Glyoxal crosslinking of electro-responsive alginate-based hydrogels: Effects on the properties.

To improve the features of alginate-based hydrogels in physiological conditions, Ca2+-crosslinked semi-interpenetrated hydrogels formed by poly(3,4-ethylenedioxythiophene):polystyrene sulfonic acid and alginate (PEDOT/Alg) were subjected to a treatment with glyoxal to form a dual ionic/covalent network. The covalent network density was systematically varied by considering different glyoxalization times (tG). The content of Ca2+ was significantly higher for the untreated hydrogel than for the glyoxalized ones, while the properties of the hydrogels were found to largely depend on tG. The porosity and swelling capacity decreased with increasing tG, while the stiffness and electrical conductance retention capacity increased with tG. The potentiodynamic response of the hydrogels notably depended on the amount of conformational restraints introduced by the glyoxal, which is a very short crosslinker. Thus, the re-accommodation of the polymer chains during the cyclic potential scans became more difficult with increasing number of covalent crosslinks. This information was used to improve the performance of untreated PEDOT/Alg as electrochemical sensor of hydrogen peroxide by simply applying a tG of 5 min. Overall, the control of the properties of glyoxalized hydrogels through tG is very advantageous and can be used as an on-demand strategy to improve the performance of such materials depending on the application.

Impact of memory bias in the dietary estimation of older adults measured through a food frequency questionnaire and weighed food records: A cross-sectional study in older adults and primary caregivers.

INTRODUCTION: changes in cognitive performance and memory of older adults (OA) can interfere in their reporting their diet. OBJECTIVE: to evaluate the impact of memory bias in dietary estimation between OA and their primary caregivers (PC) through the food frequency questionnaire (FFQ) for Mexican OA and weighed food records (WFR). METHODS: the present analysis uses the estimated dietary information based on the response provided by 51 older adults (OA) and their primary caregivers (PC) from the validation study of the FFQ for Mexicans OA was conducted during lockdowns for COVID-19. The personnel who applied FFQ and WFR were trained with standardized instruments and procedures. The Wilcoxon test was used to compare the intake per day of the foods and food groups, the Spearman correlation coefficient was used to evaluate the grams of intake per day of the food groups, and kappa coefficient was used to compare the level of food items and food groups between OA and PC. RESULTS: in 11 of 14 food groups, no significant differences were observed between the amounts of intake reported by OA and PC. In the groups of dairy products, fruits, vegetables, and legumes, moderate agreement was observed (κ = 0.63 to 0.79), and in the rest of the groups was strong to perfect (κ ≥ 0.80). Correlation of the amount of intake between OA and PC was high in all food groups (r ≥ 0.87). CONCLUSION: the high correlation and high agreement between the amounts and frequencies of the food groups consumed as reported by the older adults and primary caregivers indicate that the information from both respondents is reliable.

Diseño de una base de datos para la Revista Cubana de Tecnología de la Salud

Introducción: la Revista Cubana de Tecnología de la Salud, requiere un sistema de base de datos para el tratamiento de la información concerniente a los diferentes procesos de la gestión editorial. Esto es necesario en la automatización y a la vez humanización de la recolección, organización, procesamiento y presentación de los datos relacionados con los indicadores de evaluación de la calidad, los bibliométricos y los referentes con la indexación, por citar ejemplos. Objetivo: diseñar una base de datos para la Revista Cubana de Tecnología de la Salud. Métodos: se realizó una investigación aplicada de innovación tecnológica, en la que diseñó una base de datos relacional. Se emplearon métodos a nivel teórico y empíricos; entre ellos la entrevista para obtener una descripción detallada de las necesidades de la revista, y la modelación en la representación a través de modelos lógicos y conceptuales del universo de discurso. Resultados: la base de datos se diseñó mediante el modelo Entidad-Relación. Se obtuvieron el diagrama de entidad-relación y el esquema relacional de la base de datos. Se aplicó la teoría de la normalización para eliminar las redundancias. Conclusiones: quedó descrito el proceso de diseño de la base de datos con la cual la Revista Cubana de Tecnología de la Salud, podrá gestionar los datos de una forma centralizada y eficaz, de manera que se puedan aplicar en la evaluación de la gestión editorial y el desarrollo de estudios bibliométricos de la producción científica de la revista.

Introduction: The Cuban Journal of Health Technology requires a database system for the treatment of information concerning the different editorial management processes. This is necessary in the automation process and, at the same time, in the humanization of the collection, organization, processing, and presentation of the data related to the quality evaluation and bibliometric indicators, as well as those related to the indexing, to cite some examples. Objective: To design a database for the Cuban Journal of Health Technology. Methods: An applied research on technological innovation was carried out, in which a relational database was designed. Theoretical and empirical methods were used; among them, we can mention the interview to obtain a detailed description of the needs of the journal, and the representation modeling through logical and conceptual models of the universe of discourse. Results: The database was designed using the Entity-Relationship model. The entity-relationship diagram and the relational schema of the database were obtained. Normalization theory was applied to eliminate redundancies. Conclusions: The design process of the database that will allow the Cuban Journal of Health Technology to manage data in a centralized and efficient way was described, so that it can be applied to the evaluation of the editorial management and the development of bibliometric studies of the scientific production of the journal.

Pocillopora damicornis-associated macroinvertebrate responses to spatial gradients in the southern Mexican Pacific.

We explicitly tested for spatial changes in Pocillopora damicornis-associated invertebrates across several spatial scales in the southern Mexican Pacific. Sorting of invertebrates from 40 coral heads along 882 km of the coast yielded 325 taxa, 283% more than any other Pocillopora spp. coral host study to date, but estimators signals that richness might be 17-39% larger than the current number. Permutation, ordination, and regression analysis indicate that the composition and abundance of invertebrates vary in response to the spatial distance among coral heads: high similarity and variation occur among coral heads within localities (<500 m), probably related to faunal homogenization, but progressively modest reduction in similarity and variation as spatial distance increases suggesting a weak role for environmental sorting across southern Mexican Pacific coral reefs. Future studies should explicitly explore spatial, environmental, and historical biogeography processes that regulate and maintain community structure and biodiversity on eastern Pacific reefs.

Diagnosis of patients with Lynch syndrome lacking the Amsterdam II or Bethesda criteria.

BACKGROUND: Lynch Syndrome (LS) is an autosomal dominant inheritance disorder characterized by genetic predisposition to develop cancer, caused by pathogenic variants in the genes of the mismatch repair system. Cases are detected by implementing the Amsterdam II and the revised Bethesda criteria, which are based on family history. MAIN BODY: Patients who meet the criteria undergo posterior tests, such as germline DNA sequencing, to confirm the diagnosis. However, these criteria have poor sensitivity, as more than one-quarter of patients with LS do not meet the criteria. It is very likely that the lack of sensitivity of the criteria is due to the incomplete penetrance of this syndrome. The penetrance and risk of developing a particular type of cancer are highly dependent on the affected gene and probably of the variant. Patients with variants in low-penetrance genes have a lower risk of developing a cancer associated with LS, leading to families with unaffected generations and showing fewer clear patterns. This study focuses on describing genetic aspects of LS cases that underlie the lack of sensitivity of the clinical criteria used for its diagnosis. CONCLUSION: Universal screening could be an option to address the problem of underdiagnosis.

4D Printable Salicylic Acid Photopolymers for Sustained Drug Releasing, Shape Memory, Soft Tissue Scaffolds.

3D printing of pharmaceuticals offers a unique opportunity for long-term, sustained drug release profiles for an array of treatment options. Unfortunately, this approach is often limited by physical compounding or processing limitations. Modification of the active drug into a prodrug compound allows for seamless incorporation with advanced manufacturing methods that open the door to production of complex tissue scaffold drug depots. Here we demonstrate this concept using salicylic acids with varied prodrug structures for control of physical and chemical properties. The role of different salicylic acid derivatives (salicylic acid, bromosalicylic allyl ester, iodosalicylic allyl ester) and linker species (allyl salicylate, allyl 2-(allyloxy)benzoate, allyl 2-(((allyloxy)carbonyl)oxy)benzoate) were investigated using thiol-ene cross-linking in digital light processing (DLP) 3D printing to produce porous prodrug tissue scaffolds containing more than 50% salicylic acid by mass. Salicylic acid photopolymer resins were all found to be highly reactive (solidification within 5 s of irradiation at λ = 405 nm), while the cross-linked solids display tunable thermomechanical behaviors with low glass transition temperatures (Tgs) and elastomeric behaviors, with the carbonate species displaying an elastic modulus matching that of adipose tissue (approximately 65 kPa). Drug release profiles were found to be zero order, sustained release based upon hydrolytic degradation of multilayered scaffolds incorporating fluorescent modeling compounds, with release rates tuned through selection of the linker species. Cytocompatibility in 2D and 3D was further demonstrated for all species compared to polycarbonate controls, as well as salicylic acid-containing composites (physical incorporation), over a 2-week period using murine fibroblasts. The use of drugs as the matrix material for solid prodrug tissue scaffolds opens the door to novel therapeutic strategies, longer sustained release profiles, and even reduced complications for advanced medicine.

Microbiota composition and its impact on DNA methylation in colorectal cancer.

Colorectal cancer is a complex disease resulting from the interaction of genetics, epigenetics, and environmental factors. DNA methylation is frequently found in tumor suppressor genes to promote cancer development. Several factors are associated with changes in the DNA methylation pattern, and recently, the gastrointestinal microbiota could be associated with this epigenetic change. The predominant phyla in gut microbiota are Firmicutes and Bacteroidetes; however, an enrichment of Bacteroides fragilis, Fusobacterium nucleatum, and Streptococcus bovis, among others, has been reported in colorectal cancer, although the composition could be influenced by several factors, including diet, age, sex, and cancer stage. Fusobacterium nucleatum, a gram-negative anaerobic bacillus, is mainly associated with colorectal cancer patients positive for the CpG island methylator phenotype, although hypermethylation in genes such as MLH1, CDKN2A, MTSS1, RBM38, PKD1, PTPRT, and EYA4 has also been described. Moreover, Hungatella hathewayi, a gram-positive, rod-shaped bacterium, is related to hypermethylation in SOX11, THBD, SFRP2, GATA5, ESR1, EYA4, CDX2, and APC genes. The underlying epigenetic mechanism is unclear, although it could be implicated in the regulation of DNA methyltransferases, enzymes that catalyze the transfer of a methyl group on cytosine of CpG sites. Since DNA methylation is a reversible event, changes in gut microbiota could modulate the gene expression through DNA methylation and improve the colorectal cancer prognosis.

Enzymatic Degradation of Polylactic Acid Fibers Supported on a Hydrogel for Sustained Release of Lactate.

The incorporation of exogenous lactate into cardiac tissues is a regenerative strategy that is rapidly gaining attention. In this work, two polymeric platforms were designed to achieve a sustained release of lactate, combining immediate and prolonged release profiles. Both platforms contained electrospun poly(lactic acid) (PLA) fibers and an alginate (Alg) hydrogel. In the first platform, named L/K(x)/Alg-PLA, lactate and proteinase K (x mg of enzyme per 1 g of PLA) were directly loaded into the Alg hydrogel, into which PLA fibers were assembled. In the second platform, L/Alg-K(x)/PLA, fibers were produced by electrospinning a proteinase K:PLA solution and, subsequently, assembled within the lactate-loaded hydrogel. After characterizing the chemical, morphological, and mechanical properties of the systems, as well as their cytotoxicity, the release profiles of the two platforms were determined considering different amounts of proteinase K (x = 5.2, 26, and 52 mg of proteinase K per 1 g of PLA), which is known to exhibit a broad cleavage activity. The profiles obtained using L/Alg-K(x)/PLA platforms with x = 26 and 52 were the closest to the criteria that must be met for cardiac tissue regeneration. Finally, the amount of lactate directly loaded in the Alg hydrogel for immediate release and the amount of protein in the electrospinning solution were adapted to achieve a constant lactate release of around 6 mM per day over 1 or 2 weeks. In the optimized bioplatform, in which 6 mM lactate was loaded in the hydrogel, the amount of fibers was increased by a factor of ×3, the amount of enzyme was adjusted to 40 mg per 1 g of PLA, and a daily lactate release of 5.9 ± 2.7 mM over a period of 11 days was achieved. Accordingly, the engineered device fully satisfied the characteristics and requirements for heart tissue regeneration.

Digital Light Processing-3D Printing of Thermoset Materials with High Biodegradability from Amino Acid-Derived Acrylamide Monomers.

Six acrylamide resins, derived from l-phenylalanine and l-leucine, are designed for application in digital light processing (DLP) printers to obtain biodegradable thermoset polymers. The acrylamide copolymers are prepared under light irradiation at 405 nm and thermal post-curing processes. Low molecular weight poly(ethylene glycol)diacrylate (PEGDA) and N,N-dimethylacrylamide (DMAM), both liquid resins, are used as co-monomers and diluents for the amino acid-derived acrylamide solubilization. The presence of two phenylalanine units and two ester groups in the acrylamide monomer accuses a fast degradation rate in hydrolytic medium in 90 days. The residual products leached in the aqueous media prove to be non-cytotoxic, when 3D-printed samples are cultured with osteoblast cells (MG63), which represents an advantage for the safe disposal of printer waste materials. The scaled-up pieces derived from l-phenylalanine and diethylene glycol, as amino acid-derived acrylamide (named compound C), PEGDA and DMAM, present high dimensional stability after DLP printing of complex structures used as testing samples. Layers of 50 µm of thickness are well cohesive having isotropic behavior, as demonstrated with tensile-strain measurements performed in X-Y-Z (plane) directions. The compound C, which contains phenylalanine amino acid, reveals a promising potential to replace non-biodegradable acrylate polymers used in prototyping systems.

Smart Design of Sensor-Coated Surgical Sutures for Bacterial Infection Monitoring.

Virtually, all implantable medical devices are susceptible to infection. As the main healthcare issue concerning implantable devices is the elevated risk of infection, different strategies based on the coating or functionalization of biomedical devices with antiseptic agents or antibiotics are proposed. In this work, an alternative approach is presented, which consists of the functionalization of implantable medical devices with sensors capable of detecting infection at very early stages through continuous monitoring of the bacteria metabolism. This approach, which is implemented in surgical sutures as a representative case of implantable devices susceptible to bacteria colonization, is expected to minimize the risk of worsening the patient's clinical condition. More specifically, non-absorbable polypropylene/polyethylene (PP/PE) surgical sutures are functionalized with conducting polymers using a combination of low-pressure oxygen plasma, chemical oxidative polymerization, and anodic polymerization, to detect metabolites coming from bacteria respiration. Functionalized suture yarns are used for real-time monitoring of bacteria growth, demonstrating the potential of this strategy to fight against infections.

Multifunctional conductive hyaluronic acid hydrogels for wound care and skin regeneration.

Although the main function of skin is to act as a protective barrier against external factors, it is indeed an extremely vulnerable tissue. Skincare, regardless of the wound type, requires effective treatments to prevent bacterial infection and local inflammation. The complex biological roles displayed by hyaluronic acid (HA) during the wound healing process have made this multifaceted polysaccharide an alternative biomaterial to prepare wound dressings. Therefore, herein, we present the most advanced research undertaken to engineer conductive and interactive hydrogels based on HA as wound dressings that enhance skin tissue regeneration either through electrical stimulation (ES) or by displaying multifunctional performance. First, we briefly introduce to the reader the effect of ES on promoting wound healing and why HA has become a vogue as a wound healing agent. Then, a selection of systems, chosen according to their multifunctional relevance, is presented. Special care has been taken to highlight those recently reported works (mainly from the last 3 years) with enhanced scalability and biomimicry. By doing that, we have turned a critical eye on the field considering what major challenges must be overcome for these systems to have real commercial, clinical, or other translational impact.

Immediate-sustained lactate release using alginate hydrogel assembled to proteinase K/polymer electrospun fibers.

This work proposes a microfibers-hydrogel assembled composite as delivery vehicle able to combine into a single system both burst and prolonged release of lactate. The prolonged release of lactate has been achieved by electrospinning a mixture of polylactic acid and proteinase K (26.0 mg of proteinase K and 0.99 g of PLA dissolved in 6 mL of 2:1 chloroform:acetone in the optimal case), which is a protease that catalyzes the degradation of polylactic acid into lactate. The degradation of microfibers into lactate reflects that proteinase K preserves its enzymatic activity even after the electrospinning process because of the mild operational conditions used. Besides, burst release is obtained from the lactate-loaded alginate hydrogel. The successful assembly between the lactate-loaded hydrogel and the polylactic acid/proteinase K fibers has been favored by applying a low-pressure (0.3 mbar at 300 W) oxygen plasma treatment, which transforms hydrophobic fibers into hydrophilic while the enzymatic activity is still maintained. The composite displays both fast (< 24 h) and sustained (> 10 days) lactate release, and allows the modulation of the release by adjusting either the amount of loaded lactate or the amount of active enzyme.

Electroresponsive and pH-Sensitive Hydrogel as Carrier for Controlled Chloramphenicol Release.

Multiresponsive hydrogels, which are smart soft materials that respond to more than one external stimulus, have emerged as powerful tools for biomedical applications, such as drug delivery. Within this context and with the aim of eliminating the systematic administration of antibiotics, special attention is being paid to the development of systems for controlled delivery of antibiotic for topical treatment of bacterial infections. In this work, an electro-chemo responsive hydrogel able to release chloramphenicol (CAM), a broad spectrum antibiotic also used for anticancer therapy, is proposed. This has been prepared by grafting poly(acrylic acid) (PAA) to sodium alginate (Alg) and in situ encapsulation of poly(3,4-ethylenedioxythiophene) nanoparticles loaded with CAM (PEDOT/CAM NPs), which were obtained by emulsion polymerization. Although the response to electrical stimuli of PEDOT was the main control for the release of CAM from PEDOT/CAM NPs, the release by passive diffusion had a relatively important contribution. Conversely, the passive release of antibiotic from the whole engineered hydrogel system, Alg-g-PAA/PEDOT/CAM, was negligible, whereas significant release was achieved under electrostimulation in an acid environment. Bacterial tests and assays with cancer cells demonstrated that the biological activity of CAM remained after release by electrical stimulation. Notably, the successful dual-response of the developed hydrogel to electrical stimuli and pH changes evidence the great prospect of this smart material in the biomedical field, as a tool to fight against bacterial infections and to provide local cancer treatment.

Beyond biology: alternative uses of cantilever-based technologies.

Micromechanical cantilever sensors are attracting a lot of attention because of the need for characterizing, detecting, and monitoring chemical and physical properties, as well as compounds at the nanoscale. The fields of application of micro-cantilever sensors span from biological and point-of-care, to military or industrial sectors. The purpose of this work focuses on thermal and mechanical characterization, environmental monitoring, and chemical detection, in order to provide a technical review of the most recent technical advances and applications, as well as the future prospective of micro-cantilever sensor research.

Preparation and Characterization of Functionalized Surgical Meshes for Early Detection of Bacterial Infections.

Isotactic polypropylene (i-PP) nonabsorbable surgical meshes are modified by incorporating a conducting polymer (CP) layer to detect the adhesion and growth of bacteria by sensing the oxidation of nicotinamide adenine dinucleotide (NADH), a metabolite produced by the respiration reactions of such microorganisms, to NAD+. A three-step process is used for such incorporation: (1) treat pristine meshes with low-pressure O2 plasma; (2) functionalize the surface with CP nanoparticles; and (3) coat with a homogeneous layer of electropolymerized CP using the nanoparticles introduced in (2) as polymerization nuclei. The modified meshes are stable and easy to handle and also show good electrochemical response. The detection by cyclic voltammetry of NADH within the interval of concentrations reported for bacterial cultures is demonstrated for the two modified meshes. Furthermore, Staphylococcus aureus and both biofilm-positive (B+) and biofilm-negative (B-) Escherichia coli cultures are used to prove real-time monitoring of NADH coming from aerobic respiration reactions. The proposed strategy, which offers a simple and innovative process for incorporating a sensor for the electrochemical detection of bacteria metabolism to currently existing surgical meshes, holds considerable promise for the future development of a new generation of smart biomedical devices to fight against post-operative bacterial infections.

Diseño de base de datos para el departamento de Sistemas de Información en Salud, La Habana 2021

Introducción: La Facultad de Tecnología de la Salud dispone de una base de datos para el tratamiento de la información concerniente a los estudiantes matriculados, sin embargo, esta base de datos no cubre las necesidades propias del departamento de Sistemas de Información en Salud. Se necesita para la elaboración de estrategias organizativas por parte del departamento un sistema de gestión de información ajustado a las características del colectivo docente. Objetivo: Diseñar una base de datos para el departamento de Sistema de Información en Salud en aras de una mejor gestión de la información departamental. Método: Se realizó una investigación aplicada de innovación tecnológica en el período noviembre de 2020 - febrero de 2021, en la Facultad de Tecnología de la Salud, La Habana, en la que diseñó una base de datos relacional. Se emplearon métodos a nivel teórico y empíricos; entre ellos la entrevista para obtener una descripción detallada de las necesidades del departamento, y la modelación para representar a través de modelos lógicos y conceptuales del universo de discurso. Se empleó el Microsoft Access 2019 para la implementación de la base de datos diseñada. Resultados: La base de datos se diseñó mediante el modelo Entidad-Relación. Se obtuvieron el diagrama de entidad-relación y el esquema relacional de la base de datos. A través de Microsoft Access se crearon las tablas con sus respectivas relaciones, las consultas, los formularios e informes de la base de datos. Conclusiones: Quedó descrito todo el proceso de diseño e implementación de la base de datos que satisface los requisitos funcionales con la cual el departamento de Sistema de Información en Salud podrá gestionar sus datos de una manera centralizada y eficaz.

Introduction: The Facultad de Tecnología de la Salud has a database in use for gathering information concerning enrolled students; however, this database does not meet the needs of the department of Sistemas de Información en Salud, it is very important for professors to have a properly information management system helps them for performing the organizational strategies required. Objective: To design a database to be use in the department of Sistemas de Información en Salud for a better information management. Method: An applied research in technological innovation was conducted at the Facultad de Tecnología de la Salud, La Habana, in the period November 2020 - February 2021. A relational database was designed for practical usage. Theoretical and empirical methods were used, including the use of the interview methods focused on obtaining a better description of the department's needs, designing properly through logical and conceptual models the proposed databases. Microsoft Access database engine 2019 was used to build and implemented the databases. Results: The database was developed using the Entity-Relationship model. The entity-relationship diagram and a relational database schema were obtained. By using the Microsoft Access software were built different tables with their respective links, queries, forms and reports. Conclusions: It was designed and implemented a database that satisfies the functional requirements with which the department of Sistemas de Información en Salud will be able to manage its data, in a centralized and efficient manner. The designing and implementation processes of the database were described.

Introdução: A Facultad de Tecnología de la Salud possui um banco de dados para o tratamento das informações dos alunos matriculados, porém esse banco de dados não atende às necessidades do Departamento de Sistemas de Información en Salud. Para o desenvolvimento de estratégias organizacionais por parte do departamento, é necessário um sistema de gestão da informação ajustado às características do grupo docente. Objetivo: Projetar um banco de dados para o departamento de Sistemas de Información en Salud para melhor gerenciar as informações do departamento. Método: Foi realizada uma pesquisa aplicada sobre inovação tecnológica no período de novembro de 2020 a fevereiro de 2021, na Facultad de Tecnología de la Salud, Havana, na qual foi projetada uma base de dados relacional. Foram utilizados métodos teóricos e empíricos; entre eles a entrevista para obter uma descrição detalhada das necessidades do departamento, e a modelagem para representar por meio de modelos lógicos e conceituais o universo do discurso. O Microsoft Access 2019 foi utilizado para a implementação do banco de dados projetado. Resultados: O banco de dados foi desenhado usando o modelo entidade-relacionamento. Obteve-se o diagrama entidade-relacionamento e o esquema relacional do banco de dados. Através do Microsoft Access, foram criadas as tabelas com seus respectivos relacionamentos, as consultas, os formulários e relatórios do banco de dados. Conclusões: Foi descrito todo o processo de desenho e implementação da base de dados que satisfaça os requisitos funcionais com os quais o departamento do Sistemas de Información en Salud poderá gerir os seus dados de forma centralizada e eficiente.

Dendritic Self-assembled Structures from Therapeutic Charged Pentapeptides.

CRENKA [Cys-Arg-(NMe)Glu-Lys-Ala, where (NMe)Glu refers to N-methyl-Glu], an anti-cancer pentapeptide that induces prostate tumor necrosis and significant reduction in tumor growth, was engineered to increase the resistance to endogenous proteases of its parent peptide, CREKA (Cys-Arg-Glu-Lys-Ala). Considering their high tendency to aggregate, the self-assembly of CRENKA and CREKA into well-defined and ordered structures has been examined as a function of peptide concentration and pH. Spectroscopic studies and atomistic molecular dynamics simulations reveal significant differences between the secondary structures of CREKA and CRENKA. Thus, the restrictions imposed by the (NMe)Glu residue reduce the conformational variability of CRENKA with respect to CREKA, which significantly affects the formation of well-defined and ordered self-assembly morphologies. Aggregates with poorly defined morphology are obtained from solutions with low and moderate CREKA concentrations at pH 4, whereas well-defined dendritic microstructures with fractal geometry are obtained from CRENKA solutions with similar peptide concentrations at pH 4 and 7. The formation of dendritic structures is proposed to follow a two-step mechanism: (1) pseudo-spherical particles are pre-nucleated through a diffusion-limited aggregation process, pre-defining the dendritic geometry, and (2) such pre-nucleated structures coalesce by incorporating conformationally restrained CRENKA molecules from the solution to their surfaces, forming a continuous dendritic structure. Instead, no regular assembly is obtained from solutions with high peptide concentrations, as their dynamics is dominated by strong repulsive peptide-peptide electrostatic interactions, and from solutions at pH 10, in which the total peptide charge is zero. Overall, results demonstrate that dendritic structures are only obtained when the molecular charge of CRENKA, which is controlled through the pH, favors kinetics over thermodynamics during the self-assembly process.

Molecular Profiling of Tumor Tissue in Mexican Patients with Colorectal Cancer.

Colorectal cancer is a heterogeneous disease with multiple genomic changes that influence the clinical management of patients; thus, the search for new molecular targets remains necessary. The aim of this study was to identify genetic variants in tumor tissues from Mexican patients with colorectal cancer, using massive parallel sequencing. A total of 4813 genes were analyzed in tumoral DNA from colorectal cancer patients, using the TruSight One Sequencing panel. From these, 192 variants with clinical associations were found distributed in 168 different genes, of which 46 variants had not been previous reported in the literature or databases, although genes harboring those variants had already been described in colorectal cancer. Enrichment analysis of the affected genes was performed using Reactome software; pathway over-representation showed significance for disease, signal transduction, and immune system subsets in all patients, while exclusive subsets such as DNA repair, autophagy, and RNA metabolism were also found. Those characteristics, whether individual or shared, could give tumors specific capabilities for survival, aggressiveness, or response to treatment. Our results can be useful for future investigations targeting specific characteristics of tumors in colorectal cancer patients. The identification of exclusive or common pathways in colorectal cancer patients could be important for better diagnosis and personalized cancer treatment.

Interaction of CCND2, CDKN1A, and POLD3 Variants in Mexican Patients with Colorectal Cancer.

BACKGROUND: Colorectal cancer is the second cause of death by cancer around the world. Sporadic colorectal cancer is the most frequent (75%), and it is produced by the interaction of environmental, epigenetic, and genetic factors. The accumulation of single-nucleotide variants in genes associated with cell proliferation, DNA repair, and/or apoptosis could confer a risk to cancer. The aim of this study was to analyze the gene-gene interactions among CCND2 (rs3217901), CDKN1A (rs1059234 and rs1801270), and POLD3 (rs3824999) variants in Mexican patients with colorectal cancer. METHODS: We collected peripheral blood samples from 185 patients with sporadic colorectal cancer before treatment and from 185 unrelated blood donors as the reference group; all participants signed an informed consent form. DNA extraction was performed by Miller and Cetyltrimethylammonium bromide (CTAB)/ Dodecyltrimethylammonium bromide (DTAB) methods. Polymerase chain reaction- restriction fragment length polymorphism followed by polyacrylamide gel electrophoresis stained with AgNO3 methods were used to identify the variants rs3217901, rs1059234, rs1801270, and rs3824999. Odds ratio and single-nucleotide variant interaction were determined by single-locus analysis and Multifactorial Dimensionality Reduction software, respectively. RESULTS: No association was found for CCND2 and CDKN1A variants; yet, a significant association for the GG genotype, G allele, and recessive and additive models for the POLD3 variant was observed (P < .05). The single-nucleotide variant-single-nucleotide variant interaction revealed the combination rs1059234, rs3217901, and rs3824999 as the best model and the comparison showed an increased risk (P < .05). CONCLUSION: Single-locus and gene-gene interaction analyses disclosed that both the rs3824999 (POLD3) variant and the combination of rs3217901 (CCND2), rs1059234 (CDKN1A), and rs3824999 (POLD3) genotypes increase the risk for colorectal cancer in Mexican population.

Self-assembly pathways in a triphenylalanine peptide capped with aromatic groups.

Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphenylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N- and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylmethyloxycarbonyl and benzyl ester end-capping groups at the N- and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in ß-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm ß-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the medium on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addition, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of π-π stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which determines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.