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Dexamethasone in different routes of administration has been used to control discomfort after third molar surgery. The objective of this research is to determine if the application of dexamethasone by submucosal or intramuscular route is justified for the control of pain, edema and trismus after third molar surgery. A comparative study was carried out in a sample of 51 patients divided into three groups. Group 1 received preoperative intramuscular dexamethasone, group 2 received preoperative submucosal dexamethasone, and group 3 did not receive dexamethasone. The variables pain, trismus and edema were measured at different times. The analysis was carried out in the STATA V13 program, reporting simple frequencies for categorical variables and differences between groups with the Chi-square test, for numerical variables ANOVA and Kruskal Wallis test was applied. Of the 51 patients, 16 were male (31%) and 35 female (69%) and their mean age was 23 years (DE ± 4.8) with a range from 17 to 44. No differences were found between the groups by age and sex. When comparing the different interventions to the groups (IM dexamethasone, submucosal dexamentason and without dexamethasone), no significant differences were found between the groups in any of the parameters studied (edema, pain and trismus), neither at 2, nor at 7 days after the intervention. The administration of dexamethasone intramuscularly or submucosally does not generate important benefits for the control of edema, pain and trismus postoperatively after surgery of wisdom lower third molars. Studies with larger sample sizes are recommended.

Jasmin,1,* Gustavo Torres de Souza,2,3,* Ruy Andrade Louzada,4 Paulo Henrique Rosado-de-Castro,5 Rosalia Mendez-Otero,6 Antonio Carlos Campos de Carvalho61NUMPEX-Bio, Federal University of Rio de Janeiro, Duque de Caxias, RJ, 2Laboratory of Animal Reproduction, Embrapa Dairy Cattle, Juiz de Fora, MG, 3Laboratory of Genetics, Federal University of Juiz de Fora, Juiz de Fora, MG, Brazil; 4Institute Gustave-Roussy of Oncology, Paris-Sud University, Villejuif, France; 5Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 6Institute Carlos Chagas Filho of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil *These authors contributed equally to this work Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for diagnoses in biomedical applications, due to their unique properties and their apparent safety for humans. In general, SPIONs do not seem to produce cell damage, although their long-term in vivo effects continue to be investigated. The possibility of efficiently labeling cells with these magnetic nanoparticles has stimulated their use to noninvasively track cells by magnetic resonance imaging after transplantation. SPIONs are attracting increasing attention and are one of the preferred methods for cell labeling and tracking in preclinical and clinical studies. For clinical protocol approval of magnetic-labeled cell tracking, it is essential to expand our knowledge of the time course of SPIONs after cell incorporation and transplantation. This review focuses on the recent advances in tracking SPION-labeled stem cells, analyzing the possibilities and limitations of their use, not only focusing on myocardial infarction but also discussing other models. Keywords: nanoparticles, superparamagnetic iron oxide nanoparticles, stem cells, cell tracking, in vivo imaging, myocardial infarction

A precise orthometric height (H) and orthometric height difference (ΔH) determination is required in many fields like construction, geodesy and geophysics. H is often obtained from an ellipsoidal height (h) and geoid height (N) of a geoid model (GM) because this computation does not have the spirit leveling restrictions on long distances. However, the H accuracy depends on the GM local area adaptation, and current global geoid models (GGMs) have not been yet evaluated for Costa Rica. Therefore, this paper aims to determine which GGM maintains a better fit with a GPS/levelling baseline that contains the gravity full spectrum. A 74 km baseline was measured using GPS, spirit leveling and gravity measurements to validate the N computed from EGM2008, EIGEN-6C4, GECO, EGM96, GGM05C and GOCO05C. First, an absolute N assessment was made, where geoid height from the GGMs (NGGM) were directly compared to the geometric geoid heights (Ngeo) obtained from GPS and spirit levelling. A bias fit (Nbias) of about 2 m was computed from this comparison for most GGMs with respect to the local vertical reference surface (W0). By subtracting the Nbias, a relative geoid height (ΔN) assessment was designed to compare the differences between GGM relative geoid height (ΔNGGM) and geometric relative geoid height (ΔNgeo) on segments along the baseline. The ΔN comparison shows that EGM2008, EIGEN-6C4 and GECO better represent the Costa Rican Central Pacific Coastal Zone and over long distances, ΔH can be computed with a decimeter to centimeter precision.

Background: Concerns have been raised about cardiac inflammation in patients with long COVID-19, particularly those with myocardial injury during the acute phase of the disease. This study was conducted to examine myopericardial involvement, detected by cardiac magnetic resonance (CMR) imaging in patients hospitalized for COVID-19., Methods: Adult patients hospitalized with COVID-19 who presented myocardial injury or increased D-dimers were enrolled in this prospective study. All patients were invited to undergo CMR imaging examination after discharge. During follow-up, patients with nonischemic myocardial or pericardial involvement detected on the first CMR imaging examination underwent second examinations. CMR imaging findings were compared with those of a control group of healthy patients with no comorbidity., Results: Of 180 included patients, 53 underwent CMR imaging examination. The mean age was 58.4 ± 18.3 years, and 73.6 % were male. Myocardial and pericardial LGE was reported in 43.4 % and 35.8 % of patients, respectively. Nonischemic myocardial or pericardial involvement was reported in 26 (49.1 %) patients. The prevalence of pericardial LGE was associated inversely with the interval between hospital discharge and CMR. COVID-19 survivors had higher end-systolic volume indices (ESVis) and lower left-ventricular ejection fractions than did healthy controls. Seventeen patients underwent follow-up CMR imaging; the end-diastolic volume index, ESVi, and prevalence of pericardial LGE, but not that of nonischemic LGE, were reduced., Conclusion: Among COVID-19 survivors with myocardial injury during the acute phase of the disease, the incidences of nonischemic myocardial and pericardial LGE and CMR imaging-detected signs of cardiac remodeling, partially reversed during follow-up, were high., 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.)

Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC ( 68 Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68 Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

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.

Environmental surface surveillance is a valuable tool for detecting and controlling infectious diseases. During the COVID-19 pandemic, concerns have been raised regarding the potential for indirect transmission of SARS-CoV-2 via contaminated surfaces. However, few studies have evaluated environmental contamination in non-clinical settings during outbreaks. We conducted a study in a school community during a major outbreak, collecting 35 surface samples from high-traffic areas and testing them for SARS-CoV-2 RNA using RT-qPCR. Our results showed that 31.4% of samples were positive, including high-touch surfaces such as drinking fountains and washbasins. These findings emphasize the importance of environmental monitoring to identify and address specific areas for attention, and implementing such strategies can help prevent the indirect transmission of COVID-19 in various settings., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Objective: To describe a novel dissector device useful in laparoscopy, better definition of anatomic structures to have a better dissection, separation, and cleaning of the structures., Method: The endoscopic dissector DisePad was designed and developed at the experimental surgery department of Centro Médico Nacional 20 de Noviembre, and properly patented at Instituto Mexicano de la Propiedad Industrial (title 3512)., Results: The tip of the device is the most important component, by its direct contact with the different tissues, consists of a cotton-polyester black cloth impregnated with a special gel immersed into a hot saline solution. Once soaked the tip maintains the solution temperature on itself., Conclusions: This device has been used in 364 laparoscopic procedures demonstrating, its utility to visualize, separate and clean anatomical structures without thermal lesion, tear, hemorrhage or visceral perforation., (Copyright: © 2024 Permanyer.)

Background: Chagas heart disease (CHD) is characterized by progressive myocardial inflammation associated with myocardial fibrosis and segmental abnormalities that may lead to malignant ventricular arrhythmia and sudden cardiac death. This arrhythmia might be related to the persistence of parasitemia or inflammation in the myocardium in late-stage CHD. Positron emission tomography/computed tomography (PET/CT) has been used to detect myocardial inflammation in non-ischemic cardiomyopathies, such as sarcoidosis, and might be useful for risk prediction in patients with CHD., Methods and Results: Twenty-four outpatients with chronic CHD were enrolled in this prospective cross-sectional study between May 2019 and March 2022. The patients were divided into two groups: those with sustained ventricular tachycardia and/or aborted sudden cardiac death who required implantable cardioverter-defibrillators, and those with the same stages of CHD and no complex ventricular arrhythmia. Patients underwent 18 F-fluorodeoxyglucose ( 18 F-FDG) and 68 Ga-DOTATOC PET/CT, and blood samples were collected for qualitative parasite assessment by polymerase chain reaction. Although similar proportions of patients with and without complex ventricular arrhythmia showed 18 F-FDG and 68 Ga-DOTATOC uptake, 68 Ga-DOTATOC corrected SUV max was higher in patients with complex arrhythmia (3.4 vs 1.7; P = .046), suggesting that inflammation could be associated with the presence of malignant arrhythmia in the late stages of CHD. We also detected Trypanosoma cruzi in both groups, with a nonsignificant trend of increased parasitemia in the group with malignant arrhythmia (66.7% vs 33.3%)., Conclusion: 18 F-FDG and 68 Ga-DOTATOC uptake on PET/CT may be useful for the detection of myocardial inflammation in patients with Chagas cardiomyopathy, and 68 Ga-DOTATOC uptake may be associated with the presence of malignant arrhythmia, with potential therapeutic implications., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Background: Sudden cardiac death (SCD) can be the first clinical event of Chagas heart disease (CHD). However, current guidelines contain no clear recommendation for early cardioverter-defibrillator implantation. Using imaging modalities, we evaluated associations among autonomic denervation, myocardial hypoperfusion, fibrosis and ventricular arrhythmia in CHD., Methods and Results: Twenty-nine patients with CHD and preserved left ventricular function underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy, 99mTc-methoxyisobutylisonitrile (MIBI) myocardial perfusion and cardiac magnetic resonance imaging (MRI). They were divided into arrhythmic (≥ 6 ventricular premature complexes/h and/or non-sustained ventricular tachycardia on 24-hour Holter, n = 15) and non-arrhythmic (< 6 ventricular premature complexes/h and no ventricular tachycardia; n = 14) groups. The arrhythmic group had higher denervation scores from MIBG imaging (23.2 ± 18.7 vs 5.6 ± 4.9; P < .01), hypoperfusion scores from MIBI SPECT (4.7 ± 6.8 vs 0.29 ± 0.6: P = .02), innervation/perfusion mismatch scores (18.5 ± 17.5 vs 5.4 ± 4.8; P = .01) and fibrosis by late gadolinium enhancement on MRI (14.3% ± 13.5% vs 4.0% ± 2.9%; P = .04) than the non-arrhythmic group., Conclusion: These imaging parameters were associated with ventricular arrhythmia in early CHD and may enable risk stratification and the implementation of primary preventive strategies for SCD., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Purpose: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated., Methods: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury., Results: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8 + CD38 + mean fluorescence intensity (MFI), and percentage of CD8 + human leukocyte antigen DR isotope (HLA-DR) + CD38 - cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A) + MFI, percentage of CD8 + CD38 + cells, CD8 + HLA-DR + MFI, CD8 + NKG2A + MFI, and percentage of CD8 + HLA-DR - CD38 + cells. On multivariate regression, the CD8 + HLA-DR + MFI, CD8 + CD38 + MFI, and total lymphocyte count were associated significantly with myocardial injury., Conclusion: Our findings suggest that lymphopenia, CD8 + CD38 + MFI, and CD8 + HLA-DR + MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Conflicts of interest 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. X.J., P.W. and J.B. are Co-Editors in Chief of Neuroprotection, S.L. is the journal’s managing editor. All other authors are members of the editorial board. They were blinded from reviewing or making decisions on the manuscript. The article was subject to the journal’s standard procedures, with peer review handled independently of this Editorial Board member and their research groups. P.W. is a founder and holds equity IntraArt, LLC. Ti-com, LLC.

Dendritic cells (DCs) have a role in the development and activation of self-reactive pathogenic T cells 1,2 . Genetic variants that are associated with the function of DCs have been linked to autoimmune disorders 3,4 , and DCs are therefore attractive therapeutic targets for such diseases. However, developing DC-targeted therapies for autoimmunity requires identification of the mechanisms that regulate DC function. Here, using single-cell and bulk transcriptional and metabolic analyses in combination with cell-specific gene perturbation studies, we identify a regulatory loop of negative feedback that operates in DCs to limit immunopathology. Specifically, we find that lactate, produced by activated DCs and other immune cells, boosts the expression of NDUFA4L2 through a mechanism mediated by hypoxia-inducible factor 1α (HIF-1α). NDUFA4L2 limits the production of mitochondrial reactive oxygen species that activate XBP1-driven transcriptional modules in DCs that are involved in the control of pathogenic autoimmune T cells. We also engineer a probiotic that produces lactate and suppresses T cell autoimmunity through the activation of HIF-1α-NDUFA4L2 signalling in DCs. In summary, we identify an immunometabolic pathway that regulates DC function, and develop a synthetic probiotic for its therapeutic activation., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background  Intracerebral hemorrhage is the most serious complication of anticoagulant therapy but the effects of different types of oral anticoagulants on the expansion of these hemorrhages are still unclear. Clinical studies have revealed controversial results; more robust and long-term clinical evaluations are necessary to define their outcomes. An alternative is to test the effect of these drugs in experimental models of intracerebral bleeding induced in animals. Aims  To test new oral anticoagulants (dabigatran etexilate, rivaroxaban, and apixaban) in an experimental model of intracerebral hemorrhage induced by collagenase injection into the brain striatum of rats. Warfarin was used for comparison. Methods  Ex vivo anticoagulant assays and an experimental model of venous thrombosis were employed to determine the doses and periods of time required for the anticoagulants to achieve their maximum effects. Subsequently, volumes of brain hematoma were evaluated after administration of the anticoagulants, using these same parameters. Volumes of brain hematoma were evaluated by magnetic resonance imaging, H&E (hematoxylin and eosin) staining, and Evans blue extravasation. Neuromotor function was assessed by the elevated body swing test. Results and Conclusions  The new oral anticoagulants did not increase intracranial bleeding compared with control animals, while warfarin markedly favored expansion of the hematomas, as revealed by magnetic resonance imaging and H&E staining. Dabigatran etexilate caused a modest but statistically significant increase in Evans blue extravasation. We did not observe significant differences in elevated body swing tests among the experimental groups. The new oral anticoagulants may provide a better control over a brain hemorrhage than warfarin., Competing Interests: Conflicts of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Abstact: Plant sumoylation research has seen significant advances in recent years, particularly since high-throughput proteomic strategies have enabled the discovery of more than one thousand SUMO targets. In the present chapter, we update the previously reported SUMO (small ubiquitin-related modifier) gene network (SGN) to its v4 iteration. SGN is a curated assembly of Arabidopsis thaliana genes that have been functionally associated with sumoylation, from SUMO pathway components to targets and interactors. The enclosed tutorial helps interpret and manage these datasets and details bioinformatic tools that can be used for in silico-based hypothesis generation. The latter include tools for sumoylation site prediction, comparative genomics, and gene network analysis., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: We quantified lung glycolytic metabolic activity, clinical symptoms and inflammation, coagulation, and endothelial activation biomarkers in 2019 coronavirus disease (COVID-19) pneumonia survivors., Methods: Adults previously hospitalized with moderate to severe COVID-19 pneumonia were prospectively included. Subjects filled out a questionnaire on clinical consequences, underwent chest CT and 18 F-FDG PET/CT, and provided blood samples on the same day. Forty-five volunteers served as control subjects. Analysis of CT images and quantitative voxel-based analysis of PET/CT images were performed for both groups. 18 F-FDG uptake in the whole-lung volume and in high- and low-attenuation areas was calculated and normalized to liver values. Quantification of plasma markers of inflammation (interleukin 6), d -dimer, and endothelial cell activation (angiopoietins 1 and 2, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1) was also performed., Results: We enrolled 53 COVID-19 survivors (62.3% were male; median age, 50 years). All survivors reported at least 1 persistent symptom, and 41.5% reported more than 6 symptoms. The mean lung density was greater in survivors than in control subjects, and more metabolic activity was observed in normal and dense lung areas, even months after symptom onset. Plasma proinflammatory, coagulation, and endothelial activation biomarker concentrations were also significantly higher in survivors., Conclusion: We observed more metabolic activity in areas of high and normal lung attenuation several months after moderate to severe COVID-19 pneumonia. In addition, plasma markers of thromboinflammation and endothelial activation persisted. These findings may have implications for our understanding of the in vivo pathogenesis and long-lasting effects of COVID-19 pneumonia., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no conflicts of interest. This work was supported by grants from the D'Or Institute for Research and Education, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (numbers E-26/202.751/2018, E-26/202.785/2017, E-26/203.001/2018, E-26/203.279/2017, and E-26/211.867/2016), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (numbers 02839/2017-8, 302702/2017-2, and 312410/2017-4)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Genome-wide association studies have identified risk loci linked to inflammatory bowel disease (IBD) 1 -a complex chronic inflammatory disorder of the gastrointestinal tract. The increasing prevalence of IBD in industrialized countries and the augmented disease risk observed in migrants who move into areas of higher disease prevalence suggest that environmental factors are also important determinants of IBD susceptibility and severity 2 . However, the identification of environmental factors relevant to IBD and the mechanisms by which they influence disease has been hampered by the lack of platforms for their systematic investigation. Here we describe an integrated systems approach, combining publicly available databases, zebrafish chemical screens, machine learning and mouse preclinical models to identify environmental factors that control intestinal inflammation. This approach established that the herbicide propyzamide increases inflammation in the small and large intestine. Moreover, we show that an AHR-NF-κB-C/EBPβ signalling axis operates in T cells and dendritic cells to promote intestinal inflammation, and is targeted by propyzamide. In conclusion, we developed a pipeline for the identification of environmental factors and mechanisms of pathogenesis in IBD and, potentially, other inflammatory diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

Grafting is the preferred treatment for severe skin burns. Frequently, allogeneic tissue is the only transient option for wound coverage, but their use risks damage to surrounding tissues. MicroRNAs have been associated with acute rejection of different tissues/organs. In this study, we analyzed the expression of miR-31, miR-155, and miR-221 and associate it with graft tolerance or rejection using a murine full-thickness skin transplantation model. Recipient animals for the syngeneic and allogeneic groups were BALB/c and C57BL/6 mice, respectively; donor tissues were obtained from BALB/c mice. After 7 days posttransplantation (DPT), the recipient skin and grafts in the syngeneic group maintained most of their structural characteristics and transforming growth factor (TGF)-β1 and TGF-β3 expression. Allografts were rejected early (Banff grades II and IV at 3 and 7 DPT, respectively), showing damage to the skin architecture and alteration of TGF-β3 distribution. miRNAs skin expression changed in both mouse strains; miR-31 expression increased in the recipient skin of syngeneic grafts relative to that of allogeneic grafts at 3 and 7 DPT (P < .05 and P < .01, respectively); miR-221 expression increased in the same grafts at 7 DPT (P < .05). The only significant difference between donor tissues was observed for miR-155 expression at 7 DPT which was associated with necrotic tissue. Only miR-31 and miR-221 levels were increased in the blood of BALB/c mice that received syngeneic grafts after 7 DPT. Our data suggest that local and systemic miR-31 and miR-221 overexpression are associated with graft tolerance., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The zinc deficiency response in Arabidopsis thaliana is regulated by F-group basic region leucine-zipper (F-bZIP) transcription factors, and there is evidence of evolutionary conservation of this regulatory network in land plants. Fundamental knowledge on the zinc homeostasis regulation in crop species will contribute to improving their zinc nutritional value. Legumes are protein-rich crops, used worldwide as part of traditional diets and as animal forage, being therefore a good target for micronutrient biofortification. Here, we identified F-bZIP transcription factors in representative legume species and functionally characterized the two F-bZIPs from Medicago truncatula . Results indicate that MtFbZIP1 is the functional homolog of A. thaliana bZIP19 and bZIP23, while MtFbZIP2 does not play a role in the zinc deficiency response. Additionally, analysis of M. truncatula genes from the Zrt/Irt-like protein (ZIP) family of zinc transporters or encoding nicotianamine synthase enzymes that produce the zinc ligand nicotianamine, support the conservation of the F-bZIP-regulated zinc deficiency response in M. truncatula . Phylogenetic analysis of F-bZIP homologs enriched in legume species reinforces the branching into two groups, with MtFbZIP1 and MtFbZIP2 mapping in Groups 1 and 2, respectively. This phylogeny combined with the functional characterization of MtFbZIPs supports the suggested conservation of the zinc deficiency response associated with Group 1 F-bZIPs, and the more variable evolutionary paths associated with Group 2. Overall, we provide novel insight on the mechanisms of response to zinc deficiency in M. truncatula , which contributes to developing strategies for improving zinc content in legume crops., 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 Liao, Lilay, Castro, Azevedo and Assunção.)

The ubiquitin-like modifying peptide SMALL UBIQUITIN-LIKE MODIFIER (SUMO) has become a known modulator of the plant response to multiple environmental stimuli. A common feature of many of these external stresses is the production of reactive oxygen species (ROS). Taking into account that SUMO conjugates rapidly accumulate in response to an external oxidative stimulus, it is likely that ROS and sumoylation converge at the molecular and regulatory levels. In this study, we explored the SUMO-ROS relationship, using as a model the Arabidopsis (Arabidopsis thaliana) null mutant of the major SUMO-conjugation enhancer, the E3 ligase SAP AND MIZ 1 (SIZ1). We showed that SIZ1 is involved in SUMO conjugate increase when primed with both exogenous and endogenous ROS. In siz1, seedlings were sensitive to oxidative stress imposition, and mutants accumulated different ROS throughout development. We demonstrated that the deregulation in hydrogen peroxide and superoxide homeostasis, but not of singlet O2 (1O2), was partially due to SA accumulation in siz1. Furthermore, transcriptomic analysis highlighted a transcriptional signature that implicated siz1 with 1O2 homeostasis. Subsequently, we observed that siz1 displayed chloroplast morphological defects and altered energy dissipation activity and established a link between the chlorophyll precursor protochlorophyllide and deregulation of PROTOCHLOROPHYLLIDE OXIDOREDUCTASE A (PORA), which is known to drive overproduction of 1O2. Ultimately, network analysis uncovered known and additional associations between transcriptional control of PORA and SIZ1-dependent sumoylation. Our study connects sumoylation, and specifically SIZ1, to the control of chloroplast functions and places sumoylation as a molecular mechanism involved in ROS homeostatic and signaling events., (© American Society of Plant Biologists 2022. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tuberculosis (TB) remains one of the world's leading infectious cause of morbidity and mortality. Positron emission tomography (PET) associated with computed tomography (CT) allows a structural and metabolic evaluation of TB lesions, being an excellent noninvasive alternative for understanding its pathogenesis. DOTATOC labeled with gallium-68 (68Ga-DOTATOC) can bind to somatostatin receptors present in activated macrophages and lymphocytes, cells with a fundamental role in TB pathogenesis. We describe 68Ga-DOTATOC uptake distribution and patterns in thoracic lymph nodes (LN) and pulmonary lesions (PL) in immunocompetent patients with active postprimary TB, analyze the relative LN/PL uptake, and compare this two tracer's uptake. High uptake of both radiotracers in PL and LN was demonstrated, with higher LN/PL ratio on 68Ga-DOTATOC (P < 0.05). Considering that LN in immunocompetent patients are poorly studied, 68Ga-DOTATOC can contribute to the understanding of the complex immunopathogenesis of TB.

Aim: Intracerebral hemorrhage (ICH) has limited therapeutic options. We have shown that an intravenous injection of human umbilical cord-derived mesenchymal stromal cells (hUC-MSC) 24 h after an ICH in rats reduced the residual hematoma volume after a moderate hemorrhage but was inefficient in severe ICH. Here, we investigated whether a treatment in the hyperacute phase would be more effective in severe ICH., Materials & Methods: Wistar rats were randomly selected to receive an intravenous injection of hUC-MSC or the vehicle 1 h after a severe ICH., Results: The hyperacute treatment with hUC-MSC did not affect the 22-day survival rate, the motor function or the residual hematoma volume., Conclusion: These results indicate the need for optimization of hUC-MSC-based therapies for severe ICH., Competing Interests: Financial & competing interests disclosure This work was supported by the Departamento de Ciência e Tecnologia (DECIT) do Ministério da Saúde and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq: 402319/2013-3), the Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES: 88887.136364/2017-00, 88887.199249/2018-00; and PROBITEC: 2262/2012 – 23038.004161/2018-88), and the Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ; E-26/010.002487/2016, Edital 19/2016). The authors also thank the Brazilian funding sources (CAPES, CNPq and FAPERJ) for granting scholarships that made this study possible. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2022 The Authors.)

Grapevine ( Vitis vinifera L.) diversity richness results from a complex domestication history over multiple historical periods. Here, we used whole-genome resequencing to elucidate different aspects of its recent evolutionary history. Our results support a model in which a central domestication event in grapevine was followed by postdomestication hybridization with local wild genotypes, leading to the presence of an introgression signature in modern wine varieties across Western Europe. The strongest signal was associated with a subset of Iberian grapevine varieties showing large introgression tracts. We targeted this study group for further analysis, demonstrating how regions under selection in wild populations from the Iberian Peninsula were preferentially passed on to the cultivated varieties by gene flow. Examination of underlying genes suggests that environmental adaptation played a fundamental role in both the evolution of wild genotypes and the outcome of hybridization with cultivated varieties, supporting a case of adaptive introgression in grapevine.

Coronavirus disease 2019 (COVID-19) pathology is associated with neoangiogenesis and interstitial pneumonia. 68 Ga-PSMA-11-PET/CT is able to image in vivo PSMA (Prostate-Specific Membrane Antigen) expression on both prostate cancer (PCa) cells and neovasculature endothelial cells. The aim of the case series was to explore pulmonary PSMA expression not related to cancer in patients with PCa and concomitant COVID-19. In this retrospective, multicenter case series, patients who underwent 68 Ga-PSMA-11-PET/CT for PCa and concomitant proven COVID-19 infection were analyzed. Patients were stratified according to 68 Ga-PSMA-11 intensity of uptake in the lung (SUV max ). Low uptake: < blood pool; mild-to-moderate uptake: > blood pool and < liver; intense uptake: > liver. Potential correlation between pulmonary 68 Ga-PSMA-11 uptake not related to PCa and CT patterns typical for COVID-19 was assessed. Nine patients were included, all of them presenting abnormal 68 Ga-PSMA-11 uptake, at different grades: 2/9 low, 6/9 mild-to-moderate, 1/9 high. Uptake distribution was generally bilateral, peripheral and posterior, positively matching with ground-glass CT alterations in 7/9 (78%) patients, while mismatch was observed in 2/9 (22%). 1/9 patients presented PCa lung metastases at 68 Ga-PSMA-11. 68 Ga-PSMA-11-PET/CT detected increased PSMA uptake within the lung, not related to PCa, matching with CT typical COVID-19 patterns in almost all patients. Further studies are needed to evaluate the role of 68 Ga-PSMA-11 PET in COVID-19 patients and the potential role of PSMA overexpression as a biomarker for neoangiogenesis, in both oncological and infective disorders., Competing Interests: None., (AJNMMI Copyright © 2021.)

Dendritic cells (DCs) are potent antigen-presenting cells (APCs), which sample the exogenous and endogenous cues to control adaptive immunity, balancing effector and regulatory components of the immune response. Multiple subsets of DCs, such as plasmacytoid and conventional DCs, have been defined based on specific phenotypic markers, functions and regulatory transcriptional programs. Tolerogenic DCs (tolDCs) have been functionally defined based on their ability to expand the regulatory T-cell compartment and suppress immune responses. However, it is still unclear whether tolDCs represent a homogeneous population, a specific DC subset and/or a heterogeneous collection of DC activation/maturation states. The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) has been shown to control transcriptional programs associated to tolDCs. In this review, we discuss the role of AHR in the control of tolDCs, and also AHR-targeted approaches for the therapeutic induction of tolDCs in autoimmune diseases and allergy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cell-cell interactions control the physiology and pathology of the central nervous system (CNS). To study astrocyte cell interactions in vivo, we developed rabies barcode interaction detection followed by sequencing (RABID-seq), which combines barcoded viral tracing and single-cell RNA sequencing (scRNA-seq). Using RABID-seq, we identified axon guidance molecules as candidate mediators of microglia-astrocyte interactions that promote CNS pathology in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis (MS). In vivo cell-specific genetic perturbation EAE studies, in vitro systems, and the analysis of MS scRNA-seq datasets and CNS tissue established that Sema4D and Ephrin-B3 expressed in microglia control astrocyte responses via PlexinB2 and EphB3, respectively. Furthermore, a CNS-penetrant EphB3 inhibitor suppressed astrocyte and microglia proinflammatory responses and ameliorated EAE. In summary, RABID-seq identified microglia-astrocyte interactions and candidate therapeutic targets., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor initially identified as the receptor for dioxin. Almost half a century after its discovery, AHR is now recognized as a receptor for multiple physiological ligands, with important roles in health and disease. In this review, we discuss the role of AHR in the gut-brain axis and its potential value as a therapeutic target for immune-mediated diseases.

Zinc (Zn) is an essential micronutrient for plants and animals owing to its structural and catalytic roles in many proteins 1 . Zn deficiency affects around 2 billion people, mainly those who live on plant-based diets relying on crops from Zn-deficient soils 2,3 . Plants maintain adequate Zn levels through tightly regulated Zn homeostasis mechanisms involving Zn uptake, distribution and storage 4 , but evidence of how they sense Zn status is lacking. Here, we use in vitro and in planta approaches to show that the Arabidopsis thaliana F-group bZIP transcription factors bZIP19 and bZIP23, which are the central regulators of the Zn deficiency response, function as Zn sensors by binding Zn 2+ ions to a Zn-sensor motif. Deletions or modifications of this Zn-sensor motif disrupt Zn binding, leading to a constitutive transcriptional Zn deficiency response, which causes a significant increase in plant and seed Zn accumulation. As the Zn-sensor motif is highly conserved in F-group bZIP proteins across land plants, the identification of this plant Zn sensor will promote new strategies to improve the Zn nutritional quality of plant-derived food and feed, and contribute to tackling the global Zn-deficiency health problem.

The F-bZIP transcription factors bZIP19 and bZIP23 are the central regulators of the zinc deficiency response in Arabidopsis, and phylogenetic analysis of F-bZIP homologs across land plants indicates that the regulatory mechanism of the zinc deficiency response may be conserved. Here, we identified the rice F-bZIP homologs and investigated their function. OsbZIP48 and OsbZIP50, but not OsbZIP49, complement the zinc deficiency-hypersensitive Arabidopsis bzip19bzip23 double mutant. Ectopic expression of OsbZIP50 in Arabidopsis significantly increases plant zinc accumulation under control zinc supply, suggesting an altered Zn sensing in OsbZIP50. In addition, we performed a phylogenetic analysis of F-bZIP homologs from representative monocot species that supports the branching of plant F-bZIPs into Group 1 and Group 2. Our results suggest that regulation of the zinc deficiency response in rice is conserved, with OsbZIP48 being a functional homolog of AtbZIP19 and AtbZIP23. A better understanding of the mechanisms behind the Zn deficiency response in rice and other important crops will contribute to develop plant-based strategies to address the problems of Zn deficiency in soils, crops, and cereal-based human diets., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.)

Chronic Chagas' cardiomyopathy is the most severe and frequent manifestation of Chagas disease, and has a high social and economic burden. New imaging modalities, such as strain echocardiography, nuclear medicine, computed tomography and cardiac magnetic resonance imaging, may detect the presence of myocardial fibrosis, inflammation or sympathetic denervation, three conditions associated with risk of sudden death, providing additional diagnostic and/or prognostic information. Unfortunately, despite its high mortality, there is no clear recommendation for early cardioverter-defibrillator implantation in patients with Chagas heart disease in the current guidelines. Ideally, the risk of sudden cardiac death may be evaluated in earlier stages of the disease using new image methods to allow the implementation of primary preventive strategies.

Intracerebral hemorrhage (ICH) is as a life-threatening condition that can occur in young adults, often causing long-term disability. Recent preclinical data suggest mesenchymal stromal cell (MSC)-based therapies as promising options to minimize brain damage after ICH. However, therapeutic evidence and mechanistic insights are still limited, particularly when compared with other disorders such as ischemic stroke. Herein, we employed a model of collagenase-induced ICH in young adult rats to investigate the potential therapeutic effects of an intravenous injection of human umbilical cord Wharton's jelly-derived MSCs (hUC-MSCs). Two doses of collagenase were used to cause moderate or severe hemorrhages. Magnetic resonance imaging showed that animals treated with hUC-MSCs after moderate ICH had smaller residual hematoma volumes than vehicle-treated rats, whereas the cell therapy failed to decrease the hematoma volume in animals with a severe ICH. Functional assessments (rotarod and elevated body swing tests) were performed for up to 21 days after ICH. Enduring neurological impairments were seen only in animals subjected to severe ICH, but the cell therapy did not induce statistically significant improvements in the functional recovery. The biodistribution of Technetium-99m-labeled hUC-MSCs was also evaluated, showing that most cells were found in organs such as the spleen and lungs 24 h after transplantation. Nevertheless, it was possible to detect a weak signal in the brain, which was higher in the ipsilateral hemisphere of rats subjected to a severe ICH. These data indicate that hUC-MSCs have moderately beneficial effects in cases of less severe brain hemorrhages in rats by decreasing the residual hematoma volume, and that optimization of the therapy is still necessary.

Peripheral blood mononuclear cells (PBMCs) contain a cell fraction of mononuclear progenitor cells (MPCs), which own significant angiogenic potential. Autologous transplant of PBMC and/or platelet-rich plasma (PRP) promotes endothelial cells differentiation in experimental lower limb ischemia, which is considered a safe and effective strategy to support revascularization, either in animal models or clinical trials. In addition, thrombin has been proposed to enrich biological scaffolds, hence increasing MPC viability after intramuscular administration, whereas proangiogenic mediators such as vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-α), inhibitor of the plasminogen activator-1 (PAI-1), and chemokine (CXCL1; GRO-α) participate in the endothelial response to ischemia, through their proangiogenic effects over endothelial cells proliferation, survival, migration, endothelial integrity maintenance, and physiologic vascular response to injury. In the present study, we describe the effect of autologous PBMCs transplant and PRP, either with or without thrombin, over proangiogenic mediators (measured by enzyme-linked immunosorbent assay) and revascularization response (angiographic vascular pattern at 30 days after vascular occlusion) in a rat model of lower limb ischemia. The group treated with PBMC + PRP significantly induced PAI-1, an effect that was prevented by the addition of thrombin. Furthermore, treatment with PBMC + PRP + thrombin resulted in the induction of VEGF. GRO-α showed a sensitive induction of all proangiogenic mediators. All treatments significantly stimulated revascularization, according to angiographic assessment, whereas higher effect was observed with PBMC + PRP treatment (p < .0001). In conclusion, autologous PBMC transplant stimulates revascularization during experimental ischemia of the lower limb, whereas particular effects over proangiogenic and fibrinolytic mediators may be attributed to PBMCs and its combination with PRP and thrombin., (© 2020 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.)

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.

All living organisms require zinc as an essential micronutrient. Maintaining appropriate intracellular zinc supply, and avoiding deficiency or toxic excess, requires a tight regulation of zinc homeostasis. In Arabidopsis, bZIP19 and bZIP23 (basic-leucine zipper) transcription factors are the central regulators of the zinc deficiency response. Their targets include members of the ZIP (Zrt/Irt-like Protein) transporter family, involved in cellular zinc uptake, which are up-regulated at zinc deficiency. However, the mechanisms by which these transcription factors are regulated by cellular zinc status are not yet known. Here, to further our insight, we took advantage of the zinc deficiency hypersensitive phenotype of the bzip19 bzip23 double mutant, and used it as background to produce complementation lines of each Arabidopsis F-bZIP transcription factor, including bZIP24. On these lines, we performed complementation and localization studies, analyzed the transcript level of a subset of putative target genes, and performed elemental tissue profiling. We find evidence supporting that the zinc-dependent activity of bZIP19 and bZIP23 is modulated by zinc at protein level, in the nucleus, where cellular zinc sufficiency represses their activity and zinc deficiency is required. In addition, we show that these two transcription factors are functionally redundant to a large extent, and that differential tissue-specific expression patterns might, at least partly, explain distinct regulatory activities. Finally, we show that bZIP24 does not play a central role in the Zn deficiency response. Overall, we provide novel information that advances our understanding of the regulatory activity of bZIP19 and bZIP23.