African League Against Rheumatism (AFLAR) preliminary recommendations on the management of rheumatic diseases during the COVID-19 pandemic

Objectives To develop recommendations for the management of rheumatic and musculoskeletal diseases (RMDs) during the COVID-19 pandemic. Method A task force comprising of 25 rheumatologists from the 5 regions of the continent was formed and operated through a hub-and-spoke model with a central working committee (CWC) and 4 subgroups. The subgroups championed separate scopes of the clinical questions and formulated preliminary statements of recommendations which were processed centrally in the CWC. The CWC and each subgroup met by several virtual meetings, and two rounds of voting were conducted on the drafted statements of recommendations. Votes were online-delivered and recommendations were pruned down according to predefined criteria. Each statement was rated between 1 and 9 with 1–3, 4–6 and 7–9 representing disagreement, uncertainty and agreement, respectively. The levels of agreement on the statements were stratified as low, moderate or high according to the spread of votes. A statement was retired if it had a mean vote below 7 or a ‘low’ level of agreement. Results A total of 126 initial statements of recommendations were drafted, and these were reduced to 22 after the two rounds of voting. Conclusions The preliminary statements of recommendations will serve to guide the clinical practice of rheumatology across Africa amidst the changing practices and uncertainties in the current era of COVID-19. It is recognized that further updates to the recommendations will be needed as more evidence emerges

A 12-month clinical evaluation of pit-and-fissure sealants placed with and without etch-and-rinse and self-etch adhesive systems in newly-erupted teeth

OBJECTIVES: The objective of this one-year clinical study was to investigate the effect of two adhesive systems (Adper Single Bond, a two-step etch-and-rinse and Clearfil SE Bond, a two-step self-etch system) on pit-and-fissure sealant retention in newly-erupted teeth. This study compared the success of the sealants in mesial and distopalatal grooves with and without these two adhesive systems. MATERIAL AND METHODS: In a clinical trial, 35 children aged 6-8 years undergoing sealant placement were recruited. This one-year clinical study scored 70 mesial and 70 distopalatal sealants of newly-erupted permanent maxillary first molar, with a split-mouth design. All children received sealant alone in one permanent maxillary molar tooth. Children were randomized into two groups. One group received Self-Etch (SE) bond plus sealant and the other group received Single Bond plus sealant in another permanent maxillary molar tooth. Clinical evaluation at 3, 6 and 12 months was performed and the retention was studied in terms of the success and failure. RESULTS: The success rate of sealant in the distopalatal groove, using SEB at 3, 6 and 12 months was 93.3% (95% CI: 68.0, 99.8), 73.3% (95% CI: 44.9, 92.2) and 66.7% (95% CI: 38.4, 88.2), respectively. It was greater than that of the distopalatal groove in SB group with a success rate of 62.5% (95% CI: 35.4, 84.8), 31.3% (95% CI: 11.8, 58.7) and 31.3% (95% CI: 11.8, 58.7), at the three evaluation periods. The success rate of sealant in the mesial groove using SEB was 86.6% (95% CI: 59.5, 98.3), 53.3% (95% CI: 26.6, 78.7) and 53.3% (95% CI: 26.6, 78.7), while this was 100% (95% CI: 79.4, 100.0), 81.3% (95% CI: 54.4, 96.0) and 81.3% (95% CI: 54.4, 96.0) using SB, at 3, 6 and 12-month evaluation periods. CONCLUSIONS: These results support the use of these two bonding agents in pit-and-fissure sealants under both isolated and contaminated conditions. Further, SE bond seemed to be less sensitive to moisture contamination

Survival and Factors Associated with Failure of Pulpectomies Performed in Primary Teeth by Dental Students

Abstract Although endodontic treatment is widely recommended for compromised dental pulp, there is no information regarding the factors associated with failures in primary teeth. The aim of this study was to evaluate the survival and factors associated with failure of pulpectomies performed in primary teeth by dental students. The sample comprised patients treated at a University Dental Service and required endodontic treatment in primary teeth. The study investigated treatment-related variables and patient factors potentially associated with treatment failure. Pulpectomy survival was analyzed by Kaplan-Meier estimator followed by log-rank test (p<0.05). The analysis included 81 pulpectomies performed in 62 children (5.6±1.5 years). The survival reached 62.9% up to 12 months follow-up. Most failures occurred in the first 3 months (p<0.001). Teeth with carious lesions at the start of treatment presented more failures than those with restorations or history of trauma (p=0.002). The survival of endodontically treated teeth restored with composite was higher than the ones filled with GIC (p=0.006). Pulpectomy performed in two or more sessions resulted in more failures (p=0.028). Patients presenting gingivitis had more failures in the endodontic treatment (p=0.022). The failures of root canal treatment in primary teeth were more prone to occur in a short time and when the treatment was performed in teeth presenting carious lesions. The use of composite instead of GIC increased the survival of pulpectomies. Repeated sessions for endodontic treatment and lack of oral hygiene habits had a negative effect on the results

The Tumor Suppressor Gene, RASSF1A, Is Essential for Protection against Inflammation -Induced Injury

10.1371/journal.pone.0075483PLoS ONE810-POLN

Proteomic Modeling for HIV-1 Infected Microglia-Astrocyte Crosstalk

Background: HIV-1-infected and immune competent brain mononuclear phagocytes (MP; macrophages and microglia) secrete cellular and viral toxins that affect neuronal damage during advanced disease. In contrast, astrocytes can affect disease by modulating the nervous system’s microenvironment. Interestingly, little is known how astrocytes communicate with MP to influence disease. Methods and Findings: MP-astrocyte crosstalk was investigated by a proteomic platform analysis using vesicular stomatitis virus pseudotyped HIV infected murine microglia. The microglial-astrocyte dialogue was significant and affected microglial cytoskeleton by modulation of cell death and migratory pathways. These were mediated, in part, through F-actin polymerization and filament formation. Astrocyte secretions attenuated HIV-1 infected microglia neurotoxicity and viral growth linked to the regulation of reactive oxygen species. Conclusions: These observations provide unique insights into glial crosstalk during disease by supporting astrocytemediated regulation of microglial function and its influence on the onset and progression of neuroAIDS. The results open new insights into previously undisclosed pathogenic mechanisms and open the potential for biomarker discovery an

Metabolic Turnover of Synaptic Proteins: Kinetics, Interdependencies and Implications for Synaptic Maintenance

Chemical synapses contain multitudes of proteins, which in common with all proteins, have finite lifetimes and therefore need to be continuously replaced. Given the huge numbers of synaptic connections typical neurons form, the demand to maintain the protein contents of these connections might be expected to place considerable metabolic demands on each neuron. Moreover, synaptic proteostasis might differ according to distance from global protein synthesis sites, the availability of distributed protein synthesis facilities, trafficking rates and synaptic protein dynamics. To date, the turnover kinetics of synaptic proteins have not been studied or analyzed systematically, and thus metabolic demands or the aforementioned relationships remain largely unknown. In the current study we used dynamic Stable Isotope Labeling with Amino acids in Cell culture (SILAC), mass spectrometry (MS), Fluorescent Non-Canonical Amino acid Tagging (FUNCAT), quantitative immunohistochemistry and bioinformatics to systematically measure the metabolic half-lives of hundreds of synaptic proteins, examine how these depend on their pre/postsynaptic affiliation or their association with particular molecular complexes, and assess the metabolic load of synaptic proteostasis. We found that nearly all synaptic proteins identified here exhibited half-lifetimes in the range of 2-5 days. Unexpectedly, metabolic turnover rates were not significantly different for presynaptic and postsynaptic proteins, or for proteins for which mRNAs are consistently found in dendrites. Some functionally or structurally related proteins exhibited very similar turnover rates, indicating that their biogenesis and degradation might be coupled, a possibility further supported by bioinformatics-based analyses. The relatively low turnover rates measured here (∼0.7% of synaptic protein content per hour) are in good agreement with imaging-based studies of synaptic protein trafficking, yet indicate that the metabolic load synaptic protein turnover places on individual neurons is very substantial

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570