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Abstract Background Kilohertz high-frequency alternating current (KHFAC) stimulation has demonstrated to induce rapid and reversible nerve blocks without causing nerve damage. Previous studies have explored frequency-dependent effects using a transcutaneous approach in humans from 5 to 20 kHz. Nevertheless, its application in humans is limited by the lack of stimulators approved for frequencies above 20 kHz. Therefore, this study aimed to assess the effects and safety of transcutaneous KHFAC stimulation using a novel prototype stimulator, comparing interventions at 30, 40, and 50 kHz to sham stimulation on experimental pain, sensory, motor, and neurophysiological outcomes. Methods A randomized, double-blind, sham-controlled crossover study involving 34 healthy participants was conducted. Four interventions (30, 40, 50 kHz, and sham) were administered, and stimulation was applied for 20 min to the median nerve of the non-dominant hand. A prototype stimulator capable of delivering frequencies between 1 and 50 kHz, with a maximum peak-to-peak output current intensity of 400 mA was designed. The intensity applied during the stimulation was below motor threshold, evoking a ‘strong but comfortable’ tingling sensation. Primary outcomes included heat pain threshold (HPT), pressure pain threshold (PPT), and adverse effects. The secondary outcomes included static two-point discrimination sensitivity, isometric pinch strength, and median sensory nerve action potential (SNAP). Results Compared with the sham stimulation, all the active interventions exhibited a significantly greater increase in the PPT during and immediately after the stimulation, while only a significant increase was observed at 40 kHz (4.1 N/cm2; 95%CI 0.3 to 7.9) at 15 min post-intervention. Compared to sham stimulation, the 40 kHz intervention had a significantly greater effect on the HPT at all time points, with the greatest difference (1.4 °C; 0.6 to 2.1) occurring immediately post-intervention. Adverse effects during active interventions included petechiae, erythema, and itching, which resolved at 24 h post-intervention. For secondary outcomes, only a significant reduction in the median SNAP velocity was observed in the sham stimulation group compared to the 50 kHz group. Conclusions Active KHFAC stimulation, particularly at 40 kHz, delivered through a novel stimulator, effectively increased the PPT and HPT without affecting tactile or motor outcomes, inducing mild skin-related adverse effects. These findings have potential implications for people with pain-related pathologies. Trial registration NCT05230836.

Abstract The treatment of non-small cell lung cancer (NSCLC) patients has significantly improved with recent therapeutic strategies; however, many patients still do not benefit from them. As a result, new treatment approaches are urgently needed. In this study, we evaluated the antitumor efficacy of co-targeting G9a and DNMT1 enzymes and its potential as a cancer drug sensitizer. We observed co-expression and overexpression of G9a and DNMT1 in NSCLC, which were associated with poor prognosis. Co-targeting G9a/DNMT1 with the drug CM-272 reduced proliferation and induced cell death in a panel of human and murine NSCLC cell lines. Additionally, the transcriptomes of these cells were reprogrammed to become highly responsive to chemotherapy (cisplatin), targeted therapy (trametinib), and epigenetic therapy (vorinostat). In vivo, CM-272 reduced tumor volume in human and murine cell-derived cancer models, and this effect was synergistically enhanced by cisplatin. The expression of SCARA5 and AOX1 was induced by CM-272, and both proteins were found to be essential for the antiproliferative response, as gene silencing decreased cytotoxicity. Furthermore, the expression of SCARA5 and AOX1 was positively correlated with each other and inversely correlated with G9a and DNMT1 expression in NSCLC patients. SCARA5 and AOX1 DNA promoters were hypermethylated in NSCLC, and SCARA5 methylation was identified as an epigenetic biomarker in tumors and liquid biopsies from NSCLC patients. Thus, we demonstrate that co-targeting G9a/DNMT1 is a promising strategy to enhance the efficacy of cancer drugs, and SCARA5 methylation could serve as a non-invasive biomarker to monitor tumor progression.

Abstract A 16-year-old man presented with short VA supraventricular tachycardia and 2:1 atrioventricular ratio. The correct maneuvers allowed us to guide not only the mechanism but also the probable location of the atrioventricular block.

Reseña del libro La trinchera universal. Los voluntarios internacionales y la Guerra Civil española (Granada, Comares, 2021), de Javier Sánchez Zapatero (ed.). En este libro se estudia la producción testimonial y literaria producida por los brigadistas extranjeros que participaron en la contienda, con capítulos dedicados a voluntarios de diferente procedencia y abriendo el estudio a otros nombres que no son los míticos Hemingway, Malraux u Orwell, cuyo análisis ha dejado en un segundo plano a una variedad de autores y de testigos sobre nuestra contienda bélica nacional. El libro contiene tres grandes apartados redactados por especialistas de universidades españolas y extranjeras: "Panoramas", con estados de la cuestión sobre las literaturas anglosajonas, francófonas, germánicas e iberoamericanas y su relación con la Guerra Civil; "Semblanzas", en el que se esbozan descripciones biográficas y literarias de importantes voluntarios que combatieron en España; y "Representaciones", con dos investigaciones que analizan la figura del brigadista internacional en las literaturas inglesa y española desde 1936 hasta la actualidad.

Abstract Background Significant consequences of COVID-19 within academic/professional life are, at the psychological level, related to worry, tension, stress; coping strategies and lifestyle changes. This study describes the process of design and validation of an inventory (QPIC), which aims to assess the psychological impact that a situation of confinement can produce among university students and teachers. Methods Design of the instrument and psychometric tests. A sample of 862 students and 229 professors affiliated to Spanish and Colombian universities was used. Data were collected in April 2020 with the request of the favourable Bioethics Committee IR/2020. Results Six experts carried out the content validation. A confirmatory factor analysis of the theoretical dimensions proposed for the scales was performed and the internal consistency of each of the three initial scales was confirmed (0.866, 0.813 and 0.834). Conclusion A rigorous and reliable instrument is achieved, consisting of two final scales: (a) Worry, tension and stress scale (b) Coping scale, which helps to measure individual psychological effects in housebound situations. It is an instrument designed, constructed ad hoc to assess the impact of confinement and subjected to validation. The factor structure and reliability of the instrument are examined and good psychometric properties are obtained. The application of this inventory will make it possible to assess the impact on people’s mental health during a period of confinement.

Purpose: The aim was to analyze the accuracy of digital models and 3D-printed casts from full-arch digital impressions using two intraoral scanners (iTeroTM and PrimescanTM). Materials and methods: A crossover reliability study was designed, scanning children and teenagers with iTeroTM and PrimescanTM. Accuracy was evaluated by measuring intercanine, intermolar, and ipsilateral canine–molar distances intraorally and comparing these measurements with those from plaster casts, digital models obtained with intraoral scanners, and 3D-printed casts. A paired comparison and a general linear model with a one-way repeated measures ANOVA procedure were carried out with a confidence level of 95% (p ≤ 0.05). Results: A total of 51 subjects were analyzed (mean age 12.35 ± 2.57). Statistical differences (p < 0.05) were found in the upper and lower arch regarding accuracy in comparison to intraoral measurements, except for the iTeroTM-printed cast and canine–molar upper right and intercanine lower distances (p > 0.05 for all comparisons). Regarding a comparison between reproduction methods, the plaster cast oversized the intercanine upper distance in comparison with both intraoral scanners’ digital models and the PrimescanTM-printed cast (p = 0.001), but there were no differences in the lower arch (p > 0.05 for all comparisons). Conclusion: Intraoral scanners reproduce tooth structures with similar accuracy to conventional methods.

The aim of this study was to evaluate the comfort of children and adolescents with conventional full-arch dental impression methods compared to two intraoral scanners (iTeroTM and PrimescanTM). Methods: A monocentric, analytical, controlled crossover study was designed to compare conventional impression and digital impression with two intraoral scanners (iTeroTM and PrimescanTM) in children and teenagers. Patient comfort was evaluated using a 100 mm VAS scale adapted to Spanish and for children. A descriptive and analytical statistical method was conducted with a confidence level of 95% (p ≤ 0.05) and asymptotic or bilateral significance. Results: A total of 51 subjects were enrolled in the study (mean age = 12.35 years). Although the group of 10–14-year-olds was the most numerous, gender was equally distributed among the age groups. None of the variables on the VAS scale showed differences between the gender categories (p > 0.05). There were differences (p < 0.05) with respect to the age categories, as the middle adolescent group showed the worst general perception and total comfort during the conventional impression. Statistically significant differences were found between all VAS scale items and the three impression methods (p < 0.05). Conclusions: The digital impression technique is superior in terms of total comfort to the conventional alginate impression in children and adolescents.