Longitudinal study of humoral immunity against SARS-CoV-2 of health professionals in Brazil: the impact of booster dose and reinfection on antibody dynamics.

Introduction: The pandemic caused by SARS-CoV-2 has had a major impact on health systems. Vaccines have been shown to be effective in improving the clinical outcome of COVID-19, but they are not able to fully prevent infection and reinfection, especially that caused by new variants. Methods: Here, we tracked for 450 days the humoral immune response and reinfection in 52 healthcare workers from Brazil. Infection and reinfection were confirmed by RT-qPCR, while IgM and IgG antibody levels were monitored by rapid test. Results: Of the 52 participants, 19 (36%) got reinfected during the follow-up period, all presenting mild symptoms. For all participants, IgM levels dropped sharply, with over 47% of them becoming seronegative by the 60th day. For IgG, 90% of the participants became seropositive within the first 30 days of follow-up. IgG antibodies also dropped after this period reaching the lowest level on day 270 (68.5 ± 72.3, p<0.0001). Booster dose and reinfection increased the levels of both antibodies, with the interaction between them resulting in an increase in IgG levels of 130.3 arbitrary units. Conclusions: Overall, our data indicate that acquired humoral immunity declines over time and suggests that IgM and IgG antibody levels are not associated with the prevention of reinfection.

Comparison of diagnostic performance of RT-qPCR, RT-LAMP and IgM/IgG rapid tests for detection of SARS-CoV-2 among healthcare workers in Brazil.

BACKGROUND: COVID-19 has become a major public health problem after the outbreak caused by SARS-CoV-2 virus. Great efforts to contain COVID-19 transmission have been applied worldwide. In this context, accurate and fast diagnosis is essential. METHODS: In this prospective study, we evaluated the clinical performance of three different RNA-based molecular tests - RT-qPCR (Charité protocol), RT-qPCR (CDC (USA) protocol) and RT-LAMP - and one rapid test for detecting anti-SARS-CoV-2 IgM and IgG antibodies. RESULTS: Our results demonstrate that RT-qPCR using the CDC (USA) protocol is the most accurate diagnostic test among those evaluated, while oro-nasopharyngeal swabs are the most appropriate biological sample. RT-LAMP was the RNA-based molecular test with lowest sensitivity while the serological test presented the lowest sensitivity among all evaluated tests, indicating that the latter test is not a good predictor of disease in the first days after symptoms onset. Additionally, we observed higher viral load in individuals who reported more than 3 symptoms at the baseline. Nevertheless, viral load had not impacted the probability of testing positive for SARS-CoV-2. CONCLUSION: Our data indicates that RT-qPCR using the CDC (USA) protocol in oro-nasopharyngeal swabs samples should be the method of choice to diagnosis COVID-19.

Tirzepatide Once Weekly for the Treatment of Obesity.

BACKGROUND: Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known. METHODS: In this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population. RESULTS: At baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively. CONCLUSIONS: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

Evaluation of antimicrobial photodynamic therapy with acidic methylene blue for the treatment of experimental periodontitis.

OBJECTIVE: To investigate the security and effectiveness of antimicrobial photodynamic therapy (aPDT) with a citric acid-based methylene blue (MB) on the periodontal repair following the treatment of ligature-induced experimental periodontitis (EP) in rats. MATERIAL AND METHODS: Were used 120 male rats, randomly divided into 4 experimental groups (n = 30): no treatment (NT), SRP alone (SRP), SRP plus aPDT using conventional MB pH 7.0 (aPDT-pH7), SRP plus aPDT using acidic MB pH 1.0 (aPDT-pH1). EP was induced at day 0 by the placement of a ligature around the mandibular left first molars. Ten animals per group/period were euthanized at 14, 22 and 37 days. Histopathological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tartrate-resistant acid phosphatase [TRAP] and osteocalcin [OCN]) analyses were performed. Data were statistically analyzed. RESULTS: aPDT-pH1 showed the highest PBF as compared with the other treatments. Collectively, tissues' reaction to both dyes were controlled and healthy for the periodontium. Both aPDT protocols reduced the extent and intensity of the local inflammatory response, reduced the alveolar bone resorption, and promoted a better structural arrangement of the connective tissue as compared with SRP. TRAP expression was downregulated while OCN expression was upregulated by aPDT as compared with SRP alone. CONCLUSION: Our data implicate that the novel MB pH 1.0 is as safe as the conventional MB for use in aPDT and raises its additional benefit of increasing the amount of alveolar bone in the furcation.

Antineoplastic agents aggravate the damages caused by nicotine on the peri-implant bone: an in vivo histomorphometric and immunohistochemical study in rats.

OBJECTIVE: To assess the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the treatment of cancer. This study evaluated the influence of cisplatin (CIS) and 5-fluorouracil (5-FU) over the peri-implant tissues around osseointegrated titanium implants in animals previously exposed to nicotine. Materials and methods One hundred twenty male rats were divided into two groups, receiving via subcutaneous injection, either physiological saline solution (PSS) (n = 30) or nicotine hemissulfate (NIC) (n = 90) for 30 days prior to implants' placement. One titanium implant (4.0 × 2.2 mm) was installed in each tibia of all animals. PSS and NIC were continued for 30 days after surgery. Five days after cessation, rats were subdivided into three subgroups in accordance with systemic treatments with either PSS, CIS, or 5-FU. Euthanasia was performed at 50, 65, and 95 days post-surgery. Histometric, histopathological, and immunohistochemical analyses were performed. RESULTS: NIC-CIS and NIC-5FU presented lower BIC (50, 65, and 95 days) and bone area fraction occupancy (BAFO) (65 and 95 days) than group NIC. Intense inflammatory infiltration, severe tissue breakdown, reduced expression of bone formation biomarkers, and upregulation of TRAP were observed in NIC-CIS and NIC-5FU when compared with group NIC. TRAP expression was significantly higher in NIC-5FU as compared with NIC-CIS at 50 and 95 days. Groups NIC, NIC-CIS, and NIC-5FU presented statistically significant negative impact in all outcome parameters than group PSS. CONCLUSION: CIS and 5-FU severely disrupted the peri-implant tissues around osseointegrated implants in animals previously exposed to nicotine. CLINICAL RELEVANCE: Assessing the interaction between chemotherapy and normal tissues is critical to assure quality of life during and after the cancer treatment.

Platelet-rich fibrin for wound healing of palatal donor sites of free gingival grafts: Systematic review and meta-analysis.

BACKGROUND: Platelet-rich fibrin (PRF) has been referred to as a second-generation platelet concentrate, associated with improvements on the healing of palatal wounds followed by FGG harvesting. The aim of this systematic review and meta-analysis was to assess the complete wound epithelialization and postoperative pain when PRF was used in palatal wounds following free gingival graft (FGG) harvesting. MATERIAL AND METHODS: PubMed (Medline), EMBASE and Scopus were searched by two independent individuals up to and including March 2020 in order to identify controlled and randomized controlled clinical trials on the use of PRF at palatal donor sites of FGG. The outcomes assessed were epithelialization and postoperative pain. The risk of bias of the included studies was evaluated using Cochrane Collaboration's domain-based two-part tool. Random effects meta-analyses were conducted with 95% confidence intervals. RESULTS: The search strategy identified 555 potentially eligible articles, of which 6 randomized controlled clinical trials were included. In the qualitative analysis, most studies (83.3%) reported lower postoperative pain in treatment groups, while all studies accessing epithelialization demonstrated earlier complete wound closure in groups treated with PRF. The discomfort and complete re-epithelialization were more favorable in groups PRF when compared to control groups (P<0.00001). CONCLUSIONS: Within the limits of the present study, it can be concluded that the use of PRF for wound healing of palatal donor sites of FGG may decrease postoperative pain and induce earlier complete wound epithelialization. Key words:Wound healing, oral surgery procedures, pain, postoperative.

Influence of systemic strontium ranelate on the progression and as adjunctive therapy for the nonsurgical treatment of experimental periodontitis.

BACKGROUND: Strontium Ranelate (SR) presents overlapping osteoanabolic and anti-resorptive activity. However, the effects of SR on the progression of periodontitis through the alveolar bone and its potential applicability as adjunctive therapy to scaling and root planning remain poorly accessed. The aim of this study was to evaluate the effects of systemic (SR) both on the progression of experimental periodontitis (EP) and as adjunctive therapy to SRP. MATERIAL AND METHODS: Eighty male rats were divided into four groups (n=20): EP-PSS: EP induction and systemic administration of physiological saline solution (PSS); EP-SR: EP induction and systemic administration of SR; EP-SRP/PSS: EP induction, SRP and systemic administration of PSS; EP-SRP/SR: EP induction, SRP and systemic administration of SR. Seven days after ligature placement, SRP was performed in EP-SRP/PSS and EP-SRP/SR, as well as the systemic administration of either PSS or SR were initiated and continued until euthanasia in all groups. Animals were euthanized at 7 and 30 days after the beginning of the systemic treatments. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (tartrate-resistant acid phosphatase [TRAP], Osteocalcin [OCN] and leukocyte common antigen [CD 45]) analyses were performed. Data were statistically analyzed. RESULTS: EP-SRP/PSS showed a significantly more organized pattern of the connective tissue and alveolar bone structure than EP-SRP/SR. EP-SR showed significantly higher PBF than EP-PSS, however, EP-SRP/PSS showed no difference with EP-SRP/SR at 30 days. CONCLUSIONS: SR reduced the alveolar bone loss in non-treated animals and presented no standout benefits over the conventional forms of treating EP. Key words:Strontium Ranelate, periodontal disease, root planing, alveolar bone loss.

Association of hyaluronic acid with a deproteinized bovine graft improves bone repair and increases bone formation in critical-size bone defects.

BACKGROUND: This study is designed to evaluate the potential of different formulations of hyaluronic acid (HA) to improve new bone formation in critical-size calvaria defect (CSD) when combined with a deproteinized bovine graft (DBG) material. METHODS: Thirty male rats were used. A 5-mm-diameter CSD was created and three experimental groups (n = 10) were randomly assigned based on the treatments performed. Group DBG: CSD filled with a DBG; group DBG/LV: CSD filled by the combination of DBG and HA in a low-viscosity crosslinking agent; group DBG/HV: CSD filled by the combination of DBG and HA in a high-viscosity crosslinking agent. Animals were euthanized 30 days postoperatively. Histological, histometric (percentage of newly formed bone [PNFB], percentage of remaining graft particles, histochemical, and immunohistochemical (bone morphogenetic protein 2/4 [BMP2/4], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. RESULTS: The highest PNFB was observed in DBG/HV when compared with the other groups (P ≤0.05). DBG/LV and DBG/HV presented almost no inflammatory cells. In contrast, inflammation was observed in group DBG. Extensive resorption of graft particles was observed in group DBG, which was not present in DBG/LV and DBG/HV as confirmed by the larger size of the particles (P ≤0.05). BMP2/4 and OCN immunolabeling were higher in DBG/HV when compared with group DBG (P ≤0.05). Increased number of TRAP-positive cells was observed in DBG/LV and DBG/HV (P ≤0.05). Lower percentage of mature collagen fibers was observed in DBG/HV (P ≤0.05). CONCLUSION: The combination of HA in a high-viscosity crosslinking agent with DBG improves the bone repair process and increases the amount of newly formed bone towards CSDs in rat calvaria.

Antineoplastic agents exacerbate periodontal inflammation and aggravate experimental periodontitis.

AIM: This study evaluated the effects of 5-fluorouracil (5-FU) and cisplatin (CIS) in healthy periodontal tissues and in the early stages of experimental periodontitis (EP) in rats. METHODS: One hundred and eighty male rats were divided into three groups, which were submitted to the following systemic treatments: physiological saline solution (PSS); CIS and 5FU. Each group was subdivided into two subgroups: without (NEP) and with (EP) induction of EP. Animals were euthanized at 3, 5 and 7 days post-treatment. Histological, histometric (percentage of bone in the furcation [PBF]) and immunohistochemical (for tumour necrosis factor-α, interleukin-1ß and receptor activator of nuclear factor-κB ligand) analyses were performed. Data were statistically analysed. RESULTS: CIS-NEP and 5FU-NEP showed more inflammation than PSS-NEP at 3, 5 and 7 days. CIS-EP and 5FU-EP showed more inflammation and lower PBF than PSS-EP at all periods of evaluation. 5FU-EP showed lower PBF than CIS-EP at 5 and 7 days. CONCLUSION: 5-FU and CIS exacerbated periodontal inflammation and aggravated the progression of EP in its early stages.

Periodontal disease severity in subjects with dementia: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Despite clinical trials and reviews attempt to assess a possible relationship between dementia and periodontal disease, no meta-analysis has been performed and this issue remains undetermined. The aim of this study is to conduct a systematic review and meta-analysis to assess severity of periodontitis in subjects with dementia. METHODS: The search was conducted in Pubmed, Embase/MEDLINE. Two independent reviewers extracted data and assessed the risk bias (Newcastle-Ottawa scale). Meta-analyses were performed using the means of probing depth (PD) and clinical attachment loss (CAL) in patients with or without dementia. The mean difference were analyzed (P ≤ 0.05). RESULTS: Fourteen studies were included in the systematic review. In the qualitative analysis, most studies reported higher prevalence of periodontal disease in dementia patients. The studies had low risk of bias and two meta-analyses were performed for each parameter, including or not a cross-sectional study. The meta-analyses including the cross-sectional study demonstrated significant association between dementia and periodontal disease (mean difference: PD = 1.41; CAL = 1.40, P < 0.05), however, it wasn't confirmed when the cross-sectional study was removed (1.25 mm, P < 0.22) and CAL (1.20 mm, P < 0.22). CONCLUSION: Although the qualitative analysis have suggested worse periodontal conditions in dementia patients, due to different study types and the high heterogeneity among them, the meta-analysis does not support the association between dementia and severity of periodontal disease.

L-PRF associado ao enxerto gengival livre no "creeping attachment": estudo clínico randomizado / L-PRF associated with free gingival graft in the "creeping attachment": randomized clinical trial

O propósito do presente estudo clínico será avaliar o efeito do tratamento de recessões gengivais classe II de Miller com enxerto gengival livre (EGL), associado a fibrina rica em plaquetas e leucócitos (L-PRF) no "creeping attachement" (CA). 12 pacientes que apresentavam recessões bilaterais classe II de Miller, localizadas em pré-molares inferiores, totalizando 24 sítios, foram divididos aleatoriamente nos Grupo EGL (n=12), é o grupo controle no qual o sitio recebeu o recobrimento radicular com enxerto gengival livre (EGL); e o Grupo EGL/L-PRF (n=12), EGL associado ao L-PRF, estabilização de membrana de L-PRF no leito receptor e sutura do EGL. Para obtenção do L-PRF, foi realizada a coleta de 20 ml de sangue de cada paciente, que foi imediatamente centrifugado a 2700 rpm, por 12 minutos. Realizou a medida do recobrimento radicular o presente no período inicial e após 30 dias de pós-operatório, e foi avaliado a quantidade de CA (90, 180 e 360 dias). Após 360 dias não foi possível observar uma diferença significativa de CA entre os grupos EGL (1.81 ± 0.40) e 1.00 ± 0.70 (EGL/L-PRF ), entretanto ocorreu diferença na quantidade de mucosa queratinizada, gengiva inserida e altura da recessão. EGL e EGL/L-PRF proporcionaram aumento na mucosa queratinizada e migração tecidual em recessões classe II de Miller(AU)

The main objective of the present clinic study will be to evaluate through observation of the root covering, the "creeping attachment" (CA) on Miller class II gingival recession treated with free gingival graft combined with leucocyte and platelet rich-fibrin (PRFL). 12 patients with bilateral Miller Class II gingival recession in lower premolars were recruited. Group FGG (n=12): control group, the site will receive the root coverage with free gingival graft, and Group FGG/L-PRF (n=12): will be performed an association between free gingival graft and L-PRF, the L- PRF membrane stabilized to the receptor region and suturing the EGL. To obtain this platelet concentrate, 20 ml of blood of each patient will be collected and immediately centrifuged at 2700rpm for 12 minutes. The following parameters will be measured: O`Leary plaque index, gingival index, height of gingival recession, recession width, amount of keratinized mucosa, probing depth (PD) and then, the clinical attachment level will be conducted. The measurements will be performed at 30, 90, 180 e 360 days after the surgical procedure. The CA will be measured at 90, 180 and 360 days. Data will be analyzed statistically (p < 0.05) in a specialized computer program (Bioestat 5.0). After 360 days, significant differences were not found between the two groups for CA, however there was a significant difference for keratinized gingiva, gingival height and clinical attachment level. EGL and EGL/L-PRF are equally successful in the creeping attachment gain in gingival recession of Miller class II(AU)