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Calcium silicate-based sealers are bioactive materials that release ions when in contact with body fluids. Therefore, this study aims mapping/trace bone formation markers released by MTA Fillapex, BioRoot RCS, and experimental tricalcium silicate-based sealer (CEO) into subcutaneous tissues, bloodstream and body organs. Toward, polyethylene tubes filled with sealers were implanted into connective tissue of Wistar rats. On days 7, 15, 30, and 45 after implantation, blood samples were collected to measure calcium (Ca2+), phosphorus (P), and alkaline phosphatase (ALP) levels. Thereafter, the animals were killed, and the brain, liver, kidneys, and subcutaneous tissue were removed and processed to determine the concentrations of Ca2+ and P by ICP-OES. Similar Ca2+ levels were observed in subcutaneous tissue for all groups, although, at 45 days, it was identified a reduction in Ca2+ serum levels of CEO compared to those two other sealers and an increase in Ca2+ levels in the liver compared to those released by MTA Fillapex. In contrast, no trace of P was detected in any tissue; moreover, plasma P and ALP serum levels of MTA Fillapex were higher at day 30. Our findings showed that Ca2+ were identified in local tissues, bloodstream, and organs from all sealers. The up-regulation of bone marker levels promoted by sealers can modify body homeostasis and induce tissue damage. Besides, MTA Fillapex was associated with a raise of bone marker levels, suggesting a possible systemic effect. The sealer composition can affect not only the local repair process but also the systemic health.

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High-dose conditioning chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic sclerosis (SSc), lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), or rheumatoid arthritis (RA) was shown to allow eradication of the abnormal autoimmune compartment and "resetting" of the immune response, all contributing to the observed clinical response. A subset of patients has less favorable clinical outcomes after transplant, as auto-reactive memory cells may escape depletion or the regulatory immune network renewal be incomplete. Conditioning permits non-specific abrogation of the autoreactive T- and B-cell responses and eliminates the autoimmune repertoire. Re-infusion of autologous hematopoietic stem cells shortens the leucopenia duration and contributes to both hematologic and immune reconstitutions. After engraftment and neutrophil recovery, the first phase of immune reconstitution is characterized by clonal expansion of residual memory lymphocytes in response to early antigen stimulation and/or lymphopenia-induced proliferation. Renewal of the immune repertoire follows through exportation of de novo generated thymic-derived naïve T cells and bone marrow-derived naïve B cells, expansion of the regulatory network, and a shift from a pro-inflammatory to a more auto-tolerant profile. We review the well-described mechanisms of immune resetting and their relative contribution to disease control according to the transplantation regimen and the underlying rheumatic diseases.

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BACKGROUND: Systemic sclerosis (SSc) is a rare chronic autoimmune disease with heterogeneous manifestations. In the last decade, several clinical trials have been conducted to evaluate new treatment options for SSc. The purpose of this work is to update the recommendations of the Brazilian Society of Rheumatology in light of the new evidence available for the pharmacological management of SSc. METHODS: A systematic review including randomized clinical trials (RCTs) for predefined questions that were elaborated according to the Patient/Population, Intervention, Comparison, and Outcomes (PICO) strategy was conducted. The rating of the available evidence was performed according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. To become a recommendation, at least 75% agreement of the voting panel was needed. RESULTS: Six recommendations were elaborated regarding the pharmacological treatment of Raynaud's phenomenon, the treatment (healing) and prevention of digital ulcers, skin involvement, interstitial lung disease (ILD) and gastrointestinal involvement in SSc patients based on results available from RCTs. New drugs, such as rituximab, were included as therapeutic options for skin involvement, and rituximab, tocilizumab and nintedanib were included as therapeutic options for ILD. Recommendations for the pharmacological treatment of scleroderma renal crisis and musculoskeletal involvement were elaborated based on the expert opinion of the voting panel, as no placebo-controlled RCTs were found. CONCLUSION: These guidelines updated and incorporated new treatment options for the management of SSc based on evidence from the literature and expert opinion regarding SSc, providing support for decision-making in clinical practice.

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INTRODUCTION: The purpose of this study was to evaluate whether the mixing method of AH Plus Jet sealer affects its physicochemical and mechanical properties. METHODS: The properties of AH Plus Jet sealer were analyzed when mixed using either the Auto Mix Tip or manual mixing. The evaluated properties included radiopacity (n = 5), initial and final setting times (n = 5), flow (n = 5), and solubility (n = 3), following specifications outlined in ISO 6876/2012 and ADA Nº 57/2000. pH levels were measured at intervals of 3, 24, 72, and 168 hours (n = 10). The push-out bond strength test was conducted using a universal testing machine and using bovine teeth (n = 30). Failure modes were analyzed with stereomicroscopy. Porosity was evaluated under micro-CT (n = 5), and scanning electron microscopy was also performed (n = 5). One-way analysis of variance and Tukey, unpaired t-tests, or Mann-Whitney tests were used with a significance level of 5%. RESULTS: The Auto Mix exhibited a radiopacity value of 12.11 mmAl, whereas manual mixing resulted in 12.55 mmAl (P > .05). For initial and final setting times, Auto Mix showed 901 minutes and 1779 minutes, respectively, while manual mixing recorded values of 631 minutes and 1504 minutes (P < .05). In terms of flow, Auto Mix demonstrated higher values (25.26 mm) than manual mixing (21.71 mm) (P < .05). No statistical differences were observed between the two methods for solubility and pH (P > .05). Manual mixing presented a higher bond strength value (14.52 MPa) than Auto Mix (9.81 MPa) (P < .05). The mixed failure mode was the most frequent outcome for both methods. The highest porosity was observed for Auto Mix (P < .05). Scanning electron microscopy analysis revealed that manual mixing resulted in a smoother surface with fewer pores and smaller, more evenly distributed agglomerates compared to automatic mixing. CONCLUSION: The mixing method employed for AH Plus Jet sealer influences some physicochemical and mechanical properties of the material.

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This study aimed to investigate the effect of age at weaning of calves on non-esterified fatty acids (NEFA) and reproductive parameters of beef cows. Animals (n = 65) were randomly assigned to three treatments after calving: hyper-early weaning (W30) at 32 ± 0.89 days, early weaning (W75) at 77 ± 0.95 days, and conventional weaning (W180) at 183 ± 0.82 days. Body weight (BW) and body condition score (BCS) were evaluated at parturition (AP) and at 30, 45, 64, 81, 100 and 115 days postpartum (dPP). Blood samples were collected to analyze NEFA levels and progesterone (P4) at 30, 45, 64 and 81 dPP. Higher BW and BCS were observed from 64 to 115 dPP in W30 cows than W180 ones (p < 0.05). Cows subjected to W30 condition had higher levels of NEFA at 30 dPP compared to 64 and 81 dPP (p < 0.05). We also observed that cows from W180 group showed decreased levels of NEFA at 30 dPP compared to 45 (p < 0.01) and 64 dPP (p < 0.05). The highest P4 level was observed at 64 dPP in W30 cows compared to W75 and W180 (p < 0.05). We also observed higher CR of W30 (86%) compared to W180 (47%) at 45 dPP (p < 0.05). The overall pregnancy rate (PR) was higher for W30 (95.5%) than W180 (73.9%). In addition, higher BW at calving and P4 levels at 30 dPP were positively correlated with the possibility of pregnancy (p < 0.05). Improvement in BW and BCS were observed in cows subjected to hyper-early weaning management. However, levels of NEFA decreased as the postpartum period progressed. We concluded that cows who weaned calves hyper-early have greater chances of increasing cyclicity and PRs.

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presente revisão visa sumarizar os estudos que abordam o uso de fitocanabinóides em pacientes com doenças neuropsiquiátricas, abordando os benefícios e possíveis efeitos adversos que podem ser observados. Foi realizada uma revisão integrativa de literatura com descritores MeSH: Cannabis, Medical Marijuana, Neurology, Neuropsychiatry e as bases de dados: PubMed, MEDLINE, CINAHL, SCOPUS, Web of Science e SciELO. Selecionou-se artigos entre 2015 a 2021 utilizando como critérios de inclusão, artigos que abordassem sobre o uso de fitocanabinoides em pacientes com doenças neurológicas e/ou psiquiátricas, disponíveis integralmente nos bancos de dados sem restrição de idioma. Após análise, foram encontrados 15 artigos, que evidenciaram benefícios como: propriedades ansiolíticas, antiepilépticas, antiparkinsonianas, antipsicóticas, de estabilização de humor, além de ser benéfico na regulação do sono, na Síndrome de Tourette, na demência, dores crônicas, amenização de sintomas eméticos dos tratamentos oncológicos e da espasticidade na esclerose múltipla, no TEPT e no autismo. Além disso, os fitocanabinoides parecem ter propriedades anti-inflamatórias e de neuroproteção. Entretanto, efeitos colaterais também foram observados, sendo os principais: piora no desempenho em testes cognitivos, sintomas gastrointestinais, sonolência, agitação, piora de alguns transtornos psiquiátricos, diminuição da concentração, aumento da ansiedade social, bem como boca e olhos secos. Conclui-se portanto que os fitocanabinóides podem apresentar ação terapêutica benéfica no tratamento de condições neuropsiquiátricas, tratamento de doenças neurodegenerativas, propriedades anti-inflamatórias e neuroprotetoras e tratamento de dores crônicas, entretanto devem ser considerados e monitorados os efeitos adversos em cada paciente.

This review aims to summarize the studies that address the use of phytocannabinoids in patients with neuropsychiatric diseases, addressing the benefits and possible adverse effects that can be observed. An integrative literature review was conducted with MeSH descriptors: Cannabis, Medical Marijuana, Neurology, Neuropsychiatry and the databases: PubMed, MEDLINE, CINAHL, SCOPUS, Web of Science and SciELO. Articles were selected between 2015 and 2021 using as inclusion criteria articles that addressed the use of phytocannabinoids in patients with neurological and/or psychiatric diseases, available in full in the databases without language restriction. After analysis, 15 articles were found, which showed benefits such as: anxiolytic, antiepileptic, antiparkinsonian, antipsychotic, mood stabilization properties, besides being beneficial in sleep regulation, Tourette's syndrome, dementia, chronic pain, mitigation of emetic symptoms of cancer treatments and spasticity in multiple sclerosis, PTSD and autism. In addition, phytocannabinoids appear to have anti-inflammatory and neuroprotective properties. However, side effects have also been observed, the main ones being: worsening performance in cognitive tests, gastrointestinal symptoms, drowsiness, agitation, worsening of some psychiatric disorders, decreased concentration, increased social anxiety, as well as dry mouth and eyes. Therefore, it is concluded that phytocannabinoids may present beneficial therapeutic action in the treatment of neuropsychiatric conditions, treatment of neurodegenerative diseases, anti-inflammatory and neuroprotective properties and treatment of chronic pain, however, the adverse effects in each patient should be considered and monitored.

Esta revisión tiene como objetivo resumir los estudios que abordan el uso de fitocanabinoides en pacientes con enfermedades neuropsiquiátricas, abordando los beneficios y posibles efectos adversos que pueden observarse. Se realizó una revisión integral de la literatura con los descriptores de MeSH: Cannabis, Medical Marijuana, Neurology, Neuropsychiatry y las bases de datos: PubMed, MEDLINE, CINAHL, SCOPUS, Web of Science y SciELO. Se seleccionaron artículos entre 2015 y 2021, utilizando como criterios de inclusión artículos que abordaban el uso de fitocanabinoides en pacientes con enfermedades neurológicas y/o psiquiátricas, disponibles enteramente en las bases de datos sin restricción lingüística. Después del análisis se encontraron 15 artículos que mostraron beneficios tales como: propiedades ansiolíticas, antiepilépticas, antiparkinsonianas, antipsicóticas, estabilizadoras del estado de ánimo, además de ser beneficiosos para regular el sueño, en el síndrome de Tourette, en demencia, dolor crónico, alivio de los síntomas eméticos de los tratamientos contra el cáncer y de la espasticidad en esclerosis múltiple, TEPT y autismo. Además, los fitobarabinoides parecen tener propiedades antiinflamatorias y neuroprotectoras. Sin embargo, también se observaron efectos adversos, siendo los principales: empeoramiento del desempeño en las pruebas cognitivas, síntomas gastrointestinales, somnolencia, agitación, empeoramiento de algunos trastornos psiquiátricos, disminución de la concentración, aumento de la ansiedad social, así como sequedad de boca y ojos. Por lo tanto, se concluye que los fitocanabinoides pueden tener una acción terapéutica beneficiosa en el tratamiento de las afecciones neuropsiquiátricas, el tratamiento de las enfermedades neurodegenerativas, las propiedades antiinflamatorias y neuroprotectoras y el tratamiento del dolor crónico, sin embargo, se deben considerar y monitorizar los efectos adversos en cada paciente.

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Abstract The aim of this study was to investigate the physicochemical and biological properties of an experimental tricalcium silicate-based repair cement containing diclofenac sodium (CERD). For the physicochemical test, MTA, Biodentine and CERD were mixed and cement disc were prepared to evaluate the setting time and radiopacity. Root-end cavity were performed in acrylic teeth and filled with cements to analyze the solubility up to 7 days. Polyethylene tubes containing cements were prepared and calcium ions and pH were measured at 3h, 24h, 72h and 15 days. For the biological test, SAOS-2 were cultivated, exposed to cements extracts and cell proliferation were investigated by MTT assay at 6h, 24h and 48h. Polyethylene tubes containing cements were implanted into Wistar rats. After 7 and 30 days, the tubes were removed and processed for histological analyses. Parametric and nonparametric data were performed. No difference was identified in relation to setting time, radiopacity and solubility. Biodentine released more calcium ion than MTA and CERD; however, no difference between MTA and CERD were detected. Alkaline pH was observed for all cements and Biodentine exhibited highest pH. All cements promoted a raise on cell proliferation at 24h and 48h, except CERD at 48h. Biodentine stimulated cell metabolism in relation to MTA and CERD while CERD was more cytotoxic than MTA at 48h. Besides, no difference on both inflammatory response and mineralization ability for all cement were found. CERD demonstrated similar proprieties to others endodontic cements available.

Resumo O objetivo deste estudo foi investigar as propriedades físico-químicas e biológicas de um cimento reparador experimental à base de silicato de tricálcio contendo diclofenaco de sódio (CERD). Para o teste físico-químico, MTA, Biodentine e CERD foram manipulados e discos de cimentos foram preparados para avaliar o tempo de presa e a radiopacidade. Retrocavidades foram feitas em dentes de acrílico e preenchidas com cimentos para análise de solubilidade por 7 dias. Tubos de polietileno contendo cimentos foram preparados e os íons cálcio e o pH foram mensurados às 3h, 24h, 72h e 15 dias. Para o teste biológico, SAOS-2 foram cultivadas, expostas aos extratos de cimentos e a proliferação celular foi investigada pelo ensaio de MTT às 6h, 24h e 48h. Tubos de polietileno contendo cimentos foram implantados em ratos Wistar. Após 7 e 30 dias, os tubos foram removidos e processados para análises histológicas. Dados paramétricos e não paramétricos foram realizados. Nenhuma diferença foi identificada em relação ao tempo de presa, radiopacidade e solubilidade. Biodentine liberou mais íons de cálcio do que MTA e CERD; no entanto, nenhuma diferença entre MTA e CERD foi detectada. O pH alcalino foi observado para todos os cimentos e o Biodentine exibiu o pH mais alto. Todos os cimentos promoveram aumento na proliferação celular às 24h e 48h, exceto o CERD às 48h. Biodentine estimulou o metabolismo celular em relação ao MTA e CERD, enquanto CERD foi mais citotóxico do que MTA em 48h. Além disso, nenhuma diferença foi encontrada na resposta inflamatória e na capacidade de mineralização para todos os cimentos. CERD demonstrou propriedades semelhantes a outros cimentos endodônticos disponíveis.

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Systemic sclerosis (SSc) is a chronic autoimmune disease that includes fibrosis, diffuse vasculopathy, inflammation, and autoimmunity. Autologous hematopoietic stem cell transplantation (auto-HSCT) is considered for patients with severe and progressive SSc. In recent decades, knowledge about patient management and clinical outcomes after auto-HSCT has significantly improved. Mechanistic studies have contributed to increasing the comprehension of how profound and long-lasting are the modifications to the immune system induced by transplantation. This review revisits the immune monitoring studies after auto-HSCT for SSc patients and how they relate to clinical outcomes. This understanding is essential to further improve clinical applications of auto-HSCT and enhance patient outcomes.

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Royal jelly is an essential substance for the development of bees from larval to adult stages. Studies have identified a group of key proteins in royal jelly, denominated major royal jelly proteins (MRJPs). The group currently consists of nine proteins (MRJP1-MRJP9), with MRJP1 being the most abundant and MRJP3 being used as a microsatellite marker for the selection of queens with a greater production of royal jelly. The diet of bees is mostly composed of proteins, and supplementing this intake to encourage a higher production of their primary product is important for producers. It is estimated that, by adding probiotic and prebiotic organisms to their diets, the benefits to bees will be even greater, both for their immune systems and primary responses to stress. Circumstances that are adverse compared to those of the natural habitat of bees eventually substantially interfere with bee behavior. Stress situations are modulated by proteins termed heat shock proteins (HSPs). Among these, HSP70 has been shown to exhibit abundance changes whenever bees experience unusual situations of stress. Thus, we sought to supplement A. mellifera bee colony diets with proteins and prebiotic and probiotic components, and to evaluate the expression levels of MRJP3 and HSP70 mRNAs using qRT-PCR. The results revealed that differences in the expression of MRJP3 can be attributed to the different types of feed offered. Significant differences were evident when comparing the expression levels of MRJP3 and HSP70, suggesting that protein supplementation with pre/probiotics promotes positive results in royal jelly synthesis carried out by honey bee nurses.

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The aim of this study was to investigate the physicochemical and biological properties of an experimental tricalcium silicate-based repair cement containing diclofenac sodium (CERD). For the physicochemical test, MTA, Biodentine and CERD were mixed and cement disc were prepared to evaluate the setting time and radiopacity. Root-end cavity were performed in acrylic teeth and filled with cements to analyze the solubility up to 7 days. Polyethylene tubes containing cements were prepared and calcium ions and pH were measured at 3h, 24h, 72h and 15 days. For the biological test, SAOS-2 were cultivated, exposed to cements extracts and cell proliferation were investigated by MTT assay at 6h, 24h and 48h. Polyethylene tubes containing cements were implanted into Wistar rats. After 7 and 30 days, the tubes were removed and processed for histological analyses. Parametric and nonparametric data were performed. No difference was identified in relation to setting time, radiopacity and solubility. Biodentine released more calcium ion than MTA and CERD; however, no difference between MTA and CERD were detected. Alkaline pH was observed for all cements and Biodentine exhibited highest pH. All cements promoted a raise on cell proliferation at 24h and 48h, except CERD at 48h. Biodentine stimulated cell metabolism in relation to MTA and CERD while CERD was more cytotoxic than MTA at 48h. Besides, no difference on both inflammatory response and mineralization ability for all cement were found. CERD demonstrated similar proprieties to others endodontic cements available.

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OBJECTIVE: The aim of this study was to evaluate the concordance of the diagnoses made by senior rheumatologists and those made by residents in rheumatology and by general practitioners (GPs). METHODS: In this cohort, 497 patients referred by GPs from August 1, 2018 to December 16, 2019 were evaluated first by a second-year resident in rheumatology. After clinical rounds, the diagnoses by senior rheumatologists were assumed as the criterion standard and defined the prevalence of the rheumatic diseases, divided into 5 groups: rheumatoid arthritis, spondyloarthritis, other connective tissue diseases and vasculitis, nonautoimmune rheumatic diseases, and nonrheumatic diseases. The follow-up ended on November 30, 2020. We calculated sensibility, specificity, positive predictive value, negative predictive value, and κ coefficient of the diagnosis by GPs and residents. RESULTS: The diagnoses were changed for 58% of the referral letters. Diseases of low complexity, such as fibromyalgia and osteoarthritis, accounted for 50% of the diagnoses. Compared with senior rheumatologists, residents in rheumatology had κ > 0.6 for all the groups, whereas GPs had κ < 0.5, with the worst performance for nonautoimmune rheumatic disease (κ = -0.18) and nonrheumatic disease (κ = 0.15). In terms of level of complexity, 46% of the letters were inappropriate. CONCLUSIONS: We found a poor level of diagnostic agreement between GPs and the rheumatology team. General practitioners had difficulties diagnosing and treating rheumatic diseases, referring patients that should be treated in the primary level of health care. One year of training in rheumatology made residents' skills comparable to those of senior rheumatologists.

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BACKGROUND: Autologous hematopoietic stem cell transplantation (AHSCT) treats patients with severe and progressive systemic sclerosis (SSc). However, basic mechanisms associated with the therapeutic efficacy of the procedure are not entirely understood. We aimed to evaluate how AHSCT affects skin fibrosis in SSc patients. METHODS: Clinical data, serum, and skin samples from 39 SSc patients who underwent AHSCT were retrospectively evaluated. Skin biopsies were analyzed by immunohistochemistry with anti-MMP-1, -MMP-2, -MMP-3, -MMP-9, -TIMP-1, -α-SMA, -TGF-ß, and -NF-κB p65 antibodies, and stained with hematoxylin and eosin and picrosirius red to assess skin thickness and collagen density, respectively. Serum samples were evaluated by Multiplex Assay for COL1A1, COL4A1, FGF-1, MMP-1, MMP-3, MMP-12, MMP-13, PDGF-AA, PDGF-BB, S100A9, and TIMP-1 levels and compared to healthy controls. RESULTS: After AHSCT, SSc patients showed clinical improvement in skin involvement, assessed by modified Rodnan's skin score (mRSS). Histologically, collagen density and skin thickness decreased after AHSCT. Immunohistochemical analyses showed increased expression of MMP-2, MMP-3, MMP-9, and TIMP-1 after AHSCT, whereas expression of NF-κB p65 decreased. At baseline, serum levels of COL4A1 and S100A9 were higher than in healthy controls. Serum levels of S100A9 normalized after AHCST in SSc patients compared to controls. Serum levels of PDGF-AA, PDGF-BB, TIMP-1, and MMP-1 decreased, while COL1A1 increased after AHSCT in SSc patients. No changes were detected in MMP-3, MMP-12, MMP-13, and FGF-1 serum levels after AHSCT. CONCLUSIONS: Our results suggest that the therapeutic effects of AHSCT on skin fibrosis are related to changes in molecules associated with connective tissue maintenance and inflammation in SSc.

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Objective: Autologous hematopoietic stem cell transplantation (AHSCT) is a therapeutic option for patients with severe and progressive systemic sclerosis (SSc). Here, we aimed to investigate how AHSCT affects the vasculopathy of SSc patients. Methods: Twenty-seven SSc patients were retrospectively assessed, before and after AHSCT, for vessel morphology (nailfold capillaroscopy), skin expression of endothelial markers and serum levels of markers of inflammation, angiogenesis and endothelial activation. Skin biopsies were analyzed by immunohistochemistry (IHC) for expression of CD31, VE-cadherin, E-selectin, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), Tie-2, vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 2 (VEGFR2), and endothelin-1 before and 12 months post-AHSCT. Serum samples from SSc patients were assessed before and up to 36 months after AHSCT for IL-6, von Willebrand factor (vWF), CXC Motif Chemokine Ligand 8 (CXCL8), Endothelin-1, epidermal growth factor (EGF), VEGFA, Pentraxin-3, Intercellular Adhesion Molecule 1 (ICAM-1), E-selectin, P-selectin, Thrombomodulin and IL-18 levels, and compared to healthy control samples. Results: On nailfold capillaroscopy, the number of capillaries increased at 1 year, while giant capillaries decreased at 6 months and 1 year after AHSCT. In the skin biopsies, expression of E-selectin notably decreased and Ang1 increased after AHSCT. At baseline, all vascular markers evaluated in the serum were significantly higher in SSc patients when compared to healthy controls, except for ICAM-1. When compared at different time points after AHSCT, Thrombomodulin, Pentraxin-3, vWF, and IL-18 levels remained generally stable at high levels until 36 months after AHSCT. Conclusion: Our results suggest that AHSCT contributes to improvements of the vessel morphology and dermal microvasculopathy, but does not normalize elevated levels of serum vascular markers in SSc patients. Additional vascular therapeutic approaches might contribute to more effectively treat the endothelial injury.

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INTRODUCTION: COVID-19 may be associated with greater severity and mortality in patients with systemic sclerosis (SSc). The present study aimed to evaluate the prevalence, severity and mortality of COVID-19 in a Brazilian cohort of SSc patients. METHODS: This multicenter, retrospective, observational study included 1,042 SSc patients followed in four centers of São Paulo between March 2020 and June 2021. Diagnosis of COVID-19 was established by proper positive RT-PCR testing or by highly suspicious infection. Patients were grouped into mild (outpatient setting treatment and no need for oxygen support) and moderate-to-severe (hospitalization and/or need for oxygen support) COVID-19. RESULTS: Of the 1,042 SSc patients, 118 patients were diagnosed with COVID-19. Interstitial lung disease (SSc-ILD) was present in 65.6% of the total cohort and in 46.3% of SSc patients with COVID-19. There were 78 (66.1%) cases of mild COVID-19, and 40 (33.9%) cases of moderate-to-severe disease, with 6 (5.1%) deaths. By univariate analysis, pulmonary arterial hypertension (OR 9.50, p=0.006), SSc-ILD (OR 3.90, p=0.007), FVC <80% (OR 2.90, p=0.01), cardiac involvement (OR 5.53, p=0.003), and use of rituximab (OR 3.92, p=0.039), but not age, gender, comorbidities or use of corticosteroids, were predictors of worse outcome for COVID-19. Using multivariate analysis, only SSc-ILD was significantly associated to a higher risk of moderate-to-severe COVID-19 (OR 2.73, 95% CI 1.12-6.69, p=0.02). Forty percent of the patients remained with symptoms after presenting COVID-19, predominantly dyspnea and/or cough (17%). CONCLUSION: In this cohort of patients with SSc, those with SSc-ILD were highly impacted by COVID-19, with a higher risk of moderate-to-severe COVID-19 infection and death.

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The aim of this study was to investigate the effect of red laser (660 nm) photobiomodulation (PBM) with different energies on tumor necrosis factor-alpha(TNF-α) expression for random skin flap viability in rats. Twenty-four Wistar rats were divided into three groups: sham group (SG), PBM laser group with an energy dose of 0.29 J (0.29G), and PBM laser group with an energy dose of 7.30 J (7.30G). A cranially based dorsal skin flap measuring 10 × 4 cm was raised and a plastic barrier was placed between the flap and its bed. PBM was applied in 3 timepoints: in the immediate postoperative period, in the 1st and in the 2nd postoperative days; the animals were euthanized on the 7th postoperative day. The assessments included: TNF-α expression of 3 different flap areas (proximal, medial and distal), by immunohistochemistry; percentage of skin flap necrosis area, by the paper template method. The statistical analysis was performed through the Kruskal-Wallis and Mann-Whitney tests, the level of significance adopted was 5% (p < 0.05). TNF-α expression was significantly lower for 7.30G in the proximal area, reduced for SG in the medial point, and larger for 7.30G in the distal area. The percentage of flap necrosis area was significantly reduced for 7.30G. Higher energy doses are more efficacious than lower energy doses for modulating TNF-α expression. PBM with an energy dose of 7.30 J was effective in reducing the expression of TNF-α and increase skin flap viability.

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT. Thirty-two SCD patients were evaluated before and on long-term follow-up after HSCT. Overall survival was 94% with no severe (grade III-IV) graft-vs-host disease and a 22% rejection rate (graft failure). Hematological parameters, reticulocyte counts, and levels of lactate dehydrogenase (LDH), endothelin-1 and VCAM-1 normalized in SCD patients post-HSCT. Expression of adhesion molecules on reticulocytes and RBC was lower in patients with sustained engraftment. Levels of IL-18, IL-15 and LDH were higher in patients that developed graft failure. Increased levels of plasma pro-inflammatory cytokines, mainly TNF-α, were found in SCD patients long-term after transplantation. SCD patients with sustained engraftment after allo-HSCT showed decreased reticulocyte counts and adhesiveness, diminished hemolysis, and lower levels of vascular tonus markers. Nevertheless, systemic inflammation persists for at least five years after transplantation, indicating that allo-HSCT does not equally affect all aspects of SCD pathophysiology.

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Stem cell transplantation has been investigated as treatment for severe and progressive systemic sclerosis (SSc) for the past 25 years. To date, more than 1000 SSc patients have been transplanted worldwide. Overall and event-free survival have increased over the years, reflecting stricter patient selection criteria and better clinical management strategies. This review addresses long-term outcomes of transplanted SSc patients, considering phase I/II and randomized clinical trials, as well as observational studies and those assessing specific aspects of the disease. Clinical outcomes are discussed comparatively between studies, highlighting advances, drawbacks and controversies in the field. Areas for future development are also discussed.

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Brain injury in sickle cell disease (SCD) comprises a wide spectrum of neurological damage. Neurocognitive deficits have been described even without established neurological lesions. DTI is a rapid, noninvasive, and non-contrast method that enables detection of normal-appearing white matter lesions not detected by conventional magnetic resonance imaging (MRI). The aim of the study was to evaluate if stem cell transplantation can revert white matter lesions in patients with SCD. Twenty-eight SCD patients were evaluated with MRI and DTI before and after allogeneic hematopoietic stem cell transplantation (HSCT), compared with 26 healthy controls (HC). DTI metrics included fractional anisotropy (FA), mean diffusivity (MD), radial (RD), and axial (AD) diffusivity maps, global efficiency, path length, and clustering coefficients. Compared to HC, SCD patients had a lower FA (p = 0.0086) before HSCT. After HSCT, FA increased and was not different from healthy controls (p = 0.1769). Mean MD, RD, and AD decreased after HSCT (p = 0.0049; p = 0.0029; p = 0.0408, respectively). We confirm previous data of white matter lesions in SCD and present evidence that HSCT promotes recovery of brain injury with potential improvement of brain structural connectivity.

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The interruption of the maternal-filial bond in young calves can alter the physiological responses due to increased stress at this moment. Therefore, we aimed to analyze the association between age at weaning and the immune responses of 64 beef calves weaned abruptly. The animals were distributed in three weaning (W) treatments: hyper-early (W30), early (W75) and conventional (W180). The treatments agree with the weaning ages used in cow-calf systems in South America. Blood samples were collected of all experimental animals on the day of weaning and days 1, 2 and 7 post-weaning day of the three treatments. Blood samples were used to analyze hematological variables, total plasma proteins (TPP), fibrinogen, serum amyloid A protein (SAA) and cortisol. The variables analyzed were influenced by the sampling day (P < 0.001) and the calf gender (P < 0.05), and an interaction between treatment x sampling day was observed. Over the study period, high serum cortisol levels were observed for W30 calves. The serum amyloid A protein was significantly influenced by sampling day. When compared to W180 calves, W30 and W75 animals showed prolonged concentrations in plasma fibrinogen. In addition, they presented neutrophilia and lymphopenia during the 180-187 days period, which resulted in a greater neutrophil:lymphocyte ratio (N:L ratio). Calf gender resulted in changes in the number of blood leukocytes (P < 0.05). This result provides an alert for weaning at an early age, indicating that different management strategies must be tested to minimize physiological instabilities in critical periods of the life of animals.

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