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Purpose: The purpose of studies on antibiotics used topically on the root surface of avulsed teeth is to evaluate their antiresorptive properties which favor the repair of the periodontal ligament and the reestablishment of the dentoalveolar articulation. The aim of the present study was to determine the effect of lincomycin treatment of the root surface on tooth replantation. Methods: Ten rats were distributed into two groups (I - control; II - experimental). The right maxillary incisor of the animals was extracted and stored in milk for 30 min. The tooth in group I was rinsed with normal saline and replanted; in group II, the incisor was immersed in lincomycin for 5 min before replantation. The animals were euthanized on the 21st day postoperative. The right hemimaxilla was submitted to histological sectioning and stained with H&E for microscopic evaluation. Results: Group I: the periodontal ligament appeared dispersed, with moderate to intense lymphoplasmacytic infiltrate, and dentoalveolar articulation was not reestablished. Group II: complete repair of the ligament was evident, and there were few inflammatory cells and small areas of inflammatory resorption and ankylosis. Conclusion: The use of lincomycin allowed the repair of the periodontal ligament and reduced inflammation. There were still areas of inflammatory resorption and ankylosis. [ABSTRACT FROM AUTHOR]

Purpose: This paper reports the assessment of nutritional anthropometric parameters of three patients who were submitted to orthognathic surgery followed by intermaxillary fixation and liquid diet. Case description: This prospective case series describes the changes in nutritional parameters of three adult subjects aged 20 to 24 years, including one male and two females, who received elective orthognathic surgery followed by intermaxillary fixation with orthodontic elastics for 14 days. The hospitalized patients were instructed to go on a liquid diet with hypercaloric and hyperprotein intake. After discharge, the patients continued the liquid diet up to 28 days postoperatively. Data on weight loss, body mass index, triceps skinfold thickness, midarm circumference, and midarm muscle area were collected one week before surgery, one week after surgery, and four weeks after surgery. All three patients had severe weight loss (>2% weight loss per week). Conclusion: The interaction between nutritionist and oral surgeon is essential in order to plan an adequate dietary intervention after orthognathic surgery to minimize occasional weight loss. [ABSTRACT FROM AUTHOR]

Objectives: To carry out physicomechanical characterization of the HA/DCPA/TiO 2 and to evaluate the tissue repair in rat calvaria., Methods: Two bone defects were made in the calvaria of 36 Wistar rats, divided into groups: HA/DCPA, HA/DCPA/TiO 2 and sham (blood clot). The animals were euthanized at 30, 60 and 90 days and calvaria slides were processed with hematoxylin/eosin. The newly formed bone, connective tissue, biomaterial remnant, and total tissue repair percentages were calculated in relation to the total defect area. The HA/DCPA/TiO 2 was characterized structurally by scanning electron microscopy (SEM), and chemically by energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). It was submitted to apparent density (AD), apparent porosity (AP), water absorption (WA) and compressive strength (CS) physical tests. The ANOVA test was applied, followed by Turkey's test and Student's t-test (p ≤ 0,05)., Results: The SEM showed biomaterials inside the bone defects and newly formed bone. EDS identified oxygen, calcium, phosphorus, and titanium in the sample. The HA/DCPA/TiO 2 and HA/DCPA groups presented a total tissue repair area that was larger than the sham group (p < 0.001)., Conclusions: The physical-mechanical assays showed that HA/DCPA/TiO 2 has AD and CS properties within the limits of trabecular bone and with values higher than HA/DCPA.HA/DCPA/TiO 2 presented higher densification and compressive strength rates than HA/DCPA., Clinical Relevance: Potential as a scaffold for bone., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This paper aims to conduct a systematic review (SR) to assess Health-Related Quality of Life (HRQoL) of malaria-exposed populations for different regions where malaria is endemic, considering any health measurements., Methods: An electronic search of the Medline, Lilacs, and Embase databases was conducted until February 2nd, 2024, to identify and select studies that evaluated HRQoL. No restrictions on place or language were made., Results: Thirty-seven studies were included, among them 21 focused on African countries. The most investigated HRQoL outcome associated with malaria was Disability-Adjusted Life Years (DALYs). These studies primarily aim to analyze the epidemiological burden of the disease or to conduct economic assessments. Only four studies conducted field research using specific instruments to assess the HRQoL of individuals experiencing malaria episodes. Three of them estimated EQ-5D utility index and found scores varying from 0.349 for severe malaria (Indonesia) to 0.74 (Nigeria). The health domains that are most affected by malaria are pain and discomfort and usual activities (EQ-5D instrument) and physical domains (WHOQOL-BREF). These results reflect the main malaria symptoms which are fever, headache, and generalized pain., Conclusion: This SR highlights a significant gap in understanding the quality of life among individuals experiencing malaria. Despite being an acute illness, recurrent episodes of malaria can lead to considerable loss in quality of life. Moreover, there are significant equity implications, as malaria remains endemic in socioeconomically disadvantaged populations., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: This is a systematic review study. The Research Ethics Committee of Federal University of Minas Gerais has confirmed that no ethical approval is required., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: The aim of this study was to review the most effective topical anesthetic methods for reducing pain/discomfort prior to dental local anesthetic needle puncture for dental procedures in children and adolescents., Methods: A scoping review was conducted. Individual search strategies were developed for each of the bibliographic databases (Cochrane, Embase, LILACS, LIVIVO, Pubmed, Scopus, PsyINFO, Web of Science), and in the gray literature (Google Scholar, Open Gray), comprehensively, without restrictions on language, publication data, or level of socioeconomic development of the country in which the study was conducted. The search was conducted on April 21, 2021 and the updates on May 24, 2024. Randomized controlled studies conducted in patients up to 18 years of age were included. Variables collected: characteristics of the included studies, topical anesthetics evaluated, time and the mode of application., Results: Initially, 8579 studies were retrieved. Then 3127 were identified as eligible, of which (n = 3127), 52 studies were included in the narrative synthesis. The most commonly observed anesthetic methods with the most favorable outcomes were lidocaine, benzocaine, ice cooling, and EMLA. Spray, gel or patch were used, with application times ranging from 1 to 10 min. Mucosal cooling an ice stick was analyzed by eight studies. Only one showed a smaller reduction in pain perception scores than others., Conclusions: Cooling is a technique with numerous clinical advantages from the clinical point of view, for reduction of pain/discomfort prior to needle puncture of dental local anesthesia in children and adolescents. It is an accessible, inexpensive and pleasant method that does not resemble needles or unpleasant tastes, nor involves systemic toxicity and complications that may be associated with others anesthetics agents. Future randomized controlled studies in accordance with the Consort Statement are needed to further investigate the topic., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: The corresponding author guarantees that the article has not been published and is not being considered for publication elsewhere. This study is a scoping review and IRB approval was not required., (© 2025. The Author(s), under exclusive licence to British Dental Association.)

Peri-implantitis (PI) is an inflammatory disease that affects supportive tissues around dental implants, and its progression eventually leads to bone loss and implant failure. However, PI effects may be different based on the presence or absence of adjacent teeth., Objective: To investigate the differences in bone loss and inflammation between implants placed adjacent to a tooth or edentulous area in a ligature-induced PI model., Materials and Methods: Three-week-old C57BL/6J male mice underwent maxillary first (AT; n=12) or first and second (AE; n=8) left molar extractions. In both groups, implants were placed in the first molar region eight weeks after tooth extraction. Each group was further divided into control (C) or ligature (PI) four weeks after osseointegration. The mice were euthanized 12-14 days after ligature placement. The samples were analyzed using micro-computed tomography and histology. Statistical analysis was performed using analysis of variance and Tukey's multiple comparison test (p<0.05)., Results: Radiographic linear analysis revealed no statistically significant differences in bone levels between the C and PI groups. Linear bone loss was significantly greater in the PI group than in the C group. Volumetric analysis yielded similar results. Histologically, hematoxylin and eosin staining revealed no notable differences between the C and PI groups. The PI group showed increased levels of inflammatory infiltrates and bone resorption. Qualitative assessment of collagen through picrosirius red staining demonstrated increased collagen disorganization in the PI group compared with that in the C group. No notable differences were observed between the AT and AE groups., Conclusion: The presence or absence of an adjacent tooth does not influence PI-induced soft and hard tissue alterations., Competing Interests: All authors state that they have no conflicts of interest.

Objective: To evaluate the quality of oral health care through indicators in patients undergoing hematopoietic stem cell transplantation for the management of oral mucositis., Methods: Thirty-five patients were evaluated. Photobiomodulation was performed during the conditioning regimen, 1 day, 5 days, and 10 days after transplantation. Four process indicators and 13 outcome indicators were used to evaluate the effectiveness of the intervention, according to SQUIRE 2.0., Results: All process indicators demonstrated a compliance rate of 100% to the desired standard. Outcome indicators revealed that 66.6% of patients experienced mucositis during at least one follow-up period. A statistically significant increase was observed between periods of 1 and 5 days post-transplant, as well as between 1 and 10 days post-transplant (p < 0.05), with a predominance of grade I mucositis (p = 0.014). Four patients (16.7%) reported feeling pain, occurring between 5 and 10 days after transplantation, with moderate pain being the most prevalent. Oral mucositis did not show a statistically significant association with pain, associated treatments, leukopenia, comorbidities, or type of transplant., Conclusions: The indicators demonstrated their suitability for evaluating oral health in both the prevention and treatment of oral mucositis in these patients. Furthermore, the effectiveness of photobiomodulation in improving the quality of oral health in the patients studied was confirmed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To describe morphological features of Megaptera novaeangliae eyes using ultrasonography and histology., Animal Studied: A total of 21 globes from 19 M. novaeangliae were used for the study, including two animals with bilateral assessment. Nine stranded animals were found alive, 10 dead., Procedures: Carcasses were classified according to decomposition state. Globes were assessed ultrasonographically, biometric measurements were taken and then the tissues were sectioned for histological analysis., Results: Seventeen carcasses were classified as decomposition code 2 and two as code 3. Fifteen animals were calves, three juveniles and one adult, twelve males, and five females. The cornea was thinner in the center of the eye and thicker at the periphery. The lens had an oval shape. Fourteen animals showed a structure in the vitreous body which looked triangular and filamentous by ultrasonography and, histologically, originated in the central part of the optic nerve and extended to the posterior region of the lens, composed of connective tissue. The most common abnormalities found by ultrasonograph were retinal detachment (n = 13) and displacement of the lens into the vitreous (n = 4), along with alterations suggestive of hemorrhage, fibrin deposits, and increased echogenicity in the optic nerve (n = 2)., Conclusions: An intraocular structure not previously described in cetaceans was found in this investigation; its function remains unknown. Circulatory changes that were evident in the histopathological analysis may be due to the stranding process and raise the need to consider ophthalmic examinations before reintroducing stranded mysticetes., (© 2024 American College of Veterinary Ophthalmologists.)

Background: Based on participatory research tools and analysis with a gender focus, we aim to identify the knowledge associated with native plants of the Atlantic Forest in one Quilombola community whose territory is juxtaposed with a protected area, in South Brazil., Methods: Through the perception of the residents of the Quilombola community of São Roque, we classified the availability, harvesting intensity, abundance, and importance of fourteen plants native to the Atlantic Forest found in their territory. These fourteen plants were selected after initial interviews with a free listing of plants done with all adults (44 people), followed by plant collection and identification. A participatory workshop was built with the community to collect data through three activities: four-cell tool, environment matrix, and importance matrix. To identify the gender nuances in the knowledge within this community, all activities were separated into two groups based on the gender of the 22 participants (9 women and 13 men) and the researchers., Results: The species Pau-pra-tudo (Picrasma crenata), Quina (Coutarea hexandra), and Cipó-milome (Aristolochia triangularis) were similarly classified as important by both groups, which indicates the cultural and environmental relevance associated with them regardless of gender. The perceptions of other species were expressed differently between the groups, showing the variance of the ecological knowledge and the relationship between the sociocultural contexts of gender and the knowledge manifested. The final part of the workshop was a lecture given by two community experts about herbal medicines based on forest species found in the territory., Conclusions: Based on the multiple forms of results recorded in the workshop, we discuss the demand for inclusion of the traditional community in land management plans of environmental agencies, highlighting how individual characteristics, such as gender, can fill gaps in data about local biodiversity., (© 2024. The Author(s).)

Objective: Spinal cord injury (SCI) is a serious condition that can lead to partial or complete paraplegia or tetraplegia. Currently, there are few therapeutic options for these conditions, which are mainly directed toward the acute phase, such as surgical intervention and high-dose steroid administration. Mesenchymal stromal cells (MSC) have been shown to improve neurological function following spinal cord injury. The aim of the study was to evaluate the safety, feasibility, and potential efficacy of MSC transplantation in patients with cervical traumatic SCI., Methods: We included seven subjects with chronic traumatic SCI (> 1 year) at the cervical level, classified as American Spinal Cord Injury Association impairment scale (AIS) grade A. Subjects received two doses of autologous bone marrow derived MSC, the first by direct injection into the lesion site after hemilaminectomy and the second three months later by intrathecal injection. Neurologic evaluation, spinal magnetic resonance imaging (MRI), urodynamics, and life quality questionnaires were assessed before and after treatment., Results: Cell transplantation was safe without severe or moderate adverse effects, and the procedures were well tolerated. Neurological evaluation revealed discrete improvements in sensitivity below the lesion level, following treatment. Five subjects showed some degree of bilateral sensory improvement for both superficial and deep mechanical stimuli compared to the pretreatment profile. No significant alterations in bladder function were observed during this study., Conclusion: Transplantation of autologous MSC in patients with chronic cervical SCI is a safe and feasible procedure. Further studies are required to confirm the efficacy of this therapeutic approach., Clinical Trial Registration: https://clinicaltrials.gov/study/NCT02574572, identifier NCT02574572., 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 © 2024 Macêdo, de Freitas Souza, Villarreal, Silva, da Silva, de Souza, da Silva Paixão, da Rocha Bezerra, da Silva Moura Costa, Brazão, Marins Filho, Matos, dos Santos and Soares.)

Canine leishmaniasis (CanL) caused by Leishmania infantum commonly progresses with renal and ophthalmic lesions associated with active systemic disease. As chronic inflammation related to immune complex deposits is a pathophysiological factor in the development of both glomerulonephritis and uveitis, we aimed to evaluate renal and ocular histopathological lesions and analyze whether they were related to each other and the clinical degree of the disease. For that, we evaluated 15 dogs from CanL-endemic areas. L. infantum PCR-positive dogs were studied according to disease severity into two different groups: Group-1 (G1) had data from seven dogs with mild to moderate CanL and no history of treatment, and G2 was formed with eight dogs with severe to terminal disease that had not responded to CanL treatment. Histopathological analysis of kidneys showed higher frequencies and intensities of glomerular basement membrane thickening (p = 0.026), deposits in glomeruli (p = 0.016), epithelial necrosis (p = 0.020), tubular dilatation (p = 0.003) and interstitial fibrosis (p = 0.04) in G2 dogs than in G1 dogs. Surprisingly, the histopathology of eye bulbs showed a higher frequency and intensity of retinitis (p = 0.019) in G1 dogs than in G2 dogs. The comparative analysis showed that there was no correspondence between histopathological findings in kidneys versus eyes in milder or more severe CanL. Our findings suggested that (1) clinically undetectable eye alterations can be more precocious than those in kidneys in the development of CanL, and (2) the lower frequency of eye lesions and higher frequency of renal lesions in dogs with terminal disease even after treatment indicate that therapy may have been effective in reducing CanL-associated ophthalmic disease but not proportionally in reducing kidney disease., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation in cardiomyocytes as well as associations with cardiac arrhythmias in CCC., Methods: C57Bl/6 mice infected with Trypanosoma cruzi underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG. Histopathology, cytokine gene expression, and distribution of total Cx43 and its phosphorylated forms Cx43 S368 and Cx43 S325/328/330 were investigated. Human heart samples obtained from subjects with CCC were submitted to immunofluorescence analysis. In vitro simulation of a pro-inflammatory microenvironment (IL-1β, TNF, and IFN-γ) was performed in H9c2 cells and iPSC-derived cardiomyocytes to evaluate Cx43 distribution, action potential duration, and Lucifer Yellow dye transfer., Results: Mice chronically infected with T. cruzi exhibited impaired cardiac function associated with increased inflammation, fibrosis and upregulated IL-1β, TNF, and IFN-γ gene expression. Confocal microscopy revealed altered total Cx43, Cx43 S368 and Cx43 S325/328/330 localization and phosphorylation patterns in CCC, with dispersed staining outside the intercalated disc areas, i.e., in lateral membranes and the cytoplasm. Reduced co-localization of total Cx43 and N-cadherin was observed in the intercalated discs of CCC mouse hearts compared to controls. Similar results were obtained in human CCC heart samples, which showed Cx43 distribution outside the intercalated discs. Stimulation of human iPSC-derived cardiomyocytes or H9c2 cells with IL-1β, TNF, and IFN-γ induced alterations in Cx43 localization, reduced action potential duration and dye transfer between adjacent cells., Conclusion: Heart inflammation in CCC affects the distribution and phosphorylation pattern of Cx43, which may contribute to the generation of conduction disturbances in Chagas disease., 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 © 2024 Barreto, Neves, Cardoso, Meira, Daltro, Figueira, Santos, Silva, Távora, Neto, Macambira, Lampe, Coutinho, Kasai Brunswick, Ribeiro dos Santos, Campos de Carvalho and Soares.)

Purpose: This prospective study evaluated the effects of the metal-free crowns on the periodontal tissues of abutment teeth during a 12-month follow-up., Materials and Methods: A sample of 24 patients (N = 32 abutment teeth) who needed a single-tooth restoration were enrolled to receive either a metal-ceramic (n = 21) or lithium disilicate (n = 11). The single-unit crowns were evaluated at baseline, 3-and 12-month follow-up. The periodontal parameters were evaluated: plaque index (PI), gingival bleeding index (GBI), bleeding on probing (BOP), probing depth (PD), clinical attachment loss (CAL), radiographically and clinical crown fitting, bone resorption, and marginal finish lines. Statistical analyses were performed using the Exact Fisher and Mann-Whitney tests, and the Wilcoxon signed-rank test as a post hoc test for Friedman (95 % confidence interval)., Results: The marginal finish line showed a statistical difference with a biomaterial type (p =.004). After a 12-months, a significant increase was observed in PI and mean PD for abutment teeth of metal-ceramic crowns. The metal-free crowns presented higher values for GBI and CAL (p 2  < 0.05). Only distal cervical evaluation and dental biofilm formation in the abutment teeth showed a statistical difference between the groups at the 12-month follow-up. The supragingival margin metal-ceramic group revealed higher PI values (p 2  = 0.005) between the period and the subgingival margin of both biomaterials showed greater GBI scores (p 2  < 0.05)., Conclusions: Metal-free crowns showed better periodontal outcomes compared to metal-ceramic crowns. Single-unit crown marginal location affects the periodontal tissue condition of the abutment teeth. The marginal fit was not changed regarding the biomaterial type., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 THE AUTHORS.)

Dental implants have a high success and survival rate. However, complications such as peri-implantitis (PI) are highly challenging to treat. PI is characterized by inflammation in the tissues around dental implants with progressive loss of supporting bone. To optimize dental implants' longevity in terms of health and functionality, it is crucial to understand the peri-implantitis pathophysiology. In this regard, using mouse models in research has proven clear benefits in recreating clinical circumstances. This study aimed to describe an experimental model of ligature-induced peri-implantitis in mice and determine whether there is effectiveness in inducing this disease, given the observed bone and tissue changes. The experimental peri-implantitis induction comprehends the following steps: teeth extraction, implant placement, and ligature-inducted PI. A sample of eighteen 3-week-old C57BL/6J male mice was divided into two groups, ligature (N=9) and control non-ligature (N=9). The evaluation of clinical, radiographical, and histological factors was performed. The ligature group showed significantly higher bone loss, increased soft tissue edema, and apical epithelial migration than the non-ligature group. It was concluded that this pre-clinical model can successfully induce peri-implantitis in mice.

Optimizing early breast cancer (BC) detection requires effective risk assessment tools. This retrospective study from Brazil showcases the efficacy of machine learning in discerning complex patterns within routine blood tests, presenting a globally accessible and cost-effective approach for risk evaluation. We analyzed complete blood count (CBC) tests from 396,848 women aged 40-70, who underwent breast imaging or biopsies within six months after their CBC test. Of these, 2861 (0.72%) were identified as cases: 1882 with BC confirmed by anatomopathological tests, and 979 with highly suspicious imaging (BI-RADS 5). The remaining 393,987 participants (99.28%), with BI-RADS 1 or 2 results, were classified as controls. The database was divided into modeling (including training and validation) and testing sets based on diagnostic certainty. The testing set comprised cases confirmed by anatomopathology and controls cancer-free for 4.5-6.5 years post-CBC. Our ridge regression model, incorporating neutrophil-lymphocyte ratio, red blood cells, and age, achieved an AUC of 0.64 (95% CI 0.64-0.65). We also demonstrate that these results are slightly better than those from a boosting machine learning model, LightGBM, plus having the benefit of being fully interpretable. Using the probabilistic output from this model, we divided the study population into four risk groups: high, moderate, average, and low risk, which obtained relative ratios of BC of 1.99, 1.32, 1.02, and 0.42, respectively. The aim of this stratification was to streamline prioritization, potentially improving the early detection of breast cancer, particularly in resource-limited environments. As a risk stratification tool, this model offers the potential for personalized breast cancer screening by prioritizing women based on their individual risk, thereby indicating a shift from a broad population strategy., (© 2024. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing antibodies (NAbs) lack cross-reactivity between SARS-CoV species and variants and fail to mediate long-term protection against infection. The maintained protection against severe disease and death by vaccination suggests a role for cross-reactive T cells. We generated vaccines containing sequences from the spike or receptor binding domain, the membrane and/or nucleoprotein that induced only T cells, or T cells and NAbs, to understand their individual roles. In three models with homologous or heterologous challenge, high levels of vaccine-induced SARS-CoV-2 NAbs protected against neither infection nor mild histological disease but conferred rapid viral control limiting the histological damage. With no or low levels of NAbs, vaccine-primed T cells, in mice mainly CD8 + T cells, partially controlled viral replication and promoted NAb recall responses. T cells failed to protect against histological damage, presumably because of viral spread and subsequent T cell-mediated killing. Neither vaccine- nor infection-induced NAbs seem to provide long-lasting protective immunity against SARS-CoV-2. Thus, a more realistic approach for universal SARS-CoV-2 vaccines should be to aim for broadly cross-reactive NAbs in combination with long-lasting highly cross-reactive T cells. Long-lived cross-reactive T cells are likely key to prevent severe disease and fatalities during current and future pandemics., Competing Interests: Declaration of interests M.S. is a founder of and has shares in SVF Vaccines AB, which holds patents for vaccines. L.F. is a founder of and has shares in SVF Vaccines AB, which holds patents for vaccines. G.A. is a consultant to SVF Vaccines AB, which holds patents for vaccines., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Scleral ossicle rings of reptiles have endoskeletal functions that are not completely understood. Moreover, descriptive reports on the anatomy of those rings are scarce. We tried to make an anatomical description that could contribute to a better understanding of their functions., Animal Studied and Procedures: We quantified, histologically characterized and evaluated the morphobiometry of the scleral ossicles, and measured the aditus orbitae of 25 sea turtle (Chelonia mydas) heads., Results: The aditus orbitae represented about one-third of the total head length and the mean area of the internal opening of each ring was up to 8.37% of the aditus orbitae area. The mean internal diameter of the rings (6.32 mm) was characteristic of scotopic species and the most frequent number of ossicles per ring varied between 11 and 12. Two new classifications were proposed for the ossicle types: plus-Verzahnung (+V) and minus-Verzahnung (-V). The bone tissue revealed a lamellar arrangement typical of compact and resistant bones., Conclusion: The obtained data may be used to support and expand the understanding of functions, animal activity patterns, distinctions between taxa and taphonomic interpretations., (© 2023 American College of Veterinary Ophthalmologists.)

In this household-based seroepidemiological survey, we analyzed the dynamics of SARS-CoV-2 seroprevalence during the first year of the COVID-19 pandemic in Sergipe State, Northeast Brazil, the poorest region of the country. A total of 16,547 individuals were tested using a rapid IgM-IgG antibody test and fluorescence immunoassay (FIA). Seroprevalence rates were presented according to age, sex, and geographic region. A comparative analysis was performed between the results obtained in July 2020 (peak of the first wave), August - November 2020 (end of the first wave), and February - March 2021 (beginning of the second wave). Seroprevalence rates in the three phases were estimated at 9.3% (95% CI 8.5-10.1), 12.0% (95% CI 11.2-12.9) and 15.4% (95% CI 14.5-16.4). At the end of the first wave, there was a rise in seroprevalence in the countryside (p < 0.001). At the beginning of the second wave, we found an increase in seroprevalence among women (p < 0.001), adults aged 20 to 59 years (p < 0.001), and the elderly (p < 0.001). In this phase, we found an increase in estimates both in metropolitan areas and in the countryside (p < 0.001). This study showed an increase in SARS-CoV-2 seroprevalence over the first year of the pandemic, with approximately one in six people having anti-SARS-CoV-2 antibodies at the beginning of the second wave of COVID-19. Furthermore, our results suggest a rapid spread of COVID-19 from metropolitan areas to the countryside during the first months of the pandemic.

Background: Typing of staphylococcal cassette chromosome mec (SCCmec) elements is commonly used for studies on the molecular epidemiology of MRSA., Objectives: To perform an investigation centred on uncovering the reasons for misclassification of MRSA clonal complex 5 (CC5) SCCmec type II clinical isolates in our laboratory., Methods: MRSA isolates from CC5 were subjected to WGS and SCCmec typing., Results: This investigation led to the discovery that the classification failure was due to an insertion of IS1272 carrying the fabI gene on a transposable element (TnSha1) that confers increased MIC to the biocide triclosan. Genomic analysis revealed that fabI was present in 25% of the CC5 MRSA isolates sampled. The frequency of TnSha1 in our collection was much higher than that observed among publicly available genomes (0.8%; n = 24/3142 CC5 genomes). Phylogenetic analyses revealed that genomes in different CC5 clades carry TnSha1 inserted in different integration sites, suggesting that this transposon has entered CC5 MRSA genomes on multiple occasions. In at least two genotypes, ST5-SCCmecII-t539 and ST5-SCCmecII-t2666, TnSha1 seems to have entered prior to their divergence., Conclusions: Our work highlights an important misclassification problem of SCCmecII in isolates harbouring TnSha1 when Boye's method is used for typing, which could have important implications for molecular epidemiology of MRSA. The importance of increased-MIC phenotype is still a matter of controversy that deserves more study given the widespread use of triclosan in many countries. Our results suggest expanding prevalence that may indicate strong selection for this phenotype., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Advanced therapy medicinal products (ATMP) are medicines for human use that are based on genes, cells or tissues. Over the past years, an increasing number of ATMP entered the market for treatment of cancer, genetic disorders, skeletal defects and metabolic diseases. However, the ATMP production methods often change from the initial concept to commercialization. This change is needed to improve the manufacturing feasibility for scaling up or scaling out. Moreover, the production must adhere to current good manufacturing practices (GMP), and needs to follow a risk-based approach, which often is challenging to implement due to the novelty of the products. Since most of the early ATMP development is done in academia, an environment that is not familiar with regulatory requirements for ATMP production in GMP, the initial manufacturing choice for pre-clinical studies is usually very different from what is required for clinical use. This leads to a lengthy production process optimization, unnecessary repetition of experiments and ultimately waste of funding. This consideration prompted us to provide an intermediate step between early ATMP production in research settings to GMP manufacturing. We built a dedicated facility, and we called this environment 'pre-GMP' to highlight that it is a step toward preparation to GMP manufacturing. This environment supports process development and provides a manufacturing fitness room before transferring to GMP suites. This paper addresses the relevance of pre-GMP, underlining the advantages and the possible disadvantages of this additional framework that may be key in accelerating the pace of ATMP toward clinic., (© 2022 The Author(s).)

Background: Quantifying disease costs is critical for policymakers to set priorities, allocate resources, select control and prevention strategies, and evaluate the cost-effectiveness of interventions. Although malaria carries a very large disease burden, the availability of comprehensive and comparable estimates of malaria costs across endemic countries is scarce., Methods: A literature review to summarize methodologies utilized to estimate malaria treatment costs was conducted to identify gaps in knowledge., Results: Only 45 publications met the inclusion criteria. They utilize different methods, include distinct cost components, have varied geographical coverage (a country vs a city), include different periods in the analysis, and focus on specific parasite types or population groups (e.g., pregnant women)., Conclusions: Cost estimates currently available are not comparable, hindering broad statements on the costs of malaria, and constraining advocacy efforts towards investment in malaria control and elimination, particularly with the finance and development sectors of the government., (© 2022. The Author(s).)

The devastating disease coffee leaf rust, caused by Hemileia vastatrix , has been a major constraint to worldwide coffee production. Recently, H. vastatrix populations were shown to be structured into three divergent genetic lineages with marked host specialization (C1, C2, and C3). However, there is yet no overall understanding of the population dynamics and adaptation of the most widespread and epidemiological relevant H. vastatrix group (C3). We used restriction site-associated DNA sequencing to generate 13,804 single nucleotide polymorphisms (SNPs) across a worldwide collection of 99 H. vastatrix isolates. Phylogenetic analyses uncovered a well-supported structuring within C3, with three main subgroups (SGs; SGI, SGII, and SGIII), which seem to reflect the historical distribution, breeding, and exchange of coffee cultivars. SGI shows a ladder-like diversification pattern and occurs across all four continents sampled, SGII is mainly restricted to Africa, and SGIII is observed only in Timor, revealing a higher genetic differentiation. Outlier and association tests globally identified 112 SNPs under putative positive selection, which impacted population structure. In particular, 29 overlapping SNPs per se seemed to have an extremely strong effect on H. vastatrix population divergence. We also found exclusive and fixed alleles associated with the SGs supporting local adaptation. Functional annotation revealed that transposable elements may play a role in host adaptation. Our study provides a higher-resolution perspective on the evolutionary history of H. vastatrix on cultivated coffee, showing its strong ability to adapt and the strength of the selective force imposed by coffee hosts, which should be taken into account when designing strategies for pathogen dissemination control and selective breeding.

Objectives: This experimental study was carried out to investigate the effects of locally delivered nanoparticles (AMG-487 NP) containing a CXCR3 antagonist in inhibiting the progression of LPS-induced inflammation, osteoclastic activity, and bone resorption on a murine model., Materials and Methods: Thirty, 7-week-old C57BL/6 J male mice were used. Inflammatory bone loss was induced by Porphyromonas gingivalis-lipopolysaccharide (P.g.-LPS) injections between the first and second maxillary molars, bilaterally, twice a week for 6 weeks (n = 20). AMG-487 NP were incorporated into a liposome carrier and locally delivered on sites where P.g.-LPS was injected. Control mice (n = 10) were injected with vehicle only. Experimental groups included (1) control, (2) LPS, and (3) LPS + NP. At the end of 1 and 6 weeks, mice were euthanized, maxillae harvested, fixed, and stored for further analysis., Results: Volumetric bone loss analysis revealed, at 1 week, an increase in bone loss in the LPS group (47.9%) compared to control (27.4%) and LPS + NP (27.8%) groups. H&E staining demonstrated reduced inflammatory infiltrate in the LPS + NP group compared to LPS group. At 6 weeks, volumetric bone loss increased in all groups; however, treatment with the CXCR3 antagonist (LPS + NP) significantly reduced bone loss compared to the LPS group. CXCR3 antagonist treatment significantly reduced osteoclast numbers when compared to LPS group at 1 and 6 weeks., Conclusions: This study showed that local delivery of a CXCR antagonist, via nanoparticles, in a bone resorption model, induced by LPS injection, was effective in reducing inflammation, osteoclast numbers, and bone loss., Clinical Relevance: CXCR3 blockade can be regarded as a novel target for therapeutic intervention of bone loss. It can be a safe and convenient method for periodontitis treatment or prevention applicable in clinical practice., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Infection by Caryospora cheloniae has been reported to be responsible for green turtle strandings with high morbidity and mortality rates worldwide. Although studies have already shown the pathogenesis of these infections, many aspects of this protozoan are still poorly understood, including their life cycle and infection dynamics in free-living sea turtle populations. Due to the lack of information about the infection by this protozoan in sea turtles in Northeastern Brazil, our study aims to describe Caryospora sp. infection and its pathological findings in free-living Chelonia mydas found on the north coast of the Bahia state. Between 2018 and 2019, 64 specimens of green turtles were necropsied in partnership with Fundação Projeto Tamar; among these, 10 (1.56%) had oocysts morphologically compatible with Caryospora cheloniae in the evaluation of fecal samples and histopathological examination of intestinal samples. The infected animals were juvenile green turtles that were found stranded on the beaches of the north coast of Bahia. The pathological findings were restricted to the lower gastrointestinal tract, with different presentations and intensities. About 70% of the animals with coccidial infection exhibited erosive and ulcerative fibrinous enteritis. This is the first report of coccidiosis in green turtles on the north coast of Bahia., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cellular immunotherapies based on T cell receptor (TCR) transfer are promising approaches for the treatment of cancer and chronic viral infections. The discovery of novel receptors is expanding considerably; however, the clinical development of TCR-T cell therapies still lags. Here we provide a pipeline for process development and clinical-scale manufacturing of TCR-T cells in academia. We utilized two TCRs specific for hepatitis C virus (HCV) as models because of their marked differences in avidity and functional profile in TCR-redirected cells. With our clinical-scale pipeline, we reproduced the functional profile associated with each TCR. Moreover, the two TCR-T cell products demonstrated similar yield, purity, transduction efficiency as well as phenotype. The TCR-T cell products had a highly reproducible yield of over 1.4 × 10 9 cells, with an average viability of 93%; 97.8-99% of cells were CD3+, of which 47.66 ± 2.02% were CD8+ T cells; the phenotype was markedly associated with central memory (CD62L+CD45RO+) for CD4+ (93.70 ± 5.23%) and CD8+ (94.26 ± 4.04%). The functional assessments in 2D and 3D cell culture assays showed that TCR-T cells mounted a polyfunctional response to the cognate HCV peptide target in tumor cell lines, including killing. Collectively, we report a solid strategy for the efficient large-scale manufacturing of TCR-T cells., 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 Silva, Chrobok, Rovesti, Healy, Wagner, Maravelia, Gatto, Mazza, Mazzotti, Lohmann, Sällberg Chen, Sällberg, Buggert and Pasetto.)

Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurological disease. We review current knowledge of the therapeutic potential of MSC-based therapies for neurological diseases, as well as possible mechanisms of action that may be explored to hasten the development of new and effective treatments. We also discuss the challenges for culture conditions, quality control, and the development of potency tests, aiming to generate more efficient cell therapy products for neurological disorders., 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 Soares, Gonçalves, Vasques, da Silva-Junior, Gubert, Santos, de Santana, Sampaio, Silva, Dominici and Mendez-Otero.)

Drought is the most detrimental abiotic stress to sugarcane production. Nevertheless, transcriptomic analyses remain scarce for field-grown plants. Here we performed comparative transcriptional profiling of two contrasting sugarcane genotypes, 'IACSP97-7065' (drought-sensitive) and 'IACSP94-2094' (drought-tolerant) grown in a drought-prone environment. Physiological parameters and expression profiles were analyzed at 42 (May) and 117 (August) days after the last rainfall. The first sampling was done under mild drought (soil water potential of -60 kPa), while the second one was under severe drought (soil water potential of -75 kPa). Microarray analysis revealed a total of 622 differentially expressed genes in both sugarcane genotypes under mild and severe drought stress, uncovering about 250 exclusive transcripts to 'IACSP94-2094' involved in oxidoreductase activity, transcriptional regulation, metabolism of amino acids, and translation. Interestingly, the enhanced antioxidant system of 'IACSP94-2094' may protect photosystem II from oxidative damage, which partially ensures stable photochemical activity even after 117 days of water shortage. Moreover, the tolerant genotype shows a more extensive set of responsive transcription factors, promoting the fine-tuning of drought-related molecular pathways. These results help elucidate the intrinsic molecular mechanisms of a drought-tolerant sugarcane genotype to cope with ever-changing environments, including prolonged water deficit, and may be useful for plant breeding programs., (© 2022. The Author(s).)

Our study aimed to study the efficacy of ILIB on periodontal parameters and glycemic control in patients with periodontitis and type II diabetes. Twenty-one patients in a randomized clinical trial were divided into 2 groups: control group (CG), conventional periodontal therapy, and test group (TG), conventional periodontal treatment associated with 10 laser applications by the ILIB-Modified (ILIB-M) technique. Fasting blood glucose levels and glycated hemoglobin (HbA1c), visible plaque index (VPI), gingival bleeding index (GBI), and periodontal clinical parameters were evaluated at baseline and after 4 months (T 4 ). Regarding periodontal parameters, the intragroup analysis showed a statistically significant reduction (p < 0.05) between baseline and T 4 , for the VPI, GBI, BOP, PD, and CAL indexes. However, in the intergroup analysis, no statistically significant improvements (p > 0.05) were observed between the TG and CG for the VPI, GBI, BOP, PD, and CAL indexes. Regarding HbA1C and fasting blood glucose values, no statistically significant improvements were observed in intergroup and intragroup analyses (p > 0.05). The Modified ILIB did not improve the periodontal clinical parameters and glycemic control in patients with type II diabetes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

The purpose of this work was to apply an electrochemical sensor modified with a molecularly imprinted polymer (MIP) and carbon black (CB) for 17β-estradiol (E2) detection in river water samples. The synthesized MIP was characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM).The modification of the electrode with the MIP and CB contributed to increased sensitivity, an increase of over 173% in relation to that of the bare electrode. The experimental parameters, amount of modifiers, pH and possible interfering species were evaluated. The method showed linearity from 0.10 to 23.0 μmol L -1 and detection and quantification limits of 0.03 and 0.10 μmol L -1 , respectively. The application of the developed sensor was considered simple, resulting in a fast, low operating cost method, with recovery values between 103 and 105%.

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.

Body bones play diverse pivotal roles, including the protection of vital organs. For instance, the integrative functions of the brain controlling diverse peripheral actions can be affected by a traumatic injury on the calvaria and the reparative process of a large defect is a challenge in the integrative physiology. Therefore, the development of biomaterials and approaches to improve such defects still requires substantial advances. In this regard, the most attractive approaches have been covering the cavity with inorganic bovine bone (IBB) and, more recently, also using low-level laser therapy (LT), but this issue has opened many questions. Here, it was determined the number of LT sessions required to speed up and to intensify the recovery process of two 5-mm-diameter defects promoted in the calvaria of each subgroup of six adult Wistar rats. The quantitative data showed that 30 days post-surgery, the recovery process by using blood clot-filling was not significantly influenced by the number of LT sessions. However, in the IBB-filled defects, the number of LT sessions markedly contributed to the improvement of the reparative process. Compared to the Control group (non-irradiated), the percentage of mineralization (formation of new bone into the cavities) gradually increased 25, 49, and 52% with, respectively, 4, 7, and 11 sessions of LT. In summary, combining the use of IBB with seven sessions of LT seems to be an optimal approach to greatly improve the recovery of calvarial defects. This translational research opens new avenues targeting better conditions of life for those suffering from large bone traumas and in the present field could contribute to preserve the integrative functions of the brain., 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 Santos, Silva, Rovaris, Sousa, Dantas, Loureiro, Pereira, Meyrelles, Bertollo and Vasquez.)

We investigated the seroprevalence of SARS-CoV-2 antibodies in individuals working in radio and television stations (TV) in Sergipe state, Northeast Brazil. This cross-sectional study was conducted from December 1 to December 20, 2020, a period which was considered as the beginning of the second wave of COVID-19 in the state. One hundred and thirteen professionals from the three largest media companies in the state were included in this study. Venous blood was collected using venipuncture and a fluorescence immunoassay for qualitative detection and differentiation of IgM and IgG antibodies against SARS-CoV-2 was performed. Twenty-eight media workers had detectable levels of SARS-CoV-2 antibodies (11 IgM+, 6 IgM+/ IgG+, and 11 IgG+) and the estimated seroprevalence was 24.8 % (95 % CI 17.7 - 33.5). Our findings showed a high seroprevalence of SARS-CoV-2 antibodies in radio and TV workers during the second wave of COVID-19 in Brazil., (Copyright © 2022 Martins-Filho et al.)

Purpose: To evaluate the effects of functional and concurrent training on immune function and functional fitness in postmenopausal women., Materials and Methods: A randomized controlled trial was performed on 108 women aged 60 or older who were randomly assigned among the groups: control group (CG: n = 40; 63.88 ± 3.64 years); functional training (FT: n = 32; 63.88 ± 3.79 years); and concurrent training (CT: n = 36; 64.83 ± 4.00 years). Immune function was measured by the expression of the T-lymphocyte function-related surface markers (CD28 and CD57). Functional fitness was assessed using physical tests similar to daily activities, i.e., five times sit to stand, timed up and go, and gallon-jug shelf-transfer., Results: Regarding immune function, there was only a time effect, without between-group differences. Specifically, FT and CT show a reduction and increase in CD4 + and CD8 + T cells, respectively, without impairment in the subpopulations analyzed, while CG showed a reduction in naive T cells (CD8 + CD28 + ). For functional fitness tests, there was a time × group interaction effect for all tests, the FT and CT were superior to the CG, with FT showing differences after the fourth week, while the CT showed this effect after the eighth week of intervention., Conclusion: FT and CT do not impair immune function and similarly improve functional fitness in postmenopausal women., Clinical Trials Registry: RBR-2d56bt., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Hepatocellular carcinoma (HCC) is one of the deadliest cancer types worldwide. HCC is often diagnosed at a late stage when the therapeutic options are very limited. However, even at the earlier stages, the best treatment is liver transplantation, surgical resection or ablation. Surgical resection and ablation may carry a high risk of tumor recurrence. The recent introduction of immunotherapies resulted in clinical responses for a subgroup of patients, but there were still no effective predictive markers for response to immunotherapy or for recurrence after surgical therapy. The identification of biomarkers that could correlate and predict response or recurrence would require close monitoring of the patients throughout and after the completion of treatment. However, this would not be performed efficiently by repeated and invasive tissue biopsies. A better approach would be to use liquid biopsies including circulating tumor DNA (ctDNA), circulating RNA (e.g., microRNAs), circulating tumor cells (CTC) and extracellular vesicles (EVs) (e.g., exosomes) for disease monitoring in a non-invasive manner. In this review, we discuss the currently available technology that can enable the use of liquid biopsy as a diagnostic and prognostic tool. Moreover, we discuss the opportunities and challenges of the clinical application of liquid biopsy for immunotherapy of HCC.

Chagas disease is caused by Trypanosoma cruzi infection and remains a relevant cause of chronic heart failure in Latin America. The pharmacological arsenal for Chagas disease is limited, and the available anti- T. cruzi drugs are not effective when administered during the chronic phase. Cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) have the potential to accelerate the process of drug discovery for Chagas disease, through predictive preclinical assays in target human cells. Here, we aimed to establish a novel high-content screening- (HCS-) based method using hiPSC-CMs to simultaneously evaluate anti- T. cruzi activity and cardiotoxicity of chemical compounds. To provide proof-of-concept data, the reference drug benznidazole and three compounds with known anti- T. cruzi activity (a betulinic acid derivative named BA5 and two thiazolidinone compounds named GT5A and GT5B) were evaluated in the assay. hiPSC-CMs were infected with T. cruzi and incubated for 48 h with serial dilutions of the compounds for determination of EC50 and CC50 values. Automated multiparametric analyses were performed using an automated high-content imaging system. Sublethal toxicity measurements were evaluated through morphological measurements related to the integrity of the cytoskeleton by phalloidin staining, nuclear score by Hoechst 33342 staining, mitochondria score following MitoTracker staining, and quantification of NT-pro-BNP, a peptide released upon mechanical myocardial stress. The compounds showed EC 50 values for anti- T. cruzi activity similar to those previously described for other cell types, and GT5B showed a pronounced trypanocidal activity in hiPSC-CMs. Sublethal changes in cytoskeletal and nucleus scores correlated with NT-pro-BNP levels in the culture supernatant. Mitochondrial score changes were associated with increased cytotoxicity. The assay was feasible and allowed rapid assessment of anti- T. cruzi action of the compounds, in addition to cardiotoxicity parameters. The utilization of hiPSC-CMs in the drug development workflow for Chagas disease may help in the identification of novel compounds., Competing Interests: The authors claim no conflict of interest., (Copyright © 2021 Diogo Crispim Nascimento Portella et al.)

Leptospirosis, a zoonotic disease with worldwide distribution, is caused by spirochetes of the genus Leptospira. In dogs, this disease is frequently misdiagnosed. Few studies have attempted to associate the detection of Leptospira spp. infection with clinicopathological and renal histopathological findings using a multidisciplinary approach. The present study isolated and characterized Leptospira spp. obtained from naturally infected dogs and described relevant clinical and histopathological findings. Blood and urine were collected from 57 dogs with clinical symptomatology suggestive of leptospirosis; 38 cases were confirmed by PCR in urine or by culture or microscopic agglutination testing (titers ≥800). A total of 12 strains of pathogenic Leptospira were isolated from the studied dogs (seven in blood, four in urine and one in both blood and urine samples). All isolates were characterized as Leptospira interrogans serogroup Icterohaemorrhagiae. Of the confirmed cases, almost one-third of the animals had been vaccinated. Our analysis of laboratory testing revealed that azotemia and proteinuria were statistically significant predictors of infection. The main histopathological findings seen in kidney tissues were necrosis, degeneration, tubular regeneration, mononuclear inflammatory infiltrate and congestion. A multidisciplinary approach involving clinicopathological and histopathological characterization of renal involvement can aid in the identification of acute leptospirosis infection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aims: The present study was designed to investigate whether the antinociceptive effect of bone marrow-derived mesenchymal stem/stromal cells (MSC) during oxaliplatin (OXL)-induced sensory neuropathy is related to antioxidant properties., Main Methods: Male mice C57BL/6 were submitted to repeated intravenous administration of OXL (1 mg/kg, 9 administrations). After the establishment of sensory neuropathy, mice were treated with a single intravenous administration of MSC (1 × 10 6 ), vehicle or gabapentin. Paw mechanical and thermal nociceptive thresholds were evaluated through von Frey filaments and cold plate test, respectively. Motor performance was evaluated in the rota-rod test. Gene expression profile, cytokine levels, and oxidative stress markers in the spinal cord were evaluated by real-time PCR, ELISA and biochemical assays, respectively., Key Findings: OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia, which were completely reverted by a single administration of MSC. Repeated oral treatment with gabapentin (70 mg/kg) induced only transient antinociception. The IL-1β and TNF-α spinal levels did not differ between mice with or without sensory neuropathy. MSC increased the levels of anti-inflammatory cytokines, IL-10 and TGF-β, in the spinal cord of neuropathic mice, in addition to increasing the gene expression of antioxidant factors SOD and Nrf-2. Additionally, nitrite and MDA spinal levels were reduced by the MSC treatment., Significance: MSC induce reversion of sensory neuropathy induced by OXL possibly by activation of anti-inflammatory and antioxidant pathways, leading to reestablishment of redox homeostasis in the spinal cord., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Painful neuropathy is a common adverse effect of oxaliplatin (OXL), a platinum-derivative chemotherapeutic agent. Oxidative stress and mitochondrial dysfunction are key factors contributing to the development of OXL-induced peripheral neuropathy (OIPN). Based on the antioxidant and antinociceptive properties of mesenchymal stem/stromal cells (MSC), the present study tested the hypothesis that MSC induce antinociceptive effects during OIPN by promoting regulation of redox environment and mitochondrial homeostasis in the nociceptive primary afferents. C57Bl/6 mice submitted to the OXL-chronic neuropathy induction protocol by repeated intravenous administration of OXL (1 mg/kg) were evaluated to determine the paw mechanical and thermal nociceptive thresholds using the von Frey filaments and cold plate tests, respectively. Two weeks after the neuropathy induction, mice were treated with bone marrow-derived MSC (1 × 10 6 ), vehicle, or gabapentin (GBP, 70 mg/kg). Four weeks later, mitochondrial morphology, gene expression profile, and oxidative stress markers in the sciatic nerve and dorsal root ganglia (DRG) were evaluated by transmission electron microscopy, RT-qPCR, and biochemical assays, respectively. OXL-treated mice presented behavioral signs of sensory neuropathy, such as mechanical allodynia and thermal hyperalgesia. The behavioral painful neuropathy was completely reverted by a single administration of MSC, while the daily treatment with GBP induced only a short-lived antinociceptive effect. The ultrastructural analysis of the sciatic nerve and DRG of OIPN mice revealed a high proportion of atypical mitochondria in both myelinated and unmyelinated fibers. Importantly, this mitochondrial atypia was strongly reduced in MSC-treated neuropathic mice. Moreover, MSC-treated neuropathic mice showed upregulation of Sod and Nrf2 mRNA in the sciatic nerve and DRG. In line with this result, MSC reduced markers of nitrosative stress and lipid peroxidation in the sciatic nerve and DRG from OIPN mice. Our data suggest that the reestablishment of redox homeostasis in the nociceptive primary afferents is a mechanism by which MSC transplantation reverts the OXL-induced chronic painful neuropathy., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Anna Lethicia L. Oliveira et al.)

A captive loggerhead turtle (Caretta caretta) of unknown sex, 3 years of age, presented with bilateral mucoid secretions, severe chemosis, conjunctival hyperemia, and globe retraction. The animal was evaluated ophthalmologically and systemically, and hematological, microbiological, and conjunctival cytological and biopsy samples were collected for complementary diagnosis. The histopathological examination showed amphophilic intranuclear inclusions associated with severe inflammatory infiltrate. The diagnosis of Chelonid alphaherpesvirus 5 (ChAHV 5) was confirmed with end point PCR. Following systemic treatment with L-lysine, acyclovir and vitamin A, the ocular signs resolved. No amphophilic intranuclear inclusions were seen in a follow-up biopsy 5 months later, and there has been no recurrence of clinical ophthalmic signs during a 4-year follow-up. It is suggested that ChAHV 5 be considered as a differential diagnosis in captive marine turtles that present for conjunctival disease other than fibropapillomatosis., (© 2020 American College of Veterinary Ophthalmologists.)

3D tumor spheroids have arisen in the last years as potent tools for the in vitro screening of novel anticancer therapeutics. Nevertheless, to increase the reproducibility and predictability of the data originated from the spheroids it is still necessary to develop or optimize the techniques used for spheroids' physical and biomolecular characterization. Fluorescence microscopy, such as confocal laser scanning microscopy (CLSM), is a tool commonly used by researchers to characterize spheroids structure and the antitumoral effect of novel therapeutics. However, its application in spheroids' analysis is hindered by the limited light penetration in thick samples. For this purpose, optical clearing solutions have been explored to increase the spheroids' transparency by reducing the light scattering. In this study, the influence of agitation conditions (i.e., static, horizontal agitation, and rotatory agitation) on the Clear T and Clear T2 methods' clearing efficacy and tumor spheroids' imaging by CLSM was characterized. The obtained results demonstrate that the Clear T method results in the improved imaging of the spheroids interior, whereas the Clear T2 resulted in an increased propidium iodide mean fluorescence intensity as well as a higher signal depth in the Z-axis. Additionally, for both methods, the best clearing results were obtained for the spheroids treated under the rotatory agitation. In general, this work provides new insights on the Clear T and Clear T2 clearing methodologies and their utilization for improving the reproducibility of the data obtained through the CLSM, such as the analysis of the cell death in response to therapeutics administration.

The introduction of advanced therapy medicinal products (ATMPs) to the global pharma market has been revolutionizing the pharmaceutical industry and has opened new routes for treating various types of cancers and incurable diseases. In the past two decades, a noticeable part of clinical practices has been devoting progressively to these products. The first step to develop such an ATMP product is to be familiar with other approved products to obtain a general view about this industry trend. The present paper depicts an overall perspective of approved ATMPs in different countries, while reflecting the degree of their success in a clinical point of view and highlighting their main safety issues and also related market size as a whole. In this regard, published articles regarding safety, efficacy, and market size of approved ATMPs were reviewed using the search engines PubMed, Scopus, and Google Scholar. For some products which the related papers were not available, data on the relevant company website were referenced. In this descriptive study, we have introduced and classified approved cell, gene, and tissue engineering-based products by different regulatory agencies, along with their characteristics, manufacturer, indication, approval date, related regulatory agency, dosage, product description, price and published data about their safety and efficacy. In addition, to gain insights about the commercial situation of each product, we have gathered accessible sale reports and market size information that pertain to some of these products., 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 © 2020 Ramezankhani, Torabi, Minaei, Madani, Rezaeiani, Hassani, Gee, Dominici, Silva, Baharvand and Hajizadeh-Saffar.)

Background: Salivary tests for the new coronavirus (SARS-CoV-2) diagnosis have been suggested as alternative methods for the nasopharyngeal and oropharyngeal tests., Method: Two reviewers independently performed a search in the following electronic databases: PubMed, Medline, Cochrane Library, Web of Science, Embase and Scopus to identify cross-sectional and cohort studies that used saliva samples for SARS-CoV-2 detection. The search strategy was: ("saliva") and ("SARS-CoV-2" or "coronavirus" or "COVID-1")., Results: A total of 363 studies were identified and 39 were selected for review. Salivary samples for SARS-CoV-2 detection was as consistent and sensitive as the nasopharyngeal swabs in most studies, having been effective in detecting asymptomatic infections previously tested negative in nasopharyngeal samples. Viral nucleic acids found in saliva obtained from the duct of the salivary gland may indicate infection in that gland. Live viruses could be detected in saliva by viral culture., Conclusions: Salivary samples show great potential in SARS-CoV-2 detection and may be recommended as a simple and non-invasive alternative., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Since mesenchymal stromal/stem cells (MSCs) were discovered, researchers have been drawn to study their peculiar biological features, including their immune privileged status and their capacity to selectively migrate into inflammatory areas, including tumors. These properties make MSCs promising cellular vehicles for the delivery of therapeutic molecules in the clinical setting. In recent decades, the engineering of MSCs into biological vehicles carrying anticancer compounds has been achieved in different ways, including the loading of MSCs with chemotherapeutics or drug functionalized nanoparticles (NPs), genetic modifications to force the production of anticancer proteins, and the use of oncolytic viruses. Recently, it has been demonstrated that wild-type and engineered MSCs can release extracellular vesicles (EVs) that contain therapeutic agents. Despite the enthusiasm for MSCs as cyto-pharmaceutical agents, many challenges, including controlling the fate of MSCs after administration, must still be considered. Preclinical results demonstrated that MSCs accumulate in lung, liver, and spleen, which could prevent their engraftment into tumor sites. For this reason, physical, physiological, and biological methods have been implemented to increase MSC concentration in the target tumors. Currently, there are more than 900 registered clinical trials using MSCs. Only a small fraction of these are investigating MSC-based therapies for cancer, but the number of these clinical trials is expected to increase as technology and our understanding of MSCs improve. This review will summarize MSC-based antitumor therapies to generate an increasing awareness of their potential and limits to accelerate their clinical translation., (Copyright © 2020 Golinelli, Mastrolia, Aramini, Masciale, Pinelli, Pacchioni, Casari, Dall’Ora, Soares, Damasceno, Silva, Dominici and Grisendi.)