Flow-on-repellent biofabrication of fibrous decellularized breast tumor-stroma models.

On-the-fly biofabrication of reproducible 3D tumor models at a pre-clinical level is highly desirable to level-up their applicability and predictive potential. Incorporating ECM biomolecular cues and its complex 3D bioarchitecture in the design stages of such in vitro platforms is essential to better recapitulate the native tumor microenvironment. To materialize these needs, herein we describe an innovative flow-on-repellent (FLORE) 3D extrusion bioprinting technique that leverages expedited and automatized bioink deposition onto a customized superhydrophobic printing bed. We demonstrate that this approach enables the rapid generation of quasi-spherical breast cancer-stroma hybrid models in a mode governed by surface wettability rather than bioink rheological features. For this purpose, an ECM-mimetic bioink comprising breast tissue-specific decellularized matrix in the form of microfiber bundles (dECM-µF) and photocrosslinkable hyaluronan (HAMA), was formulated to generate triple negative breast tumor-stroma models. Leveraging on the FLORE bioprinting approach, a rapid, automated, and reproducible fabrication of physiomimetic breast cancer hydrogel beads was successfully demonstrated. Hydrogel beads size with and without dECM-µF was easily tailored by modelling droplet deposition time on the superhydrophobic bed. Interestingly, in heterotypic breast cancer-stroma beads a self-arrangement of different cellular populations was observed, independent of dECM-µF inclusion, with CAFs clustering overtime within the fabricated models. Drug screening assays showed that the inclusion of CAFs and dECM-µF also impacted the overall response of these living constructs when incubated with gemcitabine chemotherapeutics, with dECM-µF integration promoting a trend for higher resistance in ECM-enriched models. Overall, we developed a rapid fabrication approach leveraging on extrusion bioprinting and superhydrophobic surfaces to process photocrosslinkable dECM bioinks and to generate increasingly physiomimetic tumor-stroma-matrix platforms for drug screening.

Photoacoustic processing of decellularized extracellular matrix for biofabricating living constructs.

The diverse biomolecular landscape of tissue-specific decellularized extracellular matrix (dECM) biomaterials provides a multiplicity of bioinstructive cues to target cells, rendering them highly valuable for various biomedical applications. However, the isolation of dECM biomaterials entails cumbersome xenogeneic enzymatic digestions and also additional inactivation procedures. Such, increases processing time, increments costs and introduces residues of non-naturally present proteins in dECM formulations that remain present even after inactivation. To overcome these limitations, herein we report an innovative conjugation of light and ultrasound-mediated dECM biomaterial processing for fabricating dECM biomaterials. Such approach gathers on ultrasound waves to facilitate dECM-in-liquid processing and visible light photocrosslinking of tyrosine residues naturally present in dECM biomaterials. This dual step methodology unlocked the in-air production of cell laden dECM hydrogels or programmable dECM hydrogel spherical-like beads by using superhydrophobic surfaces. These in-air produced units do not require any additional solvents and successfully supported both fibroblasts and breast cancer cells viability upon encapsulation or surface seeding. In addition, the optimized photoacoustic methodology also enabled a rapid formulation of dECM biomaterial inks with suitable features for biofabricating volumetrically defined living constructs through embedded 3D bioprinting. The biofabricated dECM hydrogel constructs supported cell adhesion, spreading and viability for 7 days. Overall, the implemented photoacoustic processing methodology of dECM biomaterials offers a rapid and universal strategy for upgrading their processing from virtually any tissue. STATEMENT OF SIGNIFICANCE: Leveraging decellularized extracellular matrix (dECM) as cell instructive biomaterials has potential to open new avenues for tissue engineering and in vitro disease modelling. The processing of dECM remains however, lengthy, costly and introduces non-naturally present proteins in the final biomaterials formulations. In this regard, here we report an innovative light and ultrasound two-step methodology that enables rapid dECM-in-liquid processing and downstream photocrosslinking of dECM hydrogel beads and 3D bioprinted constructs. Such photoacoustic based processing constitutes a universally applicable method for processing any type of tissue-derived dECM biomaterials.

Computed tomography imaging in preprocedural planning of transcatheter valvular heart interventions.

Cardiac Computed Tomography (CCT) has become a reliable imaging modality in cardiology providing robust information on the morphology and structure of the heart with high temporal and isotropic spatial resolution. For the past decade, there has been a paradigm shift in the management of valvular heart disease since previously unfavorable candidates for surgery are now provided with less-invasive interventions. Transcatheter heart valve interventions provide a real alternative to medical and surgical management and are often the only treatment option for valvular heart disease patients. Successful transcatheter valve interventions rely on comprehensive multimodality imaging assessment. CCT is the mainstay imaging technique for preprocedural planning of these interventions. CCT is critical in guiding patient selection, choice of procedural access, device selection, procedural guidance, as well as allowing postprocedural follow-up of complications. This article aims to review the current evidence of the role of CCT in the preprocedural planning of patients undergoing transcatheter valvular interventions.

Endosutured Aneurysm Repair of Abdominal Aortic Aneurysms with Short Necks Achieves Acceptable Midterm Outcomes-Results from the Peru Registry.

BACKGROUND: The study aims to describe midterm outcomes following treatment of infrarenal abdominal aortic aneurysms (AAAs) with short necks by endosutured aneurysm repair using the Heli-FX EndoAnchor system. METHODS: This is a retrospective study of prospectively collected data from 9 vascular surgery departments between June 2010 and December 2019, including treated AAAs with neck lengths ≤10 mm. The decision for the use of EndoAnchors was made by the treating surgeon or multidisciplinary aortic committee according to each center's practice. There were 2 Groups further assessed according to neck length, A (≥4 and <7 mm) and B (≥7 and ≤10 mm). The main outcomes analyzed were technical success, freedom from type Ia endoleaks (TIaELs), sac size increase, all-cause and aneurysm-related mortality. RESULTS: Seventy-six patients were included in the study, 17 fell into Group A and 59 into Group B. Median follow-up for the cohort was 40.5 (interquartile range 12-61) months. A median of 6 (interquartile range 3) EndoAnchors were deployed in each subject. Technical success was 86.8% for the total group, 82.4% and 88.1% (P = 0.534) for Groups A and B respectively. Six out of 10 (60%) of TIaELs at the completion angiographies showed spontaneous resolution. Cumulative freedom from TIaEL at 3 and 5 years for the total group was 89% and 84% respectively; this was 93% and 74% for Group A and 88% at both intervals in Group B (P = 0.545). In total, there were 7 (9.2%) patients presenting with TIaELs over the entire study period. Two (11.8%) in Group A and 5 (8.5%) in Group B (P = 0.679). There were more patients with sac regression in Group B (Group A = 6-35.3% vs. Group B = 34-57.6%, P = 0.230) with no statistical significance. All-cause mortality was 19 (25%) patients, with no difference (4-23.5% vs. 15-25.4%, P = 0.874) between groups; whereas aneurysm-related mortality occurred in 1 patient from Group A and 3 from Group B. CONCLUSIONS: This study demonstrates reasonable outcomes for patients with short-necked AAAs treated by endosutured aneurysm repair in terms of TIaELs up to 5-year follow-up. EndoAnchor use should be judiciously evaluated in short necks and may be a reasonable option when anatomical constraints are encountered, mainly for those with 7-10 mm neck lengths. Shorter neck length aspects, as indicated by the results from Group A, may be an alternative when no other options are available or feasible.

Effects of exercise programs on cardiorespiratory fitness and arterial stiffness on postmenopausal women: A systematic review study.

BACKGROUND: Arterial stiffness is an important marker of cardiovascular disease, with a considerable increase in menopause. The impact of exercise, as a preventive measure, on controlling the progression of cardiovascular disease and arterial dysfunction in middle age remains under investigation. OBJECTIVE: This systematic review aims to present the results of studies that examined the effects of different exercise programs (isolated, aerobic, and resistance or combined) on arterial stiffness and cardiorespiratory fitness in postmenopausal women. METHODS: Based on PRISMA guidelines, B-On, BioMed, EBSCOhost, MEDLINE, ScienceOpen, PubMed, Science Direct, Scopus, Web of Science, Cochrane library and LILACS databases were searched using specific keywords. RESULTS: A final total of 13 manuscripts were included in the qualitative synthesis, involving 700 participants. Four studies used only cardiorespiratory exercise, three only resistance, taekwondo class or flexibility exercise, and six combined exercise programs. Most interventions ranged from 3 to 5 days per week. Carotid-femoral pulse wave velocity showed improvements between 0.22 m/s and 1.56 m/s. In addition, one study showed an improvement of 4.4 ml/kg/min in maximal oxygen consumption. In 7 studies, participation in exercise programs improved arterial stiffness. CONCLUSIONS: Combined exercise (aerobic and resistance exercise) and aerobic exercise alone (swimming) improve cardiorespiratory fitness and arterial stiffness in postmenopausal women, particularly pulse wave velocity. The combined exercise program is the most effective, promoting improvements of up to -2.6 m/s in pulse wave velocity in this climacteric phase.

Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve Repair.

It has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.

Non-technical skills and teamwork in trauma: from the emergency department to the operating room.

Management of a trauma patient is a challenging process. Swift and accurate clinical assessment is required and time-sensitive decisions and life-saving procedures must be performed in an unstable patient. This requires a coordinated response by both the emergency room (ER) and operating room (OR) teams. However, a team of experts does not necessarily make an expert team. Root cause analysis of adverse events in surgery has shown that failures in coordination, planning, task management and particularly communication are the main causes for medical errors. While most research is focused on the ER trauma team, the trauma OR team also deserves attention. In fact, OR team dynamics may resemble more the ER team than the elective OR team. ER and OR trauma teams assemble on short notice, and their members, who are from different specialties and backgrounds, may not train regularly together or even know each other beforehand. And yet, they have to perform high-risk procedures and make high stake decisions, in a time-sensitive manner. The airline industry has long recognized the role of team training and non-technical skills (NTS) in reducing hazards. The implementation of the so called crew resource management or crisis resource management (CRM) has significantly made airline travel safer and the transposition to the medical context, with specific training in non-technical skills, has also brought great benefits. In fact, it is clear that adoption of non-technical skills (NTS) in healthcare has led to an increase in patient safety. In this narrative review we recapitulate some of the key non-technical skills and their relevance in trauma, with a focus on both the emergency department (ER) and the operating room (OR) teams, as well as on the transition of care from one to the other. Also, we explore the use of debriefing the team, as well as the roles of NTS training in both undergraduate and postgraduate settings. We review some of the existing trauma training courses and their roles in developing NTS. Finally, we briefly address the challenges posed by the development of trauma hybrid operating rooms.

Nutraceutical Potential of Lentinula edodes' Spent Mushroom Substrate: A Comprehensive Study on Phenolic Composition, Antioxidant Activity, and Antibacterial Effects.

Lentinula edodes, commonly known as shiitake mushroom, is renowned for its potential health advantages. This research delves into the often-overlooked by-product of shiitake cultivation, namely spent mushroom substrate (SMS), to explore its nutraceutical properties. The SMS samples were collected and subjected to different extraction methods, namely short or long agitation, and ultrasound-assisted extractions using different temperatures and distilled water or a 50% (v/v) ethanol as solvents. The extracts were tested for phenolic content (total phenols, ortho-diphenols, and flavonoids), antioxidant capacity (DPPH, 2,2-diphenyl-1 picrylhydrazyl; ABTS, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid; and FRAP, ferric reducing antioxidant power), and antibacterial activity. The different extraction methods revealed substantial variations (p < 0.05) in phenolic composition and antioxidant capacity. The highest phenolic content and antioxidant capacity were achieved using 24 h extraction, agitation, 50 °C, and ethanol as the solvent. Furthermore, the extracted compounds displayed antibacterial activity in specific tested bacterial strains. This study highlights the nutraceutical potential of L. edodes' SMS, positioning it as a valuable dietary supplement for animal nutrition, with emphasis on its prebiotic properties. Hence, this research unveils the promising health benefits of SMS in both human and animal nutrition.

Fatores associados à Infecção latente pelo Mycobacterium Tuberculosis em Profissionais de Saúde da Atenção Primária / Factors associated with latent Mycobacterium Tuberculosis infection in primary care health professionals / Factores asociados a la Infección Latente por Mycobacterium Tuberculosis en Profesionales de Salud de Atención Primaria

Objetivo: Objetivo: analisar na literatura científica os fatores associados à infecção latente pelo Mycobacterium Tuberculosis em profissionais da Atenção Primária à Saúde. Método: revisão integrativa da literatura, com coleta realizada entre novembro e dezembro de 2021. Considerou-se como critérios de inclusão: Estudos primários relacionados à temática e que incluam os seguintes profissionais: enfermeiros, médicos, dentistas, técnicos de enfermagem e técnicos de saúde bucal, sem delimitação temporal e de idiomas. Foram critérios de exclusão: estudos oriundos de opiniões de especialistas, editoriais, trabalhos de conclusão de curso, monografias, dissertações e teses. As bases de dados Biblioteca Virtual de Saúde, Medline, Scopus; Web of Science e Embase foram utilizadas. Resultados: foram selecionados nove estudos, que apresentaram os fatores associados idade, sexo e presença de doenças crônicas, estilo de vida e condições de trabalho. Conclusão: foi possível analisar os fatores associados à ILTB, o que poderá subsidiar a realização de políticas públicas mais assertivas e contribuir para o controle deste agravo(AU)

Objective: to analyze in the scientific literature the factors associated with latent infection by Mycobacterium Tuberculosis in Primary Health Care professionals. Method: integrative review of the literature, with collection carried out between November and December 2021. The inclusion criteria were considered: Primary studies related to the theme and which include the following professionals: nurses, doctors, dentists, nursing technicians and oral health technicians, without time or language limitations. Exclusion criteria were: studies originating from expert opinions, editorials, course completion works, monographs, dissertations and theses. The Virtual Health Library, Medline, Scopus databases; Web of Science and Embase were used. Results: nine studies were selected, which presented factors associated with age, sex and presence of chronic diseases, lifestyle and working conditions. Conclusion: it was possible to analyze the factors associated with LTBI, which could support the implementation of more assertive public policies and contribute to the control of this problem(AU)

Objetivo: analizar en la literatura científica los factores asociados a la infección latente por Mycobacterium Tuberculosis en profesionales de la Atención Primaria de Salud. Método: revisión integradora de la literatura, con recolección realizada entre noviembre y diciembre de 2021. Se consideraron como criterios de inclusión los estudios primarios relacionados con el tema y que incluyan a los siguientes profesionales: enfermeros, médicos, odontólogos, técnicos en enfermería y técnicos en salud bucal, sin limitaciones de tiempo ni de idioma. Los criterios de exclusión fueron: estudios provenientes de opiniones de expertos, editoriales, trabajos de finalización de cursos, monografías, disertaciones y tesis. Se utilizaron para las investigaciones: Biblioteca Virtual de Salud, Medline, Scopus; Web of Science y Embase. Resultados: se seleccionaron nueve estudios que presentaron factores asociados a la edad, sexo y presencia de enfermedades crónicas, estilo de vida y condiciones de trabajo. Conclusión: fue posible analizar los factores asociados a la ITBL, que podrían apoyar la implementación de políticas públicas más asertivas y contribuir al control de este problema(AU)

Progressive multifocal leukoencephalopathy triggered by COVID-19 in a previously asymptomatic person living with undiagnosed HIV infection.

This report presents the case of a 47-year-old male patient who worked as a mathematics teacher and experienced the sudden onset of disorientation, aphasia, and acalculia during an online class. The current study reveals the first documented case of HIV and progressive multifocal leukoencephalopathy with the detection of SARS-CoV-2 and human polyomavirus 2 (previously known as John Cunningham virus) in the cerebrospinal fluid. Furthermore, serum analysis revealed elevated concentrations of interleukin (IL)-6, IL-17, and IL-8, which are potential factors known to reduce the expression of tight junctions and adhesion molecules in the extracellular matrix, thereby affecting the permeability of the blood-brain barrier. Finally, the study discusses whether SARS-CoV-2 triggers or exacerbates progressive multifocal leukoencephalopathy.

SARS-CoV-2 Spike protein peptides displayed in the Pyrococcus furiosus RAD system preserve epitopes antigenicity, immunogenicity, and virus-neutralizing activity of antibodies.

Amongst the potential contribution of protein or peptide-display systems to study epitopes with relevant immunological features, the RAD display system stands out as a highly stable scaffold protein that allows the presentation of constrained target peptides. Here, we employed the RAD display system to present peptides derived from the SARS-CoV-2 Spike (S) protein as a tool to detect specific serum antibodies and to generate polyclonal antibodies capable of inhibiting SARS-CoV-2 infectivity in vitro. 44 linear S-derived peptides were genetically fused with the RAD scaffold (RAD-SCoV-epitopes) and screened for antigenicity with sera collected from COVID-19-infected patients. In a second step, selected RAD-SCoV-epitopes were used to immunize mice and generate antibodies. Phenotypic screening showed that some of these antibodies were able to recognize replicating viral particles in VERO CCL-81 and most notably seven of the RAD-SCoV-epitopes were able to induce antibodies that inhibited viral infection. Our findings highlight the RAD display system as an useful platform for the immunological characterization of peptides and a potentially valuable strategy for the design of antigens for peptide-based vaccines, for epitope-specific antibody mapping, and for the development of antibodies for diagnostic and therapeutic purposes.

The Role of Multiparametric MRI in the Local Staging of Prostate Cancer.

Prostate cancer ranks as the second most frequently diagnosed cancer globally among men and stands as the fifth leading cause of cancer-related death in males. Hence, an early and precise diagnosis and staging are critical. Traditional staging is based on clinical nomograms but presents a lower performance than prostate multiparametric magnetic resonance imaging (mpMRI). Since tumor staging serves as the basis for risk stratification, prognosis, and treatment decision-making, the primary objective of mpMRI is to distinguish between organ-confined and locally advanced diseases. Therefore, this imaging modality has emerged as the optimal selection for the local staging of prostate cancer, offering incremental value in evaluating pelvic nodal disease and bone involvement, and supplying supplementary insights regarding the precise location and disease extension. As per the Prostate Imaging Reporting & Data System v2.1 guideline, a comprehensive and accurate mpMRI requires several key sequences, which include T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI) for morphological assessment, with T2WI serving as the cornerstone for local staging. Additionally, diffusion-weighted imaging (DWI) and dynamic sequences acquired with intravenous administration of paramagnetic contrast medium (DCE) are crucial components. It is worth noting that while MRI exhibits high specificity, its sensitivity in diagnosing extracapsular extension, seminal vesicle invasion, and lymph node metastases is limited. Moreover, mpMRI has its own constraints and is not as effective in detecting distant metastases or evaluating lymph nodes, for which extended pelvic lymph node dissection remains the gold standard. This review aims to highlight the significance of mpMRI in prostate cancer staging and provide a practical approach to assessing extracapsular extension, seminal vesicle invasions, and the involvement of adjacent organs and lymph nodes.

Probing the Biosafety of Implantable Artificial Secretory Granules for the Sustained Release of Bioactive Proteins.

Among bio-inspired protein materials, secretory protein microparticles are of clinical interest as self-contained, slow protein delivery platforms that mimic secretory granules of the human endocrine system, in which the protein is both the drug and the scaffold. Upon subcutaneous injection, their progressive disintegration results in the sustained release of the building block polypeptides, which reach the bloodstream for systemic distribution and subsequent biological effects. Such entities are easily fabricated in vitro by Zn-assisted cross-molecular coordination of histidine residues. Using cationic Zn for the assembly of selected pure protein species and in the absence of any heterologous holding material, these granules are expected to be nontoxic and therefore adequate for different clinical uses. However, such presumed biosafety has not been so far confirmed and the potential protein dosage threshold not probed yet. By selecting the receptor binding domain (RBD) from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein as a model protein and using a mouse lab model, we have explored the toxicity of RBD-made secretory granules at increasing doses up to ∼100 mg/kg of animal weight. By monitoring body weight and biochemical blood markers and through the histological scrutiny of main tissues and organs, we have not observed systemic toxicity. Otherwise, the bioavailability of the material was demonstrated by the induction of specific antibody responses. The presented data confirm the intrinsic biosafety of artificial secretory granules made by recombinant proteins and prompt their further clinical development as self-contained and dynamic protein reservoirs.

Diagnostic and vaccine potential of Zika virus envelope protein (E) derivates produced in bacterial and insect cells.

Introduction: In the present study we evaluated the features of different recombinant forms of Zika virus (ZIKV) proteins produced in either bacterial (Eschericha coli) or insect cells (Drosophila melanogaster). The ZIKV-envelope glycoprotein (EZIKV) is responsible for virus entry into host cells, is the main target of neutralizing antibodies and has been used as a target antigen either for serological tests or for the development of subunit vaccines. The EZIKV is composed of three structural and functional domains (EDI, EDII, and EDIII), which share extensive sequence conservation with the corresponding counterparts expressed by other flaviviruses, particularly the different dengue virus (DENV) subtypes. Methods: In this study, we carried out a systematic comparison of the antigenicity and immunogenicity of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells. For the antigenicity analysis we collected 88 serum samples from ZIKV-infected participants and 57 serum samples from DENV-infected. For immunogenicity, C57BL/6 mice were immunized with two doses of EZIKV, EDI/IIZIKV and EDIIIZIKV produced in E. coli BL21 and Drosophila S2 cells to evaluate humoral and cellular immune response. In addition, AG129 mice were immunized with EZIKV and then challenge with ZIKV. Results: Testing of samples collected from ZIKV-infected and DENV-infected participants demonstrated that the EZIKV and EDIIIZIKV produced in BL21 cells presented better sensitivity and specificity compared to proteins produced in S2 cells. In vivo analyses were carried out with C57BL/6 mice and the results indicated that, despite similar immunogenicity, antigens produced in S2 cells, particularly EZIKV and EDIIIZIKV, induced higher ZIKV-neutralizing antibody levels in vaccinated mice. In addition, immunization with EZIKV expressed in S2 cells delayed the onset of symptoms and increased survival rates in immunocompromised mice. All recombinant antigens, either produced in bacteria or insect cells, induced antigen-specific CD4+ and CD8+ T cell responses. Conclusion: In conclusion, the present study highlights the differences in antigenicity and immunogenicity of recombinant ZIKV antigens produced in two heterologous protein expression systems.

Recombinant Proteins for Assembling as Nano- and Micro-Scale Materials for Drug Delivery: A Host Comparative Overview.

By following simple protein engineering steps, recombinant proteins with promising applications in the field of drug delivery can be assembled in the form of functional materials of increasing complexity, either as nanoparticles or nanoparticle-leaking secretory microparticles. Among the suitable strategies for protein assembly, the use of histidine-rich tags in combination with coordinating divalent cations allows the construction of both categories of material out of pure polypeptide samples. Such molecular crosslinking results in chemically homogeneous protein particles with a defined composition, a fact that offers soft regulatory routes towards clinical applications for nanostructured protein-only drugs or for protein-based drug vehicles. Successes in the fabrication and final performance of these materials are expected, irrespective of the protein source. However, this fact has not yet been fully explored and confirmed. By taking the antigenic RBD domain of the SARS-CoV-2 spike glycoprotein as a model building block, we investigated the production of nanoparticles and secretory microparticles out of the versions of recombinant RBD produced by bacteria (Escherichia coli), insect cells (Sf9), and two different mammalian cell lines (namely HEK 293F and Expi293F). Although both functional nanoparticles and secretory microparticles were effectively generated in all cases, the technological and biological idiosyncrasy of each type of cell factory impacted the biophysical properties of the products. Therefore, the selection of a protein biofabrication platform is not irrelevant but instead is a significant factor in the upstream pipeline of protein assembly into supramolecular, complex, and functional materials.

The Anti-Dengue Virus Peptide DV2 Inhibits Zika Virus Both In Vitro and In Vivo.

The C-terminal portion of the E protein, known as stem, is conserved among flaviviruses and is an important target to peptide-based antiviral strategies. Since the dengue (DENV) and Zika (ZIKV) viruses share sequences in the stem region, in this study we evaluated the cross-inhibition of ZIKV by the stem-based DV2 peptide (419-447), which was previously described to inhibit all DENV serotypes. Thus, the anti-ZIKV effects induced by treatments with the DV2 peptide were tested in both in vitro and in vivo conditions. Molecular modeling approaches have demonstrated that the DV2 peptide interacts with amino acid residues exposed on the surface of pre- and postfusion forms of the ZIKA envelope (E) protein. The peptide did not have any significant cytotoxic effects on eukaryotic cells but efficiently inhibited ZIKV infectivity in cultivated Vero cells. In addition, the DV2 peptide reduced morbidity and mortality in mice subjected to lethal challenges with a ZIKV strain isolated in Brazil. Taken together, the present results support the therapeutic potential of the DV2 peptide against ZIKV infections and open perspectives for the development and clinical testing of anti-flavivirus treatments based on synthetic stem-based peptides.

Tratamiento endovascular de aneurismas de arterias viscerales. Experiencia de 10 años en un solo centro / Endovascular treatment of visceral artery aneurysms. A single center 10-year experience

RESUMEN Antecedentes : los aneurismas de arterias viscerales (AAV) tienen una frecuencia baja (0,1 a 2%). Hasta un 25% puede presentarse como rotura, con una alta mortalidad (hasta 70%). La terapia endovascular ha ganado terreno y se recomienda como primera opción según las últimas guías. Hoy en día, es posible adaptarse a casi cualquier anatomía utilizando tecnología cerebral. Objetivo : describir la experiencia y enfoque en el manejo endovascular de AAV, con resultados a corto, mediano y largo plazo. Material y métodos : llevamos a cabo una evaluación retrospectiva de pacientes tratados por AAV verdaderos por vía endovascular en un solo centro entre 2010 y 2020, con un seguimiento mínimo de 6 meses. Resultados : analizamos 19 procedimientos en 18 pacientes (9 hombres y 9 mujeres). La edad promedio fue 61,9 años; el promedio de tiempo de internación fue 1,94 días y el promedio de seguimiento de 40 meses. La arteria más involucrada fue la esplénica (n = 9, 50%). El tamaño aneurismático promedio fue 30,1 mm. La estrategia terapéutica más utilizada fue colocación de diversor de flujo (n = 8, 42,1%). Dos pacientes fueron reintervenidos (11,1%). Las tasas de exclusión completa fueron del 47,4%, 68,4% y 94,7% a los 3, 6 y 12 meses, respectivamente. No hubo casos de mortalidad a 30 días ni mortalidad relacionada con el aneurisma durante el seguimiento. Conclusión : el tratamiento endovascular de los AAV es seguro y eficaz. Sin embargo, se debe contar con la tecnología adecuada, para la planificación preoperatoria y el tratamiento.

ABSTRACT Background : the prevalence of visceral artery aneurysms (VAAs) is low (0.1 to 2%). Up to 25% may present as rupture which is associated with high mortality (up to 70%). Endovascular treatment has gained ground and is even considered the first option according to the most recent recommendations. Nowadays, almost any anatomy can be approached with endovascular techniques used to treat intracranial aneurysms. Objective : the aim of our study was to describe the experience and approach for the endovascular management of VAAs with short-, mid-, and long-term results. Material and methods : we conducted a retrospective evaluation of patients with true VAAs undergoing endovascular treatment in a single center between 2010 and 2020 who were followed up for a minimum of 6 months. Results : we analyzed 19 procedures in 18 patients (9 men and 9 women). Mean age was 61.9 years; mean length of hospital stay was 1.94 days and mean follow-up was 40 months. The splenic artery was the vessel most affected (n = 9, 50%). Mean aneurysm size was 30.1 mm. Flow diversion was the strategy most used (n = 8, 42.1%). Two patients required reintervention (11%). Complete exclusion rate was 38.4%, 47.4%, 68.4% and 94.7% at 3, 6 and 12 months, respectively. There were no cases of mortality within the first 30 days and no aneurysm-related mortality during the follow-up period. Conclusion : endovascular treatment of VAAs is a safe and efficient strategy but requires adequate technology for preoperative planning and treatment.

Identification of Zika Virus NS1-Derived Peptides with Potential Applications in Serological Tests.

Zika virus (ZIKV), a mosquito-borne pathogen, is an emerging arbovirus associated with sporadic symptomatic cases of great medical concern, particularly among pregnant women and newborns affected with neurological disorders. Serological diagnosis of ZIKV infection is still an unmet challenge due to the co-circulation of the dengue virus, which shares extensive sequence conservation of structural proteins leading to the generation of cross-reactive antibodies. In this study, we aimed to obtain tools for the development of improved serological tests for the detection of ZIKV infection. Polyclonal sera (pAb) and a monoclonal antibody (mAb 2F2) against a recombinant form of the ZIKV nonstructural protein 1 (NS1) allowed the identification of linear peptide epitopes of the NS1 protein. Based on these findings, six chemically synthesized peptides were tested both in dot blot and ELISA assays using convalescent sera collected from ZIKV-infected patients. Two of these peptides specifically detected the presence of ZIKV antibodies and proved to be candidates for the detection of ZIKV-infected subjects. The availability of these tools opens perspectives for the development of NS1-based serological tests with enhanced sensitivity regarding other flaviviruses.