Phenols and GABAA receptors: from structure and molecular mechanisms action to neuropsychiatric sequelae.

γ-Aminobutyric acid type A receptors (GABAARs) are members of the pentameric ligand-gated ion channel (pLGIC) family, which are widespread throughout the invertebrate and vertebrate central nervous system. GABAARs are engaged in short-term changes of the neuronal concentrations of chloride (Cl-) and bicarbonate (HCO3 -) ions by their passive permeability through the ion channel pore. GABAARs are regulated by various structurally diverse phenolic substances ranging from simple phenols to complex polyphenols. The wide chemical and structural variability of phenols suggest similar and different binding sites on GABAARs, allowing them to manifest themselves as activators, inhibitors, or allosteric ligands of GABAAR function. Interest in phenols is associated with their great potential for GABAAR modulation, but also with their subsequent negative or positive role in neurological and psychiatric disorders. This review focuses on the GABAergic deficit hypotheses during neurological and psychiatric disorders induced by various phenols. We summarize the structure-activity relationship of general phenol groups concerning their differential roles in the manifestation of neuropsychiatric symptoms. We describe and analyze the role of GABAAR subunits in manifesting various neuropathologies and the molecular mechanisms underlying their modulation by phenols. Finally, we discuss how phenol drugs can modulate GABAAR activity via desensitization and resensitization. We also demonstrate a novel pharmacological approach to treat neuropsychiatric disorders via regulation of receptor phosphorylation/dephosphorylation.

Zinc Inhibits the GABAAR/ATPase during Postnatal Rat Development: The Role of Cysteine Residue.

Zinc ions (Zn2+) are concentrated in various brain regions and can act as a neuromodulator, targeting a wide spectrum of postsynaptic receptors and enzymes. Zn2+ inhibits the GABAARs, and its potency is profoundly affected by the subunit composition and neuronal developmental stage. Although the extracellular amino acid residues of the receptor's hetero-oligomeric structure are preferred for Zn2+ binding, there are intracellular sites that, in principle, could coordinate its potency. However, their role in modulating the receptor function during postembryonic development remains unclear. The GABAAR possesses an intracellular ATPase that enables the energy-dependent anion transport via a pore. Here, we propose a mechanistic and molecular basis for the inhibition of intracellular GABAAR/ATPase function by Zn2+ in neonatal and adult rats. The enzymes within the scope of GABAAR performance as Cl-ATPase and then as Cl-, HCO3-ATPase form during the first week of postnatal rat development. In addition, we have shown that the Cl-ATPase form belongs to the ß1 subunit, whereas the ß3 subunit preferably possesses the Cl-, HCO3-ATPase activity. We demonstrated that a Zn2+ with variable efficacy inhibits the GABAAR as well as the ATPase activities of immature or mature neurons. Using fluorescence recording in the cortical synaptoneurosomes (SNs), we showed a competitive association between Zn2+ and NEM in parallel changes both in the ATPase activity and the GABAAR-mediated Cl- and HCO3- fluxes. Finally, by site-directed mutagenesis, we identified in the M3 domain of ß subunits the cysteine residue (C313) that is essential for the manifestation of Zn2+ potency.

Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.

OBJECTIVE: The study of autoantibody isotypes in autoimmune diseases is useful for identifying clinically relevant endotypes. This study was undertaken to study the prevalence and clinical significance of different isotypes and IgG subclasses of anti-peptidylarginine deiminase 4 (anti-PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). METHODS: In 196 RA subjects and 64 healthy controls, anti-PAD4 antibody types were determined using enzyme-linked immunosorbent assay. We investigated associations between anti-PAD4 antibodies and clinical outcomes, and relevant features were confirmed in an independent RA cohort. RESULTS: Anti-PAD4 IgG1, anti-PAD4 IgG2, anti-PAD4 IgG3, anti-PAD4 IgG4, anti-PAD4 IgA, and anti-PAD4 IgE antibodies were more frequent in RA patients than healthy controls (P < 0.001). Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE were associated with distinct clinical features. Anti-PAD4 IgG1 was predictive of progressive radiographic joint damage (odds ratio [OR] 4.88, P = 0.005), especially in RA patients without baseline joint damage (40% versus 0%, P = 0.003) or in those negative for anti-cyclic citrullinated peptide and/or rheumatoid factor (OR 32; P = 0.009). IgG1 was also associated with higher levels of C-reactive protein (P = 0.006) and interleukin-6 (P = 0.021). RA patients with anti-PAD4 IgG3 had higher baseline joint damage scores (median Sharp/van der Heijde score 13 versus 7, P = 0.046), while those with anti-PAD4 IgE had higher Disease Activity Score in 28 joints (median 4.0 versus 3.5, P = 0.025), more frequent rheumatoid nodules (31% versus 16%, P = 0.025), and more frequent interstitial lung disease (ground-glass opacification) (24% versus 9%, P = 0.014). Anti-PAD4 IgG1 antibody associations with joint damage were corroborated in an independent RA cohort. CONCLUSION: Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE antibodies identify discrete disease subsets in RA, suggesting that heavy chain usage drives distinct effector mechanisms of anti-PAD4 antibodies in RA.

Physiological Role of ATPase for GABAA Receptor Resensitization.

γ-Aminobutyric acid type A receptors (GABAARs) mediate primarily inhibitory synaptic transmission in the central nervous system. Following fast-paced activation, which provides the selective flow of mainly chloride (Cl-) and less bicarbonate (HCO3-) ions via the pore, these receptors undergo desensitization that is paradoxically prevented by the process of their recovery, referred to as resensitization. To clarify the mechanism of resensitization, we used the cortical synaptoneurosomes from the rat brain and HEK 293FT cells. Here, we describe the effect of γ-phosphate analogues (γPAs) that mimic various states of ATP hydrolysis on GABAAR-mediated Cl- and HCO3- fluxes in response to the first and repeated application of the agonist. We found that depending on the presence of bicarbonate, opened and desensitized states of the wild or chimeric GABAARs had different sensitivities to γPAs. This study presents the evidence that recovery of neuronal Cl- and HCO3- concentrations after desensitization is accompanied by a change in the intracellular ATP concentration via ATPase performance. The transition between the desensitization and resensitization states was linked to changes in both conformation and phosphorylation. In addition, the chimeric ß3 isoform did not exhibit the desensitization of the GABAAR-mediated Cl- influx but only the resensitization. These observations lend a new physiological significance to the ß3 subunit in the manifestation of GABAAR resensitization.

Dysregulation of lncRNA-miRNA-mRNA Interactome as a Marker of Metastatic Process in Ovarian Cancer.

Ovarian cancer (OC) is one of the most common types of cancer among malignancies of the female reproductive system. This pathology is asymptomatic until advanced stages and has a poor prognosis. Our study aimed to search for lncRNA-miRNA-mRNA competing triplets that promote ovarian tumorigenesis. For this purpose, we analyzed tumor samples from the TCGA database and verified the results experimentally in a set of 46 paired samples of tumor and matched histologically unchanged ovarian tissues from OC patients. The list of RNAs selected in silico for experimental studies included 13 mRNAs, 10 lncRNAs, and 5 miRNAs related to epithelial-mesenchymal transition and angiogenesis. We evaluated the expression of these RNAs by qRT-PCR and assessed the correlation between levels of miRNAs, mRNAs, and lncRNAs. Sixteen significant triplets were revealed, in some of which, e.g., OIP5-AS1-miR-203a-c-MET and OIP5-AS1-miR-203a-ZEB2, both lncRNA and mRNA had sites for miR-203a direct binding. Transfection of the OVCAR-3 and SKOV-3 cell lines with the miR-203a mimic was used to confirm the novel links of miR-203a with ZEB2 and c-MET in OC. These connections suggest that the interactomes have the potential for diagnostics of metastasis at early onset.

Validation of an algorithm to identify incident interstitial lung disease in patients with rheumatoid arthritis.

BACKGROUND/PURPOSE: Interstitial lung disease (ILD) is an important problem for patients with rheumatoid arthritis (RA). However, current approaches to ILD case finding in real-world data have been evaluated only in limited settings and identify only prevalent ILD and not new-onset disease. Our objective was to develop, refine, and validate a claims-based algorithm to identify both prevalent and incident ILD in RA patients compared to the gold standard of medical record review. METHODS: We used administrative claims data 2006-2015 from Medicare to derive a cohort of RA patients. We then identified suspected ILD using variations of ILD algorithms to classify both prevalent and incident ILD based on features of the data that included hospitalization vs. outpatient setting, physician specialty, pulmonary-related diagnosis codes, and exclusions for potentially mimicking pulmonary conditions. Positive predictive values (PPV) of several ILD algorithm variants for both prevalent and incident ILD were evaluated. RESULTS: We identified 234 linkable RA patients with sufficient data to evaluate for ILD. Overall, 108 (46.2%) of suspected cases were confirmed as ILD. Most cases (64%) were diagnosed in the outpatient setting. The best performing algorithm for prevalent ILD had a PPV of 77% (95% CI 67-84%) and for incident ILD was 96% (95% CI 85-100%). CONCLUSION: Case finding in administrative data for both prevalent and incident interstitial lung disease in RA patients is feasible and has reasonable accuracy to support population-based research and real-world evidence generation.

Whey Protein Supplementation Is Superior to Leucine-Matched Collagen Peptides to Increase Muscle Thickness During a 10-Week Resistance Training Program in Untrained Young Adults.

The purpose of this study was to investigate the effects of supplementation of whey protein (WP) versus leucine-matched collagen peptides (CP) on muscle thickness MT and performance after a resistance training (RT) program in young adults. Twenty-two healthy untrained participants were randomly assigned to either a WP (n = 11) or leucine-matched CP (n = 11) group and then submitted to a supervised 10-week RT program (3 days/week). The groups were supplemented with an equivalent amount of WP (35 g, containing 3.0 g of leucine) and CP (35 g, containing 1.0 g of leucine and 2.0 g of free leucine) during the intervention period (after each workout and in the evening on nontraining days). MT of the vastus lateralis and biceps brachii, isokinetic peak torque and mean power output of the elbow flexors, and peak power output of the lower body were assessed before and after the RT program. The WP group experienced a greater (interaction, p < .05) increase in the vastus lateralis (effect size, WP = 0.68 vs. CP = 0.38; % Δ, WP = 8.4 ± 2.5 vs. CP = 5.6 ± 2.6%) and biceps brachii muscle thickness (effect size, WP = 0.61 vs. CP = 0.35; % , WP = 10.1 ± 3.8 vs. CP = 6.0 ± 3.2%), with a similar increase in muscle performance (peak torque, mean power output, and peak power output) between groups (time p < .05). Supplementation with WP was superior to leucine content-matched CP supplementation in increasing muscle size, but not strength and power, after a 10-week RT program in young adults.

Functional outcome after inpatient rehabilitation in postintensive care unit COVID-19 patients: findings and clinical implications from a real-practice retrospective study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading worldwide, with survivors that suffer functional impairments with a consequent key role of rehabilitation in this context. To date, there is a lack of findings on the role of rehabilitation in postacute COVID-19 patients. AIM: Thus, we aimed at describing the role of a patient-tailored rehabilitation plan on functional outcome in hospitalized COVID-19 patients. DESIGN: Real-practice retrospective study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Postacute COVID-19 patients. METHODS: Medical records of patients referred to an Italian COVID-19 Rehabilitation Unit from March 10th, 2020 to April 30th, 2020 were collected. All patients underwent a rehabilitative (30 minutes/set, 2 times/day), aimed to improve gas exchanges, reducing dyspnoea, and improving muscle function. At the admission (T0) and at the discharge (T1), we evaluated as outcome measures: Barthel Index (BI), modified Medical Research Council Dyspnea Scale, 6-Minute Walking Test (6-MWT) and Borg Rating of Perceived Exertion (RPE) scale. We also assessed: type of respiratory supports needed, pulmonary function, coagulation and inflammation markers and length of stay (LOS) in Rehabilitation Unit. RESULTS: We included 41 postacute COVID-19 patients (25 male and 19 female), mean aged 72.15±11.07 years. Their mean LOS in the Rehabilitation Unit was 31.97±9.06 days, as 39 successfully completed the rehabilitation treatment and 2 deceased. We found statistically significant improvement in BI (84.87±15.56 vs. 43.37±26.00; P<0.0001), 6-MWT (303.37±112.18 vs. 240.0±81.31 meters; P=0.028), Borg RPE scale (12.23±2.51 vs. 16.03±2.28; P<0.0001). CONCLUSIONS: These findings suggest that postacute COVID-19 patients might beneficiate of a motor and respiratory rehabilitation treatment. However, further studies are advised to better understand long-term sequelae of the disease. CLINICAL REHABILITATION IMPACT: This study provides evidence on the role of rehabilitation COVID-19 postacute inpatients through a patient-tailored treatment.

Ectopic GABAA receptor ß3 subunit determines Cl- / HCO3- -ATPase and chloride transport in HEK 293FT cells.

Neuronal intracellular chloride concentration ([Cl- ]i ) is a crucial determinant of transmission mediated by the γ-aminobutyric acid type A receptor (GABAA R), which subserves synaptic and extrasynaptic inhibition as well as excitation. The Cl- ion is the main carrier of charge through the GABAA R; however, bicarbonate ions ( HCO3- ) flowing in the opposite direction can also contribute to the net current. The direction of Cl- and HCO3- fluxes is determined by the underlying electrochemical gradient, which is controlled by Cl- transporters and channels. Accumulating evidence suggests that active mechanisms of chloride transport across the GABAA R pore can underlie the regulation of [Cl- ]i . Measurement of Cl- / HCO3- -ATPase activity and Cl- transport in HEK 293FT cells expressing homomeric or heteromeric GABAA R ensembles (α2, ß3, or γ2) with fluorescent dye for chloride demonstrated that receptor subtypes containing the ß3 subunit show enzymatic activity and participate in GABA-mediated or ATP-dependent Cl- transport. GABA-mediated flow of Cl- ions into and out of the cells occurred for a short time period but then rapidly declined. However, Cl- ion flux was stabilized for a long time period in the presence of HCO3- ions. The reconstituted ß3 subunit isoform, purified as a fusion protein, confirmed that ß3 is critical for ATPase; however, only the triplet variant showed the full receptor function. The high sensitivity of the enzyme to γ-phosphate inhibitors led us to postulate that the ß3 subunit is catalytic. Our discovery of a GABAA R type that requires ATP consumption for chloride movement provides new insight into the molecular mechanisms of inhibitory signaling.

Placing Greater Torque at Shorter or Longer Muscle Lengths? Effects of Cable vs. Barbell Preacher Curl Training on Muscular Strength and Hypertrophy in Young Adults.

Muscular strength and hypertrophy following resistance training may be obtained in different degrees depending on the approach performed. This study was designed to compare the responses of the biceps brachii to two preacher curl exercises, one performed on a cable-pulley system (CAB; in which a greater torque was applied during the exercise when elbows were flexed and biceps shortened) and one performed with a barbell (BAR; in which greater torque was applied when the elbows were extended and biceps stretched). Thirty-five young adults (CAB: 13 men, 5 women; BAR: 12 men, 5 women; age = 24 ± 5 years) performed a resistance training program three times per week for 10 weeks, with preacher curl exercises performed in three sets of 8-12 repetitions. Outcomes measured included elbow flexion peak isokinetic torque at angles of 20°, 60°, and 100° (considering 0° as elbow extended), and biceps brachii thickness (B-mode ultrasound). Following the training period, there were significant increases for both groups in elbow flexion peak torque at the 20° (CAB: 30%; BAR = 39%; p = 0.046), 60° (CAB: 27%; BAR = 32%; p = 0.874), and 100° (CAB: 17%; BAR = 19%; p = 0.728), and biceps brachii thickness (CAB: 7%; BAR = 8%; p = 0.346). In conclusion, gains in muscular strength were greater for BAR only at longer muscle length, whereas hypertrophy was similar regardless of whether torque emphasis was carried out in the final (CAB) or initial (BAR) degrees of the range of motion of the preacher curl in young adults.

Early rehabilitation in post-acute COVID-19 patients: data from an Italian COVID-19 Rehabilitation Unit and proposal of a treatment protocol.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading, putting under heavy stress health systems worldwide and especially Intensive Care Units (ICU). Rehabilitation Units have a crucial role in reducing disability in order to reintroduce patients in the community. AIM: The aim of this study is to characterize pulmonary function and disability status and to propose an early rehabilitation protocol in a cohort of post-acute COVID-19 patients admitted to an Italian Rehabilitation Unit. DESIGN: Cross-sectional observational study. SETTING: Inpatients Rehabilitation Unit. POPULATION: Post-acute COVID-19 patients. METHODS: Demographic, anamnestic and clinical characteristics, laboratory exams and medical imaging findings were collected for the entire cohort. Outcome measures evaluated at the admission in Rehabilitation Unit were: type of respiratory supports needed, fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), FiO2/PaO2, Barthel Index (BI), modified Medical Research Council (mMRC) Dyspnoea Scale, and 6-Minute Walking Test (6-MWT). Furthermore, we proposed an early rehabilitation protocol for COVID-19 patients based on baseline FiO2. RESULTS: We included 32 post-acute COVID-19 patients (22 male and 10 female), mean aged 72.6±10.9 years. BI was 45.2±27.6, with patients in need of higher FiO2 (≥40%) showing lower values: 39.6±25.7 vs. 53.3±29.3. All patients had grade 4 or 5 on the mMRC Dyspnea Scale. Only 14 COVID-19 patients were able to walk (43.7%). 6-MWT was feasible in 6 (18.8%) patients with a mean distance of 45.0±100.6 meters. CONCLUSIONS: Taken together, our findings suggest that post-acute COVID-19 patients suffered from dyspnea and shortness of breath even for minimal activities, with a resulting severe disability, and only a few of them were able to perform 6-MWT with poor results. An early rehabilitation protocol was proposed according to the baseline conditions of the patients. CLINICAL REHABILITATION IMPACT: This study could provide an accurate description of COVID-19 sub-acute patients admitted to a Rehabilitation Unit along with a proposal of treatment to help physicians to tailor the best possible rehabilitative treatment.

Factors associated with the contemplative stage of readiness to initiate osteoporosis treatment.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment. INTRODUCTION: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture. METHODS: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment. RESULTS: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative. CONCLUSIONS: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Assessment of platelet respiration as emerging biomarker of disease.

Mitochondrial dysfunction is currently acknowledged as a central pathomechanism of most common diseases of the 21(st) century. Recently, the assessment of the bioenergetic profile of human peripheral blood cells has emerged as a novel research field with potential applications in the development of disease biomarkers. In particular, platelets have been successfully used for the ex vivo analysis of mitochondrial respiratory function in several acute and chronic pathologies. An increasing number of studies support the idea that evaluation of the bioenergetic function in circulating platelets may represent the peripheral signature of mitochondrial dysfunction in metabolically active tissues (brain, heart, liver, skeletal muscle). Accordingly, impairment of mitochondrial respiration in peripheral platelets might have potential clinical applicability as a diagnostic and prognostic tool as well as a biomarker in treatment monitoring. The aim of this minireview is to summarize current information in the field of platelet mitochondrial dysfunction in both acute and chronic diseases.

Assessing the feasibility of the Effectiveness of Discontinuing Bisphosphonates trial: a pilot study.

The Effectiveness of Discontinuing Bisphosphonates (EDGE) study is a planned pragmatic clinical trial to guide "drug holiday" clinical decision making. This pilot study assessed work flow and feasibility of such a study. While participant recruitment and treatment adherence were suboptimal, administrative procedures were generally feasible and minimally disrupted clinic flow. INTRODUCTION: The comparative effectiveness of continuing or discontinuing long-term alendronate (ALN) on fractures is unknown. A large pragmatic ALN discontinuation study has potential to answer this question. METHODS: We conducted a 6-month pilot study of the planned the EDGE study among current long-term ALN users (women aged ≥65 with ≥3 years of ALN use) to determine study work flow and feasibility including evaluating the administrative aspects of trial conduct (e.g., time to contract, institutional review board (IRB) approval), assessing rates of site and participant recruitment, and evaluating post-randomization outcomes, including adherence, bisphosphonate-associated adverse events, and participant and site satisfaction. We assessed outcomes 1 and 6 months after randomization. RESULTS: Nine sites participated, including seven community-based medical practices and two academic medical centers. On average (SD), contract execution took 3.4 (2.3) months and IRB approval took 13.9 (4.1) days. Sites recruited 27 participants (13 to continue ALN and 14 to discontinue ALN). Over follow-up, 22% of participants did not adhere to their randomization assignment: 30.8% in the continuation arm and 14.3% in the discontinuation arm. No fractures or adverse events were reported. Sites reported no issues regarding work flow, and participants were highly satisfied with the study. CONCLUSIONS: Administrative procedures of the EDGE study were generally feasible, with minimal disruption to clinic flow. In this convenience sample, participant recruitment was suboptimal across most practice sites. Accounting for low treatment arm adherence, a comprehensive recruitment approach will be needed to effectively achieve the scientific goals of the EDGE study.

Differential processing of small RNAs during endoplasmic reticulum stress.

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) lumen due to the disruption of the homeostatic system of the ER leads to the induction of the ER stress response. Cellular stress-induced pathways globally transform genes expression on both the transcriptional and post-transcriptional levels with small RNA involvement as regulators of the stress response. The modulation of small RNA processing might represent an additional layer of a complex stress response program. However, it is poorly understood. Here, we studied changes in expression and small RNAs processing upon ER stress in Jurkat T-cells. Induced by ER-stress, depletion of miRNAs among small RNA composition was accompanied by a global decrease of 3' mono-adenylated, mono-cytodinylated and a global increase of 3' mono-uridinylated miRNA isoforms. We observed the specific subset of differentially expressed microRNAs, and also the dramatic induction of 32-nt tRNA fragments precisely phased to 5' and 3' ends of tRNA from a subset of tRNA isotypes. The induction of these tRNA fragments was linked to Angiogenin RNase, which mediates translation inhibition. Overall, the global perturbations of the expression and processing of miRNAs and tiRNAs were the most prominent features of small RNA transcriptome changes upon ER stress.

The role of genetic variants in CRP in radiographic severity in African Americans with early and established rheumatoid arthritis.

This study investigates the association of CRP (C-reactive protein) single-nucleotide polymorphisms (SNPs) with plasma CRP levels and radiographic severity in African Americans with early and established rheumatoid arthritis (RA). Using a cross-sectional case-only design, CRP SNPs were genotyped in two independent sets of African Americans with RA: Consortium for the Longitudinal Evaluation of African Americans with RA (CLEAR 1) and CLEAR 2. Radiographic data and CRP measurements were available for 294 individuals from CLEAR 1 (median (interquartile range (IQR) 25-75) disease duration of 1 (0.6-1.6) year) and in 407 persons from CLEAR 2 (median (IQR 25-75) disease duration of 8.9 (3.5-17.7) years). In CLEAR 1, in adjusted models, the minor allele of rs2808630 was associated with total radiographic score (incident rate ratio 0.37 (95% confidence interval (CI) 0.19-0.74), P-value=0.0051). In CLEAR 2, the minor allele of rs3093062 was associated with increased plasma CRP levels (P-value=0.002). For each rs3093062 minor allele, the plasma CRP increased by 1.51 (95% CI 1.15-1.95) mg dl(-1) when all the other covariates remained constant. These findings have important implications for assessment of the risk of joint damage in African Americans with RA.

Influence of electropolishing and anodic oxidation on morphology, chemical composition and corrosion resistance of niobium.

The work presents results of the studies performed on electropolishing of pure niobium in a bath that contained: sulphuric acid, hydrofluoric acid, ethylene glycol and acetanilide. After the electropolishing, the specimens were subjected to anodic passivation in a 1moldm(-3) phosphoric acid solution at various voltages. The surface morphology, thickness, roughness and chemical composition of the resulting oxide layers were analysed. Thusly prepared niobium samples were additionally investigated in terms of their corrosion resistance in Ringer's solution. The electropolished niobium surface was determined to be smooth and lustrous. The anodisation led to the growth of barrier-like oxide layers, which were enriched in phosphorus species.

Surface characterisation of Ti-15Mo alloy modified by a PEO process in various suspensions.

This paper reports on the surface modification of a Ti-15Mo alloy by plasma electrolytic oxidation (PEO). This process was carried out in solutions of 0.1M Ca(H2PO2)2 with various concentrations of tricalcium phosphate (Ca3(PO4)2), wollastonite (CaSiO3), or silica (SiO2) using voltages of up to 350V. The surface microstructure (SEM, cross-section of coating), roughness and chemical composition (energy-dispersive X-ray spectroscopy, thin layer X-ray diffraction, X-ray photoelectron spectroscopy and Raman spectroscopy) of the porous oxide layers were investigated. The concentration of powder added to the solution changed the chemical composition and morphology of PEO coatings on the Ti-15Mo alloy surface. Calcium and phosphorous compounds were detected in the coatings formed on the substrate by the PEO process at 300V.