Sensitivity and specificity of four screening tests sleep-disordered breathing in patients with and without cardiovascular disease

Objectives: Polysomnogram is the gold standard for the diagnosis of sleep-disordered breathing (SDB); a sensitive and specific alternative strategy would be ideal, due to its low availability, and screening patients at high risk of OSA is very important. This study aimed to determine the operating characteristics of screening tests in patients with and without cardiovascular disease (CVD). Material and Methods: Epworth sleepiness scale (ESS), Berlin, STOP-bang and Pittsburgh sleep quality index (PSQI) were applied in adults with and without cardiovascular disease in three Colombian cities, as well as anthropometric measurements and a polysomnogram. Operating characteristics were calculated for each test and the best cut-off values in patients with and without CVD were obtained. Results: 964 patients (median age: 58), 662 with and 302 without CVD were included. The prevalence for SDB (AHI ≥5) were 43.4 % (OSA), 16.2% (central apnea), and 12.4 % (other). In patients without CVD, the highest sensitivity for OSA and central apnea was for PSQI (80-85%). The highest specificity was for STOP-bang (68%) and Berlin (78.6%). In CVD the best sensitivity was for PSQI (81.9%) followed by Berlin (71.9%) and the best specificity for STOP-bang (82.1%). No isolated questionnaire showed good diagnostic performance (AUC≤0.6) and the cut-off values had no variations except for ESS. Conclusion: Screening tests showed low operating characteristics for the diagnosis to SDB, but better performance in patients with CVD. They are not recommended as the only diagnostic test, but they can be useful to guide the initial diagnostic processQ2Objectives: Polysomnogram is the gold standard for the diagnosis of sleep-disordered breathing (SDB); a sensitive and specific alternative strategy would be ideal, due to its low availability, and screening patients at high risk of OSA is very important. This study aimed to determine the operating characteristics of screening tests in patients with and without cardiovascular disease (CVD). Material and Methods: Epworth sleepiness scale (ESS), Berlin, STOP-bang and Pittsburgh sleep quality index (PSQI) were applied in adults with and without cardiovascular disease in three Colombian cities, as well as anthropometric measurements and a polysomnogram. Operating characteristics were calculated for each test and the best cut-off values in patients with and without CVD were obtained. Results: 964 patients (median age: 58), 662 with and 302 without CVD were included. The prevalence for SDB (AHI ≥5) were 43.4 % (OSA), 16.2% (central apnea), and 12.4 % (other). In patients without CVD, the highest sensitivity for OSA and central apnea was for PSQI (80-85%). The highest specificity was for STOP-bang (68%) and Berlin (78.6%). In CVD the best sensitivity was for PSQI (81.9%) followed by Berlin (71.9%) and the best specificity for STOP-bang (82.1%). No isolated questionnaire showed good diagnostic performance (AUC≤0.6) and the cut-off values had no variations except for ESS. Conclusion: Screening tests showed low operating characteristics for the diagnosis to SDB, but better performance in patients with CVD. They are not recommended as the only diagnostic test, but they can be useful to guide the initial diagnostic processN/

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting

In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.This work was funded by the University of the Basque Country UPV/EHU and the Basque Country Government (IT1448-22). Supported by the fellowships granted to Fouad Al-Hakim Khalak (PRE_2021_2_0181) and Sandra Ruiz-Alonso (PRE_2021_2_0153). Likewise, the authors thank ICTS “NANBIOSIS”, in particular the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), at the University of the Basque Country (UPV/EHU) in Vitoria-Gasteiz

Control interno para mejorar las contrataciones del área de logística, Unidad de Gestión Educativa Local San Martín 2020

El presente estudio de investigación se establece por determinar mejoras en las contrataciones del área de logística en la Unidad de Gestión Educativa de San Martín, teniendo como dimensión  requisitos para la adquisición de bienes, servicios, proceso de la adquisición de bienes, servicios y políticas y normas de la adquisición de bienes. Ya que el objetivo determinar un modelo de control interno para mejorar las contrataciones del área de logística, Unidad de Gestión Educativa Local San Martín 2020; de esa manera conoce los procesos en la gestión de contrataciones. Presenta un estudio de investigación básica, con diseño no experimental, descriptivo de corte transversal. El instrumento de recolección de datos utilizado es el cuestionario y la guía de análisis, que nos permitió recabar conocimientos y experiencia sobre la temática planteada. La muestra representada por 60 trabajadores vinculados con la gestión logística, cuyos datos fueron procesados a través de un análisis estadístico descriptivo, De allí se pudo efectuar la valoración y ejecución de las normas de contrataciones. Por lo tanto, se logró establecer nunca se realiza la elaboración y aprobación de las bases del proceso de selección de acuerdo a las normas en un 8.3

Clay Minerals as Bioink Ingredients for 3D Printing and 3D Bioprinting: Application in Tissue Engineering and Regenerative Medicine

The adaptation and progress of 3D printing technology toward 3D bioprinting (specifically adapted to biomedical purposes) has opened the door to a world of new opportunities and possibilities in tissue engineering and regenerative medicine. In this regard, 3D bioprinting allows for the production of tailor-made constructs and organs as well as the production of custom implants and medical devices. As it is a growing field of study, currently, the attention is heeded on the optimization and improvement of the mechanical and biological properties of the so-called bioinks/biomaterial inks. One of the strategies proposed is the use of inorganic ingredients (clays, hydroxyapatite, graphene, carbon nanotubes and other silicate nanoparticles). Clays have proven to be useful as rheological and mechanical reinforcement in a wide range of fields, from the building industry to pharmacy. Moreover, they are naturally occurring materials with recognized biocompatibility and bioactivity, revealing them as optimal candidates for this cutting-edge technology. This review deals with the use of clays (both natural and synthetic) for tissue engineering and regenerative medicine through 3D printing and bioprinting. Despite the limited number of studies, it is possible to conclude that clays play a fundamental role in the formulation and optimization of bioinks and biomaterial inks since they are able to improve their rheology and mechanical properties, thus improving printability and construct resistance. Additionally, they have also proven to be exceptionally functional ingredients (enhancing cellular proliferation, adhesion, differentiation and alignment), controlling biodegradation and carrying/releasing actives with tissue regeneration therapeutic activities.This research was funded by the BASQUE COUNTRY GOVERNMENT/EUSKO JAURLARITZA (Department of Education, University and Research, Consolidated Groups IT907-16). Authors S.R.-A. and M.S.-R. thank the BASQUE COUNTRY GOVERNMENT for the granted fellowship (PRE_2020_2_0143) and the UNIVERSITY OF THE BASQUE COUNTRY/EUSKAL HERRIKO UNIBERTSITATEA (UPV/EHU) for the granted pre-doctoral fellowship (PIF17/79), respectively

Progress in 3D Bioprinting Technology for Osteochondral Regeneration

Osteochondral injuries can lead to osteoarthritis (OA). OA is characterized by the progressive degradation of the cartilage tissue together with bone tissue turnover. Consequently, joint pain, inflammation, and stiffness are common, with joint immobility and dysfunction being the most severe symptoms. The increase in the age of the population, along with the increase in risk factors such as obesity, has led OA to the forefront of disabling diseases. In addition, it not only has an increasing prevalence, but is also an economic burden for health systems. Current treatments are focused on relieving pain and inflammation, but they become ineffective as the disease progresses. Therefore, new therapeutic approaches, such as tissue engineering and 3D bioprinting, have emerged. In this review, the advantages of using 3D bioprinting techniques for osteochondral regeneration are described. Furthermore, the biomaterials, cell types, and active molecules that are commonly used for these purposes are indicated. Finally, the most recent promising results for the regeneration of cartilage, bone, and/or the osteochondral unit through 3D bioprinting technologies are considered, as this could be a feasible therapeutic approach to the treatment of OA.This research was funded by the BASQUE COUNTRY GOVERNMENT/EUSKO JAURLARITZA (Department of Education, University and Research, Consolidated Groups IT907- 16). Author S.R.-A. thank the BASQUE COUNTRY GOVERNMENT for the granted fellowship (PRE_2021_2_0153)

Current Insights into 3D Bioprinting: An Advanced Approach for Eye Tissue Regeneration

Three-dimensional (3D) printing is a game changer technology that holds great promise for a wide variety of biomedical applications, including ophthalmology. Through this emerging technique, specific eye tissues can be custom-fabricated in a flexible and automated way, incorporating different cell types and biomaterials in precise anatomical 3D geometries. However, and despite the great progress and possibilities generated in recent years, there are still challenges to overcome that jeopardize its clinical application in regular practice. The main goal of this review is to provide an in-depth understanding of the current status and implementation of 3D bioprinting technology in the ophthalmology field in order to manufacture relevant tissues such as cornea, retina and conjunctiva. Special attention is paid to the description of the most commonly employed bioprinting methods, and the most relevant eye tissue engineering studies performed by 3D bioprinting technology at preclinical level. In addition, other relevant issues related to use of 3D bioprinting for ocular drug delivery, as well as both ethical and regulatory aspects, are analyzed. Through this review, we aim to raise awareness among the research community and report recent advances and future directions in order to apply this advanced therapy in the eye tissue regeneration field.This research was fundedby the Basque Country Government (Department of Education, University and Research, Consolidated Groups IT907-16 and grant number PRE_2020_2_0143), and forms part of the Nanogrow project RTC-2017-6696-1. Additional funding was provided by the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), and initiative of the Carlos III Health Institute (ISCIII) and by the University of the Basque Country (UPV/EHU), post-doctoral grant number ESPDOC19/47). The APC was funded by the Basque Country Government (Department of Education, University and Research, Consolidated Groups IT907-16)

A genome-wide transcriptional study reveals that iron deficiency inhibits the yeast TORC1 pathway

Iron is an essential micronutrient that participates as a cofactor in a broad range of metabolic processes including mitochondrial respiration, DNA replication, protein translation and lipid biosynthesis. Adaptation to iron deficiency requires the global reorganization of cellular metabolism directed to optimize iron utilization. The budding yeast Saccharomyces cerevisiae has been widely used to characterize the responses of eukaryotic microorganisms to iron depletion. In this report, we used a genomic approach to investigate the contribution of transcription rates to the modulation of mRNA levels during adaptation of yeast cells to iron starvation. We reveal that a decrease in the activity of all RNA polymerases contributes to the down-regulation of many mRNAs, tRNAs and rRNAs. Opposite to the general expression pattern, many genes including components of the iron deficiency response, the mitochondrial retrograde pathway and the general stress response display a remarkable increase in both transcription rates and mRNA levels upon iron limitation, whereas genes encoding ribosomal proteins or implicated in ribosome biogenesis exhibit a pronounced fall. This expression profile is consistent with an activation of the environmental stress response. The phosphorylation stage of multiple regulatory factors strongly suggests that the conserved nutrient signaling pathway TORC1 is inhibited during the progress of iron deficiency. These results suggest an intricate crosstalk between iron metabolism and the TORC1 pathway that should be considered in many disorders.This work was supported by predoctoral contracts from the Spanish Ministry of Science, Innovation and Universities (MICINN) to AMR and LRA; a fellowship from the “Generalitat de Catalunya” (Spain) to SMM; European Union Funds (FEDER) and MICINN grants BIO2017-87828-C2-1-P to SP, BIO2017-87828-C2-2-P to MATR, BFU2016-77728-C3-3-P to JEPO, and BFU2015-71978-REDT to SP and JEPO; and Regional Government of Valencia PROMETEOII 2015/006 grant to JEPO

Characterization and assessment of new fibrillar collagen inks and bioinks for 3D printing and bioprinting

Collagen is a cornerstone protein for tissue engineering and 3D bioprinting due to its outstanding biocompatibility, low immunogenicity, and natural abundance in human tissues. Nonetheless, it still poses some important challenges, such as complicated and limited extraction processes, usually accompanied by batchto-batch reproducibility and influence of factors, such as temperature, pH, and ionic strength. In this work, we evaluated the suitability and performance of new, fibrillar type I collagen as standardized and reproducible collagen source for 3D printing and bioprinting. The acidic, native fibrous collagen formulation (5% w/w) performed remarkably during 3D printing, which was possible to print constructs of up to 27 layers without collapsing. On the other hand, the fibrous collagen mass has been modified to provide a fast, reliable, and easily neutralizable process. The neutralization with TRIS-HCl enabled the inclusion of cells without hindering printability. The cell-laden constructs were printed under mild conditions (50–80 kPa, pneumatic 3D printing), providing remarkable cellular viability (>90%) as well as a stable platform for cell growth and proliferation in vitro. Therefore, the native, type I collagen masses characterized in this work offer a reproducible and reliable source of collagen for 3D printing and bioprinting purposes.This research was funded by Viscofan (S.A.) Centro para el Desarrollo Tecnológico Industrial (CDTI) IDI-20210050 and the Basque Country Government/Eusko Jaurlaritza (Department of Education, University and Research, Consolidated Groups IT907-16). Author Sandra Ruiz-Alonso thanks the Basque Country Government for the granted fellowship PRE_2021_2_0153. José M. Rey thanks the funding from the European’s Union Horizon 2020 research and Innovation framework program (Triankle Project; Grant Agreement #952981). BioRender.com has been used as support for some figures assembly

Three-dimensional printing as a cutting-edge, versatile and personalizable vascular stent manufacturing procedure:Toward tailor-made medical devices

Vascular stents (VS) have revolutionized the treatment of cardiovascular diseases, as evidenced by the fact that the implantation of VS in coronary artery disease (CAD) patients has become a routine, easily approachable surgical intervention for the treatment of stenosed blood vessels. Despite the evolution of VS throughout the years, more efficient approaches are still required to address the medical and scientific challenges, especially when it comes to peripheral artery disease (PAD). In this regard, three-dimensional (3D) printing is envisaged as a promising alternative to upgrade VS by optimizing the shape, dimensions and stent backbone (crucial for optimal mechanical properties), making them customizable for each patient and each stenosed lesion. Moreover, the combination of 3D printing with other methods could also upgrade the final device. This review focuses on the most recent studies using 3D printing techniques to produce VS, both by itself and in combination with other techniques. The final aim is to provide an overview of the possibilities and limitations of 3D printing in the manufacturing of VS. Furthermore, the current situation of CAD and PAD pathologies is also addressed, thus highlighting the main weaknesses of the already existing VS and identifying research gaps, possible market niches and future directions.This work was funded by the Basque Country Government/Eusko Jaurlaritza (Department of Education, University and Research, Consolidated Groups IT448- 22) . Sandra Ruiz-Alonso and Fouad Al -Hakim thank the Basque Country Government for the granted fellowships PRE_2021_2_0153 and PRE_2021_2_0181, respectively. Denis Scaini gratefully acknowledges support from IKERBASQUE, the Basque Foundation of Science