Aim
To determine the presence of citrullinated histones in inflamed periodontal tissue and to determine the presence of anti‐citrullinated histone autoantibodies in sera from patients with rheumatoid ...arthritis (RA) and periodontitis (PD) patients.
Methods
The presence of citrullinated histone H3, PAD4 and CD68 was determined in 15 periodontal tissue biopsies from PD patients by immunohistochemistry. Sera from 36 healthy controls (HC), 113 PD patients and 84 patients with RA were assessed on presence of autoantibodies against citrullinated histones by Western blot and against citrullinated histone H3 by ELISA.
Results
Citrullinated histone H3, PAD4 and CD68 were present in periodontal tissue from nine (60%), 14 (93%) and 13 (87%) PD patients, respectively. Anti‐citrullinated histone H3 autoantibodies were found in 33 (39%) patients with RA compared to three (8%) HC and 11 (10%) PD patients. Anti‐citrullinated histone H3 levels were higher in anti‐cyclic citrullinated peptide (anti‐CCP)‐positive compared to anti‐CCP‐negative patients with RA (p = .0008) and correlated moderately with anti‐CCP levels (ρ = .22). No associations were found between anti‐citrullinated histone H3 levels and periodontal status or smoking behaviour of patients with RA.
Conclusion
PD patients are exposed to citrullinated histone H3 in inflamed periodontal tissue. Citrullinated histone H3 is targeted by autoantibodies present in RA sera. This supports a role for periodontitis in generation of antigens targeted by autoantibodies directed against citrullinated proteins.
Meta-analysis methodology was extended to derive comparative effectiveness information on spinal manipulation for low back pain.
Determine relative effectiveness of spinal manipulation therapies ...(SMTs), medical management, physical therapies, and exercise for acute and chronic nonsurgical low back pain.
Results of spinal manipulation treatments of nonsurgical low back pain are equivocal. Nearly 40 years of SMT studies were not informative.
Studies were chosen on the basis of inclusion in prior evidence syntheses. Effect sizes were converted to standardized mean effect sizes and probabilities of recovery. Nested model comparisons isolated nonspecific from treatment effects. Aggregate data were tested for evidential support as compared with shams.
Of 84% acute pain variance, 81% was from nonspecific factors and 3% from treatment. No treatment for acute pain exceeded sham's effectiveness. Most acute results were within 95% confidence bands of that predicted by natural history alone. For chronic pain, 66% of 98% was nonspecific, but treatments influenced 32% of outcomes. Chronic pain treatments also fit within 95% confidence bands as predicted by natural history. Though the evidential support for treating chronic back pain as compared with sham groups was weak, chronic pain seemed to respond to SMT, whereas whole systems of clinical management did not.
Meta-analyses can extract comparative effectiveness information from existing literature. The relatively small portion of outcomes attributable to treatment explains why past research results fail to converge on stable estimates. The probability of treatment superiority matched a binomial random process. Treatments serve to motivate, reassure, and calibrate patient expectations--features that might reduce medicalization and augment self-care. Exercise with authoritative support is an effective strategy for acute and chronic low back pain.
Many patients report symptomatic relief after undergoing arthroscopy of the knee for osteoarthritis, but it is unclear how the procedure achieves this result. We conducted a randomized, ...placebo-controlled trial to evaluate the efficacy of arthroscopy for osteoarthritis of the knee.
A total of 180 patients with osteoarthritis of the knee were randomly assigned to receive arthroscopic débridement, arthroscopic lavage, or placebo surgery. Patients in the placebo group received skin incisions and underwent a simulated débridement without insertion of the arthroscope. Patients and assessors of outcome were blinded to the treatment-group assignment. Outcomes were assessed at multiple points over a 24-month period with the use of five self-reported scores--three on scales for pain and two on scales for function--and one objective test of walking and stair climbing. A total of 165 patients completed the trial.
At no point did either of the intervention groups report less pain or better function than the placebo group. For example, mean (+/-SD) scores on the Knee-Specific Pain Scale (range, 0 to 100, with higher scores indicating more severe pain) were similar in the placebo, lavage, and débridement groups: 48.9+/-21.9, 54.8+/-19.8, and 51.7+/-22.4, respectively, at one year (P=0.14 for the comparison between placebo and lavage; P=0.51 for the comparison between placebo and débridement) and 51.6+/-23.7, 53.7+/-23.7, and 51.4+/-23.2, respectively, at two years (P=0.64 and P=0.96, respectively). Furthermore, the 95 percent confidence intervals for the differences between the placebo group and the intervention groups exclude any clinically meaningful difference.
In this controlled trial involving patients with osteoarthritis of the knee, the outcomes after arthroscopic lavage or arthroscopic débridement were no better than those after a placebo procedure.
Nanowire fabrication methods can be classified either as 'top down', involving photo- or electron-beam lithography, or 'bottom up', involving the synthesis of nanowires from molecular precursors. ...Lithographically patterned nanowire electrodeposition (LPNE) combines attributes of photolithography with the versatility of bottom-up electrochemical synthesis. Photolithography defines the position of a sacrificial nickel nanoband electrode, which is recessed into a horizontal trench. This trench acts as a 'nanoform' to define the thickness of an incipient nanowire during its electrodeposition. The electrodeposition duration determines the width of the nanowire. Removal of the photoresist and nickel exposes a polycrystalline nanowire--composed of gold, platinum or palladium--characterized by thickness and width that can be independently controlled down to 18 and 40 nm, respectively. Metal nanowires prepared by LPNE may have applications in chemical sensing and optical signal processing, and as interconnects in nanoelectronic devices.
Masticatory function is associated with a variety of health outcomes. The aim of this systematic review is to clarify the predictive value of masticatory function for adverse health outcomes, such as ...frailty, sarcopenia and malnutrition, in older adults.
An online literature search covered articles published in English or Dutch in three databases (PubMed, Embase and CINAHL, last searched November 4th 2022). Inclusion criteria were: an observational study design, focus on adults aged ≥65 years and evaluation of the association between masticatory function and health outcomes. Reviews and articles published before the year 2000 were excluded. Methodological quality and risk of bias were assessed using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the U.S. National Institutes of Health. Study population demographics, methods for assessing masticatory function, and the association between masticatory function and adverse health outcomes were extracted.
From the 34 included studies, 5 studies had a prospective design, 2 had a retrospective design, and the other 27 studies had cross-sectional design. The majority of the studies were conducted in Japan (74%, n = 26). Twenty studies (59%) used one indicator for masticatory function, the other 41% used two (n = 9) or more (n = 5) indicators. Masticatory function was most frequently assessed with the maximum occlusal force (MOF) (79%, n = 27). The identified health outcomes were clustered into 6 categories: physical parameters and sarcopenia, history of falling, nutritional status, frailty, cognitive function and mortality.
Despite the complex and multidimensional character of both masticatory function and most identified adverse health outcomes, some significant associations were reported. Prospective studies showed that reduced masticatory function in older adults is associated with incidence of frailty and frailty progression, cognitive decline and all-cause mortality. Regarding the other identified adverse health outcomes, i.e., physical measures and sarcopenia, history of falling and nutritional status, only cross-sectional studies were available and results were less concordant. As all prospective studies showed that reduced masticatory function in older adults is associated with adverse health outcomes, prevention of decline of masticatory function by adequate oral care may contribute to healthy ageing.
The physicochemical properties of aluminum trifluoromethanesulfonate in diglyme have been investigated. The spectroscopic and electrochemical properties have been examined to determine speciation, ...conductivity, and electrochemical stability. Gaussian calculations provide optimized molecular geometries and offer insight into the electrochemical behavior of the solutions. The ions in solution appear to exhibit very straightforward behavior, with contact ion pairs forming at very low concentrations. In addition, the electrochemical window of the electrolyte initially decreases with increasing salt concentration to a minimum value of approximately 5.5 V around 1 M and then steadily rises to a maximum value above 8 V.
In the absence of preorganization, macrocyclization reactions are often plagued by oligomeric and polymeric side products. Here, a network of hydrogen bonds was identified as the basis for ...quantitative yields of macrocycles derived from the dimerization of monomers. Oligomers and polymers were not observed. Macrocyclization, the result of the formation of two hydrazones, was hypothesized to proceed in two steps. After condensation to yield the monohydrazone, a network of hydrogen bonds formed to preorganize the terminal acetal and hydrazine groups for cyclization. Experimental evidence for preorganization derived from macrocycles and acyclic models. Solution NMR spectroscopy and single-crystal X-ray diffraction revealed that the macrocycles isolated from the cyclization reaction were protonated twice. These protons contributed to an intramolecular network of hydrogen bonds that engaged distant carbonyl groups to realize a long-range order. DFT calculations showed that this network of hydrogen bonds contributed 8.7 kcal/mol to stability. Acyclic models recapitulated this network in solution. Condensation of an acetal and a triazinyl hydrazine, which adopted a number of conformational isomers, yielded a hydrazone that adopted a favored rotamer conformation in solution. The critical hydrogen-bonded proton was also evident. DFT calculations of acyclic models showed that the rotamers were isoenergetic when deprotonated. Upon protonation, however, energies diverged with one low-energy rotamer adopting the conformation observed in the macrocycle. This conformation anchored the network of hydrogen bonds of the intermediate. Computation revealed that the hydrogen-bonded network in the acyclic intermediate contributed up to 14 kcal/mol of stability and preorganized the acetal and hydrazine for cyclization.
Seropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and ...defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP.
Thirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12). SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin.
Treg numbers were similar between HC, SAP and RA patients. Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047).
Numbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.
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