Lymphatic Regeneration after Popliteal Lymph Node Excision and Implantation of Aligned Nanofibrillar Collagen Scaffolds: An Experimental Rabbit Model.

Lymphedema presents significant challenges to patients' quality of life, prompting the exploration of innovative treatments, such as collagen scaffolds, aimed at treating and reducing the risk of lymphedema. We aimed to evaluate the preventive and therapeutic efficacy and the lymphangiogenic potential of implanted aligned nanofibrillar collagen scaffolds (BioBridgeTM) following the induction of secondary lymphedema in a rabbit model. Thirty rabbits were divided into treatment (G1), prevention (G2), and control (G3) groups. Secondary lymphedema was induced in all groups. BioBridgeTM implantation was performed in G2 and G1 on days 0 and 60, respectively. Follow-ups included hindlimb circumference measurements and indocyanine green lymphography at 0, 60, and 90 days. None of the study rabbits exhibited dermal backflow on day 0 before surgery. At 60 days, the incidence rates of dermal backflow in G1, G2, and G3 were 100%, 44.4%, and 90%, respectively. Furthermore, at 90 days, the incidence rates were 22.2%, 44.4%, and 90%, respectively. New linear lymphatic observation was seen in rabbits with resolved dermal backflow. The findings of this study demonstrated the capacity of BioBridgeTM scaffolds to induce new lymphatic vessel formation and reduce dermal backflow in secondary lymphedema in a rabbit model.

Lymphatic Patterns in the Superficial Circumflex Iliac Artery Perforator Flap.

BACKGROUND: Lymphedema is a chronic condition, characterized by fluid buildup and tissue swelling and is caused by impairment of the lymphatic system. The lymph interpositional flap transfer technique, in which lymph flow is restored with a flap that includes subdermal lymphatic channels, is an option for surgical reconstruction. The superficial circumflex iliac artery perforator (SCIP) flap can be used for this purpose. This study aimed to describe and characterize the lymphatic patterns within the vascular territory of the SCIP flap. METHODS: This cross-sectional multicenter study involved 19 healthy volunteers aged ≥18 years of both sexes assessing the bilateral SCIP flap zone. Superficial lymphatic patterns were evaluated at 4-, 14-, and 24 minutes after indocyanine green (ICG) lymphography injection. Standardized procedures were implemented for all participants in both hospitals. RESULTS: The linear pattern was predominant bilaterally. The median number of lymphatic vessels and their length increased over time. Most lymphatic vessels in the SCIP flap were oriented toward the inguinal lymph node (ILN). However, the left SCIP zone lymphatic vessels were directed opposite to the ILN. CONCLUSION: The two sides SCIP zones were not significantly different. The primary direction of the bilateral lymphatic vessels was toward the ILN, although only single-side lymphatic vessels were in the opposite direction. These findings emphasize the importance of assessing lymphatic axiality and coherent lymphatic patterns prior to undertaking the SCIP as an interposition flap, to ensure effective restoration of lymphatic flow.

Lymphaticovenous anastomosis in rabbits: A novel live experimental animal model for supermicrosurgical training.

BACKGROUND: Lymphaticovenous anastomosis is widely used in lymphedema management. Although its effectiveness in reducing edema in patients can be clinically observed, evaluating the long-term outcomes of this technique can be complex. This study established an animal model to assess the outcomes of lymphaticovenous anastomosis technique at 15 and 30-days post-surgery using indocyanine green lymphography, Patent Blue V dye injection, and histopathological examination. METHODS: An experimental model was established in the hindlimbs of 10 rabbits using the popliteal vein and afferent lymphatic vessels in the popliteal area. The subjects were divided into two groups: the first group (n = 5) underwent patency assessment at 0 and 15 days, and the second group (n = 5) at 0 and 30-days, resulting in 20 anastomoses. Patency was verified at 0, 15, and 30-days using indocyanine green lymphography and Patent Blue V injection. Histopathological examinations were performed on the collected anastomosis samples. RESULTS: The patency rate was 90% (19/20) initially, 60% (6/10) at 15 days post-surgery, and 80% (8/10) at 30-days. The average diameter of lymphatic vessels and veins was 1.0 mm and 0.8 mm, respectively. The median number of collateral veins was 3; the median surgical time was 65.8 min. Histopathology revealed minimal endothelial damage and inflammatory responses due to the surgical sutures, with vascular inflammation and thrombosis in a single case. Local vascular neoformations were observed. CONCLUSION: This study highlights the reliability and reproducibility of using rabbits as experimental models for training in lymphaticovenous anastomosis technique owing to the accessibility of the surgical site and dimensions of their popliteal vasculature.

PEDOT-Coated PLA Fibers Electrospun from Solutions Incorporating Fe(III)Tosylate in Different Solvents by Vapor-Phase Polymerization for Neural Regeneration.

Therapeutic solutions for injuries in the peripheral nervous system are limited and not existing in the case of the central nervous system. The electrical stimulation of cells through a cell-supporting conductive scaffold may contribute to new therapeutic solutions for nerve regeneration. In this work, biocompatible Polylactic acid (PLA) fibrous scaffolds incorporating Fe(III)Tosylate (FeTos) were produced by electrospinning a mixture of PLA/FeTos solutions towards a rotating cylinder, inducing fiber alignment. Fibers were coated with the conductive polymer Poly(3,4 ethylenedioxythiophene) (PEDOT) formed by vapor-phase polymerization of EDOT at 70 °C for 2 h. Different solvents (ETH, DMF and THF) were used as FeTos solvents to investigate the impact on the scaffold's conductivity. Scaffold conductivity was estimated to be as high as 1.50 × 10-1 S/cm when FeTos was dissolved in DMF. In vitro tests were performed to evaluate possible scaffold cytotoxicity, following ISO 10993-5, revealing no cytotoxic effects. Differentiation and growth of cells from the neural cell line SH-SY5Y seeded on the scaffolds were also assessed, with neuritic extensions observed in cells differentiated in neurons with retinoic acid. These extensions tended to follow the preferential alignment of the scaffold fibers.

Effects of intrauterine exposure to SARS-CoV-2 on infants' development: a rapid review and meta-analysis.

Potential medium- and long-term neurodevelopmental sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy have not been ruled out. We aimed to systematically review and summarize the evidence regarding the effects of intrauterine exposure to SARS-CoV-2 on infant development and behavior. Scopus, PubMed, Web of Science, CINAHL, and PsycNet databases were searched for studies published up to February 6, 2023, investigating the effects of gestational SARS-CoV-2 on infant development and behavior. We performed narrative synthesis according to updated protocols. Studies using comparison groups and with the Ages and Stages Questionnaires-Third Edition (ASQ-3) scores available were included in a meta-analysis performed according to Cochrane protocols. We used the Newcastle-Ottawa Quality Assessment Scale to analyze the risk of bias. Heterogeneity was calculated using the I2 statistic. The search identified 2,782 studies. After removing duplicates and applying the eligibility criteria, we performed a narrative synthesis of 10 included studies and a meta-analysis of three. There was no evidence of higher developmental delay rates in infants exposed to SARS-CoV-2 during pregnancy compared to non-exposed infants. However, the exposed infants scored lower than either the non-exposed children or pre-pandemic cohorts in some domains. Pooled results from the random-effects model indicated that SARS-CoV-2-exposed infants had lower scores on fine motor (mean difference [MD] = -4.70, 95% confidence interval [CI]: -8.76; -0.63), and problem-solving (MD = -3.05, 95% CI: -5.88; -0.22) domains than non-exposed infants (heterogeneity: I2 = 69% and 88%, respectively). There was no difference between the exposed and non-exposed infants in the communication, gross motor, and personal-social ASQ-3 domains.  Conclusion: We did not find evidence confirming the association between SARS-CoV-2 gestational exposure and neurodevelopmental delays. However, the meta-analysis indicated that gestational exposure negatively affected fine motor and problem-solving skills. Robust evidence on this topic is still incipient, and the available studies present methodological inconsistencies that limit the drawing of clear-cut conclusions.   PROSPERO registration: #CRD42022308002; March 14, 2022. What is Known: • COVID-19 is associated with adverse pregnancy outcomes potentially linked to neurodevelopmental delays. • SARS-CoV-2 vertical transmission is rare; however, infections during pregnancy can be deleterious to the fetus, possibly mediated by maternal immune activation and other inflammatory mechanisms. What is New: • No evidence of increased developmental delay rates among SARS-CoV-2 gestational-exposed infants was found. However, a meta-analysis of three studies showed lower scores in fine motor and personal social ASQ-3 domains among exposed infants. • SARS-CoV-2 gestational exposure and the pandemic can affect child development via many mechanisms. Potential neurodevelopmental sequelae of SARS-CoV-2 exposure during gestation have not been ruled out.

Popliteal Vascular Lymph Node Resection in the Rabbit Hindlimb for Secondary Lymphedema Induction.

Lymphedema is a common condition often associated with cancer and its treatment, which leads to damage to the lymphatic system, and current treatments are mostly palliative rather than curative. Its high incidence among oncologic patients indicates the need to study both normal lymphatic function and pathologic dysfunction. To reproduce chronic lymphedema, it is necessary to choose a suitable experimental animal. Attempts to establish animal models are limited by the regenerative capacity of the lymphatic system. Among the potential candidates, the rabbit hindlimb is easy to handle and extrapolate to the human clinical scenario, making it advantageous. In addition, the size of this species allows for better selection of lymphatic vessels for vascularized lymph node resection. In this study, we present a procedure of vascular lymph node resection in the rabbit hindlimb for inducing secondary lymphedema. Anesthetized animals were subjected to circumferential measurement, patent blue V infiltration, and indocyanine green lymphography (ICG-L) using real-time near-infrared fluorescence, a technique that allows the identification of single popliteal nodes and lymphatic channels. Access to the identified structures is achieved by excising the popliteal node and ligating the medial and lateral afferent lymphatics. Special care must be taken to ensure that any lymphatic vessel that joins the femoral lymphatic system within the thigh without entering the popliteal node can be identified and ligated. Postoperative evaluation was performed at 3, 6, and 12 months after induction using circumferential measurements of the hindlimb and ICG-L. As demonstrated during follow-up, the animals developed dermal backflow that was maintained until the 12th month, making this experimental animal useful for novel long-term evaluations in the management of lymphedema. In conclusion, the approach described here is feasible and reproducible. Additionally, during the time window presented, it can be representative of human lymphedema, thus providing a useful research tool.

Serological survey for IgG antibodies against SARS-CoV-2 from newborns and their mothers.

This serological survey, conducted in five Brazilian municipalities, evaluated the use of dried blood spots (DBS), obtained from newborns and their mothers, to detect SARS-CoV-2 IgG antibodies. DBS were obtained from 4,803 neonates aged up to seven days and their mothers, both asymptomatic, at public health care clinics during newborn screening. DBS were processed by ELISA to detect IgG antibodies against SARS-CoV-2 nucleocapsid antigen. Mothers of seropositive neonates were interviewed about sociodemographic characteristics and clinical and laboratory antecedents. Non-satisfactory samples, dyads with incomplete data, and vaccinated mothers were excluded. Of the 1,917 DBS dyads samples analyzed, 14.7% of neonates showed IgG antibodies against SARS-CoV-2. Among seropositive neonates, 73.2% of their mothers were also seropositive. More than half of the mothers with seropositive neonates denied clinical or laboratory suspicion of COVID-19 during pregnancy. Suspicion occurred in the third trimester for 24.6% of the mothers. This study tested an innovative strategy to improve the understanding of COVID-19 antibody dynamics during pregnancy and suggests the feasibility of a universal serological survey in puerperal women and neonates.

New Polymeric Composites Based on Two-Dimensional Nanomaterials for Biomedical Applications.

The constant evolution and advancement of the biomedical field requires robust and innovative research. Two-dimensional nanomaterials are an emerging class of materials that have risen the attention of the scientific community. Their unique properties, such as high surface-to-volume ratio, easy functionalization, photothermal conversion, among others, make them highly versatile for a plethora of applications ranging from energy storage, optoelectronics, to biomedical applications. Recent works have proven the efficiency of 2D nanomaterials for cancer photothermal therapy (PTT), drug delivery, tissue engineering, and biosensing. Combining these materials with hydrogels and scaffolds can enhance their biocompatibility and improve treatment for a variety of diseases/injuries. However, given that the use of two-dimensional nanomaterials-based polymeric composites for biomedical applications is a very recent subject, there is a lot of scattered information. Hence, this review gathers the most recent works employing these polymeric composites for biomedical applications, providing the reader with a general overview of their potential.

Idiopathic Nephrotic Syndrome in Pediatrics: An Up-to-date.

BACKGROUND: Idiopathic or Primary Nephrotic Syndrome (INS) is a common glomerular disease in pediatric population, characterized by proteinuria, edema and hypoalbuminemia with variable findings in renal histopathology. OBJECTIVE: This review aims to summarize current data on the etiopathogenesis diagnosis, protocols of treatment and potential therapeutic advances in INS. METHODS: This narrative review searched for articles on histopathology, physiopathology, genetic causes, diagnosis and treatment of INS in pediatric patients. The databases evaluated were PubMed and Scopus. RESULTS: INS is caused by an alteration in the permeability of the glomerular filtration barrier with unknown etiology. There are several gaps in the etiopathogenesis, response to treatment and clinical course of INS that justify further investigation. Novel advances include the recent understanding of the role of podocytes in INS and the identification of genes associated with the disease. The role of immune system cells and molecules has also been investigated. The diagnosis relies on clinical findings, laboratory exams and renal histology for selected cases. The treatment is primarily based on steroids administration. In case of failure, other medications should be tried. Recent studies have also searched for novel biomarkers for diagnosis and alternative therapeutic approaches. CONCLUSION: The therapeutic response to corticosteroids still remains the main predictive factor for the prognosis of the disease. Genetic and pharmacogenomics tools may allow the identification of cases not responsive to immunosuppressive medications.

Serological survey for IgG antibodies against SARS-CoV-2 from newborns and their mothers / Inquérito sorológico para anticorpos IgG contra SARS-CoV-2 de recém-nascidos e suas mães / Encuesta serológica de anticuerpos IgG contra el SARS-CoV-2 de recién nacidos y sus madres

This serological survey, conducted in five Brazilian municipalities, evaluated the use of dried blood spots (DBS), obtained from newborns and their mothers, to detect SARS-CoV-2 IgG antibodies. DBS were obtained from 4,803 neonates aged up to seven days and their mothers, both asymptomatic, at public health care clinics during newborn screening. DBS were processed by ELISA to detect IgG antibodies against SARS-CoV-2 nucleocapsid antigen. Mothers of seropositive neonates were interviewed about sociodemographic characteristics and clinical and laboratory antecedents. Non-satisfactory samples, dyads with incomplete data, and vaccinated mothers were excluded. Of the 1,917 DBS dyads samples analyzed, 14.7% of neonates showed IgG antibodies against SARS-CoV-2. Among seropositive neonates, 73.2% of their mothers were also seropositive. More than half of the mothers with seropositive neonates denied clinical or laboratory suspicion of COVID-19 during pregnancy. Suspicion occurred in the third trimester for 24.6% of the mothers. This study tested an innovative strategy to improve the understanding of COVID-19 antibody dynamics during pregnancy and suggests the feasibility of a universal serological survey in puerperal women and neonates.

Este inquérito sorológico, realizado em cinco municípios brasileiros, avaliou o uso de sangue seco em papel filtro (DBS), obtidas de recém-nascidos e suas mães, para detectar anticorpos IgG SARS-CoV-2. DBS foram obtidas de 4.803 neonatos com até sete dias de vida e suas mães, ambos assintomáticos, em unidades de saúde pública durante a triagem neonatal. DBS foram processadas ​​por ELISA para detectar anticorpos IgG contra o antígeno do nucleocapsídeo SARS-CoV-2. As mães de neonatos soropositivos foram entrevistadas quanto às características sociodemográficas e antecedentes clínicos e laboratoriais. Foram excluídas amostras insatisfatórias, díades com dados incompletos e mães vacinadas. Das 1.917 amostras analisadas, 14,7% dos neonatos apresentaram anticorpos IgG contra SARS-CoV-2. Entre os recém-nascidos soropositivos, 73,2% era filho de mulheres também soropositivas. Mais da metade das mães com recém-nascidos soropositivos negaram suspeita clínica ou laboratorial de COVID-19 durante a gravidez. A suspeita de COVID-19 ocorreu no terceiro trimestre para 24,6% das mães. Este estudo testou uma estratégia inovadora para melhorar a compreensão da dinâmica de anticorpos contra SARS-CoV-2 durante a gravidez e sugere a viabilidade de realização de um inquérito sorológico universal em puérperas e neonatos.

Esta encuesta serológica, realizada en cinco municipios brasileños, evaluó el uso de manchas de sangre seca (DBS), obtenidas de recién nacidos y sus madres, para detectar anticuerpos IgG contra el SARS-CoV-2. Se obtuvieron DBS de 4.803 recién nacidos de hasta siete días de edad y sus madres, ambos asintomáticos, en clínicas de salud pública durante el cribado neonatal. Las DBS se procesaron mediante ELISA para detectar anticuerpos IgG contra el antígeno de la nucleocápside del SARS-CoV-2. Se entrevistó a madres de recién nacidos seropositivos sobre características sociodemográficas y antecedentes clínicos y de laboratorio. Se excluyeron muestras no satisfactorias, díadas con datos incompletos y madres vacunadas. De las 1.917 muestras de díadas DBS analizadas, el 14,7 % de los recién nacidos mostró anticuerpos IgG contra el SARS-CoV-2. Entre los recién nacidos seropositivos, el 73,2% de sus madres también eran seropositivas. Más de la mitad de las madres con recién nacidos seropositivos negaron sospecha clínica o de laboratorio de COVID-19 durante el embarazo. La sospecha ocurrió en el tercer trimestre para el 24,6% de las madres. Este estudio probó una estrategia innovadora para mejorar la comprensión de la dinámica de anticuerpos de COVID-19 durante el embarazo y sugiere la viabilidad de una encuesta serológica universal en mujeres puérperas y recién nacidos.

Efeito da criolipólise na região abdominal / Effects of cryolipolysis in the abdominal region

O tecido adiposo forma uma camada abaixo da pele, na hipoderme, no qual se encontra o predomínio de adipócitos, um tipo de célula que acumula gotículas de lipídios em seu citoplasma. A técnica de criolipólise foi desenvolvida por pesquisadores da Universidade de Harvard, nos Estados Unidos, é um método não invasivo, que utiliza baixas temperaturas para eliminar a gordura localizada, assim não necessitando de anestesia ou qualquer substância injetável, indicado para pessoas que tenham gordura localizada, não sobrepeso. O objetivo desse trabalho foi verificar os resultados da criolipólise na região abdominal. Para realização do procedimento foram selecionadas três voluntarias do sexo feminino, com idades entre 26 e 34 anos, sendo as três com adiposidade localizada na região abdominal inferior e superior. Foi aplicado o procedimento de criolipólise no abdome, com duração de 60 minutos. Através da aplicação do procedimento podem-se observar resultados satisfatórios com a redução de medida. Assim conclui-se que o método de criolipólise foi eficaz na adiposidade localizada na região abdominal. (AU)

The adipose tissue forms a layer beneath the skin in the hypodermis, in which is the predominance of adipocytes, a type of cell that accumulates lipid droplets in its cytoplasm. The technique of cryolipolysis, developed at Harvard University in the United States, is a noninvasive method that uses low temperatures to eliminate localized fat, thus not requiring anesthesia or any injectable substance, indicated for people with localized fat, not for overweight. The aim of this study was to verify the results of cryolipolysis in the abdominal region. Three volunteers were selected to perform the procedure, with ages ranging from 26 to 34 years old, and three with adiposity located in the lower and upper abdominal regions. The cryolipolysis procedure was applied to the abdomen, with duration of 60 minutes. Through the application of the procedure satisfactory results could be observed with the measurement reduction. Thus, it was concluded that the cryolipolysis method was effective in localized adiposity in the abdominal region. (AU)

Evaluation of the anti-nitrative effect of plant antioxidants using a cowpea Fe-superoxide dismutase as a target.

Nitric oxide cytotoxicity arises from its rapid conversion to peroxynitrite (ONOO(-)) in the presence of superoxide, provoking functional changes in proteins by nitration of tyrosine residues. The physiological significance of this post-translational modification is associated to tissue injury in animals, but has not been yet clarified in plants. The objective of this study was to establish new approaches that could help to understand ONOO(-) reactivity in plants. A recombinant Fe-superoxide dismutase from cowpea (Vigna unguiculata (L.) Walp.), rVuFeSOD, was the target of the ONOO(-)-generator SIN-1, and the anti-nitrative effect of plant antioxidants and haemoglobins was tested in vitro. Nitration on rVuFeSOD was evaluated immunochemically or as the loss of its enzymatic activity. This assay proved to be useful to test a variety of plant compounds for anti-nitrative capacity. Experimental data confirmed that rice (Oryza sativa L.) haemoglobin-1 (rOsHbI) and cowpea leghaemoglobin-2 exerted a protective function against ONOO(-) by diminishing nitration on rVuFeSOD. Both plant haemoglobins were nitrated by SIN-1. The chelator desferrioxamine suppressed nitration in rOsHbI, indicating that Fe plays a key role in the reaction. The removal of the haem moiety in rOsHbI importantly suppressed nitration, evidencing that this reaction may be self-catalyzed. Among small antioxidants, ascorbate remarkably decreased nitration in all tests. The phenolic compounds caffeic acid, gallic acid, pyrogallol, 4-hydroxybenzoic acid and the flavonoid gossypin also diminished tyrosine nitration and protected rVuFeSOD to different extents. It is concluded that small plant antioxidants, especially ascorbate, and haemoglobins may well play key roles in ONOO(-) homeostasis in vivo.

Two Fe-superoxide dismutase families respond differently to stress and senescence in legumes.

Three main families of SODs in plants may be distinguished according to the metal in the active center: CuZnSODs, MnSOD, and FeSOD. CuZnSODs have two sub-families localized either in plant cell cytosol or in plastids, the MnSOD family is essentially restricted to mitochondria, and the FeSOD enzyme family has been typically localized into the plastid. Here, we describe, based on a phylogenetic tree and experimental data, the existence of two FeSOD sub-families: a plastidial localized sub-family that is universal to plants, and a cytosolic localized FeSOD sub-family observed in determinate-forming nodule legumes. Anti-cytosolic FeSOD (cyt_FeSOD) antibodies were employed, together with a novel antibody raised against plastidial FeSOD (p_FeSOD). Stress conditions, such as nitrate excess or drought, markedly increased cyt_FeSOD contents in soybean tissues. Also, cyt_FeSOD content and activity increased with age in both soybean and cowpea plants, while the cyt_CuZnSOD isozyme was predominant during early stages. p_FeSOD in leaves decreased with most of the stresses applied, but this isozyme markedly increased with abscisic acid in roots. The great differences observed for p_FeSOD and cyt_FeSOD contents in response to stress and aging in plant tissues reveal distinct functionality and confirm the existence of two immunologically differentiated FeSOD sub-families. The in-gel FeSOD activity patterns showed a good correlation to cyt_FeSOD contents but not to those of p_FeSOD. This indicates that cyt_FeSOD is the main active FeSOD in soybean and cowpea tissues. The diversity of functions associated with the complexity of FeSOD isoenzymes depending of the location is discussed.