ROS-scavenging lipid-based liquid crystalline as a favorable stem cell extracellular vesicles delivery vector to promote wound healing.

Wound management is a critical clinical challenge due to the dynamic and complex pathological characteristics of inflammation, proliferation, and matrix remodeling. To address this challenge, the regulation and management of this multi-stage pathological microenvironment may provide a feasible approach to wound healing. In this work, we synthesized a new lipid material (DA) with reactive oxygen species (ROS) scavenging effect to prepare DA-based liquid crystalline (DALC). Then, DALC was incorporated with adipose mesenchymal stem cells-derived extracellular vesicles (AMSC-EVs) to fabricate a novel scaffold dressing (EVs@DALC) for the treatment of the wound. DALC not only endowed EVs@DALC with ROS scavenging sites for relieving the oxidative stress and inflammation in the microenvironment of the wound site, but also facilitated cellular uptake and transfection of microRNA and growth factors contained in AMSC-EVs. Benefiting from DALC, AMSC-EVs effectively transferred microRNA and growth factors into the skin cells to induce cell proliferation and migration and accelerate angiogenesis. The results of wound healing effect in vivo indicate EVs@DALC achieved multi-stage pathological modulation for accelerating wound healing through alleviating inflammation, promoting cell proliferation and migration, and angiogenesis. Taken together, this work provides an effective strategy based on antioxidant lipid liquid crystalline delivering extracellular vesicles in treating skin wounds and paves a way for stem cell extracellular vesicles clinical translation.

Unraveling the relationship between high-sensitivity C-reactive protein and frailty: evidence from longitudinal cohort study and genetic analysis.

BACKGROUND: This study aimed to investigate the association of high-sensitivity C-reactive protein (hs-CRP) with incident frailty as well as its effects on pre-frailty progression and regression among middle-aged and older adults. METHODS: Based on the frailty index (FI) calculated with 41 items, 6890 eligible participants without frailty at baseline from China Health and Retirement Longitudinal Study (CHARLS) were categorized into health, pre-frailty, and frailty groups. Logistic regression models were used to estimate the longitudinal association between baseline hs-CRP and incident frailty. Furthermore, a series of genetic approaches were conducted to confirm the causal relationship between CRP and frailty, including Linkage disequilibrium score regression (LDSC), pleiotropic analysis, and Mendelian randomization (MR). Finally, we evaluated the association of hs-CRP with pre-frailty progression and regression. RESULTS: The risk of developing frailty was 1.18 times (95% CI: 1.03-1.34) higher in participants with high levels of hs-CRP at baseline than low levels of hs-CRP participants during the 3-year follow-up. MR analysis suggested that genetically determined hs-CRP was potentially positively associated with the risk of frailty (OR: 1.06, 95% CI: 1.03-1.08). Among 5241 participants with pre-frailty at baseline, we found pre-frailty participants with high levels of hs-CRP exhibit increased odds of progression to frailty (OR: 1.39, 95% CI: 1.09-1.79) and decreased odds of regression to health (OR: 0.84, 95% CI: 0.72-0.98) when compared with participants with low levels of hs-CRP. CONCLUSIONS: Our results suggest that reducing systemic inflammation is significant for developing strategies for frailty prevention and pre-frailty reversion in the middle-aged and elderly population.

Effectiveness of internet-based nursing interventions for the treatment of patients with periodontitis.

BACKGROUND: Periodontitis, one of the most common oral diseases, is a chronic inflammatory condition occur in response to bacterial plaque biofilms. Plaque control and oral hygiene instructions are the most widely used and effective nonsurgical treatment for periodontitis, which is based on a partnership between patient and clinician and requires a life-long commitment. The objective of this study was to analyze the effectiveness of internet-based nursing interventions for the treatment of patients with periodontitis. The findings from this study may help to enhance the therapeutic outcomes for patients with periodontitis. METHODS: A total of 80 patients with periodontitis treated in Zhejiang Province Stomatology hospital from December 2021 to January 2023 were randomly selected and divided into control group and intervention group with 40 cases each. The control group was given routine oral health guidance and the intervention group received internet based nursing intervention. The periodontal pocket depth, percentage of periodontal pocket depth (PD) ≥ 4 mm, bleeding on probing (BOP)%, and self-efficacy scale for oral health care (SESS) were assessed and compared at four time points: initial visit, 6-8-weeks follow-up, 3-months follow-up, and 6-months follow-up. RESULTS: There was no significant difference between the two groups in terms of age, gender, initial visit PD, initial visit PD ≥ 4 mm (%), initial visit BOP (%), and initial visit SESS (P > 0.05). The intervention group showed a significantly decreased percentage of PD ≥ 4 mm at 6-8 weeks and 6-months follow-up compared to the control group (P < 0.05). The PD, BOP%, and SESS scores of the intervention group were significantly better than those of the control group at 6-months follow-up (P < 0.05). There was no statistically significant difference in patient satisfaction between the two groups. CONCLUSIONS: This study confirmed that the internet-based nursing intervention in conjunction with periodontal treatment was able to improve the periodontal pocket depth, gingival bleeding and the level of self-efficacy of patients, suggesting that it is necessary to carry out the extended oral hygiene instructions via internet-based platforms for the patients in clinical practice.

Genetic causal association between rheumatoid arthritis and periodontitis: a bidirectional two-sample Mendelian randomization analysis.

BACKGROUND: A link between rheumatoid arthritis (RA) and periodontitis (PD) has been established. However, their causal relationship remains unclear and the effect of different serotypes of RA on the PD development has not been investigated. This study aims to elucidate the causal association between PD and different serotypes of RA using Mendelian randomization (MR). METHODS: A bidirectional two-sample MR analysis was performed using available large-scale genome-wide association studies statistics. The inverse-variance weighted (IVW) or multiplicative random-effects IVW was used to determine causality, depending on the heterogeneity of instrumental variables. Additional sensitivity analyses were also performed. RESULTS: The forward MR analysis identified that seropositive RA (odds ratio (OR), 1.26; 95% confidence interval (CI), 1.07-1.44; p = 0.0018), but not seronegative RA (OR, 1.01; 95% CI, 0.95-1.06; p = 0.9098), was associated with an increased risk of PD. The reverse MR analysis did not show any significant causal effect of PD on RA, independent of the serotypes. The sensitivity tests (p > 0.05) confirmed the robustness and accuracy of these findings. CONCLUSION: This study revealed that there was a genetic causal effect of seropositive RA on PD, suggesting that this subtype of RA patients may require specific clinical attention to prevent the development of PD.

High sensitivity C-reactive protein and prediabetes progression and regression in middle-aged and older adults: A prospective cohort study.

BACKGROUND: This study aimed to investigate the effect of systemic inflammation, assessed by high sensitivity C-reactive protein (hs-CRP) levels, on prediabetes progression and regression in middle-aged and older adults based on the China Health and Retirement Longitudinal Study (CHARLS). METHODS: Participants with prediabetes from CHARLS were followed up 4 years later with blood samples collected for measuring fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). The level of hs-CRP was assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow-up was defined primarily according to the American Diabetes Association (ADA) criteria. Logistic regression models were used to estimate the odds ratios (ORs) and confidence intervals (CIs). We also performed stratified analyses according to age, gender, BMI, the presence of hypertension, and the disease history of heart disease and dyslipidemia and sensitivity analyses excluding a subset of participants with incomplete data. RESULTS: Of the 2,874 prediabetes included at baseline, 834 participants remained as having prediabetes, 146 progressed to diabetes, and 1,894 regressed to normoglycemia based on ADA criteria with a 4 year follow-up. After multivariate logistics regression analysis, prediabetes with middle (0.67-1.62 mg/L) and high (>1.62 mg/L) hs-CRP levels had an increased incidence of progressing to diabetes compared with prediabetes with low hs-CRP levels (<0.67 mg/L; OR = 1.846, 95%CI: 1.129-3.018; and OR = 1.632, 95%CI: 0.985-2.703, respectively), and the incidence of regressing to normoglycemia decreased (OR = 0.793, 95%CI: 0.645-0.975; and OR = 0.769, 95%CI: 0.623-0.978, respectively). Stratified analyses and sensitivity analyses showed consistent results. CONCLUSIONS: Low levels of hs-CRP are associated with a high incidence of regression from prediabetes to normoglycemia and reduced odds of progression to diabetes.

Schiff Base Reaction in a Living Cell: In Situ Synthesis of a Hollow Covalent Organic Polymer To Regulate Biological Functions.

Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.

Representational Geometries Reveal Differential Effects of Response Correlations on Population Codes in Neurophysiology and Functional Magnetic Resonance Imaging.

Two sensory neurons usually display trial-by-trial spike-count correlations given the repeated representations of a stimulus. The effects of such response correlations on population-level sensory coding have been the focal contention in computational neuroscience over the past few years. In the meantime, multivariate pattern analysis (MVPA) has become the leading analysis approach in functional magnetic resonance imaging (fMRI), but the effects of response correlations among voxel populations remain underexplored. Here, instead of conventional MVPA analysis, we calculate linear Fisher information of population responses in human visual cortex (five males, one female) and hypothetically remove response correlations between voxels. We found that voxelwise response correlations generally enhance stimulus information, a result standing in stark contrast to the detrimental effects of response correlations reported in empirical neurophysiological studies. By voxel-encoding modeling, we further show that these two seemingly opposite effects actually can coexist within the primate visual system. Furthermore, we use principal component analysis to decompose stimulus information in population responses onto different principal dimensions in a high-dimensional representational space. Interestingly, response correlations simultaneously reduce and enhance information on higher- and lower-variance principal dimensions, respectively. The relative strength of the two antagonistic effects within the same computational framework produces the apparent discrepancy in the effects of response correlations in neuronal and voxel populations. Our results suggest that multivariate fMRI data contain rich statistical structures that are directly related to sensory information representation, and the general computational framework to analyze neuronal and voxel population responses can be applied in many types of neural measurements.SIGNIFICANCE STATEMENT Despite the vast research interest in the effect of spike-count noise correlations on population codes in neurophysiology, it remains unclear how the response correlations between voxels influence MVPA in human imaging. We used an information-theoretic approach and showed that unlike the detrimental effects of response correlations reported in neurophysiology, voxelwise response correlations generally improve sensory coding. We conducted a series of in-depth analyses and demonstrated that neuronal and voxel response correlations can coexist within the visual system and share some common computational mechanisms. These results shed new light on how the population codes of sensory information can be evaluated via different neural measurements.

Multivariate and spatio-temporal groundwater pollution risk assessment: A new long-time serial groundwater environmental impact assessment system.

Groundwater pollution risk assessment is an important part of environmental assessment. Although it has been developed for many years, there has not yet been a multi-dimensional method that takes into account long time series and spatial factors. We proposed a new method combines the advantages of remote sensing cloud computing, long-term groundwater modeling simulation and GIS technology to solve it efficiently. A coastal industrial park in Hainan was used as the study area. The depth of groundwater level, rainfall, topography and geomorphology, soil moisture, pollution source, pollution toxicity and other more than 10 parameters were used as the indexes. A comprehensive model with remote sensing cloud computing, DRASTIC model and Modflow + MT3DMS was established to assess the pollution risk from 2014 to 2021. The multi-year results indicated that the risk assessment of groundwater pollution was usually on the vertical coastal direction, and the risk increased from far away to near coast. With the discharge of pollutants in the industrial park, the pollution risk in the area 5 km away from the centre increased year by year until it became stable in 2019, and the risk in the centre of the park reached 1 level, covered an area of up to 145400 square metres, accounted for 0.012% of the whole study area. The assessment results in 2020 and 2021 fluctuate slightly compared with those in 2019. Therefore, in terms of groundwater resource protection and resource management, it is necessary to focus on the detection of pollution in the coastal zone and the pollution within 5 km of the centre to strictly control pollution discharge. In this study, the comprehensive assessment includes surface indicators, subsurface indicators, and pollutant indicators. Finally, we achieve a multivariate, spatial and long time series groundwater pollution risk assessment system, which is a new groundwater environmental impact assessment (GEIA) system.

The Oral Microbiome and Its Role in Systemic Autoimmune Diseases: A Systematic Review of Big Data Analysis.

Introduction: Despite decades of research, systemic autoimmune diseases (SADs) continue to be a major global health concern and the etiology of these diseases is still not clear. To date, with the development of high-throughput techniques, increasing evidence indicated a key role of oral microbiome in the pathogenesis of SADs, and the alterations of oral microbiome may contribute to the disease emergence or evolution. This review is to present the latest knowledge on the relationship between the oral microbiome and SADs, focusing on the multiomics data generated from a large set of samples. Methodology: By searching the PubMed and Embase databases, studies that investigated the oral microbiome of SADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren's syndrome (SS), were systematically reviewed according to the PRISMA guidelines. Results: One thousand and thirty-eight studies were found, and 25 studies were included: three referred to SLE, 12 referred to RA, nine referred to SS, and one to both SLE and SS. The 16S rRNA sequencing was the most frequent technique used. HOMD was the most common database aligned to and QIIME was the most popular pipeline for downstream analysis. Alterations in bacterial composition and population have been found in the oral samples of patients with SAD compared with the healthy controls. Results regarding candidate pathogens were not always in accordance, but Selenomonas and Veillonella were found significantly increased in three SADs, and Streptococcus was significantly decreased in the SADs compared with controls. Conclusion: A large amount of sequencing data was collected from patients with SAD and controls in this systematic review. Oral microbial dysbiosis had been identified in these SADs, although the dysbiosis features were different among studies. There was a lack of standardized study methodology for each study from the inclusion criteria, sample type, sequencing platform, and referred database to downstream analysis pipeline and cutoff. Besides the genomics, transcriptomics, proteomics, and metabolomics technology should be used to investigate the oral microbiome of patients with SADs and also the at-risk individuals of disease development, which may provide us with a better understanding of the etiology of SADs and promote the development of the novel therapies.

Groundwater pollution risk assessment based on groundwater vulnerability and pollution load on an isolated island.

Prolonged leakage of surface pollutants has an impact on groundwater quality, especially in shallow groundwater. This paper proposes a new method combining Modflow and geographic information system data for groundwater pollution risk assessment. First, hydrogeological information of the study area was obtained through a field investigation and data referencing, and the groundwater flow field in the study area was constructed. The actual drilling water level data were then used for verification. A groundwater solute transport model was constructed based on the groundwater flow field, combined with pollution source sampling and detection data. Finally, based on the simulation of the migration value of pollutants, the groundwater in the study area was evaluated by constructing a groundwater pollution risk assessment system that combined groundwater vulnerability and pollution load. The results showed that in the study area, the heavy-risk area accounted for 38%, the high-risk area accounted for 29%, the medium-risk area accounted for 22%, and the low-risk area accounted for 11%. Approximately 70% of the area was rated as high-risk or above, indicating that the groundwater in the study area was more susceptible to surface pollutants. Once groundwater is contaminated, recovery is difficult; therefore, groundwater pollution risk assessments are necessary. The groundwater pollution risk assessment system constructed by the groundwater numerical simulation and multi-index comprehensive evaluation method has significance as a reference for regional groundwater pollution risk identification and scientific management.

Efficacy of strontium supplementation on implant osseointegration under osteoporotic conditions: A systematic review.

STATEMENT OF PROBLEM: Strontium has been validated for potent bone-seeking and antiosteoporotic properties and elicits a potentially beneficial impact on implant osseointegration in patients with osteoporosis. However, the efficacy of strontium supplementation on improving new bone formation and implant osseointegration in the presence of osteoporotic bone is still unclear. PURPOSE: The purpose of this systematic review was to comprehensively assess the efficacy of strontium supplementation, encompassing oral intake and local delivery of strontium, on implant osseointegration in patients with osteoporosis. MATERIAL AND METHODS: Searches on electronic databases (MEDLINE or PubMed, Web of Science, EBSCO, Embase, and Clinicaltrials.gov) and manual searches were conducted to identify relevant preclinical animal trials up to June 2020. The primary outcomes were the percentage of bone-implant contact and bone area; the secondary outcomes were quantitative parameters of biomechanical tests and microcomputed tomography (µCT). RESULTS: Fourteen preclinical trials (1 rabbit, 1 sheep, and 12 rat), with a total of 404 ovariectomized animals and 798 implants, were eligible for analysis. The results revealed a significant 17.1% increase in bone-implant contact and 13.5% increase in bone area, favoring strontium supplementation despite considerable heterogeneity. Subgroup analyses of both bone-implant contact and bone area exhibited similar outcomes with low to moderate heterogeneity. Results of biomechanical and µCT tests showed that strontium-enriched implantation tended to optimize the mechanical strength and microarchitecture of newly formed bone despite moderate to generally high heterogeneity. CONCLUSIONS: Based on the available preclinical evidence, strontium supplementation, including local and systemic delivery, showed promising results for enhancing implant osseointegration in the presence of osteoporosis during 4 to 12 weeks of healing. Future well-designed standardized studies are necessary to validate the efficacy and safety of strontium supplementation and to establish a standard methodology for incorporating Sr into implant surfaces in a clinical setting.

Which can explain the pip-and-pop effect during a visual search: Multisensory integration or the oddball effect?

In a dynamic search task, participants were instructed to search for a visual target among various distractors. An auditory stimulus presented in synchrony with a color change of the visual target can improve the efficiency of the search, which is known as the pip-and-pop effect. Some researchers have suggested that the underlying mechanism of this effect is multisensory integration, while others have thought it is due to an oddball stimulation that attracts attention. Utilizing the eye movement technique, we conducted 3 experiments to investigate the pip-and-pop effect and its causes. In Experiment 1, we used a static search paradigm and controlled for the presence or absence of sound cues when the visual target was presented. It turned out that sound had no effect on a static search; that is, no pip-and-pop effect was found. In Experiment 2, we used a dynamic search paradigm in which the participants were instructed to search for vertical or horizontal line segments among various directional distractor segments and as the color of individual segments changed randomly during the stimulus presentation, with and without the sound cue. We found that the pip-and-pop effect was present. The irrelevant sound reduced the mean fixation number and expanded the mean saccade amplitude. In Experiment 3, we also used a dynamic search paradigm and controlled the frequency of synchronization between the sound and the target color change. There were 3 types of sound conditions: No-sound, 1-sound, and 2-sound. The results suggest that as the frequency of synchronization between the sound and the target color change increases (2-sound condition), the pip-and-pop effect also increases. Therefore, we propose that the pip-and-pop effect is more likely to result from the attention attracted by oddball stimuli than from the multisensory integration of synchronized auditory-visual stimuli. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Impact of Distracting Emotional Stimuli on the Characteristics of Movement Performance: A Kinematic Study.

It is well-documented that emotional stimuli impact both the cognitive and motor aspects of "goal-directed" behavior. However, how emotional distractors impact motor performance remains unclear. This study aimed to characterize how movement quality was impacted during emotional distractors. We used a modified oddball paradigm and documented the performance of pure movement. Participants were designated to draw a triangle or a polygon, while an emotional stimulus was presented. Speed was assessed using reaction time and movement time. The quality and precision of movement were assessed by calculating the accuracy and root-mean-square error (RMSE). Compared to drawings of triangles, polygons had higher accuracy under negative stimuli, but lower RMSE under positive stimuli. The results indicate that distracting emotional stimuli impact different aspects of movement quality, with movement complexity influencing accuracy under negative distractors and precision under positive distractors. This study provides further evidence that movement precision is an important feature of emotional embodiment that should be incorporated in future studies.

Dysbiosis in the oral microbiomes of anti-CCP positive individuals at risk of developing rheumatoid arthritis.

OBJECTIVES: An increased prevalence of periodontitis and perturbation of the oral microbiome has been identified in patients with rheumatoid arthritis (RA). The periodontal pathogen Porphyromonas gingivalis may cause local citrullination of proteins, potentially triggering anti-citrullinated protein antibody production. However, it is not known if oral dysbiosis precedes the onset of clinical arthritis. This study comprehensively characterised the oral microbiome in anti-cyclic citrullinated peptide (anti-CCP) positive at-risk individuals without clinical synovitis (CCP+at risk). METHODS: Subgingival plaque was collected from periodontally healthy and diseased sites in 48 CCP+at risk, 26 early RA and 32 asymptomatic healthy control (HC) individuals. DNA libraries were sequenced on the Illumina HiSeq 3000 platform. Taxonomic profile and functional capability of the subgingival microbiome were compared between groups. RESULTS: At periodontally healthy sites, CCP+at risk individuals had significantly lower microbial richness compared with HC and early RA groups (p=0.004 and 0.021). Microbial community alterations were found at phylum, genus and species levels. A large proportion of the community differed significantly in membership (523 species; 35.6%) and structure (575 species; 39.1%) comparing CCP+at risk and HC groups. Certain core species, including P. gingivalis, had higher relative abundance in the CCP+at risk group. Seventeen clusters of orthologous gene functional units were significantly over-represented in the CCP+at risk group compared with HC (adjusted p value <0.05). CONCLUSION: Anti-CCP positive at-risk individuals have dysbiotic subgingival microbiomes and increased abundance of P. gingivalis compared with controls. This supports the hypothesis that the oral microbiome and specifically P. gingivalis are important in RA initiation.

Limitations of concurrently representing objects within view and in visual working memory.

Representing visibly present stimuli is as limited in capacity as representing invisible stimuli in visual working memory (WM). In this study, we explored whether concurrently representing stimuli within view affects representing objects in visual WM, and if so, whether this effect is modulated by the storage states (active and silent state) of memory contents? In experiment 1, participants were asked to perform the change-detect task in a simultaneous-representing condition in which WM content and the continuously-visible stimuli in view were simultaneously represented, as well as a baseline condition in which only the representations of visual WM content were maintained. The results showed that the representations in visual WM would be impaired when the continuously-visible stimuli in view were concurrently represented, revealed by the reduced CDA amplitude and the lower behavior performance. In experiment 2, a dual-serial retro-cue paradigm was adopted to guide participants to maintain memory items in two different storage states, and the results revealed that simultaneously representing the continuously-visible stimuli and the WM content would only impair the WM representations in the active state. These evidences demonstrated that only the visual WM representations that were maintained in the active state would definitely share the limited resources with the representations of continuously-visible information, and further supported the dissociation between the active state and silent state of visual WM storage.

Association of Hepatic Global DNA Methylation and Serum One-Carbon Metabolites with Histological Severity in Patients with NAFLD.

OBJECTIVE: Clinical relevance of global DNA methylation and one-carbon metabolite levels with histological severity remains uncertain in patients with nonalcoholic fatty liver disease (NAFLD). This study aimed to evaluate hepatic global DNA methylation and serum one-carbon metabolite concentrations in patients with NAFLD and the possible associations of these parameters with liver histology. METHODS: Liver biopsies from 18 control participants and 47 patients with NAFLD were evaluated. RESULTS: The hepatic global DNA methylation level was significantly lower in the NAFLD group than in the control group among participants with overweight. Participants with moderate inflammation and mild fibrosis had significantly lower levels of global DNA methylation than those without these characteristics. Participants with borderline nonalcoholic steatohepatitis had significantly lower global DNA methylation levels than controls. The hepatic global DNA methylation level tended to decrease with the increasing hepatic inflammation grade and disease progression. The NAFLD group had a significantly higher serum homocysteine concentration than the control group among participants with overweight. This level tended to increase with increasing hepatic steatosis grade and disease progression. CONCLUSIONS: Patients with NAFLD exhibited lower hepatic levels of global DNA methylation and elevated serum homocysteine concentrations, which are associated with the histological severity of NAFLD.

Prevalence of Periodontal Disease and Periodontopathic Bacteria in Anti-Cyclic Citrullinated Protein Antibody-Positive At-Risk Adults Without Arthritis.

Importance: The prevalence of periodontitis is increased in patients with rheumatoid arthritis (RA) and periodontopathic bacteria can citrullinate proteins. Periodontitis may, therefore, be an initiator of RA and a target for prevention. Periodontal disease and periodontal bacteria have not been investigated in at-risk individuals with RA autoimmunity but no arthritis. Objective: To examine periodontal disease and periodontopathic bacteria in anti-cyclic citrullinated protein (anti-CCP) antibody-positive at-risk individuals without arthritis. Design, Setting, and Participants: This cross-sectional study took place at a teaching hospital from April 27, 2015, to May 8, 2017. Forty-eight anti-CCP-positive individuals without arthritis (CCP+ at-risk) were recruited nationally. Twenty-six patients with early RA (ERA) and 32 healthy control individuals were recruited locally. Data were analyzed between June 1, 2017, and December 1, 2017. Interventions: Periodontal assessment and examination of joints using ultrasonography. Main Outcomes and Measures: Prevalence of diseased periodontal sites, clinical periodontitis, and periodontal inflamed surface area in CCP+ at-risk individuals compared with patients with ERA and healthy individuals matched for age and smoking. Paired-end sequencing of DNA from subgingival plaque from diseased and healthy periodontal sites was performed and DNA was profiled and analyzed. Results: A total of 48 CCP+ at-risk individuals (mean [SD] age, 51.9 [11.4] years; 31 [65%] female), 26 patients with ERA (mean [SD] age, 54.4 [16.7] years; 14 [54%] female), and 32 healthy individuals (mean [SD] age, 49.4 [15.3] years; 19 [59%] female) were recruited. Of 48 CCP+ at-risk individuals, 46 had no joint inflammation on ultrasonography. Thirty-five CCP+ at-risk individuals (73%), 12 healthy individuals (38%), and 14 patients with ERA (54%) had clinical periodontitis. The median (interquartile range) percentage of periodontal sites with disease was greater in CCP+ at-risk individuals compared with healthy individuals (3.3% [0%-11.3%] vs 0% [0%-0.7%]) and similar to patients with ERA (1.1% [0%-13.1%]). Median (interquartile range) periodontal inflamed surface area was higher in CCP+ at-risk individuals compared with healthy individuals (221 mm2 [81-504 mm2] vs 40 mm2 [12-205 mm2]). Patients with CCP+ at-risk had increased relative abundance of Porphyromonas gingivalis (but not Aggregatibacter actinomycetemcomitans) at healthy periodontal sites compared with healthy individuals (effect size, 3.00; 95% CI, 1.71-4.29) and patients with ERA (effect size, 2.14; 95% CI, 0.77-3.52). Conclusions and Relevance: This study found increased prevalence of periodontitis and P gingivalis in CCP+ at-risk individuals. This suggests periodontitis and P gingivalis are associated with disease initiation and could be targets for preventive interventions in RA.

Ultrasound-Guided Continuous Femoral Nerve Block with Dexmedetomidine Combined with Low Concentrations of Ropivacaine for Postoperative Analgesia in Elderly Knee Arthroplasty.

OBJECTIVES: This study aims to investigate the clinical effect of dexmedetomidine (DEX) combined with low concentrations of ropivacaine in ultrasound-guided continuous fem-oral nerve block for postoperative analgesia in elderly patients with total knee arthroplasty (TKA). MATERIALS AND METHODS: Patients were divided into three groups: group C, group D1, and group D2. For postoperative analgesia, patients in group C were given 0.15% ropivacaine, patients in group D1 were given 0.15% ropivacaine + 0.02 µg × kg-1 × h-1 DEX, and patients in group D2 were given 0.15% ropivacaine + 0.05 µg × kg-1 × h-1 DEX. The visual analogue scores in the resting state, active state (AVAS), and passive functional exercise state (PVAS), degree of joint bending, and Ramsay scores were recorded. RESULTS: The Ramsay scores were significantly higher, AVAS scores were significantly lower, PVAS scores were significantly decreased, the degree of joint bending was significantly higher, and the time to the first postoperative ambulation was shorter in groups D1 and D2 than group C. Furthermore, the time to the first postoperative ambulation was shorter in group D2 than in group D1, patients in groups D1 and D2 were more satisfied than patients in group C, and patients in group D2 were more satisfied than patients in group D1. CONCLUSION: The protocol of 0.05 µg × kg-1 × h-1 of DEX combined with 0.15% ro-pivacaine in ultrasound-guided continuous femoral nerve block for postoperative analgesia in elderly patients with TKA provides a better analgesic effect than without DEX performance.X.-Y.Z. and E.-F.Z. have contributed equally to this research.

Periodontal disease and periodontal bacteria as triggers for rheumatoid arthritis.

There is an epidemiological association between periodontitis and rheumatoid arthritis (RA), which is hypothesised to lead to enhanced generation of RA-related autoantibodies that can be detected years before the onset of RA symptoms. Periodontitis is a common dysbiotic disease; tissue damage occurs because the immune system fails to limit both the resident microbial community and the associated local immune response. Certain periodontal bacteria, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, may contribute to RA autoantibody production through direct post-translational modification of proteins or, indirectly, by influencing neutrophil-mediated neo-epitope generation. Oral bacteria that invade the blood may also contribute to chronic inflammatory responses and generation of autoantibodies. The putative association between periodontitis and the development of RA raises the potential of finding novel predictive markers of disease and disease progression and for periodontitis treatment to be included in the future as an adjunct to conventional RA immunotherapy or as part of a preventive strategy.