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Multiple oxaliplatin-resistance mechanisms have been proposed such as increase of anti-inflammatory M2 macrophages and lack of cytotoxic T-cells. Thereby oxaliplatin chemotherapy promotes an immunosuppressive tumor microenvironment and inhibits anti-tumor efficacy. It has been shown that toll-like receptor (TLR) agonists are capable of triggering broad inflammatory responses, which may potentially reduce oxaliplatin-resistance and improve the efficacy of chemotherapy. In this study, we established colorectal tumor-bearing zebrafish and mice, and investigated the effects of TLR agonists and oxaliplatin in macrophage function and anti-tumor T cell immunity as well as tumor growth control in vivo. To increase the potential of this strategy as well minimize side effects, neutral liposomes carrying oxaliplatin and cationic liposomes co-loaded with TLR agonists Poly I:C and R848 were employed for maximum immune activation. Both of two liposomal systems exhibited good physicochemical properties and excellent biological activities in vitro. The combination strategy delivered by liposomes showed more pronounced tumor regression and correlated with decreased M2 macrophage numbers in both zebrafish and mice. Increasing numbers of dendritic cells, DC maturation and T cell infiltration mediated via immunogenic cell death were observed in treated mice. Our study offers valuable insights into the potential of liposomal combination therapy to improve cancer treatment by reprogramming the tumor microenvironment and enhancing immune responses., Competing Interests: Declaration of competing interest The authors declare no conflicts of financial interest., (Copyright © 2024. Published by Elsevier B.V.)

Induced pluripotent stem cells (iPSCs) are reprogrammed cells with a remarkable capacity for unlimited expansion and differentiation into various cell types. Companies worldwide are actively engaged in developing clinical-grade iPSC lines to address the needs of regenerative medicine, immunotherapies, and precision medicine. However, ensuring the safety and quality of iPSCs is essential, with adherence to Good Manufacturing Practices (GMP) and ethical considerations being paramount. Perinatal cell and tissue banks, such as umbilical cord (UC) blood and tissue banks, are emerging as ideal sources for generating iPSCs due to their unique characteristics and GMP compliance. These banks provide access to immature cells with limited environmental exposure, known family and medical histories of donors, and readily available resources, thereby reducing the time and cost associated with personalized treatment strategies. This study describes the establishment of the first clinical-grade iPSC lines from umbilical cord mesenchymal stromal cells in Brazil. The process involved rigorous quality control measures, safety assessments, and adherence to regulatory standards, resulting in iPSCs with the necessary characteristics for clinical use, including sterility, genomic integrity, and stability. Importantly, the study contributes to the development of a Current Good Manufacturing Practice-compliant iPSC production pipeline in Brazil, using commercially available, chemically defined, and xeno-free products, along with validation by national outsourced laboratories, thereby facilitating the adoption of this technology within the country. The study emphasizes Brazil's contribution to the progress of translational medicine and the promotion of scientific advancements within the field of regenerative and precision medicine., (© The Author(s) 2024. Published by Oxford University Press.)

The adnexa fetal tissues are sources of mesenchymal stromal cells (MSCs) due to their noninvasive harvest, with all biological material discarded most of the time. MSCs are a promise regarding to their plasticity, self-renewal, differentiation potentials, immunomodulatory and anti-inflammatory properties, which have made clinical stem cell therapy a reality. The present study aimed to characterize and evaluate the immunomodulation ability of bovine mesenchymal cells collected from bovine amniotic fluid (bAFMSCs) isolated and subjected to sixth consecutive culture passages in vitro . The multilineage properties of the bAFMSCs collections confirmed the ability to undergo adipogenic, chondrogenic and osteogenic differentiation. The mesenchymal gene transcription CD106, CD73, CD29, CD90 and CD166 were detected in bAFMSCs, whereas CD34 and CD45 were not detected. Regarding cytokine mRNA expression, IL2, IL6, INFα, INFβ, INFγ, TNFα and TNFβ were downregulated, while IL10 was highly regulated in all studied passages. The present study demonstrated the immunological properties and multipotency of in vitro bAFMSCs collections, and thus, they can be tested in cattle pathological treatments or multiplication by nuclear transfer cloning., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Purpose: To evaluate the accuracy of defining characteristics and causal relationships of the etiological factors of the nursing diagnosis deficient knowledge in individuals with heart failure ., Data Sources: An analytical, cross-sectional study on the diagnostic accuracy of the defining characteristics and causal relationships of the etiological factors of the nursing diagnosis. The sample consisted of 140 patients with chronic HF and in outpatient follow-up. The latent class analysis method was used to test the accuracy of measurements and estimate the prevalence of the diagnosis. The calculation of subsequent probabilities and the odds ratio ( were also parameters employed. The study was approved by the Research Ethics Committee of the Federal University of Pernambuco., Data Synthesis: The diagnosis had an estimated prevalence of 38.57% in the sample. The inaccurate statements about the disease and/or therapy, self-care deficient performance, and inadequate behavior were the clinical indicators that best predicted the presence of the diagnosis and demonstrated the same sensitivity value (1.0000), specificity (1.0000), and 95% confidence interval (0.9999-1.0000) for all. The populations at risk was elderly (OR = 2.12, confidence interval 95% = 1.05-4.27), and illiterate individuals (OR = 2.07, confidence interval 95% = 1.03-4.16) had an approximately twofold great chance of developing havening deficient knowledge., Conclusion: The evaluation of the accuracy of clinical indicators, corresponding to the defining characteristics in the study, contributed to screening and diagnostic establishment capacity in clinical practice, and to the translation of theoretical and practical knowledge., Implications for Nursing Practice: Accurate clinical indicators of the nursing diagnosis deficient knowledge facilitate the clinical reasoning of nurses and favor the professional's role in the development of health education strategies focused on the acquisition of knowledge about the disease by patients, family members, and caregivers., (© 2023 NANDA International, Inc.)

The influence of environmental factors on Salmonella sensitivity to nisin in vitro and in refrigerated orange juice were investigated. Nisin activity was observed in the different conditions, but the highest efficiency was achieved at lower pH (4.0) and with higher bacteriocin concentration (174 µM). Moreover, the bactericidal action was directly proportional to the incubation period. When tested in orange juice, nisin caused a reduction of up to 4.05 logarithm cycles in the Salmonella population. So, environmental factors such as low pH and low temperature favored the sensitization of Salmonella cells to the bactericidal action of nisin. Therefore, this may represent an alternative to control Salmonella in refrigerated foods., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Immunotherapies targeting immune checkpoints have revolutionized cancer treatment by normalizing the immunosuppressive microenvironment of tumors and reducing adverse effects on the immune system. Indoleamine 2,3-dioxygenase (IDO) inhibitors have garnered attention as a promising therapeutic agent for cancer. However, their application alone has shown limited clinical benefits. Cabozantinib, a multitarget tyrosine kinase inhibitor, holds immunomodulatory potential by promoting infiltration and activation of effector cells and inhibiting suppressive immune cells. Despite its potential, cabozantinib as a monotherapy has shown limited efficacy in terms of objective response rate. In this study, IDO-IN-7 and cabozantinib are coencapsulated into liposomes to enhance tumor accumulation and minimize adverse effects. The liposomal combination exhibits potent cytotoxicity and inhibits the function of IDO enzyme. Furthermore, the dual-targeted treatment effectively inhibits tumor development and reverses the suppressive tumor microenvironment by regulating both adaptive and innate branch of immune system. This is evidenced by pronounced infiltration of T cells and B cells, a decrease of regulatory T lymphocytes, a shift to a proinflammatory phenotype of tumor-associated macrophages, and increases levels of neutrophils. This is the first developed of a liposome-delivered combination of IDO inhibitors and cabozantinib, and holds great potential for future clinical application as a promising anticancer strategy., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Objective: To determine whether a combination of a single intramuscular (IM) dose of pentamidine (7 mg/kg) followed by oral tamoxifen 40 mg/day for 20 days is non-inferior to three IM doses of pentamidine 7 mg/kg in the treatment of cutaneous leishmaniasis with a margin of 15%., Methods: Phase II, randomised, controlled, open-label, non-inferiority clinical trial. Primary outcome was the complete healing of the lesions 6 months after starting treatment. Secondary outcomes were healing 3 months after starting treatment and determining the presence and severity of adverse effects (AE)., Results: The research was concluded with 49 patients; Leishmania (Viannia) guyanensis was the most frequent species isolated. In the primary outcome, 18 (72%) (95% CI: 52.4%-85.7%) of the 25 patients allocated to the intervention group and 24 (100%) (95% CI: 86.2%-100%) of the control group (p = 0.015) met the established criteria of cure. There was no AE with tamoxifen., Conclusion: Although a 72% cure rate presented by the combination of tamoxifen and pentamidine was lower than in the control group that achieved a 100% cure, it is still a safe and is a clinically relevant result. It indicates that the therapeutic scheme evaluated may be a promising option for populations in remote areas, however it should be further studied, in order to include a larger number of patients., (© 2023 John Wiley & Sons Ltd.)

Northeast Brazil is a region with great international tourist potential. Among the states that make up this region, Paraíba stands out due to the presence of vulnerable groups and factors that contribute to adverse outcomes of COVID-19. Therefore, the aim of this study was to analyze the epidemiological data on the incidence, mortality, and case fatality of COVID-19 in Paraíba. An ecological, population-based study was performed, with data extracted from the Brazilian Ministry of Health database. All cases and deaths from COVID-19 from March 2020 to December 2022 were included. The time series was built by applying the Prais-Winsten regression model, and the daily percent change was calculated to analyze the trends. The highest case fatality of the entire period was in April 2020 (7.8%), but in March 2021, the state broke the dismal record of 1248 deaths and the highest mortality rate (30.5 deaths per 100,000 inhabitants). Stationary mortality and case fatality were better in 2022; however, in February 2022, the mortality rate was at levels similar to the same month of the previous year. These results illustrate that COVID-19 is evolving and needs to be constantly monitored.

Analyzing the stability of reference genes already described as universal is an important methodology to lead gene expression analysis because different studies have shown that the expression of universal reference genes may vary between experimental treatments. In this sense, the glyceraldehyde 3-phosphate dehydrogenase (GAPDH), Succinate dehydrogenase complex subunit A (SDHA) and Ribosomal Protein L-19 (RPL-19) reference genes (already described in other studies with sheep from different regions, breeds and infectious agents or in organisms evolutionarily close to sheep) were investigated in the abomasum, small and large intestines of resistant and susceptible crossbred sheep groups to gastrointestinal nematode infections in the Semi-arid region in Northeast of Brazil. The animals were naturally infected to determine the resistance or susceptibility status by counting eggs per gram (EPG) of feces from the gastrointestinal tract after 33 weeks of observations of infection evolution. Relative gene expression was performed by RT-qPCR methodology using Sybr green and relative gene expression stability was tested by different software programs such as REST, BestKeeper, geNorm and Normfinder. Our results showed the susceptible animals had increase in egg counts per gram of feces than resistant animals (p < 0.001), and both groups showed a mixed infection by nematodes of the genus Haemonchus, Trichostrongylus, Oesophagostomum and Trichuris. Furthermore, we show the importance of analyzing different genes in different software programs and the importance to choose ideal reference genes. In this sense, GAPDH was the most stable gene in the abomasum, whereas SDHA was the most stable in the small and large intestines. In addition, we discuss about variables which can interfere in relative expression such as breed, species, climate and tissue. However, utilizing other reference genes already described in other studies with the same and different variables should be performed., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Silicone implants have been used to improve volume and body contour in buttocks for almost 45 years. Although the intramuscular plane continues to be the standard, surgeons still diverge on the best incision technique: using a vertical incision, and thus without the preservation of the intergluteal groove, or preserving this area through a triangular dissection. The goal of this research study was to evaluate and compare these techniques of intramuscular augmentation gluteoplasty., Methods: Two randomized groups were formed with 53 patients in each group. One of the groups underwent intramuscular gluteoplasty with a vertical incision in the intergluteal groove, and therefore without the preservation of said intergluteal groove (group A). In the other group, intramuscular gluteoplasty was performed using a triangular dissection, thus preserving the intergluteal groove (group B). The groups were compared in relation to the incidence of complications (ie, dehiscence, hematoma, seroma, and infection)., Results: A total of 7.5% of patients in group A presented dehiscence and 1.9% presented seroma. In group B, however, 28.3% of patients presented dehiscence and 7.5% presented seroma and dehiscence during the first 21 days after surgery. No patient had hematoma or infection in either group., Conclusion: In the comparison between the groups of patients, the technique with a vertical incision in the intergluteal groove showed a lower number of surgical wounds, dehiscences, and seromas when compared with the technique that preserves the intergluteal groove., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 by the American Society of Plastic Surgeons.)

The human cerebral cortex is one of the most evolved regions of the brain, responsible for most higher-order neural functions. Since nerve cells (together with synapses) are the processing units underlying cortical physiology and morphology, we studied how the human neocortex is composed regarding the number of cells as a function of sex and age. We used the isotropic fractionator for cell quantification of immunocytochemically labeled nuclei from the cerebral cortex donated by 43 cognitively healthy subjects aged 25-87 years old. In addition to previously reported sexual dimorphism in the medial temporal lobe, we found more neurons in the occipital lobe of men, higher neuronal density in women's frontal lobe, but no sex differences in the number and density of cells in the other lobes and the whole neocortex. On average, the neocortex has ~10.2 billion neurons, 34% in the frontal lobe and the remaining 66% uniformly distributed among the other 3 lobes. Along typical aging, there is a loss of non-neuronal cells in the frontal lobe and the preservation of the number of neurons in the cortex. Our study made possible to determine the different degrees of modulation that sex and age evoke on cortical cellularity., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The application of mesenchymal stem cells (MSC) in bone tissue regeneration can have unpredictable results due to the low survival of cells in the process since the lack of oxygen and nutrients promotes metabolic stress. Therefore, in this work, polymeric membranes formed by organic-inorganic hybrid materials called ureasil-polyether for modified glucose release were developed in order to overcome the problems posed by a of lack of this nutrient. Thus, membranes formed by polymeric blend of polypropylene oxide (PPO4000) and polyethylene oxide (PEO500) with 6% glucose incorporation were developed. Physical-chemical characterization techniques were performed, as well as tests that evaluated thermal properties, bioactivity, swelling, and release in SBF solution. The results of the swelling test showed an increase in membrane mass correlated with an increase in the concentration of ureasil-PEO500 in the polymeric blends. The membranes showed adequate resistance when subjected to the application of a high compression force (15 N). X-ray diffraction (XRD) evidenced peaks corresponding to orthorhombic crystalline organization, but the absence of glucose-related peaks showed characteristics of the amorphous regions of hybrid materials, likely due to solubilization. Thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses showed that the thermal events attributed to glucose and hybrid materials were similar to that seen in the literature, however when glucose was incorporated into the PEO500, an increase in rigidity occurs. In PPO400, and in the blends of both materials, there was a slight decrease in Tg values. The smaller contact angle for the ureasil-PEO500 membrane revealed the more hydrophilic character of the material compared to other membranes. The membranes showed bioactivity and hemocompatibility in vitro. The in vitro release test revealed that it is possible to control the release rate of glucose and the kinetic analysis revealed a release mechanism characteristic of anomalous transport kinetics. Thus, we can conclude that ureasil-polyether membranes have great potential to be used as a glucose release system, and their future application has the potential to optimize the bone regeneration process.

Amniotic membrane (AM) has been widely used as a biological dressing for many pathologies and illnesses worldwide, and products derived from this tissue have been commercially available in several countries. In Brazil, regulatory agencies have recently authorized its clinical use as a non-experimental therapy for burns, diabetic and venous stasis ulcers, and intrauterine adhesions. In this study, we present our pathway through validating the first available service in the country of AM cryopreservation, with a protocol for long-term storage in high-efficiency nitrogen cryogenic freezers and a specific way of packing the tissue for optimal clinical handling and efficient storage space utilization while preserving live cells and the tissue's biological properties. Using gauze as support, cryoprotectant dimethyl sulfoxide and product presentation as a multilayer roll exhibited the best cell viability results and maintained the tissue integrity and presence of stem/progenitor cells. Essential proteins involved in tissue regeneration and immune and antimicrobial control were detected from the secretome of cryopreserved tissue similar to fresh tissue. Furthermore, immunogenic markers, such as human leukocyte antigens, were detected at very low levels in the tissue, confirming their low immunogenicity. Finally, we demonstrate that the tissue can be kept under refrigerated conditions for up to 7 d for further use, maintaining sterility and considerable cell viability. Our cryopreservation and storage protocol kept the AM viable for at least 20 months. In conclusion, this study enabled us to determine a novel efficient protocol for long-term AM preservation for future clinical applications., (© 2023 IOP Publishing Ltd.)

Social bees harbor conserved gut microbiotas that may have been acquired in a common ancestor of social bees and subsequently codiversified with their hosts. However, most of this knowledge is based on studies on the gut microbiotas of honey bees and bumblebees. Much less is known about the gut microbiotas of the third and most diverse group of social bees, the stingless bees. Specifically, the absence of genomic data from their microbiotas presents an important knowledge gap in understanding the evolution and functional diversity of the social bee microbiota. Here, we combined community profiling with culturing and genome sequencing of gut bacteria from six neotropical stingless bee species from Brazil. Phylogenomic analyses show that most stingless bee gut isolates form deep-branching sister clades of core members of the honey bee and bumblebee gut microbiota with conserved functional capabilities, confirming the common ancestry and ecology of their microbiota. However, our bacterial phylogenies were not congruent with those of the host, indicating that the evolution of the social bee gut microbiota was not driven by strict codiversification but included host switches and independent symbiont gain and losses. Finally, as reported for the honey bee and bumblebee microbiotas, we found substantial genomic divergence among strains of stingless bee gut bacteria, suggesting adaptation to different host species and glycan niches. Our study offers first insights into the genomic diversity of the stingless bee microbiota and highlights the need for broader samplings to understand the evolution of the social bee gut microbiota. IMPORTANCE Stingless bees are the most diverse group of the corbiculate bees and represent important pollinator species throughout the tropics and subtropics. They harbor specialized microbial communities in their gut that are related to those found in honey bees and bumblebees and that are likely important for bee health. Few bacteria have been cultured from the gut of stingless bees, which has prevented characterization of their genomic diversity and functional potential. Here, we established cultures of major members of the gut microbiotas of six stingless bee species and sequenced their genomes. We found that most stingless bee isolates belong to novel bacterial species distantly related to those found in honey bees and bumblebees and encoding similar functional capabilities. Our study offers a new perspective on the evolution of the social bee gut microbiota and presents a basis for characterizing the symbiotic relationships between gut bacteria and stingless bees.

Objective: To analyze the content of the nursing diagnosis deficient knowledge in individuals with heart failure., Methods: Methodological study to validate the content of a nursing diagnosis based on the predictive model of diversity, carried out through the organization of the phenomenon of interest and analysis by judges using the collective wisdom model. The NANDA-I Knowledge Deficient diagnosis was evaluated by 48 judges and considered valid when it presented a median content validity index ≥ 0.8 in the confidence intervals., Results: Note that 66.6% of the judges indicated that the new definition proposed was more adequate than the definition adopted by NANDA-I. After the experts' analysis, the following defining characteristics were considered valid: inaccurate statements about the disease and/or therapy, inadequate performance in the management of intercurrences, increase in hospital readmissions, worsened quality of life, deficit in self-care performance, and follow-up of inadequate instruction; related factors are as follows: inadequate guidance offered by health professionals, nonparticipation of the patient in the planning of their health care, weakened relationship between professional and individual; populations at risk-elderly and low level of education of the individual and/or caregiver and the associated condition, mild cognitive impairment. Anxiety, depression, and impaired social interaction were elements considered not relevant to the content domain., Conclusion: The validation of the content of the aforementioned diagnosis in patients with heart failure, through the analysis of judges with different degrees of expertise, made it possible to improve the definition and expansion of new diagnostic indicators., Implications for Nursing Practice: Updated diagnostic elements for the nursing diagnosis deficient knowledge in individuals with heart failure will facilitate accurate clinical judgment and the establishment of a therapeutic plan aimed at etiological factors modifiable by nurses., (© 2022 NANDA International, Inc.)

Gender differences in spatial abilities favor males in both childhood and adulthood. During early development, this discrepancy can be attributed, among other things, to the influence of an early testosterone surge in boys, societal stereotypes, and expectations about gender. In the present work, we created a spatial task (including letter rotation and letter mirroring) which used letters as stimuli and evaluated the performance of school-aged children (6-10 years old). During this age period, children are being taught literacy skills which rely on the reorganization of cortical networks and the breakdown of mirror generalization. We divided our sample ( N  = 142, 73 females) into two age groups: 1 st -2 nd (literacy acquisition; N  = 70, 33 females) and 3 rd -5 th (literacy consolidation; N  = 72, 40 females) graders. While boys performed significantly better in letter rotation in the older group, girls' performance remained substandard in both groups. This pattern is reversed for the mirror task, with older girls outperforming their younger counterparts and boys having similar performance in the two groups. Since the age period of our sample is not associated with large variations in the levels of reproductive steroids, we propose that the similarity of performance between younger and older girls in mental rotation of letters could be associated with society's traditional attitudes and expectations on the relationship between visual-spatial skills and gender. As for the mirror task, while only girls had a significant difference between the two age groups, boys did show an improvement, as expected for the inhibition of mirror generalization for letters during reading acquisition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Resque, de Moura Lobato, da Silva, da Cruz Filho, da Fonseca, de Oliveira Matos and Pereira.)

Therapeutic cancer drug efficacy can be limited by insufficient tumor penetration, rapid clearance, systemic toxicity and (acquired) drug resistance. The poor therapeutic index due to inefficient drug penetration and rapid drug clearance and toxicity can be improved by using a liposomal platform. Drug resistance for instance against pemetrexed, can be reduced by combination with docetaxel. Here, we developed a specific liposomal formulation to simultaneously deliver docetaxel and pemetrexed to enhance efficacy and safety. Hydrophobic docetaxel and hydrophilic pemetrexed were co-encapsulated into pH-sensitive liposomes using a thin-film hydration method with high efficiency. The physicochemical properties, toxicity, and immunological effects of liposomes were examined in vitro. Biodistribution, anti-tumor efficacy, and systemic immune response were evaluated in vivo in combination with PD-L1 immune checkpoint therapy using two murine colon cancer models. In cellular experiments, the liposomes exhibited strong cytotoxicity and induced immunogenic cell death. In vivo, the treatment with the liposome-based drug combination inhibited tumor development and stimulated immune responses. Liposomal encapsulation significantly reduced systemic toxicity compared to the delivery of the free drug. Tumor control was strongly enhanced when combined with anti-PDL1 immunotherapy in immunocompetent mice carrying syngeneic MC38 or CT26 colon tumors. We showed that treatment with liposome-mediated chemotherapy of docetaxel and pemetrexed combined with anti-PD-L1 immunotherapy is a promising strategy for the treatment of colon cancers., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (Copyright © 2022. Published by Elsevier B.V.)

Mammals are routinely cloned by introducing somatic nuclei into enucleated oocytes. Cloning contributes to propagating desired animals, to germplasm conservation efforts, among other applications. A challenge to more broader use of this technology is the relatively low cloning efficiency, which inversely correlates with donor cell differentiation status. Emerging evidence suggests that adult multipotent stem cells improve cloning efficiency, while the greater potential of embryonic stem cells for cloning remains restricted to the mouse. The derivation of pluripotent or totipotent stem cells from livestock and wild species and their association with modulators of epigenetic marks in donor cells should increase cloning efficiency., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Our cord blood banking facility planned and executed a transferral of its entire operation to a new site in the South of Brazil. Transporting LN2 freezers is a complex process in which extensive planning is essential to minimize the risks of damaging products or storage units., Methods: To fulfill this objective, we constructed a detailed relocation plan consisting of four phases and risk mitigation measures, collaborated with the representatives of all departments, regulating agencies, and professionals from the transport company, and assembled a validation plan for cryogenic freezers and the viability of cord blood units., Results: The new facility was prepared in accordance with the project plan, local legislation, quality system program requirements, and accreditation agency guidance. A 12-h operation of moving the cryogenic freezers was conducted successfully, with no loss or damage of client samples or equipment., Conclusion: Through the development and execution of a transferral plan, the engagement of appropriate partners, and compliance with security measures from health and government agencies, a successful transferral of a cord blood banking facility operation in its entirety can be successfully accomplished., (© 2022 AABB.)

The search for gold-standard materials for bone regeneration is still a challenge in reconstruction surgery. The ratio between hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) in biphasic calcium phosphate ceramics (BCPs) is one of the most important factors in osteoinduction promotion and controlled biodegradability, configurating what is currently considered as a possible gold standard material for bone substitution in reconstructive surgery. Exploring the natural genesis of the HAp and β-TCP phases in fishbones during their postnatal growth, this study developed a biphasic bioceramic obtained from the calcination of Nile tilapia (Oreochromis niloticus) bones as a function of their ages. The natural genesis dynamics of the structural evolution of the β-TCP and HAp phases were characterized by physicochemical methods, taking into account of the age of the fish and the material processing conditions. Thermal analysis (TGA / DTA) showed complete removal of the organic matter and transitions associated with the transformation of carbonated hydroxyapatite (CDHA) to HAp and β-TCP phases. After calcination at 900 °C, the material was characterized by: X-ray diffraction (XRD) and refinement by the Rietveld method; Fourier Transform Infrared Spectroscopy with Attenuated Total Reflection (FTIR-ATR); Raman spectroscopy; Scanning Electron Microscopy (SEM) and Flame Atomic Absorption Spectroscopy (FAAS). The analysis allowed identification and quantitative estimate of the variations of the HAp and β-TCP phases in the formation of the BCPs. The results showed that the decrease in β-TCP against the increase in the HAp phases is symmetrical to the dynamics of the natural genesis of these phases, surprisingly maintaining the balanced phase proportion even when bones of young fishes were used. The microstructure analysis confirms the observed transformation. In addition, in vivo tests demonstrated the osteoinductive potential of BCP scaffolds implanted in an ectopic site, and their remarkable regenerative functionality, as bone graft, was demonstrated in alveolar bone after tooth extraction. MTT cytotoxicity assay for BCP samples for MC3T3-E1 pre-osteoblasts and L929 fibroblasts cells showed viability equal or higher than 100%. A logistic empirical model is presented to explain the three stages of HAp natural formation with fish age and it is also compared to the fish size evolution., (Copyright © 2022 Elsevier B.V. All rights reserved.)

During the first semester of 2021, all of Brazil has suffered an intense wave of COVID-19 associated with the Gamma variant. In July, the first cases of Delta variant were detected in the state of Rio de Janeiro. In this work, we have employed phylodynamic methods to analyse more than 1 600 genomic sequences of Delta variant collected until September in Rio de Janeiro to reconstruct how this variant has surpassed Gamma and dispersed throughout the state. After the introduction of Delta, it has initially spread mostly in the homonymous city of Rio de Janeiro, the most populous of the state. In a second stage, dispersal occurred to mid- and long-range cities, which acted as new close-range hubs for spread. We observed that the substitution of Gamma by Delta was possibly caused by its higher viral load, a proxy for transmissibility. This variant turnover prompted a new surge in cases, but with lower lethality than was observed during the peak caused by Gamma. We reason that high vaccination rates in the state of Rio de Janeiro were possibly what prevented a higher number of deaths.

Physical barrier membranes have been used to release active substances to treat critical bone defects; however, hydrophilic membranes do not present a prolonged release capacity. In this sense, hydrophobic membranes have been tested. Thus, this study aimed to develop hydrophobic membranes based on mixtures of ureasil-polyether-type materials containing incorporated dexamethasone (DMA) for the application in guided bone regeneration. The physicochemical characterization and biological assays were carried out using small-angle X-ray scattering (SAXS), an in vitro DMA release study, atomic force microscopy (AFM), a hemolysis test, and in vivo bone formation. The swelling degree, SAXS, and release results revealed that the u-PPO400/2000 membrane in the proportion of 70:30 showed swelling (4.69% ± 0.22) similar to the proportions 90:10 and 80:20, and lower than the proportion 60:40 (6.38% ± 0.49); however, an equal release percentage after 134 h was observed between the proportions 70:30 and 60:40. All u-PPO materials presented hemocompatibility (hemolysis ≤2.8%). AFM results showed that the treatments with or without DMA did not present significant differences, revealing a flat/smooth surface, with no pores and/or crystalline precipitates. Finally, in vivo results revealed that for both the commercial hydrophilic membrane and u-PPO400/2000 (70:30) after 60 days, the bone formation volume was 21%. In conclusion, hybrid membranes present unique characteristics for treating critical bone defects, considering the delayed and prolonged release results associated with the physical barrier capacity.

Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI.

In this study, we report the first case of intra-host SARS-CoV-2 recombination during a coinfection by the variants of concern (VOC) AY.33 (Delta) and P.1 (Gamma) supported by sequencing reads harboring a mosaic of lineage-defining mutations. By using next-generation sequencing reads intersecting regions that simultaneously overlap lineage-defining mutations from Gamma and Delta, we were able to identify a total of six recombinant regions across the SARS-CoV-2 genome within a sample. Four of them mapped in the spike gene and two in the nucleocapsid gene. We detected mosaic reads harboring a combination of lineage-defining mutations from each VOC. To our knowledge, this is the first report of intra-host RNA-RNA recombination between two lineages of SARS-CoV-2, which can represent a threat to public health management during the COVID-19 pandemic due to the possibility of the emergence of viruses with recombinant phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Francisco Junior, Almeida, Lamarca, Cavalcante, Martins, Gerber, Guimarães, Salviano, dos Santos, de Oliveira, de Souza, de Carvalho, Ribeiro, Carvalho, da Silva, Garcia, de Souza, da Silva, Ribeiro, Cavalcanti, de Mello, Tanuri and Vasconcelos.)

In silico methodologies can be used in the discovery of new drugs for measuring toxicity, predicting effects of substances not yet analyzed by in vivo methodologies. The ADMET Predictor® software (absorption, distribution, metabolism, elimination, and toxicity [ADMET]) was used in this work to predict toxic effects of microcystin variants MC-LR, MC-YR, MC-RR, and MC-HarHar. In the case of rodents, predictive results for all analyzed variants indicated carcinogenic potential. The predictive model of respiratory sensitivity in this group differentiated microcystins into 2 categories: sensitizer (MC-LR and -YR) and non-sensitizer (MC-HarHar and -RR). Predictive results for humans indicated that MC-LR and -RR are phospholipidosis inducers; on the other hand, MC-LR showed the highest predictive value of permeability in rabbit cornea and probability of crossing lipoprotein barriers (MC-LR>-YR>-HarHar>-RR). Considering bioavailable fractions, microcystins are more likely to cause biological effects in rats than humans, showing significant differences between models. The results of ADMET predictions add valuable information on microcystin toxicity, especially in the case of variants not yet studied experimentally., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Titica vine ( Heteropsis flexuosa ) is a typical plant of the Amazon region commonly used for making baskets, bags, brooms and furniture, owing to its stiff fibers. In spite of its interesting properties, there is so far no reported information regarding the use of titica vine fibers (TVFs) in engineering composite materials. In this work, the TVF and its epoxy composites were for the first time physically, thermally and mechanically characterized. Additionally, the effect of two kinds of chemical treatments, one with sodium carbonate and one with calcium lignosulfonate, as well as different volume fractions, 10, 20, 30 and 40 vol%, of TVF-reinforced composites were assessed for corresponding basic properties. The thermogravimetric results of the composites reveal enhanced thermal stability for higher TVF content. In addition, the composite incorporated with 40 vol% of TVFs treated with sodium carbonate absorbed 19% more water than the composites with untreated fibers. By contrast, the calcium lignosulfonate treatment decreased water absorption by 8%. The Charpy and Izod impact tests showed that the composites, incorporated with the highest investigated volume fraction (40 vol%) of TVF, significantly increased the absorbed energy by 18% and 28%, respectively, compared to neat epoxy. ANOVA and Tukey statistical analyses displayed no direct influence of the chemical treatments on the energy absorption of the composites for either impact tests. SEM images revealed the main fracture mechanisms responsible for the performance of TVF composites.

In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAID and sequenced 1927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (>90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2), firstly reported in this study. Our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in Rio de Janeiro. Altogether, this might have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8 + T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8 + T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8 + T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors.

Youths living in crowded impoverished urban areas face higher risk of infection by SARS-CoV-2. This article presents lessons learned from a preventive intervention project intersected by the COVID-19 crisis that moved from a mix-methods study design to online ethnography. The 'home-officed' research team e-witnessed high-school students' daily lives and collaborated in youths' and community-based organisations' responses in the territories where they study and live. Psychosocial distress increased, also driven by the disastrous governmental response to the health and economic crises. There was growing anxiety about meeting friends and dating, with structural limits for sustaining the recommended social distancing, which added to gender/sexuality-based violence. Simultaneously, we observed students becoming relevant actors through co-producing preventive practices, surpassing risk-group notions and combining SARS-CoV-2 prevention with sexuality, gender, racism and mental-health issues. They managed internet-mediated applications to promote critical thinking and collective actions aimed at health promotion among their peers, from their homes. Freire's concept of 'untested-feasibility' fostered researchers', students' and community leaders' imaginations in the face of this unprecedented crisis, thereby enhancing social responses to the epidemic to become rights-based comprehensive dialogical preventive activities. This ongoing intervention-research stresses how prevention sciences can go beyond reduction of this pandemic to a viral event.

Guided bone regeneration (GBR) technique helps to restore bone tissue through cellular selectivity principle. Currently no osteoinductive membrane exists on the market. Osteogenic growth peptide (OGP) acts as a hematopoietic stimulator. This association could improve the quality of bone formation, benefiting more than 2.2 million patients annually. The objective of this work was to develop membranes from ureasil-polyether materials containing OGP. The membranes were characterized by differential scanning calorimetry (DSC) and small angle X-ray scattering (SAXS). OGP was synthesized by the solid phase method. Sterilization results using gamma radiation at 24 kGy did not change the structure of the material, as confirmed by DSC. The SAXS technique revealed the structural homogeneity of the matrix. OGP was incorporated in 66.25 × 10 -10  mol and release results showed that the ureasil-PPO400/PEO500 and ureasil-PPO400/PEO1900 membranes released 7% and 21%, respectively, after 48 h. In vivo results demonstrated that the amount and quality of bone tissue formed in the bone defects in the presence of ureasil-polyether membranes with OGP were similar to commercial collagen material with BMP. The results allow us to conclude that membranes with OGP have characteristics that make them potential candidates for the GBR., (© 2021 John Wiley & Sons Ltd.)

A hydrogel containing exocellular (1 → 6)-β-D-glucan (lasiodiplodan, LAS) was developed and its wound healing potential was evaluated. β-Glucans have attracted much interest by the cosmetic industry sector because of their bioactive and functional properties and in promoting skin health. In the present work an β-glucan was studied as a healing biomaterial that has not hitherto been reported in the scientific literature. LAS produced by the ascomycete Lasiodiplodia theobromae MMPI was used in the formulation of a healing hydrogel. Physicochemical and microbiological quality parameters, antioxidant potential and stability of the formulation was evaluated. FTIR, thermal analysis and SEM techniques were also employed in the characterization. Wistar rats were used as a biological model to investigate the wound healing potential. Histological analyses of cutaneous tissue from the dorsal region were conducted after 4, 7, 10 and 14 days of treatment, and evaluated re-epithelialization, cell proliferation and collagen production. Physicochemical stability, microbiological quality and antioxidant potential, especially in relation to its ability to scavenge hydroxyl radicals were found. The hydrogel stimulated cell re-epithelialization and proliferation during all days of the treatment, and stimulated an increase of collagen fibers. Lasiodiplodan showed immunomodulatory activity in wound healing and this biomacromolecule could be an alternative compound in wound care., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study aims to describe the sociodemographic determinants associated with exposure to Zika Virus (ZIKV) in pregnant women during the 2015-2016 epidemic in Salvador, Brazil., Methods: We recruited women who gave birth between October 2015 and January 2016 to a cross-sectional study at a referral maternity hospital in Salvador, Brazil. We collected information on their demographic, socioeconomic, and clinical characteristics, and evaluated their ZIKV exposure using a plaque reduction neutralization test. Logistic regression was then used to assess the relationship between these social determinants and ZIKV exposure status., Results: We included 469 pregnant women, of whom 61% had a positive ZIKV result. Multivariate analysis found that lower education (adjusted Prevalence Rate [aPR] 1.21; 95%CI 1.04-1.35) and food insecurity (aPR 1.17; 95%CI 1.01-1.30) were positively associated with ZIKV exposure. Additionally, age was negatively associated with the infection risk (aPR 0.99; 95%CI 0.97-0.998)., Conclusion: Eve after controlling for age, differences in key social determinants, as education and food security, were associated with the risk of ZIKV infection among pregnant women in Brazil. Our findings elucidate risk factors that can be targeted by future interventions to reduce the impact of ZIKV infection in this vulnerable population., Competing Interests: The authors declare that there is no conflict of interest.

The zebrafish (Danio rerio) is widely used as a promising translational model organism for studying various brain disorders. Zebrafish are also commonly used in behavioral and drug screening assays utilizing individually tested (socially isolated) fish. Various sounds represent important exogenous factors that may affect fish behavior. Mounting evidence shows that musical/auditory environmental enrichment can improve welfare of laboratory animals, including fishes. Here, we show that auditory environmental enrichment mitigates anxiogenic-like effects caused by acute 24-h social isolation in adult zebrafish. Thus, auditory environmental enrichment may offer an inexpensive, feasible and simple tool to improve welfare of zebrafish stocks in laboratory facilities, reduce unwanted procedural stress, lower non-specific behavioral variance and, hence, collectively improve zebrafish data reliability and reproducibility., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polymeric nanoparticles (NPs) find many uses in nanomedicine, from drug delivery to imaging. In this regard, poly (lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG) particles are the most widely applied types of nano-systems due to their biocompatibility and biodegradability. Here we developed novel fluorinated polymeric NPs as vectors for multi-modal nanoprobes. This approach involved modifying polymeric NPs with trifluoroacetamide (TFA) and loading them with a near-infrared (NIR) dye for different imaging modalities, such as magnetic resonance imaging (MRI) and optical imaging. The PLGA-PEG-TFA NPs generated were characterized in vitro using the C28/I2 human chondrocyte cell line and in vivo in a mouse model of osteoarthritis (OA). The NPs were well absorbed, as confirmed by confocal microscopy, and were non-toxic to cells. To test the NPs as a drug delivery system for contrast agents of OA, the nanomaterial was administered via the intra-articular (IA) administration method. The dye-loaded NPs were injected in the knee joint and then visualized and tracked in vivo by fluorine-19 nuclear magnetic resonance and fluorescence imaging. Here, we describe the development of novel intrinsically fluorinated polymeric NPs modality that can be used in various molecular imaging techniques to visualize and track OA treatments and their potential use in clinical trials.

Cancer immunotherapy has shown remarkable progress in recent years. Nanocarriers, such as liposomes, have favorable advantages with the potential to further improve cancer immunotherapy and even stronger immune responses by improving cell type-specific delivery and enhancing drug efficacy. Liposomes can offer solutions to common problems faced by several cancer immunotherapies, including the following: (1) Vaccination: Liposomes can improve the delivery of antigens and other stimulatory molecules to antigen-presenting cells or T cells; (2) Tumor normalization: Liposomes can deliver drugs selectively to the tumor microenvironment to overcome the immune-suppressive state; (3) Rewiring of tumor signaling: Liposomes can be used for the delivery of specific drugs to specific cell types to correct or modulate pathways to facilitate better anti-tumor immune responses; (4) Combinational therapy: Liposomes are ideal vehicles for the simultaneous delivery of drugs to be combined with other therapies, including chemotherapy, radiotherapy, and phototherapy. In this review, different liposomal systems specifically developed for immunomodulation in cancer are summarized and discussed.

Background: Scaffolds have considerably advanced in recent years. In orthopaedic surgery, scaffolds have been used as grafts in procedures involving tendon and ligament reconstruction. This paper aimed to produce and evaluate decellularized tendon scaffolds (DTSs) from biomechanical, microscopic, macroscopic and in vivo perspectives., Methods: Bilateral gastrocnemius muscle tendons from 18 adult New Zealand rabbits were collected. Of these 36 tendons, 11 were used as controls (Group A - control), and 25 were used in the decellularization protocol (Group B - DTS). The groups were subjected to histological, biomechanical and macroscopic analyses, and Group B - DTS was subjected to an additional in vivo evaluation. In the decellularization protocol, we used a combination of aprotinin, ethylenediamine tetraacetic acid (EDTA), sodium dodecyl sulfate (SDS) and t-octyl-phenoxypolyethoxyethanol (Triton X-100) for six days. During this period, the scaffolds were kept at room temperature on an orbital shaker with constant motion., Results: The DTSs showed an increased cross-sectional area and inter-fascicular distance and no change in parallelism or matrix organization. The nuclear material was not organized in the DTSs as it was in the control. In the biomechanical analysis, no significant differences were found between the groups after analysing the ultimate tensile load, stiffness, and elongation at the ultimate tensile load. During the in vivo evaluation, mononuclear cell infiltration was noted., Conclusions: The evaluated decellularization protocol generated a tendon scaffold, maintained the most important biomechanical characteristics and permitted cell infiltration.

The objective was to evaluate the effect of different cultivars of Brachiaria brizantha on the dynamics and concentration of the larval stages of gastrointestinal nematodes in the soil and forage strata, as well as their effects on the performance of naturally infected lambs. Overall, 48 90-day-old lambs with an initial weight of 19.04 ± 0.96 kg were observed. Moreover, a randomised block factorial design with four cultivars of Brachiaria brizantha (Marandu, Xaraés, Piatã and Paiaguás grasses) under intermittent stocking (with a pre-grazing canopy height of 40 cm and post-grazing canopy height of 20 cm) for two grazing cycles was used. The following variables were analysed: faecal egg counting, faecal culture, mean corpuscular volume, FAMACHA© score, weight and body condition score, the recovery of larvae from pasture and soil samples, nutritional value and the production and structural components of forage. Lambs grazing Marandu grass demonstrated the highest level of nematode infection (P < 0.05). However, the nutritional value did not differ between cultivars. Marandu grass had the highest pasture density (P < 0.05), while Paiaguás grass had the highest percentage of dead material (P < 0.05). The various genera of gastrointestinal nematodes found in the faecal cultures, regardless of the cultivars, include Haemonchus (92.01%), Trichostrongylus (4.55%), Strongyloides (3.06%) and Oesophagostomum (0.37%). Lambs grazing Xaraés grass had the lowest body weight (P < 0.05). Furthermore, larvae concentrations were highest in Marandu and Paiaguás pastures; infective Haemonchus and Trichostrongylus larvae were recovered from pasture and soil samples. The different cultivars of Brachiaria brizantha produce diverse and relevant microclimatic conditions to contaminate soil, pastures and animals. Animal performance was not compromised despite the Marandu and Paiaguás cultivars having the highest levels of contamination and infection. Based on parasitological aspects, the Brachiaria brizantha cultivars Xaraés and Piatã are recommended for grass-based sheep production systems over the other cultivars since they contribute to the reduction of larval contamination and infection., Competing Interests: The authors have declared that no competing interests exist.

Several environmental impacts are resulting from the process of anthropization and climate variability that have caused degradation of biomes and humid environments. Thus, the objective of this study was to evaluate the effect of the anthropic process and the variation of climatic conditions on the dynamics of the marsh vegetation in the Pandeiros River preservation area in the north of Minas Gerais, Brazil. The Enhanced Vegetation Index (EVI) of product MOD13Q1 and the gross primary productivity (GPP) of product MOD17A2 of the Moderate Resolution Imaging Spectroradiometer (MODIS) were used for the period from 2001 to 2017 were used in this process. Rain and air temperature data were obtained from the Conventional Weather Station of Januária-MG. The time series were submitted to the nonparametric statistical test of Mann-Kendall. The process of anthropization of the swamp area in the environmental protection area of the Pandeiros River/MG (EPA) showed a pattern of expansion of vegetation cover associated with the reduction of the water table, a phenomenon resulting from the silting process and reduction of the incidence of rain in this region, which contributes to the reduction of ecosystem services. Thus, understanding the influence of climatic variables on the dynamics of vegetation in humid environments, such as the EPA swamp area on the Pandeiros River, is essential for the preservation and recovery of these ecosystems and for the implementation of public policies for preservation and conservation.

The bioactive compounds and the antioxidant activity of extracts made with various parts of banana inflorescences (bracts, male flowers, rachis, and whole inflorescence) were evaluated in the first part of this study. The extract made with male flowers (EMF) had a higher content of phenolics and flavonoids, lower IC 50 value, and higher FRAP value. Thus, EMF was selected to be used in sausage formulations at the concentrations of 0, 0.5, 1, 1.5, and 2%. The effect of this reformulation on the physicochemical, oxidative, and sensory characteristics of the sausages was evaluated during the refrigerated storage (28 days). EMF presented an effective antioxidant activity, with no major changes on pH, aw, and color parameters. In addition, the sensory quality of the product was not affected by the addition of up to 2% EMF. Therefore, EMF has great potential to be used as a natural antioxidant in meat products., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To improve the efficacy of cancer vaccines we aimed to modulate the suppressive tumor microenvironment. In this study, the potential of intratumoral immune modulation with poly (I:C), Resiquimod (R848) and CCL20 (MIP3α) was explored. Biodegradable polymeric nanoparticles were used as delivery vehicles for slow and sustained release of these drugs in the tumor area and were combined with specific immunotherapy based on therapeutic peptide vaccination in two aggressive murine carcinoma and lymphoma tumor models. Whereas nanoparticle delivery of poly (I:C) or R848 improved therapeutic efficacy, the combination with MIP3α remarkably potentiated the cancer vaccine antitumor effects. The long-term survival increased to 75-100% and the progression free survival nearly doubled on mice with established large carcinoma tumors. The potent adjuvant effects were associated with lymphoid and myeloid population alterations in the tumor and tumor-draining lymph node. In addition to a significant influx of macrophages into the tumor, the phenotype of the suppressor tumor-associated macrophages shifted towards an acute inflammatory phenotype in the tumor-draining lymph node. Overall, these data show that therapeutic cancer vaccines can be potentiated by the combined nanoparticle mediated co-delivery of poly (I:C), R848 and MIP3α, which indicates that a more favorable milieu for cancer fighting immune cells is created for T cells induced by therapeutic cancer vaccines., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Chemoimmunotherapy is an emerging combinatorial modality for the treatment of cancers resistant to common first-line therapies, such as chemotherapy and checkpoint blockade immunotherapy. We used biodegradable nanoparticles as delivery vehicles for local, slow and sustained release of doxorubicin, two immune adjuvants and one chemokine for the treatment of resistant solid tumors. Methods: Bio-compatible poly(lactic-co-glycolic acid)-PEG nanoparticles were synthesized in an oil/water emulsion, using a solvent evaporation-extraction method. The nanoparticles were loaded with a NIR-dye for theranostic purposes, doxorubicin cytostatic agent, poly (I:C) and R848 immune adjuvants and CCL20 chemokine. After physicochemical and in vitro characterization the nanoparticles therapeutic efficacy were carried-out on established, highly aggressive and treatment resistant TC-1 lung carcinoma and MC-38 colon adenocarcinoma models in vivo . Results: The yielded nanoparticles average size was 180 nm and -14 mV surface charge. The combined treatment with all compounds was significantly superior than separate compounds and the compounds nanoparticle encapsulation was required for effective tumor control in vivo . The mechanistic studies confirmed strong induction of circulating cancer specific T cells upon combined treatment in blood. Analysis of the tumor microenvironment revealed a significant increase of infiltrating leukocytes upon treatment. Conclusion: The multi-drug loaded nanoparticles mediated delivery of chemoimmunotherapy exhibited excellent therapeutic efficacy gain on two treatment resistant cancer models and is a potent candidate strategy to improve cancer therapy of solid tumors resistant to first-line therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Inflammatory conditions of the temporomandibular joint (TMJ) and peripheral tissues affect many people around the world and are commonly treated with non-steroidal anti-inflammatory drugs (NSAIDs). However, in order to get desirable results, treatments with NSAIDs may take weeks, causing undesirable side effects and requiring repeated administration. In this sense, this work describes the development of an optimized nanostructured lipid carrier (NLC) formulation for intra-articular administration of naproxen (NPX). An experimental design (2 3 ) selected the best formulation in terms of its physicochemical and structural properties, elucidated by different methods (DLS, NTA, TEM, DSC, and ATR-FTIR). The chosen formulation (NLC-NPX) was tested on acute inflammatory TMJ nociception, in a rat model. The optimized excipients composition provided higher NPX encapsulation efficiency (99.8%) and the nanoparticles were found stable during 1 year of storage at 25 °C. In vivo results demonstrated that the sustained delivery of NPX directly in the TMJ significantly reduced leukocytes migration and levels of pro-inflammatory cytokines (IL-1β and TNF-α), for more than a week. These results point out the NLC-NPX formulation as a promising candidate for the safe treatment of inflammatory pain conditions of TMJ or other joints.

Cancer immunotherapy is emerging as a candidate treatment modality for treating post-surgical metastasis and recurrences. Despite the great promises with therapeutic cancer vaccines and checkpoint blocking antibodies in pre-clinical studies, response rates in the clinic still remain unsatisfactory. The evaluation of immunotherapy after surgery in patients could confront significant unexpected hurdles. Surgery itself tends to cause immune suppression, while wound healing factors also stimulate tumor cell outgrowth and metastasis. Regarding the marked changes in the post-surgical tumor microenvironment, one can anticipate that better tumor growth control is attainable by combining cancer vaccines with immune checkpoint blockade. However, it is important that vaccines and checkpoint blocking antibodies are delivered efficiently to their target cells, are released sustained and locally and do not induce cytotoxic effects. The generation of effective anti-tumor immunity and durable response rates could largely depend on these parameters. In the last decade, researchers spend tremendous effort in optimizing the delivery of immunotherapeutic compounds with the use of nanomedicine. Biocompatible nanoparticle based delivery systems demonstrated intriguing results with regard to specific immune cell activation, improved drug delivery, cell targeting, limiting off target toxicity and improving treatment outcome. It therefore makes sense, to speculate on the promises of combined cancer vaccination and immune checkpoint blocking immunotherapy with the aid of nanomedicine. A powerful nanoparticle combination immunotherapy conferring durable therapeutic benefit whilst leaving healthy tissue untouched represents the base for more efficient post-surgical cancer treatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)