This clinical study was conducted to quantify cultivable bacteria and endotoxin in root canals with post-treatment apical periodontitis by correlating their levels with clinical features and to ...evaluate the effect of chemo-mechanical preparation (CMP) with 2 % chlorhexidine gel + 17 % EDTA on bacterial and endotoxin removal/elimination. Moreover, target strict Gram-negative anaerobic bacteria were investigated by polymerase chain reaction (PCR). Fifteen teeth with post-treatment apical periodontitis were sampled before (s1) and after (s2) CMP. Culture techniques determined the number of colony-forming units (CFU). PCR (16S rDNA) and limulus amebocyte lysate (LAL) assay were used for bacterial and endotoxin detection, respectively.
Prevotella nigrescens
(4/15),
Prevotella intermedia
(2/15), and
Tannerella forsythia
(2/15) were the most frequently detected species. Endotoxin was recovered in 100 % of the samples. At s1, bacteria and endotoxin were detected at a median value of 5.14 × 10
3
CFU/mL and 3.96 EU/mL, respectively. Higher levels of endotoxin were related to a larger size of radiolucent area (>5 mm) (
p
< 0.05). CMP was more effective in reducing bacteria (99.61 %) than endotoxin (60.6 %) (both
p
< 0.05). Our findings indicated that the levels of endotoxin found in infected root canals were related to a larger size of radiolucent area in the periapical region. Moreover, CMP was effective in reducing both bacterial and endotoxin contents in post-treatment apical periodontitis.
To provide species distribution and antifungal susceptibility profiles of 358 Trichosporon clinical isolates collected from 24 tertiary-care hospitals.
Species identification was performed by ...sequencing the IGS1 region of rDNA. Antifungal susceptibility testing for amphotericin B, fluconazole, voriconazole and posaconazole followed the Clinical and Laboratory Standards Institute reference method. Tentative epidemiologic cutoff values (97.5% ECVs) of antifungals for Trichosporon asahii were also calculated.
Isolates were cultured mostly from urine (155/358, 43.3%) and blood (82/358, 23%) samples. Trichosporon asahii was the most common species (273/358, 76.3%), followed by T. inkin (35/358, 9.7%). Isolation of non–T. asahii species increased substantially over the last 11 years 11/77 (14.2%) from 1997 to 2007 vs. 74/281, (26.3%) from 2008 to 2018, p0.03. Antifungal susceptibility testing showed high amphotericin B minimum inhibitory concentrations against Trichosporon isolates, with higher values for T. faecale. The ECV for amphotericin B and T. asahii was set at 4 μg/mL. Among the triazole derivatives, fluconazole was the least active drug. The ECVs for fluconazole and posaconazole against T. asahii were set at 8 and 0.5 μg/mL, respectively. Voriconazole showed the strongest in vitro activity against the Trichosporon isolates; its ECV for T. asahii was set at 0.25 μg/mL after 48 hours' incubation.
Trichosporon species diversity has increased over the years in human samples, and antifungal susceptibility profiles were species specific. Trichosporon asahii antifungal ECVs were proposed, which may be helpful to guide antifungal therapy.
The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease ...caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear.
We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 μg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization.
A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events.
Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).
This article compares the creep testing behavior of AISI 4340 high-strength steel in the as-received and coated conditions. The coating material used was a NiCrBSi self-fluxing alloy. The ...microstructural characterization was carried out using optical and scanning electron microscopy. The creep tests were conducted at a temperature of 550 °C and with loads of 200, 250, and 300 MPa. The microstructure analysis of the deposited layer revealed some inclusions, very low porosity, and good adhesion to the substrate. The results of the creep tests indicated a decrease in the time to rupture under loads of 250 and 300 MPa for the coated steel. At a load of 200 MPa, the coated steel presented longer times to rupture and higher yield strength, demonstrating an improvement over the uncoated steel under these test condition. The fracture surface inspection showed a failure by a ductile fracture in both samples, with and without coating.
Aim
To evaluate in a clinical trial the efficacy of reciprocating and ultrasonic activation of 6% sodium hypochlorite (NaOCl) in the microbial composition and reduction in microbial load as well as ...in levels of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) in teeth with primary endodontic infections.
Methodology
Samples were collected from 24 root canals with pulp necrosis and periapical lesions, before and after chemo‐mechanical canal preparation. The teeth were randomly divided according to the activation protocol as follows: control group without activation (WA, n = 8), reciprocating activation group using Easy Clean tip (EC, n = 8) and ultrasonic activation group using Irrisonic insert (US, n = 8). Microbiological specimens were processed using a culture technique and microbiota composition was analysed using the checkerboard technique. The levels of LPS and LTA were quantified using limulus amebocyte lysate (LAL) and enzyme‐linked immunosorbent assay (ELISA), respectively. The Fisher's exact test, Kruskal–Wallis, Dunn’s and Wilcoxon’s test with a significance level of P < 0.05 were used for statistical analysis.
Results
All initial specimens had growth of viable bacteria in fastidious anaerobe agar (FAA), with an average of 105 CFU mL−1, whereas only one case had such growth after chemo‐mechanical canal preparation. LPS and LTA were recovered in 100% of the cases. Chemo‐mechanical canal preparation significantly decreased the levels of LPS and LTA (P < 0.05), but no significant differences were found between the groups (P > 0.05). Through the checkerboard technique, bacteria were found in 100% of the initial specimens with concentrations between <105 and 106. The most frequently identified microorganisms were Prevotella nigrescens and Enterococcus hirae. After chemo‐mechanical canal preparation, many species were not detected in any of the three groups tested. A significant reduction occurred in Group US, followed by Groups EC and WA.
Conclusions
Activation of 6% NaOCl reduced the levels of LPS and LTA with no differences between the groups. However, ultrasonic activation was associated with a greater reduction in microbial load within root canals.
Embryo mortality is responsible for greater losses in litter size in pigs. It is well known that pregnancy establishment is a complex process, and important changes occur continuously in both the ...corpora lutea and the endometrium, which varies depending on the pre-natal development phase: embryonic, pre-implantation or fetal stages. The placenta is a key organ responsible for the exchange of nutrients, metabolites and respiratory gases between mother and fetuses. The porcine placenta is diffuse, epitheliochorial, and placentation begins with implantation, which involves specialized cell adhesion and cell migration, leading to the attachment of the trophectoderm to the uterine endometrial lumen epithelium. The efficiency with which the placenta provides adequate amounts of nutrients and oxygen to the fetus is crucial for proper fetal growth and development. In the last decades, emphasis on selection for sow prolificacy has resulted in a substantial increase in the number of piglets born per litter, which had a direct effect on piglet quality, compromising birth weight and litter uniformity. Placental insufficiency will lead to fetal intrauterine growth restriction. This review addresses the main events of early embryo development, including preimplantation and implantation periods. In addition, placentation and its role on fetal development are covered, as well as intrauterine growth restriction, as it is a natural condition in the pig, with long lasting detrimental effects to the production chain.
Abstract
Chikungunya virus (CHIKV) is the causative agent of Chikungunya fever, an acute febrile and arthritogenic illness with no effective treatments available. The development of effective ...therapeutic strategies could be significantly accelerated with detailed knowledge of the molecular components behind CHIKV replication. However, drug discovery is hindered by our incomplete understanding of their main components. The RNA-dependent RNA-polymerase (nsP4-CHIKV) is considered the key enzyme of the CHIKV replication complex and a suitable target for antiviral therapy. Herein, the nsP4-CHIKV was extensively characterized through experimental and computational biophysical methods. In the search for new molecules against CHIKV, a compound designated LabMol-309 was identified as a strong ligand of the nsp4-CHIKV and mapped to bind to its active site. The antiviral activity of LabMol-309 was evaluated in cellular-based assays using a CHIKV replicon system and a reporter virus. In conclusion, this study highlights the biophysical features of nsP4-CHIKV and identifies a new compound as a promising antiviral agent against CHIKV infection.
Aim
This clinical study was conducted to investigate the influence of 17% ethylenediaminetetraacetic acid (EDTA) ultrasonic activation after chemomechanical preparation (CMP) on eliminating/reducing ...oral bacterial lipopolysaccharides (known as endotoxins) and cultivable bacteria in teeth with pulp necrosis and apical periodontitis.
Methodology
Samples were taken from 24 root canals at several clinical periods: S1 – before CMP; S2 – after CMP; S3 – after EDTA: G1 – with ultrasonic activation (n = 12) and G2 – without ultrasonic activation (n = 12). Root canals were instrumented using Mtwo rotary files. Culture techniques were used to determine the number of colony‐forming units (CFU). Limulus amebocyte lysate (LAL) was used to measure endotoxin levels. Friedman's and Wilcoxon signed‐rank tests were used to compare the amount of bacteria and endotoxin levels in each period (P < 0.05).
Results
Endotoxins and cultivable bacteria were recovered in 100% of the initial samples (S1). CMP was effective in reducing endotoxins and bacterial load (all with P < 0.05). Higher values of endotoxin reduction were achieved with EDTA ultrasonic activation G1, 0.02 EU mL−1 (range 0.01–0.75) compared with the no activation group G2, 1.13 EU mL−1 (range 0.01–8.34) (P < 0.05). Regarding bacterial reduction, no statistically significant difference was found in S3, regardless of the group (G1, G2, P > 0.05).
Conclusions
Chemomechanical preparation was effective in reducing bacteria and endotoxins, but could not completely eliminate them. The ultrasonic activation of EDTA was effective in further reducing endotoxin levels in the root canals of teeth with pulp necrosis and apical periodontitis.
Sarcopenia is a pathology resulting from a progressive and severe loss of muscle mass, strength, and function in the course of aging, which has deleterious consequences on quality of life. Among the ...most widespread studies on the issue are those focused on the effect of different types of physical exercise on patients with sarcopenia. This randomized controlled study aimed to compare the effects of a whole-body vibration exercise (WBV) session on the inflammatory parameters of non-sarcopenic (NSG, n=22) and sarcopenic elderly (SG, n=22). NSG and SG participants were randomly divided into two protocols: intervention (squat with WBV) and control (squat without WBV). After a one-week washout period, participants switched protocols, so that everyone performed both protocols. Body composition was assessed by dual-energy radiological absorptiometry (DXA) and function through the six-minute walk test (6MWD) and Short Physical Performance Battery (SPPB). Plasma soluble tumor necrosis factor receptors (sTNFR) were determined by enzyme-linked immunosorbent assay (ELISA) and measured before and immediately after each protocol. After exercise with WBV, there was an increase in sTNFR2 levels in the NSG (P<0.01; d=-0.69 (-1.30; -0.08) and SG (P<0.01, d=-0.95 (-1.57; -0.32) groups. In conclusion, an acute session of WBV influenced sTNFr2 levels, with sarcopenic individuals showing a greater effect. This suggested that WBV had a more pronounced impact on sTNFr2 in those with loss of muscle strength and/or physical performance. Additionally, WBV is gaining recognition as an efficient strategy for those with persistent health issues.
To investigate how ANP32A, previously linked to the antioxidant response, regulates Wnt signaling as unraveled by transcriptome analysis of Anp32a-deficient mouse articular cartilage, and its ...implications for osteoarthritis (OA) and diseases beyond the joint.
Anp32a knockdown chondrogenic ATDC5 cells were cultured in micromasses. Wnt target genes, differentiation markers and matrix deposition were quantified. Wnt target genes were determined in articular cartilage from Anp32a-deficient mice and primary human articular chondrocytes upon ANP32A silencing, using qPCR, luciferase assays and immunohistochemistry. Co-immunoprecipitation, immunofluorescence and chromatin-immunoprecipitation quantitative PCR probed the molecular mechanism via which ANP32A regulates Wnt signaling. Anp32a-deficient mice were subjected to the destabilization of the medial meniscus (DMM) OA model and treated with a Wnt inhibitor and an antioxidant. Severity of OA was assessed by cartilage damage and osteophyte formation. Human Protein Atlas data analysis identified additional organs where ANP32A may regulate Wnt signaling. Wnt target genes were determined in heart and hippocampus from Anp32a-deficient mice, and cardiac hypertrophy and fibrosis quantified.
Anp32a loss triggered Wnt signaling hyper-activation in articular cartilage. Mechanistically, ANP32A inhibited target gene expression via histone acetylation masking. Wnt antagonist treatment reduced OA severity in Anp32a-deficient mice by preventing osteophyte formation but not cartilage degradation, contrasting with antioxidant treatment. Dual therapy ameliorated more OA features than individual treatments. Anp32a-deficient mice also showed Wnt hyper-activation in the heart, potentially explaining the cardiac hypertrophy phenotype found.
ANP32A is a novel translationally relevant repressor of Wnt signaling impacting osteoarthritis and cardiac disease.
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