Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.

Hepatic endotheliitis in Golden Syrian hamsters (Mesocricetus auratus) experimentally infected with SARS-CoV-2.

Hepatic injuries in COVID-19 are not yet fully understood and indirect pathways (without viral replication in the liver) have been associated with the activation of vascular mechanisms of liver injury in humans infected with SARS-CoV-2. Golden Syrian hamsters are an effective model for experimental reproduction of moderate and self-limiting lung disease during SARS-CoV-2 infection. As observed in humans, this experimental model reproduces lesions of bronchointerstitial pneumonia and pulmonary vascular lesions, including endotheliitis (attachment of lymphoid cells to the luminal surface of endothelium). Extrapulmonary vascular lesions are well documented in COVID-19, but such extrapulmonary vascular lesions have not yet been described in the Golden Syrian hamster model of SARS-CoV-2 infection. The study aimed to evaluate microscopic liver lesions in Golden Syrian hamsters experimentally infected with SARS-CoV-2. In total, 38 conventional Golden Syrian hamsters, divided into infected group (n=24) and mock-infected group (n=14), were euthanized at 2-, 3-, 4-, 5-, 7-, 14-, and 15-days post infection with SARS-CoV-2. Liver fragments were evaluated by histopathology and immunohistochemical detection of SARS-CoV-2 Spike S2 antigens. The frequencies of portal vein endotheliitis, lobular activity, hepatocellular degeneration, and lobular vascular changes were higher among SARS-CoV-2-infected animals. Spike S2 antigen was not detected in liver. The main results indicate that SARS-CoV-2 infection exacerbated vascular and inflammatory lesions in the liver of hamsters with pre-existing hepatitis of unknown origin. A potential application of this animal model in studies of the pathogenesis and evolution of liver lesions associated with SARS-CoV-2 infection still needs further evaluation.

Comparative Analysis of Internal Tapered Implant-Abutment Connections: Evaluating the Morse Effect.

The purpose of the present study was to evaluate the Morse effect of different internal tapered implant-abutment connections (ITCs) using a pullout test. Implants with different ITCs were selected: Short (Bicon, USA), G1; Novo Colosso (Medens, Brazil), G2; Epkut (SIN, Brazil), G3; Strong SW (SIN, Brazil), G4; Flash (Conexão, Brazil), G5 and Bone Level (Straumann, Switzerland), G6. The respective computer-aided design (CAD) files were loaded into the analysis software to measure each ITC's taper angle and implant-abutment contact area. Six implants from each group were embedded in acrylic resin blocks, and the respective universal abutments were fixed using a mallet (G1) or by applying 20 Ncm of torque (G2 to G6). After 10 minutes, each abutment's retention screw was removed, and the force necessary for abutment rupture was recorded using a universal testing machine at a crosshead speed of 0.5 mm/min. The groups were compared using a one-way analysis of variance and Tukey's test. Spearman's correlation was used to check the correlation of the taper angle and contacting area with the pullout strength. G1, a no-screw abutment with a 3° taper, and G2, a 10° tapered abutment tightened by 20 Ncm, presented the highest pullout strength (P < .05). The increased taper angle of G4, compared to G3, reduced the Morse effect despite their similar implant-abutment contacting areas (P < .05). The G5 and G6 abutments loosened after screw removal and did not exhibit pullout resistance. The closer the tapered angle (r = -.958) and the higher the implant-abutment contact area (r = .880), the higher the pullout strength (P < .001). Within the limits of this study, the Morse effect is different among tapered implant-abutment connections. The closer the tapered angle and the higher the interface area, the higher the Morse effect between the abutment and the implant.

Roadmap to enhance operational excellence in emerging countries.

This paper addresses the dearth of studies examining the status of Operational Excellence (OE) implementation and offers a roadmap for enhancing OE maturity levels. The study encompassed three phases: (1) face-to-face interviews with industry OE experts in 57 companies across seven sectors, (2), classification of companies based on their maturity levels, and (3) development of a roadmap for companies to enhance their OE maturity. Through face-to-face interviews with OE experts in fifty-seven companies across various sectors, the study classified organizations into five maturity levels, with only 7 % reaching the champion level. The proposed roadmap, comprising twenty-three variables across six hierarchical levels, outlines a path for companies to progress towards champion-level OE maturity, with an estimated timeframe of 4.5-5 years from a zero level. This research contributes valuable insights into the OE implementation status in emerging countries and provides practical guidance for organizations aiming to elevate their OE maturity, emphasizing the importance of strategic planning, economic sustainability, environmental sustainability, and social sustainability variables tailored to the specific challenges and opportunities faced by businesses in emerging nations.

Lower limb balance, ankle dorsiflexion, orofacial tissue pressure, and occlusal force of rugby players.

This cross-sectional study examined the lower limb balance, ankle dorsiflexion, orofacial tissue pressure, and occlusal strength of rugby players. Twenty-six participants were divided into groups: rugby players (n â€‹= â€‹13) and healthy sedentary adults (n â€‹= â€‹13). Participants underwent an analysis of lower limb balance using a composite score (Y-Balance Test). Ankle dorsiflexion was measured using the Lunge Test. The Iowa Oral Performance Instrument was employed to measure orofacial tissue pressure. Bite force was measured with a dynamometer, and T-Scan assessed occlusal contact distribution. Data were analyzed using the t-test (p â€‹< â€‹0.05) and ANCOVA with age and weight as covariates, where it is possible to verify that these factors did not influence the results obtained. Significant differences were observed in the balance of the right (p â€‹= â€‹0.07) and left (p â€‹= â€‹0.02) lower limbs, where rugby players had lower composite scores. There were significant differences in the right (p â€‹= â€‹0.005) and left (p â€‹= â€‹0.004) lunges, with rugby players showing lower values, as well as lower tongue pressure (p â€‹= â€‹0.01) and higher lip pressure (p â€‹= â€‹0.03), with significant differences to sedentary participants. There was no significant difference in molar bite force and distribution occlusal contacts between groups. Rugby seems to reduce lower limb displacement, cause ankle hypomobility, lead to changes in orofacial tissues, particularly the tongue and lips. This study is significant for identifying significant differences between rugby players and sedentary individuals, providing new insights into the impact of rugby on health and performance, which can benefit sports training and injury prevention.

Safety and efficacy of teplizumab in the treatment of type 1 diabetes mellitus: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software. RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01). CONCLUSION: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.

Zika virus infection impairs synaptogenesis, induces neuroinflammation, and could be an environmental risk factor for autism spectrum disorder outcome.

Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6-7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.

Immune Evasion of SARS-CoV-2 Omicron Subvariants XBB.1.5, XBB.1.16 and EG.5.1 in a Cohort of Older Adults after ChAdOx1-S Vaccination and BA.4/5 Bivalent Booster.

The recently emerged SARS-CoV-2 Omicron sublineages, including the BA.2-derived XBB.1.5 (Kraken), XBB.1.16 (Arcturus), and EG.5.1 (Eris), have accumulated several spike mutations that may increase immune escape, affecting vaccine effectiveness. Older adults are an understudied group at significantly increased risk of severe COVID-19. Here we report the neutralizing activities of 177 sera samples from 59 older adults, aged 62-97 years, 1 and 4 months after vaccination with a 4th dose of ChAdOx1-S (Oxford/AstraZeneca) and 3 months after a 5th dose of Comirnaty Bivalent Original/Omicron BA.4/BA.5 vaccine (Pfizer-BioNTech). The ChAdOx1-S vaccination-induced antibodies neutralized efficiently the ancestral D614G and BA.4/5 variants, but to a much lesser extent the XBB.1.5, XBB.1.16, and EG.5.1 variants. The results showed similar neutralization titers between XBB.1.16 and EG.5.1 and were lower compared to XBB.1.5. Sera from the same individuals boosted with the bivalent mRNA vaccine contained higher neutralizing antibody titers, providing a better cross-protection against Omicron XBB.1.5, XBB.1.16 and EG.5.1 variants. Previous history of infection during the epidemiological waves of BA.1/BA.2 and BA.4/BA.5, poorly enhanced neutralization activity of serum samples against XBBs and EG.5.1 variants. Our data highlight the continued immune evasion of recent Omicron subvariants and support the booster administration of BA.4/5 bivalent vaccine, as a continuous strategy of updating future vaccine booster doses to match newly emerged SARS-CoV-2 variants.

Neutralizing antibody response after immunization with a COVID-19 bivalent vaccine: Insights to the future.

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.

The Association of Nanostructured Carbonated Hydroxyapatite with Denatured Albumin and Platelet-Rich Fibrin: Impacts on Growth Factors Release and Osteoblast Behavior.

Platelet-rich Fibrin (PRF), a second-generation blood concentrate, offers a versatile structure for bone regeneration due to its composition of fibrin, growth factors, and cytokines, with adaptations like denatured albumin-enriched with liquid PRF (Alb-PRF), showing potential for enhanced stability and growth factor dynamics. Researchers have also explored the combination of PRF with other biomaterials, aiming to create a three-dimensional framework for enhanced cell recruitment, proliferation, and differentiation in bone repair studies. This study aimed to evaluate a combination of Alb-PRF with nanostructured carbonated hydroxyapatite microspheres (Alb-ncHA-PRF), and how this association affects the release capacity of growth factors and immunomodulatory molecules, and its impact on the behavior of MG63 human osteoblast-like cells. Alb-PRF membranes were prepared and associated with nanocarboapatite (ncHA) microspheres during polymerization. MG63 cells were exposed to eluates of both membranes to assess cell viability, proliferation, mineralization, and alkaline phosphatase (ALP) activity. The ultrastructural analysis has shown that the spheres were shattered, and fragments were incorporated into both the fibrin mesh and the albumin gel of Alb-PRF. Alb-ncHA-PRF presented a reduced release of growth factors and cytokines when compared to Alb-PRF (p < 0.05). Alb-ncHA-PRF was able to stimulate osteoblast proliferation and ALP activity at lower levels than those observed by Alb-PRF and was unable to positively affect in vitro mineralization by MG63 cells. These findings indicate that the addition of ncHA spheres reduces the biological activity of Alb-PRF, impairing its initial effects on osteoblast behavior.

Hepatic endotheliitis in Golden Syrian hamsters (Mesocricetus auratus) experimentally infected with SARS-CoV-2

ABSTRACT Hepatic injuries in COVID-19 are not yet fully understood and indirect pathways (without viral replication in the liver) have been associated with the activation of vascular mechanisms of liver injury in humans infected with SARS-CoV-2. Golden Syrian hamsters are an effective model for experimental reproduction of moderate and self-limiting lung disease during SARS-CoV-2 infection. As observed in humans, this experimental model reproduces lesions of bronchointerstitial pneumonia and pulmonary vascular lesions, including endotheliitis (attachment of lymphoid cells to the luminal surface of endothelium). Extrapulmonary vascular lesions are well documented in COVID-19, but such extrapulmonary vascular lesions have not yet been described in the Golden Syrian hamster model of SARS-CoV-2 infection. The study aimed to evaluate microscopic liver lesions in Golden Syrian hamsters experimentally infected with SARS-CoV-2. In total, 38 conventional Golden Syrian hamsters, divided into infected group (n=24) and mock-infected group (n=14), were euthanized at 2-, 3-, 4-, 5-, 7-, 14-, and 15-days post infection with SARS-CoV-2. Liver fragments were evaluated by histopathology and immunohistochemical detection of SARS-CoV-2 Spike S2 antigens. The frequencies of portal vein endotheliitis, lobular activity, hepatocellular degeneration, and lobular vascular changes were higher among SARS-CoV-2-infected animals. Spike S2 antigen was not detected in liver. The main results indicate that SARS-CoV-2 infection exacerbated vascular and inflammatory lesions in the liver of hamsters with pre-existing hepatitis of unknown origin. A potential application of this animal model in studies of the pathogenesis and evolution of liver lesions associated with SARS-CoV-2 infection still needs further evaluation.

Clinical and Biochemical Evaluation of the Use of Alb-PRF versus L-PRF in Mandibular Third Molar Extractions: A Split-Mouth Randomized Clinical Trial.

Bone tissue engineering seeks biomaterials that enable cell migration, angiogenesis, matrix deposition, and tissue regeneration. Blood concentrates like platelet-rich fibrin (L-PRF) offer a cost-effective source of cells and growth factors to enhance healing. The present study aimed to evaluate heated serum albumin with liquid PRF (Alb-PRF) and L-PRF clinically and biochemically after placement in dental sockets following mandibular third molar extraction. In a controlled, split-mouth study involving 10 volunteers, 20 extracted molars were treated with either Alb-PRF or L-PRF. Post-extraction, pain, trismus, infection presence, and swelling were measured. The concentrations of different analytes in the surgical sites were also examined. The data were statistically analyzed, with significance defined at p < 0.05 (t-test). No significant difference was noted between the groups for pain and trismus, but Alb-PRF showed a significant reduction in swelling on day seven. The Alb-PRF group showed lower levels of pro-inflammatory cytokines (GM-CSF, IL-1b, IL-6, IFNy, IL-8, IL-15, RANTES, and MIP-1a) after seven days, with only higher expressions of MIP-1b, IL-1b, and MCP-1 found in the L-PRF group. Differences were observed in the release of analytes between L-PRF and Alb-PRF, with Alb-PRF significantly reducing edema after seven days. Alb-PRF reduced edema, while L-PRF increased inflammatory cytokines. When compared to L-PRF, Alb-PRF reduced edema and the release of inflammatory cytokines, suggesting promising effects in socket healing while underscoring the role of growth factors and cytokines in potential applications of blood concentrates.

The Interplay of Raloxifene and Sonochemical Bio-Oss in Early Maxillary Sinus Bone Regeneration: A Histological and Immunohistochemical Analysis in Rabbits.

The study aimed to assess the efficacy of using Raloxifene with ultrasonic processing to enhance Bio-Oss®, a bone graft substitute, for maxillary sinus bone height reconstruction. A total of 24 rabbit maxillary sinuses were distributed into three groups, each receiving different treatments: Bio-Oss® only, sonicated Bio-Oss, and sonicated Bio-Oss® with Raloxifene. Surgical procedures and subsequent histomorphometric and immunohistochemistry analyses were conducted to evaluate the bone formation, connective tissue, and remaining biomaterial, as well as the osteoblastic differentiation and maturation of collagen fibers. Results indicated that the sonicated Bio-Oss® and Bio-Oss® groups showed similar histological behavior and bone formation, but the Raloxifene group displayed inflammatory infiltrate, low bone formation, and disorganized connective tissue. The statistical analysis confirmed significant differences between the groups in terms of bone formation, connective tissue, and remaining biomaterial. In conclusion, the study found that while sonicated Bio-Oss® performed comparably to Bio-Oss® alone, the addition of Raloxifene led to an unexpected delay in bone repair. The findings stress the importance of histological evaluation for accurate bone repair assessment and the necessity for further investigation into the local application of Raloxifene. Future research may focus on optimizing bone substitutes with growth factors to improve bone repair.

Varnish with S-PRG filler reduces dentin permeability after erosive/abrasive challenge.

PURPOSE: To evaluate the effect of different varnishes on dentin permeability to erosive/abrasive challenges. METHODS: 60 superficial dentin discs were randomly allocated to six groups (n=10): Duraphat, PRG Barrier Coat, Clinpro XT, Profluorid, Fluor Protector S and untreated (control). Permeability tests were carried out: after acid conditioning, after treatment, and after abrasive/erosive challenges. The abrasive-erosive challenges were performed for 5 days (citric acid and in remineralizing saliva), as well as abrasion with toothpaste slurry (Colgate Total 12). Scanning electron microscopy (SEM) images were obtained of the dentin surfaces (5,000x) after the treatments, and after the erosive/abrasive challenges. RESULTS: Kruskal-Wallis and Dunn tests showed that all the varnishes promoted a decrease in dentin permeability directly after application, with Clinpro XT showing the highest percentage (69.52%) of dentin sealing (P= 0.0188). After the erosive/abrasive challenge, only PRG Barrier Coat varnish showed dentin sealing ability with reduced dentin permeability (42.16%) (P= 0.0014). However, none of the applied varnishes promoted a statistically significant difference in the percentage of dentin sealing, compared with the control group (P> 0.05). Clinpro XT showed a higher percentage of dentin sealing, while only PRG Barrier Coat showed reduced dentin permeability after the erosive/abrasive challenge. CLINICAL SIGNIFICANCE: Varnish containing S-PRG filler has the efficacy needed to be used as a coating material to reduce dentin permeability in situations of erosive/abrasive challenges.

Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters.

The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.

Harnessing the Power of PAOO and Invisalign: An Interdisciplinary Approach to Orthodontic Care.

The present article explores the benefits of combining periodontally accelerated osteogenic orthodontics (PAOO) with Invisalign for optimal orthodontic treatment outcomes. PAOO is an interdisciplinary dental technique that minimizes complications and accelerates tooth movement while enhancing various orthodontic treatments. In conjunction with Invisalign, PAOO provides a discreet and comfortable solution for patients seeking to improve their smile. The study presents two challenging cases successfully treated using this combined approach, emphasizing the technique's potential to reduce treatment times and improve orthodontic outcomes. The interdisciplinary approach of PAOO ensures long-term success and stability by preserving periodontal structures and addressing potential bony defects. By incorporating bone grafting materials, PAOO helps prevent common concerns in traditional orthodontic treatments, such as bony defects and gingival recession. Furthermore, the combination with Invisalign offers a more aesthetically pleasing and comfortable treatment experience, allowing patients to maintain their self-esteem and confidence throughout the treatment. Despite the potential advantages, dental professionals must manage patient expectations and address potential complications to ensure the best possible results. Overall, the integration of PAOO and Invisalign demonstrates a viable alternative for patients who do not want to proceed with orthognathic surgery, enhancing patient satisfaction and overall treatment outcomes.

Standardization of Animal Models and Techniques for Platelet-Rich Fibrin Production: A Narrative Review and Guideline.

Experimental research is critical for advancing medical knowledge and enhancing patient outcomes, including in vitro and in vivo preclinical assessments. Platelet-rich fibrin (PRF) is a blood by-product that has garnered attention in the medical and dental fields due to its potential for tissue regeneration and wound healing. Animal models, such as rabbits and rats, have been used to produce PRF and examine its properties and applications. PRF has demonstrated potential in the dental and medical fields for reducing inflammation, promoting tissue repair, and accelerating wound healing. This narrative review aims to compare existing evidence and provide guidelines for PRF animal research, emphasizing the importance of standardizing animal models, following ethical considerations, and maintaining transparency and accountability. The authors highlight the necessity to use the correct relative centrifugal force (RCF), standardize centrifugal calibration, and report detailed information about blood collection and centrifuge parameters for reproducible results. Standardizing animal models and techniques is crucial for narrowing the gap between laboratory research and clinical applications, ultimately enhancing the translation of findings from bench to bedside.

Sentinel lymph node biopsy following neoadjuvant chemotherapy: an evidence-based review and recommendations for current practice.

Sentinel lymph node biopsy (SLNB) at upfront surgery is the gold-standard surgical method for axillary lymph node staging in early stage breast cancer: the technique provides adequate information regarding axillary status, with similar oncological safety and lower morbidity compared to axillary dissection, despite the false negative rates. Neoadjuvant chemotherapy (NACT), traditionally used for locally advanced breast cancer, plays an important role in the treatment of early stage breast cancer, making downstaging possible in axillary lymph node and breast cancer, thus minimizing the impact of surgery and reducing morbidity, as well as enabling patients with residual disease to be selected for adjuvant treatment. In this respect, the role of SLNB has proved controversial, particularly in view of the lack of data from randomized clinical trials on this subject. Currently, the de-escalation of axillary surgery after NACT is mainly based on retrospectives studies and false negative rates. This paper reviews current evidence on the management of axillary surgery following NACT under different circumstances, with suggested recommendations in each scenario: clinically negative nodes at diagnosis and SLNB after NACT, clinically positive nodes at diagnosis and SLNB after NACT, positive SLNB following NACT and finally the possibility of omitting axillary surgery in good responders.

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.

Satisfacción de estudiantes con la virtualidad en la asignatura Metodología de la Investigación en Medicina / Student satisfaction with virtuality in the Medicine Research Methodology course

Fundamento: la utilización de entornos virtuales de enseñanza aprendizaje es una tendencia que las instituciones de educación superior ponen en práctica en sus estrategias de desarrollo y perspectiva académica. Objetivo: evaluar el grado de satisfacción de los estudiantes con la virtualidad de la asignatura Metodología de la Investigación en la carrera de Medicina, de la Facultad de Ciencias Médicas de Sagua la Grande durante el período 2020-2021. Métodos: se realizó una investigación de tipo descriptiva transversal donde se aplicaron métodos teóricos: análisis-síntesis e inducción-deducción y empíricos: un cuestionario constituido por 15 ítems, cuyas respuestas fueron evaluadas a través de una escala aditiva tipo Likert. Para el procesamiento de la información se emplearon la estadística descriptiva y herramientas estadísticas. Resultados: el aula virtual diseñada para la asignatura se estructuró según unidades temáticas, además de un módulo donde se situaron las orientaciones generales. Las frecuencias que predominaron para todas las dimensiones estuvieron entre los niveles Satisfecho y Muy satisfecho. Se destacaron las dimensiones Resultados y Contenido con predominio de respuestas positivas; en las dimensiones Orientaciones generales del curso y Disponibilidad/estabilidad, fue donde manifestaron mayor negatividad. Conclusiones: la utilización de la virtualidad demostró que el nivel de satisfacción de los estudiantes alcanzado en la asignatura Metodología de la Investigación en la carrera de Medicina es elevado por lo que se recomienda su aplicación por los docentes como apoyo a la clase presencial.

Background: the use of virtual teaching-learning environments is a trend that higher education institutions put into practice in their development strategies and academic perspective. Objective: to evaluate the degree of satisfaction of the students with the virtuality of the Research Methodology subject in the Medicine degree, of Sagua la Grande Faculty of Medical Sciences during from 2020 to 2021. Methods: a cross-sectional descriptive investigation was carried out where theoretical methods were applied: analysis-synthesis and induction-deduction and empirical: a questionnaire consisting of 15 items, whose answers were evaluated through a Likert-type additive scale. For the information processing, descriptive statistics and statistical tools were used. Results: the virtual classroom designed for the subject was structured according to thematic units, as well as a module where the general orientations were located. The frequencies that prevailed for all dimensions were between the Satisfied and Very Satisfied levels. The Results and Content dimensions with a predominance of positive responses were highlighted; in the General orientations of the course and Availability/stability dimensions, it was where they manifested the greatest negativity. Conclusions: the use of virtuality showed that the level of student satisfaction achieved in the Research Methodology subject in the Medicine degree is high, so its implementation by teachers is recommended as support for the face-to-face class.