COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

TREATMENT RESULTS OF 3 CONSECUTIVE BRAZILIAN COOPERATIVE CHILDHOOD ALL PROTOCOLS - GBTLI-80, GBTLI-82 AND GBTLI-85

The Brazilian Cooperative Group for Treatment of Childhood Acute Lymphocytic Leukemia (GBTLI) has started clinical activities trials in 1980. Three consecutive multicenter studies in children with unprevious treated ALL have been completed including 994 patients. The first GBTLI-80 accrued 203 children from 1980 to 1982. It was delineated with the standard three drugs induction therapy, CNS protection for all pts comprised cranial irradiation and intrathecal Methotrexate. For low risk pts cranial irradiation with 18Gy was compared in a randomized trial with 24Gy. Maintenance therapy continued for 120 weeks. The 12 years of the event free survival rates for all risk groups is 50% (SD 5%). Regarding CNS relapses there was no significant stastitical difference between pts that received 18 or 24Gy. The treatment strategy of GBTLI-82(n=360) from 1982 to 1985, consisted of the same previous induction,consolidation, CNS therapy with cranial irradiation 18 Gy (low risk) or 24 Gy (high risk), followed by continuous maintenance for 2 years. The main question in this study was the comparison between sequential rotation or pulses of 3 pairs of drugs during maintenance. At a median follow-up of 10 years, the overall event free survival rates for all children is 58% (SD 4%). There was no significant difference between the two maintenance regimens. The successor GBTLI-85 ran from 1985 to 1988 and registered 431 pts. For the first time no cranial radiation was given to children with very good prognosis. For them, CNS protection was done with triple intrathecal therapy during all treatment. A consolidation therapy with high dose ARA-C was introduced for high risk pts and infants The 6,5 years event free survival for all children is 70% (SD 4%). Significant better results were achieved for high risk and infants pts (EFS 50%). Early intensification therapy and rotational combination chemotherapy improved the outcome in childhood ALL in Brazil.72S142S14

Periodontal status of individuals with Down syndrome: sociodemographic, behavioural and family perception influence

The aim of the present study was to assess the periodontal condition of individuals with Down syndrome and the association with sociodemographic and behavioural characteristics and family perception of oral health. Methods This cross-sectional observational study was performed at a referral centre for dental assistance to disabled persons in Aracatuba, Brazil. Parents of the individuals were interviewed, and the visible plaque index, bleeding on probing, probing pocket depth and clinical attachment level were recorded by one periodontist in six sites per tooth of all teeth. The individual was the unit of analysis. The significance level was set at 5%. Results Sixty-four subjects (23.8 +/- 8.3 years old) were included. Eighteen (28.1%) were diagnosed with gingivitis and 46 (71.9%) with periodontitis. In the multiple logistic regression final model, age and self-reported oral hygiene practices were associated with the occurrence of periodontitis. The chance of having periodontitis was 4.7 times higher among individuals older than 20 years and approximately 4 times higher in patients whose oral hygiene was performed by themselves and their parents, compared with those who performed oral hygiene alone. Sex, follow-up time in the centre, education, degree of participants' dependence, flossing and family history of periodontal disease were not associated with the occurrence of periodontitis. Higher levels of plaque and bleeding were observed for participants with parents reporting bad gingival health (76.2% and 46.9%) and deficient oral hygiene (79.5% and 47.3%). The perception of parents regarding gingival bleeding was correlated with higher bleeding detected clinically (P = 0.01; 50.1%). Conclusions The prevalence of periodontitis in individuals with Down syndrome is high and increases with age, even in the face of the parents' perception about their children's oral condition631011811192sem informaçãosem informaçã