Phenotypic characteristics and differentiation potential of gingival mesenchymal stem cells in hyperglycemia ­ an ex vivo exploratory study / Características fenotípicas y potencial de diferenciación de las células madre mesenquimales gingivales en la hiperglucemia: un estudio exploratorio ex vivo

Background: The therapeutic use of gingival mesenchymal stem cells (GMSCs) as autologous cells may pose the challenge of alterations inflicted by the hyperglycemic environment. Objective: This study aims to assess the effects of hyperglycemia on the characteristics of GMSCs in diabetics. Materials and Methods: 10 patients who consented and fulfilled the criteria for inclusion and exclusion were recruited and categorized as test (HbA1c > 6.5) and control (HbA1c < 6.0). Gingival explants were obtained from gingival collar of teeth, washed, digested and cultured. The cells were subjected to microscopic observation to assess phenotype characteristics, and flow cytometry and qRT-PCR to assess differentiation potential. Stem cell markers CD90, CD73, CD105, CD34, CD45, HLA DR & HLA ABC, osteogenic differentiation markers RUNX2 & OCN, adipogenic differentiation markers PPARG2 & FABP4 and chondrogenic differentiation markers SOX9 & AGCN were evaluated. Results: Microscopic appearance of spindle shaped cells was found to be comparable in both groups. Flow cytometry results demonstrated comparable expressions with both groups, samples being positive for CD90, CD73, CD105, HLA ABC and negative for CD34, CD45 & HLA DR. There were variations in the expression of markers when assessed for differentiation potentials. Conclusions: The hyperglycemic environment did not manifest any changes in the phenotypic characteristics of GMSCs among diabetics. However, the expression of certain differentiation markers was significantly altered in the diabetic test population included. Further research is being conducted to understand the GMSCs in a hyperglycemic environment with an aim to develop strategies to optimize its clinical implications. Keywords: Gingiva; Mesenchymal stem cells; Diabetes mellitus; Cell Differentiation; Hyperglycemia; Flow cytometry.

Antededentes: El uso terapéutico de células madre mesenquimales gingivales(GMSC) como células autólogas puede plantear el desafío de las alteraciones infligidas por el entorno hiperglucémico. Objetivo: Este estudio tiene como objetivo evaluar los efectos de la hiperglucemia sobre las características de las GMSC en diabéticos. Materiales y Métodos: Se reclutaron y categorizaron 10 pacientes que dieron su consentimiento y cumplieron los criterios de inclusión y exclusión como prueba (HbA1c > 6,5) y control (HbA1c < 6,0). Los explantes gingivales se obtuvieron del cuello gingival de los dientes, se lavaron, digirieron y cultivaron. Las células se sometieron a observación microscópica para evaluar las características fenotípicas y a citometría de flujo y qRT-PCR para evaluar el potencial de diferenciación. Se evaluaron los marcadores de células madre CD90, CD73, CD105, CD34, CD45, HLA DR y HLA ABC, marcadores de diferenciación osteogénica RUNX2 y OCN, marcadores de diferenciación adipogénica PPARG2 y FABP4 y marcadores de diferenciación condrogénica SOX9 y AGCN. Resultados: Se encontró que la apariencia microscópica de las células fusiformes era comparable en ambos grupos. Los resultados de la citometría de flujo demostraron expresiones comparables en ambos grupos, siendo las muestras positivas para CD90, CD73, CD105, HLA ABC y negativas para CD34, CD45 y HLA DR. Hubo variaciones en la expresión de los marcadores cuando se evaluaron los potenciales de diferenciación. Conclusiones: El entorno hiperglucémico no manifestó ningún cambio en las características fenotípicas de las GMSC entre los diabéticos. Sin embargo, la expresión de ciertos marcadores de diferenciación se alteró significativamente en la población de prueba de diabetes incluida. Se están realizando más investigaciones para comprender las GMSC en un entorno hiperglucémico con el objetivo de desarrollar estrategias para optimizar sus implicaciones clínicas.

Epidemiologia da anafilaxia no Brasil: Registro Brasileiro de Anafilaxia (RBA) da Associação Brasileira de Alergia e Imunologia (ASBAI) / Epidemiology of anaphylaxis in Brazil: The Brazilian Registry of Anaphylaxis (RBA) of the Brazilian Association of Allergy and Immunology (ASBAI)

INTRODUÇÃO: A anafilaxia é uma reação alérgica multissistêmica grave, de início agudo e potencialmente fatal. Poucos são os dados sobre sua epidemiologia no Brasil. O Registro Brasileiro de Anafilaxia da Associação Brasileira de Alergia e Imunologia (RBAASBAI) teve como objetivo ampliar o conhecimento sobre anafilaxia em indivíduos brasileiros. MÉTODOS: Estudo observacional transversal com questionário online sobre dados demográficos, desencadeantes suspeitos, manifestações clínicas, atendimento durante a reação, investigação diagnóstica e aconselhamento após a reação de pacientes que experimentaram uma reação anafilática. RESULTADOS: Entre junho/2021 e abril/2023, foram incluídos 237 pacientes (131 femininos): 99 crianças/adolescentes; 127 adultos e 11 idosos. Houve predomínio de meninos entre crianças/adolescentes (55,5%), e de mulheres entre os adultos (64,5%), e mediana de idade de 22 anos (< 1 a 77 anos). As manifestações cutâneas (92,8%) foram as mais frequentes, seguidas pelas respiratórias (70,1%), gastrointestinais (52,3%), neurológicas (36,3%) e cardiovasculares (35,3%). Os principais desencadeantes foram: alimentos (43,0%), medicamentos (26,2%), himenópteros (21,6%) e látex (2,5%); os alimentos entre crianças (leite, ovo, amendoim/castanhas), e os fármacos (anti-inflamatórios e antibióticos) entre os adultos. Quanto ao tratamento, 61,1% recebeu adrenalina (52,7% por profissional e 8,4% via autoinjetor de adrenalina -AIA). Uma adolescente (12 anos) faleceu após picada de abelha. A maioria recebeu plano escrito de emergência (78,1%) e foi ensinada a usar o AIA (70%). CONCLUSÃO: Os alimentos foram os desencadeantes mais comuns entre crianças/adolescentes, e os fármacos entre adultos brasileiros. A adrenalina continua sendo subutilizada, reforçando a necessidade de maior disseminação do tratamento adequado da anafilaxia.

INTRODUCTION: Anaphylaxis is a life-threatening, acute, severe multisystem allergic reaction.There is little data on its epidemiology in Brazil. The Brazilian Anaphylaxis Registry of the Brazilian Association of Allergy and Immunology (RBA-ASBAI) was devised to expand knowledge about anaphylaxis in Brazilian individuals. METHODS: Cross-sectional observational study using an online questionnaire to collect data on demographics, suspected triggers, clinical manifestations, treatment during the reaction, diagnostic workup, and post-reaction counseling in patients who have experienced an anaphylactic reaction. RESULTS: Between June 2021 and April 2023, 237 patients were included (131 female): 99 children/adolescents (<18yo), 127 adults (18-64yo), and 11 older adults (65-77yo). There was a male predominance in the pediatric group (55.5%), while females were predominant among adults (64.5%). The median age was 22 years (range, <1 to 77). The most frequent clinical manifestations were cutaneous (92.8%), followed by respiratory (70.1%), gastrointestinal (52.3%), neurological (36.3%), and cardiovascular (35.3%). The most common triggers were foods (43.0%), drugs (26.2%), venoms (21.6%), and latex (2.5%). Foods (milk, egg, peanuts/tree nuts) predominated among children, versus drugs (mostly nonsteroidal anti-inflammatory drugs and antibiotics) among adults. Regarding treatment, 61.1% received epinephrine (52.7% by a healthcare professional and 8.4% via epinephrine auto-injector [EAI]). One teenager (12yo) died due to a bee sting. Most patients received a written emergency plan (78.1%) and were taught how to use the EAI (70%). CONCLUSION: Foods were the most common triggers of anaphylaxis among Brazilian children and adolescents, while drugs predominated among adults. Epinephrine continues to be underused, highlighting the need for greater awareness of proper treatment of anaphylaxis.

Could nanotechnology improve exercise performance? Evidence from animal studies

Abstract This review provides the current state of knowledge regarding the use of nutritional nanocompounds on exercise performance. The reviewed studies used the following nanocompounds: resveratrol-loaded lipid nanoparticles, folic acid into layered hydroxide nanoparticle, redox-active nanoparticles with nitroxide radicals, and iron into liposomes. Most of these nutritional nanocompounds seem to improve performance in endurance exercise compared to the active compound in the non-nanoencapsulated form and/or placebo. Nutritional nanocompounds also induced the following physiological and metabolic alterations: 1) improved antioxidant activity and reduced oxidative stress; 2) reduction in inflammation status; 3) maintenance of muscle integrity; 4) improvement in mitochondrial function and quality; 5) enhanced glucose levels during exercise; 6) higher muscle and hepatic glycogen levels; and 7) increased serum and liver iron content. However, all the reviewed studies were conducted in animals (mice and rats). In conclusion, nutritional nanocompounds are a promising approach to improving exercise performance. As the studies using nutritional nanocompounds were all conducted in animals, further studies in humans are necessary to better understand the application of nutritional nanocompounds in sport and exercise science.

Role of collagen and immunostaining for TGF-ß in the clinical and microscopic findings of pyogenic granuloma and peripheral ossifying fibroma.

BACKGROUND: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-ß) in the clinical and microscopic findings of PG and POF. MATERIAL AND METHODS: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-ß) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). RESULTS: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-ß+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-ß suffered from modifications by the time of evolution and the size of the lesion. CONCLUSIONS: Although PG and POF are reactive gingival lesions, the expression of TGF-ß and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components.

Abusive Consumption of Alcoholic Beverages and Associated Factors in Brazilian University Students.

The university is considered an environment that favors the initiation and use of substances, especially those that are legal, such as alcohol. This consumption can be differentiated in university students, which makes it necessary to better understand this behavior. Taking into account these aspects, we analyzed the abusive consumption of alcoholic beverages in university students and its association with socioeconomic and behavioral factors. We conducted a cross-sectional study with regularly enrolled students. We assessed the abusive consumption of alcoholic beverages using the binge drinking pattern. We collected socioeconomic and behavioral data using a questionnaire. The association between the variables was verified using logistic regression. Abusive consumption of alcoholic beverages was high, with a high weekly frequency. The association with sociodemographic and behavioral factors can increase the health risk. Education campaigns within institutions with students in the classroom and with all those who can influence these students are important. As there are few studies that consider other health risk factors that have not been analyzed yet, such as those treated in our study, with the abusive consumption of alcoholic beverages, this study seeks to contribute to the knowledge of the relationships between these variables and in the elaboration of actions aimed at improving the lifestyle and health of university students.

Effect of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19

Abstract Objective: To investigate the effect of a single oral dose of 200,000 IU of vitamin D3 on antiphospholipid antibodies in hospitalized patients with moderate to severe COVID-19. Methods: This is a post-hoc, exploratory analysis from a double-blind, placebo-controlled, randomized clinical trial performed in two centers in São Paulo, Brazil. Hospitalized patients with COVID-19 were randomly assigned to receive either vitamin D3 (n = 97) or placebo (n = 97). In this post-hoc analysis, the endpoints were titers and frequency of anti-β2-Glycoprotein-I (aβ2-GP) and Anticardiolipin (aCL) antibodies [Immunoglobulin G, M and A (IgG, IgM and IgA)]. Results: Overall mean (SD) age was 55.3 (13.9) years, Body Mass Index (BMI) was 32.2 (7.1 kg/m²), and 106 participants (54.6 %) were male. There was a significant group by time interaction (p = 0.046) for frequency of aCL IgG, with increased values from baseline to discharge in the placebo group [n (%), from 13 (13.4) to 25 (25.8)] compared to the vitamin D3 [from 25 (25.8) to 29 (29.9)]. However, the frequency of aCL IgG did not change between the groups on discharge. No significant differences between vitamin D3 and placebo groups were found for any other autoantibodies. Conclusion: These findings do not support the use of a single oral dose of 200,000 IU of vitamin D3 to modulate autoantibodies in hospitalized patients with moderate to severe COVID-19.

Outcomes of lower trapezius transfer with hamstring tendons for irreparable rotator cuff tears.

Background: The aim of this study was to evaluate the results of the transfer of the lower trapezius with a graft from hamstring tendons in the treatment of irreparable rotator cuff tears . Level IV; Case Series; Treatment Study. Methods: Ten patients diagnosed with irreparable tears of the supraspinatus and infraspinatus tendons, were evaluated retrospectively -preoperatively, 6 and 12 months postoperatively. They underwent transfer of the prolonged lower trapezius with an autologous graft of the knee flexor tendons. Results: The Shoulder Subjective Value increased from 47 (preoperative) to 71 (1 year after surgery), American Shoulder and Elbow Surgeons Score increased from 26.63 to 75.24. Pain improved from 7.9 to 2.5 on the Visual Analogue Scale. The mean lateral rotation improved from 31° to 51°, flexion from 84° to 122°, and abduction from 76° to 101°. These results have not changed significantly between 6 and 12 months. Discussion: The transfer of the lower trapezius with autologous grafts from the hamstring tendons showed good results in patients under 65 years of age with irreparable rotator cuff tears . Longer follow-up and a greater number of cases are necessary to confirm the efficacy of the transfer.

Bone erosions associated with systemic bone loss on HR-pQCT in women with longstanding polyarticular juvenile idiopathic arthritis.

OBJECTIVES: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. METHODS: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. RESULTS: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and µ-finite element parameters were decreased in patients compared to HC (p < 0.05). CONCLUSION: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.

Risk factors for mortality in 1528 Brazilian childhood-onset systemic lupus erythematosus patients.

OBJECTIVES: To identify associations between mortality in cSLE patients and their characteristics: clinical and laboratory features, disease activity and damage scores, and treatment; to evaluate risk factors associated with mortality in cSLE; and to determine the most frequent causes of death in this group of patients. METHODS: We performed a multicenter retrospective cohort using data from 1,528 cSLE patients followed in 27 pediatric rheumatology tertiary centers in Brazil. Patients' medical records were reviewed according to a standardized protocol, in which information regarding demographic and clinical features, disease activity and damage scores, and treatment were collected and compared between deceased cSLE patients and survivors. Univariate and multivariate analyses by Cox regression model were used to calculate risk factors for mortality, whereas survival rates were analyzed by Kaplan-Meier plots. RESULTS: A total of 63/1,528 (4.1%) patients deceased, 53/63 were female (84.1%), median age at death was 11.9 (9.4-13.1) years and median time interval between cSLE diagnosis and death was 3.2 (0.5-5.3) years. Sepsis was the main cause of death in 27/63 (42.8%) patients, followed by opportunistic infections in 7/63 (11.1%), and alveolar hemorrhage in 6/63 (9.5%) patients. The regression models resulted in neuropsychiatric lupus (NP-SLE) (HR = 2.56, 95% CI = 1.48-4.42) and chronic kidney disease (CKD) (HR = 4.33, 95% CI = 2.33-4.72), as risk factors significantly associated with mortality. Overall patient survival after cSLE diagnosis at 5, 10, and 15 years were 97%, 95.4%, and 93.8%, respectively. CONCLUSIONS: This study confirmed that the recent mortality rate in cSLE in Brazil is low, but still of concern. NP-SLE and CKD were the main risk factors for mortality, indicating that the magnitude of these manifestations was significantly high.

Heterogeneity of humoral response patterns in mildly symptomatic, non-hospitalized COVID-19 patients: A one-year longitudinal study.

The duration and protectiveness of antibodies against SARS-CoV-2 in infected subjects are still uncertain; nonetheless, anti-S-specific antibodies can contribute to protective immunity against new infections. It has been described that the level of antibodies produced in COVID-19 is related to the severity of symptoms, and the majority of the humoral response studies have been conducted in hospitalized patients who have been, then, followed over time. However, about 80% of SARS-CoV-2 infections in unvaccinated people are mild to asymptomatic, and this percentage reaches more than 95% in vaccinated individuals. Therefore, understanding the long-term dynamics of the antibody responses in this predominant part of the COVID-19-affected population is essential. In this study, we followed a cohort of individuals with mild COVID-19 who did not require hospitalization. We collected blood samples at sequential times after the SARS-CoV-2-positive qRT-PCR result. From 65 recruited patients, 50 had detectable antibodies at screening. Anti-SARS-CoV-2 IgM levels peaked around two weeks post-COVID-19 diagnostics, becoming undetectable after 65 days. IgG levels reached a peak in approximately one month and remained detectable for more than one year. In contrast to the levels of anti-SARS-CoV-2, antibody neutralization potency indexes persisted over time. In this study, humoral responses in mild COVID-19 patients persisted for more than one year. This is an important long-term follow-up study that includes responses from COVID-19 patients before and after vaccination, a scenery that has become increasingly difficult to evaluate due to the growing vaccination of the world human population.

Unraveling the relationship between conditions of ultrasonic-assisted extraction of chia mucilage and viscosity.

BACKGROUND: The application of chia mucilage still remains restricted due to the difficulty in achieving high extraction yields. The effect of ultrasonic-assisted extraction (UAE) conditions (temperature, seed:water ratio and time) on the rheological properties of chia mucilage extracts and the relation to the proportion of translucent phase (TP) and opaque phase (OP) of the mucilage in the extract were evaluated. RESULTS: UAE allowed the efficient extraction of chia mucilage from chia seeds. The desired overall optimal combination to maximize both yield and apparent viscosity was achieved at a seed:water ratio 1:10, a temperature of 25.3 °C and 53.7 min extraction time; the optimal conditions to obtain the maximum yield and minimum apparent viscosity were a seed:water ratio close to 1:20, temperature of 48.8 °C and 208.4 min extraction time. CONCLUSION: The results obtained in the present work demonstrated that the differences in rheological properties of chia mucilage extracts are due to the extraction methods used. Therefore, it is possible to modulate the extraction conditions in order to obtain different characteristics of the mucilage, maintaining a high extraction yield. © 2022 Society of Chemical Industry.

[Mobile child psychiatric team in French Guiana: Analyzing Amerindian teenager issues]. / Équipe mobile de pédopsychiatrie en territoire guyanais : questionnement de l'adolescent amérindien.

INTRODUCTION: Since their French naturalization in 1969, Amerindians of French Guiana have been facing a full and fast reorganization of their way of life. Teenagers, at the forefront of this cultural transition, are challenging French school institutions, as well as cultural society and care system organizations in Amazonian French remote villages. Rates of autolytic behaviors such as toxic substance abuse or suicide attempts, but mostly completed suicides, are alarming among this adolescent population. To improve care delivery to those teenagers, a mobile child psychiatric team was implemented in 2013. METHODS: We describe this device, its activities and the problematics encountered. RESULTS: This team's purpose is to lead a psychiatric evaluation of teenagers in order to determine a possible psychiatric diagnosis and elaborate a care plan. Although the results are mostly encouraging, this device seems to show some limitations: lack of time dedicated to these interventions, lack of psychiatric care available for follow-up in these villages, tremendous numbers of social distress situations implicated in psychological issues. Moreover, it appears that cultural aspects must be considered in the analysis of the Amerindian adolescent population's issues and the determination of providing care. CONCLUSION: Implementation of actions based on more educational and social levels might be a solution.

Biotransformed soybean cream as a new nutraceutical for skin care: collagen stimulation in vitro and ex vivo

Treatments that attenuate the effects of hypoestrogenism in menopausal women have been gaining visibility. This study investigated the skin response to a phytoestrogen-enriched cosmetic formulation created by incorporating a biotransformed soybean extract (BE) into a cream-like matrix. Collagen-I expression was analyzed both in vitro (fibroblast cells) and ex vivo (skin explants). The results revealed an increased amount of collagen-I both in fibroblasts and human skin when treated with BE and BE-incorporated cream. Also, this collagen-I overexpression was inhibited by PHTPP, indicating a dependence on estrogen hormone receptor beta (ERβ) signaling. Moreover, BE was not harmful to skin microbiota, showing a promising nutricosmetic potential. Thus, this work presented a fully functional cream-like formulation that was shown to be safe and effectively increase collagen-I levels both in vitro and ex vivo.

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Abstract Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05-0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05-0.88, p = 0.034). After six months (D69-D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698).

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

Estudio de caso, paciente en hemodiálisis, antecedentes heredofamiliares con el modelo de Virginia Henderson / Case study, hemodialysis patient, family history with the Virginia Henderson model

El siguiente estudio de caso se realizó en una persona con enfermedad renal crónica secundaria a diabetes mellitus tipo 1 en tratamiento de hemodiálisis desde hace 7 años, se realizó con el fin llevar acabo las acciones e intervenciones encaminadas a contribuir en los cuidados de rehabilitación, así como aminorar las complicaciones de esta enfermedad para que la persona logre su independencia. La metodología está basada en el modelo de Virginia Henderson donde se encontraron necesidades de nutrición e hidratación, eliminación, evitar peligros y aprendizaje alterados, posteriormente se realiza los diagnósticos de enfermería y la planificación del cuidado mediante la taxonomía Nanda, Noc y Nic. Para esto se requisita la NOM-012-SSA3. 2012, mediante el cual se obtiene el consentimiento informado de la persona para ejecutar el plan de cuidados con los criterios que establece la norma para ejecutar las intervenciones con el fin de investigación para la salud, se realizó visita domiciliaria para una evaluación del plan de cuidados donde se concluye que en relación con la implicación familiar se logró cierto grado de independencia en el paciente, observando cambios positivos, conocimiento de la enfermedad y un mejor apego a su alimentación.

The following case study was carried out in a person with chronic kidney disease secondary to type 1 diabetes mellitus on hemodialysis treatment for 7 years, it was carried out in order to carry out actions and interventions aimed at contributing to rehabilitation care, as well how to reduce the complications of this disease so that the person can achieve independence. The methodology is based on the Virginia Henderson Model where needs for nutrition and hydration, elimination, danger avoidance and altered learning were found, subsequently nursing diagnoses and care planning are carried out using the Nanda, Noc and Nic taxonomy. For this, the NOM-012-SSA3 is required. 2012, through which the informed consent of the person is obtained to execute the care plan with the criteria established by the norm to execute the interventions for the purpose of health research, a home visit is made with which a evaluation of the care plan where it is concluded that in relation to family involvement, a certain degree of independence was achieved in the patient, positive changes were observed, a better knowledge of the disease, better adherence to their diet.

Phosphoric acid containing proanthocyanidin enhances bond stability of resin/dentin interface

Abstract Proanthocyanidin (PA) is a promising dentin biomodifier due to its ability to stabilize collagen fibrils against degradation by matrix metalloproteinases (MMPs); however, the most effective protocol to incorporate PA into bonding procedures is still unclear. This study evaluated the effect of dentin biomodification with a PA acid etchant on MMP activity, adhesive interface morphology and resin-dentin microtensile bond strength. Sound extracted human molars were flattened to expose dentin and acid-etched for 15 s according to the groups: EXP - experimental phosphoric acid; EXP+PA - experimental phosphoric acid 10% PA; TE - total-etching system; SE - self-etching system. Samples were restored with composite resin and stored in distilled water (37ºC). MMP activity and interface morphology were analyzed after 24 h by in situ zymography (n=6) and scanning electron microscopy (n=3), respectively. The resin-dentin microtensile bond strength (μTBS) was evaluated after 24 h and 6 months storage (n=6). Significantly higher MMP activity was detected in etched dentin compared with untreated dentin (p<0.05), but no difference among acid groups was found. Resin tags and microtags, indicative of proper adhesive system penetration in dentinal tubules and microtubules, were observed along the hybrid layer in all groups. There was no difference in μTBS between 24 h and 6 months for EXP+PA; moreover, it showed higher long-term μTBS compared with TE and EXP (p<0.05). The results suggest that 15 s of biomodification was not sufficient to significantly reduce MMP activity; nonetheless, EXP+PA was still able to improve resin-dentin bond stability compared with total- and self-etching commercial systems.

Resumo A proantocianidina (PA) é um biomodificador dentinário promissor devido a sua capacidade de estabilizar as fibrilas colágenas contra a degradação por metaloproteinases da matriz (MMPs); no entanto, o protocolo mais eficaz para a incorporação de PA em procedimentos adesivos ainda não está claro. Este estudo avaliou o efeito da biomodificação da dentina com um condicionador ácido contendo PA na atividade de MMPs, morfologia da interface adesiva e resistência à microtração resina-dentina. Molares humanos extraídos foram lixados para exposição da dentina e condicionados com ácido por 15 s de acordo com os grupos: EXP - ácido fosfórico experimental; EXP+PA - ácido fosfórico experimental com 10% PA; TE - sistema total-etch; SE - sistema self-etch. As amostras foram restauradas com resina composta e armazenadas em água destilada (37ºC). A atividade de MMP e morfologia da interface foram analisadas após 24 h por zimografia in situ (n=6) e microscopia eletrônica de varredura (n=3), respectivamente. A resistência à microtração resina-dentina (μTBS) foi avaliada após 24 horas e 6 meses de armazenamento (n=6). Atividade de MMP detectada na dentina condicionada foi significativamente maior em comparação com a dentina não tratada (p <0,05), mas não houve diferenças entre os diferentes ácidos. Tags e microtags de resina, indicativos de uma penetração adequada do sistema adesivo nos túbulos e microtúbulos dentinários, foram observadas ao longo da camada híbrida em todos os grupos. Não houve diferença entre os valores de μTBS de 24 h e 6 meses para EXP+PA; além disso, EXP+PA apresentou maiores valores de μTBS após 6 meses em comparação com TE e EXP (p <0,05). Os resultados sugerem que a biomodificação por 15 s não foi suficiente para reduzir significativamente a atividade de MMP; apesar disso, EXP + PA foi capaz de melhorar a estabilidade da interface resina-dentina em comparação com sistemas total- e self-etch comerciais.

Combined antibiofilm activity of synthetic peptides and antifungal drugs against Candida spp.

Introduction: Candida krusei and Candida albicans are biofilm-forming drug-resistant yeasts that cause bloodstream infections that can lead to death. Materials & methods: nystatin and itraconazole were combined with two synthetic peptides, PepGAT and PepKAA, to evaluate the synergistic effect against Candida biofilms. Additionally, scanning electron and fluorescence microscopies were employed to understand the mechanism behind the synergistic activity. Results: Peptides enhanced the action of drugs to inhibit the biofilm formation of C. krusei and C. albicans and the degradation of mature biofilms of C. krusei. In combination with antifungal drugs, peptides' mechanism of action involved cell wall and membrane damage and overproduction of reactive oxygen species. Additionally, in combination, the peptides reduced the toxicity of drugs to red blood cells. Conclusion: These results reveal that the synthetic peptides enhanced the antibiofilm activity of drugs, in addition to reducing their toxicity. Thus, these peptides have strong potential as adjuvants and to decrease the toxicity of drugs.

Candida krusei and Candida albicans are biofilm-forming, drug-resistant yeasts that cause bloodstream infections that can lead to death. In this study, biofilms of C. krusei and C. albicans were treated with a solution composed of synthetic peptides and antifungal drugs, none of which were effective alone. The synthetic peptides reduced the toxicity of drugs to red blood cells. These results may pave the way to the application of synthetic peptides as a beneficial additional to antifungal drugs to treat fungi that cannot be killed by drugs alone.

Social impact of disease parameters and damage accrual in adult Brazilian patients with childhood-onset Systemic Lupus Erythematosus.

OBJECTIVES: To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with childhood-onset Systemic Lupus Erythematosus (cSLE). METHODS: In this multicenter cross-sectional retrospective cohort study including cSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, receipt of government financial assistance, work status, quality of life, economic classification, disease activity, and damage accrual. Disease activity and disease damage were measured at the study visit. RESULTS: Sixty-nine cSLE patients with a median age of 21 years from two Brazilian tertiary centers were included (median disease duration 9 years). Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement pension. Work unemployment was associated with higher damage scores (OR 1.83, 95% CI 1.08 to 3.09, p = 0.024), and the need of financial assistance was associated with longer disease duration (OR 1.15, 95% CI 1.00 to 1.31, p = 0.045) and worse economic score (OR 0.87, 95% CI 0.77 to 0.99, p = 0.038). Emotional health and body image perception were the most compromised domains of quality of life but showed no association with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (ß = -1.377, p = 0.014) and scores of adverse effects of medications (ß = -1.286, p = 0.020). CONCLUSION: cSLE is a disease with severe outcomes and high social burden that profoundly impacts patients. Damage accrual is a major contributor to unemployment during adulthood and its prevention must be central in the management of cSLE.