dietitians was κ = 0.82. The feasibility of the MST was adequate for clinical use. The results for criterion validity between STRONGkids and anthropometric assessment was κ = 0.56, and the criterion validity between STRONGkids and length of hospital stay was κ = 0.20. The sensitivity of the MST was 86% and the specificity was 72%. CONCLUSIONS: The SV of the MST showed good reliability and feasibility. The validity is moderate, and the MST could be considered a useful resource for early detection of malnutrition risk.